What does the research say?
In a review that pooled 123 animal studies, CBD showed a moderate effect on depression-like behaviors; however, the same authors noted that the evidence in humans is limited and inconclusive.
In one human study, 180 university students who were stressed and at risk of depression were randomly assigned to three groups: they took low-dose full-spectrum CBD oil, an inactive oil (placebo) or nothing at all. There was no difference on any measure between those taking CBD and those taking placebo; both groups improved more in stress and depression symptoms than those who took nothing (the groups did not differ in anxiety and sleep). This shows how strong an effect expectation can have.
In another study with health care workers, CBD reduced emotional exhaustion and, as a secondary measure, depression scores; however, this study had no placebo group, participants knew they were taking CBD, depression was not the main measure, and all of the serious side effects occurred in people taking CBD. A large 2026 review of 54 studies also reported that there is no evidence from well-designed studies for treating depression. For products containing THC, evidence of benefit for depression is scarce; side effects and stopping because of side effects are more common.
CBD studies in other groups that also measured depression symptoms paint a similar picture. In patients with brain tumors and anxiety, 600 mg of CBD a day did not reduce depression symptoms more than an inactive pill (placebo); no clear difference was seen in advanced cancer or in hand osteoarthritis either. An anxiety study conducted in India also reported improvement in depression scores; however, six of its seven authors worked for pharmaceutical companies (five of them at the company that funded the pharmacokinetic part of the trial), the reported effect was much larger than seen in similar studies, and the details could not be verified.
Products containing THC have been tried very little in depression. In two small studies in the 1970s with hospitalized patients with depression, THC did not improve depression; about half of the patients could not continue treatment because of reactions such as intense anxiety or panic. In the US, when people who wanted to use medical cannabis for anxiety or depression were randomly assigned to two groups that could get cannabis either right away or after 12 weeks, depression symptoms did not improve in those who started right away; cannabis use disorder, on the other hand, became about three times more likely. In registry studies following patients who use medical cannabis, depression scores went down; however, these studies mostly had no comparison group, and most were carried out by teams with ties to cannabis companies.
In studies following the link between recreational cannabis use and depression over many years, people who used cannabis were found to be slightly more likely to develop depression later (about 1.3 times; similar in those who used it during adolescence). However, in an analysis that included only general population studies and accounted for tobacco separately, this link was not significant; it has not been proven that cannabis causes depression. In people with depression, cannabis use went along with a harder recovery in most studies; a Canadian mental health guideline group, noting that the evidence is limited, recommends that people with major depression avoid cannabis. In teenagers who used cannabis at least once a week, stopping for 4 weeks neither worsened nor improved depression symptoms.
Strength of evidence: ●○○○ Very weak evidence. Finding: Not studied enough. What does this mean?
Ongoing research on this topic
Trials testing CBD for this topic on ClinicalTrials.gov: 4 under way (2 recruiting); results are awaited from 3 that ended in the last two years. A trial being under way does not show that CBD works.
- NCT06290063: Phase 2, recruiting, target 385 participants
- NCT07696871: Phase 1/2, recruiting, target 120 participants
- NCT05066308: Phase 2, completed, results awaited, 69 participants
Possible side effects and drug interactions
In the health care worker study, four liver value elevations (one of them serious) and one severe drug rash were seen in people taking CBD. Across mental health studies, people taking cannabis-derived substances were more likely to have side effects; there was no difference in serious side effects. In two old, small studies in which THC was tried in patients with depression, 10 of 21 patients could not continue treatment because of reactions such as intense anxiety, panic or a feeling of detachment from oneself. Cannabis use disorder (uncontrolled, problematic use) developed more often in people who started using medical cannabis for anxiety or depression. A single case was also reported of a person who developed an episode of extreme elation (mania) after vaping a high dose of a product whose purity could not be verified.
CBD can slow the breakdown of some medicines in the body. In healthy adults, CBD increased the amount of the antidepressant citalopram in the body by 43%; a single dose of CBD also raised amitriptyline levels slightly. In an emergency department survey, 69.7% of people who used CBD at home were taking a medicine with a risk of interaction; antidepressants were the most common of these.
Interactions with medicines used for this condition
Interactions reported for these medicines in peer-reviewed publications and official prescribing information. A medicine that is not listed can still interact with CBD; tell your doctor about every medicine you take.
| Medicine | Importance | Warning | Source |
|---|---|---|---|
| Citalopram (SSRI) (Cipram, Citol, Relaxol) | Caution | Citalopram, escitalopram: CBD raised citalopram blood levels: a significant rise in a series of 6 patients; in healthy volunteers, citalopram exposure (AUC) rose by 43% after 12 days of approved CBD (2.5 mg/kg twice a day). If you take these medicines, talk to your doctor. | PMID 34121064, PMID 41622700 |
| Amitriptyline (tricyclic) (Laroxyl) | Caution | Amitriptyline: In healthy volunteers, a single 30 mg dose of CBD oil raised the blood level (AUC) of amitriptyline by 13% and its peak level by 17%; the effect is said to possibly be larger with ongoing use. Tell your doctor or pharmacist. | PMID 41398552 |
To check interactions with the medicines you take: CBD drug interaction checker.
How was CBD used in studies?
There is no dose that has been shown to work for depression. In the health care worker study, 300 mg a day of pure CBD (study dose; not a personal recommendation) was used for 28 days, split into two doses. In the student study, full-spectrum CBD oil was given for 30 days; the dose started at 0.02 mg per kilogram per day and was raised every three days, reaching 1 mg on day 30 (at most about 85 mg a day for someone weighing 85 kilograms). In the study with brain tumor patients, 600 mg a day of pure CBD was used for 3 weeks.
Study details (for health professionals)
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).
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 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
These are doses researchers gave under medical supervision; they are not a recommended dose for you. "mg/kg/day" means milligrams per kilogram of body weight per day.
| Study | Participants | Product | Dose and titration | Duration | Result | Source |
|---|---|---|---|---|---|---|
| Winkler 2025 RCT, 3 arms (CBD oil / placebo oil / no treatment) | 180 randomized (CBD oil 59, placebo oil 61, no treatment 60); 166 analyzed (52/58/56) Stressed university students at risk of depression | 10% full-spectrum CBD oil (nonprescription product; 1000 mg CBD per 10 mL, a small amount of THC, amount not reported); placebo hemp seed oil | By body weight: 0.02 mg/kg on day 1, 1 mg/kg on day 30 (about 1.7–85 mg a day for 85 kg) Increased every three days (0.02 → 1 mg/kg) | 30 days | Primary outcomes were stress (PSS-10) and depression symptoms (DASS-21). No difference between CBD oil and placebo oil on any outcome (difference in change in depression symptoms 0.23 points; p = 0.774; d = 0.05). Both oil groups improved more than the group that received nothing in stress, depression symptoms and physical complaints (for depression, CBD d = 0.65, placebo d = 0.61); the groups did not differ in anxiety, sleep or well-being. The authors attribute the improvement largely to the placebo effect Side effects: not reported (side effects were asked about on day 30, but the article does not report the results) | PMID 41316488, doi:10.1186/s42238-025-00366-9, German Clinical Trials Register DRKS00030971 (preregistered on December 22, 2022) |
| Crippa 2021 Open-label RCT (no placebo) | 214 people assessed; 120 randomized (61 CBD, 59 control); 118 analyzed Frontline health care workers during the COVID-19 period | Pure CBD (99.6%), 150 mg/mL in MCT oil + standard care | 300 mg/day (150 mg × 2) None | 28 days | Primary outcome was emotional exhaustion: it decreased in the CBD + standard care group compared with control on days 14, 21 and 28 (difference at day 28 4.01 points; 95% CI 0.43–7.59). Secondary outcome was depression symptoms (PHQ-9): group × time interaction significant (p < 0.001), a 2.72-point drop from baseline at day 28 in the CBD group (95% CI 0.95–4.48); the number of people with PHQ-9 above 10 decreased only in the CBD group. There was no placebo and participants knew what they were taking. 7 of 24 authors are patent holders or applicants related to CBD compounds (the patents are outside the subject of this study); the CBD was donated by a company Side effects: 5 serious side effects, all in the CBD group: 4 liver enzyme elevations (1 critical, 3 mild), 1 severe drug rash; CBD was stopped in 2 people, both recovered fully. The most common side effects (drowsiness, tiredness) were similar in both groups | PMID 34387679, doi:10.1001/jamanetworkopen.2021.20603, NCT04504877, no results in the registry), 3-month follow-up publication by the same team (anxiety outcomes): Souza 2022, PMID 36263136 |
| Kotin 1973 Double-blind, placebo-controlled small study (inpatient; 7 days placebo, 7 days THC, 7 days placebo) | 8 (4 unipolar, 4 bipolar depression); 4 people completed the THC period Hospitalized, unmedicated adults with moderate to severe depression (US National Institute of Mental Health research unit) | THC (oral) | Oral THC; dose contradictory in the secondary source (Stanciu 2021 text: 0.3 mg/kg twice daily; the same review's table: from 5 mg a day to 2 × 20 mg a day) not reported (original article could not be read) | 3 weeks (7 days of THC) | THC did not improve depression on subjective or observer-rated mood measures; scale scores not reported, no separate result for the unipolar depression subgroup. The original article and its abstract could not be read; information from the Stanciu 2021 review Side effects: 4 of 8 patients stopped THC because of side effects (in two, severe anxiety with a feeling of detachment from oneself after the first dose); drowsiness in those who completed | PMID 4569675, doi:10.1001/archpsyc.1973.01750330041007 |
| Ablon 1974 Double-blind, placebo-controlled small study (inpatient; THC or placebo after 3 weeks of observation) | 13 (8 unipolar, 5 bipolar depression) Hospitalized adults with depression (US National Institute of Mental Health research unit) | THC (oral) | Oral THC; dose contradictory in the secondary source (Stanciu 2021 text: from 5 mg a day to 2 × 20 mg a day; the same review's table: 0.3 mg/kg twice daily, 7 days) Contradictory in the secondary source: according to the Stanciu 2021 text, raised from 5 mg a day to 2 × 20 mg a day; according to its table, 0.3 mg/kg twice daily (original article could not be read) | not reported (unclear in the secondary source) | Depression symptoms did not improve; standard scale scores not reported. A distressing (dysphoric) reaction was seen in 7 of 13 patients: 6 had unipolar and 1 had bipolar depression. The original article and its abstract could not be read; information from the Stanciu 2021 review Side effects: 6 patients could not continue the study after the first dose because of panic or psychosis-like reactions | PMID 4592555, doi:10.1176/ajp.1974.131.4.448 |
| Gilman 2022 Pragmatic RCT (getting a medical cannabis card right away or after 12 weeks; 2:1 randomization; participants were not blinded, only assessors were blinded) | 269 randomized; 186 analyzed (105 immediate, 81 delayed; those with baseline and at least one follow-up measurement; in the immediate group, only those who got the card: 53 of the 173 people assigned to this group did not get a card); depression analysis in 83 people who applied for anxiety or depression (46/37) Adults aged 18–65 seeking medical cannabis for pain, insomnia, or anxiety or depression symptoms; daily cannabis users and people with cannabis use disorder were excluded (US, Boston) | Cannabis products chosen by participants themselves at a dispensary (THC and/or CBD; ratios in a supplementary table, not read) | Participant's choice (product, dose and frequency unrestricted) Participant's choice | 12 weeks | On depression symptoms, one of the primary outcomes (HADS-depression; only in those who applied for anxiety or depression), no difference between groups (mean difference −0.5; 95% CI −1.4 to 0.4; p = 0.30); no difference in anxiety or pain either, only the insomnia score improved (−2.90; 95% CI −4.31 to −1.51). Cannabis use disorder symptoms increased (0.28; 95% CI 0.15–0.40). At baseline, the mean HADS-depression score was below the clinical threshold (6.1 and 5.2) Side effects: At 12 weeks, cannabis use disorder in 17.1% of those who got the card right away and 8.6% of those who waited (adjusted OR 2.88; 95% CI 1.17–7.07); among those who applied for anxiety or depression, 28.3% vs 10.8% | PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, frequency of cannabis use increased in those who got the card, no improvement in depression symptoms at 12 weeks, the depression score was found to be very slightly lower on days when cannabis was used, but when limited to those whose use was confirmed by urine testing, this difference was not significant) |
| Belgers 2026 Double-blind, placebo-controlled crossover RCT (Bayesian analysis); stopped early because of slow recruitment | 20 randomized (55 planned); 15 completed both periods Adults with brain tumors, stable disease and clinically significant anxiety (S-STAI ≥ 44) (Netherlands); not selected because of depression | Pure CBD tablet (more than 99% CBD, less than 0.1% THC) | 600 mg/day not reported (not in the research letter) | 2 × 3 weeks (with at least a 2-week washout in between) | Primary outcome was anxiety; depression symptoms (CES-D) secondary. Anxiety and depression symptoms decreased more in the placebo period than in the CBD period; the probability that CBD improved depression symptoms was 11% (median difference +1.61 points, against CBD; 95% credible interval −0.97 to 4.21). The authors do not recommend further research on CBD for anxiety and depression in this patient group; the study is small and statistically underpowered Side effects: Side effects similar (3 events in the CBD period, one grade 3; 6 events in the placebo period, all grade 1 or 2); a rash in one patient during the CBD period (may have been due to the carrier substance) | PMID 42750778, doi:10.1093/nop/npag025, Netherlands Trial Register NL9623 (GRASS study) |
| Gundugurti 2024 Multicenter, double-blind, placebo-controlled RCT (phase 3) | 178 randomized (89 CBD, 89 placebo); number analyzed not in the abstract Adults with mild to moderate anxiety disorder (India); not selected because of depression | Nanodispersed CBD oral solution (150 mg per mL); purity and manufacturer not stated in the abstract | not reported (not in the abstract) not reported (not in the abstract) | 15 weeks (study duration in the abstract; treatment duration not given separately in the abstract) | Primary outcomes were anxiety (GAD-7, HAM-A): CBD was reported to be superior to placebo (GAD-7 difference in change −7.02; standard error 0.25; 95% CI −7.52 to −6.52; p < 0.0001). In a study of 89 vs 89 people, this standard error means the spread between people was only about 1.7 points on a 0–21 scale; this is unusually small for a psychiatry study, and the effect is much larger than in other anxiety studies; the result has not been independently replicated. The study was also reported to have met its target for depression symptoms measured with PHQ-9, a secondary outcome; there are no depression numbers in the abstract, the full text could not be read, and the analysis method could not be verified. Six of the seven authors are tied to pharmaceutical companies (five are executives or employees of Leiutis Pharmaceuticals, which funded the pharmacokinetic part of the trial, and one is medical director of Biophore Pharma) Side effects: No serious side effects (abstract); side effect numbers not in the abstract | PMID 38797087, doi:10.1016/j.ajp.2024.104073, Clinical Trials Registry – India CTRI/2023/01/049110. Pharmacokinetic study that is part of the same trial: Gundugurti 2026, PMID 41613360, single dose of 300 mg, funded by Leiutis Pharmaceuticals). Research letter from the same team: Gundugurti 2026, PMID 42901095, new patient data could not be verified) |
| Vela 2022 Double-blind, placebo-controlled RCT | 136 randomized; 129 analyzed Patients with hand osteoarthritis or psoriatic arthritis with moderate pain despite treatment (Denmark); not selected because of depression | Synthetic CBD, oral; no THC | Started at 10 mg/day; 20 mg/day at week 2; 30 mg/day at week 4 if no response Stepwise: 10 → 20 → 30 mg/day | 12 weeks | No significant difference between CBD and placebo in depression (HADS; exploratory outcome) or anxiety (depression numbers not in the abstract). No difference in the primary outcome, pain, either (0.23 mm; 95% CI −9.41 to 9.90; p = 0.96) Side effects: Side effects in 33 patients in the CBD group and 26 with placebo; serious events 2 vs 2, none attributed to the drug | PMID 34510141, doi:10.1097/j.pain.0000000000002466, NCT03693833 |
| Hardy 2023 (MedCan1-CBD) Double-blind, placebo-controlled, dose-escalation RCT (phase 2b) | 144 randomized; 121 at day 14 (58 CBD, 63 placebo) Patients with advanced cancer and a high symptom burden receiving palliative care (Australia); not selected because of depression | Synthetic pure CBD oil (100 mg per mL) | Started at 0.5 mL (50 mg) once daily, up to a maximum of 2 mL three times daily (600 mg/day); median dose chosen by patients 400 mg/day Increased over the first 14 days according to response and side effects | 28 days | On depression, a secondary outcome (and on anxiety and quality of life), CBD had no detectable effect (scale and numbers not in the abstract). The primary outcome, total symptom burden, fell by 3.0 points with CBD and 6.2 points with placebo at day 14; no difference (p = 0.24) Side effects: Side effects similar between groups; shortness of breath more common with CBD | PMID 36409969, doi:10.1200/JCO.22.01632, ANZCTR ACTRN12618001220257, protocol: Good 2019, PMID 31810437 |
| Cooke 2021 RCT (4 weeks of cannabis abstinence with financially incentivized support, or monitoring only) | 179 randomized (112 abstinence, 67 monitoring); in the abstinence group, 90 people did not use for 4 weeks Healthy adolescents and young adults who used cannabis at least once a week and were not seeking treatment (US; including participants under 18) | Recreational cannabis (THC) | Not applicable (abstinence study) None | 4 weeks | Depression and anxiety symptoms (MASQ) decreased slightly over time in all participants; no difference between the abstinence and monitoring groups (p > 0.46). In exploratory analyses, there was a trend suggesting that abstinence may bring more improvement in those who used cannabis to cope with negative emotions and in those using at risky levels. According to the authors, 4 weeks of abstinence did not worsen symptoms Side effects: not reported | PMID 34276449, doi:10.3389/fpsyt.2021.689957 |
| Black 2019 Systematic review and meta-analysis | 83 studies (40 RCTs, n=3067); 42 studies for depression, 23 of them RCTs (n=2551) Mental disorders | All cannabinoids | No RCT examining depression as the primary diagnosis was found. In 12 placebo-controlled THC (± CBD) studies measuring depression symptoms, mostly in patients with MS and chronic pain, no significant difference (SMD −0.05; 95% CI −0.20 to 0.11; very low certainty of evidence); there was no CBD RCT measuring a depression outcome (search up to April 30, 2018). Across all mental disorders, THC increased side effects and stopping because of side effects Side effects: THC: side effects OR 1.99; stopping because of side effects OR 2.78 | PMID 31672337, doi:10.1016/S2215-0366(19)30401-8, Correction: Lancet Psychiatry 2020, 7(1):e3, PMID 31860461 | ||
| Wilson 2026 Systematic review and meta-analysis | 54 RCTs, 2477 people Mental and substance use disorders | All cannabinoids | No RCT evidence for treating depression; insufficient data for meta-analysis in bipolar disorder Side effects: Any side effect OR 1.75 (NNTH 7); no difference in serious side effects | PMID 41856154, doi:10.1016/S2215-0366(26)00015-5, Correction: Lancet Psychiatry 2026, 13(8):e11, PMID 42302809, 2026, the axis of a figure and the study counts in the table were corrected, results unchanged) | ||
| Bharat 2026 Systematic review and meta-analysis of experimental and observational studies (up to May 2025; PROSPERO CRD42023467536) | 82 experimental and 118 observational studies Adults with ADHD, anxiety, depression, PTSD, psychosis, Tourette syndrome or substance use disorder, or in whom these symptoms were measured | THC, CBD, combinations of the two and other cannabinoids; medical cannabis | In RCTs, the effect of cannabinoids on depression symptoms was negligibly small and not significant (SMD −0.20; 95% CI −0.43 to 0.04; I² 91.6%); most of the depression evidence was measured as a secondary outcome in other conditions. The certainty of evidence is mostly very low; observational studies suggest improvement but have a high risk of bias. The authors see no benefit in depression and do not support cannabinoids as a first-choice treatment Side effects: The only significant safety finding: stopping because of side effects was more common with THC (OR 2.78; 95% CI 1.66–4.65) | PMID 42617303, doi:10.1016/j.psychres.2026.117380 | ||
| Stanciu 2021 Systematic review of controlled studies (1970–February 5, 2020; 8 databases; no meta-analysis) | 8 controlled studies; two in patients with depression (21 people, 12 with unipolar depression) People with mood disorders, anxiety disorders and post-traumatic stress disorder | CBD, THC or nabilone (THC-like synthetic cannabinoid) at defined doses | In two small 1970s studies with THC in depression, depression did not improve, and anxiety, panic or psychosis-like reactions were seen in more than half of the patients. No prospective placebo-controlled studies were found in mood disorders with CBD, a defined ratio of THC and CBD, or the cannabis plant (the search ended in February 2020). The authors conclude that cannabinoids should not be recommended in these disorders Side effects: In the depression studies, intense anxiety, a feeling of detachment from oneself, panic and psychosis-like reactions | PMID 33530732, doi:10.1176/appi.ps.202000189 | ||
| Churchill 2025 Systematic review and meta-analysis of longitudinal studies (up to March 31, 2023; update of the Lev-Ran 2014 meta-analysis) | 22 longitudinal studies (14 from the previous meta-analysis) General population samples that accounted for baseline depression (in 12, participants were under 18 at the first measurement); studies examining only specific patient groups were not included | Cannabis use (from occasional use to use disorder) | People who use cannabis are more likely to develop depression later (OR 1.29; 95% CI 1.13–1.46); large variation between studies (prediction interval 0.75–2.20). The odds are higher with heavy use; no significant difference between early and late onset. The previous meta-analysis had found OR 1.17 (1.05–1.30), and 1.62 (1.21–2.16) for heavy use (Lev-Ran 2014). Observational; the measurement of cannabis use is the main source of bias, confounders cannot be fully ruled out, and cause and effect cannot be shown | PMID 39936870, doi:10.1017/S0033291724003143 | ||
| Burke 2024 Systematic review and meta-analysis of longitudinal studies in the general population (up to November 2022; PROSPERO CRD42021243903) | 75 studies (7 for cannabis and new mood disorders) General population samples | Cannabis use (compared with tobacco) | The link between cannabis use and new-onset mood disorders was not significant (RR 1.31; 95% CI 0.92–1.86; 7 studies); cannabis was linked to psychotic disorders (RR 3.19). Tobacco use was linked to mood disorders (RR 1.39; 43 studies). Confounder analyses suggest that the effects may have been overestimated; only 27% of the studies were high quality | PMID 39620474, doi:10.1017/S0033291724002587 | ||
| Tourjman 2023 (CANMAT) Systematic review and clinical recommendation (Canadian CANMAT task force; from inception to October 2020; PubMed, Embase, PsycINFO, CINAHL, Cochrane; GRADE; no meta-analysis) | 56 studies (1 RCT, 3 prospective, 26 longitudinal or cohort, 26 cross-sectional); 21 in major depression, 11 in both major depression and bipolar disorder; 408,223 people in the major depression studies (5,044 with cannabis use or use disorder) People with major depression or bipolar disorder (meeting diagnostic criteria) | Cannabis use and cannabis use disorder (THC/CBD content not specified in the studies) | In major depression, cannabis use was linked to more severe depression symptoms (especially inability to feel pleasure) and, in some studies, lower functioning; no link was seen with the number of episodes or age at onset, and the link with suicide was sparse and inconsistent (suicide attempts more common in one adolescent study, no difference in the others); no study looked at remission or relapse. In the only RCT testing combined treatment of major depression and cannabis use disorder (fluoxetine added to cognitive behavioral therapy, 70 people), there was no difference from placebo. Findings are more consistent in bipolar disorder than in major depression. The certainty of evidence is low for most outcomes (studies mostly observational, amount of cannabis measured in different ways, THC/CBD content not specified, common causes cannot be ruled out). Recommendation: people with major depression should avoid cannabis (in the recommendation table, certainty of evidence low to moderate, strength of recommendation conditional); in bipolar disorder the same recommendation is strong | PMID 35711159, doi:10.1177/07067437221099769 | ||
| Sorkhou 2024 Systematic review (from inception to November 2023; EMBASE, PsycINFO, PubMed, MEDLINE; no meta-analysis) | 78 studies (1 RCT, 52 longitudinal, 25 cross-sectional); 31 examined cannabis and later depression, 11 the course of major depression The general population and people with major depression and bipolar disorder | Cannabis use and cannabis use disorder; one CBD RCT | Of 31 prospective studies examining cannabis and later depression, 22 found a temporal association, and 9 did not once confounders were taken into account. In 10 of 11 studies looking at the course of major depression, cannabis use was linked to a worse course or treatment outcome (more inability to feel pleasure, suicidal thoughts, lower medication adherence); no evidence was found that cannabis improves clinical outcomes in depression. In an uncontrolled 11-person study, stopping cannabis for 28 days reduced depression symptoms. Most studies are observational; cause and effect cannot be shown | PMID 38655516, doi:10.3389/fpubh.2024.1346207 | ||
| Lillywhite 2026 (UK Medical Cannabis Registry) Case series without a comparison group (patient registry; patient-reported measures) | 698 (those treated for depression out of 34,563 patients in the registry) Adults started on prescribed cannabis products for depression (UK); half had severe anxiety at baseline | Prescribed cannabis products (product type and THC/CBD breakdown not in the abstract) | not reported (in the abstract) not reported (in the abstract) | 24 months | PHQ-9 depression score, anxiety, sleep and quality of life improved from baseline at all measurement times (p < 0.001), most in the first 3 months; numbers not in the abstract. In the same registry's earlier analysis of 129 patients, median PHQ-9 fell from 16 to 7 at month 6 (Mangoo 2022). No comparison group; cause and effect cannot be shown. 16 of 17 authors are employees or contractors of the clinic that prescribed these products to the patients (Curaleaf Clinic) Side effects: At least one side effect in 63 patients (9%); 87% of events mild or moderate (Mangoo 2022: 153 side effects in 18 of 129 patients) | PMID 41506388, doi:10.1016/j.jad.2025.121130, Earlier analysis of the same registry: Mangoo 2022, PMID 36573268, 6 months) |
| Specka 2024 Retrospective longitudinal study (telemedicine platform records; no comparison group) | 59 (22% had stopped by week 18) Outpatients aged 20–54 with major depression who had previously received antidepressant treatment (Germany); 73% men, one third had used cannabis regularly at times in the last 5 years | Medical cannabis prescribed through a telemedicine platform (product and THC/CBD content not in the abstract) | not reported (in the abstract) not reported (in the abstract) | 18 weeks | Depression severity (0–10 rating; the abstract does not name a standard depression scale) fell from 6.9 to 3.8 (95% CI for the difference 2.4–3.8; p < 0.001); at week 18, a drop of more than half in 50.8% of patients. Antidepressant use (31%) did not affect the outcome. No comparison group, measurements at monthly visits. Four of the seven authors are employees, executives or former employees of the company that runs the platform (Algea Care). The authors write that the risk of cannabis use disorder should be kept in mind Side effects: One third of patients reported side effects; none severe | PMID 38211630, doi:10.1055/a-2215-6114 |
| Martin 2021 Observational, prospective online survey study (comparison group of cannabis users and non-users; follow-up every 3 months) | 538 (368 users, 170 non-users); at follow-up, 36 new starters, 121 continuing users, 23 who did not start Adults reporting a diagnosis of anxiety or depression (US; mostly women and white); from the Realm of Caring patient registry | Medical cannabis products: of those who knew the content, 82% used CBD-dominant and 23% THC-dominant products; 26% did not know the content | In CBD-dominant products with a certificate of analysis obtained, an oral mean of 61 mg CBD a day (median 30 mg) and 2.1 mg THC (median 1 mg) Participant's choice | Follow-up at 3-month intervals (duration varies by person) | At baseline, users' depression score (HADS) was lower than non-users', with no difference in anxiety. At follow-up, depression (−2.57 points) and anxiety scores fell in those who started cannabis and did not change in those who did not start. CBD-dominant product use was linked to a lower depression score, but this was not significant after correction for multiple comparisons. No randomization, all measures self-reported; the authors write that an expectation effect cannot be ruled out. The study was supported by a nonprofit cannabinoid patient foundation (Realm of Caring) and US National Institute on Drug Abuse fellowship programs; two of the seven authors have ties to cannabis companies (one a Canopy Growth employee) Side effects: Side effect reports were more common among THC-dominant product users (38% vs 26%); no difference between CBD-dominant product users and non-users | PMID 34566726, doi:10.3389/fpsyt.2021.729800 |
| Yana 2023 Retrospective, propensity score–matched cohort (Ontario health databases) | 54,006 patients authorized for medical cannabis and 161,265 matched people Adults authorized to use medical cannabis (Canada, Ontario); 16% had a prior anxiety or mood disorder | Medical cannabis authorization (no information on products used) | Authorizations 2014–2019; follow-up duration not in the abstract | In people authorized for cannabis, the risk of an emergency department visit or hospitalization for a depressive disorder was about twice as high (adjusted HR 2.02; 95% CI 1.83–2.22); HR 2.23 (1.95–2.55) in those with no prior mental disorder. Observational; how much the authorized people actually used is unknown, and cause and effect cannot be shown. Three of the six authors have ties to a medical cannabis company (Aurora Cannabis) | PMID 36638694, doi:10.1016/j.psychres.2022.115047 | |
| Fontanella 2021 Retrospective, population-based cohort (Ohio Medicaid records and death certificates; weighted models) | 204,780 (10.3% with cannabis use disorder) Young people aged 10–24 diagnosed with a mood disorder in 2010–2017 (US, Ohio); breakdown of diagnoses not in the abstract | Doctor-diagnosed cannabis use disorder | 1 year after diagnosis | Cannabis use disorder was linked to nonfatal self-harm (adjusted HR 3.28; 95% CI 2.55–4.22) and death from any cause (HR 1.59; 1.13–2.24); deaths from accidental overdose and homicide were also more common. The link with suicide was not significant in adjusted models. Observational; cannabis use disorder may be a risk marker, and cause and effect cannot be shown | PMID 33464286, doi:10.1001/jamapediatrics.2020.5494 | |
| Young-Wolff 2026 Retrospective cohort (Kaiser Permanente Northern California electronic health records; 2016–2023) | 463,396 adolescents (26,345 reported using cannabis in the past year) Adolescents aged 13–17 who were asked about cannabis use at a routine well-child visit (US) | Cannabis use in the past year (self-reported on a confidential screening form) | Mean follow-up of 3.3 years for depression (up to age 25 at most) | Cannabis use was linked to a higher risk of a new depressive disorder diagnosis later (HR 1.34 adjusted for sex, ethnicity, deprivation, insurance, alcohol and other substance use; 95% CI 1.30–1.39); HR 1.33 (1.29–1.38) when prior mental disorders were also taken into account. The link with depression and anxiety weakened as the adolescents got older. Observational; cannabis use is self-reported, diagnoses come from records | PMID 41719031, doi:10.1001/jamahealthforum.2025.6839 | |
| Auf 2025 Case report | 1 31-year-old man with no psychiatric history | Vaporized CBD (product purity not verified) | Increasing, 'high dose' (mg not reported) Self-directed increase | 3 months | Manic episode; resolved when CBD was stopped and treatment was given Side effects: Mania | PMID 40630971, doi:10.64719/pb.4542 |
| Jantsch 2026 Systematic review and meta-analysis of animal studies (not human data) | 123 animal studies Animal models | CBD | Various | In animals, CBD consistently reduced anxiety- and depression-like behaviors (moderate-sized effect in some tests); according to the authors, clinical evidence in humans is still limited and inconclusive | PMID 42380607, doi:10.1038/s41380-026-03733-x |
Reported side effects
- Crippa 2021 (300 mg/day): 4 liver enzyme elevations (1 critical), 1 severe drug rash
- Side effects with any cannabinoid OR 1.75 (NNTH 7) (Wilson 2026)
- A single case of mania after high-dose vaporized CBD (Auf 2025)
- THC (1970s, hospitalized patients with depression): 10 of 21 patients could not continue because of intense anxiety, a feeling of detachment from oneself, panic or psychosis-like reactions (Kotin 1973, Ablon 1974; details from a secondary source, Stanciu 2021)
- Medical cannabis card (12 weeks): cannabis use disorder 17.1% vs 8.6% (adjusted OR 2.88); among those applying for anxiety or depression, 28.3% vs 10.8% (Gilman 2022)
Monitoring done in studies
- Doctor monitoring for changes in medicine levels in people taking antidepressants
Who should be careful
- Depression is a serious illness; there is no evidence that CBD can replace prescription treatment
- If someone taking an antidepressant adds CBD, medicine levels may change
- Risk of label/content mismatch in nonprescription products (Auf 2025)
- Depression symptoms did not improve with medical cannabis products; cannabis use disorder developed more often in those randomly assigned to start early (Gilman 2022)
- In young people with mood disorders, cannabis use disorder went along with an increased risk of self-harm (observational; Fontanella 2021)
- A Canadian mental health guideline group (CANMAT) recommends that people with major depression avoid cannabis; the certainty of evidence is low to moderate, and the recommendation is conditional (Tourjman 2023)
Drug interactions
- Citalopram: in healthy adults, CBD (2.5 mg/kg twice daily, 12 days) increased citalopram exposure (AUC) by 43% (Salcedo 2026, PMID 41622700)
- 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)
- 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)
- Reports of interactions with antidepressants, antiepileptics, opioids and alcohol were reviewed (Balachandran 2021, PMID 33515191)
Abbreviations: RCT, randomized controlled trial (a study in which participants are assigned to groups by chance); placebo, an inactive substance; SMD, OR and RR, effect measures used in analyses that pool studies; CYP, liver enzymes that break down medicines.
If you are considering CBD
- There are treatments that have been shown to work for depression; there is no evidence that CBD can replace them.
- If you take an antidepressant, talk to your doctor before adding CBD; medicine levels may change.
- In nonprescription products, what is on the label may not match what is in the bottle; read the label and check the certificate of analysis (COA).
- Do not stop or cut down your medicine on your own; plan every change together with your doctor.
- If you feel very bad or have thoughts of harming yourself, contact your doctor or the nearest emergency department without waiting.
Choose your age group, medicines and situation to prepare a short summary you can take to your doctor. Nothing you enter is sent anywhere.
Bottom line
Curiosity about CBD for depression is understandable, but human research has not yet shown a benefit. More research is needed to confirm the animal study results in people. Cannabis containing THC has not been shown to improve depression; in most observational studies, regular use went along with a worse course of depression. For now, the most reliable path is the treatment you continue together with your doctor.
Frequently asked questions
Does CBD oil work for depression?
There is not enough evidence to say. No well-designed human study that directly examined depression and found a positive result has been published. In a study with students, CBD oil gave no different result from an inactive oil (placebo); in a small study of patients with brain tumors, high-dose CBD did not reduce depression symptoms more than placebo either. Animal studies are promising, but these results have not been shown in people.
Can CBD replace an antidepressant?
No, there is no evidence for that. Depression is a serious illness; it is not right to stop or cut down an antidepressant on your own. Plan every change to your medicine together with your doctor.
Can CBD and an antidepressant be used together?
This calls for caution. In healthy adults, CBD increased the amount of citalopram in the body by 43%; amitriptyline levels also rose. If you take an antidepressant, do not add CBD without talking to your doctor.
Can CBD make your mood worse?
A large review found no difference in serious side effects with cannabis-derived substances, but general side effects were more common. A single case of mania was reported with a high dose of a product whose purity could not be verified. The picture is different for cannabis containing THC: in old studies with patients with depression, THC often caused intense anxiety, and in observational studies regular cannabis use went along with a worse course of depression. If you notice an unusual change in your mood, tell your doctor.
Can CBD oil for depression be obtained with a prescription in Turkey?
In Turkey, cannabis-derived products are governed by the Kenevirden Elde Edilen Ürünlere Dair Yönetmelik (Regulation on Products Derived from Hemp) dated January 31, 2026. These products, including CBD, can be sold only in pharmacies. Those classed as medicines and health products are dispensed with a prescription; for supplement products and cosmetics with a THC content of no more than 0.3%, the regulation does not state a prescription requirement. As of October 2026, there is no approved (licensed) CBD medicine in Turkey. If you are thinking of using it, talk with your doctor first.
References
Show 26 references
- Winkler 2025. RCT, 3 arms (CBD oil / placebo oil / no treatment). PMID 41316488, doi:10.1186/s42238-025-00366-9, German Clinical Trials Register DRKS00030971 (preregistered on December 22, 2022)
- Crippa 2021. Open-label RCT (no placebo). PMID 34387679, doi:10.1001/jamanetworkopen.2021.20603, NCT04504877, no results in the registry), 3-month follow-up publication by the same team (anxiety outcomes): Souza 2022, PMID 36263136
- Kotin 1973. Double-blind, placebo-controlled small study (inpatient; 7 days placebo, 7 days THC, 7 days placebo). PMID 4569675, doi:10.1001/archpsyc.1973.01750330041007
- Ablon 1974. Double-blind, placebo-controlled small study (inpatient; THC or placebo after 3 weeks of observation). PMID 4592555, doi:10.1176/ajp.1974.131.4.448
- Gilman 2022. Pragmatic RCT (getting a medical cannabis card right away or after 12 weeks; 2:1 randomization; participants were not blinded, only assessors were blinded). PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, frequency of cannabis use increased in those who got the card, no improvement in depression symptoms at 12 weeks, the depression score was found to be very slightly lower on days when cannabis was used, but when limited to those whose use was confirmed by urine testing, this difference was not significant)
- Belgers 2026. Double-blind, placebo-controlled crossover RCT (Bayesian analysis); stopped early because of slow recruitment. PMID 42750778, doi:10.1093/nop/npag025, Netherlands Trial Register NL9623 (GRASS study)
- Gundugurti 2024. Multicenter, double-blind, placebo-controlled RCT (phase 3). PMID 38797087, doi:10.1016/j.ajp.2024.104073, Clinical Trials Registry – India CTRI/2023/01/049110. Pharmacokinetic study that is part of the same trial: Gundugurti 2026, PMID 41613360, single dose of 300 mg, funded by Leiutis Pharmaceuticals). Research letter from the same team: Gundugurti 2026, PMID 42901095, new patient data could not be verified)
- Vela 2022. Double-blind, placebo-controlled RCT. PMID 34510141, doi:10.1097/j.pain.0000000000002466, NCT03693833
- Hardy 2023 (MedCan1-CBD). Double-blind, placebo-controlled, dose-escalation RCT (phase 2b). PMID 36409969, doi:10.1200/JCO.22.01632, ANZCTR ACTRN12618001220257, protocol: Good 2019, PMID 31810437
- Cooke 2021. RCT (4 weeks of cannabis abstinence with financially incentivized support, or monitoring only). PMID 34276449, doi:10.3389/fpsyt.2021.689957
- Black 2019. Systematic review and meta-analysis. PMID 31672337, doi:10.1016/S2215-0366(19)30401-8, Correction: Lancet Psychiatry 2020, 7(1):e3, PMID 31860461
- Wilson 2026. Systematic review and meta-analysis. PMID 41856154, doi:10.1016/S2215-0366(26)00015-5, Correction: Lancet Psychiatry 2026, 13(8):e11, PMID 42302809, 2026, the axis of a figure and the study counts in the table were corrected, results unchanged)
- Bharat 2026. Systematic review and meta-analysis of experimental and observational studies (up to May 2025; PROSPERO CRD42023467536). PMID 42617303, doi:10.1016/j.psychres.2026.117380
- Stanciu 2021. Systematic review of controlled studies (1970–February 5, 2020; 8 databases; no meta-analysis). PMID 33530732, doi:10.1176/appi.ps.202000189
- Churchill 2025. Systematic review and meta-analysis of longitudinal studies (up to March 31, 2023; update of the Lev-Ran 2014 meta-analysis). PMID 39936870, doi:10.1017/S0033291724003143
- Burke 2024. Systematic review and meta-analysis of longitudinal studies in the general population (up to November 2022; PROSPERO CRD42021243903). PMID 39620474, doi:10.1017/S0033291724002587
- Tourjman 2023 (CANMAT). Systematic review and clinical recommendation (Canadian CANMAT task force; from inception to October 2020; PubMed, Embase, PsycINFO, CINAHL, Cochrane; GRADE; no meta-analysis). PMID 35711159, doi:10.1177/07067437221099769
- Sorkhou 2024. Systematic review (from inception to November 2023; EMBASE, PsycINFO, PubMed, MEDLINE; no meta-analysis). PMID 38655516, doi:10.3389/fpubh.2024.1346207
- Lillywhite 2026 (UK Medical Cannabis Registry). Case series without a comparison group (patient registry; patient-reported measures). PMID 41506388, doi:10.1016/j.jad.2025.121130, Earlier analysis of the same registry: Mangoo 2022, PMID 36573268, 6 months)
- Specka 2024. Retrospective longitudinal study (telemedicine platform records; no comparison group). PMID 38211630, doi:10.1055/a-2215-6114
- Martin 2021. Observational, prospective online survey study (comparison group of cannabis users and non-users; follow-up every 3 months). PMID 34566726, doi:10.3389/fpsyt.2021.729800
- Yana 2023. Retrospective, propensity score–matched cohort (Ontario health databases). PMID 36638694, doi:10.1016/j.psychres.2022.115047
- Fontanella 2021. Retrospective, population-based cohort (Ohio Medicaid records and death certificates; weighted models). PMID 33464286, doi:10.1001/jamapediatrics.2020.5494
- Young-Wolff 2026. Retrospective cohort (Kaiser Permanente Northern California electronic health records; 2016–2023). PMID 41719031, doi:10.1001/jamahealthforum.2025.6839
- Auf 2025. Case report. PMID 40630971, doi:10.64719/pb.4542
- Jantsch 2026. Systematic review and meta-analysis of animal studies (not human data). PMID 42380607, doi:10.1038/s41380-026-03733-x
Points that could not be verified from the full text
- No published RCT in treatment-resistant depression (PubMed and ClinicalTrials.gov, October 19, 2026; checked again on October 27, 2026, no change). NCT04732169 was withdrawn due to lack of funding (0 people); NCT07696871 (THC-containing full-spectrum oil, 12 weeks, target 120) has been recruiting since June 2026
- NCT07651930 (anxiety/depression in Parkinson’s; 30/60/300 mg/day full-spectrum oil, no placebo, 60 days, 27 people) was completed in November 2024; no results on ClinicalTrials.gov and no publication on PubMed (October 19, 2026; checked again on October 27, 2026)
- NCT05041647 (insomnia in major depression; CBD:THC 25:1 and 5:1 oil vs placebo, pilot, 14 people) was completed in January 2025, and NCT05066308 (measurement of brain inflammation with pure CBD in people with low back pain and depression symptoms, 69 people) in May 2026; neither has results on ClinicalTrials.gov or a publication on PubMed (October 27, 2026)
- Kotin 1973 and Ablon 1974 (THC, hospitalized patients with depression): the original articles and their abstracts could not be read; details come from the Stanciu 2021 review, and the review's text and table give the two studies' doses the other way around
- In the 1940s, a synthetic substance similar to THC (synhexyl) was tried in depression (Stockings 1947, Pond 1948); these articles have no abstract on PubMed and their full texts could not be accessed, so their results could not be verified
- The full text of the Wilson 2026 meta-analysis could not be read; its correction published in the journal (Lancet Psychiatry 2026;13(8):e11) was read on October 29, 2026: only the axis of one figure and the study counts in a table were corrected, and the results did not change
Research history
Here we record what changed on this page, when and why, with dates. The newest change is at the top.
On October 28, 2026, two sources found for this page during the searches for other topics were incorporated. In the medical cannabis card study (Gilman 2022), the number of people was corrected: 269 people were randomly assigned to groups, and 186 were analyzed; the daily survey analysis of the same trial (Tervo-Clemmens 2023) was added, which also found no improvement in depression symptoms at 12 weeks. In the anxiety study in India (Gundugurti 2024), the description of the company tie was corrected in the table and the text: the authors' conflict-of-interest statement does not say that the company developed the product; according to the pharmacokinetic publication of the same trial, that part was funded by the pharmaceutical company where most of the authors worked. The trial registration and the pharmacokinetic publication were added to the table as sources. The conclusion and the strength of evidence did not change.
PubMed, Cochrane and ClinicalTrials.gov were systematically searched again in October 2026 (3,707 records on PubMed, 730 on ClinicalTrials.gov; together with an independent second check). There is still no published controlled CBD study in patients diagnosed with depression. Added: placebo-controlled CBD studies measuring depression symptoms (brain tumors, advanced cancer, hand osteoarthritis and anxiety disorder), two small studies in which THC was tried in patients with depression in the 1970s, two studies testing randomized access to medical cannabis and stopping cannabis, three meta-analyses and three systematic reviews including the review by a Canadian mental health guideline group, medical cannabis registries, and large observational studies on cannabis use and depression risk. Studies asking the same question and covered by the reviews in the table were not added separately. Corrected: the dose of the student study (it was reported in the full text) and its outcome numbers, the depression outcome and company ties of the health care worker study, the number for the depression finding in the review, the table description of the animal studies review, and the table order. The conclusion and the strength of evidence did not change.
Related studies: Kotin 1973, published March 1973 (PMID 4569675, doi:10.1001/archpsyc.1973.01750330041007); Ablon 1974, published April 1974 (PMID 4592555, doi:10.1176/ajp.1974.131.4.448); Gilman 2022, published March 1, 2022 (PMID 35302633, doi:10.1001/jamanetworkopen.2022.2106, NCT03224468, PMID 36638745, 181 people, frequency of cannabis use increased in those who got the card, no improvement in depression symptoms at 12 weeks, the depression score was found to be very slightly lower on days when cannabis was used, but when limited to those whose use was confirmed by urine testing, this difference was not significant)); Belgers 2026, published October 2026 (online March 22, 2026) (PMID 42750778, doi:10.1093/nop/npag025, Netherlands Trial Register NL9623 (GRASS study)); Gundugurti 2024, published July 2024 (online May 18, 2024) (PMID 38797087, doi:10.1016/j.ajp.2024.104073, Clinical Trials Registry – India CTRI/2023/01/049110. Pharmacokinetic study that is part of the same trial: Gundugurti 2026, PMID 41613360, single dose of 300 mg, funded by Leiutis Pharmaceuticals). Research letter from the same team: Gundugurti 2026, PMID 42901095, new patient data could not be verified)); Vela 2022, published June 1, 2022 (PMID 34510141, doi:10.1097/j.pain.0000000000002466, NCT03693833); Hardy 2023 (MedCan1-CBD), published March 1, 2023 (PMID 36409969, doi:10.1200/JCO.22.01632, ANZCTR ACTRN12618001220257, protocol: Good 2019, PMID 31810437); Cooke 2021, published July 1, 2021 (PMID 34276449, doi:10.3389/fpsyt.2021.689957); Bharat 2026, published November 2026 (online August 11, 2026) (PMID 42617303, doi:10.1016/j.psychres.2026.117380); Stanciu 2021, published April 2021 (PMID 33530732, doi:10.1176/appi.ps.202000189); Churchill 2025, published February 12, 2025 (PMID 39936870, doi:10.1017/S0033291724003143); Burke 2024, published November 2024 (PMID 39620474, doi:10.1017/S0033291724002587); Sorkhou 2024, published April 9, 2024 (PMID 38655516, doi:10.3389/fpubh.2024.1346207); Lillywhite 2026 (UK Medical Cannabis Registry), published April 15, 2026 (online January 6, 2026) (PMID 41506388, doi:10.1016/j.jad.2025.121130, Earlier analysis of the same registry: Mangoo 2022, PMID 36573268, 6 months)); Specka 2024, published March 2024 (online January 11, 2024) (PMID 38211630, doi:10.1055/a-2215-6114); Martin 2021, published September 9, 2021 (PMID 34566726, doi:10.3389/fpsyt.2021.729800); Yana 2023, published February 2023 (PMID 36638694, doi:10.1016/j.psychres.2022.115047); Fontanella 2021, published April 1, 2021 (PMID 33464286, doi:10.1001/jamapediatrics.2020.5494); Young-Wolff 2026, published February 6, 2026 (PMID 41719031, doi:10.1001/jamahealthforum.2025.6839); Tourjman 2023 (CANMAT), published May 2023 (online June 16, 2022) (PMID 35711159, doi:10.1177/07067437221099769)
The names of the finding labels were simplified: this page's "Not enough research" label became "Not studied enough". The assessment did not change.
Older changes (2)
The full texts of the studies were reread and the information on the page was checked against its sources. Corrected: side effect and product information in the study table. The year of one publication named on the page was corrected to the journal's print year instead of the online publication year. The conclusion and the strength of evidence did not change.
Page published. This first review looked at 6 studies.