CBD for physicians and pharmacists

In two double-blind RCTs (GWPCARE1 and GWPCARE2), prescription pure CBD added to existing medicines reduced convulsive seizures more than placebo over 14 weeks. 10 and 20 mg/kg/day had a similar effect; 10 mg/kg/day was better tolerated. Complete seizure freedom was rare (5% vs. 0% in GWPCARE1), and seizures also decreased in the placebo group. In a dose-ranging safety RCT with 5–20 mg/kg/day in 34 children aged 4–10, CBD levels rose in proportion to the dose, clobazam's active metabolite rose, and liver enzymes rose in 6 patients taking valproate (all returned to normal). The efficacy studies were all 14 weeks long, add-on treatment and manufacturer-funded; the EMA writes that efficacy has not been proven in patients not taking clobazam. The Stockings 2018 review in the table found CBD superior to placebo for a reduction in seizures of at least half, but rated the certainty of the evidence as low (GRADE); this assessment was based on a search up to October 2017 and, for this outcome, on two RCTs (291 patients). Later meta-analyses combining four RCTs (Lattanzi 2018; Lattanzi 2020, clobazam status) and the meta-analysis combining the three RCTs in Dravet only (Lattanzi 2020, Dravet meta-analysis: seizure reduction of at least half RR 1.69; 95% CI 1.21–2.36; stopping treatment 9.0% vs. 2.3%) gave results in the same direction; the guide's "strong" assessment rests on this whole body of evidence. The latest version of the Cochrane review of medicines in Dravet (2017) predates the CBD studies, so it does not include CBD. In analyses that split the same four RCTs by clobazam use, CBD was better than placebo in patients not taking clobazam too. The reduction in seizure count was smaller in patients without clobazam (both conditions and both doses combined, the ratio of seizure frequency vs. placebo was 0.59 with clobazam and 0.85 without clobazam; looking at the two doses separately, the difference was not significant without clobazam; manufacturer analysis, Devinsky 2020); in the share of patients whose seizures fell by at least half, the difference from placebo was similar in the two groups (RR 1.85 and 1.80 in an independent meta-analysis; Lattanzi 2020, clobazam status). In 89 patients with Dravet taking both stiripentol and clobazam, CBD's effect was numerically favorable but not significant (Devinsky 2020). Because whether patients took these medicines was not decided at random, these comparisons are not conclusive. In two network meta-analyses comparing Dravet medicines (there are no studies comparing the medicines directly; the comparisons are indirect), the share of patients whose seizures fell by at least half was lower with CBD than with fenfluramine and stiripentol (vs. fenfluramine OR 0.20; 95% CI 0.07–0.54; Lattanzi 2023); the result was the same when looking only at patients using it together with clobazam (Guerrini 2024). The certainty of these comparisons is limited: stiripentol rests on two small studies (64 children) done an estimated 15–20 years ago, 33–49% of patients in the CBD studies were already taking stiripentol, and one of the analyses was funded by the maker of stiripentol. The picture for side effects is different: in one analysis, the share of patients with side effects was lower with CBD than with fenfluramine and stiripentol, while stopping treatment was more common with CBD than with stiripentol (Lattanzi 2023). In the open-label extension of the two RCTs, the median reduction in convulsive seizures in 315 patients stayed between 45% and 74% in 12-week periods up to 156 weeks; according to the final results on ClinicalTrials.gov (registry, not a peer-reviewed publication), 170 of the patients completed the study and the median reduction in the last 12 weeks was 40%; liver enzymes rose markedly in 22% of patients, 84% of whom were taking valproate (Scheffer 2021). In everyday-practice studies, mostly from Europe, the share of patients with Dravet whose seizures fell by at least half ranged from 22% to 51%; in a study in adults in England, seizures fell by more than 30% in only 3 of 17 patients, and in the 15 patients using it without clobazam the rate was 13–21%; these studies have no comparison group, and in most of them some authors have financial ties to the manufacturer. There is no controlled study of unapproved cannabis products in Dravet. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 3 placebo-controlled RCTs with cannabinoids on this topic (one a dose study mainly measuring safety and drug levels) and 6 systematic reviews (2 of them indirect comparisons with other Dravet medicines) were found; these are in the table below together with a manufacturer-supported pooled analysis of the same studies, 10 studies without randomized comparison (long-term extension, access programs, everyday practice, and unapproved or THC-containing products) and 3 drug-level studies measuring drug interactions (two placebo-controlled in patients with epilepsy, one in healthy volunteers). No controlled study with THC-containing products in Dravet was found.

Evidence assessment: Strong (double-blind, placebo-controlled RCTs + meta-analyses)

• CBD alone: Approved, purified medicinal CBD (Epidiolex/Epidyolex) was found effective as an add-on treatment in Dravet syndrome (two double-blind RCTs and meta-analyses; strong evidence); the effect continued in long-term follow-up with no comparison group, and in indirect comparisons with limited certainty against the other medicines approved for Dravet (fenfluramine, stiripentol), its effect on reducing seizures looked smaller; this result cannot be applied to CBD oils whose content and dose are unknown.
• Products containing THC: There is no controlled study with THC-containing products in Dravet syndrome. In the only prospective study specific to Dravet, a cannabis oil also containing a small amount of THC (CBD:THC 50:1) was tried in 20 children for 20 weeks and seizures decreased (median 70.6% for motor seizures); but because there was no placebo group and the contribution of THC could not be separated from that of CBD, this result does not show a benefit of THC. The study was largely funded by the company that makes the product. (insufficient evidence) Evidence: Insufficient: no controlled study with a THC-containing product in Dravet; there is only one small open-label study of 20 children with no comparison group
• Approval: FDA (≥1 year, no clobazam requirement): start at 2.5 mg/kg twice daily (5 mg/kg/day); after 1 week, maintenance dose 5 mg/kg twice daily (10 mg/kg/day). If further seizure reduction is needed, increase weekly by 2.5 mg/kg twice daily up to a maximum of 10 mg/kg twice daily (20 mg/kg/day); for faster titration, increase no more often than every other day. Label: 20 mg/kg/day gives somewhat greater seizure reduction but more side effects. EMA (≥2 years, add-on treatment only together with clobazam): 5 mg/kg/day for 1 week, then maintenance 10 mg/kg/day; increases above 10 mg/kg/day based on individual benefit-risk and with the full monitoring schedule, maximum 20 mg/kg/day. Hepatic impairment: moderate (Child-Pugh B) start at 1.25 mg/kg twice daily, severe (Child-Pugh C) 0.5 mg/kg twice daily. Stopping is done gradually. Source: FDA label (05/2026) §2.1–2.2, §2.5–2.6; EMA product information §4.1–4.2 (last updated in the EPAR on August 20, 2026). Turkey: Epidyolex/cannabidiol is not on the TİTCK (Turkish Medicines and Medical Devices Agency) list of approved products (October 16, 2026); on the TİTCK Foreign Active Ingredient List (September 28, 2026), cannabidiol oral solution (YDN02BG1099) is listed as a red-prescription drug and among the medicines that cannot be imported without TİTCK's written approval.
• Dose range in studies: 10–20 mg/kg/day in the labeling and RCTs (divided into two equal doses); up to a ceiling of 25–50 mg/kg/day in the open-label expanded access program; at most 30 mg/kg/day (mean 22 mg/kg/day) in the open-label extension study; in everyday-practice studies in Europe, the median or mean dose was mostly 11–16 mg/kg/day
• Starting dose and titration (in studies): Labeling: start at 5 mg/kg/day, 10 mg/kg/day after 1 week; if needed, increase by 5 mg/kg/day weekly up to a maximum of 20 mg/kg/day. In the RCTs, a 2-week titration (10 mg/kg/day reached in 7 days, 20 mg/kg/day in 11 days), followed by 12 weeks of maintenance
• Interaction: Clobazam: CBD raises the active metabolite N-desmethylclobazam ~3-fold (FDA) / 3–4-fold (EMA) (total exposure 2.6-fold in a placebo-controlled study in patients with epilepsy taking clobazam, VanLandingham 2020; 3.4-fold in healthy volunteers, Morrison 2019; this increase was not seen in 4 children with Dravet also taking stiripentol, Devinsky 2018); clobazam also raises 7-OH-CBD (AUC 47%). If sleepiness occurs, reducing the clobazam dose is considered
• Interaction: Valproate: raised liver enzymes increase markedly; diarrhea and decreased appetite also increase (EMA). If enzymes rise, CBD and/or valproate is reduced or stopped
• Interaction: Stiripentol: in healthy volunteers, Cmax 28%, AUC 55% (Morrison 2019); in a placebo-controlled study in patients with epilepsy, Cmax up 17%, AUC up 30% (Ben-Menachem 2020). Side effects are closely monitored
• Interaction: Everolimus: exposure rises ~2.5-fold; levels are monitored, and in patients using CBD, everolimus is started at a lower dose
• Interaction: Topiramate, rufinamide, zonisamide, eslicarbazepine: in an open-label study, serum levels rose as the CBD dose increased (most stayed within the therapeutic range)
• Interaction: Sirolimus, tacrolimus, digoxin (oral P-gp substrates): exposure may rise; level monitoring and dose reduction are considered
• Interaction: Strong CYP3A4/CYP2C19 inducers (rifampin; EMA: carbamazepine, enzalutamide, mitotane, St. John's wort): rifampin lowered CBD by ~32% and 7-OH-CBD by ~63% (FDA); FDA (05/2026): with a strong inducer, increasing the Epidiolex dose up to at most 2-fold may be considered based on response and tolerability
• Interaction: CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC rose 95%; dose reduction is considered for narrow-range medicines
• Interaction: CYP2C19 prodrugs such as clopidogrel: the active metabolite may decrease
• Interaction: Alcohol and other CNS depressants: sleepiness and sedation increase; alcohol also increases CBD exposure (Cmax 93%, AUC 63%)
• Monitoring in studies: Before starting: ALT, AST and total bilirubin (FDA and EMA)
• Monitoring in studies: Liver tests at months 1, 3 and 6, then periodically or as clinically needed
• Monitoring in studies: FDA: within 1 month after a dose change or after adding a medicine that affects the liver; EMA: the monitoring schedule starts over when going above 10 mg/kg/day or when a medicine that affects the liver is changed
• Monitoring in studies: People using valproate and those with high baseline ALT/AST: per the EMA, at week 2 and months 1, 2, 3 and 6, then periodically
• Monitoring in studies: Stopping rule (FDA and EMA): CBD is stopped if transaminases are >3×ULN and bilirubin >2×ULN, or if transaminases are persistently >5×ULN
• Monitoring in studies: If liver symptoms occur (unexplained nausea, vomiting, right upper abdominal pain, tiredness, loss of appetite, jaundice, dark urine), check ALT/AST/bilirubin right away
• Monitoring in studies: Blood levels and side effects of co-administered antiseizure medicines (Gaston 2017, PMID 28782097)

References (23)

Study table (dose, duration, result) · Topic page

In two double-blind RCTs (GWPCARE3 and GWPCARE4), prescription pure CBD added to existing medicines reduced drop seizures more than placebo over 14 weeks (about 37–44% vs. 17–22%). Because seizures also decreased in the placebo group, the absolute difference is about 17–25 points. Some patients see clear benefit and some see none. The EMA writes that efficacy has not been proven in patients not taking clobazam and restricts the approval to use with clobazam. In analyses that separated the same four RCTs by clobazam use, CBD was also better than placebo in patients not taking clobazam. For the reduction in the number of seizures, the effect was smaller in patients without clobazam (with both diseases and both doses combined, the ratio of seizure frequency vs. placebo was 0.59 with clobazam and 0.85 without; when the two doses were looked at separately, the difference was not significant in those without clobazam; manufacturer analysis, Devinsky 2020); for the proportion of patients whose seizures were at least halved, the difference from placebo was similar in the two groups (RR 1.80 and 1.85 in an independent meta-analysis; Lattanzi 2020). Because whether patients took clobazam was not decided by chance, these comparisons are not conclusive. In everyday-practice data on 92 LGS patients taking CBD without clobazam, the proportion of patients whose drop seizures were at least halved was 19% at month 3 and 30% at month 12 (Nabbout 2023; no control group, manufacturer-supported). The Stockings 2018 review in the table found CBD superior to placebo for at least halving seizures but rated the certainty of the evidence as low (GRADE); this rating was based on a search up to October 2017 and, for this outcome, on two RCTs (291 patients). Later meta-analyses combining four RCTs (Lattanzi 2018 LGS and Dravet, Lattanzi 2020) gave results in the same direction; the guide's 'Strong' rating is based on this whole body of evidence. The Cochrane review of medicines in LGS (Brigo 2021) included the two CBD studies. Because the information in the two studies' publications was not enough to calculate the response rate for all seizure types (the studies' main outcome was drop seizures), the review remained uncertain about whether CBD reduces all seizures; it did, however, find with high certainty that stopping because of side effects was more common with CBD (RR 6.62). This uncertainty comes not from a result pointing the other way but from this outcome not being reported in the studies; the guide's rating is based on drop seizures, the studies' main outcome. In a network meta-analysis comparing LGS treatments, CBD's effect on drop seizures was not significantly different from other LGS medicines such as clobazam, rufinamide and fenfluramine; high-dose clobazam was ahead in the ranking, but there are no studies comparing the medicines directly, and the comparisons are indirect (Zhu 2025). In the open-label extension of the two RCTs, the median reduction in drop seizures in 366 patients stayed between 48% and 71% for up to 156 weeks; according to the final results on ClinicalTrials.gov (a registry, not a peer-reviewed publication), 243 of the patients completed the study, and the median reduction in drop seizures over each patient's last 12 weeks in the study, including those who left early, was 59%; liver enzymes rose markedly in 15% of patients, most of whom were taking valproate (Patel 2021). Everyday-practice studies from France and Germany and two studies in adults with LGS in England point in the same direction, while in a small study of children from Korea the response decreased at month 6; these have no comparison group, and most have manufacturer funding or authors with financial ties to the manufacturer. There is no controlled study of unlicensed cannabis products in LGS. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 2 controlled treatment studies with cannabinoids and 7 systematic reviews (one of them Cochrane) were found on this topic; these appear in the table below, together with a manufacturer-supported pooled analysis of the same studies, 10 studies without a comparison group (long-term extension, access programs, everyday practice, and unlicensed or THC-containing products), and 2 drug-level studies measuring drug interactions, mainly with clobazam (one placebo-controlled in patients with epilepsy, one in healthy volunteers). No controlled study of THC-containing products in LGS was found.

Evidence assessment: Strong (double-blind, placebo-controlled RCTs + meta-analyses)

• CBD alone: The approved, purified pharmaceutical CBD reduced drop seizures as an add-on treatment in Lennox–Gastaut syndrome; this evidence does not apply to unregulated CBD oils.
• Products containing THC: There is no controlled study of THC-containing products in Lennox–Gastaut syndrome. The only data come from a small observational study: in 29 people (11 with LGS) followed for at least 24 weeks on two CBD-rich, low-THC cannabis products (at most 6 mg of THC a day), no significant change in seizure frequency was seen. (insufficient evidence) Evidence: Insufficient: there is no controlled study of a THC-containing product in LGS; there is only a small observational study without a comparison group that included 11 LGS patients
• Approval: FDA (≥1 year, no clobazam requirement): start at 2.5 mg/kg twice daily (5 mg/kg/day); after 1 week, the maintenance dose is 5 mg/kg twice daily (10 mg/kg/day). If further seizure reduction is needed, increase weekly by 2.5 mg/kg twice daily up to a maximum of 10 mg/kg twice daily (20 mg/kg/day); for faster titration, increases no more often than every other day. Label: 20 mg/kg/day gives slightly more seizure reduction but more side effects. EMA (≥2 years, add-on treatment only together with clobazam): 5 mg/kg/day for 1 week, then maintenance 10 mg/kg/day; increases above 10 mg/kg/day only with an individual benefit–risk assessment and a full monitoring schedule, maximum 20 mg/kg/day. Liver impairment: moderate (Child-Pugh B) start at 1.25 mg/kg twice daily, severe (Child-Pugh C) 0.5 mg/kg twice daily. Stopping is done gradually. Source: FDA label (05/2026) §2.1–2.2, §2.5–2.6; EMA product information §4.1–4.2 (last updated in the EPAR on August 20, 2026). Turkey: Epidyolex/cannabidiol is not on the list of licensed products of TİTCK (Turkish Medicines and Medical Devices Agency) (October 16, 2026); however, on TİTCK's Foreign Active Substance List (September 28, 2026), cannabidiol oral solution (YDN02BG1099) is listed as a red-prescription medicine among those that cannot be imported without TİTCK's written approval.
• Dose range in studies: In the labeling and RCTs, 10–20 mg/kg/day (split into two equal doses); in the open-label expanded access program, up to a ceiling of 25–50 mg/kg/day; in the open-label extension study, at most 30 mg/kg/day (mean 24 mg/kg/day); in everyday-practice studies in Europe and England, the median dose was mostly 10–15 mg/kg/day
• Starting dose and titration (in studies): Labeling: start at 5 mg/kg/day, then 10 mg/kg/day after 1 week; if needed, increase weekly by 5 mg/kg/day up to a maximum of 20 mg/kg/day. In the RCTs, a 2-week titration (to 10 mg/kg/day in 7 days, to 20 mg/kg/day in 11 days), followed by 12 weeks of maintenance
• Interaction: Clobazam: CBD increases the active metabolite N-desmethylclobazam ~3-fold (FDA) / 3–4-fold (EMA) (total exposure 2.6-fold in a placebo-controlled study in epilepsy patients taking clobazam, VanLandingham 2020; 3.4-fold in healthy volunteers, Morrison 2019); clobazam also increases 7-OH-CBD (AUC 47%). If drowsiness occurs, lowering the clobazam dose is considered
• Interaction: Valproate: liver enzyme elevations increase markedly; diarrhea and decreased appetite also increase (EMA). If enzymes rise, CBD and/or valproate is reduced or stopped
• Interaction: Stiripentol: in healthy volunteers, Cmax increased 28% and AUC 55%; in patients, Cmax increased 17% and AUC 30%. Side effects are monitored closely
• Interaction: Everolimus: exposure increases ~2.5-fold; levels are monitored, and in a patient taking CBD, everolimus is started at a lower dose
• Interaction: Topiramate, rufinamide, zonisamide, eslicarbazepine: in an open-label study, serum levels rose as the CBD dose increased (most stayed within the therapeutic range)
• Interaction: Sirolimus, tacrolimus, digoxin (oral P-gp substrates): exposure may increase; level monitoring and dose reduction are considered
• Interaction: Strong CYP3A4/CYP2C19 inducers (rifampin; EMA: carbamazepine, enzalutamide, mitotane, St. John's wort): rifampin reduced CBD by ~32% and 7-OH-CBD by ~63% (FDA); FDA (05/2026): with a strong inducer, increasing the Epidiolex dose up to at most 2-fold may be considered based on response and tolerability
• Interaction: CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC increased 95%; dose reduction is considered for narrow-range medicines
• Interaction: CYP2C19 prodrugs such as clopidogrel: the active metabolite may decrease
• Interaction: Alcohol and other CNS depressants: drowsiness and sedation increase; alcohol also increases CBD exposure (Cmax 93%, AUC 63%)
• Monitoring in studies: ALT, AST, and total bilirubin before starting (FDA and EMA)
• Monitoring in studies: Liver tests at months 1, 3, and 6, then periodically or as clinically needed
• Monitoring in studies: FDA: within 1 month after a dose change or after adding a medicine that affects the liver; EMA: the monitoring schedule starts over when the dose goes above 10 mg/kg/day or when a medicine that affects the liver is changed
• Monitoring in studies: People taking valproate and those with high baseline ALT/AST: per the EMA, at week 2 and at months 1, 2, 3, and 6, then periodically
• Monitoring in studies: Stopping rule (FDA and EMA): CBD is stopped if transaminases are >3×ULN and bilirubin is >2×ULN, or if transaminases are persistently >5×ULN
• Monitoring in studies: If liver symptoms occur (unexplained nausea, vomiting, right upper abdominal pain, fatigue, loss of appetite, jaundice, dark urine), check ALT/AST/bilirubin right away
• Monitoring in studies: Blood levels and side effects of concomitant antiepileptic drugs (Gaston 2017, PMID 28782097)

References (22)

Study table (dose, duration, result) · Topic page

In a single double-blind RCT (GWPCARE6), prescription pure CBD reduced TSC-associated seizures more than placebo over 16 weeks (48.6% vs. 26.5%). For the prespecified key secondary endpoint, the share of patients whose seizures were at least halved, the difference was not statistically significant (36% vs. 22.4%; p = 0.0692; European product information). 50 mg/kg/day showed no additional benefit over 25 mg/kg/day, but side effects increased. People taking oral mTOR inhibitors (everolimus, sirolimus) were not included in the study; data on use with these medicines come only from uncontrolled and observational studies. In the open-label extension of the same study (199 patients, mean 27 mg/kg/day), the reduction in seizures persisted for 48 weeks (median 54–68%); because there was no control group, this part shows durability rather than efficacy; liver enzyme increases occurred in 9%, mostly in those taking valproate; in the final results on ClinicalTrials.gov (follow-up of up to 4 years, no peer-reviewed publication), ≥50% response was 106/199 and discontinuation due to side effects was 18/199. Other data without a comparison group point in the same direction: in 34 TSC patients in the expanded access program, the median reduction in total seizures over 12-week periods stayed between 44% and 87% for 144 weeks (36–74% when those who stopped were counted with their last values; Weinstock 2024); in a 27-center retrospective real-world study, among patients who took CBD for at least 3 months, the share whose seizures were at least halved was 55.9% in the group of 36 patients with a change in the TSC2 gene and 2/5 in the 5 patients with a change in TSC1 (Cerulli Irelli 2025). These studies show durability and results in everyday practice, not efficacy; because those who stopped the medicine early were not included in the analysis or in later periods, the results may be skewed in a favorable direction. In a small retrospective series, 6 of 7 renal angiomyolipomas and 3 of 3 subependymal giant cell tumors grew during CBD treatment; there was no comparison group (Barnett 2020). Meta-analyses add no new data for TSC; their TSC estimates are again based on GWPCARE6 (Talwar 2023: OR 1.99 for ≥50% response; 95% CI 1.06–3.76). This estimate most likely combines the two dose groups; the approved dose alone was not significant on this measure. The evidence rests on a single RCT, and doses below 25 mg/kg/day have not been studied in TSC (FDA). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 1 controlled study and 3 reviews (2 of them meta-analyses) of cannabinoids on this topic were found; these are in the table below, together with 2 long-term studies without a comparison group, 1 drug interaction study in healthy volunteers, and 4 observational studies. There is no Cochrane review covering TSC. No study with published results in TSC was found for a product known to contain THC; a retrospective cohort from Israel also includes "CBD-based products" with unstated THC content (Shlomovitz 2021), and a placebo-controlled study of full-spectrum cannabis extract is ongoing in Spain (THC content not stated in the registry; NCT07403266).

Evidence assessment: Moderate (a single pivotal RCT; no second controlled study)

• CBD alone: The approved, purified pharmaceutical CBD reduced seizures in TSC as an add-on treatment; this result cannot be applied to unregulated CBD products.
• Products containing THC: There is no controlled study with published results using THC-containing products in tuberous sclerosis (October 2026 search). In a retrospective patient cohort from Israel, a response of about 30–40% was reported with CBD-based products whose THC content was not stated; these data without a comparison group do not show an effect. A placebo-controlled study of full-spectrum cannabis extract is ongoing in Spain (NCT07403266). (insufficient evidence) Evidence: THC-containing: Insufficient; no controlled study with results
• Approval: FDA (≥1 year): start at 2.5 mg/kg twice daily (5 mg/kg/day); increase weekly by 2.5 mg/kg twice daily (5 mg/kg/day) as tolerated; for faster titration, no more often than every other day. Recommended maintenance 12.5 mg/kg twice daily (25 mg/kg/day); the efficacy of doses below 25 mg/kg/day has not been studied in TSC. EMA (≥2 years, add-on treatment, no clobazam requirement): 5 mg/kg/day for 1 week, 10 mg/kg/day in week 2 (response and tolerability are assessed), then weekly increases of 5 mg/kg/day; above 10 mg/kg/day only with a benefit–risk assessment and full monitoring, maximum 25 mg/kg/day. In moderate liver impairment, 6.25 mg/kg twice daily for TSC; in severe impairment, 2.5 mg/kg twice daily (the maintenance dose in the FDA label, the maximum dose in the EMA label). Source: FDA label (05/2026) §2.3, §2.6; EMA product information §4.2, Table 2 (last updated in the EPAR on August 20, 2026). Turkey: Epidyolex/cannabidiol is not on the list of licensed products of TİTCK (Turkish Medicines and Medical Devices Agency) (October 16, 2026); however, on TİTCK's Foreign Active Substance List (September 28, 2026), cannabidiol oral solution (YDN02BG1099) is listed as a red-prescription medicine among those that cannot be imported without TİTCK's written approval.
• Dose range in studies: 25 or 50 mg/kg/day in the RCT; recommended maintenance in the labeling 25 mg/kg/day
• Starting dose and titration (in studies): Labeling: start at 5 mg/kg/day, increase by 5 mg/kg/day weekly to a maintenance dose of 25 mg/kg/day; 4-week titration in the RCT (25 mg/kg/day reached in 9 days)
• Interaction: Clobazam: CBD increases the active metabolite N-desmethylclobazam ~3-fold (FDA) / 3–4-fold (EMA); clobazam also increases 7-OH-CBD (AUC 47%). If drowsiness occurs, lowering the clobazam dose is considered
• Interaction: Valproate: liver enzyme elevations increase markedly; diarrhea and decreased appetite also increase (EMA). If enzymes rise, CBD and/or valproate is reduced or stopped
• Interaction: Stiripentol: in healthy volunteers, Cmax increased 28% and AUC 55%; in patients, Cmax increased 17% and AUC 30%. Side effects are monitored closely
• Interaction: Everolimus: exposure increases ~2.5-fold (in healthy volunteers, CBD 25 mg/kg a day with a single dose of everolimus; Wray 2023); levels are monitored, and in a patient taking CBD, everolimus is started at a lower dose
• Interaction: Topiramate, rufinamide, zonisamide, eslicarbazepine: in an open-label study, serum levels rose as the CBD dose increased (most stayed within the therapeutic range)
• Interaction: Sirolimus, tacrolimus, digoxin (oral P-gp substrates): exposure may increase; level monitoring and dose reduction are considered
• Interaction: Strong CYP3A4/CYP2C19 inducers (rifampin; EMA: carbamazepine, enzalutamide, mitotane, St. John's wort): rifampin reduced CBD by ~32% and 7-OH-CBD by ~63% (FDA); FDA (05/2026): with a strong inducer, increasing the Epidiolex dose up to 2-fold may be considered based on response and tolerability
• Interaction: CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC increased 95%; dose reduction is considered for drugs with a narrow therapeutic range
• Interaction: CYP2C19 prodrugs such as clopidogrel: the active metabolite may decrease
• Interaction: Alcohol and other CNS depressants: drowsiness and sedation increase; alcohol also increases CBD exposure (Cmax 93%, AUC 63%)
• Interaction: mTOR inhibitors in TSC: in an observational study (n=25), everolimus/sirolimus levels rose in 76% of patients; median +9.8 ng/mL (everolimus), +5.1 ng/mL (sirolimus), 2–3-fold in some (Ebrahimi-Fakhari 2020, PMID 31924480)
• Monitoring in studies: ALT, AST, and total bilirubin before starting (FDA and EMA)
• Monitoring in studies: Liver tests at months 1, 3, and 6, then periodically or as clinically needed
• Monitoring in studies: FDA: within 1 month after a dose change or after adding a medicine that affects the liver; EMA: the monitoring schedule starts over when the dose goes above 10 mg/kg/day or when a medicine that affects the liver is changed
• Monitoring in studies: People taking valproate and those with high baseline ALT/AST: per the EMA, at week 2 and at months 1, 2, 3, and 6, then periodically
• Monitoring in studies: Stopping rule (FDA and EMA): CBD is stopped if transaminases are >3×ULN and bilirubin is >2×ULN, or if transaminases are persistently >5×ULN
• Monitoring in studies: If liver symptoms occur (unexplained nausea, vomiting, right upper abdominal pain, fatigue, loss of appetite, jaundice, dark urine), check ALT/AST/bilirubin right away
• Monitoring in studies: Blood levels and side effects of concomitant antiepileptic drugs (Gaston 2017, PMID 28782097)

References (11)

Study table (dose, duration, result) · Topic page

In adults with drug-resistant focal epilepsy, a synthetic CBD gel applied to the skin (a daily total of 195 or 390 mg, divided into two applications) did not change seizure frequency differently from placebo in a 188-person double-blind RCT. In a small 27-person controlled study in frontal lobe epilepsy, liposomal CBD by mouth (up to 210 mg/day) was reported to improve seizures; however, the change in seizure frequency over time was not statistically different between the two groups (p = 0.187), the difference in the proportion of patients who improved at week 8 was also not significant (p = 0.069), at baseline the CBD group's monthly seizure count was about 2.5 times that of the control group (86.5 vs. 34.0), and the publication is not clear about whether the control group received placebo. An expanded access program reported seizure reductions for up to 144 weeks in 140 patients with focal epilepsy, but there is no control group. In other drug-resistant epilepsies such as CDKL5 deficiency, Aicardi, Dup15q and Doose, there are only open-label data without a placebo arm; seizure reductions were reported, but because reductions of 13–27% were also seen in the placebo arms of the approved medicine's RCTs, these findings cannot be counted as a drug effect. There is no approval for these epilepsies. Data on unregulated CBD/cannabis oils are mostly retrospective parent reports; in a prospective study that recorded seizures for 4 weeks before treatment, the response rate was at placebo level, and increased seizures have been reported. The manufacturer's studies in epilepsy with myoclonic-atonic seizures (NCT05288283; 2 patients randomized, ended by a business decision) and in children under 2 years (NCT04485104; 3 patients, ended due to low enrollment) produced no interpretable efficacy data. In a pilot study in infantile spasms (9 babies, 40 mg/kg/day, 2 weeks), the spasms did not stop in any baby; the randomized phase was not started. In a double-blind RCT in 162 adults with focal seizures using CBDV, a plant compound closely related to CBD, seizures fell similarly in both groups (40.5% vs. 37.7%; p = 0.648; manufacturer funding). Old controlled trials of pure CBD by mouth are very small: the 15-patient placebo-controlled study from 1980 has no statistical comparison; together with three small trials from the same period, one published as a letter to the editor and one as a conference abstract (48 patients in total), a Cochrane review (search 2013) wrote that no reliable conclusions can be drawn from these reports. In childhood absence epilepsy, in an uncontrolled study of 20 children by the maker of a synthetic CBD (results only on ClinicalTrials.gov, no peer-reviewed publication), the mean change in absence seizures counted on EEG, one of the primary outcomes, was not in the direction of a decrease (+41% and +35% in the two dose groups; highly variable from patient to patient), while the other primary outcome, time to first absence with hyperventilation, became longer; because the two outcomes pointed in different directions, the result is unclear. In real-world studies (Germany, France, Denmark, Colombia), the proportion of patients with off-label diagnoses whose seizures fell by at least half was reported as between 22% and 69%; in the comparisons in Germany and France, this rate was close to that in approved diagnoses, while in the Danish study it was clearly lower (22% vs. 70% at month 3). None of these studies has a control group; seizure outcomes rely on doctors' notes, seizure diaries and family reports, and some of those who stopped early are left out of the analysis. Two systematic reviews pooling epilepsies other than Dravet syndrome and LGS (2021 and 2026; the second was funded by the manufacturer) found only open-label data apart from TSC; 33 of the 57 studies in the 2026 review were case reports or small series. The UK's national guideline (NICE 2019) made no practice recommendation for cannabis-based products in these epilepsies, nor a recommendation against their use; it called for research into the efficacy of CBD in these epilepsies and into the effect of adding THC to CBD compared with CBD alone and with placebo. There are no controlled studies of CBD-rich products that contain THC or have an unknown THC content: in the only structured study, which prospectively followed 29 patients on a low-THC product, seizures did not change; the high response rates reported in open-label series in Israel and Colombia and the improvement reported in a national cohort in Thailand have no comparison group (evidence for THC is very weak). In unregulated products: in a pooled analysis of observational studies comparing CBD-rich extracts with purified CBD, the proportion of patients whose seizures fell by at least half was similar in both groups (37% vs. 42%; uncontrolled studies, and all three authors of the analysis had ties to cannabis companies); in product analyses, content often differed from the label, and THC, solvents, heavy metals and pesticides were found; in spontaneous side effect reports in Europe, in about 39% of serious reports involving unlicensed CBD, the product was being used for epilepsy. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 4 controlled studies with cannabinoids on this topic (one with CBDV instead of CBD) and more than 30 systematic reviews of cannabinoid use in epilepsy were found (most rely on studies in Dravet syndrome, LGS and TSC); all the controlled studies, the 4 reviews most relevant to these epilepsies (including Cochrane) and the UK's national guideline are in the table below. The three small trials from 1978–1990 in the Cochrane review are not separate rows; they are mentioned in the review's row. The other studies in the table are open-label or observational studies without a comparison group, and product analyses; later publications from the same programs and studies with overlapping patients are in the other sources section of the relevant row.

Evidence assessment: Weak (mostly uncontrolled, open-label; Class III); in adult focal epilepsy, two large RCTs (CBD applied to the skin and CBDV, a compound closely related to CBD) were negative; in real-world studies, response rates reported in off-label diagnoses were mostly close to those in approved diagnoses (clearly lower in one study), but all are uncontrolled. Unregulated ('artisanal') CBD/cannabis oils: Very low

• CBD alone: Purified medicinal CBD has mostly been tested in uncontrolled studies in other drug-resistant epilepsies; in adult focal epilepsy, CBD applied to the skin in a 188-person RCT, and CBDV, a compound closely related to CBD, in a 162-person RCT, were no different from placebo; in real-world studies, seizures fell by at least half in 22% to 69% of patients using it off-label, but none of these studies has a comparison group; with unregulated CBD oils, the effect stayed at placebo level, and dose and content are unreliable.
• Products containing THC: Some unregulated products contain THC; the effect of THC-containing cannabis extracts has not been shown in controlled studies: in the only structured study, which prospectively followed 29 patients taking low-THC tablets, seizures did not change; the high response rates reported in open-label series in Israel and Colombia with CBD-rich oils containing small amounts of THC have no comparison group. In Australia, families believed CBD was dominant in most of the extracts they used, but THC or the raw form of THC (THCA) was found in 98% of the samples. (very weak evidence) Evidence: Very weak (no controlled studies; no effect was seen in the only prospective structured study, and the other data come from uncontrolled series and unregulated oils)
• Approval: Not approved. CBD's approval as a medicine covers only seizures in Dravet syndrome, Lennox–Gastaut syndrome and TSC, and covers only purified, standard-dose medicinal CBD (Epidiolex/Epidyolex, 100 mg/ml). In Turkey, medicinal CBD is not approved (list of TİTCK, the Turkish Medicines and Medical Devices Agency, October 16, 2026). On the TİTCK Foreign Active Ingredient List (September 28, 2026), cannabidiol oral solution (YDN02BG1099) is listed as a red-prescription medicine and among the medicines that cannot be imported without TİTCK's written approval.
• Dose range in studies: In open-label studies, starting at 2–10 mg/kg/day, up to a ceiling of 25–50 mg/kg/day; in children using unregulated oils, median highest dose 0.9 mg/kg/day; CBD gel on the skin, a daily total of 195 or 390 mg, divided into two applications (focal epilepsy RCT); in frontal lobe epilepsy, 70–210 mg/day by mouth; CBDV in focal seizures up to 1,600 mg per day (RCT); synthetic CBD in childhood absence epilepsy 20 or 30 mg/kg/day
• Starting dose and titration (in studies): In open-label studies, gradual increase varying by center; no common schedule reported
• Interaction: Clobazam: CBD increases the active metabolite N-desmethylclobazam ~3-fold (FDA) / 3–4-fold (EMA); clobazam also increases 7-OH-CBD (AUC 47%). If sleepiness occurs, reducing the clobazam dose is considered
• Interaction: Valproate: raised liver enzymes increase markedly; diarrhea and decreased appetite also increase (EMA). If enzymes rise, CBD and/or valproate is reduced or stopped
• Interaction: Stiripentol: in healthy volunteers, Cmax up 28%, AUC 55%; in patients, Cmax up 17%, AUC 30%. Side effects are monitored closely
• Interaction: Everolimus: exposure increases ~2.5-fold; levels are monitored, and in patients taking CBD, everolimus is started at a lower dose
• Interaction: Topiramate, rufinamide, zonisamide, eslicarbazepine: in an open-label study, serum levels rose as the CBD dose increased (most stayed within the therapeutic range)
• Interaction: Sirolimus, tacrolimus, digoxin (oral P-gp substrates): exposure may increase; level monitoring and dose reduction are considered
• Interaction: Strong CYP3A4/CYP2C19 inducers (rifampin; EMA: carbamazepine, enzalutamide, mitotane, St. John's wort): rifampin lowered CBD by ~32% and 7-OH-CBD by ~63% (FDA); FDA (05/2026): with a strong inducer, increasing the Epidiolex dose up to at most 2-fold may be considered, based on response and tolerability
• Interaction: CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC rose 95%; dose reduction is considered for narrow-range medicines
• Interaction: CYP2C19 prodrugs such as clopidogrel: the active metabolite may decrease
• Interaction: Alcohol and other CNS depressants: sleepiness and sedation increase; alcohol also increases CBD exposure (Cmax 93%, AUC 63%)
• Monitoring in studies: Before starting: ALT, AST and total bilirubin (FDA and EMA)
• Monitoring in studies: Liver tests at months 1, 3 and 6, then periodically or as clinically needed
• Monitoring in studies: FDA: within 1 month after a dose change or after adding a medicine that affects the liver; EMA: the monitoring schedule restarts when the dose goes above 10 mg/kg/day or when a medicine affecting the liver is changed
• Monitoring in studies: People taking valproate and those with high baseline ALT/AST: per EMA, at week 2 and months 1, 2, 3 and 6, then periodically
• Monitoring in studies: Stopping rule (FDA and EMA): CBD is stopped if transaminases are >3×ULN and bilirubin >2×ULN, or if transaminases stay >5×ULN
• Monitoring in studies: If liver symptoms occur (unexplained nausea, vomiting, upper right abdominal pain, tiredness, loss of appetite, jaundice, dark urine), check ALT/AST/bilirubin right away
• Monitoring in studies: Blood levels and side effects of antiseizure medicines used at the same time (Gaston 2017)

References (40)

Study table (dose, duration, result) · Topic page

A 15-week, 178-person RCT in India reported a very large effect (6 of the 7 authors are executives or employees of pharmaceutical companies; the reported spread is unusually small for a psychiatry study); its dose is unknown, the result has not been independently repeated, and in November 2024 the drug regulator's expert committee questioned the absence of a placebo response in the placebo group of a phase 3 application whose features match this study (178 people, 150 mg/mL CBD solution, mild to moderate anxiety disorder; no trial identifier in the minutes). In May 2026, the same committee recommended approving the product on condition that a phase 4 study comparing it with an active medicine be done and that it be sold only with a psychiatrist's prescription; this recommendation is not the result of an independent repeat, and the approval document itself could not be found. In people with high levels of worry, 300 mg/day for 2 weeks did not reduce worry, and anxiety symptoms decreased somewhat. Other placebo-controlled studies measuring anxiety found no difference: a single 400 mg dose for pre-scan anxiety in advanced breast cancer (n=50; Nayak 2024), a CBD-rich extract before root canal treatment (de Andrade Silva 2024) and a low-dose full-spectrum oil for 30 days in stressed students (n=180; Winkler 2025); anxiety also did not improve with early access to medical cannabis by lottery for anxiety or depression (n=83; Gilman 2022). In a small double-blind part comparing full-spectrum and pure CBD with placebo (31 people; NCT02548559, no peer-reviewed publication), self-reported anxiety fell clearly in all groups, including placebo, and interviewer-rated anxiety fell more in the CBD arms; in the registry, the groups were not compared statistically. Positive results in open-label studies therefore cannot be separated from the expectation effect. The small nabilone (a synthetic THC-like cannabinoid) studies from 1978–1981 are inconsistent (Fabre 1981 positive; Glass 1980 and Nakano 1978 weak or ineffective). In artificially created anxiety in the lab, single-dose results are inconsistent: no effect was seen on exam anxiety, in emotional face tasks or in a virtual reality paranoia setting; results in lab anxiety do not substitute for treatment of anxiety disorders. THC can increase anxiety in the lab (Hutten 2022; at a high dose in Childs 2017); a low dose of THC slightly reduced distress after a stress test (n=42; Childs 2017); in regular users, the stress-reducing effect of vaporized THC was similar to placebo (n=120; Cuttler 2026). Meta-analyses find the evidence of low or very low certainty: in RCTs in people whose primary diagnosis is a mental disorder, no significant difference from placebo for anxiety (Wilson 2026); in the analysis that also included anxiety measured as a secondary outcome in other diseases, a small to moderate reduction, but very low certainty (Bharat 2026); in the analysis split by drug type, no cannabinoid alone is significant (Bilbao 2022). Real-world data go both ways: in a UK patient registry, patients mostly prescribed THC-rich flower reported reduced anxiety (no control; most of the authors are linked to the clinic chain that runs the registry; Rifkin-Zybutz 2023), while in a 5,075-person registry in Canada the average change was clinically meaningless (Lee 2022). The pooled association between cannabis use and later development of generalized anxiety disorder is not significant (OR 1.44; 95% CI 0.94–2.22; observational; Xue 2021). The anxiety disorder guidelines that could be read (Germany 2022, Brazil 2024) do not mention cannabinoids. Studies in social anxiety, panic disorder and PTSD are on their own pages. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 21 controlled studies with cannabinoids on this topic were found; 11 in patients or people experiencing anxiety or stress (8 placebo-controlled; only 1 placebo-controlled study with more than 100 people was done in patients diagnosed with an anxiety disorder; the follow-up publication of one is also in the table), 10 in volunteers in a lab or experimental setting (THC was also tested in 3). Alongside these, the table has 4 studies with no control group, 7 systematic reviews (5 of them meta-analyses) and 5 observational studies (one a meta-analysis of observational studies). Older lab experiments and meta-analyses whose question is answered by a newer or larger study or review in the table were not added separately. No Cochrane review and no treatment study from Turkey were found.

Evidence assessment: Weak: the only positive large RCT has not been independently repeated; the other controlled studies are small and most found no difference from placebo

• CBD alone: The results of controlled anxiety studies with pure CBD are mixed; the only large positive RCT has not been repeated and its dose was not reported in the abstract. In anxious cancer patients, a single 400 mg dose was no different from placebo on the primary outcome; of the two meta-analyses that looked at CBD separately, one found an effect in the pure CBD subgroup (wide confidence interval) and the other did not; in both, the certainty of the evidence is low.
• Products containing THC: There are no controlled studies showing a benefit of THC-containing products in anxiety disorders. In a small double-blind part with a low-THC full-spectrum product, self-reported anxiety decreased in all groups, including placebo, and interviewer-rated anxiety decreased more in those taking the full-spectrum product; but nearly half of this arm came from the open-label first phase and the groups were not compared statistically (registry only). In an RCT giving access to medical cannabis by lottery, anxiety did not improve; in a study without placebo comparing cannabis flowers, THC-dominant flower was linked to a smaller drop in anxiety than CBD-dominant flower. In the lab, THC and THC+CBD increased state anxiety (THC+CBD less than THC alone); a low dose of THC slightly reduced distress after stress, and a higher dose increased anxiety. (very weak evidence) Evidence: Very weak: there are no controlled studies showing a benefit of THC-containing products in anxiety disorders; there is a small double-blind part whose groups were not compared statistically (registry only), a negative RCT that assigned access to medical cannabis by lottery, and data without placebo and observational data. Lab findings go both ways: increased anxiety at high doses, a slight reduction in distress after stress at low doses
• Dose range in studies: In controlled studies, 30–300 mg/day (2–4 weeks) and, in one study, a low dose increased step by step according to body weight (at most 1 mg/kg/day); single doses 32–600 mg; in open-label studies about 30–800 mg/day; in an uncontrolled case series 25–175 mg/day
• Starting dose and titration (in studies): The only anxiety study that reported the dose-increase schedule in detail is Berger 2022: it started at 200 mg/day and, if the response was inadequate, increased in 200 mg steps (at most 400 at week 1, 600 at week 4 and 800 mg/day at week 8). Most other controlled studies used a fixed dose; in stressed students, a low-dose full-spectrum oil was increased step by step according to body weight over 30 days (Winkler 2025); the schedule of Gundugurti 2024 is unknown
• Interaction: Citalopram/escitalopram: when CBD (200–800 mg/day) was added, citalopram blood levels rose significantly in 6 patients; in the lab, breakdown through CYP3A4 and CYP2C19 was inhibited (Anderson 2021, PMID 34121064)
• Interaction: Sertraline, fluoxetine, mirtazapine: in the lab, CBD affected their breakdown very little; not measured in patients (Anderson 2021, PMID 34121064)
• Interaction: In people taking serotonergic antidepressants, CBD affected the re-extinction of subjective fear worse than placebo (Kwee 2024, PMID 38044339, exploratory subgroup)
• Interaction: Clobazam: in 13 children with epilepsy, the active metabolite N-desmethylclobazam rose by an average of 500%; the rise in clobazam itself (average 60%) was uncertain (confidence interval −2 to 91). In healthy volunteers, clobazam did not change and the metabolite rose ~3-fold (FDA/EMA). Side effects in 10 of 13 patients, which resolved when the clobazam dose was reduced (Geffrey 2015, PMID 26114620)
• Interaction: Other benzodiazepines (alprazolam, clonazepam, etc.): no direct interaction study was found in an anxiety population
• Interaction: THC-containing products: CBD does not consistently reduce THC's effects; full-spectrum products may contain THC (e.g., 0.23 mg/mL)
• Interaction: Antipsychotic + 1000 mg/day CBD (schizophrenia) was well tolerated (McGuire 2017, PMID 29241357)
• Interaction: No direct interaction study was found with venlafaxine, duloxetine, pregabalin, buspirone or hydroxyzine
• Monitoring in studies: With long-term use, monitoring of liver tests is the physician's decision

References (38)

Study table (dose, duration, result) · Topic page

No RCT testing CBD on its own in panic disorder was found. In treatment-resistant panic disorder and social anxiety, adding 300 mg of CBD to exposure therapy gave no benefit. In a study in healthy volunteers using inhalation of 10% CO₂ (a panic model), no effect was seen at any dose. The review reporting a positive result (Soares 2017) relies on animal, healthy volunteer and social anxiety patient data; it includes no panic disorder patients. The two most recent reviews gathering cannabinoid RCTs in mental health conditions add no new data for panic disorder: in a meta-analysis of 54 RCTs, there was no significant difference between cannabinoids and placebo in anxiety-related outcomes, and no separate result is given for panic disorder (Wilson 2026; certainty of evidence low for most outcomes); a scoping review of RCTs found no RCT targeting panic disorder (Cooling 2026). There is no treatment study of THC-containing products in panic disorder. Prospective observational studies looking at whether panic disorder develops later with recreational cannabis use are conflicting: in a cohort followed from adolescence to young adulthood, cannabis use and dependence were associated with panic disorder, but the association disappeared once daily smoking and other substance dependencies were taken into account (Zvolensky 2008); in adults in the Netherlands, the association was not significant after adjustment (van Laar 2007); one analysis from the US national follow-up (NESARC) found that weekly use predicted panic disorder with agoraphobia (Cougle 2015; the size of the risk is not in the abstract), while another from the same data found no significant association between cannabis dependence and panic disorder and, conversely, showed that people with panic disorder at baseline started cannabis more often (Feingold 2016); in a meta-analysis pooling van Laar 2007, Zvolensky 2008 and Feingold 2016 from these three cohorts, the association was not significant (OR 1.52; 95% CI 0.96–2.40; Xue 2021). In patients being treated for panic disorder, using cannabis at least once a month did not change the effect of treatment on panic symptoms (Bricker 2007; observational secondary analysis of a trial). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 2 controlled studies with cannabinoids on this topic were found (one with CBD added to therapy in patients, one a lab study in healthy volunteers; the fear-conditioning substudy of the first was published separately and is mentioned in the main study’s row in the table); there are no controlled studies with THC-containing products, no Cochrane review, and no study with registered but unpublished results. Besides these, the table has 2 recent reviews gathering cannabinoid trials in mental health conditions, 1 meta-analysis on cannabis use and panic disorder risk, 5 observational studies and 1 narrative review.

Evidence assessment: Insufficient

• CBD alone: There is no controlled human study showing an effect of pure CBD in panic disorder; the existing controlled data are negative.
• Products containing THC: No treatment study of THC-containing products (cannabis, THC, nabilone, dronabinol, a mouth spray containing THC and CBD) in panic disorder was found. The results of observational studies following recreational cannabis use over years do not agree with each other: in some, panic disorder was later seen more often in cannabis users, in others it was not; in the analysis pooling three follow-up studies, the link was not statistically clear. In one study the link disappeared once smoking was taken into account; in another, people with panic disorder were more likely to start cannabis later, meaning the link may go both ways. There is no evidence for treatment; because the findings on risk are only observational and conflicting, they are weak and do not show cause and effect. (insufficient evidence) Evidence: Insufficient: no treatment studies; findings on cannabis use come only from observational studies
• Dose range in studies: In controlled studies, 300 mg (before a therapy session) and 150–600 mg single doses
• Interaction: Citalopram/escitalopram: when CBD (200–800 mg/day) was added, citalopram blood levels rose significantly in 6 patients; in the lab, breakdown via CYP3A4 and CYP2C19 was inhibited (Anderson 2021, PMID 34121064)
• Interaction: Sertraline, fluoxetine, mirtazapine: in the lab, CBD affected breakdown very little; not measured in patients (Anderson 2021, PMID 34121064)
• Interaction: In people taking serotonergic antidepressants, CBD affected the re-extinction of subjective fear worse than placebo (Kwee 2024, substudy of the Kwee 2022 trial; exploratory subgroup)
• Interaction: Clobazam: in 13 children with epilepsy, the active metabolite N-desmethylclobazam rose by an average of 500%; the rise in clobazam itself (average 60%) was uncertain (confidence interval −2 to 91). In healthy volunteers, clobazam did not change and the metabolite rose ~3-fold (FDA/EMA). In 10 of 13 patients, side effects resolved when the clobazam dose was reduced (Geffrey 2015, PMID 26114620)
• Interaction: Other benzodiazepines (alprazolam, clonazepam, etc.): no direct interaction study in an anxiety population was found
• Interaction: THC-containing products: CBD does not consistently reduce THC’s effects; full-spectrum products may contain THC (e.g., 0.23 mg/mL)
• Interaction: Antipsychotic + 1000 mg/day CBD (schizophrenia) was well tolerated (McGuire 2017, PMID 29241357)
• Interaction: No direct interaction study was found with venlafaxine, duloxetine, pregabalin, buspirone or hydroxyzine
• Monitoring in studies: With long-term use, monitoring of liver tests is the physician’s decision

References (11)

Study table (dose, duration, result) · Topic page

In untreated patients with social anxiety, a single 600 mg dose reduced public speaking anxiety (n=24); a single 400 mg dose reduced subjective anxiety (n=10). In 37 young people aged 18–19, 300 mg/day for 4 weeks was found positive; but the randomization method was not described, 3 people who dropped out were left out of the analysis, side effects were not systematically monitored, and another CBD study by the author (2025, in cats) was retracted for lack of ethics approval (the journal's retraction notice dated June 2026). In treatment-resistant patients, adding 300 mg to exposure therapy gave no benefit (n=80). In healthy volunteers, only the medium dose (300 mg) appeared effective in the speaking test ('inverted U'); this finding could not be repeated in other anxiety models. Other controlled laboratory studies are not consistent either: in patients with Parkinson's disease, a single 300 mg dose reduced anxiety in the speaking test (n=24, crossover; de Faria 2020); in people at high risk of psychosis, 600 mg/day for one week made no significant difference from placebo in anxiety and cortisol response during a social stress test (n=33; Appiah-Kusi 2020); in healthy volunteers, 300–900 mg did not change responses to social exclusion and negative stimuli (n=38; Arndt 2017). All six single-dose laboratory studies with positive results were carried out with the involvement of the same Brazilian research group (Ribeirão Preto); in Zuardi 2017 and Linares 2019, 4 of the 7 authors are inventors on a patent for a CBD derivative. Two studies from other centers (London, Chicago) found no difference between CBD and placebo. These experiments lasted a single session or one week; they do not show the effect on social anxiety in daily life. In a 12-week study in young people without a control group, anxiety scores fell, but no separate result was given for social anxiety (n=31; Berger 2022). Two systematic reviews specific to social anxiety found CBD promising (Fliegel 2022, 7 studies up to June 2021; Andreoli 2026); a meta-analysis pooling 54 RCTs in mental disorders, however, found no significant difference from placebo in anxiety outcomes (Wilson 2026; certainty of evidence low for most outcomes). There is no treatment study of THC-containing products in social anxiety disorder; in healthy volunteers, 12.5 mg of THC increased distress and anxiety in a social stress test, and 7.5 mg slightly reduced distress after the test (n=42; Childs 2017). The link between cannabis use and later development of social anxiety disorder is inconsistent in follow-up studies: in a US national follow-up, regular use predicted new social phobia (Cougle 2015), while in an analysis pooling three follow-up studies the link was not significant (OR 1.12; 95% CI 0.61–2.05; Xue 2021; observational). As of October 2026, the results of three completed social anxiety studies have not been published (the largest with 239 people; NCT05600114). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 11 controlled studies with cannabinoids were found on this topic; 4 were in patients with social anxiety disorder (one in a group mixed with panic disorder), 2 in other patient groups (people with Parkinson's disease and people at high risk of psychosis), and 5 in healthy volunteers; the only controlled study with a THC-containing product was also in healthy volunteers. No Cochrane review and no clinical guideline assessing cannabinoids were found. Alongside these, the table includes 1 study without a control group, 1 case report, 4 systematic reviews (2 of them meta-analyses), 1 meta-analysis looking at cannabis use and social anxiety risk, and 1 follow-up study; all are in the table below.

Evidence assessment: Weak: a short-term positive signal, but laboratory results are inconsistent and the only large study (Kwee) was negative

• CBD alone: Single-dose pure CBD reduced speaking anxiety in some small studies, but was no different from placebo in similar experiments at other centers; in the largest and longest study, it gave no extra benefit on top of therapy.
• Products containing THC: There is no treatment study in social anxiety disorder with THC-containing products (cannabis, THC or dronabinol, a mouth spray containing THC and CBD) or with the THC-like synthetic drug nabilone. In a single-session study of 42 healthy volunteers, 12.5 mg of THC taken before a social stress test increased distress and anxiety; 7.5 mg helped distress after the test pass more quickly (Childs 2017). The link between cannabis use and later development of social anxiety disorder is inconsistent in follow-up studies (Cougle 2015; Xue 2021). That the cannabis oil in Masataka 2019 contained no THC rests only on the product's own claim; there is no independent analysis. There is no controlled treatment study showing that THC-containing products ease social anxiety. (insufficient evidence) Evidence: Insufficient (for treatment): there is no controlled treatment study of THC-containing products in social anxiety disorder. Findings pointing to increased anxiety are separate: in the only controlled social stress study in healthy volunteers, 12.5 mg of THC increased distress and anxiety, and 7.5 mg slightly reduced distress after the test (42 people, single session); follow-up studies looking at cannabis use and later development of social anxiety disorder are inconsistent, and in an analysis pooling three studies the link was not significant (observational; does not show cause and effect)
• Dose range in studies: Single dose 100–900 mg (those found effective 300–600 mg); 300 mg/day for 4 weeks; 300 mg before therapy sessions; 600 mg/day for 1 week (people at high risk of psychosis); 200–800 mg/day for 12 weeks (no control group, young people)
• Starting dose and titration (in studies): Single dose in laboratory studies, no titration; in the 12-week study in young people, treatment started at 200 mg/day and was increased in 200 mg steps according to response, up to 800 mg/day (study dose; not a personal recommendation)
• Interaction: Citalopram/escitalopram: when CBD (200–800 mg/day) was added, citalopram blood levels rose significantly in 6 patients; in the laboratory, breakdown via CYP3A4 and CYP2C19 was inhibited (Anderson 2021, PMID 34121064)
• Interaction: Sertraline, fluoxetine, mirtazapine: in the laboratory, CBD had very little effect on their breakdown; not measured in patients (Anderson 2021, PMID 34121064)
• Interaction: In people taking serotonergic antidepressants, CBD affected the re-extinction of subjective fear worse than placebo (Kwee 2024, exploratory subgroup)
• Interaction: Clobazam: in 13 children with epilepsy, the active metabolite N-desmethylclobazam rose by an average of 500%; the rise in clobazam itself (average 60%) was uncertain (confidence interval −2 to 91). In healthy volunteers, clobazam did not change and the metabolite rose ~3-fold (FDA/EMA). Side effects in 10 of the 13 patients resolved when the clobazam dose was reduced (Geffrey 2015, PMID 26114620)
• Interaction: Other benzodiazepines (alprazolam, clonazepam, etc.): no direct interaction study in an anxiety population was found
• Interaction: THC-containing products: CBD does not consistently reduce THC's effects; full-spectrum products may contain THC (e.g., 0.23 mg/mL)
• Interaction: Antipsychotic + 1000 mg/day CBD (schizophrenia) was well tolerated (McGuire 2017, PMID 29241357)
• Interaction: No direct interaction studies were found with venlafaxine, duloxetine, pregabalin, buspirone or hydroxyzine
• Monitoring in studies: Monitoring liver tests with long-term use is a doctor's decision

References (19)

Study table (dose, duration, result) · Topic page

A single 300 mg dose did not reduce anxiety during trauma recall; it reduced only the 'cognitive impairment' subscale, and in a secondary analysis the effect was seen only in non-sexual trauma. In trauma-exposed people, 300 mg/day for 1 week was ineffective; in alcohol use disorder + PTSD, 600 mg/day for 6 weeks was ineffective. In a 21-person pilot study in which 500 mg/day was added to prolonged exposure therapy for 18 days (registry results only), two scales differed in opposite directions, and no statistics were published. In a 96-person RCT in veterans in which CBD (600 mg/day according to the protocol) was added to the same therapy for 16 weeks (NCT03518801; registry results only, October 28, 2026), scores on the clinician-rated CAPS-5 scale fell in both groups (36.9 and 35.1 at baseline; 22.6 and 23.1 at the end of treatment; 21.2 and 21.9 at month 3); the registry gives no between-group statistics, and 23 of 50 people in the CBD group and 15 of 46 in the placebo group did not complete the study. The only clearly positive data for CBD are an open-label case series of 11 patients. In an RCT with smoked cannabis in veterans (80 people), no type of cannabis, including one containing 11% CBD, reduced PTSD symptoms more than placebo. For PTSD-related nightmares, in a 10-person crossover RCT with nabilone, a THC-like synthetic medicine, nightmares decreased more than with placebo. In a 171-patient multicenter RCT, dronabinol (synthetic THC, 2.5–15 mg at night, 10 weeks) lowered the nightmare score by 1.50 points more than placebo (0–8 scale; 95% CI 0.71–2.28); on the main secondary outcome measuring overall PTSD severity (clinician assessment), the difference was not significant (p = 0.08). Of the people taking dronabinol who answered the question, 81% correctly guessed which group they were in, reports of improvement were strongly linked to this guess, and the drug's manufacturer supported the study with an unrestricted grant; the nightmare finding rests on a single large study. In two uncontrolled case series with nabilone (47 and 104 people), nightmares decreased clearly. In two laboratory RCTs with a single dose of THC in people with PTSD, brain activity changed but the fear response did not. Real-world data point both ways: in a follow-up of 2,276 veterans, symptoms were more severe in those who started cannabis after treatment, and in a cohort of 361 veterans, cannabis use was linked to more intense intrusive memories in the following months; on the other hand, a 150-person cohort comparing cannabis users with non-users (5 of 7 authors with company ties) and two patient registries in the UK (no comparison group) reported improvement. In none of these studies were the groups formed by random assignment. In data from 410 people with PTSD who also had alcohol or substance problems, cannabis users benefited from trauma-focused therapy as much as non-users. The most recent meta-analysis, which finished its search before the nightmare study (2026, 54 RCTs), found no significant effect in PTSD; the 2023 guideline of the US Departments of Veterans Affairs and Defense makes a strong recommendation against cannabis, and the American Academy of Sleep Medicine (2018), relying only on the 10-person study, states that nabilone "may be used" for nightmares. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 11 controlled studies with cannabinoids on this topic (6 treatment studies lasting weeks; 5 single-dose or short laboratory studies, one in healthy volunteers) and 4 systematic reviews were found; together with 2 guidelines and 9 observational studies, all are in the table below. Cochrane has no review dedicated to this question; 2 controlled studies that were completed but whose results have not been released, and studies left unfinished, are under "unverifiable".

Evidence assessment: Weak; controlled studies are mostly negative

• CBD alone: In controlled studies in PTSD, pure CBD did not reduce anxiety or symptoms more than placebo. These studies are small (21–42 people) and short (from a single dose to 6 weeks). Results from a 96-person study of veterans in which CBD or placebo was added for 16 weeks to prolonged exposure therapy (NCT03518801) were released in October 2026, only in the trial registry: on a clinician-rated scale (0–80), scores fell in both groups, and at the end of treatment they were 22.6 in the CBD group and 23.1 in the placebo group; the groups were not compared statistically and there is no peer-reviewed publication.
• Products containing THC: For overall PTSD symptoms: smoked cannabis containing THC or THC+CBD did not reduce symptoms more than placebo over 3 weeks (Bonn-Miller 2021); in the nightmare study, dronabinol was also not clearly different from placebo on the main secondary outcome measuring overall PTSD severity (clinician assessment); on the scale patients filled in themselves the difference favored dronabinol, but this was an additional analysis without correction for multiple comparisons (Roepke 2026). For nightmares: dronabinol, a synthetic THC, reduced the frequency and intensity of nightmares more than placebo in a multicenter, 10-week RCT with 171 patients (Roepke 2026); nabilone, a THC-like synthetic medicine, gave a similar result in a small crossover RCT with 10 soldiers (Jetly 2015). There is only one large study, most people taking dronabinol noticed which group they were in, and the drug's manufacturer supported the study; the finding needs to be repeated. Real-world data point both ways: some studies following cannabis users reported improvement, others a more severe course; the 2023 guideline of the US Departments of Veterans Affairs and Defense makes a strong recommendation against cannabis in the treatment of PTSD. (weak evidence) Evidence: Weak for overall PTSD symptoms (no clear difference from placebo in two RCTs); moderate for nightmares (a 171-person multicenter dronabinol RCT and a 10-person nabilone RCT were positive; the large study is the only one and is manufacturer-supported, and most people taking dronabinol noticed which group they were in)
• Dose range in studies: 300 mg single dose, 300 mg/day (1 week), 500 mg/day (18 days, added to therapy; NCT05132699), 600 mg/day (16 weeks, added to therapy; according to the protocol; NCT03518801), 600–1200 mg/day (6–8 weeks); 25–100 mg/day in the open-label case series; THC-containing: dronabinol 2.5–15 mg/day at night (10 weeks; single doses of 5–10 mg in laboratory studies), nabilone 0.5–3 mg/day (RCT) and 0.2–6 mg/day in case series, smoked cannabis up to 1.8 g a day
• Interaction: Citalopram/escitalopram: when CBD (200–800 mg/day) was added, citalopram blood levels rose significantly in 6 patients; in the laboratory, breakdown via CYP3A4 and CYP2C19 was inhibited (Anderson 2021, PMID 34121064)
• Interaction: Sertraline, fluoxetine, mirtazapine: in the laboratory, CBD affected their breakdown very little; not measured in patients (Anderson 2021, PMID 34121064)
• Interaction: In people taking serotonergic antidepressants, CBD affected the re-extinction of subjective fear worse than placebo (Kwee 2024, PMID 38044339, exploratory subgroup)
• Interaction: Clobazam: in 13 children with epilepsy, the active metabolite N-desmethylclobazam rose by an average of 500%; the rise in clobazam itself (average 60%) was uncertain (confidence interval −2 to 91). In healthy volunteers, clobazam did not change and the metabolite rose ~3-fold (FDA/EMA). Side effects in 10 of the 13 patients, which resolved when the clobazam dose was reduced (Geffrey 2015, PMID 26114620)
• Interaction: Other benzodiazepines (alprazolam, clonazepam, etc.): no direct interaction study was found in the anxiety population
• Interaction: THC-containing products: CBD does not consistently reduce the effects of THC; full-spectrum products may contain THC (e.g., 0.23 mg/mL)
• Interaction: Antipsychotic + 1000 mg/day CBD (schizophrenia) was well tolerated (McGuire 2017, PMID 29241357)
• Interaction: No direct interaction study was found with venlafaxine, duloxetine, pregabalin, buspirone or hydroxyzine
• Monitoring in studies: Monitoring liver tests during long-term use is the doctor's decision

References (27)

Study table (dose, duration, result) · Topic page

There is no published RCT with a positive result that targeted depression as its primary outcome. A 2026 Lancet Psychiatry meta-analysis reported that there is no RCT evidence for treating depression. Low-dose full-spectrum CBD oil was no different from placebo in stressed students; in an open-label study, 300 mg/day reduced burnout in health care workers and, as a secondary outcome, depression scores (PHQ-9), but there was no placebo and 5 serious side effects were seen only in the CBD arm. Other placebo-controlled CBD studies measuring depression symptoms found no difference: 600 mg a day in 20 patients with brain tumors and anxiety (stopped early; Belgers 2026), 144 patients with advanced cancer (Hardy 2023), 136 patients with hand osteoarthritis and psoriatic arthritis (Vela 2022, exploratory outcome). A 178-person study in anxiety disorder in India also reported improvement in depression scores; but the reported effect is much larger than in other anxiety studies, its statistics are unusual for a study of this size, the result has not been independently replicated, six of the seven authors are tied to pharmaceutical companies, and the full text could not be read (Gundugurti 2024). The consistent effect in animal studies has not carried over to humans (Jantsch 2026). For THC-containing products: in two small 1970s studies with hospitalized patients with depression, THC gave no benefit and frequently caused distressing reactions (Kotin 1973, Ablon 1974; details from Stanciu 2021); in a 269-person study in which a medical cannabis card was randomly given either right away or after 12 weeks (186 analyzed), depression symptoms did not change and cannabis use disorder increased (Gilman 2022). Meta-analyses pooling depression symptoms measured in other conditions found no difference (Black 2019: SMD −0.05; Bharat 2026: SMD −0.20, 95% CI −0.43 to 0.04; very low certainty of evidence). In studies without a comparison group that followed patients with depression using medical cannabis, depression scores went down (Lillywhite 2026, Specka 2024); a follow-up study comparing users with non-users, most of whose participants used CBD-dominant products, gave a similar result (Martin 2021). Most of these were carried out by teams tied to cannabis companies or cannabis clinics, and the expectation effect cannot be separated out; in Canada, meanwhile, among people authorized to use medical cannabis, the risk of emergency visits and hospitalization for depression was about twice as high (Yana 2023). For recreational use, a meta-analysis of longitudinal studies shows that depression develops slightly more often later in cannabis users (OR 1.29, Churchill 2025; HR 1.34 in a cohort of 463,396 adolescents, Young-Wolff 2026), but in a meta-analysis that included only general population studies and dealt with tobacco separately, the link was not significant (RR 1.31; 95% CI 0.92–1.86; Burke 2024). In people with depression, cannabis use goes along with more severe symptoms and a worse course in most studies (Sorkhou 2024); the systematic review by the Canadian CANMAT guideline group found these findings less consistent in major depression than in bipolar disorder and made avoiding cannabis a conditional recommendation for people with major depression (low to moderate certainty of evidence; Tourjman 2023). In young people with mood disorders, cannabis use disorder was linked to a threefold increase in the risk of self-harm (Fontanella 2021). In a study in which teenagers who used cannabis at least once a week were randomly assigned to 4 weeks of abstinence or to monitoring only, stopping did not change depression symptoms (Cooke 2021). Observational studies do not show cause and effect. CBD cannot be recommended as a treatment for depression; it does not replace prescription antidepressants. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 10 controlled studies with cannabinoids on this topic were found that focused on depression or mood or measured depression symptoms with CBD (only 2 in patients diagnosed with depression, with THC in the 1970s; 1 tests stopping cannabis), along with 8 systematic reviews or meta-analyses (one by a mental health guideline group); Cochrane has no review on this topic. All are in the table below, together with 6 observational studies, 1 case report and 1 meta-analysis pooling animal studies. THC-containing product studies that measured depression only as a secondary outcome in other conditions, and studies asking the same question that are covered by the reviews in the table, were not included one by one.

Evidence assessment: Very weak (animal data consistent; no CBD RCT in people diagnosed with depression, and most small RCTs measuring depression symptoms show no difference from placebo)

• CBD alone: There is no published RCT showing that pure CBD is effective in depression; no CBD RCT in patients diagnosed with depression has been published either. Most placebo-controlled CBD studies that measured depression symptoms found no difference: stressed students (Winkler 2025), brain tumors (Belgers 2026), advanced cancer (Hardy 2023), hand osteoarthritis (Vela 2022). The positive results come from a study without placebo (Crippa 2021) and from an anxiety study whose authors were mostly tied to pharmaceutical companies, whose details could not be read, and whose reported effect is much larger than in the other studies (Gundugurti 2024). The strength of evidence is very weak.
• Products containing THC: There are only two small, old controlled studies with THC in patients with depression: THC did not improve depression, and 10 of 21 patients could not continue because of side effects such as intense anxiety or panic (Kotin 1973, Ablon 1974; information from a review). Meta-analyses that pooled studies measuring depression symptoms in other conditions found no significant difference from placebo, either with THC-containing medicines (Black 2019) or with cannabinoids in general (Bharat 2026); across studies of mental disorders, THC increased side effects (OR 1.99) and stopping because of side effects (OR 2.78) (Black 2019). In people randomly assigned to start medical cannabis early for anxiety or depression, depression symptoms did not improve and cannabis use disorder developed more often (Gilman 2022). In observational studies, cannabis use goes along with a small increase in the later risk of depression (about 1.3 times) (Churchill 2025, Young-Wolff 2026); but in a meta-analysis that included only general population studies, the link was not significant (Burke 2024), and cause and effect has not been shown. The Canadian CANMAT guideline group recommends that people with major depression avoid cannabis; the certainty of evidence is low to moderate, and the recommendation is conditional (Tourjman 2023). (very weak evidence) Evidence: Very weak: in patients with depression there are only two small 1970s studies and one randomized medical cannabis study, none showing benefit; no difference in meta-analyses; the data pointing to harm are observational (Black 2019, Bharat 2026, Gilman 2022)
• Dose range in studies: In controlled studies, pure CBD 20–600 mg a day (in hand osteoarthritis, starting at 10 mg and going up to 20–30 mg; 300 mg in health care workers; 600 mg in brain tumors; in advanced cancer, a median dose of 400 mg chosen by patients); in the student study, full-spectrum oil from 0.02 mg to 1 mg per kilogram per day
• Starting dose and titration (in studies): In the student study, the dose was raised every three days; in the cancer study, patients adjusted the dose over the first 14 days based on effect and side effects; in the hand osteoarthritis study, the dose was stepped up from 10 mg to 20 and 30 mg
• Interaction: Citalopram: in healthy adults, CBD (2.5 mg/kg twice daily, 12 days) increased citalopram exposure (AUC) by 43% (Salcedo 2026, PMID 41622700)
• Interaction: Amitriptyline: a single 30 mg dose of CBD increased amitriptyline AUC by 13% and Cmax by 17%; the effect may be larger with continuous use (Gorbenko 2026, PMID 41398552)
• Interaction: In an emergency department survey, 69.7% of people using CBD at home were taking a medicine with interaction potential; the most common group was antidepressants (64.4%) (Geneau 2025, PMID 41227172)
• Interaction: Reports of interactions with antidepressants, antiepileptics, opioids and alcohol were reviewed (Balachandran 2021, PMID 33515191)
• Monitoring in studies: Doctor monitoring for changes in medicine levels in people taking antidepressants

References (26)

Study table (dose, duration, result) · Topic page

As add-on treatment in bipolar depression, 150–300 mg/day of pure CBD did not lower the depression score (MADRS) differently from placebo at 8 weeks; both groups had a drop of about 15 points (strong placebo effect). An exploratory subanalysis shows a signal in favor of 300 mg; no difference was seen in the development of mania. In mania, 600–1200 mg/day of CBD was ineffective in 2 patients. A phase 3 study of 360 people is underway (according to its registry entry, the estimated completion for primary outcomes is December 2029). Treatment data for THC-containing products in bipolar depression consist only of two small double-blind studies from the 1970s in hospitalized patients with depression (21 people, 9 of them bipolar): THC did not improve depression, and about half of the patients could not continue treatment because of side effects such as intense anxiety or psychosis-like reactions (Kotin 1973, Ablon 1974; original articles could not be read, details from Stanciu 2021). The 2026 single-dose THC laboratory study (Miranda 2026) looked only at cognitive tests. The most recent meta-analysis of RCTs did not find enough data in bipolar disorder to pool (Wilson 2026). Most studies following cannabis use in people with bipolar disorder are negative: in a 2-year follow-up of 1922 people in Europe, those who kept using had less recovery and more frequent new episodes, while outcomes in those who stopped during the episode were similar to those who never used (Zorrilla 2015); among those followed after a first hospitalization for mania, cannabis was associated with more time spent in episodes and with rapid cycling (Strakowski 2007); over 24 months, remission of depressive symptoms was less frequent in regular users (Kim 2015, unadjusted); in a long follow-up of 788 people, periods of increased cannabis use were followed by a small increase in suicidal thoughts (Smith 2025); in diaries kept by 24 people for 6 days, cannabis use was followed by increases in manic and depressive symptoms, while depressive symptoms did not predict use (Tyler 2015). On the other hand, in two follow-up studies cannabis did not independently predict new episodes or rehospitalization (Lagerberg 2021, Olivier 2025). Systematic reviews point in the same direction (Sorkhou 2024; Tourjman 2023, with low certainty of evidence for most outcomes); in cross-sectional data, cannabis use disorder is weakly associated with suicide attempts (OR 1.35; Bartoli 2019). Cannabis users also smoke and drink alcohol more often, and a reverse relationship, such as symptoms increasing use, cannot be ruled out; cause and effect has not been shown. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 4 controlled studies with cannabinoids on this topic were found (1 CBD RCT in bipolar depression; 2 old THC studies in which some patients were bipolar; 1 single-dose THC laboratory study), along with 6 systematic reviews or meta-analyses and 1 umbrella review; there is no Cochrane review and no unpublished study with registered results, and 1 phase 3 study is underway. All of them, together with 8 observational studies, 2 case reports and 1 clinical review, are in the table below.

Evidence assessment: Very weak: a single small RCT that was ended early and gave results no different from placebo (Pinto 2024)

• CBD alone: Pure CBD was not superior to placebo in bipolar depression; safety data rest on a single small RCT.
• Products containing THC: THC-dominant cannabis can worsen manic symptoms and functioning in bipolar disorder; people with bipolar or psychotic disorders are advised to avoid cannabis (Kansagara 2026; the systematic review by Canada's CANMAT guideline group makes the same recommendation: Tourjman 2023). In two small, old controlled studies in which THC was tested in patients with depression (some of them bipolar), depression did not improve and about half of the patients could not continue treatment because of side effects (Kotin 1973, Ablon 1974; information from a review). In most studies following people with bipolar disorder, cannabis users recovered less and had episodes more often (Zorrilla 2015, Strakowski 2007); these findings are observational and do not show cause and effect. (very weak evidence) Evidence: Very weak; with THC products there are only two small controlled studies from the 1970s in patients with depression (some of them bipolar) (no benefit, frequent distressing reactions; Kotin 1973, Ablon 1974, details from a secondary source); the harm signal rests on observational studies: with continued use in bipolar disorder, less recovery and more frequent episodes (Zorrilla 2015; Sorkhou 2024 and Tourjman 2023 reviews, with low certainty of evidence for most outcomes in Tourjman), and a later diagnosis of bipolar disorder and mania more common in cannabis users (Sanjuan-Ortiz 2027, unadjusted; 1.7–2-fold in a large adjusted cohort: Young-Wolff 2026); a recommendation to avoid it in a guideline and a clinical review (Tourjman 2023, Kansagara 2026)
• Dose range in studies: 150–300 mg/day in the RCT; 600–1200 mg/day in a case report in mania
• Starting dose and titration (in studies): In Pinto 2024, 150 → 300 mg/day (the dose was increased at week 2 in non-responders)
• Interaction: Citalopram: in healthy adults, CBD (2.5 mg/kg twice a day, 12 days) increased citalopram exposure (AUC) by 43% (Salcedo 2026, PMID 41622700)
• Interaction: Amitriptyline: a single 30 mg dose of CBD increased amitriptyline AUC by 13% and Cmax by 17%; the effect may be larger with continuous use (Gorbenko 2026, PMID 41398552)
• Interaction: In an emergency department survey, 69.7% of people using CBD at home were taking a medicine with interaction potential; the most common group was antidepressants (64.4%) (Geneau 2025, PMID 41227172)
• Interaction: Reports of interactions with antidepressants, antiepileptics, opioids and alcohol were reviewed (Balachandran 2021, PMID 33515191)
• Interaction: Lithium: a single case of lithium toxicity developing weeks after CBD was added (Singh 2020, PMID 32851114)
• Monitoring in studies: Monitoring by a doctor for symptoms of mania (monitored in the studies)

References (23)

Study table (dose, duration, result) · Topic page

Pure CBD has been tested only in addition to an antipsychotic or for short periods. One RCT saw a small reduction in positive symptoms (the difference in total score was not significant), and another saw no improvement at all; in the comparison with amisulpride, equivalence could not be shown statistically. In the maker's unpublished 12-week phase 2 study (77 patients randomized; results only in the registry), 300 and 1000 mg/day were no different from placebo on the PANSS total; the study was stopped early by company decision. Two meta-analyses in 2026 reached different conclusions; a 2026 meta-analysis covering all cannabinoids found no significant effect in psychotic disorders, and the Cochrane review (2014) found the evidence for CBD insufficient; Denmark's 2026 national guideline recommends not using cannabinoids for negative symptoms. Other small controlled studies also found no difference: an 18-person crossover study with results only in the registry (NCT02504151), an open-label pilot study with CBD-rich cannabis cigarettes (Köck 2021) and an attention test with a single dose (Hallak 2010); in a 15-patient single-dose study, the drop in symptoms was larger on the CBD day, but this was a secondary measure tested one-sided (O'Neill 2021). In 33 people at high risk of psychosis, the main outcome of the only placebo-controlled study was brain measurements; it was reported years later in a short letter that symptom scores were lower in the CBD group after 21 days of use (not a pre-registered outcome; Bhattacharyya 2018). In Parkinson's psychosis there is only an open-label series of 6 patients (Zuardi 2009). In people with schizophrenia who also have cannabis use disorder, 1000 mg CBD given before marijuana did not reduce but increased marijuana's memory-impairing and psychosis-increasing effects (30-person crossover RCT); in healthy volunteers, CBD added to cannabis also did not reduce THC's psychosis-like effects (Englund 2023, Lawn 2023); results of earlier small studies were mixed (Freeman 2019). The doses studied (mostly 600–1000 mg/day) are far above the doses of CBD oils on the market; do not stop an antipsychotic and switch to CBD. THC: treatment data are almost nonexistent (an uncontrolled series of 6 patients); experimental studies and their meta-analyses show that THC temporarily increases psychosis symptoms, and large observational studies show that frequent and high-THC use is associated with an increase in psychosis risk (association; causation is debated). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 16 controlled studies of cannabinoids on this topic (11 with CBD in patients or people at high risk of psychosis, one of them with CBD-rich cannabis cigarettes; 3 with THC; 2 in healthy volunteers), 4 small uncontrolled series, 12 systematic reviews or meta-analyses (one Cochrane), 2 guidelines or consensus reports and 4 large observational studies were found; all are in the table below. Reviews repeating the same question, and volunteer studies already covered by the reviews in the table, were not listed one by one.

Evidence assessment: Weak (conflicting)

• CBD alone: Pure CBD (mostly 600–1000 mg/day, added to an antipsychotic) produced a small reduction in positive symptoms in the largest study, but the difference in total symptom score was not significant (McGuire 2018); most other controlled studies saw no benefit (Boggs 2018, NCT04421456, NCT02504151, Hallak 2010). One meta-analysis found a small benefit on total symptoms (Di Francesco 2026), while two that looked at CBD and at all cannabinoids found no significant effect (Marchi 2026, Wilson 2026); the Cochrane review found the evidence insufficient. No effect was seen on symptoms of schizophrenia such as social withdrawal and lack of motivation (negative symptoms) (Di Francesco 2026); Denmark's national guideline recommends not using cannabinoids to treat these symptoms (Norlin Mølgaard 2026). In the only placebo-controlled study in 33 people at high risk of psychosis, those taking CBD for 3 weeks had slightly lower symptom scores, but this was not the pre-specified main outcome and was reported years later in a short letter (Bhattacharyya 2018); in Parkinson's psychosis there is only an uncontrolled series of 6 patients (Zuardi 2009). CBD taken before marijuana did not reduce marijuana's harm in people with schizophrenia (Chesney 2025), nor did it in healthy volunteers in newer studies (Englund 2023, Lawn 2023). The strength of evidence is weak; it does not replace standard treatment.
• Products containing THC: In schizophrenia and psychosis, THC-containing products have been studied mainly for their possible harms. In controlled laboratory studies, a single dose of THC clearly increased psychosis-like symptoms in healthy volunteers (Hindley 2020; an umbrella review rated the certainty of this finding as high: Solmi 2023), temporarily worsened symptoms and memory problems in people with schizophrenia (D'Souza 2005), and increased suspiciousness in 6 people at high risk of psychosis (Vadhan 2017); in patients who used cannabis regularly, 15 mg dronabinol did not increase symptoms within a few hours but impaired learning (Brunette 2025). In observational studies, weekly or more frequent and high-THC use goes hand in hand with a higher risk of psychosis (Robinson 2023, Di Forti 2019); relapses are more common in those who keep using after psychosis begins (Schoeler 2016); among people with medical cannabis authorization, emergency visits and hospital admissions for psychosis are also slightly more common (Dubois 2024). These observational findings are associations; according to experts, there are signs supporting causation, but reverse causation and confounding factors cannot be fully ruled out (D'Souza 2022). Someone with a history of psychosis should not use THC-containing products. As a treatment, no benefit of THC has been shown: Denmark's national guideline recommends not using cannabinoids for negative symptoms, and there are no controlled treatment studies; the only data are an uncontrolled series of 6 patients (Schwarcz 2009). (insufficient evidence) Evidence: Insufficient (for treatment): there are no controlled studies of THC-containing products for treating schizophrenia or psychosis; there is only an uncontrolled series of 6 patients. The evidence of harm is much stronger: in controlled laboratory studies and their meta-analysis, THC temporarily increased psychosis symptoms (high certainty in an umbrella review); in large observational studies, frequent and high-THC use went hand in hand with a higher risk of psychosis (association; does not show cause and effect on its own)
• Dose range in studies: 300–1000 mg/day in treatment studies (mostly 600–1000 mg; median 800 mg/day in a meta-analysis), 3–12 weeks; 300–1000 mg in single-dose studies
• Starting dose and titration (in studies): Leweke 2012: started at 200 mg/day and increased by 200 mg each day (research protocol)
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: Adding 1000 mg/day CBD to antipsychotics was well tolerated; side effect rates were similar to placebo (McGuire 2017/2018)

References (38)

Study table (dose, duration, result) · Topic page

In cannabis use disorder, 400–800 mg of pure CBD reduced use when given together with psychological support; but this is a single, small phase 2a study. For other substances, CBD reduced cue-induced craving in some lab studies (heroin, opioids, alcohol; single dose or a few days); in young people, however, no effect on alcohol craving was seen. Outside cannabis, none of the RCTs that measured use or relapse showed CBD to be better than placebo (for smoking, a single small study reported only a within-group reduction): in cocaine use disorder, 800 mg/day (78 people, 12 weeks) did not reduce craving or relapse, and in crack cocaine use, 300 mg/day (31 people, 10 days) did not change craving; in alcohol use, 150 mg/day (44 people, 8 weeks) and 600–1200 mg/day did not change the amount of drinking. In opioid use disorder, use or relapse was not measured in the published RCTs: in 30 people on buprenorphine, 600 mg/day (28 days) was not superior to placebo for craving, withdrawal or mood; in 23 methadone patients with chronic pain, a single dose of 400–1,200 mg CBD did not change opioid craving. In 76 people on methadone or buprenorphine, 4 weeks of CBD gave craving and anxiety similar to placebo and close rates of urine opioids (registry results only, no statistics, no peer-reviewed publication). In a 2026 meta-analysis, there was no significant effect in opioid use disorder; in cocaine use, craving increased more with cannabinoids, but in the 78-person study in this area the difference was not statistically significant (p = 0.069). For cannabis, according to Cochrane 2025, quitting at the end of treatment with THC-containing medicines is no different from placebo (RR 1.04; moderate certainty). There are 6 clinical RCTs of THC-containing or THC-like medicines for cannabis: nabiximols reduced withdrawal (Allsop 2014, 51 people) and reduced use days over 12 weeks (Lintzeris 2019, 128 people; difference 18.6 days, 95% CI 3.5–33.7; it persisted 3 months later), but in a 40-person study there was no significant difference in use between groups (Trigo 2018); dronabinol (Levin 2011, 156 people; with lofexidine, Levin 2016, 122 people) and nabilone (Hill 2017, 18 people) did not increase quitting. In lab or inpatient studies lasting a few days, withdrawal decreased (only some symptoms in Haney 2008; Haney 2013, Schlienz 2018, Herrmann 2019; Trigo 2016, 9 people, with nabiximols; Slagle 2026, conducted by the company with a nabilone + gabapentin combination); the effect on relapse to cannabis smoking in the lab was inconsistent (reduced: Haney 2013, Schlienz 2018; did not reduce: Haney 2008, Herrmann 2019). A single dose of THC reduced craving triggered by marijuana cues in a one-session measurement (Lundahl 2015, 14 people). These are small lab studies; they do not show a treatment effect. A single dose of CBD did not change the reinforcing effects of marijuana (Haney 2016). In opioid withdrawal, dronabinol reduced symptoms but did not change retention in treatment (Bisaga 2015, 60 people); in the lab, its effect was limited and it raised heart rate at 20 mg and above (Lofwall 2016, 12 people). Cannabis use during opioid treatment was not associated with illicit opioid use (Costa 2024; 10 observational studies). In heavy drinkers, THC-containing marijuana reduced alcohol consumption at that moment in the lab but did not change an alcohol craving scale (Metrik 2026, 157 people; single session). For smoking, there are 2 small RCTs with CBD: over one week, the number of cigarettes smoked with an inhaler fell by about 40% in the CBD group and did not change in the placebo group (Morgan 2013, 24 people; within-group change, no direct comparison of the two groups in the abstract); a single 800 mg dose reduced attentional bias but did not change craving or withdrawal (Hindocha 2018, 30 people). On the harm side: cannabis use disorder can develop with THC-containing cannabis products (Gilman 2022 RCT: 17.1% vs. 8.6%; about 25% among medical cannabis users, Dawson 2024 observational meta-analysis, PMID 38493566); CBD itself was found to have low abuse potential (Schoedel 2018, PMID 30286443; Babalonis 2017). Recent reviews point the same way: cannabinoids can ease short-term symptoms (withdrawal, craving) but have not been shown to bring about lasting abstinence (Zammit Dimech 2026; Wilson 2026, evidence quality generally low); CBD alone has not been shown to be effective (Redonnet 2025). It does not replace proven medicines in opioid treatment (e.g., buprenorphine/methadone). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov; separately for each substance): 35 controlled studies with cannabinoids on this topic (34 rows; one reports two separate trials together) and 7 systematic reviews or meta-analyses (one combines only observational studies) were found; all are in the table below. The table also includes 1 patient registry analysis without a control group (Ghosh 2025, 34 people); it does not show cause and effect. Of the controlled studies, 16 are on cannabis (13 with THC-containing or THC-like medicines, 3 with CBD; 8 are single-session or few-day lab, inpatient or short withdrawal studies), 7 on opioids, 7 on alcohol, 2 on cocaine and 2 on tobacco; 1 measures the risk of cannabis use disorder with THC-containing cannabis products; the results of 2 are available only on ClinicalTrials.gov. Lab studies by the same research group using the same method were given in a single row (the other publications are in that row's source information; those whose results do not agree are in separate rows); uncontrolled studies other than the patient registry and reviews repeating the same question were not listed individually. The only Cochrane review on this topic that assesses cannabinoid products is for cannabis use disorder (Spiga 2025); no controlled human studies with cannabinoids were found for methamphetamine or other stimulants.

Evidence assessment: Cannabis: weak (pure CBD reduced use in a single small phase 2a RCT; in Cochrane 2025 and a 2026 network meta-analysis, the evidence for CBD is low certainty; a single-dose lab study and the registry results of a 10-person study without a statistical comparison showed no benefit) · Alcohol, opioids, cocaine, tobacco: weak (craving may decrease in the lab; it has not been shown to reduce use or relapse)

• CBD alone: Pure CBD reduced cannabis use in a single phase 2a RCT; in cocaine use, craving (and in one, relapse) did not differ from placebo in two RCTs; in alcohol use, despite reduced craving in the lab, it did not reduce drinking; in opioid use, cue-induced craving decreased in two small studies (single dose and 3 days), did not differ from placebo in a 28-day study or in a single-dose pain study, and was also similar in the registry results of a 4-week study; the result of the only RCT that measured use is available only in a trial registry (at week 4, urine opioids 76% vs. 81% in people on methadone and 13% vs. 20% in people on buprenorphine; no statistical analysis). For smoking, a small one-week RCT found fewer cigarettes smoked with a CBD inhaler (within-group change only); a single 800 mg dose did not change craving or withdrawal but reduced attention to cigarette images. For cannabis, the registry results of a 10-person RCT and a single-dose lab study showed no benefit.
• Products containing THC: In cannabis use disorder, CBD+THC together reduced withdrawal and the amount used (Wilson 2026; most of the evidence is low certainty); however, the quit rate at the end of treatment with THC-containing medicines was no different from placebo (Cochrane 2025, RR 1.04, moderate certainty). In individual studies, nabiximols reduced withdrawal and increased retention in treatment (Allsop 2014, 51 people), and reduced cannabis-use days by 18.6 days over 12 weeks (Lintzeris 2019, 128 people; 95% CI 3.5–33.7); in a 40-person study, however, the between-group difference in use was not significant (Trigo 2018). Dronabinol reduced withdrawal in one study (Levin 2011) and did not even change withdrawal when given with lofexidine (Levin 2016); neither increased quitting. Nabilone did not reduce use (Hill 2017, 18 people). In lab studies lasting a few days, withdrawal decreased, while the effect on relapse was inconsistent. In opioid withdrawal, dronabinol eased symptoms but did not change retention in treatment (Bisaga 2015, 60 people); in the lab, its effect was limited and it caused a racing heart at high doses (Lofwall 2016). In heavy drinkers, THC-containing marijuana reduced alcohol consumed in the lab by 19–27% but did not change an alcohol craving scale (Metrik 2026; single session). There are no studies of THC-containing products for tobacco. THC-containing products can also be addictive: among people given a medical cannabis card, cannabis use disorder developed about twice as often within 12 weeks (Gilman 2022). In cocaine use, a meta-analysis found craving increased more with cannabinoids than with placebo; in the 78-person study in this area, the difference was not significant; in alcohol use, full-spectrum CBD containing a little THC reduced craving but did not change the amount of drinking (Mueller 2025). (weak evidence) Evidence: THC-containing medicines for cannabis: may reduce withdrawal (2 clinical RCTs and short lab studies; no difference in 2 RCTs; small effect in a meta-analysis, low quality); reduced use in a single RCT, quit rate no different from placebo (Cochrane 2025, moderate certainty). For opioids and alcohol, a single RCT or lab study; no studies for tobacco
• Dose range in studies: Cannabis: 400–800 mg/day (4 weeks); cocaine: 800 mg/day (12 weeks); heroin/opioids: 400–800 mg, 1 dose a day (3 days), single dose 600 mg, 600 mg/day (28 days); alcohol: about 150 mg/day (8 weeks), single dose 600–800 mg, 800 mg/day (3 days), 600–1200 mg/day; crack cocaine: 300 mg/day (10 days); tobacco: single dose 800 mg; opioids (registry results): 400 mg/day (4 weeks), then 800 mg/day. THC-containing medicines: for cannabis, nabiximols up to 86.4 mg THC + 80 mg CBD a day, dronabinol 40–60 mg/day, nabilone 2 mg/day; for opioid withdrawal, dronabinol 30 mg/day
• Starting dose and titration (in studies): In the cocaine study, 400 mg/day for 2 days, then 800 mg/day; for alcohol, in Bogenschutz 2026, an increase to 1200 mg/day after 4 weeks
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: No clear problems were seen with opioids in small studies: in healthy volunteers who had used opioids before, 400–800 mg of CBD by mouth given together with intravenous fentanyl did not cause respiratory depression or heart and blood vessel problems (Manini 2015, PMID 25748562); in 7 people on methadone or buprenorphine, a single dose of 400–1,200 mg CBD did not cause marked sedation (Costa 2026b, open-label, PMID 41496743); no significant interaction was reported with 28 days of CBD in 30 people on buprenorphine (London 2025). These are short, small studies; an interaction case with methadone has been reported

References (42)

Study table (dose, duration, result) · Topic page

Most RCTs of pure CBD showed no superiority over placebo: low back pain in the emergency department, ureteroscopy, root canal treatment and total knee replacement (topical). In shoulder arthroscopy there was a difference in pain and satisfaction only on day 1, which then disappeared, and opioid consumption did not change; no difference or harm was seen at 1-year follow-up either. After eye laser surgery (PRK), CBD 50 mg × 2 in 35 patients gave pain control similar to codeine-acetaminophen; this study had no placebo. In emergency dental pain, a single small RCT reported a positive result with very high doses (10–20 mg/kg). In 36 patients who had both knees replaced at once, oral CBD 400 or 800 mg (4 doses around surgery) did not significantly reduce the primary outcome, 72-hour opioid consumption, compared with placebo; the reduction at 400 mg was seen only in a post hoc analysis, and side effects increased at 800 mg. In healthy volunteers given experimental pain, CBD alone (50–1600 mg) did not reduce pain intensity; when given with an opioid, it increased the opioid's effect on some acute pain measures but not on the prespecified primary measure. CBD added to THC also did not increase THC's analgesic effect. In a meta-analysis combining 18 experimental pain studies of cannabis, THC and THC-like drugs, pain threshold and pain tolerance rose slightly, but pain intensity did not decrease. None of the eight placebo-controlled studies of postoperative and acute pain with THC-containing products or the THC-like drug nabilone clearly reduced pain or opioid requirements; these include two knee replacement RCTs published in 2026, with 111 and 163 patients. Because most studies were small and THC doses were low, the evidence for THC is also weak. In an open-label trial of 469 trauma patients, the daily opioid amount was similar in both groups (median 17 and 15 mg morphine equivalents; results only in the registry, no statistical comparison reported). The studies that reported a benefit had no placebo: an open-label trial of 68 patients in coronary bypass surgery, an uncontrolled dose-escalation study and two retrospective comparisons. Meta-analyses of postoperative and acute pain found no clinically meaningful benefit; in the only meta-analysis that found a small benefit, the effect came from a single study of an experimental synthetic cannabinoid (intramuscular levonantradol). The São Paulo Society of Anesthesiology (2024) does not recommend cannabinoids for acute pain; the American (ASRA 2023) and Canadian (PAIN 2021) guidelines focus on perioperative management of patients who use cannabis. Postoperative nausea and vomiting: none of the four controlled studies of nabilone, dronabinol and IV THC (the largest with 340 patients, a single low dose of nabilone) showed superiority over placebo or standard antiemetics; the strength of evidence for nausea is weak, and no study of pure CBD has published results. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 29 controlled studies of cannabinoids on this topic (19 in patients with postoperative or acute pain, 4 in postoperative nausea, 6 in experimental pain in healthy volunteers with CBD-containing products) and 6 systematic reviews were found; all are in the table below. Experimental pain studies in healthy volunteers using only THC or THC-like drugs are not listed individually in the table: those up to 2017 are represented by a meta-analysis, and later ones were not added separately; three postoperative pain studies with selective or experimental synthetic cannabinoids fell outside the site's scope. There is no Cochrane review; a Cochrane protocol for postoperative nausea was published in 2022, but the review itself could not be found in October 2026.

Evidence assessment: Weak; mostly no benefit

• CBD alone: In most RCTs, pure CBD was no different from placebo for postoperative and acute pain and did not reduce opioid use. In a 36-patient pilot RCT in bilateral knee replacement, the primary outcome (72-hour opioid consumption) was also no different from placebo; the reduction at 400 mg appeared only in a post hoc analysis. No study of pure CBD for postoperative nausea has published results.
• Products containing THC: In a meta-analysis of cannabinoids after surgery (most containing THC), there was no difference in opioid consumption or pain at 24 hours; at 12 hours there was an increase in pain and a hypotension signal (OR 3.24). In two knee replacement RCTs published in 2026 (111 and 163 patients), dronabinol did not reduce opioid consumption or pain; in a 469-person open-label trial in trauma patients, the daily opioid amount was similar in both groups (results only in the registry, with no statistical comparison). Positive results came only from small studies without placebo or from retrospective studies. For preventing nausea and vomiting, nabilone, dronabinol and IV THC were no better than placebo or standard anti-nausea medicines in four controlled studies. (weak evidence) Evidence: Weak, pointing to no effect: no clinically meaningful benefit in eight placebo-controlled studies or in meta-analyses; the studies are small, THC doses were low, and there is no meta-analysis combining the new trials
• Dose range in studies: In pure CBD studies, from 20 mg/day to a 400 mg single dose; in bilateral knee replacement, 4 doses of 400 or 800 mg around surgery; after PRK, 100 mg/day; in experimental pain models, 50–1600 mg single dose; in dental pain, 10–20 mg/kg single dose
• Interaction: Opioids: no increase in side effects with fentanyl + 400–800 mg CBD; 'bad effects' increased with hydromorphone + 200 mg CBD; pain threshold fell with methadone + 1200 mg CBD. An opioid-sparing effect has not been proven; monitor for sedation
• Interaction: CNS depressants (gabapentin, pregabalin, benzodiazepines, alcohol): additive sedation; somnolence 32% vs 11% with Epidiolex. No direct clinical study of CBD + gabapentinoids has been reported
• Interaction: NSAIDs: on the label, no significant change with the CYP2C9 substrate tolbutamide; no direct study of CBD + NSAIDs has been reported; no documented significant interaction
• Interaction: Acetaminophen (paracetamol): in knee OA, enzyme elevations were more common with acetaminophen 3 g + CBD 600 mg; monitor liver enzymes
• Interaction: Warfarin: in a case report, INR rose and the warfarin dose was reduced; monitor INR when starting or stopping CBD
• Interaction: Clopidogrel: antiplatelet effect may be reduced via CYP2C19 (label); consult cardiology
• Interaction: DOACs (apixaban, rivaroxaban): no direct data reported; uncertain, should be reported and monitored
• Interaction: Valproate (liver, high risk) and clobazam (sedation 46% vs 16%)
• Interaction: Tizanidine, theophylline (CYP1A2): the label recommends considering a dose reduction
• Interaction: Tacrolimus, sirolimus, everolimus, digoxin: monitoring or dose reduction (label)
• Interaction: Strong inducers such as rifampin: CBD levels fall by ~32%
• Interaction: Note: label data come from high-dose prescription CBD; the size of interactions may differ with non-prescription products, but the direction should be assumed to be the same
• Monitoring in studies: Epidiolex label: at 10–20 mg/kg/day, ALT >3× ULN in 13% (placebo 1%); the risk rises markedly with valproate; monitor at baseline, at months 1, 3 and 6, and after dose changes
• Monitoring in studies: In healthy adults, at 5 mg/kg/day, ALT/AST >3× ULN in 5.6% (placebo 0%) and eosinophilia (Florian 2025, PMID 40622698); at 1500 mg/day, >5× ULN in 31% (Watkins 2021, PMID 33022751)
• Monitoring in studies: Liver enzymes should be monitored when CBD is combined with acetaminophen (paracetamol) and other medicines that burden the liver (Pramhas 2023, PMID 38033459)

References (43)

Study table (dose, duration, result) · Topic page

Low-dose oral pure CBD was not superior to placebo in two RCTs: 5–50 mg/day in various peripheral nerve pains (8 weeks; on one scale the result was worse than placebo) and up to 45 mg/day in nerve pain from MS or spinal cord injury (6 weeks). In a crossover RCT (40 people) in neuropathic pain from spinal cord injury with titration to 800 mg/day, the pain score was 0.54 points (0–10 scale) lower than with placebo; the effect is small and rests on a single small study. There are two small RCTs of CBD applied to the skin: a methodologically weak study (29 people) in lower-extremity peripheral neuropathy reported a positive result; a crossover pilot study of pure CBD cream in chemotherapy-induced neuropathy (40 people, 2 + 2 weeks) found no difference from placebo. In HIV-associated neuropathy, CBDV, a cannabinoid closely related to CBD (400 mg/day, 32 people), was also not superior to placebo. In a series of single-patient crossover trials in 24 people with persistent symptoms due to neurological diseases such as MS and spinal cord injury (Wade 2003; each product for 2 weeks), pain was significantly better with a CBD-rich plant extract than with placebo; the patients were not selected for neuropathic pain, the THC content of the extract was not reported and the abstract gives no effect size, so the finding counts as very weak evidence. There are 28 RCTs of products containing THC: THC:CBD oromucosal spray (nabiximols) showed a small benefit in two 4–5-week studies; in two large 14–15-week studies the difference in mean pain was not significant (in one, the ≥30% responder rate was significantly higher with the spray); the manufacturer’s negative results in diabetic neuropathy (297 people) and spinal cord injury (116 people) are available only on ClinicalTrials.gov. Small studies of inhaled cannabis lasting from a single day to 5 days showed short-term pain reduction (individual patient data meta-analysis of 5 RCTs: NNT 5.6). Dronabinol was beneficial in a small 3-week study in MS and ineffective in a 16-week, 240-person study. A single-center, 100-person, 12-week RCT of a THC-dominant oil (THC:CBD:CBN) applied to the skin in diabetic neuropathy reported a very large benefit; it has not been independently confirmed. Of 3 RCTs with nabilone (15–96 people), one found it worse than dihydrocodeine, and two (one with an enriched design enrolling only initial responders) found it beneficial. Cochrane 2026 (21 RCTs, 2,187 people; only double-blind studies lasting at least 2 weeks): no clear effect on ≥50% relief for any of THC-dominant, balanced THC:CBD or CBD-dominant products (very low certainty); with the balanced product, ≥30% relief and the patient’s global impression may increase slightly (RD 0.07; low certainty); nervous system side effects increased (RD 0.25–0.39; low to very low certainty); two-thirds of the studies were funded by drug companies. Reviews reach different conclusions: a meta-analysis of 8 RCTs reported a moderate-certainty benefit for pain and sleep. Guidelines and expert bodies do not recommend cannabinoids as a first choice for nerve pain; where they differ is on whether they can be tried when other treatments have not been enough. The neuropathic pain special interest group of the International Association for the Study of Pain (NeuPSIG) issued a weak recommendation against using cannabinoids in 2015; cannabinoids are also absent from the first-, second- and third-line treatments recommended in the group’s 2025 update. The German Neurological Society’s 2019 guideline does not recommend cannabinoids because their effect is small and their side effects common; it states that, when other treatments have failed, they may be tried off-label only in individual patients as part of a multimodal treatment plan. A 2022 Canadian primary care guideline (PEER) finds the benefit of cannabinoids in nerve pain uncertain and lists them among options that can be discussed with the patient after treatments with clear benefit have been considered. There are also more favorable views: the Canadian Pain Society recommended cannabinoids as third-line treatment in 2014 (and wrote that they may be considered first-line for pain from spinal cord injury); the European Pain Federation’s 2018 position paper states that, when first- and second-line drugs do not work well enough or are not tolerated, experienced physicians may consider cannabis-based products as part of multimodal treatment, preferably as add-on drugs; and the Brazilian Academy of Neurology in 2020 placed products containing THC and CBD at the third line for central nerve pain, not as monotherapy but as add-on drugs in selected patients who have not responded to other drugs. The same academy’s 2021 position paper, however, states that for peripheral nerve pain the evidence points more toward their being ineffective, and that in some situations without an established evidence-based treatment (nerve pain from spinal cord injury, central post-stroke pain, chemotherapy or trauma) they may be considered as add-on treatment within an individual plan (one of its 49 authors is an executive at a CBD company); in chemotherapy-induced nerve damage, three small controlled studies published after this paper (2024–2025) found that pain or neuropathy symptoms did not improve more than with placebo. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 35 controlled studies of cannabinoids in patients with neuropathic pain were found (all randomized; 3 with results only in the registry); all of them are in the table below, together with 6 topic-specific systematic reviews (including the 2018 and 2026 versions of the Cochrane review) and 4 real-world studies (one specific to complex regional pain syndrome). Complex regional pain syndrome was searched separately on October 28, 2026 (PubMed, ClinicalTrials.gov): no controlled study specific to this condition was found; three short studies of inhaled cannabis in mixed nerve pain groups also included patients with this syndrome (in one, most of the patients), but no separate result was given for them; a study comparing a CBD-rich extract with placebo is ongoing according to its registration. There is no separate page for burning mouth syndrome (burning pain inside the mouth that persists without a visible cause); it was searched separately on October 29, 2026 (PubMed, ClinicalTrials.gov): in a single-center, single-blind study comparing full-spectrum CBD oil (THC content not reported) with placebo in 26 patients (Parise 2026), pain decreased more than in the placebo group from the third assessment onward, and oral health–related quality of life also improved in the CBD group; in a 4-week study without a control group in 17 patients using an oil made from cannabis flowers (Gambino 2021), symptoms were reported to decrease over time. Both are very small and the evidence is very weak; the placebo-controlled study is in the table (not added to the neuropathic pain counts above), and the uncontrolled study is mentioned only here and in the research section. Studies in groups not selected for neuropathic pain (except Wade 2003, which also tested a CBD-rich extract: that study is in the table to show every piece of data on the CBD side, but it was not added to the count of controlled studies above), experimental synthetic drugs that target the body’s own cannabinoid system, and three small registry records whose comparative pain results could not be interpreted were not included in the table; completed studies with unpublished results are listed under unverifiable items.

Evidence assessment: Weak; conflicting (oral 45–50 mg/day negative in two RCTs, 800 mg/day small benefit in a single small RCT; Cochrane 2026: no clear effect with CBD-dominant products, very low certainty)

• CBD alone: Low-dose pure CBD by mouth (45–50 mg/day) was no better than placebo in two RCTs (in Zubcevic 2023, +1.14 NRS worse on one scale); at a very high dose (800 mg/day), a single small RCT in spinal cord injury showed a small benefit (−0.54/10). In a 40-person crossover pilot RCT (2 + 2 weeks) of pure CBD cream applied to the skin in chemotherapy-related neuropathy, there was no difference. In Cochrane 2026, CBD-dominant products (5 studies, 208 people) showed no clear effect on ≥50% relief (RD −0.08; 95% CI −0.20 to 0.05; very low certainty); the high-dose study was published after this review’s search. In an old 24-person crossover study in people with persistent symptoms due to neurological diseases (Wade 2003), pain decreased significantly more with a CBD-rich plant extract than with placebo; but the patients were not selected for neuropathic pain, each product was tried for only 2 weeks and the THC content of the extract was not reported (very weak evidence).
• Products containing THC: There are 28 RCTs of products containing THC (THC:CBD spray, dronabinol, sublingual THC, sublingual THC:CBD oil, inhaled cannabis, CBD+THC capsules, THC oil applied to the skin; 3 have results only in the registry, and 2 are the THC arms of four-arm CBD studies). In most studies lasting from a single day to 5 weeks, pain decreased slightly more than with placebo; in most studies lasting 6 weeks or longer, there was no clear difference (a single 100-person study with an oil applied to the skin reported a large but unconfirmed benefit). Cochrane 2026: no clear effect on ≥50% relief (THC-dominant RD 0.14, 95% CI −0.07 to 0.37; balanced THC:CBD RD 0.04, 0.00–0.08; very low certainty); with the balanced product, ≥30% relief may increase slightly (RD 0.07; low certainty). Nervous system side effects increased (THC-dominant RD 0.25, low certainty; balanced RD 0.39, very low certainty). There are also 3 RCTs with nabilone (15–96 people). (weak evidence) Evidence: Low to very low certainty (Cochrane 2026): benefit uncertain or small, nervous system side effects more common
• Dose range in studies: Oral pure CBD 5–50 mg/day (6–8 weeks) and up to 800 mg/day (6 weeks); topical 250 mg CBD / 3 fl oz oil; pure CBD cream twice a day (amount not reported). For products containing THC: mouth spray up to 12–48 sprays a day (2.5–2.7 mg THC per spray), dronabinol up to 10–15 mg a day, nabilone 1–4 mg/day, inhaled cannabis 1–9.4% THC (mostly single sessions; in one study 0.5–1 mg THC with a metered-dose device), CBD+THC capsules 125–300 mg CBD + 6–15 mg THC a day, THC-dominant oil on the skin 1–6 drops depending on pain intensity (3.2 mg THC per drop)
• Starting dose and titration (in studies): Flexible dosing in Zubcevic 2023; 3-week titration in Hansen 2023; in Robertson 2026, increased by 200 mg every 4 days to 800 mg/day on day 13; in the nabiximols study, patients self-titrated
• Interaction: Opioids: no increase in side effects with fentanyl + 400–800 mg CBD; 'bad drug effect' increased with hydromorphone + 200 mg CBD; pain threshold decreased with methadone + 1,200 mg CBD. An opioid-sparing effect has not been proven; monitor for sedation
• Interaction: CNS depressants (gabapentin, pregabalin, benzodiazepines, alcohol): additive sedation; somnolence with Epidiolex 32% vs. 11%. No direct clinical study of CBD + gabapentinoids has been reported
• Interaction: NSAIDs: the label shows no significant change in tolbutamide, a CYP2C9 substrate; no direct study of CBD + NSAIDs has been reported; no documented significant interaction
• Interaction: Acetaminophen (paracetamol): in knee OA, enzyme elevations were more frequent with acetaminophen 3 g + CBD 600 mg; monitor liver enzymes
• Interaction: Warfarin: in a case report, INR rose and the warfarin dose was reduced; monitor INR when starting or stopping CBD
• Interaction: Clopidogrel: antiplatelet effect may be reduced via CYP2C19 (label); consult cardiology
• Interaction: DOACs (apixaban, rivaroxaban): no direct data reported; uncertain, should be disclosed and monitored
• Interaction: Valproate (liver, high risk) and clobazam (sedation 46% vs. 16%)
• Interaction: Tizanidine, theophylline (CYP1A2): the label recommends considering a dose reduction
• Interaction: Tacrolimus, sirolimus, everolimus, digoxin: monitoring or dose reduction (label)
• Interaction: Strong inducers such as rifampin: CBD levels fall by ~32%
• Interaction: Note: label data come from high-dose pharmaceutical CBD; with nonprescription products the size of an interaction may differ, but its direction should be assumed to be the same
• Monitoring in studies: Epidiolex label: at 10–20 mg/kg/day, ALT >3×ULN in 13% (placebo 1%); risk rises markedly with valproate; monitor at baseline, at months 1, 3 and 6, and after dose changes
• Monitoring in studies: In healthy adults, 5 mg/kg/day led to ALT/AST >3×ULN in 5.6% (placebo 0%) and eosinophilia (Florian 2025, PMID 40622698); 1,500 mg/day led to >5×ULN in 31% (Watkins 2021, PMID 33022751)
• Monitoring in studies: Liver enzymes should be monitored with acetaminophen (paracetamol) and other medicines that strain the liver (Pramhas 2023, PMID 38033459)

References (47)

Study table (dose, duration, result) · Topic page

Three RCTs found no superiority of oral CBD over placebo: hand osteoarthritis/psoriatic arthritis (20–30 mg, 12 weeks), knee osteoarthritis (600 mg/day, 8 weeks) and knee osteoarthritis (45 mg/day CBD-rich oil, 60 days). In the 600 mg/day study, side effects and raised liver enzymes were more common in the CBD group. Small studies of topical products show conflicting results (see topical CBD). With products containing THC: in rheumatoid arthritis, a single RCT of a THC:CBD mouth spray (58 people, 5 weeks) showed a small improvement in pain and DAS28, with more frequent nervous system side effects (Cochrane: weak evidence, potential harms outweigh the small benefit; GRADE: low certainty; the reviews’ risk-of-bias assessments disagree); in knee osteoarthritis, a single 10 mg dose of dronabinol did not reduce clinical pain more than placebo in two crossover laboratory RCTs (37 and 21 people). A randomized study without placebo comparing three cannabinoid capsules (Kruger 2026) and patient registries (UK, Australia) reported improvement from baseline; with no comparison group, they do not count as evidence of effectiveness. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 8 randomized studies of cannabinoids in this area (7 placebo-controlled), 1 open-label study, 5 reviews (one Cochrane) and 3 observational studies were found; all are in the table below. Not included in the table: a skin gel study announced only as a conference abstract, a non-peer-reviewed 12-person preprint (oral CBD in knee osteoarthritis), completed studies with unpublished results (see unverifiable items) and studies with hemp seed oil (seed oil is not a CBD or THC product; these studies did not report cannabinoid content).

Evidence assessment: Moderate (pointing to no benefit for oral CBD)

• CBD alone: Oral pure CBD did not reduce pain more than placebo in osteoarthritis and hand arthritis; at high doses, raised liver enzymes were more common. There is no published study comparing pure CBD with placebo in rheumatoid arthritis or ankylosing spondylitis (October 2026); the results of a completed study in rheumatoid arthritis (NCT04911127) have not yet been published.
• Products containing THC: There is a single controlled study lasting several weeks of products containing THC in this area: in rheumatoid arthritis, a mouth spray containing THC and CBD showed slightly more improvement in pain and disease activity than placebo over 5 weeks, but nervous system side effects such as dizziness were also more common (58 people; low-certainty evidence). The Cochrane review wrote that the potential harms seem to outweigh this small benefit. In knee osteoarthritis, a single dose of dronabinol (synthetic THC) did not reduce joint pain more than placebo in two laboratory studies. In patient registries, people using THC-containing products reported improvement in pain, but there was no comparison group. Controlled studies testing THC for weeks in osteoarthritis are ongoing (NCT06878417, NCT04992624). (weak evidence) Evidence: Weak (a single small RCT in rheumatoid arthritis; in knee osteoarthritis, only single-dose laboratory studies)
• Dose range in studies: Oral CBD 20–30 mg/day, 45 mg/day and 600 mg/day; topical 6.2 mg/mL (1 mL twice a day) and 4% gel; with THC: in RA, THC:CBD mouth spray averaging ~14.6 mg THC + 13.5 mg CBD/day; in knee OA, a single 10 mg dose of dronabinol
• Starting dose and titration (in studies): Vela 2022: 10 → 20 → 30 mg/day; Pramhas 2023: 600 mg/day in three equal steps during the first week; Mojoli 2025: fixed 45 mg/day; Blake 2006: started with 1 spray in the evening and increased every 2 days (up to 6)
• Interaction: Opioids: no increase in side effects with fentanyl + 400–800 mg CBD; 'bad drug effect' increased with hydromorphone + 200 mg CBD; pain threshold decreased with methadone + 1,200 mg CBD. In knee OA, hydromorphone + a single 10 mg dose of dronabinol: no additional analgesia; the feeling of being high increased, and moderate side effects (Campbell 2023) and nausea (Hamilton 2026; compared with hydromorphone alone) were more frequent. An opioid-sparing effect has not been proven; monitor for sedation
• Interaction: CNS depressants (gabapentin, pregabalin, benzodiazepines, alcohol): additive sedation; somnolence with Epidiolex 32% vs. 11%. No direct clinical study of CBD + gabapentinoids has been reported
• Interaction: NSAIDs: the label shows no significant change in tolbutamide, a CYP2C9 substrate; no direct study of CBD + NSAIDs has been reported; no documented significant interaction
• Interaction: Acetaminophen (paracetamol): in knee OA, enzyme elevations were more frequent with acetaminophen 3 g + CBD 600 mg; monitor liver enzymes
• Interaction: Warfarin: in a case report, INR rose and the warfarin dose was reduced; monitor INR when starting or stopping CBD
• Interaction: Clopidogrel: antiplatelet effect may be reduced via CYP2C19 (label); consult cardiology
• Interaction: DOACs (apixaban, rivaroxaban): no direct data reported; uncertain, should be disclosed and monitored
• Interaction: Valproate (liver, high risk) and clobazam (sedation 46% vs. 16%)
• Interaction: Tizanidine, theophylline (CYP1A2): the label recommends considering a dose reduction
• Interaction: Tacrolimus, sirolimus, everolimus, digoxin: monitoring or dose reduction (label)
• Interaction: Strong inducers such as rifampin: CBD levels fall by ~32%
• Interaction: Note: label data come from high-dose pharmaceutical CBD; with nonprescription products the size of an interaction may differ, but its direction should be assumed to be the same
• Monitoring in studies: Epidiolex label: at 10–20 mg/kg/day, ALT >3×ULN in 13% (placebo 1%); risk rises markedly with valproate; monitor at baseline, at months 1, 3 and 6, and after dose changes
• Monitoring in studies: In healthy adults, 5 mg/kg/day led to ALT/AST >3×ULN in 5.6% (placebo 0%) and eosinophilia (Florian 2025, PMID 40622698); 1,500 mg/day led to >5×ULN in 31% (Watkins 2021, PMID 33022751)
• Monitoring in studies: Liver enzymes should be monitored with acetaminophen (paracetamol) and other medicines that strain the liver (Pramhas 2023)

References (17)

Study table (dose, duration, result) · Topic page

In chronic pain, CBD was not superior to placebo in 15 of 16 RCTs that used pharmaceutical-grade pure CBD (Moore 2024). In the fibromyalgia RCT (50 mg/day, 24 weeks), placebo did better than CBD. In chronic pelvic pain due to endometriosis, a CBD-rich oil (up to 150 mg/day, 10 weeks, 102 people) was no better than placebo, and the study was stopped at an interim analysis; in jaw joint muscle pain, 20 mg/day of CBD oil (3 months, 54 people) also did not change pain. No RCT has been reported showing an opioid-reducing effect of pure CBD in chronic pain. Oral medical cannabis containing THC gave a small to very small improvement in pain (moderate certainty), and the BMJ guideline made this a weak recommendation. IASP (2021) does not support the general use of cannabinoids for pain. According to the 2026 update from the US Agency for Healthcare Research and Quality (AHRQ) (25 RCTs, 2303 people), oral THC and balanced THC:CBD products may reduce pain slightly (low or moderate certainty), while CBD-dominant products may not; according to Stockings 2018, 24 people need to be treated for one person to get meaningful relief, and 1 in every 6 people has an additional side effect. The UK's national guideline (NICE 2019) does not recommend THC-containing products for chronic pain and recommends CBD only in clinical trials; the American College of Physicians (ACP 2025) says that in young adults and adolescents, in people with a substance use disorder or serious mental illness, and in frail patients, the harms most likely outweigh the benefits, and that inhaled cannabis should not be used. A clinical guideline prepared in Canada (Bell 2024), however, summarizes the evidence as 'at least a moderate benefit in most studies' and recommends cannabinoid-based medicines for chronic pain at the level of 'strong recommendation, moderate-quality evidence'; the guideline itself also writes that the strongest evidence is for THC-containing products, not for CBD. This guideline's search ends in 2019, it also counts uncontrolled studies, a cannabis company took part in its funding, and 7 of its 20 authors reported ties to cannabis companies; meta-analyses that pool only placebo-controlled studies, on the other hand, find the benefit small or very small. Small THC RCTs in chronic abdominal pain and sickle cell disease found no difference from placebo; in the safety study in hemodialysis patients, pain was not compared statistically. On the opioid reduction question, opioid dose did not fall in RCTs (Noori 2021, very low certainty); in the only study where cannabis use was assigned by lottery to 87 adults with chronic pain taking opioids, opioid dose and pain at 24 weeks also did not differ from the waiting group (results only in the ClinicalTrials.gov registry). While uncontrolled studies based on patients' own reports describe a clear decrease in opioid use (in the observational studies pooled by Nielsen 2022, the pooled proportion who said they had lowered their dose was 85%; in an uncontrolled series of 1000 patients with chronic low back pain followed for 10 years in Israel, opioid dose fell by 90% among those who completed follow-up, and the authors themselves write that observational bias plays a part in this, Khatib 2026), studies using prescription records or a comparison group show no effect (Campbell 2018, Goedel 2022), a small effect (Nguyen 2023, Slawek 2026) or an effect in the opposite direction (Fontaine 2026: starting long-term opioids was more common in older adults). In a network meta-analysis that indirectly compared cannabis and opioid studies, no difference in pain was seen (low certainty), and fewer people stopped cannabis because of side effects (Jeddi 2024); in a large registry study comparing people who started nabilone with those who started opioids, falls, fractures and deaths were less common, while mental health problems related to substance use were more common (Vozoris 2024). In healthy volunteers, it is inconsistent whether THC increases the painkilling effect of opioids; THC may increase the abuse-related effects of opioids (Nielsen 2022). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 20 randomized controlled trials with cannabinoids on this topic were found (8 with CBD alone; 2 laboratory studies in healthy volunteers done together with an opioid; 3 with results only in the ClinicalTrials.gov registry), along with 11 systematic reviews, 1 publication bias analysis, 5 guidelines or position statements and 12 observational or uncontrolled studies; all are in the table below. Cochrane has no review specific to general chronic pain. Laboratory studies in healthy volunteers that tested CBD together with an opioid are listed one by one in the table; the 5 laboratory studies that tested THC together with an opioid were not listed individually but are summarized through the Nielsen 2022 row. The many small patient registries and uncontrolled studies were also not listed individually; they are summarized through reviews (Nielsen 2022, Noori 2021, Bialas 2022, Zeraatkar 2022).

Evidence assessment: Moderate (no benefit seen with pure CBD; placebo did better in the fibromyalgia RCT); opioid reduction: very low certainty (opioid dose did not fall in RCTs)

• CBD alone: Pure CBD was not found to be better than placebo in chronic pain (Moore 2024: 15 of 16 RCTs; AHRQ living review: no difference in pain in 4 RCTs of oral pure CBD, moderate certainty), and an opioid-reducing effect has not been shown in RCTs; no conclusions can be drawn from two small CBD studies in patients taking opioids (an RCT that finished with 6 people and an uncontrolled cohort of 97 people).
• Products containing THC: Oral THC-containing cannabinoids give a small improvement in pain (Wang 2021: −0.50 cm VAS; AHRQ 2026: oral THC −0.78, THC:CBD oral spray −0.54 points/10), with increased dizziness, drowsiness and nausea; in chronic low back pain, a THC-dominant full-spectrum extract gave −0.6 NRS versus placebo. In the open-label manufacturer study comparing the same extract with opioids, constipation was less common; the difference in pain was small (0.34 points) and not significant in the confirmatory analysis carried out in the pre-specified order. Small RCTs in chronic abdominal pain and sickle cell disease found no difference from placebo (in the safety study in hemodialysis patients, pain was not compared statistically between groups); NICE (2019) does not recommend them for chronic pain. (moderate evidence) Evidence: Moderate certainty, small to very small effect (Wang 2021); AHRQ 2026: low–moderate certainty, small effect; BMJ guideline weak recommendation, NICE (2019) does not recommend
• Dose range in studies: Pure CBD in pain RCTs 6–1600 mg (Moore 2024); fibromyalgia 50 mg/day; endometriosis 10–150 mg/day; jaw pain 20 mg/day; 50–1200 mg single doses in laboratory opioid interaction studies; 600 mg/day in patients with radicular pain taking opioids (6 people). In studies of THC-containing or THC-like products: nabilone (a synthetic THC-like cannabinoid) 0.25–1 mg/day, dronabinol 10–20 mg single dose, purified THC up to 24 mg/day (abdominal pain), THC-dominant extract with a dose unit of 2.5 mg THC and at most 13 units a day (low back pain) (study doses; not a personal recommendation)
• Starting dose and titration (in studies): Schedules used in the studies (not a personal recommendation): in most CBD studies the dose was fixed from the start; in the endometriosis study, the CBD-rich oil was raised from 10 mg/day in weekly steps to 150 mg/day by week 9. In studies of THC-containing products, the dose was increased little by little every few days (e.g., every 3 days in the low back pain study), and side effects were seen most often during this increase period
• Interaction: Opioids: fentanyl + 400–800 mg CBD, no increase in side effects; hydromorphone + 200 mg CBD, 'bad effects' increased; methadone + 1200 mg CBD, pain threshold fell. Inhaled cannabis did not significantly change total blood levels of morphine and oxycodone (Abrams 2011); in laboratory studies in healthy volunteers, THC could increase the abuse-related effects of opioids (Nielsen 2022). An opioid-reducing effect has not been proven; sedation should be monitored
• Interaction: CNS depressants (gabapentin, pregabalin, benzodiazepines, alcohol): additive sedation; with Epidiolex, somnolence 32% versus 11%. No direct clinical study of CBD + gabapentinoids has been reported
• Interaction: NSAIDs: on the label, no significant change in the CYP2C9 substrate tolbutamide; no direct study of CBD + NSAIDs has been reported; no documented significant interaction
• Interaction: Acetaminophen (paracetamol): in knee OA, enzyme elevations were more common with acetaminophen 3 g + CBD 600 mg; liver enzymes should be monitored
• Interaction: Warfarin: in a case report, INR rose and the warfarin dose was reduced; INR should be monitored when CBD is started or stopped
• Interaction: Clopidogrel: the antiplatelet effect may be reduced via CYP2C19 (label); cardiology should be consulted
• Interaction: DOACs (apixaban, rivaroxaban): no direct data reported; uncertain, should be disclosed and monitored
• Interaction: Valproate (liver, high risk) and clobazam (sedation 46% versus 16%)
• Interaction: Tizanidine, theophylline (CYP1A2): the label recommends considering a dose reduction
• Interaction: Tacrolimus, sirolimus, everolimus, digoxin: monitoring or dose reduction (label)
• Interaction: Strong inducers such as rifampin: CBD levels fall by ~32%
• Interaction: Note: label data come from high-dose pharmaceutical CBD; with non-prescription products the size of an interaction may differ, but its direction should be assumed to be the same
• Monitoring in studies: Epidiolex label: at 10–20 mg/kg/day, ALT >3× ULN in 13% (placebo 1%); the risk rises markedly with valproate; monitoring at baseline, at months 1, 3 and 6, and after dose changes
• Monitoring in studies: In healthy adults, 5 mg/kg/day gave ALT/AST >3× ULN in 5.6% (placebo 0%) and eosinophilia (Florian 2025, PMID 40622698); 1500 mg/day gave >5× ULN in 31% (Watkins 2021, PMID 33022751)
• Monitoring in studies: Liver enzymes should be monitored when combined with acetaminophen (paracetamol) and other medicines that strain the liver (Pramhas 2023, PMID 38033459)

References (49)

Study table (dose, duration, result) · Topic page

A small crossover RCT in arthritis of the thumb base joint (n=18), an RCT in jaw joint muscle pain (n=60) and an RCT with an intraoral CBD gel in jaw muscle pain due to bruxism (n=60; 10% and 5% gels better than placebo for pain, no between-group difference in teeth-grinding severity) reported positive results. No benefit was seen after total knee replacement (n=80), in chemotherapy-induced neuropathy (n=40) or in muscle soreness after exercise (three small studies). In vestibulodynia, a CBD + myrcene gel (n=40) did not differ from placebo for pain; only pain during intercourse fell more, but the baseline score was higher in this group. Samples are small and product contents vary; the carrier oil's own effect, blinding and measurement of systemic absorption are inadequate. The two positive RCTs in jaw pain come from the same university department and their participants were mostly in their 20s; the first was registered retrospectively, and the number of participants and date in the second one's registration do not match the paper; in both studies, groups were assigned by choosing numbers. In recurrent canker sores, in a 69-person, three-arm (CBD, steroid, placebo) RCT with a 0.1% CBD paste applied to the ulcers, ulcers shrank faster than with placebo, but pain was lower than with placebo only on day 5. In a study with no control group (4% CBD gel in hand osteoarthritis, n=18), pain decreased from baseline. With THC-containing products: in diabetic neuropathy, a single-center RCT with a THC-dominant oil (n=100, 12 weeks) reported a large benefit (NPSI-T difference −17.3), but it has not been confirmed and the numbers in the paper are inconsistent; in an open-label study without placebo (n=21) comparing CBD and THC ointments in hand pain caused by aromatase inhibitors, both ointments were well tolerated, and the groups were not compared statistically. The evidence for THC-containing products is very weak. Systematic reviews: high risk of bias in topical CBD studies (2023); the AHRQ 2025 living review found the evidence for topical CBD and for the THC:CBD:CBN oil insufficient; a 2025 review of medicines applied through the skin or inside the mouth in jaw disorders saw a short-term benefit in two CBD studies but did not perform a pooled analysis. In healthy volunteers (n=46), CBD passed into the blood with three of five commercial products; there was no THC in the blood, but in 9 people the oral fluid test exceeded the THC threshold. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 13 randomized studies measuring pain with cannabinoid products applied to the skin or inside the mouth (12 placebo- or vehicle-controlled; 2 with a THC-containing product) and 3 systematic reviews were found; all of them are in the table below, along with 1 study with no control group and 1 study of absorption in healthy volunteers. Cochrane has no review specific to this topic. Not included in the table: hemp seed oil products (seed oil is not a CBD or THC product), a wound pain study in which CBD was also given by mouth, two small studies with no control group using products that contained camphor, methyl salicylate or other undisclosed substances alongside CBD (it cannot be separated whether the improvement came from CBD or the other substances), publications in which pain was not measured or that are at the level of case reports, and a knee gel study published only as a conference abstract; studies whose results are unpublished are listed under the unverifiable items.

Evidence assessment: Weak; conflicting (many small RCTs, results in both directions)

• CBD alone: With topical CBD, the results conflict; the positive studies are small and single-center (the two positive RCTs in jaw pain come from the same research group), and the negative studies include knee replacement (80 people) and chemotherapy neuropathy (40 people). In mouth ulcers (canker sores, 69 people), a CBD paste sped up ulcer shrinkage, but pain was lower than with placebo on only one measurement day. A small study with no control group (hand osteoarthritis, 18 people) reported improvement from baseline; because there was no comparison group, it does not count as evidence of effectiveness. Systematic reviews find the evidence insufficient or the risk of bias high (AHRQ 2025, a 2023 review of topical CBD); a 2025 review evaluating the two jaw pain studies sees a short-term benefit but makes no strong recommendation.
• Products containing THC: There are two studies with THC-containing products rubbed on the skin. In nerve pain caused by diabetes, a THC-dominant cannabis oil (THC:CBD:CBN) reduced pain symptoms much more than placebo in a 100-person, 12-week, single-center placebo-controlled study (NPSI-T difference −17.3 points); some numbers in the paper do not match each other and there is no second study confirming the result. In a 21-person open-label study without placebo comparing THC-dominant and CBD-dominant ointments in hand joint pain caused by a breast cancer medicine (aromatase inhibitor), both ointments were well tolerated; the share of people reporting clear improvement was given as 50% with the THC ointment and 18% with the CBD ointment, but the two groups were not compared statistically and participants knew which ointment they were using, so these rates do not show that one ointment is better. The AHRQ 2025 review found the evidence for the THC:CBD:CBN oil insufficient. (very weak evidence) Evidence: Very weak (a single placebo-controlled study with a THC-containing product rubbed on the skin: single-center, not confirmed by another study, some numbers in the paper inconsistent; plus a small feasibility study without placebo)
• Dose range in studies: In topical studies, 6.2 mg/mL (1 mL twice a day), 4% gel 3 times a day, ~100 mg per application, intraoral 5–10% gel (20–40 mg/day), 5% CBD + myrcene gel once a day; in canker sores, 0.1% CBD paste 3 times a day; THC-dominant oil on the skin, 1–6 drops depending on pain severity (3.2 mg of THC per drop); hand ointments 3 times a day (2210 mg of CBD or 375 mg of THC per jar); most did not report the concentration

References (18)

Study table (dose, duration, result) · Topic page

No controlled human study in migraine with pure CBD oil published as a full article was found. A small preliminary study in Argentina comparing CBD with placebo for 3 months in 30 people with chronic migraine reported a reduction in monthly migraine days compared with placebo at the European Headache Congress in December 2025; however, it was presented only as a short abstract: the number of people in each group, confidence intervals, how the product was taken, whether it contained THC and the daily amount were not stated, no full article or study registration was found, and 4 of the 10 authors are from the research department of the pharmaceutical company that supplied the product. A 79-person study (2017) comparing oral drops containing THC and CBD with a migraine medicine (amitriptyline) for migraine prevention also exists only as a conference abstract. Because neither abstract could be verified, they were not counted as evidence and were not included in the table. In the only placebo-controlled study in acute migraine (92 people enrolled, 73 treated a total of 247 attacks), CBD-dominant vaporized and inhaled marijuana was not clearly different from placebo at 2 hours; the mixture containing both THC and CBD reduced pain at 2 hours. The positive result came from an inhaled product containing THC; it does not count as evidence for CBD oil taken by mouth. The other controlled study is small and indirect: in a 30-person study in medication overuse headache (headache caused by overusing pain relievers) comparing the synthetic THC-like medicine nabilone with ibuprofen, nabilone reduced pain and pain reliever use more, while there was no difference in the number of headache days; no placebo group was used. Observational studies without a comparison group (charts of 121 patients in the US and 32 in Italy, and a 203-person patient registry in the United Kingdom) reported fewer complaints, but cannot separate out the placebo effect and spontaneous improvement; in the charts of 368 patients with chronic migraine, medication overuse headache was more common among cannabis users (an association; cause and effect not shown). There are no controlled studies in cluster headache or tension-type headache. On ClinicalTrials.gov, the results of two studies have not been published: one completed in 2007 (inhaled dronabinol, acute migraine) and one that stopped enrolling after an interim analysis and ended in 2025 (CBD, CBG and low THC, chronic migraine). Two small studies done in other conditions that tracked headache as a secondary outcome (nabilone in chronic musculoskeletal pain, an intraoral CBD gel in teeth clenching) were not counted because they were not done in migraine patients. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 2 controlled studies and 3 systematic reviews of cannabinoid treatment on this topic were found (no Cochrane review); the two controlled studies and the two most comprehensive reviews are in the table below, and the third review, which includes only observational studies and overlaps with these two reviews, was not included in the table. A second search on October 28, 2026 (including child and adolescent migraine, oral, inhaled and sublingual products, nabilone and dronabinol, patient registries, ClinicalTrials.gov results, guidelines and conference abstracts) found no new study to add to the table; a 2024 network meta-analysis comparing treatments for medication overuse headache included the nabilone study but did not give a separate result for nabilone. None of the guidelines and position statements reviewed recommend cannabinoids: the 2022 medication overuse headache guideline of the German Society of Neurology and the German Migraine and Headache Society states that the small study with cannabinoids gives no firm conclusion because of weaknesses in its methods and that this treatment cannot be recommended; the Brazilian Academy of Neurology's 2021 position statement (written before the acute migraine study) states that there are no clinical studies supporting cannabinoid use in primary headaches; the Canadian Headache Society's 2024 migraine prevention guideline did not assess cannabinoids.

Evidence assessment: Pure CBD: Insufficient

• CBD alone: There is no controlled study in migraine with pure CBD oil published as a full article; the positive results of a small 30-person preliminary study in chronic migraine appeared only in a conference abstract and could not be verified, so they were not counted as evidence. The CBD-dominant product tested in the only controlled study in acute migraine was also not an oil but inhaled marijuana (it also contained 0.35% THC), and it was not clearly different from placebo at 2 hours; in an additional measurement at 1 hour, relief was more common in this group (59% vs. 37%), but this was not the study's main outcome.
• Products containing THC: Vaporized and inhaled marijuana containing THC and CBD eased pain more than placebo at 2 hours in acute migraine (67.2% vs. 46.6%); inhaled marijuana containing THC alone also eased pain (68.9%), but was no different from placebo for the pain going away completely. Inhaled products containing THC can cause a high and mental fogginess; these effects can let participants figure out which group they are in and make the result look better than it is (in the study's measurement, guesses in the THC and CBD group were mostly at the level of chance). In medication overuse headache, the synthetic THC-like medicine nabilone reduced pain and pain reliever use more than ibuprofen in a 30-person preliminary study (no placebo group). Registry studies without a comparison group following migraine patients prescribed cannabis reported fewer complaints; in the charts of patients with chronic migraine, medication overuse headache was more common among cannabis users (81% vs. 41%); this is an association, and it was not shown that cannabis caused it. (moderate evidence) Evidence: THC+CBD: Moderate (acute migraine, inhaled; single controlled study); nabilone: Very weak (medication overuse headache; single 30-person study, no placebo)
• Dose range in studies: In the acute migraine study, vaporized and inhaled marijuana (11% CBD and/or 6% THC); amount not reported in mg; in medication overuse headache, oral nabilone 0.5 mg/day
• Interaction: The migraine studies on this page did not systematically assess drug interactions. CBD can slow the breakdown of some medicines in the body; if you take medicines regularly, talk to your doctor or pharmacist.

References (8)

Study table (dose, duration, result) · Topic page

For pure CBD, the best evidence is negative: in a 200-person, 24-week RCT, CBD 50 mg a day reduced pain less than placebo. This result says nothing about higher doses; those doses were not tested. For THC-containing products there are only small pilot signals; adding vaporized THC+CBD to oxycodone gave no added benefit in an 81-patient open-label RCT, and one-third of those taking cannabis stopped because of side effects; in a single-dose experimental study, no product was clearly different from placebo. There are two small RCTs with nabilone, a synthetic THC-like medicine (40 people, 4 weeks vs. placebo; 31 people, 2 weeks vs. amitriptyline): pain and quality of life improved in one and sleep in the other; the Cochrane review (2016) rated this evidence as very low certainty. A THC-rich cannabis oil lowered the fibromyalgia impact score more than placebo in an 8-week RCT of 17 women (the product was not standardized; the two oils differed in color and taste); in a crossover lab study (20 people) with a single dose of THC oil under the tongue, the change in pain from baseline was not significantly different from the placebo session (the analysis in the full text does not support the 'superior to placebo' wording in the abstract); of the two central pain inhibition tests the study mainly measured, one did not change, and in the other only one indicator strengthened. In a randomized study without placebo comparing three different cannabinoid capsules (164 people, 64 with fibromyalgia), improvement was reported in all groups; it cannot be interpreted because there was no placebo. In analyses combining RCTs in fibromyalgia, there is no significant difference from placebo in pain (3 RCTs, 83 people; low certainty); the before–after improvement in a meta-analysis that also included uncontrolled studies (12 studies, 1,248 people) is not a comparison with placebo. In large real-world studies (Israel 367, United Kingdom 497, Canada 323, Italy 102 patients), those who stayed on treatment reported improvement; however, there was no control group, rates of stopping treatment or dropping out of follow-up were high (75% dropped out of follow-up within 12 months in Canada), and in the UK registry nearly half of patients reported side effects. In a German comparison of 120 inpatients, pain went down slightly more in those taking dronabinol (synthetic THC), but the groups were not randomly assigned. The result of a dronabinol RCT (NCT00176163) listed as completed on ClinicalTrials.gov (completion May 2009; fibromyalgia and low back pain) has been neither published nor posted to the registry. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 9 randomized studies with cannabinoids on this topic (6 placebo-controlled) and 1 non-randomized comparative study were found; all are in the table below. More than 10 systematic reviews specific to fibromyalgia or examining fibromyalgia separately were found; the 4 most recent and comprehensive (including Cochrane) and 4 large observational studies are also in the table.

Evidence assessment: Pure CBD: moderate (negative result)

• CBD alone: Pure CBD 50 mg a day gave a worse result than placebo for fibromyalgia pain (difference −0.7; p=0.0028, in favor of placebo). No other controlled study comparing pure CBD with placebo in fibromyalgia was found (October 2026).
• Products containing THC: In fibromyalgia, all RCTs comparing THC-containing products and nabilone with placebo or another drug are small (17–81 people) and short (from a single dose to 16 weeks). There are positive signs in a pilot study with a 1:1 THC:CBD oil, in a 17-person study with a THC-rich oil, and in two small studies with nabilone; in contrast, vaporized cannabis did not differ from placebo at a single dose, gave no added benefit when added to oxycodone, and with a single dose of THC oil under the tongue the change in pain was not clearly different from placebo. In analyses combining placebo-controlled studies, there was no significant difference from placebo in pain (low or very low certainty). The results cannot be applied to pure CBD. (weak evidence) Evidence: THC-containing: weak (small, short RCTs; inconsistent results)
• Dose range in studies: Pure CBD 50 mg/day (24 weeks); 18.4 mg CBD in a single inhalation; with the 1:1 THC:CBD oil, final dose 5–35 mg THC + 5–35 mg CBD a day (median 10 + 10 mg; calculated from mL and product concentration); nabilone 0.5–2 mg/day; THC-rich oil about 4.4 mg THC/day on average; dronabinol 14.8 mg/day on average; single dose of THC under the tongue 0.2 mg/kg (average 13.1 mg)
• Starting dose and titration (in studies): In Kurlyandchik 2026, over 4 weeks: started at 0.25 mL and increased by 0.25 mL every 2 days (up to 3.5 mL/day); in Skrabek 2008, nabilone from 0.5 mg to 2 × 1 mg over 4 weeks; in Chaves 2020, from 1 drop a day, increased by at most 1 drop every 10 days; in Bettstetter 2024, dronabinol over 13.4 days on average
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section

References (18)

Study table (dose, duration, result) · Topic page

No RCT of pure CBD in chemotherapy nausea was found. Current evidence comes from THC-containing products given in addition to standard treatment in patients whose nausea continued despite standard anti-nausea medicines: a 1:1 THC:CBD capsule raised the complete response from 8% to 24%. In gynecologic cancer, a 1:1 THC:CBD oil (very low dose) reduced the nausea score slightly more than placebo (54-person crossover RCT; 2.11 vs. 2.99); two-thirds of the patients had dizziness and sleepiness. The table includes 26 controlled studies done between 1975 and 1995 with dronabinol (synthetic THC) and nabilone (a synthetic THC-like cannabinoid) whose results can be read in their abstracts; 7 had a placebo group, and 19 compared only with the anti-nausea medicines of that era (prochlorperazine, metoclopramide, domperidone, etc.). Four controlled chemotherapy studies done in the same period with levonantradol, an experimental synthetic cannabinoid that was never approved, are not in the table under the site's rule and are mentioned here only as background: levonantradol was more effective than an anti-nausea medicine of that era (chlorpromazine, metoclopramide) in two studies, similar to prochlorperazine in one, and more effective than placebo in one; side effects such as low mood, sleepiness and a drop in blood pressure were common (Hutcheon 1983, PMID 6352278; Heim 1984, PMID 6467496; Sheidler 1984, PMID 6373843; Stambaugh 1984, PMID 6392353). According to reviews pooling the studies of this period, these medicines were better than placebo and similar to or slightly better than the anti-nausea medicines of that era; side effects and stopping because of side effects were more common (Tramèr 2001, 30 studies: complete control of nausea vs. the medicines of that era RR 1.38; Smith 2015 Cochrane: complete absence of nausea and vomiting vs. placebo RR 2.9, no difference vs. prochlorperazine; Chow 2025: vs. placebo RR 2.65, no difference vs. active medicines). The most recent review, examining 32 RCTs up to June 2024, rated no study as high quality and considered the evidence insufficient to recommend cannabinoids (Kemmner 2026). Compared with the strongest regimen of that era, high-dose metoclopramide plus dexamethasone, the nabilone regimen was less effective (Cunningham 1988); dronabinol added to an intensive anti-nausea regimen before bone marrow transplant gave no extra benefit (Gilbert 1995). Comparisons with today's medicines are few: dronabinol gave results similar to ondansetron for delayed nausea (Meiri 2007, 61 people, manufacturer-supported); with dronabinol added to palonosetron and dexamethasone, complete protection in the registry record was 35% vs. 16% (NCT00553059, 62 people; no statistical analysis and no peer-reviewed publication). In children there are 4 small RCTs with nabilone and THC; the results are conflicting and side effects are common (Phillips 2016 Cochrane). In radiotherapy nausea: during radiation therapy for head and neck cancer, nabilone did not affect nausea differently from placebo (Côté 2016, 56 people; nausea a secondary outcome, p = 0.71); in 40 patients with nausea during radiotherapy, nabilone was similarly effective to metoclopramide, with more side effects (Priestman 1987, crossover RCT); THC was found "slightly more helpful" than prochlorperazine (Ungerleider 1984; number of participants and statistics not in the abstract); levonantradol, an experimental synthetic cannabinoid, did not affect vomiting differently from chlorpromazine in single-session palliative radiation therapy (Lucraft 1982, PMID 6754212; not in the table because it is an experimental synthetic cannabinoid). There is no study of pure CBD in radiotherapy nausea. NICE's evidence review found only one study in radiotherapy nausea (Priestman 1987) and made no recommendation because there were no efficacy data; the MASCC 2022 review also counted only one RCT on this. In a recent RCT examining general symptoms in advanced cancer, pure CBD (MedCan1) did not reduce nausea more than placebo; this study was not designed for chemotherapy nausea. ASCO 2024 writes that THC-containing options may be added only in this refractory situation (weak recommendation). In the 1:1 capsule study, only 10% of patients had received olanzapine, and the study closed early with 151 patients instead of the planned 250. MASCC 2022 found the evidence insufficient to recommend cannabinoids for chemotherapy nausea; as reported by ASCO, the same document says they should not be used for first-line prevention but may be considered in refractory cases in patients not receiving checkpoint inhibitors. The MASCC/ESMO 2023 guideline on chemotherapy and radiotherapy nausea contains no recommendation for cannabinoids; the recommended medicine for nausea that continues despite standard treatment is olanzapine. The UK's national guideline NICE (2019, updated 2021) says nabilone may be considered as add-on treatment in adults for chemotherapy nausea that continues despite optimized standard anti-nausea medicines (NICE uses the word "consider" for recommendations where the benefit is less certain); its rationale is limited evidence, mostly from old and low-quality studies. It made no recommendation for other cannabis products or for children, and recommended research. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 36 controlled studies with cannabinoids on this topic with readable results were found (35 in chemotherapy nausea, one of them with results only on ClinicalTrials.gov; one a pure CBD study on general symptoms in advanced cancer); all except the 4 with levonantradol are in the table below (one trial appears in two rows, with two separate publications; levonantradol is an experimental synthetic cannabinoid, so under the site's rule it is mentioned only in this text). Of the many systematic reviews examining this question, the 7 most recent and comprehensive (two of them Cochrane) and one observational study in children are also in the table. Eight older controlled studies with no abstract, or with no results in their abstract, could not be included in the table. In the October 2026 completion round, radiotherapy nausea was added to the page: 4 controlled studies with cannabinoids on this question were found; the 3 with THC or nabilone are in the table, and the one with the experimental synthetic cannabinoid levonantradol is only in this text under the site's rule; a comparative study published in Hebrew without an abstract could not be read. There are no cannabinoid registrations on ClinicalTrials.gov for radiotherapy nausea. The NICE guideline is also in the table. A single-arm study looking at the tolerability of dronabinol during chemotherapy in glioma patients (NCT00314808, 33 people) was not included because it had no comparison group and tracked nausea only as a secondary outcome, with a quality-of-life scale and without comparison.

Evidence assessment: Pure CBD: Insufficient; no RCTs in chemotherapy or radiotherapy nausea; in one RCT looking at general symptoms in advanced cancer, no difference from placebo for nausea

• CBD alone: There are no controlled studies of pure CBD oil in chemotherapy or radiotherapy nausea; there is no evidence for CBD oil. In the only pure CBD study looking at general symptoms in advanced cancer (144 people, placebo-controlled), CBD did not reduce any symptom, including nausea, more than placebo; this study was not designed for chemotherapy nausea.
• Products containing THC: A 1:1 THC:CBD capsule, oil or mouth spray added to standard anti-nausea medicines gave better results than placebo for nausea or vomiting in three recent RCTs (two of them in patients whose nausea continued despite standard treatment; the largest had 147 people). According to reviews pooling the controlled studies from 1975–1995, synthetic THC (dronabinol) and the THC-like medicines nabilone and levonantradol were better than placebo and similar to or slightly better than the anti-nausea medicines of that era; dizziness, feeling high and low mood were more common. Comparisons with today's medicines are very few: dronabinol gave results similar to ondansetron for delayed nausea (61 people); the result for dronabinol added to palonosetron and dexamethasone exists only in a ClinicalTrials.gov record, without statistical analysis. When added to an intensive, older-type anti-nausea regimen given before bone marrow transplant, dronabinol gave no additional benefit. For radiation-therapy (radiotherapy) nausea, the evidence is very limited and mostly old: nabilone was no better than placebo (56 people; nausea a secondary outcome) or metoclopramide (40 people), and had more side effects than metoclopramide; THC was found slightly more helpful than prochlorperazine in one study (number of participants and statistics not in the abstract). These results cannot be carried over to CBD oil. (weak evidence) Evidence: Weak (our assessment: most of the studies were done before today's anti-nausea medicines). ASCO 2024 (Recommendation 3.1): quality of evidence moderate for dronabinol and nabilone, low for 1:1 THC:CBD extract; strength of recommendation weak. NICE 2019: nabilone may be considered as add-on treatment in adults only for chemotherapy nausea that continues despite optimized standard treatment. For radiotherapy nausea, very weak (3 controlled studies, two of them from the 1980s; no difference in two; number of participants 56 and 40 in two, not given in the abstract in one)
• Dose range in studies: No pure CBD studies in chemotherapy nausea; THC-containing 1:1 capsule from 2.5 mg THC + 2.5 mg CBD 3 times a day up to 10 mg + 10 mg 3 times a day; in older studies, nabilone 1–2 mg 2–4 times a day, dronabinol 5–15 mg/m² 2–6 times a day
• Starting dose and titration (in studies): In the THC:CBD capsule studies, patients adjusted the dose themselves according to nausea and side effects
• Interaction: Everolimus: exposure increased ~2.5-fold; label: start everolimus at a lower dose and monitor levels (high, human PK data)
• Interaction: Tacrolimus, sirolimus, digoxin (P-gp substrates): the label states that levels may increase (moderate)
• Interaction: Oral P-gp substrate chemotherapy/targeted drugs (e.g., many tyrosine kinase inhibitors): theoretical; no human data
• Interaction: CYP2C19 substrates and prodrugs (clopidogrel): substrate levels rise, and the active metabolite of prodrugs may decrease; no human data for oncology drugs
• Interaction: Warfarin: case report of INR rise; INR should be monitored
• Interaction: CYP3A4 substrates (taxanes, irinotecan, docetaxel, many TKIs): midazolam unchanged on the label (licensed CBD 750 mg twice daily); a single dose of a CBD-dominant extract (640 mg CBD + 20 mg THC) increased midazolam AUC by 56% (Bansal 2023, PMID 37313955); herbal cannabis tea did not affect irinotecan and docetaxel PK (n=24); nabiximols did not affect temozolomide PK; these results cannot be generalized
• Interaction: Immunotherapy: nivolumab response rate 15.9% vs. 37.5% in cannabis users (mostly THC-containing cannabis) (Taha 2019, PMID 30670598, n=140); in a prospective observational study, time to progression and survival were shorter (Bar-Sela 2020, PMID 32872248, n=102); causality not proven, no data specific to pure CBD
• Interaction: Opioids: in MedCan1, CBD dose was unrelated to opioid use; no opioid-sparing effect shown with THC-containing products; somnolence increases with CNS depressants
• Interaction: Citalopram/escitalopram: citalopram levels rose significantly in 6 patients who added CBD (200–800 mg/day) (Anderson 2021, PMID 34121064)
• Interaction: Valproate and liver-toxic drugs (some chemotherapies, methotrexate): no data on use together with hepatotoxic chemotherapies
• Interaction: Tamoxifen: in one case, endoxifen was found to be low with CBD 40 mg/day (Parihar 2020, PMID 33191836)
• Interaction: No clinical studies reported with direct oral anticoagulants (apixaban, rivaroxaban)
• Monitoring in studies: Prescription CBD label: liver tests at baseline and at months 1, 3 and 6, then periodically; stop if ALT/AST >3×ULN + bilirubin >2×ULN, or if transaminases stay >5×ULN
• Monitoring in studies: INR in people taking warfarin
• Monitoring in studies: Drug blood levels in people taking everolimus/tacrolimus/sirolimus

References (45)

Study table (dose, duration, result) · Topic page

In advanced cancer, CBD oil (median 400 mg/day chosen by patients) provided no added benefit to palliative care (low certainty). In large studies with THC-containing nabiximols (Sativex), opioid-refractory cancer pain was no different from placebo (moderate certainty): the positive primary result of the 2010 study and the positive findings of the 2012 study, which were seen only in secondary analyses, were not repeated in three phase 3 studies involving a total of 1,202 patients, and opioid use did not decrease either. The positive measures referred to as 'quality of life' in these studies were global impression and satisfaction questionnaires. The positive results seen in US patients come from post hoc exploratory subgroup analyses; in one study, the result in patients outside the US favored placebo, so these findings do not count as evidence of an effect. In two small studies from the 1970s with single oral doses of THC, high doses reduced pain more than placebo but were not superior to codeine and caused marked drowsiness and mental clouding (low certainty); in two small RCTs with nabilone, a synthetic THC-like drug, pain was no different from placebo (low certainty). With a 1:1 THC:CBD oil, a small pain benefit was seen at the cost of more psychotomimetic side effects (single study, secondary outcome). In chemotherapy-induced neuropathy, in none of four small RCTs with cannabinoids (a THC:CBD spray, two CBD-dominant low-THC capsules, a pure CBD cream applied to the skin) did pain decrease more than with placebo (in one, neuropathy scores in the cannabis arm were worse than with placebo; low certainty); in aromatase inhibitor–related joint pain, pure CBD (up to 200 mg/day) reduced worst pain by ≥2 points in 44% of patients in an uncontrolled phase 2 study; in a 21-person randomized study comparing CBD and THC ointments for the same pain, there was no placebo and the pain results were not given in the abstract. In registries following cancer patients prescribed cannabis (Canada, United Kingdom, Israel, Thailand), pain decreased from baseline over months; but these studies had no comparison group, a large share of patients dropped out of follow-up in the Israeli and Thai registries, the daily amount of THC in the oil used in Thailand (about 0.2 mg) was far below the doses in pain studies, and the improvement in a 2025 meta-analysis pooling this kind of data is not a comparison with placebo (low or very low certainty). In a 6-month open-label spray study in advanced cancer, pain did not change from baseline and more than a third of participants stopped because of adverse events (including disease progression). In a single-arm, open-label dronabinol study in 14 women with breast cancer that had spread to the bone and who were using opioids, according to the authors 4 women reduced their opioid dose by at least 20% by a predefined criterion (according to the paper's table, the reduction in one of them was 19.7%; no control group; very low certainty). In a retrospective chart review of 513 patients receiving oxaliplatin, grade 2–3 nerve damage was less common in those using medical cannabis (15.3% versus 27.9%); the groups were not balanced, product and dose were not recorded, and pain was not measured (very low certainty). ASCO 2024 finds the evidence insufficient to make a recommendation for or against their use in cancer pain; MASCC 2023 recommends against using cannabinoids as add-on painkillers; the BMJ guideline (2021), which covers cancer and non-cancer long-term pain together, gives a weak recommendation for trying non-inhaled (oral or topical) cannabinoids when standard treatment is not enough, but most of the studies it relied on were in non-cancer pain and there was no significant difference in the cancer pain studies. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): on this topic, 18 randomized studies with cannabinoids (15 of them placebo-controlled; one publication reports two studies together), 1 observational study comparing people taking nabilone with those not taking it, 1 retrospective study comparing the frequency of chemotherapy-related nerve damage between cannabis users and non-users (pain not measured), 3 studies without a control group, 4 systematic reviews and meta-analyses (one of them Cochrane), 3 guidelines and 4 patient registries or cohorts were found; all are in the table below. Not included in the table: two 1970s single-dose studies with experimental synthetic THC analogs (Jochimsen 1978, Staquet 1978; outside the site's scope), two expert documents repeating the same recommendation as the guidelines in the table (European Pain Federation 2018, São Paulo Society of Anesthesiology 2024), a review (2026) that summarizes the three small neuropathy studies in the table without pooling them, an uncontrolled pure CBD study in which pain was measured only together with exercise, and other small studies without a control group. The recommendation on cannabinoids in the ESMO 2018 cancer pain guideline could not be re-verified in this search (see the unverifiable points section).

Evidence assessment: Weak (pure CBD)

• CBD alone: Pure CBD oil did not improve symptoms, including pain, more than placebo in advanced cancer (Hardy 2023; Cochrane 2023 interpretation: low certainty); in chemotherapy-induced nerve pain, a CBD cream applied to the skin was also no different from placebo (D'Andre 2024, 40-person pilot). For aromatase inhibitor–related joint pain, there is only a small study of oral pure CBD without a control group (Fleege 2025).
• Products containing THC: In opioid-refractory cancer pain, nabiximols/THC was no different from placebo (Cochrane 2023, moderate certainty); with a 1:1 THC:CBD oil, a small benefit came with more side effects (single study, secondary outcome); opioid needs did not decrease (Creangă-Murariu 2026 meta-analysis, low certainty), and in none of the three small RCTs of THC-containing products in chemotherapy-induced nerve pain did pain decrease more than with placebo (low certainty). In the small single-dose studies of the 1970s, THC was better than placebo but no different from codeine (low certainty). (moderate evidence) Evidence: Moderate, pointing to no effect: in cancer pain that continues despite opioids, a mouth spray containing THC and CBD (nabiximols) is no different from placebo; for single-dose THC, nabilone and other products, the evidence is low
• Dose range in studies: Pure CBD: 50–600 mg/day (median chosen 400 mg/day), 50–200 mg/day in aromatase inhibitor pain; in chemotherapy neuropathy ~130 mg CBD + 6–11 mg THC/day or at most 300 mg CBD + 15 mg THC/day; THC-containing products: nabiximols 1–16 sprays/day, 1:1 oil from 2.5+2.5 mg up to 30+30 mg/day; in the 1970s single-dose studies, 5–20 mg oral THC (marked side effects at 20 mg); nabilone 0.5–2 mg/day
• Starting dose and titration (in studies): In MedCan1, an increase every 3 days; in the nabiximols studies, 2 weeks of self-titration
• Interaction: Everolimus: exposure increased ~2.5-fold; label: start everolimus at a lower dose and monitor levels (high, human PK data)
• Interaction: Tacrolimus, sirolimus, digoxin (P-gp substrates): the label states that levels may increase (moderate)
• Interaction: Oral P-gp substrate chemotherapy/targeted drugs (e.g., many tyrosine kinase inhibitors): theoretical; no human data
• Interaction: CYP2C19 substrates and prodrugs (clopidogrel): substrate levels rise, and the active metabolite of prodrugs may decrease; no human data for oncology drugs
• Interaction: Warfarin: case report of INR rise; INR should be monitored
• Interaction: CYP3A4 substrates (taxanes, irinotecan, docetaxel, many TKIs): midazolam unchanged on the label (licensed CBD 750 mg twice daily); a single dose of a CBD-dominant extract (640 mg CBD + 20 mg THC) increased midazolam AUC by 56% (Bansal 2023, PMID 37313955); herbal cannabis tea did not affect irinotecan and docetaxel PK (n=24); nabiximols did not affect temozolomide PK; these results cannot be generalized
• Interaction: Immunotherapy: nivolumab response rate 15.9% vs. 37.5% in cannabis users (mostly THC-containing cannabis) (Taha 2019, PMID 30670598, n=140); in a prospective observational study, time to progression and survival were shorter (Bar-Sela 2020, PMID 32872248, n=102); causality not proven, no data specific to pure CBD
• Interaction: Opioids: in MedCan1, CBD dose was unrelated to opioid use; no opioid-sparing effect shown with THC-containing products; somnolence increases with CNS depressants
• Interaction: Citalopram/escitalopram: citalopram levels rose significantly in 6 patients who added CBD (200–800 mg/day) (Anderson 2021, PMID 34121064)
• Interaction: Valproate and liver-toxic drugs (some chemotherapies, methotrexate): no data on use together with hepatotoxic chemotherapies
• Interaction: Tamoxifen: in one case, endoxifen was found to be low with CBD 40 mg/day (Parihar 2020, PMID 33191836)
• Interaction: No clinical studies reported with direct oral anticoagulants (apixaban, rivaroxaban)
• Monitoring in studies: Prescription CBD label: liver tests at baseline and at months 1, 3 and 6, then periodically; stop if ALT/AST >3×ULN + bilirubin >2×ULN, or if transaminases stay >5×ULN
• Monitoring in studies: INR in people taking warfarin
• Monitoring in studies: Drug blood levels in people taking everolimus/tacrolimus/sirolimus
• Monitoring in studies: ASCO 2024 recommendation 3.2: oral CBD ≥300 mg/day is not recommended for symptom burden outside clinical trials (no efficacy; risk of reversible liver enzyme abnormalities)

References (33)

Study table (dose, duration, result) · Topic page

No pure CBD RCT that selected patients for loss of appetite and weight loss in cancer was found; in an RCT on symptom burden in advanced cancer (144 patients, 28 days, median 400 mg/day), all ESAS items, including appetite, improved in both groups, with no difference between the groups; in a small non-randomized study, 300 mg/day of CBD during chemotherapy did not change lean body mass and reported improvement in taste discrimination. THC-containing cannabis extract and THC were no different from placebo; dronabinol was worse than megestrol. In a 46-patient pilot RCT in patients with taste and smell disorders, dronabinol improved taste and smell perception, appetite before meals and the share of calories from protein more than placebo; total calorie intake, the primary outcome in the registry, increased in both groups, with no difference between the groups. Nabilone was no different from placebo for appetite and weight during radiotherapy in head and neck cancer; THC:CBD 1:1 oil did not change the appetite score differently from placebo in advanced cancer (p = 0.32); in a waitlist-controlled open pilot study in pancreatic cancer, the difference in appetite improvement was not significant (56% vs. 30%; p = 0.37). In a 177-patient RCT of cancer pain, the appetite score fared worse over 2 weeks with the THC+CBD mouth spray than with placebo (difference 0.83 points; 95% CI 0.16–1.51; p = 0.016), and with the THC-only spray the difference was borderline (p = 0.056); this secondary outcome is not in the publication but in the ClinicalTrials.gov registry (NCT00674609). In lung cancer, nabilone was no different from placebo for appetite and weight in a small pilot RCT; calorie intake increased in the nabilone group, but the abstract does not state whether the difference from placebo was significant, and the only result reported as significantly higher than placebo was carbohydrate intake (47 randomized, 33 analyzed). Uncontrolled studies and patient registries reported improvement in appetite, but there was no comparison group, and in a cohort followed for 6 months average weight did not change; in 2,873 cancer patients in Thailand, the appetite-loss score (0–10) decreased by 1.67 points over 3 months with an oil containing only about 0.2 mg of THC a day (uncontrolled; patients were not selected for appetite loss, baseline score 2.45; the public institution that makes the product funded the study; the authors point to the possible role of the placebo effect). Systematic reviews (Simon 2022, Razmovski-Naumovski 2022, Creangă-Murariu 2025) showed no significant benefit for appetite or weight; certainty low or very low. The ASCO 2020 cachexia guideline had given a weak recommendation against cannabinoids (as reported in ASCO 2024). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 9 randomized studies with cannabinoids on this topic and 2 non-randomized studies with a comparison group were found; all are in the table below. 4 of the randomized studies were done in patients with loss of appetite, weight loss or taste disorders; the other 5 were done for symptom burden in advanced cancer, cancer pain or quality of life during radiation therapy and measured appetite as a secondary outcome. The 4 most comprehensive and most recent systematic reviews answering the same question are also in the table; there is no Cochrane review. Although chemotherapy nausea studies measured appetite as a side outcome, they were assessed under the nausea and vomiting topic. A 109-patient phase 3 study comparing dronabinol with placebo for symptoms during chemotherapy in pancreatic cancer (NCT03984214; weight loss and lean body mass among the secondary outcomes) was completed in September 2024; its results have not yet been published.

Evidence assessment: Pure CBD: Insufficient; no RCT for loss of appetite; in 1 RCT on symptom burden, appetite no different from placebo

• CBD alone: There is no pure CBD RCT that selected patients for appetite loss/cachexia in cancer; in a symptom-burden RCT in advanced cancer (144 patients), there was no difference from placebo in the ESAS items, including appetite (secondary outcome); in a small non-randomized study, lean body mass did not change.
• Products containing THC: No benefit for appetite and weight has been shown with THC-containing products and nabilone (low to very low evidence); small studies reported improvement in taste perception and in the intake of some foods. (very weak evidence) Evidence: Very weak
• Dose range in studies: In the non-randomized study, CBD 300 mg/day (8 days in each chemotherapy cycle); in the symptom-burden RCT, CBD 50–600 mg/day (median 400 mg); in THC-containing products, THC mostly 2.5 mg twice a day (increased up to 20–30 mg/day in some studies), median 15 + 15 mg/day in the THC:CBD 1:1 oil; nabilone 0.5–2 mg/day
• Starting dose and titration (in studies): In most studies, the dose was started low and increased over 1–2 weeks based on response and side effects: dronabinol from 2.5 mg a day, nabilone from 0.5 mg, CBD oil from 50 mg a day, THC:CBD oil from 2.5 + 2.5 mg a day (study doses; not a personal recommendation). In the Israeli capsule study, where side effects were seen at the higher dose, the dose was halved.
• Interaction: Everolimus: exposure increased ~2.5-fold; label: start everolimus at a lower dose and monitor levels (high, human PK data)
• Interaction: Tacrolimus, sirolimus, digoxin (P-gp substrates): the label states that levels may increase (moderate)
• Interaction: Oral P-gp substrate chemotherapy/targeted drugs (e.g., many tyrosine kinase inhibitors): theoretical; no human data
• Interaction: CYP2C19 substrates and prodrugs (clopidogrel): substrate levels rise, and the active metabolite of prodrugs may decrease; no human data for oncology drugs
• Interaction: Warfarin: case report of INR rise; INR should be monitored
• Interaction: CYP3A4 substrates (taxanes, irinotecan, docetaxel, many TKIs): midazolam unchanged on the label (licensed CBD 750 mg twice daily); a single dose of a CBD-dominant extract (640 mg CBD + 20 mg THC) increased midazolam AUC by 56% (Bansal 2023, PMID 37313955); herbal cannabis tea did not affect irinotecan and docetaxel PK (n=24); nabiximols did not affect temozolomide PK; these results cannot be generalized
• Interaction: Immunotherapy: nivolumab response rate 15.9% vs. 37.5% in cannabis users (mostly THC-containing cannabis) (Taha 2019, PMID 30670598, n=140); in a prospective observational study, time to progression and survival were shorter (Bar-Sela 2020, PMID 32872248, n=102); causality not proven, no data specific to pure CBD
• Interaction: Opioids: in MedCan1, CBD dose was unrelated to opioid use; no opioid-sparing effect shown with THC-containing products; somnolence increases with CNS depressants
• Interaction: Citalopram/escitalopram: citalopram levels rose significantly in 6 patients who added CBD (200–800 mg/day) (Anderson 2021, PMID 34121064)
• Interaction: Valproate and liver-toxic drugs (some chemotherapies, methotrexate): no data on use together with hepatotoxic chemotherapies
• Interaction: Tamoxifen: in one case, endoxifen was found to be low with CBD 40 mg/day (Parihar 2020, PMID 33191836)
• Interaction: No clinical studies reported with direct oral anticoagulants (apixaban, rivaroxaban)
• Monitoring in studies: Prescription CBD label: liver tests at baseline and at months 1, 3 and 6, then periodically; stop if ALT/AST >3×ULN + bilirubin >2×ULN, or if transaminases stay >5×ULN
• Monitoring in studies: INR in people taking warfarin
• Monitoring in studies: Drug blood levels in people taking everolimus/tacrolimus/sirolimus

References (19)

Study table (dose, duration, result) · Topic page

In advanced cancer, CBD oil did not improve total symptom burden, quality of life or anxiety more than placebo (MedCan1). A 1:1 THC:CBD oil also made no difference in total symptom burden. In studies of a THC+CBD spray for cancer pain, the Cochrane 2023 meta-analysis found no difference from placebo in sleep problems (4 RCTs, 1,314 people; SMD −0.06; moderate certainty); a 2022 meta-analysis calculated a 'very small' improvement (−0.19 cm on a 10 cm scale). In two small RCTs of CBD-dominant, low-THC capsules for chemotherapy-induced nerve damage, sleep was no better than placebo; in one, it went worse with cannabis. For anxiety before a scan, a single 400 mg dose of CBD was ineffective on the primary outcome. In patients with brain tumors, 600 mg/day of pure CBD for 3 weeks did not reduce anxiety and depression symptoms more than placebo (a small crossover RCT stopped early). There is no randomized THC study in cancer that targets psychological symptoms as its primary goal; there is only a small placebo-controlled pilot from 1974 in 12 anxious lung cancer patients, with randomization not stated (THC improved night-time sleep but caused tiredness and confusion; its effect on anxiety was not reported in the abstract, and there are no numerical results). In two THC/nabilone RCTs that used quality of life as their main measure (243 and 56 patients), there was no difference from placebo; in a pooled analysis of cachexia RCTs, quality of life improved slightly less with cannabinoids than in those taking placebo or an appetite-stimulating drug (megestrol) (SMD −0.25). For psychological symptoms in cancer, the MASCC 2023 guideline reviewed 15 RCTs and wrote that none of them used these symptoms as the primary outcome and that there is no high-quality evidence sufficient to recommend cannabis; a 2024 meta-analysis also found no clinically meaningful effect on depression, anxiety or stress. Patient registries in Israel, Canada, the US, the UK and Thailand reported improvement from baseline in anxiety, sleep and quality of life; but these studies had no comparison group, in most of them patients mainly used THC products, patients who died or stopped were not included in the analysis, and some were run by authors linked to organizations that make or prescribe cannabis products. In the Thai cohort (2,873 cancer patients; quality of life +0.13, anxiety −1.46 points; sleep not measured separately), the daily amount of THC in the oil used was only about 0.2 mg, and the public agency that makes the product funded the study; the authors also point to the possible share of the placebo effect. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 13 studies with cannabinoids that had a comparison group (11 placebo-controlled, 1 waitlist-controlled, 1 comparing two THC:CBD ratios) and 8 systematic reviews were found on this topic; all are in the table below. The table also includes 1 open-label study, 8 observational studies and 2 safety sub-analyses of the same trials. Four cancer pain RCTs that examined sleep only as a secondary measure were not listed one by one; their sleep results are included in pooled form in the Cochrane review in the table.

Evidence assessment: Weak (pure CBD: anxiety and quality of life); there is no pure CBD study that targets sleep as its main goal; all 3 placebo-controlled studies with pure CBD found no difference from placebo on their main measure

• CBD alone: Pure CBD oil was no different from placebo for anxiety, quality of life or total symptom burden in advanced cancer; in brain tumors, 600 mg/day also did not reduce anxiety; in breast cancer, a single 400 mg dose before imaging was no different from placebo for anxiety on the main measure (in an exploratory comparison, the anxiety level after the dose was lower in the CBD group); there is no pure CBD study that targets sleep as its main goal (in a small open-label study done for joint pain, sleep and anxiety did not change when all participants were analyzed together). In real-world data, sleep and anxiety improved slightly more in those taking higher CBD doses, but most of these patients were using THC-dominant products and there was no comparison group; in one patient registry, CBD-dominant products did not bring clear relief.
• Products containing THC: A 1:1 THC:CBD oil did not change total symptom burden; it was also no different from placebo for anxiety, depression or quality of life (on the quality-of-life scale, only the pain domain favored the THC oil), and general well-being improved more with placebo on day 14. In analyses pooling placebo-controlled studies for cancer pain, there was either no difference in sleep (Cochrane 2023: 4 studies, 1,314 people) or a very small improvement (2022 meta-analysis: −0.19 cm on a 10 cm scale); in two small studies of CBD-dominant, low-THC capsules for nerve damage, sleep was no better than placebo, and in one it was worse. In studies that used quality of life as their main measure, THC, cannabis extract or the THC-like drug nabilone was no different from placebo; in a pooled analysis of cachexia studies, quality of life improved slightly less in those taking cannabinoids than in those taking placebo or an appetite-stimulating drug (megestrol). Real-world registries reported improvement in anxiety, sleep and quality of life, but there was no comparison group. (weak evidence) Evidence: Moderate for sleep (effect very small or absent; from cancer pain studies); very low for anxiety and depression (no randomized study used these symptoms as its main measure; studies that looked at them as a secondary measure found no significant difference from placebo); low for quality of life (no benefit or a small negative effect)
• Dose range in studies: Pure CBD: 50–600 mg/day (MedCan1, median chosen dose 400 mg/day), 600 mg/day in brain tumors (3 weeks), single dose 400 mg (Nayak 2024), 200 mg/day for joint pain in breast cancer (15 weeks, open-label; Fleege 2025); THC-containing 1:1 oil: from 2.5+2.5 mg up to 30+30 mg/day; THC or cannabis extract (2.5 mg THC, + 1 mg CBD in the extract) 2 times a day (Strasser 2006, Brisbois 2011); nabilone starting at 0.5 mg, up to 2 mg/day (Côté 2016)
• Starting dose and titration (in studies): MedCan1: increased every 3 days; MedCan2: increased over 14 days according to tolerance/effect
• Interaction: Everolimus: exposure increased ~2.5-fold; label: start everolimus at a lower dose, monitor levels (high; human PK data)
• Interaction: Tacrolimus, sirolimus, digoxin (P-gp substrates): the label states that their levels may rise (moderate)
• Interaction: Oral chemotherapy/targeted drugs that are P-gp substrates (e.g., many tyrosine kinase inhibitors): theoretical; no human data
• Interaction: CYP2C19 substrates and prodrugs (clopidogrel): substrate levels rise, and the active metabolite of prodrugs may fall; no human data for cancer drugs
• Interaction: Warfarin: case report of INR elevation; INR should be monitored
• Interaction: CYP3A4 substrates (taxanes, irinotecan, docetaxel, many TKIs): on the label, midazolam was unchanged (licensed CBD 750 mg twice daily); a single dose of a CBD-dominant extract (640 mg CBD + 20 mg THC) increased midazolam AUC by 56% (Bansal 2023, PMID 37313955); herbal cannabis tea did not affect irinotecan and docetaxel PK (n=24); nabiximols did not affect temozolomide PK; these results cannot be generalized
• Interaction: Immunotherapy: in people using cannabis (mostly THC-containing), the nivolumab response rate was 15.9% versus 37.5% (Taha 2019, PMID 30670598, n=140); in a prospective observational study, time to progression and survival were shorter (Bar-Sela 2020, PMID 32872248, n=102); causation not proven, no data specific to pure CBD
• Interaction: Opioids: in MedCan1, CBD dose was unrelated to opioid use; no opioid-sparing effect was shown with THC-containing products; somnolence increases with CNS depressants
• Interaction: Citalopram/escitalopram: in 6 patients who added CBD (200–800 mg/day), citalopram levels rose significantly (Anderson 2021, PMID 34121064)
• Interaction: Valproate and liver-toxic drugs (some chemotherapies, methotrexate): no data on use together with hepatotoxic chemotherapies
• Interaction: Tamoxifen: in one case, endoxifen was found to be low with 40 mg/day CBD (Parihar 2020, PMID 33191836)
• Interaction: No clinical studies have been reported with direct oral anticoagulants (apixaban, rivaroxaban)
• Monitoring in studies: Prescription CBD label: liver tests at baseline, at months 1, 3 and 6, then periodically; stop if ALT/AST >3× ULN + bilirubin >2× ULN, or if transaminases stay >5× ULN
• Monitoring in studies: INR in people taking warfarin
• Monitoring in studies: Drug blood levels in people taking everolimus/tacrolimus/sirolimus

References (32)

Study table (dose, duration, result) · Topic page

Based on current evidence, CBD does not treat cancer, shrink tumors or boost the effect of chemotherapy. In the secondary analysis of the controlled study with pure CBD oil, disease progression and survival did not change. Lab and animal findings have not been confirmed in humans; uncontrolled case series (of 15 and 119 patients) and published case reports carry no evidential value; 81% of 77 published cases were rated as weak evidence for this claim. In a phase 1 safety study with 600–800 mg/day Epidiolex in 21 patients with biochemical recurrence of prostate cancer, PSA stayed stable in most patients; because there was no control group, an anti-tumor effect cannot be considered shown. ASCO 2024: cannabis/cannabinoids should not be used in place of cancer treatment (strong recommendation) and should not be recommended outside of clinical trials to boost the effect of tumor-directed treatment either. In three of six observational studies examining cannabis use in people receiving immunotherapy, worse response or survival was seen, and in three it was not; these studies do not show cause and effect, but ASCO recommends caution in these patients. In observational studies of people who were using or had previously used cannabis when they were diagnosed with cancer, no clear difference was seen in survival, in cancer coming back or in a second cancer developing (in HPV-related oropharyngeal cancer, 47 patients matched with 47; at the same center, among 513 head and neck cancer patients, a second primary cancer occurred in 2 of 59 cannabis users and 23 of 454 non-users; in the matched analysis of a French cohort of 8,999 patients with lung cancer, HR 0.90, 95% CI 0.68–1.18; in 1,472 patients with bladder cancer that had not spread into the muscle layer, recurrence in the first 2 years, HR 0.87, 95% CI 0.56–1.33 in current users); in lung cancer, people who smoked tobacco along with cannabis were diagnosed at a younger age than those who smoked only tobacco, and aggressive tumor types were more common. These studies are observational, cannabis use relies mostly on self-report and the share of tobacco cannot be fully separated; they do not show cause and effect (very low certainty). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): only 2 small studies were found that measured a tumor or survival outcome in humans and randomly compared patients receiving cannabinoids with those not receiving them (one a secondary analysis of a symptom study with pure CBD, the other a 21-person safety study with a spray containing THC and CBD); the result of a third, with 122 patients, has not been published. In addition, 1 randomized study comparing two THC:CBD ratios, 3 uncontrolled trials, 2 case series, 10 observational comparisons, 5 observational studies examining the course of the disease in people who were using or had previously used cannabis when they were diagnosed with cancer, 2 systematic reviews (one Cochrane), 1 review assessing published case reports, 1 narrative review and the ASCO guideline were found; all are in the table below.

Evidence assessment: Insufficient: no RCT measuring anti-tumor effect as the primary outcome; the only placebo-controlled data are a secondary analysis of a symptom study (no difference)

• CBD alone: Pure CBD has not been shown to have an anti-tumor effect in humans; in the MedCan1 secondary analysis, progression and survival did not change. The prostate cancer phase 1 study and the two case series reporting positive results (15 and 119 patients) are uncontrolled.
• Products containing THC: Studies measuring tumor response or survival with THC-containing products are small and mostly safety-focused: the nabiximols + temozolomide phase 1b study in glioblastoma (21 people randomized) was not powered for survival; the 88-patient glioma study had no comparison group without cannabis; in chronic lymphocytic leukemia, a single dose of spray slightly reduced cancer cells in the blood for only a few hours. The result of the 122-patient phase II randomized study (ARISTOCRAT) has not been published as of October 2026. Observational findings on cannabis use in people receiving immunotherapy are conflicting: some show worse response and survival, some show no difference. (very weak evidence) Evidence: Very weak: the only randomized data comparing with a no-cannabis group are a small subgroup (21 people) of a phase 1b safety study; observational studies are conflicting; no approval/evidence
• Dose range in studies: 400–600 mg/day CBD in the uncontrolled glioblastoma series; 600–800 mg/day in the prostate cancer phase 1; up to 12 sprays/day (30 mg CBD + 32.4 mg THC) in the nabiximols phase 1b; median dose chosen by patients 400 mg/day in the pure CBD RCT in advanced cancer; in the glioma study, a single nightly dose averaging about 10 mg THC + 11 mg CBD (1:1) or 27 mg THC + 7 mg CBD (4:1)
• Interaction: Everolimus: exposure rose ~2.5-fold; label: start everolimus at a low dose, monitor levels (high, human PK data)
• Interaction: Tacrolimus, sirolimus, digoxin (P-gp substrates): the label states that levels may rise (moderate)
• Interaction: Oral P-gp substrate chemotherapy/targeted drugs (e.g., many tyrosine kinase inhibitors): theoretical; no human data
• Interaction: CYP2C19 substrates and prodrugs (clopidogrel): substrate levels rise, and with prodrugs the active metabolite may decrease; no human data for oncology drugs
• Interaction: Warfarin: case report of raised INR; INR should be monitored
• Interaction: CYP3A4 substrates (taxanes, irinotecan, docetaxel, many TKIs): in the label, midazolam did not change (approved CBD 750 mg twice daily); a single dose of a CBD-dominant extract (640 mg CBD + 20 mg THC) raised midazolam AUC by 56% (Bansal 2023, PMID 37313955); herbal cannabis tea did not affect the PK of irinotecan and docetaxel (n=24); nabiximols did not affect temozolomide PK; these results cannot be generalized
• Interaction: Immunotherapy: in cannabis users (mostly THC-containing), nivolumab response rate 15.9% vs. 37.5% (Taha 2019; in the 116 of 140 patients who lived longer than 2 months); in a prospective observational study, shorter time to progression and survival (Bar-Sela 2020, n=102); shorter survival in 28 patients, most using dronabinol (Hadid 2024); on the other hand, no link with survival was found in 201 lung cancer patients receiving pembrolizumab (Waissengrin 2023), in a pooled trial analysis of 684 patients (Coschi 2025) or in 201 head and neck cancer patients (Alsavaf 2025); in two Israeli studies, most of the p-values in the baseline tables could not be obtained with the test stated in the article in an independent reanalysis, and group differences not reported in the articles were found; the main results could not be recalculated because raw data were not available (Piper 2024); causation has not been proven, and there are no data specific to pure CBD
• Interaction: Opioids: in MedCan1, CBD dose was unrelated to opioid use; no opioid-sparing effect has been shown with THC-containing products; somnolence increases with CNS depressants
• Interaction: Citalopram/escitalopram: in 6 patients who added CBD (200–800 mg/day), citalopram levels rose significantly (Anderson 2021, PMID 34121064)
• Interaction: Valproate and liver-toxic drugs (some chemotherapies, methotrexate): no data on use together with hepatotoxic chemotherapies
• Interaction: Tamoxifen: in one case, endoxifen was found to be low with 40 mg/day CBD (Parihar 2020, PMID 33191836)
• Interaction: No clinical studies have been reported with direct oral anticoagulants (apixaban, rivaroxaban)
• Monitoring in studies: Prescription CBD label: liver tests at baseline and at months 1, 3 and 6, then periodically; stop if ALT/AST >3×ULN + bilirubin >2×ULN or transaminases persistently >5×ULN
• Monitoring in studies: INR in people using warfarin
• Monitoring in studies: Drug blood levels in people using everolimus/tacrolimus/sirolimus

References (29)

Study table (dose, duration, result) · Topic page

On the question of cannabis and cancer risk, there are no randomized controlled trials and none are expected; the evidence comes from case-control, cohort and Mendelian randomization studies and reviews of them. Testis: in meta-analyses of the same three US case-control studies, current use (OR 1.62), at least weekly use (1.92) and use for more than 10 years (1.50; 1.36 and 'low' strength of evidence in Ghasemiesfe 2019) were linked to testicular germ cell tumors, especially the nonseminoma type; in the Swedish cohort, HR 2.57 (1.02–6.50) with heavy use; in the 2026 French study, the link was with seminoma; no link in UK Biobank (HR 0.85; 29 cases, participants aged 40–69); NASEM 2017 saw 'limited' evidence for the nonseminoma type. Lung: in the ILCCO pool (2159 cases), OR 0.96 (0.66–1.38) for habitual use and 1.03 in never-tobacco-smokers; in the Swedish cohort, HR 2.12 (1.08–4.14) with heavy use; in the US registry cohort, RR 3.87 (3.43–4.38; method disputed) with use disorder; in the North African pool, OR 2.4 (all cannabis smokers also smoked tobacco); in Mendelian randomization, OR 1.22 for the squamous type; Ghasemiesfe 2019 found the evidence insufficient, and NASEM 2017 saw moderate evidence of no association (both before the registry cohorts). Head and neck: in the INHANCE pool (4029 cases), OR 0.88 (0.67–1.16); NASEM 2017: moderate evidence of no association; 1.02 and 1.26 in meta-analyses (not significant); 1.24 for the oropharynx (0.99 with HPV adjustment), 0.47 for tongue cancer; 0.66 in an oral cancer meta-analysis; in US registry cohorts, RR 3.49 and OR 3.25 with use disorder, but in one hospital registry the link disappeared after adjusting for alcohol and smoking; in North Africa, OR 1.83 for nasopharyngeal cancer (1.54 after adjusting for cigarette smoking, not significant). Bladder, kidney, prostate: a decrease in prospective cohorts (bladder HR 0.55; kidney 0.61; prostate 0.83), an increase in a registry cohort (bladder RR 4.21; kidney 3.70; prostate 2.80). Glioma: 2.8-fold in a single cohort. Childhood cancers: in five small case-control studies between 1989 and 2006, 2–11-fold associations with the mother's or father's marijuana use (in one, any mind-altering drug) (not significant for astrocytoma; NASEM 2017: insufficient evidence); in the largest leukemia study, no link or a link in the opposite direction. In chronic pancreatitis, pancreatic cancer HR 0.26 (less detection). In most Mendelian randomization studies, no link or a very small one. Umbrella reviews summarize the evidence as 'suggestive rather than conclusive' (Nargis 2025) and find no strong evidence class for cancer (Solmi 2023). Pure CBD: no studies of cancer risk in people; in 2-year animal studies of the approved medicine, according to the US label, an increase in hepatocellular adenoma in male mice at the highest dose and no significant increase in tumors in rats; according to the European product information, hepatocellular adenoma increased in male mice at all doses and in female mice at the highest dose, Leydig cell hyperplasia and adenoma increased in male rats at all doses, and 1 Leydig cell carcinoma was seen at the highest dose (according to the document, the relevance of Leydig tumors in rats to humans is generally limited); genotoxicity tests negative; EFSA 2026 wrote that data gaps remain for genotoxicity and long-term use. THC itself was not carcinogenic in a 2-year rat study and equivocal in mice (thyroid adenoma, not dose-related). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): no randomized controlled trials on this question; no human study of cancer risk with pure CBD was found. For smoked cannabis, 2 umbrella reviews, 1 institutional assessment (NASEM 2017), 8 systematic reviews and meta-analyses, 4 Mendelian randomization studies, 12 cohort or registry studies, 4 pooled case-control analyses and 7 case-control studies were found; for pure CBD, 1 institutional assessment and 1 animal study (the approved medicine's US and European product information); for THC, 1 animal study; all are in the table below. Two 2026 meta-analyses were not included in the table: the results of the testicular meta-analysis were identical to earlier meta-analyses of the same three studies, and the cohort result of the lung meta-analysis rested on two numbers that did not match the source study. No Cochrane review, no study from Turkey and no ongoing study on ClinicalTrials.gov examining this question was found.

Evidence assessment: Pure CBD: Insufficient (no human studies of cancer risk; only two-year animal studies of the approved medicine and the European Food Safety Authority assessment)

• CBD alone: No study was found that looked at cancer risk from pure CBD or CBD oil in people. The US and European product information summarize the two-year animal studies of the approved pure CBD medicine in different detail. According to the US label, benign liver tumors (hepatocellular adenoma) increased in male mice at the highest dose (300 mg per kilogram per day), and there was no statistically significant increase in tumors in rats. According to the European product information, however, these liver tumors increased in male mice at all doses and in female mice at the highest dose; in male rats, overgrowth and benign tumors of the Leydig cells in the testis increased at all doses, and a malignant Leydig cell tumor was seen in one rat at the highest dose; the document states that the relevance of these rat tumors to humans is generally considered limited. CBD and its two main breakdown products were negative in genotoxicity (genetic damage) tests. The European Food Safety Authority (2026) wrote that, despite publications suggesting that pure CBD itself does not cause genetic damage, manufacturing and formulation may introduce new hazards, and that the effects of long-term use are unknown. It has not been shown that CBD either raises or lowers cancer risk.
• Products containing THC: The findings come almost entirely from smoking marijuana and differ by type of cancer. Testis: a link with testicular germ cell tumors after long-term (more than 10 years) or frequent use; meta-analyses of the same three US case-control studies (OR about 1.4–1.9), the Swedish cohort (HR 2.57 with heavy use) and the 2026 French study showed an increase, but the tumor type affected differed between studies, and there was no link in the UK cohort with older participants and few cases; the US National Academies in 2017 saw 'limited' evidence for the nonseminoma type (weak evidence). Lung: no increase in the pooled analysis of 2159 patients or in never-smokers, and the US National Academies (2017) saw moderate evidence of no association; an increase with heavy use in the Swedish cohort (HR 2.12) and the US registry cohort (RR 3.87); hard to separate from tobacco (mixed, very weak). Head and neck and oral: no increase in large pooled analyses and meta-analyses, a lower risk in some (US National Academies 2017: moderate evidence of no association); in US registry cohorts, with use disorder, any head and neck cancer about 3.5-fold and oral cancer 2.5–3.3-fold, but in one hospital registry the link disappeared after adjusting for alcohol and smoking (conflicting, very weak). Bladder, prostate, kidney: findings in two directions (insufficient). Brain (glioma): a single cohort (insufficient). Childhood cancers (use during pregnancy): small and conflicting case-control studies (insufficient). There are no human cancer data for THC taken by mouth (as a medicine); THC did not cause cancer in a two-year rat study, and in mice there was an equivocal finding in the thyroid that was not dose-related. (weak evidence) Evidence: Smoked cannabis and THC-containing products: Weak evidence on whether they raise cancer risk (only observational studies and Mendelian randomization; the most consistent signal is for testicular cancer, with low strength of evidence; conflicting and very weak for lung and head and neck; insufficient for bladder, prostate, kidney, brain and childhood cancers; no human data for oral THC)
• Dose range in studies: No treatment dose (risk page). Exposure measures in human studies: ever having used; joint-years (≥10, ≥60); number of lifetime uses (>50 times, ≥2000 times); at least weekly or daily use; ≥10 years of use; a diagnosis of cannabis use disorder in records. Animal studies (2 years): pure CBD 30–300 mg/kg/day in mice and 15–150 mg/kg/day in rats; THC 12.5–50 mg/kg in rats and 125–500 mg/kg in mice (5 days a week); these are study doses, not personal recommendations
• Starting dose and titration (in studies): Not applicable: the studies measured a usage habit, not a treatment; there is no dose adjustment
• Interaction: The studies on this page did not examine drug interactions; details are in the site's drug interactions section
• Interaction: CBD interacts with the enzymes in the liver that break down medicines; people being treated for cancer should consult their oncologist before starting (EFSA 2026)
• Monitoring in studies: No ongoing or planned study measuring the cancer risk of cannabis or CBD use was found on ClinicalTrials.gov (October 2026)
• Monitoring in studies: It has been suggested that routine oral exams may be useful in people with cannabis use disorder (Cuomo 2025)
• Monitoring in studies: The European Food Safety Authority wants genetic damage in CBD products to be assessed product by product; data gaps for long-term use remain (EFSA 2026)

References (41)

Study table (dose, duration, result) · Topic page

Pure CBD has not clearly shown an effect on insomnia in controlled studies: in the most recent meta-analysis, CBD alone did not significantly improve sleep quality compared with placebo (SMD 0.13). In primary insomnia, 150 mg of CBD at night for 2 weeks did not change insomnia severity, time to fall asleep or night awakenings; in healthy people, a single 300 mg dose did not change sleep structure. With THC-containing products, subjective improvement is more consistent; objective measures, however, diverge by type of measurement: in a single-dose pilot lab study, THC/CBD reduced total sleep and REM sleep, in a two-week study polysomnography did not change, and in one meta-analysis sleep time measured with an electronic device got longer. According to a review pooling polysomnography studies, the drop in REM comes mostly from older, small studies with high THC doses. In the 2026 Cochrane review (9 RCTs, 537 people), medical cannabis adds little or nothing meaningful to sleep quality, total sleep and daytime functioning (very low certainty); side effects may increase (low certainty). In healthy young people, 50 mg/day of CBD for 8 weeks raised the questionnaire sleep score, but superiority over placebo on the overall score was not shown (there was a difference on only one subscale); sleep time measured at the wrist did not change (28 people); in systemic sclerosis, a low-dose THC+CBD oil made no significant difference in sleep quality. Studies added in October 2026 did not change the picture for pure CBD: in people with high levels of worry, 300 mg of CBD for 2 weeks did not differ from placebo for sleep problems; two positive findings come from small or weakly designed studies (in 1981, longer sleep reported with 160 mg in 15 people with insomnia; in 60 young people who clench their teeth in their sleep, PSQI improved with a CBD gel applied inside the mouth to the chewing muscle: a secondary publication of a pain trial, the sleep measure is not in the study’s registration, and the CBD groups had worse starting scores). With THC-containing products, insomnia patients who got a cannabis card right away had insomnia scores on average 2.9 points lower than those who waited over the 12-week period (participants knew their group; cannabis use disorder rose across the whole sample); in Thailand, with a traditional blend containing cannabis leaf and with a cannabis oil, sleep quality improved over 4 weeks about as much as in those taking lorazepam (one a double-blind study testing whether it was not worse than lorazepam, the other a small open-label study that did not test equivalence; neither had a placebo); a supplement containing very little THC and plant ingredients reduced sleep disturbance slightly more than placebo in an online 620-person RCT (company study); in healthy volunteers, 15 mg of THC taken at bedtime caused sleepiness and weaker memory the next morning. Nabilone was better than amitriptyline in fibromyalgia patients with insomnia (no placebo); CBG did not differ from placebo in veterans with sleep problems. A 2026 meta-analysis (10 RCTs, 2,134 people) reported a positive pooled result, while Cochrane rated the evidence as very low certainty; the Brazilian Sleep Association’s 2023 guideline does not recommend cannabis, CBD or THC for insomnia. In sleep apnea, dronabinol reduced breathing pauses in a 73-person, 6-week RCT and in a 9-person crossover study combined with acetazolamide (in the large study, 11–13 events per hour fewer than placebo; part of the difference comes from a rise in the placebo group), but sleep structure and oxygen levels did not change; in the open-label study combining it with atomoxetine, the main measure was negative; the studies are short and side effects common; the American Academy of Sleep Medicine’s 2018 position statement recommends against its use; there are no CBD data. In REM sleep behavior disorder (acting out dreams) in Parkinson’s patients, CBD did not differ from placebo on the primary measures in a 33-person RCT; the Brazilian Academy of Neurology’s 2025 Parkinson’s guideline, based on this study, also states that CBD does not clearly affect how often these behaviors occur and does not list CBD among the treatments it recommends. In restless legs, the only controlled data are a negative analysis done afterward (18 people); an 18-person open-label THC+CBD study is positive; the German guideline does not recommend it. In PTSD-related nightmares, a 171-person multicenter dronabinol RCT and a 10-person nabilone RCT are positive (the large study is the only one and was manufacturer-supported; most people taking dronabinol figured out which group they were in); the American Academy of Sleep Medicine lists nabilone among the options that 'may be used' for these nightmares. The studies are small and short (1 night–14 weeks in controlled studies). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): the table includes 29 controlled studies with cannabinoids on this topic, 6 studies without a control group or whose control could not be verified and 1 patient registry, 8 systematic or scoping reviews, and 4 guidelines or position statements. Additional publications of the same trials are in the 'other source' section of the relevant row; pain, Parkinson’s, MS and epilepsy trials in which sleep was only a secondary measure, 1970s sleep EEG studies of a few people each, and older reviews answering the same question were not included in the table (the reviews pooling them are in the table). Completed studies whose results have not been published in a peer-reviewed journal (e.g., a 121-person dronabinol combination study in sleep apnea, a 208-person CBD study in insomnia) and ongoing studies (e.g., a 519-person CBD insomnia study) are not in the table.

Evidence assessment: Weak / inconsistent (pure CBD — insomnia); no pure CBD data in sleep apnea; in restless legs, the only controlled data (a small analysis done afterward) are negative

• CBD alone: Pure CBD did not significantly improve sleep quality compared with placebo (meta-analysis SMD 0.13; 95% CI −0.38 to 0.65); in newer studies too, 300 mg of CBD for 2 weeks in worried people did not differ from placebo. Positive findings come from small or weakly designed studies: in a 1981 study of 15 people, longer sleep was reported with 160 mg; in 60 young people who clench their teeth in their sleep, sleep scores improved with a CBD gel applied inside the mouth to the chewing muscle (a secondary publication of a pain trial; the sleep measure was not in the study’s registration and the CBD groups had worse starting scores). There is no CBD study in sleep apnea; in restless legs and REM sleep behavior disorder, the only controlled data are negative.
• Products containing THC: With THC-containing formulas, subjective sleep is better (meta-analysis SMD 0.82), but measured sleep differs by type of measurement: in a single-dose lab study total sleep and REM decreased, in a two-week study the lab measurement did not change, and in one meta-analysis sleep time measured with an electronic device got longer; according to Cochrane 2026, medical cannabis adds little or nothing meaningful to sleep quality and total sleep (very low certainty); in people who got a medical cannabis card for insomnia, insomnia scores fell over 12 weeks, but participants knew their group, and in the same study cannabis use disorder developed about twice as often in those who got a card (most in those who applied for anxiety or depression); in sleep apnea, dronabinol reduced breathing pauses in short RCTs (11–13 events per hour fewer than placebo in 73 people; part of the difference comes from a rise in the placebo group), but the American Academy of Sleep Medicine recommends against its use; in PTSD-related nightmares, a 171-person dronabinol RCT found nightmares decreased more than with placebo (most people taking dronabinol figured out which group they were in); THC’s addiction and driving risks are separate. (weak evidence) Evidence: Weak (small RCTs, blinding problems, mostly subjective measures); CBN: very low/low; dronabinol in sleep apnea: low (two small and short RCTs, one combined with acetazolamide; the American Academy of Sleep Medicine does not recommend it); THC+CBD in restless legs: very low (a single uncontrolled study); dronabinol and nabilone in PTSD-related nightmares: moderate (same assessment as the PTSD page: a single large 171-person RCT and a 10-person RCT are positive; the large study was manufacturer-supported, and most people taking dronabinol figured out which group they were in)
• Dose range in studies: In pure CBD studies, 15–300 mg (at night or as a single dose), 50 mg/day for 8 weeks; with THC-containing products, ~2–20 mg THC + ~0.5–22.5 mg CBD/day (plus 1–2 mg CBN in ZTL-101) or a single dose of 10 mg THC + 200 mg CBD; CBN 15–300 mg; nabilone 0.25–1.75 mg/day (0.5–1 mg in insomnia; at most 3 mg for PTSD nightmares); CBG 25–50 mg/day; dronabinol in sleep apnea 2.5–10 mg (alone or with acetazolamide or atomoxetine); dronabinol for PTSD nightmares 2.5–15 mg/day; in other THC-containing products, from very-low-dose supplements (0.35–0.85 mg THC) up to 30 mg THC in an old study; in one patient registry the THC dose rose clearly over time (observational; the authors write it may be a sign of tolerance)
• Starting dose and titration (in studies): Fixed dose in most studies; in Ried 2023, increase from 0.2 → 1.5 mL/day; in de Almeida 2021, 75 → 300 mg/day; in sleep apnea, weekly 2.5 → 5 → 10 mg dronabinol in Prasad 2013, in Carley 2018 the 10 mg group started with 2.5 and 5 mg in the first two weeks, in Messineo 2023 weekly 2.5 → 5 → 10 mg together with atomoxetine; in Emerson 2026, CBG 25 → 50 mg after 2 weeks
• Interaction: Clobazam: in 13 children with epilepsy, the active metabolite N-desmethylclobazam rose by an average of 500%; the rise in clobazam itself (average 60%) was uncertain (confidence interval −2 to 91). In healthy volunteers, clobazam did not change and the metabolite rose ~3-fold (FDA/EMA). In 10 of 13 patients, side effects resolved when the clobazam dose was reduced (Geffrey 2015, PMID 26114620)
• Interaction: No short-term increase in side effects was seen in people taking benzodiazepines/antipsychotics (advanced cancer, Downs 2026, PMID 39539239)
• Interaction: Alcohol: 200 mg CBD + alcohol was not clearly different from the impairment caused by alcohol alone (Consroe 1979, PMID 120541; 10 people, old and small)
• Interaction: Pure oral CBD (15–1500 mg) did not cause THC-positive results on roadside saliva tests (McCartney 2022, PMID 34412166)
• Monitoring in studies: With pure CBD, 150 mg at night did not impair daytime cognitive performance (Narayan 2024); with THC-containing products, next-day sedation should be monitored
• Monitoring in studies: With THC-containing products, signs of cannabis use disorder should be monitored (Gilman 2022); in people with sleep apnea, cannabis products should not replace treatment, and follow-up with a sleep physician should continue (Ramar 2018)

References (48)

Study table (dose, duration, result) · Topic page

There are 6 small placebo-controlled studies (n 29–150, 8–12 weeks), and the products vary widely: pure CBD, 20:1 and 9:1 CBD:THC extracts, and a full-spectrum extract with a THC ratio <0.3%. The two RCTs with pure CBD were not clearly different from placebo on the primary outcomes; positive findings were seen on secondary measures or in a manufacturer-supported study. For sleep, two RCTs showed no advantage over placebo; there are no controlled data in adults or in epilepsy occurring alongside ASD. The placebo effect is strong, and most uncontrolled studies rely on parent reports. The "No effect found" label is based on the evidence for pure CBD (on this site, the CBD label is given for pure CBD, and products that also contain THC are rated separately): in the two controlled studies of pure CBD in autism, the primary outcomes were negative (the fragile X study was not used as a basis for the label because it was done in a different condition); positive findings were seen with extracts that also contain more or less THC (20:1 and 9:1 CBD:THC extracts, and a full-spectrum extract with a THC ratio below 0.3%) and mostly on secondary measures; the only study that was positive on a primary measure was manufacturer-supported. In fragile X syndrome, the 212-child RCT with pure CBD gel applied to the skin (CONNECT-FX) was negative on the primary outcome; a difference was seen only in an exploratory subgroup analysis that was not in the study's original plan, and the results of the second, 257-person RCT in this subgroup (RECONNECT) had not been published as of October 2026, either in the registry or in a peer-reviewed journal. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 7 controlled studies with cannabinoids in autism (6 treatment studies, one with results only in the registry; one single-dose brain imaging study in adults; one sub-analysis was not counted separately and is mentioned in the main study's row), 1 controlled study in fragile X syndrome, 1 small controlled study in intellectual disability and severe behavior problems (8 children; feasibility study) and 4 systematic reviews were found; all are in the table below. There is no Cochrane review assessing cannabinoids. There are three more controlled studies with unpublished results: 86 children with pure CBD in autism (CASCADE), 257 people in fragile X (RECONNECT) and 132 children with pure CBD in intellectual disability (Australia; ended in August 2025). Publications from the same Israeli group of children were combined in a single row in the table (Hacohen 2022). In an additional search in October 2026 (intellectual disability and severe behavior problems only; PubMed, Cochrane, ClinicalTrials.gov, Europe PMC), the only controlled study on this question to be included in the table was the 8-child pilot study (Efron 2021; all the children in the CBD group were autistic, so there is no separate result for intellectual disability without autism). The results of a 20-person uncontrolled pilot study with nabilone in adults with intellectual disability (ended in August 2025) and of single-patient crossover trials for behavior problems in rare genetic conditions (tuberous sclerosis, MPS III, fragile X) that began in the Netherlands in 2025 had not been published as of October 2026.

Evidence assessment: Pure CBD: Weak (in autism, only two controlled studies, 39 and 103 children, 8–12 weeks, one with results only in the registry; in both, the primary outcomes were negative; positive findings come from small studies without a control group). The studies of gel applied to the skin in fragile X syndrome were not used as a basis for this level because they were done in a different condition, and neither was the 8-child pilot study in intellectual disability, because it was not designed to measure the effect (feasibility study; the groups were not compared statistically). The results of CBD-rich products that also contain THC or have an unclear THC amount were assessed under the THC evidence

• CBD alone: In the two controlled studies with pure CBD (Trauner 2026: 39 boys aged 7–14, crossover; NCT04745026: 103 children, results only in the registry), no advantage over placebo was seen on the primary outcomes for behavior problems; the single-dose brain imaging study in adults (Pretzsch 2019) did not measure clinical effect. Two small studies without a control group (23 and 20 children) reported improvement. In fragile X syndrome, pure CBD gel applied to the skin was no different from placebo on the primary outcome in a controlled study of 212 children (CONNECT-FX); the difference in a subgroup analysis that was not in the original plan is exploratory and has not yet been confirmed. In children with intellectual disability and severe behavior problems, pure CBD has been compared with placebo only in an 8-child feasibility study (Efron 2021; the authors reported a signal in favor of CBD, but the number of children is far too small for a conclusion, and all the children in the CBD group were autistic); the result of the large 132-child study had not been published as of October 2026.
• Products containing THC: There are four controlled studies with CBD-rich extracts that also contain more or less THC or have an unclear THC amount, and their results are not consistent. In a 150-child study with a 20:1 CBD:THC extract (Aran 2021), only one of the two main measures, the doctor's overall assessment, was better than placebo (clear improvement in 49% versus 21%); the other main measure was negative. In a 60-child study with a 9:1 CBD:THC extract (Silva 2024), there was no difference on standard scales; only some symptoms improved on an interview form prepared by the authors. In a 34-child crossover study with a CBD oil reported to contain at most 1 mg THC per milliliter (Parrella 2026), the main measure was negative and some secondary measures were positive. In a manufacturer-funded study of 61 children with a full-spectrum extract containing very little THC and made up mainly of CBDA, the acid form of CBD (Keating 2026), the main measure (overall illness severity) was positive; the analysis included only the 54 children who completed the study. A meta-analysis pooling two of these studies found a small effect (Köck 2024); a 2026 meta-analysis pooling all cannabinoid products also saw a small reduction in autistic traits; this result rests on 2 studies done with products containing both THC and CBD, with low certainty of evidence (Wilson 2026). Studies and registries without a control group from Israel, Brazil, Turkey and the UK reported improvement; in Israel's national data, only about a quarter of children continued treatment for a year. Cases of psychosis and mania were reported in some young people with THC-containing products. (weak evidence) Evidence: Weak (four short RCTs in 34–150 children with CBD-rich extracts that also contain THC or have an unclear THC amount: one positive on the main measure but manufacturer-funded and analyzed only in completers, one positive on one of two main measures, one positive only on the authors' interview form, one negative on the main measure; low certainty in meta-analyses; uncontrolled studies are low-level evidence)
• Dose range in studies: In the studies, target 5–20 mg/kg/day for pure CBD or low-THC products; 7.5–10 mg/kg/day CBD for THC-containing 20:1 extracts (THC ceiling 0.375–0.5 mg/kg/day); averages reached 0.7–5.9 mg/kg/day (in studies where the dose was adjusted for each person, most with extracts that also contained THC; in the two controlled studies with pure CBD, the dose was the same for everyone, 10 or 20 mg/kg/day); in fragile X, pure CBD gel applied to the skin at 250 or 500 mg a day depending on weight (125–750 mg in the extension)
• Starting dose and titration (in studies): In the studies, the dose was started low (e.g. 1 mg/kg/day or 5 mg/kg/day, 1–6 drops a day) and raised at rates ranging from +1 mg/kg every other day to +5 mg/kg a week; reaching the target took 2 weeks to 2 months; the total dose was split into 2–3 a day; when stopping, it was tapered over 1–2 weeks
• Interaction: Antiepileptics (epilepsy cohort, not specific to ASD): as the CBD dose went up, N-desmethylclobazam, topiramate and rufinamide levels rose and the clobazam level fell; in adults, zonisamide and eslicarbazepine rose; with valproate, AST/ALT were high (Gaston 2017, PMID 28782097)
• Interaction: CYP: CBD is broken down by CYP2C19 and CYP3A4, THC by CYP2C9 and CYP3A4; ketoconazole raised CBD and THC levels with the THC/CBD mouth spray; rifampin lowered exposure to approved oral CBD by ~32% (FDA label), and with low-dose THC/CBD mouth spray the drop was ~50–60% (Stott 2013, PMID 23750331)
• Interaction: Barchel 2018 discussion (not its own data; citing a review in the context of products that also contain THC): phenytoin levels may rise; possible interaction with SSRIs, tricyclic antidepressants and CNS depressants. For pure CBD, the EMA product information states that no dose adjustment is needed for CYP2C9 substrates such as phenytoin
• Interaction: CBD blood levels were lower on average in those taking antipsychotics, SSRIs, alpha-2 agonists, stimulants or mood stabilizers (Trauner 2026)
• Interaction: All 3 patients who had serious side effects were taking multiple medicines, including antipsychotics; in two, the antipsychotic had been stopped suddenly without supervision (Fleury-Teixeira 2019)
• Interaction: Barchel 2018, based on animal studies, reports that THC may reverse the effect of risperidone
• Interaction: Sleepiness was more common in those taking chronic medication (Aran 2021)
• Interaction: CNS depressants and anticholinergics: effects such as drowsiness and ataxia may add up (Campos 2024, PMID 38794183)
• Interaction: NCT04745026 excluded people taking these medicines (not evidence of interaction; a sponsor safety limit): clobazam; omeprazole, lansoprazole; tolbutamide; warfarin; sirolimus, everolimus, temsirolimus, tacrolimus; repaglinide, pioglitazone, rosiglitazone; montelukast, bupropion, efavirenz
• Monitoring in studies: At the start, liver and kidney function, complete blood count and fasting blood sugar (Silva 2024)
• Monitoring in studies: Every two weeks, complete blood count, comprehensive metabolic panel, cannabinoid levels and ECG (Trauner 2026)
• Monitoring in studies: At the start and at month 3, complete blood count, liver enzymes, kidney, lipids, thyroid and prolactin (interim safety analysis of the Hacohen 2022 cohort: Stolar 2022, PMID 36249785)
• Monitoring in studies: Safety blood tests at the start and at weeks 4, 8 and 16 (Keating 2026)
• Monitoring in studies: Asking about side effects with a structured scale or by phone every 2 weeks (Aran 2021; Barchel 2018; Hacohen 2022)
• Monitoring in studies: With CBD gel applied to the skin, a skin examination of the application site at every visit; also ECG, safety blood tests and screening for suicidal thoughts (Berry-Kravis 2022)

References (25)

Study table (dose, duration, result) · Topic page

All six randomized controlled trials of cannabinoids in Tourette syndrome and chronic tic disorders used THC. The largest (CANNA-TICS; 97 adults, mouth spray containing THC and CBD, 13 weeks) did not show superiority on the primary outcome: at least a 25% reduction in tic score in 21.9% versus 9.1% (p = 0.076; results in the EU clinical trials register); the protocol had set the response threshold at 30%, according to the register the 25% threshold was set during a blinded data review before the groups were unblinded, and with the 30% threshold the difference was also not significant (12.5% versus 3.0%; p = 0.063); secondary measures showed a trend toward improvement, and at one site 17% of participants asked afterward said they had found out which group they were in. In a crossover study of 22 adults with severe Tourette syndrome, an oil containing THC and CBD lowered the tic score more than placebo (8.9 versus 2.5 points; p = 0.008), but 8 people had cognitive side effects. Two small studies with pure THC in 2002 and 2003 (12 and 24 people) reported reductions on some scales; based on these two, a Cochrane review (2009) found the evidence insufficient, and it has not been updated since. In the 12-person study testing single doses of inhaled marijuana, there was no difference on the primary measure; the THC-rich product did better on secondary measures (urge before tics, distress, overall impression), no benefit was reported for the CBD-rich product, and most participants could tell the product from placebo. In teens (ages 12–18) there are only two pilot studies of 10 people each: one a placebo-controlled crossover feasibility study (according to an editorial, no statistical test of effectiveness was done), the other uncontrolled. Meta-analyses conflict: a 2026 meta-analysis covering 54 RCTs in mental health conditions found a reduction in tic severity (the abstract does not make clear how many studies and which products it is based on; certainty low for most outcomes); another 2026 meta-analysis covering adults found a negligible effect in Tourette syndrome (certainty mostly very low); a 2026 meta-analysis specific to Tourette syndrome compared only before and after treatment. The American Academy of Neurology's 2019 guideline, based on two older pure-THC studies, gave THC 'low confidence', counted cannabis-based medicines as an option that may be considered only in adults who have not improved with other treatments, and recommended avoiding them in children and adolescents and not using them in pregnancy, breastfeeding and psychosis; the European Tourette guideline (2022) lists cannabis-based medicines among options that may be considered only in treatment-resistant cases and recommends education and behavioral therapy as first-line treatment. Uncontrolled studies and clinic records (10–98 people) reported improvement in tics and quality of life; in a 70-person registry there was no significant improvement in tics, and in long-term users the THC dose rose from year to year; in Israel, more than half of children under 12 with Tourette syndrome who were prescribed medical cannabis oil stopped within the first three months. There are no controlled studies with oral CBD oil. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, EU clinical trials register, Europe PMC): 6 randomized controlled trials of cannabinoids on this topic (177 randomized participants; about 170 people, because two older studies shared patients; all with THC-containing products, one of which also had a CBD-dominant arm), 3 uncontrolled prospective studies, 5 systematic reviews and meta-analyses (1 Cochrane, 1 the evidence review behind the American Academy of Neurology guideline), 1 clinical guideline and 4 observational studies were found; all are in the table below. There is one RCT planned with 60 people whose results were never published (THC and palmitoylethanolamide; according to the EU register, terminated early in Germany in 2019); no studies from Turkey were found.

Evidence assessment: Pure CBD: Insufficient (no studies with CBD oil; CBD-dominant inhaled marijuana was tested only as a single dose, in a 12-person study)

• CBD alone: There are no controlled studies of pure CBD or oral CBD oil in Tourette syndrome. CBD-dominant vaporized marijuana (which also contains a small amount of THC) was tested only as a single dose given once, in a study of 12 adults (9 completed); no clear difference from placebo in tics was reported. Positive results seen with products that also contain CBD cannot be separated from THC: in studies that measured blood levels, improvement was linked to THC and its breakdown products, not to CBD. In Israel, most of the products given to children under 12 with Tourette syndrome who were prescribed medical cannabis oil were CBD-rich, but almost all of them also contained THC (96% of the first bottles dispensed); more than half of these children stopped treatment within the first three months, and the registry did not measure effectiveness.
• Products containing THC: The results of six small controlled studies (about 170 people in total) with pure THC, a mouth spray or oil containing THC and CBD, and inhaled marijuana are not consistent: in a 22-person crossover study, the tic score fell more with the THC and CBD oil than with placebo; in two small studies with pure THC, a reduction was seen only on some scales; in the largest study, with 97 people (mouth spray, 13 weeks), the share of people whose tics fell by at least a quarter was 21.9% versus 9.1%, but the difference was not statistically significant (nor was it with the 30% threshold in the study plan); with a single dose of inhaled marijuana there was no difference on the main measure. In teens there are only two pilot studies of 10 people each. Of two meta-analyses in 2026, one found fewer tics and the other a negligible effect; the certainty of the evidence is low or very low. THC caused slowed thinking, dizziness and sleepiness; in one study most participants could tell which group they were in. (weak evidence) Evidence: THC and THC+CBD: Weak (6 small controlled studies, 10–97 people; the largest did not show superiority on the main measure; meta-analyses conflict, certainty low to very low; only two pilot studies in children and adolescents)
• Dose range in studies: Pure THC single dose 5–10 mg and at most 10 mg/day (6 weeks); nabiximols 1–12 sprays/day (at most 32.4 mg THC + 30 mg CBD); THC+CBD oil (5+5 mg/mL) 1–4 mL/day (at most 20 mg THC + 20 mg CBD); in teens THC+CBD oil (10+15 mg/mL) at most 10 or 20 mg THC/day; dronabinol at most 10 mg/day + palmitoylethanolamide 800 mg/day; inhaled marijuana single dose 0.25 g; no studies with CBD oil
• Starting dose and titration (in studies): Nabiximols: started at 1 spray a day and raised, depending on the person, to at most 12 over 4 weeks (CANNA-TICS protocol); THC+CBD oil: from 1 mL/day, increased by 1 mL a week to at most 4 mL (Mosley 2023); in teens from 1 mg THC/day to 5 or 10 mg over about 3 weeks, and if there was no response, increased for 3 more weeks to 10 or 20 mg (Eapen 2025); dronabinol from 2.5 mg to 10 mg over 1 week (Bloch 2021); these are research protocols
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: Most participants were taking other medicines for tics, ADHD or OCD: in the studies, the doses of these medicines were kept stable for at least 30 days beforehand (CANNA-TICS protocol) or had to be unchanged for the past 4 weeks (Eapen 2025)
• Monitoring in studies: In a person using a THC-containing product, thinking, attention, mood and obsessive-compulsive symptoms should be monitored with a doctor; these side effects were common in the studies
• Monitoring in studies: In the study with teens, kidney function and electrolytes were checked at baseline, and liver tests and a urine drug screen were done at baseline and on day 85 (Eapen 2025)
• Monitoring in studies: Planned study: a crossover study comparing THC (dronabinol) combined with palmitoylethanolamide against placebo in 164 adults (NCT05126888) is listed in the registry as 'not yet recruiting' as of October 2026 (planned start June 2026, completion February 2028)

References (19)

Study table (dose, duration, result) · Topic page

In the only randomized controlled trial of cannabinoids in ADHD (Cooper 2017; 30 adults, mouth spray containing THC and CBD, 6 weeks), there was no difference from placebo on the primary outcome (QbTest cognitive performance and activity) (estimate −0.17; 95% CI −0.40 to 0.07; p = 0.16); the improvement in hyperactivity-impulsivity (p = 0.03) and on an inhibition measure (p = 0.05) did not remain significant after correction for multiple testing. There are no controlled studies with pure CBD. In studies of Tourette syndrome and chronic tic disorder, ADHD was examined only as a co-occurring condition and with THC-containing products; these studies are in the table of the site's Tourette Syndrome page: in the 97-adult RCT (CANNA-TICS; mouth spray containing THC and CBD, 13 weeks), the reduction in tics looked larger versus placebo in those with ADHD but was not statistically significant (exploratory subgroup analysis; Müller-Vahl 2023, PMID 36878177; subgroup result Czech 2026, PMID 42123126), and the result of the ADHD symptom scale planned as a secondary outcome in the protocol appears neither in the article's abstract nor in the EU clinical trials register; in the uncontrolled study with 10 adolescents with Tourette syndrome (oil containing THC and CBD, 12 weeks), the parent-rated ADHD score fell from 32.8 to 25.4, but the change was not significant (p = 0.063; Eapen 2025, PMID 40636988). Uncontrolled data: in 53 children and young people with autism and ADHD symptoms, improvement in teacher ratings over 3–6 months with CBD-rich cannabis oil (Barchel 2026; the product in the same center's autism program was CBD:THC 20:1, meaning it contains a small amount of THC); in a manufacturer-supported, 12-week study in 14 children with pediatric acute-onset neuropsychiatric syndrome (PANS) using a CBDA-dominant extract with a small amount of THC, the ADHD symptom scale (Conners), one of the secondary measures, also improved (p = 0.028); all of the children had OCD symptoms and continued their other medicines (Keating 2026, PMID 41513541; the study is in the table of the site's OCD and Hair Pulling page); in the UK Medical Cannabis Registry, in 68 adults prescribed it for ADHD (mostly inhaled flower; median 209 mg THC and 15 mg CBD/day), improvement in anxiety and sleep scores up to 12 months and in quality of life up to 6 months; ADHD symptoms were not measured, 49% of patients were assessed at month 12, the registry belongs to a private chain of clinics, and 5 of the 6 authors have business ties to this chain or to the cannabis company that makes the most commonly prescribed products (Ittiphakorn 2023). A 2026 meta-analysis pooling cannabinoid RCTs in mental health conditions did not find enough data to run a pooled analysis for ADHD (Wilson 2026); a 2026 meta-analysis pooling experimental and observational studies reported that the effect in adult ADHD was negligible or absent, with certainty mostly very low (Bharat 2026); according to a 39-study scoping review, in most studies cannabis worsened ADHD symptoms or had no effect on them (Francisco 2023). Cannabis use in people with ADHD: lifetime prevalence of cannabis use disorder 26.9%, risk 2.85 times the general population (Froude 2024; 14 studies); childhood ADHD is associated with later cannabis use (OR 2.78; 95% CI 1.64–4.74) and with cannabis abuse or dependence (OR 2.29; 1.32–3.99) (Lee 2011); in the long-term follow-up of the multicenter MTA study, weekly use in adulthood was 32.8% versus 21.3% (Molina 2018); Mendelian randomization suggested a causal effect running from ADHD predisposition to cannabis use (OR 7.9; 95% CI 3.72–15.51) and found no effect in the reverse direction (Soler Artigas 2020); in a survey, 75% of adults with ADHD had used cannabis at least once, and use disorder was more common among daily users (62% versus 38%; Ryan 2026); under the influence of cannabis, impulsivity decreased in people with ADHD, but performance dropped on five cognitive measures (Stueber 2026); 31.3% of parents of children diagnosed with ADHD, autism or anxiety had given an unapproved CBD product (Schwaller 2023). In 11 studies looking at the effects of cannabis on the brain and cognition in young people with ADHD, no interacting harm of ADHD and cannabis was seen on executive function tests; early onset was associated with worse test results in one study (exploratory analysis) and with differences in brain structure in another; 5 of the 11 studies came from the same (MTA) cohort (Cawkwell 2021); there is little evidence that cannabis-related psychosis risk is additionally raised in people with ADHD (Suetani 2026; 3 studies). In adolescents (studies not specific to ADHD, and therefore not included in the table): cannabis use is associated with a later diagnosis of psychotic disorder (adjusted HR 2.19; Young-Wolff 2026, PMID 41719031), the risk of addiction in young people who use regularly is 33% (Leung 2020, PMID 32485547), inhaled THC also impaired memory in adolescents aged 16–17 and CBD did not reduce this (Lawn 2023, PMID 36750134), and cognitive decline in frequent users is small and not clear after more than 72 hours of abstinence (Scott 2018, PMID 29710074). Cannabis use in pregnancy is slightly associated with ADHD in the child (adjusted OR 1.13; Bassalov 2024); in the largest screened cohort there is no association (Young-Wolff 2025). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 1 controlled study of cannabinoids on this topic was found (mouth spray containing THC and CBD, 30 adults; Tourette studies that measured ADHD only as a co-occurring condition were not counted and are mentioned above); there are no controlled studies with pure CBD, no Cochrane review of cannabinoids in ADHD, and no registered unpublished studies with results. In addition, the table includes 2 uncontrolled studies, 3 reviews that also cover ADHD, 9 observational studies and reviews on cannabis use and its risks in people with ADHD, and 2 studies on cannabis use in pregnancy and ADHD in the child; all are in the table below. 4 sources on the risks of cannabis in adolescence that are not specific to ADHD are mentioned only in the text. There is one study that was stopped with 8 people because participants could not be found, with no results released; 3 controlled studies are ongoing or of unknown status (no results); no studies of cannabinoid treatment in ADHD from Turkey were found.

Evidence assessment: Pure CBD: Insufficient (no controlled studies with pure CBD or CBD oil in ADHD; in the only study without a comparison group, in autistic children, the CBD-rich oil used also contained a small amount of THC; a planned controlled study with THC-free CBD oil has no results)

• CBD alone: There are no controlled studies of pure CBD or CBD oil in ADHD. In a study without a comparison group in children and young people with autism and ADHD symptoms, the CBD-rich oil also contained a small amount of THC (a CBD to THC ratio of 20 to 1 in the same center's autism program); so its result is in the THC-containing products section. A 120-person study in children and teens comparing a THC-free CBD oil with added terpenes against placebo is registered in Israel under a company's sponsorship; the record has not been updated since August 2024, and as of October 2026 it has no results.
• Products containing THC: There is only one controlled study of THC-containing products in ADHD: in 30 adults over 6 weeks, a mouth spray containing THC and CBD was not clearly different from placebo on the main measure; the signs of improvement in hyperactivity and impulsivity did not survive correction for multiple comparisons. In 53 children and young people with autism and ADHD symptoms, improvement in teacher ratings over 3–6 months was reported with a CBD-rich oil that also contains a small amount of THC, but there was no comparison group. In a registry of 68 adults, most using inhaled cannabis, anxiety and sleep improved, but ADHD symptoms were not measured. In adults with ADHD using their own cannabis, impulsivity decreased somewhat, but performance dropped on many attention and memory tests. Two large reviews found insufficient evidence of benefit; according to a 39-study scoping review, in most studies cannabis worsened ADHD symptoms or had no effect on them. There are no controlled ADHD studies of THC-containing products in children and adolescents; cannabis use in adolescence is linked to risks of psychosis and addiction (observational). (very weak evidence) Evidence: THC and THC+CBD: Very weak (a single small 6-week controlled study with 30 adults with ADHD, no difference on the main measure; other data come from uncontrolled studies (CBD-rich oil with a little THC in autistic children; UK patient registry), observational studies and surveys; no controlled studies in children and adolescents)
• Dose range in studies: Nabiximols (mouth spray containing THC and CBD) at most 37.8 mg THC + 35 mg CBD/day, 6 weeks (the only controlled study; highest dose from review tables); in the UK registry the median prescribed amount was 209 mg THC + 15 mg CBD/day (mostly inhaled flower); no ADHD studies with pure CBD or CBD oil
• Interaction: Detailed information and monitoring recommendations are on the 'ADHD medications' page in the site's drug interactions section (methylphenidate and atomoxetine)
• Interaction: Methylphenidate: in 12 healthy volunteers, 750 mg of approved CBD twice a day for 3 days raised the total blood exposure of a single 10 mg dose of methylphenidate by 9% on average (geometric mean ratio 1.09; 90% CI 0.89–1.32); the researchers considered this clinically insignificant (Markowitz 2022, PMID 36467779). Laboratory and modeling studies predict a larger increase with repeated high CBD doses; this has not been confirmed in humans (Qian 2022, PMID 35512806)
• Interaction: Atomoxetine: no human studies have examined it together with CBD; CBD slowed CYP2D6, the enzyme that breaks down atomoxetine, in the laboratory, but a CBD-dominant cannabis extract did not slow it in healthy volunteers (PMID 21821735; PMID 37313955)
• Interaction: THC and methylphenidate: in 16 volunteers without mental illness who used cannabis occasionally, increases in heart rate added up when 10 mg of oral THC was taken together with 10 or 40 mg of methylphenidate (peak heart rate averaged 89, 96 and 102 beats/min when 0, 10 and 40 mg of methylphenidate were added to THC); THC increased the number of errors on an attention test (Kollins 2015, PMID 25175495)
• Interaction: No human studies were found examining CBD with amphetamine derivatives (lisdexamfetamine, dexamfetamine), guanfacine or clonidine (October 2026 search). There are a few small laboratory studies with THC: in volunteers, cannabis smoked after 10 mg of dextroamphetamine added to the increases in heart rate and blood pressure (Evans 1976, PMID 782773); in volunteers who used cannabis regularly, guanfacine (2–3 mg a day) was well tolerated together with smoked cannabis or 20 mg of oral THC, a small drop in blood pressure was seen, and THC's heart-rate-raising effect did not change (Haney 2019, PMID 29659126; Mathai 2018, PMID 28641496); in a 15-patient open-label study testing atomoxetine together with dronabinol (synthetic THC) for sleep apnea, side effects were common and one third of patients stopped treatment (Messineo 2023, PMID 36805833)
• Interaction: In the UK registry, over 12 months, 5 of 13 people taking lisdexamfetamine and 3 of 20 taking methylphenidate stopped their medicine; during the same period 3 people newly started methylphenidate and 2 started dexamfetamine (Ittiphakorn 2023); this is an uncontrolled observation, not evidence of benefit or of an interaction
• Monitoring in studies: Screening for cannabis use disorder and co-occurring mental health diagnoses is recommended in people with ADHD who use cannabis (Froude 2024; Ryan 2026)
• Monitoring in studies: Because both ADHD medicines and CBD can reduce appetite, weight and height are monitored by a doctor in children; details are on the site's ADHD medications page (methylphenidate and atomoxetine product information, product information for approved CBD)
• Monitoring in studies: Ongoing studies (October 2026): in Israel, THC-free CBD oil with added terpenes versus placebo in 120 children and teens aged 6–18 (NCT06542445; according to the record it started in August 2024, estimated completion September 2026; the record has not been updated since August 2024 and its status is 'unknown'); in the US, a single 80 mg dose of cannabigerol (CBG) versus placebo in 76 adults aged 18–55, with attention and memory tests (NCT06115603; the record was last updated in May 2026 and appears as 'recruiting'; planned completion was July 2026); in Brazil, a full-spectrum oil containing CBG, CBD and THC versus placebo in 60 young people aged 12–17, 12 weeks (NCT07592390; recruiting, estimated completion December 2026). None has results yet

References (17)

Study table (dose, duration, result) · Topic page

Low-dose pure CBD was ineffective in Crohn’s disease. A CBD oil containing THC eased symptoms (in the analysis adjusted for differences in age, sex and disease duration, the difference was not confirmed), but endoscopy, CRP and calprotectin, which show inflammation in the bowel, did not change. In ulcerative colitis, the primary outcome was negative with a CBD-rich extract that also contained THC. In two small RCTs with THC-rich marijuana cigarettes (21 people in Crohn’s disease, 32 in ulcerative colitis), symptoms and quality of life improved compared with placebo; but in Crohn’s disease the difference in complete remission was not significant, and in ulcerative colitis there was no difference from placebo in endoscopy, CRP or calprotectin, and blinding was weak. Reviews assessing the RCTs (Cochrane 2018, Doeve 2021, Kang 2025, Jugl 2026) found no significant difference from placebo in remission, endoscopy or inflammation markers; some report improvement in symptom scores and quality of life, but the certainty of evidence ranges from very low to moderate, and all rest on the same small studies. In a 14-patient uncontrolled pilot study with a CBD + sodium propionate enema in ulcerative proctitis, the Mayo score improved; there was no control group, and the product contains another active ingredient besides CBD. A patient may 'feel well' while the disease progresses; CBD should not replace standard treatment (biologic medicines, steroids, etc.). The 2019 position statement of the Canadian Association of Gastroenterology also states that, based on the evidence at the time, cannabis did not appear to change the course of these conditions for better or worse, that the evidence is insufficient to recommend it as a treatment that reduces inflammation, and that it should not be used in place of approved treatment (expert opinion without a formal grading of evidence; 3 of the 7 authors have ties to cannabis or cannabinoid companies). The results of observational studies comparing patients who use cannabis with those who do not are conflicting: in Canada, use for more than 6 months was linked to surgery in Crohn’s disease; in a large US study based on health records, emergency visits, hospital admissions, and steroid and opioid use were more common in cannabis users, but there was no difference in surgery or death; in coded data of hospitalized patients, some complications were less common and others more common. People with more severe disease using cannabis more often may explain these links; these studies do not show cause and effect. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 5 randomized controlled trials with cannabinoids on this topic (all small: 20–60 people, 8–10 weeks) and 9 systematic reviews or meta-analyses, including two Cochrane reviews, were found; all of the controlled trials, the most comprehensive and up-to-date reviews, the 2019 position statement of the Canadian Association of Gastroenterology (added in the October 28, 2026 completion round) and the main observational studies are in the table below. There are no controlled studies in children and adolescents; a 15-person RCT with pure CBD in steroid-dependent Crohn’s disease was completed in 2022, but its results have not been published.

Evidence assessment: Weak (a single small RCT with pure CBD, low dose)

• CBD alone: The only RCT with pure, low-dose CBD (10 mg twice a day) was negative in Crohn’s disease. There is no published study comparing pure CBD with placebo in ulcerative colitis; in a 14-person uncontrolled study in mild to moderate ulcerative colitis limited to the rectum (proctitis) with an enema containing both synthetic CBD and sodium propionate, which is not a cannabinoid, the disease score improved, but because there was no placebo group and the product contained a second active ingredient, the effect of CBD cannot be shown on its own. A 15-person RCT with synthetic pure CBD in steroid-dependent Crohn’s patients was completed in 2022, but its results have been neither published nor posted to the registry (October 2026).
• Products containing THC: There are 4 small RCTs with THC-containing products (21–60 people, 8–10 weeks). In Crohn’s disease, with a CBD/THC oil the disease activity score and quality of life improved more than with placebo, but once differences in age, sex and disease duration between the two groups were taken into account, this difference was not statistically confirmed; objective measures of inflammation (endoscopy, CRP, calprotectin) did not change either. In Crohn’s disease, clinical response was more common with THC-rich marijuana cigarettes, but the difference in the primary outcome, complete remission, was not significant. In ulcerative colitis, the primary outcome (remission) was negative with a CBD-rich extract that also contained THC; THC-rich marijuana cigarettes improved the symptom score, but there was no difference from placebo on endoscopy. Because the effect of THC can be felt, blinding was weak. Reviews find no difference in remission or inflammation; the certainty of evidence ranges from very low to moderate. (weak evidence) Evidence: Weak (4 small RCTs; signs of improvement in symptoms, no difference shown in inflammation)
• Dose range in studies: Pure CBD 10 mg twice a day (Crohn’s disease); 100–500 mg/day CBD in a THC-containing extract (ulcerative colitis); in the CBD/THC oil in Crohn’s disease, from 2 × 1 drop a day up to at most 2 × 20 drops (according to secondary sources, about 8 mg CBD + 2 mg THC per drop); THC-rich marijuana cigarettes, 2 a day (Crohn’s disease and ulcerative colitis); in ulcerative proctitis, 60 mg synthetic CBD in 1 enema a day
• Starting dose and titration (in studies): Drop-by-drop increase with the CBD/THC oil (at most 40 drops a day); with the CBD-rich capsules, from 2 × 50 mg to 2 × 250 mg if tolerated; in the cigarette study in ulcerative colitis, from half a cigarette to 2 × 0.5 g a day
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Monitoring in studies: Even when symptoms improve, inflammation checks (calprotectin, CRP, endoscopy) continue according to the doctor’s plan; in the studies, these measurements did not change differently from placebo while symptoms improved (Naftali 2021, Crohn’s disease and ulcerative colitis)

References (16)

Study table (dose, duration, result) · Topic page

Most of the evidence in MS spasticity concerns the prescription THC:CBD medicine nabiximols (Sativex): it increases the number of people reporting a significant reduction in spasticity in the short term (moderate certainty), with little or no effect on quality of life; the difference in doctor-measured muscle tone, however, is very small or absent (Cochrane: −0.23 points on the Ashworth scale, low certainty); in a 2024 RCT (68 people) with muscle tone as the primary endpoint there was no difference from placebo, and a small difference was found only in its 31-person companion study of the same design, whose results were published only on ClinicalTrials.gov; in the same program's 137-person parallel study, there was no difference in the number of muscle spasms that patients recorded in a diary (these two studies were stopped early by a business decision of the sponsor). The largest differences come from studies that first gave the drug to everyone and then randomized those who responded (enriched designs); a 2026 review of 27 studies through the end of 2025 rated the certainty of the patient-reported benefit as low. In the largest study with oral cannabis extract or synthetic THC (CAMS, 630 people), there was no difference in doctor-measured spasticity, but patient-reported spasticity improved; in the 279-person MUSEC trial, the number of people reporting relief of muscle stiffness was about twice that with placebo (29.4% vs. 15.7%). For pure CBD, there are only two small, short RCTs (55 people in total received pure CBD): in the study that raised the dose to 80 mg/day over 4 weeks (49 people), spasticity was no different from placebo, and only the walking test and peak pain improved more; in the CBD arm that took up to 45 mg/day for 6 weeks (31 people), there was no difference in spasticity or pain. Higher doses have not been tested in controlled parallel studies. Oral synthetic THC (dronabinol) did not slow disease progression over 3 years in progressive MS (498-person RCT). Nabiximols results cannot be applied to pure CBD oil. Two RCTs looked specifically at bladder problems caused by MS, both with THC-containing products: in the CAMS bladder substudy, incontinence frequency adjusted for baseline imbalance decreased by 38% with cannabis extract, by 33% with THC, and by 18% with placebo (both active groups significantly better than placebo; absolute difference vs. placebo 0.21 and 0.16 episodes a day, as calculated by Torres-Moreno 2018); in the 135-person nabiximols RCT done specifically for the bladder (8 weeks, sponsored by the manufacturer), there was no difference in the primary outcome, the daily number of incontinence episodes (−0.11; 95% CI −0.47 to 0.26), while secondary measures such as nighttime urination, the daily number of urinations, and the patient's overall bladder assessment favored nabiximols. Two large RCTs that assessed the bladder as a secondary measure found no difference: in Wade 2004 (160 people, spray), on the bladder problem VAS (difference −6.3; 95% CI −14.9 to 2.4; p = 0.15) and on the bladder control test (p = 0.89; ClinicalTrials.gov result), and in CUPID (498 people, 3 years, oral THC), on secondary measures including the bladder (full report; Torres-Moreno 2018). In the 2018 meta-analysis pooling placebo-controlled RCTs, the effect on bladder function was very small (standardized mean difference −0.11; 95% CI −0.22 to −0.0008) and was not significant once the studies supported by the manufacturer were removed. The MS-specific 2017 meta-analysis (2 RCTs and 1 study without a comparison group, 426 patients) reported a reduction in urinary incontinence but considered the evidence base weak; from the abstract it is not clear what its pooled figure (−0.35 episodes a day) compares with what, and this figure is larger than the differences vs. placebo in the included RCTs (0.11–0.21 a day). A 2026 scoping review (12 studies, 3 of them RCTs) also found the evidence limited and largely observational. In three small studies without a comparison group (15–31 people; Brady 2004, PMID 15327041; Maniscalco 2018, PMID 29052091; Torri Clerici 2023, PMID 37062198), urinary symptoms and some urodynamic measures improved. There are no bladder studies of pure CBD in MS. In a controlled study of 40 people with MS who had smoked cannabis almost daily for a long time and had cognitive impairment (groups were assigned by registration number, not randomly), those who stopped for 28 days showed clear improvement on tests of memory, processing speed, and executive function, while those who continued did not (Feinstein 2019). The UK national guideline (NICE, 2019) recommends a 4-week trial of the THC:CBD spray for moderate to severe MS spasticity that has not improved with other medicines, and continuing it if patient-reported symptoms decrease by at least 20%; the committee judged most of the evidence to be of low quality and noted that the evidence for other cannabis products was much more limited. The American Academy of Neurology's guideline on complementary therapies in MS (2014; reaffirmed on February 21, 2026) lists oral cannabis extract (level A), THC, and the THC:CBD spray (level B) as options for patient-reported spasticity symptoms and pain (excluding central neuropathic pain); it states that these products are probably ineffective for doctor-measured spasticity, and that the spray is probably helpful for urinary frequency and probably ineffective for urinary incontinence (level B); the guideline is based on studies up to September 2013. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 25 randomized controlled trials examining spasticity or the course of the disease with cannabinoids in people with MS (three with results only in the ClinicalTrials.gov registry) and more than 20 systematic reviews asking the same question were found; all of the randomized trials, the 3 most comprehensive reviews, and 3 large real-world and safety registries from different countries are in the table below. Only two of the randomized trials tested pure CBD. In an additional October 2026 search (bladder problems in MS only; PubMed and ClinicalTrials.gov), the only separate RCT on bladder problems, two reviews on this topic, and the American Academy of Neurology's MS guideline were added to the table; the CAMS bladder substudy is in the CAMS row, the bladder results of the other RCTs in the table and of the 2018 meta-analysis are in their own rows, and the three small bladder studies without a comparison group are mentioned only in this text. The NICE guideline and the controlled study of the effect of stopping on thinking skills in long-term cannabis users were also added to the table. Trials in MS done only for pain were not included in this table; no studies from Turkey were found. In an additional October 2026 search (MS-related tremor and ataxia only; PubMed, Cochrane, ClinicalTrials.gov, Europe PMC), the only randomized study that looked specifically at tremor (Fox 2004: 14 people, crossover, oral cannabis extract; no difference from placebo on objective tremor measures, finger tapping faster with placebo), an 8-person THC study without a comparison group (open-label) (Clifford 1983; improvement in coordination on examination in 2 patients) and a systematic review on this topic (Pourmohammadi 2022; did not recommend cannabis-based medicines) were added to the table; the tremor result of Wade 2004 (no difference in the patient-reported tremor score: −6.85; 95% CI −20.31 to 6.60) was written into its own row. There are no studies of pure CBD in MS-related tremor; the evidence for tremor is weak.

Evidence assessment: Pure CBD: weak (two small, short RCTs, both negative for spasticity; low doses: 45–80 mg/day)

• CBD alone: In two small RCTs, pure CBD did not reduce spasticity more than placebo (45–80 mg/day, 4–6 weeks); one study found improvement in a walking test and in peak pain. Pure CBD has never been tested for MS-related bladder problems or tremor.
• Products containing THC: Nabiximols (THC:CBD about 1:1, prescription) reduces perceived spasticity in the short term (OR 2.51; pooled from four spray studies and one oral cannabis extract study; moderate certainty, a 2026 review rated certainty as low); the difference in doctor-measured muscle tone is very small or absent (low certainty; the 2024 RCT was negative, its unpublished 31-person companion study was positive); in the same program's unpublished 137-person study, there was no difference in the number of muscle spasms patients recorded in a diary; results with oral cannabis extract and THC are mixed (in the largest study, benefit only in patient reports); nervous system and psychiatric side effects may be increased. In MS-related tremor, oral cannabis extract (14-person crossover RCT) and THC:CBD spray (tremor measurement in a 160-person RCT) were no different from placebo. (moderate evidence) Evidence: Nabiximols: moderate (benefit in patient-reported spasticity; certainty moderate in Cochrane 2022, low in a 2026 review; difference in doctor-measured muscle tone very small or absent); MS-related tremor: weak (a single 14-person RCT looking specifically at tremor and a secondary tremor measurement in one RCT; no difference in either)
• Approval: Pure CBD is not approved for MS spasticity. Nabiximols (a mouth spray containing THC and CBD; 2.7 mg THC + 2.5 mg CBD per spray) is approved in many countries, including the United Kingdom (in 29 countries, according to a 2024 publication by authors from the manufacturer), as an add-on to existing treatment for moderate to severe MS spasticity in adults who have not responded adequately to other spasticity medicines and who show clear improvement during an initial trial period. Treatment is started and supervised by a specialist doctor experienced in treating these patients. Dosing schedule in the product information: 1 spray in the evening on day 1; a morning dose is added on day 5; the daily number is increased gradually up to a maximum of 12 by day 14 (at least 15 minutes between sprays); in clinical studies, the median was 8 sprays/day; more than 12 a day is not recommended. If there is no clinically meaningful improvement in spasticity symptoms after 4 weeks (at least 20% on a 0–10 scale in studies), treatment is stopped. Not recommended under 18 years of age or in moderate or severe liver impairment. Source: UK product information (text revision April 2, 2026) §4.1, §4.2. Turkey: the active substance (tetrahydrocannabinol and cannabidiol, oromucosal spray) is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency) (September 28, 2026), among medicines that require a red prescription and can be imported with the agency's written approval.
• Dose range in studies: Pure CBD 45–80 mg/day (4–6 weeks); nabiximols up to 12 sprays a day (32.4 mg THC + 30 mg CBD); mean 8.3 sprays/day in Novotna 2011; mean 6.4–12.4 sprays/day in the other spray studies; oral cannabis extract and THC capsules up to 10–30 mg THC/day (CAMS and MUSEC 25 mg, CUPID 28 mg)
• Starting dose and titration (in studies): Mousavi 2025: from 5 mg/day to 70 mg/day over 2 weeks, then 80 mg/day; Hansen 2023: standard 3-week titration; Bethoux 2024: 14 days of dose adjustment in each period; nabiximols product information: start with 1 spray in the evening on day 1, increase the number gradually up to a maximum of 12 by day 14 (at least 15 minutes between sprays), stop if there is no clear improvement at 4 weeks (at least 20% on a 0–10 scale in studies); MUSEC: from 5 to 25 mg THC/day over 2 weeks
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: Product information for the THC:CBD spray (§4.5): strong CYP3A4 inhibitors such as ketoconazole raise THC and CBD levels (the dose may need to be readjusted if itraconazole, ritonavir, or clarithromycin is started or stopped); fluconazole increases THC exposure; strong inducers such as rifampin, carbamazepine, phenytoin, phenobarbital, and St. John's wort should be avoided if possible; sedative effects and fall risk may increase with sleep medicines, muscle relaxants, and alcohol; hormonal contraceptives may become less effective
• Monitoring in studies: CANSEP in Canada (NCT05092191): pure CBD (up to 200 mg a day), THC, and the two together vs. placebo; 250 people planned, participant-blinded only; primary outcome patient-reported spasticity. The registry was last updated in December 2024; no results as of October 2026
• Monitoring in studies: DroSpas-1 (NCT03756974): a 397-person phase 3 placebo-controlled study of oral dronabinol was completed in March 2021; as of October 2026, there are no results in the registry and no publication was found in PubMed
• Monitoring in studies: A double-blind study in Canada (University of Calgary) comparing oral THC with CBD for 15 weeks in 30 people with MS, with thinking skills and bladder symptoms as the main outcomes (NCT06261489; no placebo group): started in December 2025, estimated completion September 2027; as of October 2026, the registry shows 'recruiting'

References (40)

Study table (dose, duration, result) · Topic page

All RCTs with CBD-containing products for motor symptoms, levodopa-related involuntary movements, pain and REM sleep behavior disorder were negative; on some measures (sleep, cognition, quality of life), placebo did better. In most of these RCTs, the CBD came with a small amount of THC. For psychosis there is only one 6-patient open-label study; no RCT was found. The tremor and anxiety data come from a single-dose laboratory test; they do not count as evidence for daily use. Two small RCTs with a THC-like synthetic drug (nabilone), however, reported positive results: a 7-person crossover study on levodopa-related involuntary movements and a 38-person study on non-movement symptoms in which drug responders were selected first (enriched design); both are small and their designs may inflate the effect. In the 6-month open extension study with responders, the improvement in sleep and pain continued; the improvement in the total non-movement symptom score, however, was borderline, and there was no control group. Studies without a comparison group (high-dose pure CBD, smoked marijuana, medical marijuana at doses patients adjusted themselves, a chart review of patients given medical marijuana in routine practice) reported improvement; these designs cannot separate out the effect of expectation, and liver enzymes rose with high-dose CBD. In a 1–3-year matched comparison of medical marijuana users, no worsening was seen in disease progression or mental health symptoms (observational). The most recent meta-analysis pooling the RCTs (Messak 2026) found no significant benefit for movement and non-movement symptoms; a meta-analysis that separated the drugs by type (Bilbao 2022) found a difference in favor of CBD when it pooled three small studies with pure CBD, but these studies had measured different outcomes, and studies published after October 2021 were not included in this analysis. The Brazilian Academy of Neurology wrote that there are no scientific data supporting the use of cannabinoids in Parkinson’s; the academy’s 2025 Parkinson’s guideline also found the evidence for cannabis in pain insufficient. Cannabinoids are not included in the UK’s NICE Parkinson’s guideline or in the International Parkinson and Movement Disorder Society’s evidence-based treatment reviews for non-motor symptoms (2019) and motor fluctuations (2025). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): on this topic we found 10 randomized, placebo-controlled studies with cannabinoids (the largest 101 people), 6 studies without a comparison group, 1 observational comparison, 3 systematic reviews and a position paper from a national academy of neurology; there is no Cochrane review. All are in the table below. An 8-person dose-finding study that did not measure efficacy and a guideline that was later withdrawn were not included in the table.

Evidence assessment: Weak

• CBD alone: In three small controlled studies with pure CBD, there was no clear difference from placebo in movement symptoms (21 people, 6 weeks) or REM sleep behavior disorder (33 people, 14 weeks); a single 300 mg dose reduced anxiety and tremor triggered in the laboratory. A 2022 meta-analysis pooling these three studies found a difference in favor of CBD; however, the studies had measured different things, and in two of them the movement or sleep measures were no different from placebo. In a 13-person uncontrolled study with a very high dose (20–25 mg per kilogram of body weight a day), improvement in movement scores was reported; the tremor score, however, did not change clearly (this result is only on the study’s registry page and was not tested statistically), and liver enzymes rose in 5 people. For psychosis there is only one 6-patient open-label study. The strength of evidence is weak.
• Products containing THC: RCTs with products containing CBD + low THC showed no benefit for motor symptoms, pain or cognition; some results favored placebo. Cannabis extract capsules containing THC and CBD did not reduce levodopa-related involuntary movements (19-person crossover RCT); with short-term CBD + low THC, a slight worsening was seen on a verbal fluency test. Two small RCTs with the THC-like synthetic drug nabilone reported positive results (levodopa-related involuntary movements, 7 people; non-movement symptoms, 38 people in a study in which only drug responders were randomized); in the 6-month open extension study of responders, the improvement in sleep and pain continued (no control group). Three uncontrolled studies with smoked marijuana (22 people) and medical marijuana (a 50-person prospective and a 69-person retrospective study) reported improvement in movement or non-movement symptoms; because there was no comparison group, the effect of expectation cannot be separated out. In a 1–3-year matched comparison of 76 patients using medical marijuana, no relative worsening was seen in disease progression or in psychosis, depression and cognition (observational). The strength of evidence is weak. (weak evidence) Evidence: Weak (RCTs with products containing THC and CBD negative; two small RCTs with nabilone positive)
• Dose range in studies: Pure CBD 75–300 mg/day and a single 300 mg dose; in an uncontrolled safety study, pure CBD up to 20–25 mg/kg/day; CBD + low THC products ~15.6–191.8 mg CBD + 0.6–6.4 mg THC/day; nabilone 0.25–2 mg/day
• Starting dose and titration (in studies): In the studies, treatment started at a low dose and was raised to the target dose over 1–2 weeks (Liu 2024: 2.5 mg/kg/day over 2 weeks; Kanjanarangsichai 2022: 2 weeks of individual titration); these are research protocols
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site’s Drug interactions section
• Monitoring in studies: People with Parkinson’s take many medicines: drug interactions, liver enzymes and falls/sedation should be monitored with the doctor

References (21)

Study table (dose, duration, result) · Topic page

No effect on itching attributable to CBD or THC has been shown. Two sources previously described on this page as a signal of a small reduction were reread, found not to have been done with a cannabinoid product, and removed from the table. The small reduction (SMD −0.29) in a 2025 meta-analysis (Sermsaksasithorn 2025, PMID 41181596) came from 6 studies with products that contained no CBD or THC (PEA creams, hemp seed oil, and the synthetic research compounds HU-210 and lenabasum). The cream in the 60-person study that reduced itching in dialysis patients 1.1 points more than placebo (Anumas 2024, PMID 39328960) was made with hemp seed oil pressed from the seeds (1.27 mg of CBD and 0.13 mg of THC per kilogram of oil), and the difference in reduction from baseline was not significant. In the only RCT with a cannabinoid in dialysis itch, the THC-like nabilone was no better than placebo (14 people, crossover). In recurrent canker sores, a 0.1% CBD product shrank the sores faster than placebo (69 people, 7 days). In atopic dermatitis, in the manufacturer's 200-person RCT, a 4% synthetic CBD solution was no better than vehicle at 12 weeks (clear or almost clear: 12% vs. 19%; results only on ClinicalTrials.gov, no statistical comparison); in a small RCT completed by 57 people, the cream containing CBD alone was no different from placebo, and improvement was seen only with the combination of CBD and aspartame. In psoriasis, oral CBD oil did not improve PASI (28 people). Two reviews report that a placebo-controlled study comparing the two halves of the body in 51 people with a 2.5% CBD ointment applied to the skin (Puaratanaarunkon 2022, PMID 35536599) had a positive result; the publication has no abstract, its full text could not be obtained, and the result could not be verified. In a secondary analysis of an RCT with a CBD-rich, low-THC extract in people with Parkinson's disease, there was also no difference in seborrheic dermatitis (53 people, 16 days). In acne there is no peer-reviewed published RCT result; in the results of the only 368-person RCT (BTX 1503), available only on ClinicalTrials.gov, the CBD arms were no better than vehicle. The 2026 systematic review in acne (Komane) found the evidence preliminary; this review screened only 50 records and does not include the BTX 1503 registration. In epidermolysis bullosa, in an 8-person crossover RCT with THC+CBD oil under the tongue, the main measure (emotional burden of pain) did not change; in an uncontrolled study of 10 children taking pure CBD by mouth, itching and pain decreased. For finger ulcers in systemic sclerosis, CBD oil reduced pain in a non-randomized comparison; for scalp psoriasis, seborrheic dermatitis and hair loss there are only uncontrolled series. The studies are small and short; the effect of cosmetic products cannot be attributed to CBD because of the other ingredients they contain. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 9 controlled studies (8 randomized), 5 uncontrolled studies and 2 systematic reviews with cannabis products and cannabinoids on this topic were found; all are in the table below. There is no Cochrane review. Not included in the table: reviews examining cannabinoids in dermatology as a whole (most of the controlled studies they pooled were done with PEA creams, hemp seed oil or synthetic lenabasum; the CBD studies within them are separate rows in the table), studies with hemp seed oil (seed oil is not a CBD or THC product; it contains cannabinoids only in trace amounts), lenabasum, a synthetic drug candidate tested in systemic sclerosis and dermatomyositis (not a plant cannabinoid; in a 365-patient phase 3 study it was no different from placebo on the main measure), studies of cosmetic and wound products that contain CBD together with ginger, salicylic acid or other active ingredients and have no CBD-only group or no comparison group, and 2 randomized studies whose results could not be read or have not been released (see unverifiable points).

Evidence assessment: Very weak; conflicting (RCTs with CBD applied to the skin in acne and atopic dermatitis, with oral CBD in psoriasis, and with a CBD-rich extract in seborrheic dermatitis were negative; positive results come from a single small RCT in canker sores, a cream in which CBD was combined with another substance, a psoriasis RCT whose result could not be verified, and small non-randomized or uncontrolled studies)

• CBD alone: Controlled evidence for CBD in the skin is very limited and conflicting: in canker sores, a 0.1% CBD product shrank the sores quickly; in psoriasis, 60 mg/day of oral CBD did not improve PASI; in atopic dermatitis, no significant difference was reported for the CBD-only arm. In the manufacturer's RCTs, a CBD solution applied to the skin was no better than the solution without CBD in acne (368 people) and atopic dermatitis (200 people) (results only in the registry, no statistical comparison). Two reviews report that a 51-person controlled study of a 2.5% CBD ointment applied to the skin in psoriasis was positive; the publication itself could not be read. Other positive results come from small, non-randomized or uncontrolled studies: finger ulcer pain in systemic sclerosis (45 people) and itching and pain in children with epidermolysis bullosa (10 people).
• Products containing THC: There are two small randomized studies with THC-containing products, and neither found a difference from placebo: in epidermolysis bullosa, THC+CBD oil under the tongue did not change the emotional burden of pain, the main measure, differently from placebo (8 people; pain and painkiller use decreased on secondary measures); in people with Parkinson's disease, a CBD-rich extract that also contained a little THC did not change seborrheic dermatitis differently from placebo in a secondary analysis (53 people). The synthetic THC-like nabilone was also no better than placebo for itching in dialysis patients (14 people). For hair loss, there are only uncontrolled series with hemp extracts containing trace amounts of THC. The dialysis itch cream previously described in this box was made with hemp seed oil pressed from the seeds (0.13 mg of THC per kilogram of oil); because seed oil is not considered a THC product, it is no longer assessed here. (very weak evidence) Evidence: Very weak (two small RCTs, both negative, one only a secondary analysis; a small RCT with the THC-like drug nabilone was also negative; the rest uncontrolled series)
• Dose range in studies: Oral 60 mg/day (psoriasis); 0.075–5% CBD shampoo, solution or cream on the skin 1–2 times a day (acne, eczema, scalp); oral 5–20 mg/kg/day in children (epidermolysis bullosa, uncontrolled); 0.1% CBD 3 times a day (canker sores); concentration not reported for some cosmetic products

References (16)

Study table (dose, duration, result) · Topic page

CBD did not improve blood sugar or insulin results compared with placebo; no human RCT was found that supports the claim that "CBD regulates blood sugar." In fatty liver disease, in the manufacturer's small 8-week RCT (25 people; results only in the ClinicalTrials.gov record, no peer-reviewed publication), three different doses of CBD did not significantly reduce liver fat compared with placebo. After a single dose of CBD, more food was eaten at lunch; the promise of weight control is unsupported by evidence. Pharmaceutical-grade CBD, on the other hand, can reduce appetite: in a meta-analysis combining RCTs of approved cannabinoids in different conditions, decreased appetite was more common with CBD than with placebo (OR 2.46; moderate certainty). According to the US prescribing information for the approved CBD medicine, losing at least 5% of body weight was also more common in people taking CBD in high-dose controlled epilepsy studies (16% vs 8% in Lennox–Gastaut and Dravet syndromes, 31% vs 8% in tuberous sclerosis). This is an unwanted side effect; it is not evidence supporting use for weight loss. There are three small RCTs reporting positive results with THC-containing products and other substances in cannabis (a very low-dose CBD:THC spray in type 2 diabetes, an oral strip containing THCV and CBD in obesity, and the THC-like drug nabilone); all three have serious limitations: inconsistent numbers in the publication, analysis of only those who completed the study, or early stopping because of poor tolerability. In single-dose or 4-week studies compared with placebo or a control condition, THC, nabilone or marijuana did not clearly change blood sugar regulation (in a single-dose mechanistic study in healthy men, nabilone slightly increased insulin sensitivity). In population studies, type 2 diabetes and fatty liver are seen less often in cannabis users, but most of these studies are cross-sectional; for type 2 diabetes, the results of three large studies that followed people for years disagree, and genetic analyses did not support the idea that cannabis use changes the risk of type 2 diabetes or body weight. These observational data do not show cause and effect. In type 1 diabetes, ketoacidosis was more common in cannabis users (three observational studies; the largest with 2,108 adolescents and young adults with type 1 diabetes in the US) and HbA1c was higher (observational). Delayed stomach emptying due to diabetes (diabetic gastroparesis) is covered on the site's Irritable Bowel and Stomach Problems page: in a 4-week single-center RCT of 44 patients with gastroparesis, 12 of them diabetic, pharmaceutical-grade CBD reduced symptoms more than placebo but did not speed up gastric emptying (it slowed it on some measurements); no separate result was reported for people with diabetes, and the finding has not yet been tested in another study (Zheng 2023, PMID 37482172). In people with type 1 diabetes who use cannabis daily, cannabinoid hyperemesis syndrome can be mistaken for gastroparesis (Akturk 2025, PMID 40741458). No treatment study with a cannabis or CBD product was found for diabetic eye damage (diabetic retinopathy). The only controlled study in this condition with a drug targeting cannabinoid receptors tested an experimental synthetic drug that is not a cannabis product and binds selectively to the CB2 receptor (vicasinabin): in 139 patients, after 36 weeks of treatment, the rate of at least a two-step improvement in retinopathy severity was no different from placebo (the manufacturer-funded CANBERRA study, PMID 39802207). Because selective synthetic drugs are not counted as cannabis products on this site, it is not in the table. Diabetes medicines should not be replaced with CBD. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 14 controlled studies of cannabinoids on this topic (12 randomized, one with registry results only; between 7 and 125 people, the longest 13 weeks), 6 systematic reviews on CBD or cannabis use and 9 observational studies were found (including one meta-analysis and one observational study added in the completion round on October 28, 2026); all are in the table below.

Evidence assessment: Insufficient (negative)

• CBD alone: In type 2 diabetes, in overweight people and in fatty liver disease, pure CBD did not affect blood sugar, blood lipid or liver fat results clearly differently from placebo; in a single-dose study in overweight men, only insulin and triglyceride values right after a meal were briefly measured lower (all small, short studies; the fatty liver study's results are only in the registry).
• Products containing THC: Controlled studies of THC-containing products are very small and short. The numbers in the only study reporting a positive result in type 2 diabetes, with a very low-dose CBD:THC spray, are inconsistent; the obesity study of the THC-like drug nabilone was stopped early because of poor tolerability; dronabinol over 4 weeks did not change metabolic values, and a single use of marijuana or an edible product did not change insulin sensitivity. Some population studies report less type 2 diabetes in cannabis users, but these do not show cause and effect and were not supported by genetic analyses; in type 1 diabetes, ketoacidosis was more common in cannabis users (observational). (insufficient evidence) Evidence: Insufficient (small, short and conflicting studies)
• Dose range in studies: In studies, 30 mg as a single dose or 2 times a day, 100 mg 2 times a day, 298 mg single dose, and 200–800 mg a day in fatty liver
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's Drug interactions section

References (29)

Study table (dose, duration, result) · Topic page

In small RCTs, pure CBD lowered blood pressure by a few mmHg (about 5 mmHg in 24-hour systolic pressure); increasing the dose gave no additional benefit. In healthy men, the drop after the first dose disappeared within 7 days (tolerance), and a single dose raised heart rate. The results of the other small RCTs in healthy volunteers are mixed: in 17 people who did not use cannabis, a single dose of 200–800 mg CBD lowered blood pressure slightly; in four studies that gave 100 mg a day for 12 weeks, a single 100 mg dose by mouth or vaporized, a single 300 mg dose, and a single 200–800 mg dose in people who regularly smoke marijuana, blood pressure and heart rate did not change differently from placebo. A 2026 systematic review of four RCTs that measured blood pressure says the drop was seen at higher doses and especially under stress or during sleep, and that the studies were small and short. The two RCTs in patients with high blood pressure came from the same research group; both used a patented CBD formulation designed for better absorption, and both were funded by the company that owns the formulation. In the abstract of the 70-person study, it is not clear whether the 4.76 mmHg drop was compared with placebo or with baseline. The effect is small and short-lived; there are no data showing an effect on heart events (stroke, heart attack). This is not evidence of a treatment. In heart inflammation, pharmaceutical-grade CBD (up to 20 mg/kg/day) was tested in two phase 2 studies: in acute myocarditis (109 people, 12 weeks), the primary MRI measurements were no different from placebo; in recurrent pericarditis (27 people, uncontrolled), pain and CRP decreased. Both studies were funded by the drug's manufacturer; in the myocarditis study, the registered primary outcome, extracellular volume percentage, also showed no difference. A placebo-controlled phase 3 study in recurrent pericarditis is ongoing (NCT06708299, October 2026). The same medicine was also compared with placebo in 90 people hospitalized with COVID-19 who had cardiovascular disease or risk factors; the study was stopped early because not enough patients could be enrolled, and it was not published in a peer-reviewed journal. According to the registry results, the combined outcome of death, intensive care or breathing support, and cardiovascular complications occurred in 3 of 45 people in the CBD group and in 2 of 45 in the placebo group (the difference was not significant; the study was not large enough to show a difference). Serious side effects occurred in 5 people in the CBD group and 4 in the placebo group; among those in the CBD group there was one case each of heart failure and QTc prolongation, and 2 people in the placebo group died (the groups were not compared statistically for side effects; the numbers are small). These are not approved uses. No study has aimed to treat blood pressure or heart disease with THC-containing products. In controlled studies, THC raised heart rate (by an average of 8 beats/min in a pooled analysis) and could cause a drop in blood pressure on standing up (relative risk 3.16 in RCTs of medical cannabinoids); in a 1975 study of 10 patients with angina that did not use a placebo, it brought on chest pain earlier during exercise. In a few small studies of patients with high blood pressure, blood pressure fell or did not change after THC products; these are very small studies or studies without a comparison group. In meta-analyses of observational studies, cannabis use was linked to acute coronary syndrome (relative risk 1.29), stroke (1.20; 1.37 in another meta-analysis) and atrial rhythm disorders (odds ratio 1.71); in a meta-analysis based on cohorts with long follow-up, the link was not significant for heart attack and stroke individually, and in some cohorts with long follow-up (CARDIA, Swedish conscripts, veterans with heart disease, UK Biobank), no link was found. These studies do not show cause and effect. Similar links are seen in people who use medical cannabis: in Denmark, among chronic pain patients starting medical cannabis by prescription, new heart rhythm problems in the first 6 months (0.8% vs. 0.4%), and in Canada, among people authorized to use medical cannabis, emergency visits or admissions for heart attack-like events or stroke (hazard ratio 1.44) were more common. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 19 controlled studies with cannabinoids on this topic (11 with CBD, one of which used a product with an unclear THC content; 8 with THC-containing products) and 9 systematic reviews were found; these appear in the table below, together with 2 uncontrolled studies and 10 observational studies. There is no Cochrane review on this topic; the many older laboratory studies measuring THC's effect on heart rate and the blood pressure data measured in CBD anxiety laboratory studies are included not one by one but through the meta-analyses that combine them.

Evidence assessment: Weak (2 small RCTs with pure CBD in high blood pressure, 16 and 70 people, at most 5 weeks, both from the same research group and with the same company's formulation; 7 small RCTs with CBD in healthy volunteers, with mixed results; 1 phase 2 RCT in heart muscle inflammation, with a negative main result; 1 phase 2/3 RCT in patients hospitalized with COVID-19 who had cardiovascular risk, stopped early and with results only in the registry, with no difference in the main outcome)

• CBD alone: Pure CBD may lower blood pressure by a few mmHg: there are 2 small RCTs in high blood pressure (16 and 70 people, at most 5 weeks; both from the same research group, using the same company's patented formulation). In healthy people, results are mixed: in some studies blood pressure fell slightly (in one, the effect disappeared within a week), and in others it did not change at all. In heart muscle inflammation, a 109-person phase 2 RCT found the main MRI measurements no different from placebo. This is not evidence of a treatment; for people taking blood pressure medicine, it is a drug interaction issue.
• Products containing THC: No study has aimed to treat high blood pressure or heart disease with THC-containing products; the information we have is about safety. In controlled studies, THC raised heart rate (by an average of 8 beats/min in a pooled analysis) and, in some people, caused a drop in blood pressure on standing up and dizziness. In a few small studies of patients with high blood pressure, blood pressure fell or did not change after THC products; because these studies were very small or had no comparison group, they do not count as evidence of a treatment. In a 1975 study of 10 patients with chest pain (angina) that did not use a placebo, one marijuana cigarette cut in half the time patients could exercise before the pain began. In most large observational studies, cannabis use was linked to heart attack, stroke and atrial rhythm problems (in a 2025 meta-analysis, relative risk 1.29 for heart attack and similar events and 1.20 for stroke); in two large cohorts there was no link with new high blood pressure, and in some studies with long follow-up there was no link with heart events. These are association studies; they do not show cause and effect, and most concern smoked cannabis. (insufficient evidence) Evidence: Insufficient: there are no treatment studies of THC-containing products for blood pressure or heart disease. Information pointing to harm comes from controlled laboratory studies (raised heart rate, a drop in blood pressure on standing) and large observational studies; observational findings are associations and do not show cause and effect
• Dose range in studies: In the studies, 600 mg as a single dose, 600 mg/day (7 days), 450 mg/day (24 hours), 225–450 mg/day (5 weeks); in the heart inflammation studies, 5–20 mg/kg/day; in the other studies in healthy volunteers, a single dose of 100–800 mg and 100 mg/day (12 weeks)
• Starting dose and titration (in studies): In Dujic 2024, an increase from 225–300 mg/day to 375–450 mg/day (no additional benefit)
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: Losartan: a CBD-dominant extract (which also contained 20 mg THC) increased losartan AUC by 77% (Bansal 2023, PMID 37313955)
• Monitoring in studies: In people taking blood pressure medicine, monitoring of blood pressure and dizziness (with a doctor)
• Monitoring in studies: In people using THC-containing products, monitoring of pulse and dizziness on standing; with a doctor in people with heart disease

References (40)

Study table (dose, duration, result) · Topic page

In a small study of 6 patients, a CBD-dominant cannabis extract given under the tongue did not lower the pressure inside the eye at all; 4 hours after the 40 mg dose, pressure rose temporarily (23.2 → 25.9 mmHg; p = 0.028), but in a 2022 meta-analysis comparing the same data with placebo, the difference was not significant (p = 0.08). Animal data are mixed: CBD eye drops showed opposing effects in mice, lowered pressure or left it unchanged in other mice, and in a study of horses given CBD by mouth with no comparison group, pressure fell. Animal findings do not show the effect in humans. THC's lowering of eye pressure is short-lived and comes with psychoactive effects: in older studies, the fall in eye pressure went hand in hand with a fall in blood pressure and lasted 3–4 hours; a racing heart, a drop in blood pressure on standing up and mental changes were common; all 9 patients with advanced glaucoma stopped treatment within 1–9 months. A single dose of synthetic THC (dronabinol) increased blood flow at the head of the optic nerve without changing eye pressure: at 10 mg in a 23-patient study of glaucoma (5 mg had no effect), and at 5 mg in 24 healthy volunteers; the long-term effect is unknown. In a placebo-controlled study of 120 cancer patients receiving chemotherapy, pressures inside the eye stayed within normal limits after oral THC; an unexpected rise was seen only in the 5 mg group. THC given as eye drops did not lower pressure in three controlled studies, one of them in patients with glaucoma; a drop that turns into THC in the eye was also not clearly different from placebo after two weeks in 56 patients with glaucoma or ocular hypertension (results only in the ClinicalTrials.gov record; no peer-reviewed publication). In a 2026 meta-analysis that pooled THC studies (5 studies, 99 people), the largest drop averaged 14.7%, but in the four studies with a comparison group the difference from control was not significant (6.9%; p = 0.41). The European Glaucoma Society's 2025 guideline (low level of evidence, strong recommendation) and the American Glaucoma Society do not recommend cannabinoids for treating glaucoma; the US National Academies' 2017 report concluded that there is limited evidence that cannabinoids are ineffective in improving the pressure inside the eye in glaucoma. A genetic analysis found no cause-and-effect link between cannabis use and the risk of glaucoma. CBD is not a treatment recommendation for glaucoma. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 12 controlled human studies of cannabinoids in glaucoma or on the pressure inside the eye and optic nerve blood flow were found: 6 in patients with glaucoma or ocular hypertension (one with results only in the ClinicalTrials.gov record; for one, the sources conflict on whether it was placebo-controlled), 5 in healthy volunteers and 1 in cancer patients receiving chemotherapy. Only 1 looked at CBD (6 patients, single dose). There are also 2 uncontrolled studies, 2 systematic reviews and meta-analyses, 1 expert committee report, 2 guidelines or professional society position statements and 2 observational studies; there is no Cochrane review. All that met the criteria, together with 3 animal studies, are in the table below.

Evidence assessment: Insufficient (in a single small study, CBD did not lower pressure; the temporary rise after 40 mg is not significant in the comparison with placebo)

• CBD alone: There is no human glaucoma study of pure CBD. In the only human study, a CBD-dominant extract derived from cannabis, given under the tongue, did not lower the pressure inside the eye; the temporary rise seen 4 hours after the 40 mg dose was not significant in the comparison with placebo.
• Products containing THC: THC lowered the pressure inside the eye temporarily (for about 4 hours) and brought psychoactive effects; it also caused a drop in blood pressure and a racing heart; in an uncontrolled program, all 9 patients stopped within 1–9 months. THC given as eye drops did not lower pressure; a drop that turns into THC in the eye, used for two weeks by patients with glaucoma, was also not clearly different from placebo (results only in the registry). In the 2026 meta-analysis pooling THC studies, the difference from control was not significant in the studies with a comparison group; the European Glaucoma Society (2025) and the American Glaucoma Society do not recommend it for treating glaucoma. There is no study showing that it keeps pressure low over the long term or slows vision loss. (insufficient evidence) Evidence: Insufficient (THC: drops lasting hours in small, short studies; the longest controlled study lasted 2 weeks and found no clear difference from placebo; no long-term studies; guidelines do not recommend it)
• Dose range in studies: In humans, a single dose of 20 and 40 mg CBD (6 patients)
• Monitoring in studies: If someone with glaucoma is going to use CBD, their eye doctor should monitor the pressure inside the eye
• Monitoring in studies: THC-containing products can make the pressure inside the eye read low for a few hours; if one was used before an eye exam, the eye doctor should be told

References (24)

Study table (dose, duration, result) · Topic page

Controlled studies with cannabinoids for behavioral symptoms in dementia (agitation, aggression) are small (15–75 people), short (2 weeks to 6 months) and contradict each other. There are only two RCTs with pure CBD: in vascular dementia, a 30-person study with 300 mg of CBD a day showing borderline superiority over placebo on the NPI and BPRS (three of the eight authors are inventors on CBD-related patents), and in Alzheimer’s, a 15-person feasibility study with up to 600 mg of CBD a day that did not test efficacy (dizziness 63%). With CBD-rich products that also contain THC, the results point both ways: in a 60-person, manufacturer-supported RCT with an oil reaching an average of 528 mg of CBD and 22 mg of THC a day, agitation response was 60% vs. 30% (p = 0.06 with the continuity correction prespecified in the statistical plan; all dropouts in the treatment group; memory loss and hallucinations numerically more common); with a THC:CBD 1:2 oil (25 people, crossover), a mouth spray containing THC and CBD (29 people, feasibility) and a THC:CBD 3:2 oil (21 people, crossover), no difference on behavioral measures (in the last, a reduction in agitation only at the end of treatment); in a 28-person study with a very low-dose THC-CBD extract, only the MMSE favored the drug. THC and nabilone: two RCTs with a low-dose THC tablet were negative; in a 75-person multicenter RCT with dronabinol, only one of two co-primary measures was positive; in a 39-person crossover RCT with nabilone, agitation went down and sedation went up (45% vs. 16%); a very small 1997 dronabinol study with 15 Alzheimer’s patients who refused to eat reported positive signs for weight and behavior. Studies without a comparison group (19–60 people) reported marked improvement; these designs cannot separate out the effect of expectation and of improvement that happens on its own over time, and the same team’s later controlled study (Geneva) did not confirm the positive observation. Cochrane 2021 (4 RCTs, 126 people) wrote that it cannot be said with confidence whether there is benefit or harm, with low certainty for behavioral symptoms and very low certainty for cognition. Three meta-analyses in 2026 reached different conclusions: one found no effect (9 RCTs; moderate certainty for behavior), one found a significant reduction in agitation only when studies at high risk of bias were included (10 RCTs), and the third, limited to Alzheimer’s, found a small to moderate benefit (6 RCTs and 1 open-label study); in all three, sleepiness was about twice as common (RR 2.03–2.25). The 2025 guideline of the Canadian Coalition for Seniors’ Mental Health gives synthetic cannabinoids a conditional place, based on low-quality evidence, in severe agitation that has not responded to other medicines (the guideline authors include two investigators from the nabilone study in the table); the 2026 assessment by Canada’s Drug Agency found the nabilone evidence uncertain; the Brazilian Academy of Neurology (2021) does not recommend use in dementia; cannabinoids are not included in the Korean (2025) and Taiwanese (2026) guidelines or in the recommendations of Canada’s 5th consensus conference on dementia (2020). There is no human study with published results that used a cannabinoid to prevent or slow dementia; in large observational studies, having used cannabis was not significantly linked to cognitive decline, and cannabis use disorder was not significantly linked to dementia risk (UK Biobank, US veterans; no causality in Mendelian randomization), but middle-aged and older adults who received emergency care because of cannabis were diagnosed with dementia more often over the next 5 years (Ontario; observational). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): on this topic we found 12 randomized controlled studies with cannabinoids (the largest 75 people; only 2 small studies with pure CBD), 1 non-randomized controlled study, 5 studies without a comparison group, 2 large observational studies looking at dementia risk, 6 systematic reviews (2 of them Cochrane, 1 a safety review in older adults), 1 guideline, 1 position paper and 1 health technology assessment; all are in the table below. 3 controlled studies that were completed but whose results have not been released, and ongoing trials, are listed under “unverified”; open-label studies with fewer than 15 people, case reports, a crossover study completed with only 2 patients, and a 24-person study that did not report the dronabinol result separately were not included in the table.

Evidence assessment: Very weak: there are only two small RCTs with pure CBD (30 and 15 people, 4–6 weeks); one is borderline positive and three of its authors are inventors on CBD-related patents, the other is a feasibility study that did not test efficacy; there is one non-randomized 20-person comparison with CBD drops of unknown THC content. Results for products rich in CBD but also containing THC were assessed under the THC evidence

• CBD alone: There are only two small controlled studies with pure CBD: in 30 people with vascular dementia, 300 mg of CBD a day for four weeks reduced behavioral symptoms slightly more than placebo (right at the edge of statistical significance; three of the eight authors among the inventors on two CBD-related patents); a six-week pilot study with 15 Alzheimer’s patients (up to 600 mg a day) was not designed to test whether it works, and dizziness was common. A 20-person study that did not assign people to groups by chance reported improvement with CBD drops; whether the product contained THC is not stated. As of October 2026, several controlled studies with pure CBD are under way. The strength of evidence is very weak.
• Products containing THC: The results of 10 small controlled studies with THC-containing products and with the THC-like synthetic drug nabilone are conflicting. Two studies with a low-dose THC tablet (50 and 22 people) found no difference; in a 75-person multicenter study with dronabinol, benefit was seen on only one of the two main scales (there were differences between the groups at the start); in a 39-person crossover study with nabilone, agitation went down and sleepiness went up. In a 60-person study with an oil rich in CBD but reaching an average of 22 mg of THC a day, agitation went down, but with the statistical correction the authors had set in advance the difference on the main measure was borderline (p = 0.06), and everyone who dropped out was in the treatment group; four studies with oils, sprays and extracts containing THC and CBD found no clear difference in agitation (in one, a reduction only at the end of treatment). The Cochrane review rated the certainty of the evidence low or very low; three meta-analyses in 2026 reached different conclusions, and in all of them sleepiness was about twice as common. Canada’s 2025 guideline lists synthetic cannabinoids such as nabilone among the last options for severe agitation that has not responded to other treatments, as a conditional recommendation based on low-quality evidence; the 2026 assessment by Canada’s Drug Agency, however, found the benefit of nabilone uncertain because it rests on a single small study. (weak evidence) Evidence: Weak: 10 small, short controlled studies with THC-containing products and nabilone (the largest 75 people, 3 weeks), with conflicting results; certainty low to very low according to Cochrane; the most consistent finding is that sleepiness was about twice as common
• Dose range in studies: Pure CBD 300 mg/day and from 200 mg up to 600 mg/day; CBD-rich oil avg. ~528 mg CBD + 22 mg THC/day; THC:CBD 1:2 oil at most 20 mg THC + 40 mg CBD/day; THC:CBD mouth spray at most 10.8 mg THC + 10 mg CBD/day; THC:CBD 3:2 oil at most 50 mg THC/day (protocol); very low-dose extract 0.35 mg THC + 0.245 mg CBD/day; dronabinol 2.5–10 mg/day; low-dose THC tablet 1.5–4.5 mg/day; nabilone 0.5–2 mg/day
• Starting dose and titration (in studies): In most studies, treatment started at a low dose and was raised to the target dose over 1–6 weeks (over 15 days with the THC:CBD 1:2 oil; with the CBD-rich oil, by adding one drop every two days over at most 6 weeks; with dronabinol, 5 mg in week 1, then 10 mg/day); these are research protocols
• Interaction: In 15 patients with severe dementia who used an oil containing THC and CBD for months, the activity of the enzymes CYP1A2 and CYP2C19 was slightly reduced; these enzymes help break down certain medicines in the body (Pautex 2022)
• Interaction: In a controlled study with an oil containing THC and CBD for 8 weeks in patients with severe dementia taking many medicines, no problem due to drug interactions was reported (Bianchi 2026)
• Interaction: Dementia studies did not systematically examine interactions with antidepressants, antipsychotics and sedatives; details are in the site’s Drug interactions section (antidepressants, antipsychotics and lithium, anxiety and sleep medicines)
• Monitoring in studies: If a cannabinoid is used in a person with dementia, sleepiness, falls, confusion, blood pressure and appetite should be monitored with the doctor
• Monitoring in studies: With high-dose or long-term CBD use, liver tests are the doctor’s decision (raised liver enzymes were reported with up to 600 mg of pure CBD a day; Velayudhan 2024)
• Monitoring in studies: If other medicines are taken, drug interactions should be assessed with the pharmacist and doctor

References (29)

Study table (dose, duration, result) · Topic page

Pure CBD has not been tested on its own for muscle stiffness (spasticity) from causes other than MS: in the only controlled study that tested pure CBD as a separate group (Denmark, 134 people, at most 45 mg a day), 119 patients had MS and 15 had spinal cord injury; muscle stiffness was no different from placebo, and no separate result was given for those with spinal cord injury. Nearly all the evidence concerns THC-containing products or THC-like medicines, and it varies by cause. In ALS and primary lateral sclerosis, THC:CBD mouth spray slightly reduced muscle stiffness as measured by the doctor over 6 weeks in a 60-person phase 2 study (difference −0.32; 95% CI −0.57 to −0.07), but side effects were about three times as common in the spray group; for cramps in ALS, THC by mouth (27 people) was ineffective, and Cochrane reviews wrote that THC is probably ineffective for cramps; a 2022 meta-analysis combining these two controlled studies in ALS found no difference in favor of cannabinoids on ALS-specific overall scales (daily functioning, quality of life) (pooled standardized mean difference 0.31; 95% CI −0.02 to 0.63; p = 0.07; leaning slightly toward placebo according to the authors). The results of the only controlled study examining the effect of cannabinoids on the course of ALS (17 people, an oil rich in CBD and containing a small amount of THC) had not been published as of October 2026. After stroke, in the only controlled study (41 people, crossover), the spray did not change muscle stiffness differently from placebo, whether as felt by the patient or as shown by the doctor's and electrical measurements. In children with cerebral palsy or brain injury, two placebo-controlled studies (72 people, THC:CBD spray, 12 weeks; 53 people, oil containing 10 times more CBD than THC, 6 weeks) found no difference in muscle stiffness; 3 cases of hallucination were reported with the spray and marked sleepiness with the 10:1 oil; a 25-child study without placebo comparing two CBD-rich oils reported improvement in both groups. In spinal cord injury the results are mixed: nabilone (12 people) and a mostly open-label study of THC by mouth (25 people) reported a reduction in doctor-measured muscle stiffness; 1:1 THC:CBD oil (16 people) did not change the doctor's measurement and only slightly improved patients' own ratings; in a 116-person nerve pain study by the maker of the THC:CBD spray, with results available only in the registry, there was no difference in muscle stiffness and spasms. In upper motor neuron syndrome, nabilone (13 people) reduced related pain, not muscle stiffness itself. England's NICE evidence review (2019) found only 3 controlled studies for causes other than MS and made no recommendation for these causes; the product information for the THC:CBD spray does not recommend use under age 18. Two real-world studies without a comparison group (spray in spinal cord injury; synthetic THC in 63 severely ill hospitalized children) reported improvement in muscle stiffness from baseline or by subjective rating, but they cannot separate out the effect of expectation; in the children's series, standard 24-hour records did not show a reduction in restlessness and seizures, and 3 serious breathing problems were seen with synthetic THC; in the records of 344 ALS patients, medical marijuana was not associated with improvement in muscle stiffness. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 12 controlled studies of cannabinoids for muscle stiffness from causes other than MS and for cramps in ALS were found (10 randomized and placebo-controlled, 1 a two-product comparison without placebo, 1 with a 13-person controlled part; one available only in the ClinicalTrials.gov record; in one, most patients had MS); all of them, together with 5 topic-specific systematic reviews, a general meta-analysis that gives a separate analysis for ALS, and 3 observational studies, are in the table below. One more study in which most patients had MS and that gave no separate result for non-MS patients (24 people, 6 without MS) is in the table on the MS spasticity page; small uncontrolled series and satisfaction surveys were not included in the table. In none of these studies was pure CBD assessed separately in non-MS patients; 4 controlled studies with unreported results (two completed, two listed with status 'unknown' in the registry) are being followed; no studies from Turkey were found. In an additional October 2026 search (ALS only; PubMed, Cochrane, ClinicalTrials.gov, Europe PMC), no other controlled study or registry entry with results for cannabinoids in ALS was found; the meta-analysis combining the two ALS studies was added to the table; surveys, case reports and a 9-patient single-dose drug level study (its safety finding is in the warnings) were not included in the table.

Evidence assessment: Pure CBD: Insufficient (pure CBD has not been tested on its own for causes other than MS; in the only study with a pure CBD group, most patients had MS and muscle stiffness was no different from placebo)

• CBD alone: There is no separate controlled study of pure CBD oil for muscle stiffness from causes other than MS. In the only study that tested pure CBD (at most 45 mg a day, 6 weeks) as a separate group (Denmark, 134 people), 119 patients had MS and 15 had spinal cord injury; muscle stiffness was no different from placebo, and no separate result was given for patients with spinal cord injury. All the CBD-dominant oils tested in children also contained THC (see the section on THC-containing products). In ALS, the result of a 17-person study of a CBD-rich oil that also contains a small amount of THC (50 mg CBD per mL, less than 2 mg THC) had not been published as of October 2026.
• Products containing THC: A mouth spray containing roughly equal amounts of THC and CBD reduced muscle stiffness as measured by the doctor slightly more than placebo over 6 weeks in 60 patients with ALS or primary lateral sclerosis (difference on the Modified Ashworth Scale −0.32; 95% CI −0.57 to −0.07); the same spray was no different from placebo for muscle stiffness after stroke (41 people, crossover) or in children with cerebral palsy or brain injury (72 people, 12 weeks); in the study of nerve pain due to spinal cord injury (116 people, registry results only), there was also no difference in muscle stiffness and spasms. In spinal cord injury, a 25-patient study of THC by mouth, most of it open-label, reported benefit (the comparison for the 13-person controlled part is not in the publication's abstract); an oil containing equal THC and CBD did not change the doctor's measurement in a 16-person crossover study and only slightly improved patients' own ratings. An oil containing 10 times more CBD than THC did not reduce muscle stiffness in 53 people with severe cerebral palsy. For cramps in ALS, THC by mouth (10 mg a day) was no different from placebo (27 people); in a meta-analysis combining the two controlled studies in ALS, there was no difference in favor of cannabinoids on overall ALS scales (daily functioning, quality of life). The synthetic THC-like medicine nabilone reduced muscle stiffness as measured by the doctor in spinal cord injury in a 12-person crossover study; in 13 patients with upper motor neuron syndrome, however, it reduced the related pain, not the muscle stiffness itself. In children, hallucinations and marked sleepiness were reported with THC-containing products. (weak evidence) Evidence: THC-containing products: Weak (1–4 small controlled studies depending on the cause; in ALS, small benefit in doctor-measured muscle stiffness in a single 60-person study; no difference after stroke in 41 people or in children with cerebral palsy in studies of 72 and 53 people; mixed results in spinal cord injury); THC-like nabilone: Very weak (two studies of 12 and 13 people)
• Approval: There is no approved CBD or cannabinoid medicine for muscle stiffness from causes other than MS. The mouth spray containing THC and CBD (nabiximols; 2.7 mg THC + 2.5 mg CBD per spray) is licensed in the United Kingdom only in adults, for moderate to severe MS spasticity that has not responded well enough to other spasticity medicines and that shows clear improvement during a trial period; it is not recommended under age 18 because efficacy was not shown in a placebo-controlled study in children with cerebral palsy or brain injury (UK product information, text revision April 2, 2026, §4.1, §4.2, §5.1). According to NICE's 2019 evidence review, this spray is not licensed for motor neuron disease or spinal cord injury, and the guideline made no recommendation for cannabinoid products for causes other than MS. Turkey: the spray's active substance (tetrahydrocannabinol and cannabidiol, oromucosal spray) is on the TİTCK (Turkish Medicines and Medical Devices Agency) List of Active Substances from Abroad (September 28, 2026), among medicines that require a red prescription and can be imported with the agency's written approval.
• Dose range in studies: THC:CBD mouth spray at most 12 sprays a day (at most 32.4 mg THC + 30 mg CBD; an average of 8 sprays/day in ALS and a median of 9 after stroke; the maker's spinal cord study allowed at most 48 sprays a day); THC by mouth 10 mg/day (ALS cramps) and an average of 31 mg/day (spinal cord injury); 1:1 THC:CBD oil an average of 11.6 mg THC/day; nabilone 0.5–1 mg/day; pure CBD at most 45 mg/day (multi-arm study in which most patients had MS); synthetic THC in severely ill hospitalized children an average of 0.21 mg per kilogram a day (started in the unit) and 0.48 mg (already using it)
• Starting dose and titration (in studies): Gradual increase over about 14 days in the spray studies (9 weeks in the children's study); in the stroke study, 1 spray every 2 days for the first 4 days, then an increase of 1 each day; nabilone started at 0.5 mg/day and increased to 1 mg/day; 1 week of dose adjustment with the 1:1 oil; THC by mouth started with a single 10 mg dose, then individually adjusted; these are research protocols
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Interaction: Product information for the THC:CBD spray (§4.5): with muscle relaxants (baclofen, benzodiazepines), muscle tone and strength may decrease and the risk of falls may increase; with sleep-inducing and sedative medicines and alcohol, the sedative effect may increase; strong CYP3A4 inhibitors such as ketoconazole raise THC and CBD levels (the dose may need readjusting if itraconazole, ritonavir or clarithromycin is started or stopped); fluconazole increases THC exposure; strong inducers such as rifampin, carbamazepine, phenytoin, phenobarbital and St. John's wort are avoided where possible
• Interaction: Children with cerebral palsy and people with severe neurological disease often take several seizure medicines; CBD can interact with some seizure medicines (details on the epilepsy pages and in the drug interactions section)
• Monitoring in studies: EMERALD (NCT03690791, Australia): effect of a CBD-rich oil (50 mg CBD per mL, less than 2 mg THC) on disease progression in ALS; 17 people, double-blind, placebo-controlled; estimated completion January 2024; the registry entry has not been updated since April 2023 and its status is 'unknown'; no results in the registry and no publication found in PubMed in October 2026 (protocol: Urbi 2019, PMID 31719072); its 7-person open-label extension (NCT04997954) also has no results
• Monitoring in studies: NCT01222468 (Canada): nabilone (at most 3 mg a day) in spinal cord injury, muscle stiffness and nerve pain; 12 people, crossover; completed in February 2015; no results in the registry and no publication in PubMed
• Monitoring in studies: NCT04057456 (Canada): nabilone and an anti-inflammatory diet in spinal cord injury; primary outcome nerve pain, muscle stiffness secondary; 14 people; completed in December 2024; no results in October 2026
• Monitoring in studies: NCT06190470 (Thailand): THC-containing cannabis extract in spinal cord injury; nerve pain and muscle stiffness; 20 people planned, crossover; estimated completion June 2024; the record has not been updated since March 2024, no results

References (21)

Study table (dose, duration, result) · Topic page

In gastroparesis (44 patients with gastric emptying measured as delayed; 32 idiopathic, 12 diabetic), pharmaceutical-grade CBD used at up to 20 mg per kilogram a day for 4 weeks clearly lowered the total symptom score compared with placebo (p = 0.008); inability to finish a normal meal (p = 0.029), number of vomiting episodes a day (p = 0.006) and overall severity (p = 0.034) were also better, and in the nutrient drink test the volume to comfortable fullness and the maximum tolerated volume increased. In the same study, CBD slowed the emptying of solid food (time to 10% emptying 101 versus 77 minutes, p = 0.030; emptied at hour 4, 52% versus 63%, p = 0.045; for the main measure, half-emptying time, p = 0.088), and diarrhea was common (12/21 versus 2/23). The study was single-center and supported by the US National Institutes of Health (the authors declared no relevant conflicts of interest); at the start, the symptom score in the CBD group was numerically higher, and the result has not been repeated. In the publication, the total symptom score appears as one of the main outcomes, but it is not in the study's ClinicalTrials.gov registration (February 2024 version): the main measures in the registration are gastric emptying, gastric volume and the nutrient drink test, and among symptoms only overall severity and number of vomiting episodes are secondary measures. In the unadjusted week-4 medians in the registration, overall severity was similar in the two groups (1.8 versus 1.6), and daily vomiting was lower in the CBD group (0 versus 0.2). After an interim analysis, the target sample size was lowered from 48 to 44. In a study run at the same time under the same registration (NCT03941288) in 48 people with functional dyspepsia and normal gastric emptying, CBD did not change symptoms, gastric emptying, gastric volumes or the satiation test differently from placebo. In a crossover RCT of 50 mg CBD gum in irritable bowel syndrome (40 randomized, 32 women analyzed), the difference in pain reduction was 0.1 points (95% CI −0.3 to 0.5; p = 0.61), and there was no difference in quality of life either; the gums were used little, and the publication does not state the purity of the CBD in the gum. A meta-analysis of cannabinoids in chronic primary pain (2022), based on this study, wrote that CBD may not reduce pain in irritable bowel syndrome (low certainty). In irritable bowel syndrome, there are 3 short physiology RCTs with dronabinol and THC: a single dose of dronabinol reduced colon contractions on an empty stomach (75 patients; marked in the diarrhea and alternating types), 2 days of dronabinol did not change bowel transit (36 patients with diarrhea), and THC did not change rectal sensitivity (10 patients, 12 healthy volunteers); in a 2022 meta-analysis, the effect was zero (very low certainty), and the US National Academies (2017) found the evidence insufficient. In healthy volunteers, THC (13 people) and dronabinol (30 people) slowed the emptying of solid food from the stomach, dronabinol (52 people) relaxed the colon and raised pain scores in response to stretching; low-dose THC given into a vein did not change liquid emptying (7 people). In gastroparesis, there is no controlled study of THC-containing products: in an uncontrolled series of 24 patients, symptom scores fell with dronabinol or medical marijuana; in a multicenter patient registry, 12% of patients used marijuana and most users reported benefit (user reports). Observational studies conflict: cannabis use was linked to more emergency visits and admissions in a patient registry (406 people) and in a matched analysis of electronic records of 41,374 people, while in US hospital data length of stay and in-hospital death were lower; in irritable bowel syndrome, hospital records showed more frequent admission and less readmission with cannabis use disorder. These do not show cause and effect. In people with type 1 diabetes, all 11 patients diagnosed with gastroparesis by gastric emptying test while using cannabis every day met the criteria for cannabinoid hyperemesis syndrome. The American Gastroenterological Association (2025) conditionally suggests that CBD not be used as a first-line treatment for gastroparesis; the Gastroenterological Society of Australia (2026) found the evidence insufficient to recommend; Germany's functional dyspepsia guideline (2026) recommends that cannabinoids not be used routinely, and ESPGHAN/NASPGHAN (2025) recommends that cannabis not be used for irritable bowel syndrome and functional abdominal pain in children. The Canadian Association of Gastroenterology's 2019 position statement, on the other hand, writes that short-term use may help with persistent nausea, vomiting, diarrhea or abdominal pain when standard treatments are not enough, but that long-term effectiveness and safety in functional bowel disorders are unknown and cannabinoids should not be considered first-line treatment (3 of the 7 authors have ties to companies that make cannabis or cannabinoid products). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): 6 controlled studies with cannabinoids were found in these three conditions: 3 with pharmaceutical-grade or pure CBD (one each in gastroparesis, functional dyspepsia and irritable bowel syndrome; the longest 4 weeks) and 3 short physiology studies with dronabinol or THC in irritable bowel syndrome (single dose or 2 days). There are also 4 controlled studies measuring the effect of THC on stomach and colon movement in healthy volunteers, 3 systematic reviews, 1 expert committee report, 5 guidelines or position statements, 2 uncontrolled studies and 7 observational studies; all are in the table below. Six of the controlled studies (the gastroparesis and dyspepsia studies and the four dronabinol studies in patients and healthy volunteers) come from the same research group (Mayo Clinic, US). There is no Cochrane review; all 3 studies with results posted on ClinicalTrials.gov have been published; in October 2026, no ongoing cannabinoid study was found in these conditions; there are no studies from Turkey. Not included in the table: an irritable bowel syndrome study with the selective synthetic CB2 drug olorinab and stomach studies with the CB1 blocker rimonabant (site rule: not a cannabis or CBD product), substances that are not cannabinoid products such as PEA and hemp husk fiber, other US hospital database analyses with similar results, a retracted nabilone series, studies of chronic pancreatitis or postoperative abdominal pain, a small dronabinol study in functional chest pain, a single-center survey asking about use and perceived benefit in gastroparesis, and a review that examines the effect of CBD on bowel movement mostly through animal studies.

Evidence assessment: Weak; differs by condition (in each condition, a single small RCT with pure or pharmaceutical-grade CBD, the longest 4 weeks: in gastroparesis, improvement in symptoms, but on a measure not defined in the registration and not repeated; in functional dyspepsia and irritable bowel syndrome, no difference from placebo)

• CBD alone: In gastroparesis, pharmaceutical-grade CBD (up to 20 mg per kilogram a day, 4 weeks, 44 people) clearly lowered the total symptom score compared with placebo (p = 0.008; this score is not among the measures in the study's ClinicalTrials.gov registration) and reduced vomiting; but it slowed the emptying of solid food from the stomach slightly more, and diarrhea was common (12 of 21 people, 2 of 23 on placebo); the result is from a single center and has not been repeated. The same dose was no different from placebo in symptoms, stomach measurements or quality of life in functional dyspepsia with normal stomach emptying (48 people). In irritable bowel syndrome, gum containing 50 mg CBD (32 women, crossover design, 3 weeks each) was no different from placebo gum in pain or quality of life. The American Gastroenterological Association (2025) suggests that CBD not be used as a first-line treatment for gastroparesis (conditional recommendation).
• Products containing THC: In irritable bowel syndrome, there are only short physiology studies with THC: a single dose of dronabinol reduced colon contractions on an empty stomach in 75 patients, dronabinol taken for 2 days did not change bowel transit time in 36 patients with diarrhea, and THC did not change bowel sensitivity in 10 patients; in a meta-analysis pooling the single-dose studies, the effect was zero (very low certainty). There is no controlled THC study following symptoms over weeks; no THC study was found in functional dyspepsia. In gastroparesis, there is only an uncontrolled series (24 patients, improvement in symptoms) and user reports in a patient registry; in healthy volunteers, THC and dronabinol slowed the emptying of solid food from the stomach. In a patient registry and in a large analysis of electronic records, cannabis users with gastroparesis had more frequent emergency visits and hospital admissions (in coded in-hospital data, however, length of stay was shorter; these do not show cause and effect). Long-term heavy cannabis use can cause recurring bouts of vomiting that can be mistaken for gastroparesis. (insufficient evidence) Evidence: Insufficient (no controlled THC study following symptoms in patients over weeks; in irritable bowel syndrome, only 3 single-dose or 2-day physiology RCTs, with negative or unclear results; in gastroparesis, only an uncontrolled series and user reports; in healthy volunteers, THC slowed stomach emptying)
• Dose range in studies: Pharmaceutical-grade pure CBD: from 2.5 mg up to 20 mg per kilogram a day, two doses a day, 4 weeks (gastroparesis, functional dyspepsia); 50 mg CBD gum as needed, at most 6 a day (300 mg), 3 weeks (irritable bowel syndrome; use less than 1 a day); THC-containing: dronabinol single dose 2.5–7.5 mg or 2.5–5 mg twice a day for 2 days, THC single dose 5–10 mg and 10 mg/m² (physiology studies); in the uncontrolled gastroparesis series, dronabinol 2–10 mg 2–4 times a day and medical marijuana of variable ratio
• Starting dose and titration (in studies): In the gastroparesis and functional dyspepsia studies, started at 2.5 mg/kg/day and raised by 2.5–5 mg/kg every two days up to 20 mg/kg/day; at the end of 4 weeks, tapered off over 10 days (study dose; not a personal recommendation)
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's drug interactions section
• Monitoring in studies: Cannabis and cannabinoid use should be reported to the physician before a gastric emptying test; the American College of Gastroenterology's 2022 gastroparesis guideline writes that, among medicines that may affect the result, stopping cannabinoids 48 hours before the test is usual practice (Camilleri 2022, PMID 35926490)
• Monitoring in studies: In the gastroparesis study in which high-dose pharmaceutical-grade CBD was tested, liver tests were measured at the start and at week 4, and no change was seen; with longer use, monitoring liver tests is the physician's decision (Zheng 2023)

References (28)

Study table (dose, duration, result) · Topic page

Most randomized studies of cannabinoids in loss of appetite and weight loss not related to cancer were done in HIV/AIDS and with THC-containing products. In the largest (Beal 1995; 139 randomized, 88 evaluable, 6 weeks), dronabinol 2.5 mg twice a day increased appetite more than placebo (38% vs 8%; p = 0.015), while the difference in weight was not significant (p = 0.14); the US approval is based on this study. In Struwe 1993 (12 randomized, 5 completed), only body fat percentage increased; in Timpone 1997 (52 patients, open-label), megestrol produced much more weight gain than dronabinol and adding dronabinol did not increase it; in Abrams 2003 (67 patients, 21 days), smoked cannabis and dronabinol did not adversely affect viral load or CD4 count, and weight, a secondary outcome, rose more than with placebo (as reported by reviews). Three laboratory studies of people with HIV who regularly smoked cannabis (Haney 2005 and 2007, Bedi 2010; 7–30 people) showed that cannabis and dronabinol increased calorie intake, and that at the highest dose this effect disappeared after 8 days. The Cochrane review (Lutge 2013; 7 RCTs) found the evidence on efficacy and safety insufficient; the Mücke 2018 meta-analysis found superiority over placebo in HIV for weight (2 RCTs: Abrams 2003 and Beal 1995; SMD 0.57) and appetite (Beal 1995 only; SMD 0.57) but rated the quality of evidence for the HIV outcomes as very low; NASEM 2017 found the evidence limited for HIV/AIDS and insufficient for anorexia nervosa; Bilbao 2022 found a benefit of moderate certainty for appetite with dronabinol (SMD −0.51; high heterogeneity between studies) and no difference in comparisons with active drugs. In the only placebo-controlled study of CBD in people living with HIV (Barré 2024; 80 people, 12 weeks, CBD-rich full-spectrum oil), the main quality-of-life scores did not change and appetite was not measured; in the safety publication, viral load did not change. In older age: in patients over 65 with reduced appetite, a spray containing THC and CBD did not change calorie intake over one day (Nielsen 2025; 17 of 73 completed; +10 kcal, 95% CI −55 to 75); in 15 people with Alzheimer's disease who refused to eat, weight rose more with dronabinol (Volicer 1997); two uncontrolled chart reviews (28 and 40 people) reported improvement. In systemic sclerosis, an oil containing THC and CBD was no different from placebo for appetite, weight and calories over 4 weeks (Pisprasert 2025; 27 patients); in the records of 344 patients with ALS who did or did not use medical marijuana, use was linked with fewer complaints of poor appetite in the short term but not with maintaining weight (Austin 2024). In anorexia nervosa, dronabinol produced a small weight gain over 4 weeks compared with placebo without changing symptoms (Andries 2014; 25 women); THC was no different from diazepam and 3 patients had severe dysphoria (Gross 1983; 11 women); pure CBD was well tolerated in a 3-week pilot study, with a small difference in body mass index (p = 0.046) and no difference in the prespecified behavioral measures (Sahota 2026; 32 women); a 2026 meta-analysis pooling 54 RCTs in mental health conditions found no significant effect on outcomes related to anorexia nervosa (Wilson 2026). CBD's effect on appetite: in the epilepsy studies of the approved CBD medicine, reduced appetite was 16–22% vs 5% (US prescribing information); two reviews showed that reduced appetite was more common with CBD (Spanagel 2021: OR 2.46; Pinto 2022); in 15 healthy volunteers, 193 kcal more was eaten after a single dose of pure CBD (Johnson 2026). October 2026 search (PubMed, Cochrane, ClinicalTrials.gov, Europe PMC): on this topic we found 15 randomized controlled trials with cannabinoids (12 placebo-controlled, 3 with an active drug or comparing two products; 11 with THC-containing products, 2 with pure CBD [one in healthy volunteers], 1 with a CBD-rich oil, 1 comparing pure CBD with THC:CBD), 1 non-randomized controlled laboratory study, 2 retrospective cohorts with a comparison group, 3 observational studies without a comparison group and 10 systematic reviews, meta-analyses or expert reports (1 Cochrane); all are in the table below. Of these, 12 concern HIV/AIDS, 5 older age, 5 anorexia nervosa, 3 other illnesses not related to cancer, 3 CBD's general effect on appetite and 3 more than one area. The results of a dronabinol study in HIV treatment-related nausea, which enrolled 103 people and ended in 2005, were never published; no studies from Turkey were found.

Evidence assessment: Pure CBD: very weak (in patients with loss of appetite, the only pure CBD study is a 3-week pilot study of 32 people with anorexia nervosa; in HIV, a CBD-rich oil was tested for quality of life, not appetite; in the epilepsy studies, CBD lowered appetite)

• CBD alone: There is only one controlled study of pure CBD in patients with loss of appetite or weight loss: in a 3-week pilot study of 32 people with anorexia nervosa, approved (licensed) pure CBD was well tolerated and there was a small difference in body mass index compared with placebo (p = 0.046), but no difference in the main outcomes measured, anxiety and eating disorder symptoms. In 80 people living with HIV, a CBD-rich full-spectrum oil (THC below 0.3%) did not change the main quality-of-life scores over 12 weeks; appetite and weight were not measured; viral load and immune values were not affected. Pure CBD has not been tested for loss of appetite in older age, HIV-related wasting or other illnesses not related to cancer. In the epilepsy studies of the approved CBD medicine, CBD lowered appetite and increased weight loss (dose-dependent); in 15 healthy volunteers, on the other hand, people ate slightly more after a single dose of pure CBD.
• Products containing THC: In HIV/AIDS, dronabinol (synthetic THC) increased appetite more than placebo in a 6-week study of 139 people (38% vs 8%; p = 0.015), but the difference in weight was not significant (stable weight vs −0.4 kg; p = 0.14); in a comparison of 52 people, megestrol led to much more weight gain (+6.5 kg vs −2.0 kg). Smoked cannabis and high-dose dronabinol increased calories eaten in the laboratory among people with HIV who regularly smoked cannabis; in a 21-day study, weight rose slightly more than with placebo and viral load did not change. Most of these studies were small, short and done before the era of effective HIV treatment. The Cochrane review found the evidence insufficient and the US National Academies found it limited; a meta-analysis based on two small studies found better results than placebo for appetite and weight in HIV but rated the quality of evidence as very low. In 17 patients over 65 with reduced appetite, a spray containing THC and CBD did not change the amount eaten over one day; in 15 people with Alzheimer's disease who refused to eat, weight rose more with dronabinol. In a study of 27 patients with systemic sclerosis, an oil containing THC and CBD was no different from placebo. In anorexia nervosa, dronabinol produced a small weight gain in a study of 25 people but did not change symptoms; an older 11-person study with THC found no difference and three people had severe restlessness; a 2026 meta-analysis pooling mental health studies also found no significant effect in anorexia nervosa. (weak evidence) Evidence: THC-containing products: weak (in HIV/AIDS, 4 small-to-medium RCTs and 3 small laboratory studies: appetite rose, the effect on weight was small and inconsistent, weaker than megestrol; most done before effective HIV treatment; no difference in one small RCT each in older adults and in systemic sclerosis; in anorexia nervosa, one of two small RCTs found a small weight gain and the other found no difference; insufficient evidence according to Cochrane, limited according to the US National Academies)
• Approval: Pure CBD is not approved for loss of appetite or weight loss. Dronabinol, a synthetic THC (capsule and oral solution), is approved in the US in adults for AIDS-related loss of appetite with weight loss (the drug's first US approval was in 1985; this use was added in 1992). The starting dose in the prescribing information is 2.5 mg twice a day (1 hour before lunch and dinner); for older adults or if side effects occur, starting with 2.5 mg once a day in the evening or at bedtime is recommended; the maximum is 10 mg twice a day. The approval is based on the 6-week study of 139 people (Beal 1995). Source: US prescribing information (DailyMed: dronabinol capsule, versions February 14, 2023 and May 13, 2026; dronabinol oral solution, version April 21, 2026) §1, §2.1, §14.1. The prescribing information reviewed lists no use for loss of appetite in older age, anorexia nervosa or other illnesses not related to cancer. Turkey: dronabinol, nabilone and any other THC or CBD medicine are not on the Licensed Human Medicinal Products List of TİTCK (Turkish Medicines and Medical Devices Agency) (October 16, 2026); dronabinol and nabilone do not appear on the Foreign Active Substance List (September 28, 2026), where only cannabidiol oral solution and a mouth spray containing THC and CBD are listed among medicines that require a red prescription (Turkey's controlled-drug prescription) and can be imported with TİTCK's written approval.
• Dose range in studies: Dronabinol in HIV/AIDS 2.5 mg twice a day (2.5 mg/day with side effects; label maximum 10 mg twice a day); in HIV laboratory studies 10–30 mg single dose and 5–10 mg four times a day; in Alzheimer's disease 5 mg/day; in anorexia nervosa dronabinol 2.5 mg twice a day, THC 7.5–30 mg/day; smoked cannabis 1.8–3.95% THC; nabiximols (older adults) 2 × 3 sprays in one day (each 8.1 mg THC + 7.5 mg CBD); THC:CBD oil (systemic sclerosis) 2.92 mg THC + 3.24 mg CBD/day; pure CBD in anorexia nervosa 2.5–12.5 mg/kg/day (3 weeks); CBD-rich oil in HIV 2 mg/kg/day; pure CBD in the open HIV study 200–800 mg/day
• Starting dose and titration (in studies): Dronabinol: per the prescribing information, start at 2.5 mg twice a day, or 2.5 mg in the evening for older adults or with side effects; increased slowly if needed. In anorexia nervosa, CBD was increased weekly: 1.25 → 3.75 → 6.25 mg per kilogram twice a day; in systemic sclerosis, THC:CBD oil from 1 drop to 2 drops twice a day after 1 week; in the open HIV study, participants increased the dose themselves as tolerated; with the CBD-rich oil (HIV), the dose was not increased. These are research protocols, not personal recommendations
• Interaction: The studies on this page did not systematically assess drug interactions; details are in the site's Drug interactions section
• Interaction: Dronabinol is broken down in the body by the enzymes CYP2C9 and CYP3A4: ritonavir, ketoconazole, itraconazole, clarithromycin, erythromycin and grapefruit juice (CYP3A4), as well as amiodarone and fluconazole (CYP2C9), can raise dronabinol levels and its side effects (US prescribing information §7.3)
• Interaction: Sleep-inducing medicines, alcohol, benzodiazepines and opioids: sleepiness and dizziness increase when combined with dronabinol (prescribing information §5.1, §7.1)
• Interaction: Highly protein-bound drugs with a narrow therapeutic range (warfarin, cyclosporine, amphotericin B): side effects should be monitored when starting dronabinol; this interaction has not been confirmed in the body (prescribing information §7.4)
• Interaction: HIV protease inhibitors: smoked cannabis lowered the peak blood level of indinavir by 14% over 14 days, with no significant change for nelfinavir; the researchers judged this to have no clinical importance in the short term (Kosel 2002, Abrams 2003 trial)
• Interaction: CBD and HIV medicines: no systematic data; in a case of hepatitis seen with high-dose CBD, the researchers also counted a possible interaction with HIV medicines among the factors (Mboumba Bouassa 2022)
• Interaction: In people whose CYP2C9 enzyme works poorly, blood levels of dronabinol may rise (prescribing information §8.6)
• Monitoring in studies: When starting dronabinol and when increasing the dose, blood pressure, pulse and fainting are monitored; fall precautions are taken in older adults (dronabinol prescribing information §5.2, §8.5)
• Monitoring in studies: Liver enzymes should be monitored in people using high-dose CBD; hidden liver disease should be looked for (Mboumba Bouassa 2022)
• Monitoring in studies: In people living with HIV: studies found no harmful change in viral load or CD4 count in the short term (Abrams 2003; Barré 2024 and Couton 2026; Mboumba Bouassa 2022); there are no long-term data
• Monitoring in studies: Ongoing trials (October 2026): studies are under way in people living with HIV looking at the effect of THC and CBD on cognitive function (NCT04883255; 138 people, recruiting), gut microbiota and brain inflammation (NCT05514899; 90 people, recruiting) and blood levels of HIV medicines (NCT04800159; 40 people); no ongoing CBD study with appetite or weight as the main outcome was found (although the anorexia nervosa study's registration appears ongoing, its results have been published)

References (31)

Study table (dose, duration, result) · Topic page