Tuberous Sclerosis and CBD Oil: Research, Dosage and Warnings

What does the research say?

The study enrolled 224 patients aged 1 to 65 years. Patients were randomly assigned to groups; neither the patients nor the doctors knew who was getting CBD and who was getting placebo. After 16 weeks, seizures related to tuberous sclerosis decreased by 48.6% and 47.5% in the two CBD groups and by 26.5% in the placebo group. The share of patients whose seizures were at least halved was 36% at the approved dose and 22% with placebo; this difference was not statistically significant.

The effect of the two doses was almost the same: the higher dose provided no extra benefit but increased side effects such as diarrhea and drowsiness. That is why the approved labeling recommends the lower dose. Doses below this have never been studied in tuberous sclerosis, so it is not known whether lower doses work.

A total of 199 patients who completed this study continued the medicine on an open-label basis. Over about a year, the reduction in seizures continued, and most families reported an overall improvement; the most common side effects were diarrhea, seizures, and decreased appetite. Because this part had no comparison group, the results should be read as a sign that the effect lasts. In follow-up of up to three years of 34 patients who received the medicine through an expanded access program in the US before approval, the reduction in seizures also continued. In a study based on the patient records of 27 centers, most of them in Europe, the share of patients whose seizures were at least halved was 56% in the group of 36 patients with a change in the TSC2 gene; among 5 patients with a change in the TSC1 gene, it was 2 out of 5. Neither of these two studies had a comparison group. There are very few data on symptoms other than seizures: in a small retrospective review, most kidney and brain tumors grew while patients were taking CBD; because there was no comparison group, it is not known whether this differed from the natural course of the disease, but there is no finding that CBD shrinks these tumors. An open-label study of behavior problems was completed in 2026, but its results have not yet been published.

These results apply to the approved medicine and cannot be applied to unregulated CBD products. The labels of oils on the market may not be reliable; products may contain THC or contaminants, and there are reports of increased seizures with these products.

Strength of evidence: ●●●○ Moderate evidence. Finding: Proven effect. What does this mean?

Ongoing research on this topic

Trials testing CBD for this topic on ClinicalTrials.gov: 2 under way; results are awaited from 1 that ended in the last two years. A trial being under way does not show that CBD works.

NCT05044819: Phase 4, active, not recruiting, 154 participants
NCT05864846: Phase 4, completed, results awaited, 79 participants
NCT05485831: Observational study, active, not recruiting, 111 participants

Registries in other countries also list 1 recruiting trial on this topic: other registries.

All trials on this topic and their history

Possible side effects and drug interactions

In the study, diarrhea occurred in 31% of patients at the lower dose, 56% at the higher dose, and 25% with placebo; drowsiness occurred in 13%, 26%, and 9%, respectively. Liver enzymes rose to more than three times normal in 12% of patients at the lower dose and 26% at the higher dose, and in none in the placebo group; most of these patients were also taking valproate, and the increases mostly began within the first month. The medicine's US prescribing information also gives this degree of increase in the liver enzyme ALT as 12% at the lower dose and 25% at the higher dose (the 1% placebo rate in the prescribing information is the combined figure from the studies of three diseases).

CBD can slow the breakdown of some medicines in the body. Blood levels of everolimus and sirolimus, which are often used in tuberous sclerosis, can rise with CBD; in one observational study, they rose in 76% of patients; in healthy volunteers, the amount of everolimus in the body also increased about 2.5-fold. There are also important interactions with clobazam and valproate. Because seizures can increase if CBD is stopped suddenly, treatment is stopped gradually.

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.

Tuberous Sclerosis: medicines used and their interactions with CBD
Medicine	Importance	Warning	Source
Clobazam	High importance	Clobazam: If you take clobazam, CBD can raise the medicine's active metabolite about 3-fold and can increase drowsiness. Do not start without talking to your neurologist.	FDA Epidiolex label §7.2, §12.3 (05/2026), EMA prescribing information §4.5, PMID 26114620
Valproate (valproic acid) (Depakin, Convulex)	High importance	Valproate and the liver: Liver enzyme elevations were more common when CBD was used together with valproate. Your doctor should monitor your liver tests.	DailyMed Epidiolex label 5.1, PMID 28782097
Everolimus, Sirolimus	High importance	Everolimus, sirolimus: In a controlled study in healthy volunteers taking approved CBD, the blood level of everolimus rose about 2.5-fold; in patients with TSC (tuberous sclerosis complex), everolimus and sirolimus levels rose in most patients when CBD was added. The prescribing information for both medicines recommends close monitoring of blood levels with CBD, and lowering the dose if needed. Do not start without talking to your doctor; your drug level should be monitored.	EMA Epidyolex SmPC 4.5, PMID 37132402, PMID 31924480, Everolimus (Afinitor) prescribing information §2.11 and §7.1, dailymed.nlm.nih.gov, Everolimus (Zortress) prescribing information §5.22 and §7.1, dailymed.nlm.nih.gov, Sirolimus prescribing information §5.21 and §7.5, dailymed.nlm.nih.gov
Stiripentol, Topiramate, Rufinamide, Zonisamide, Eslicarbazepine	Caution	Other epilepsy medicines: With epilepsy medicines, CBD can change the blood levels of some of them. Your doctor may monitor your drug levels and side effects.	PMID 28782097, PMID 33541771, PMID 37593907, PMID 31211851, PMID 30791225
Carbamazepine (Tegretol)	Caution	Strong enzyme inducers: These medicines can lower the level of CBD in the blood: with rifampin it fell by about one third. There are no direct measurements with others such as carbamazepine; the prescribing information expects a similar drop. Tell your doctor.	DailyMed Epidiolex label 7.1, EMA Epidyolex SmPC 4.5

To check interactions with the medicines you take: CBD drug interaction checker.

How was CBD used in studies?

In the study, the dose was calculated in milligrams per kilogram of body weight per day: 25 or 50 mg per kilogram per day (study dose; not a personal recommendation). The dose was increased slowly over 4 weeks, and the daily amount was split into two equal parts.

The maintenance dose recommended in the approved labeling is 25 mg per kilogram per day (study dose; not a personal recommendation); the dose is adjusted over weeks under a doctor's supervision. Lower doses are specified for people with liver impairment.

Study details (for health professionals)

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).

Evidence: THC-containing: Insufficient; no controlled study with results

Approved drug regimen

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

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)

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.

Tuberous Sclerosis and CBD: studies reviewed
Study	Participants	Product	Dose and titration	Duration	Result	Source
Thiele 2021 (GWPCARE6) Double-blind, placebo-controlled RCT, 46 centers	224 randomized; 201 completed Tuberous sclerosis complex, ages 1–65 (median 11.4); people taking oral mTOR inhibitors (everolimus, sirolimus) were not included	Epidiolex/Epidyolex (100 mg/mL oral solution, plant-derived purified CBD)	25 or 50 mg/kg/day 4 weeks: started at 5 mg/kg/day; 25 mg/kg/day reached on day 9 and 50 mg/kg/day on day 29; then 12 weeks of maintenance	16 weeks	Reduction in TSC seizures 48.6% (25 mg) and 47.5% (50 mg), placebo 26.5%; vs. placebo 30.1% (p<0.001) and 28.5% (nominal p=0.002); ≥50% response 36% (25 mg) and 40% (50 mg), placebo 22%; difference not significant for 25 mg (p=0.0692, EMA) Side effects: Diarrhea 31% / 56% (placebo 25%); drowsiness 13% / 26% (placebo 9%). Discontinuation 8 / 10 (placebo 2). Transaminase increase to more than 3 times normal 9/75 (12%) at 25 mg, 19/73 (26%) at 50 mg, 0 with placebo (18.9% for the two doses combined); 22 of the 28 affected patients were taking valproate, most began within the first 30 days, none met Hy's law criteria (full text). 25 mg is safer	PMID 33346789, doi:10.1001/jamaneurol.2020.4607, NCT02544763, post hoc analysis: Wu 2022, PMID 35175622
Thiele 2022 (GWPCARE6 open-label extension) Open-label extension (those who completed GWPCARE6); interim analysis	199 Seizures due to TSC (ages 1–57, mean 13); in the extension, 9 patients took everolimus and 25 took sirolimus, mTOR inhibitors that had been prohibited in the double-blind phase; the interaction was not assessed	Epidiolex/Epidyolex (100 mg/mL oral solution)	Target 25 mg/kg/day, up to 50 mg/kg/day depending on response; mean 27 mg/kg/day Reduction, or increase up to 50 mg/kg/day, based on response and tolerability	Median 267 days (18–910); efficacy 48 weeks	In 12-week periods, median seizure reduction 54–68%; ≥50% response 53–61%; at week 26, 87% of patients/caregivers reported improvement; no control group. This is an interim analysis (February 2019 data); in the final results on ClinicalTrials.gov (up to 4 years, no peer-reviewed publication), median reduction in TSC seizures was 56% (those who received CBD in the double-blind phase, 124 patients) and 47% (those who received placebo, 75 patients), ≥50% response 106/199; according to the registry, 34 of the 199 patients completed the extension (for most of those who left, the reason was 'other') Side effects: Side effects 92% (diarrhea 42%, seizures 22%, decreased appetite 20%); discontinuation due to side effects 6%; liver enzyme increases 9% (12 of the 17 patients were taking valproate). Final results (ClinicalTrials.gov, up to 4 years): side effects 192/199, serious side effects 56/199, permanent discontinuation due to side effects 18/199, 1 death	PMID 34957550, doi:10.1111/epi.17150, NCT02544750, no peer-reviewed publication, 3-year results only as a conference abstract: American Epilepsy Society 2022)
Weinstock 2024 (expanded access program) Open-label, uncontrolled expanded access program (35 centers in the US); pooled analysis of the TSC subgroup	34 (same for safety and efficacy analysis) TSC and drug-resistant epilepsy; ages 1.8–31.2 years (mean 12.4); median 3 antiepileptic drugs at baseline (clobazam 59%, valproate 18%)	Epidiolex (100 mg/mL oral solution, plant-derived purified CBD)	Up to 25–50 mg/kg/day depending on the center; median 25–28 mg/kg/day in the first 36 weeks, then 20–50 mg/kg/day; median highest dose 40 mg/kg/day, 62% of patients went above 25 mg/kg/day Started at 2–10 mg/kg/day and increased as tolerated	Median 1,102 days of CBD; efficacy up to 144 weeks, safety up to 233 weeks	In 12-week periods, up to 144 weeks: median reduction in total seizures 44–87% (convulsive 44–81%, focal 51–87%); ≥50% response for total seizures 46–79%, seizure freedom 0–13%. When those who stopped were counted with their last values (LOCF), reduction in total seizures 36–74%. 8 patients (24%) stopped, most commonly for lack of effect (4 patients). No control group, and the number of patients decreases in later periods; supported by the manufacturer (GW Research/Jazz). Side effects: Side effects 94% (drowsiness 32%, diarrhea 29%); serious side effects 47% (unrelated to treatment according to the investigator; status epilepticus, vomiting, viral infection, and seizures in 3 patients each); treatment-related side effects 68% (full text; 71% in the abstract); discontinuation due to side effects 2 patients; liver-related side effect 1 patient (was taking valproate, resolved without changing medicines); no deaths	PMID 39088193, doi:10.1002/epi4.13013, Hess 2016, PMID 27696387, 18 TSC patients (included among these 34 patients), at month 3, median reduction in weekly seizures 48.8%, ≥50% response 50%
Wray 2023 (everolimus interaction) Phase 1, single-center, open-label, fixed-sequence drug interaction study (everolimus alone and with CBD in the same person)	not reported (in the abstract) Healthy adult volunteers	Epidiolex (100 mg/mL oral solution) + single dose of everolimus 5 mg	CBD 12.5 mg/kg morning and evening (25 mg/kg/day), after a standard meal; everolimus 5 mg on days 1 and 13	17 days (everolimus on day 1, 7 days of washout, CBD on days 9–17)	At steady-state CBD levels, everolimus peak blood level and total exposure (AUC) increased about 2.5-fold; half-life did not change markedly. The authors recommend monitoring everolimus blood levels and reducing the dose when they are used together. The authors are employees of the manufacturer. Side effects: The single dose of everolimus was well tolerated with CBD (abstract); no details in the abstract	PMID 37132402, doi:10.1002/cpdd.1262
Talwar 2023 (meta-analysis) Systematic review and meta-analysis; subgroup analysis by syndrome	6 RCTs (Dravet, Lennox–Gastaut, TSC); the TSC subgroup is likely based on GWPCARE6 (224 patients), the only TSC RCT found in this search (full text could not be read) Drug-resistant epilepsy due to Dravet syndrome, Lennox–Gastaut syndrome, and TSC	Epidiolex (purified CBD, oral)	10–50 mg/kg/day in the studies	Up to 16 weeks in the studies	In the TSC subgroup, the likelihood of patients having their seizures at least halved was higher with CBD than with placebo (OR 1.99; 95% CI 1.06–3.76). This estimate most likely combines the two dose groups of GWPCARE6; in the same study, the approved dose alone was not significantly different from placebo on this measure (p = 0.0692). Across all studies, OR 2.45 (1.81–3.32). According to the authors, dose and concomitant clobazam use were associated with both the effect and side effects. Side effects: Across all studies, side effects OR 1.81 (1.33–2.46), serious side effects OR 2.86 (1.63–5.05); diarrhea, drowsiness, sedation	PMID 36206805, doi:10.1016/j.expneurol.2022.114238
Tong 2024 (network meta-analysis) Systematic review and network meta-analysis (6 newer antiepileptic drugs; indirect comparison)	20 RCTs, 5,516 patients (all epilepsy types) Adults with focal epilepsy; patients with Dravet, Lennox–Gastaut, and TSC (the abstract says 'adolescents'; the CBD study in TSC, GWPCARE6, covered ages 1–65)	Purified CBD (oral); everolimus among the drugs compared	not reported (in the abstract)	not reported (in the abstract)	In the indirect comparison for ≥50% response in TSC, everolimus targeting high blood levels ranked ahead of CBD (SUCRA 89.7%). There is no study directly comparing CBD with everolimus; this kind of ranking does not show definite superiority. The authors state that the findings need to be confirmed. Side effects: Not given separately for TSC (in the abstract); serious side effect and discontinuation rates were compared between drugs	PMID 38277848, doi:10.1016/j.yebeh.2024.109653
Samanta 2022 (scoping review) Scoping review, TSC only	not reported (in the abstract) Seizures due to TSC	Approved, purified CBD	not reported (in the abstract)	not applicable (review)	States that the evidence for short-term efficacy and safety rests on a single pivotal RCT. Data are lacking on which patients and which seizure types respond better, its place in the treatment sequence, use with other medicines, early treatment in infants, seizure severity, and cognitive/behavioral effects. No new numerical results. Side effects: No separate figures; interactions with other antiepileptic drugs are discussed (abstract)	PMID 35151190, doi:10.1016/j.yebeh.2022.108577, PMID 35581136, PMID 35500511
Cerulli Irelli 2025 (real-world, TSC subgroup) Retrospective, multicenter real-world study (27 centers, most in Europe, including Argentina); no control group	266 patients with single-gene epilepsy; 41 with TSC epilepsy (36 with a change in the TSC2 gene, 5 in TSC1) Single-gene drug-resistant epilepsy; median age 12 years when starting CBD	Epidiolex (Europe) or Convupidiol (Argentina); >99% purified CBD	Mean initial target dose 8.5 mg/kg/day for the whole group; not given separately for TSC	Median follow-up 17 months (IQR 12–24); at least 3 months of CBD	At last follow-up, compared with baseline: in the group of 36 patients with a change in the TSC2 gene, mean seizure reduction 48.4%, ≥50% response 55.9% (rate in the table; number of patients assessed not stated), improvement on doctor assessment (CGI-I) 83.3%; in the 5 patients with TSC1, mean reduction 21.4%, ≥50% response 2/5. There was no difference in results between diagnostic groups (Lennox–Gastaut, Dravet, TSC, other encephalopathies) (unadjusted p > 0.4; p = 0.83 after accounting for the degree of intellectual disability and the longest seizure-free period before CBD). Because only those who took CBD for at least 3 months were included, those who stopped early were left out; retrospective and uncontrolled. Side effects: Not given separately for TSC; in the whole group, side effects 38.5% during follow-up (21.8% at last follow-up; most common drowsiness 12.9%, digestive complaints 5.3%)	PMID 40126049, doi:10.1111/epi.18378
Ebrahimi-Fakhari 2020 (mTOR inhibitor levels) Retrospective records review; comparison before and after CBD in the same patients	25 (18 everolimus, 7 sirolimus) TSC patients who had CBD added while taking an mTOR inhibitor (everolimus or sirolimus) (US, Cincinnati Children's Hospital); age not stated in the abstract	CBD (product name not stated in the abstract)	not reported (in the abstract)	not reported (in the abstract)	After CBD was added, the trough blood level of the mTOR inhibitor rose significantly in 76% of patients (p = 0.0003); median increase +9.8 ng/mL for everolimus, +5.1 ng/mL for sirolimus. In some patients, the level rose 2–3-fold; some had clinical toxicity and laboratory abnormalities. The authors recommend level monitoring and an upfront dose reduction in patients prone to toxicity. Side effects: Side effects 40% (most common diarrhea, 3 patients); no severe side effects	PMID 31924480, doi:10.1016/j.pediatrneurol.2019.11.017
Barnett 2020 (tumor volume) Retrospective records review, single center (Massachusetts General Hospital); no control group	Number of patients not in the abstract; 7 dominant renal angiomyolipomas and 3 subependymal giant cell tumors were measured TSC patients taking CBD for epilepsy who had renal angiomyolipomas or subependymal giant cell tumors; those taking mTOR inhibitors and those who had surgery for these tumors were excluded	Epidiolex (plant-derived purified CBD, oral solution)	not reported (in the abstract)	not reported (in the abstract)	During CBD treatment, 6 of 7 kidney tumors and 3 of 3 brain tumors grew; the 1 tumor that shrank was not considered significant. According to the authors, unlike mTOR inhibitors, CBD does not shrink these tumors. Because there was no comparison group, it is not known whether the growth differed from the natural course of the disease. Very small, uncontrolled series. Side effects: not reported (in the abstract)	PMID 32409220, doi:10.1016/j.jocn.2020.05.030
Shlomovitz 2021 (Israeli TSC cohort) Retrospective, single-center cohort (2008–2018); results of CBD-based products, vagus nerve stimulation, and the ketogenic diet side by side; no randomization or placebo	91 TSC patients; number of patients taking CBD-based products not reported (in the abstract) Tuberous sclerosis complex, children and adults; median age 15.6 years at last follow-up (Israel, single center)	"CBD-based products" (product name and THC content not stated in the abstract)	not reported (in the abstract)	Mean follow-up about 2.5 years (0–9.5 years; abstract)	No difference in efficacy was found between CBD-based products, vagus nerve stimulation, and the ketogenic diet; the response rate was about 30–40% for all three. The definition of response and the number of patients taking CBD are not in the abstract; retrospective, uncontrolled. Side effects: not reported (in the abstract)	PMID 34491422, doi:10.1007/s00381-021-05348-9

Reported side effects

Drowsiness/sedation: Epidiolex (LGS/Dravet) 32% (10 mg/kg/day 27%, 20 mg/kg/day 34%), placebo 11%
Diarrhea, decreased appetite, vomiting, fever, fatigue (common in RCTs)
Liver enzyme (ALT) >3×ULN: in controlled studies, LGS/Dravet 13%, TSC 12% (placebo 1%, controlled studies of the three diseases combined; FDA label, increase to more than 3 times normal — in the Thiele 2021 full text, transaminase (ALT or AST) >3×ULN: 12% at 25 mg/kg/day, 26% at 50 mg/kg/day, 0 with placebo; 22 of the 28 affected patients were taking valproate); 17% at 20 mg/kg/day, 1% at 10 mg/kg/day; >20×ULN <1%
ALT >3×ULN with valproate (TSC study, 25 mg/kg/day): valproate+clobazam 20%, valproate alone 25%, clobazam alone 0%, neither 6% (FDA)
Drowsiness/sedation in the TSC study 19% (placebo 17%); 33% in those taking clobazam, 14% in those not taking it (FDA)
Discontinuation due to side effects: in the TSC study, 8/75 (11%) at 25 mg/kg/day, 10/73 (14%) at 50 mg/kg/day, 2/76 (3%) with placebo (Thiele 2021); 8.9% vs. 1.8% in a Dravet/LGS meta-analysis (Lattanzi 2018, PMID 30390221)
Labeling warnings: suicidal thoughts and behavior (class warning for all antiepileptic drugs), hypersensitivity (including to sesame oil), increased seizures on sudden discontinuation; EMA: seizure frequency may increase, weight loss/failure to gain weight
Postmarketing: cholestatic/mixed-type liver injury and (mostly in those taking valproate/clobazam) elevated ammonia have been reported (FDA)
Weight loss: in the TSC study (25 mg/kg/day), a decrease in measured weight of at least 5% from baseline was seen in 31% of those taking CBD and 8% with placebo; weight loss reported as a side effect was 7% vs. 0%. In the LGS/Dravet controlled studies (10 and 20 mg/kg/day), weight loss of at least 5% was 16% vs. 8% (FDA, product information 05/2026)

Monitoring done in studies

ALT, AST, and total bilirubin before starting (FDA and EMA)
Liver tests at months 1, 3, and 6, then periodically or as clinically needed
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
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
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
If liver symptoms occur (unexplained nausea, vomiting, right upper abdominal pain, fatigue, loss of appetite, jaundice, dark urine), check ALT/AST/bilirubin right away
Blood levels and side effects of concomitant antiepileptic drugs (Gaston 2017, PMID 28782097)

Who should be careful

Epilepsy treatment is started, changed, and stopped by a neurologist's decision; antiepileptic medicines are not stopped on your own
CBD is stopped by gradually lowering the dose; stopping suddenly carries a risk of increased seizures and status epilepticus (FDA §2.5, §5.5). EMA: in studies, tapering was done over ~10 days, reducing the dose by ~10% a day
In moderate (Child-Pugh B) and severe (Child-Pugh C) liver impairment, the labeling specifies lower starting and maintenance doses; no adjustment is needed in mild impairment
Hypersensitivity to sesame oil is a contraindication (Epidyolex contains 736 mg of refined sesame oil and 79 mg of ethanol per mL)
People taking valproate or clobazam need more frequent monitoring for liver effects and sedation
Age: FDA ≥1 year, EMA ≥2 years
The medicine is always taken the same way in relation to food; a high-fat meal increases Cmax 5-fold and AUC 4-fold. Doses are measured with a calibrated syringe; a household spoon is not suitable
Unregulated (artisanal) CBD/cannabis oils are not a substitute for the approved medicine: labels are unreliable, they may contain THC and contaminants, and there are reports of increased seizures

Drug interactions

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
Valproate: liver enzyme elevations increase markedly; diarrhea and decreased appetite also increase (EMA). If enzymes rise, CBD and/or valproate is reduced or stopped
Stiripentol: in healthy volunteers, Cmax increased 28% and AUC 55%; in patients, Cmax increased 17% and AUC 30%. Side effects are monitored closely
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
Topiramate, rufinamide, zonisamide, eslicarbazepine: in an open-label study, serum levels rose as the CBD dose increased (most stayed within the therapeutic range)
Sirolimus, tacrolimus, digoxin (oral P-gp substrates): exposure may increase; level monitoring and dose reduction are considered
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
CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC increased 95%; dose reduction is considered for drugs with a narrow therapeutic range
CYP2C19 prodrugs such as clopidogrel: the active metabolite may decrease
Alcohol and other CNS depressants: drowsiness and sedation increase; alcohol also increases CBD exposure (Cmax 93%, AUC 63%)
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)

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

You can talk with your neurologist about whether the approved CBD medicine is suitable for you or your child.
If everolimus or sirolimus is being used, plan with your doctor how the blood levels of these medicines will be monitored.
Set the schedule for liver tests from the start; monitoring may be more frequent if clobazam or valproate is being used.
Do not stop epilepsy medicines or CBD suddenly.
If a product on the market is being considered, review its label and independent certificate of analysis with your doctor.

Choose your age group, medicines and situation to prepare a short summary you can take to your doctor. Nothing you enter is sent anywhere.

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Bottom line

In tuberous sclerosis, the approved CBD medicine is an add-on treatment option supported by a single but well-designed controlled study. The higher dose provided no further benefit and only increased side effects. Decisions are made together with the doctor, also taking interactions with other medicines into account.

Frequently asked questions

Does CBD oil work for tuberous sclerosis?

When added to existing medicines, the approved, purified CBD medicine reduced seizures more than an inactive treatment (placebo). The evidence rests on a single large controlled study and is moderate; in long-term studies without a comparison group, the reduction in seizures lasted up to three years. This result does not apply to unregulated CBD oils.

Can CBD oil be used in children?

Children aged 1 year and older also took part in the study. However, a separately planned study for babies younger than 2 years was able to enroll only 2 babies with tuberous sclerosis and was stopped early because of low enrollment; there are very few data in this age group. The approved medicine is authorized from 1 year of age in the US and from 2 years of age in the European Union; it is used on the decision of a pediatric neurologist and with regular blood tests. CBD oils on the market are not a substitute for this medicine.

Can CBD be taken while using everolimus?

CBD can raise the blood levels of everolimus and sirolimus; in a study of 25 patients with tuberous sclerosis, levels rose in 76% of patients; in a study in healthy volunteers, the amount of everolimus in the body also increased about 2.5-fold. For this reason, when they are used together, drug levels are monitored and doses are adjusted if needed. This decision is made by your doctor. Because patients using these medicines were not included in the placebo-controlled study of the approved medicine, information on using them together comes from these smaller studies.

Does a higher dose mean a stronger effect?

In the study, the higher dose did not provide more benefit than the lower dose; however, side effects such as diarrhea and drowsiness increased. That is why the approved labeling recommends the lower dose.

Can CBD oil be obtained with a prescription for tuberous sclerosis in Turkey?

In Turkey, products derived from hemp are regulated 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 classified as medicines and health products are dispensed with a prescription; the regulation does not state a prescription requirement for supplement products and cosmetics with a THC content of no more than 0.3%. As of October 2026, there is no approved CBD medicine in Turkey; the active substance of the approved CBD medicine is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency), and importing it from abroad requires the agency's written approval. If you are considering using it, talk to your doctor first.

References

Show 11 references

Thiele 2021 (GWPCARE6). Double-blind, placebo-controlled RCT, 46 centers. PMID 33346789, doi:10.1001/jamaneurol.2020.4607, NCT02544763, post hoc analysis: Wu 2022, PMID 35175622
Thiele 2022 (GWPCARE6 open-label extension). Open-label extension (those who completed GWPCARE6); interim analysis. PMID 34957550, doi:10.1111/epi.17150, NCT02544750, no peer-reviewed publication, 3-year results only as a conference abstract: American Epilepsy Society 2022)
Weinstock 2024 (expanded access program). Open-label, uncontrolled expanded access program (35 centers in the US); pooled analysis of the TSC subgroup. PMID 39088193, doi:10.1002/epi4.13013, Hess 2016, PMID 27696387, 18 TSC patients (included among these 34 patients), at month 3, median reduction in weekly seizures 48.8%, ≥50% response 50%
Wray 2023 (everolimus interaction). Phase 1, single-center, open-label, fixed-sequence drug interaction study (everolimus alone and with CBD in the same person). PMID 37132402, doi:10.1002/cpdd.1262
Talwar 2023 (meta-analysis). Systematic review and meta-analysis; subgroup analysis by syndrome. PMID 36206805, doi:10.1016/j.expneurol.2022.114238
Tong 2024 (network meta-analysis). Systematic review and network meta-analysis (6 newer antiepileptic drugs; indirect comparison). PMID 38277848, doi:10.1016/j.yebeh.2024.109653
Samanta 2022 (scoping review). Scoping review, TSC only. PMID 35151190, doi:10.1016/j.yebeh.2022.108577, PMID 35581136, PMID 35500511
Cerulli Irelli 2025 (real-world, TSC subgroup). Retrospective, multicenter real-world study (27 centers, most in Europe, including Argentina); no control group. PMID 40126049, doi:10.1111/epi.18378
Ebrahimi-Fakhari 2020 (mTOR inhibitor levels). Retrospective records review; comparison before and after CBD in the same patients. PMID 31924480, doi:10.1016/j.pediatrneurol.2019.11.017
Barnett 2020 (tumor volume). Retrospective records review, single center (Massachusetts General Hospital); no control group. PMID 32409220, doi:10.1016/j.jocn.2020.05.030
Shlomovitz 2021 (Israeli TSC cohort). Retrospective, single-center cohort (2008–2018); results of CBD-based products, vagus nerve stimulation, and the ketogenic diet side by side; no randomization or placebo. PMID 34491422, doi:10.1007/s00381-021-05348-9

Points that could not be verified from the full text

No official source was found on whether the route of importing a medicine for personal treatment with a doctor's report (TİTCK permission) has been used for Epidyolex in Turkey

Trusted sources from around the world

Show 3 references

Epidiolex drug label (DailyMed)US National Library of Medicine, English, May 2026
The official prescribing information for the approved CBD medicine: approved uses, side effects, liver monitoring and interactions.
Epidyolex (European Medicines Agency)European Medicines Agency (EMA), English
The European assessment report and product information for the approved CBD medicine.
Epilepsy Foundation: Medical cannabis and CBDEpilepsy Foundation (US), English, July 2025
The difference between the approved CBD medicine and unregulated CBD products; interactions with clobazam and valproate.

These sources sell no products. All trusted sources

Research history

Here we record what changed on this page, when and why, with dates. The newest change is at the top.

October 29, 2026
The plain label changed from "Effect shown (single controlled study)" to "Proven effect", the same as the result label used elsewhere on the site. The result and the strength of evidence (moderate) did not change.
October 28, 2026
On October 28, 2026, three sources found for this page during the searches for other topics were read in their primary sources. Weight loss figures from the US prescribing information of the approved CBD medicine were added to the side effects list: in the tuberous sclerosis study, the share of patients whose weight dropped by at least 5% from baseline was 31% in the CBD group and 8% in the placebo group. The 9 tuberous sclerosis patients in a real-world study from Germany were not added to the page because their seizure results were not reported separately, and the Brazilian Academy of Neurology's 2021 position paper was not added because it brought no new data for tuberous sclerosis. The conclusion and the strength of evidence did not change.
October 27, 2026
In October 2026, PubMed, Cochrane, and ClinicalTrials.gov were systematically searched again (390 PubMed and 10 ClinicalTrials.gov records were reviewed). Studies added: Weinstock 2024 (34 patients in the expanded access program, follow-up of up to three years), Wray 2023 (everolimus interaction in healthy volunteers), Talwar 2023 and Tong 2024 (meta-analyses), Samanta 2022 (review), Cerulli Irelli 2025 (real-world data), Ebrahimi-Fakhari 2020 (everolimus and sirolimus levels), Barnett 2020 (tumor volume), and Shlomovitz 2021 (tuberous sclerosis cohort from Israel). Corrected: the definition of liver enzyme elevation in the main study and its rates by dose were added from the full text; it was noted that the 1% placebo rate in the US prescribing information is the combined figure from the studies of three diseases; the rate of discontinuation due to side effects was given using the tuberous sclerosis study's own data; it was noted that people taking everolimus or sirolimus were not included in the main study; the final results of the open-label extension on ClinicalTrials.gov were added; the absence of controlled studies with results for THC-containing products, and the strength of evidence for this area (insufficient), were stated for the first time. No second controlled study was found. The evidence level text was aligned with the badge ('Moderate' instead of 'Moderate–high'); the conclusion and the strength of evidence in the badge did not change.
Related studies: Weinstock 2024 (expanded access program), published October 2024 (PMID 39088193, doi:10.1002/epi4.13013, Hess 2016, PMID 27696387, 18 TSC patients (included among these 34 patients), at month 3, median reduction in weekly seizures 48.8%, ≥50% response 50%); Wray 2023 (everolimus interaction), published September 2023 (PMID 37132402, doi:10.1002/cpdd.1262); Talwar 2023 (meta-analysis), published January 2023 (PMID 36206805, doi:10.1016/j.expneurol.2022.114238); Tong 2024 (network meta-analysis), published March 2024 (PMID 38277848, doi:10.1016/j.yebeh.2024.109653); Samanta 2022 (scoping review), published March 2022 (PMID 35151190, doi:10.1016/j.yebeh.2022.108577, PMID 35581136, PMID 35500511); Cerulli Irelli 2025 (real-world, TSC subgroup), published July 2025 (PMID 40126049, doi:10.1111/epi.18378); Ebrahimi-Fakhari 2020 (mTOR inhibitor levels), published April 2020 (PMID 31924480, doi:10.1016/j.pediatrneurol.2019.11.017); Barnett 2020 (tumor volume), published July 2020 (PMID 32409220, doi:10.1016/j.jocn.2020.05.030); Shlomovitz 2021 (Israeli TSC cohort), published December 2021 (PMID 34491422, doi:10.1007/s00381-021-05348-9)

Older changes (6)

October 27, 2026
The plain label and plain summary were rewritten to show clearly that the result rests on a single controlled study for now ('Effect shown (single controlled study)'). The conclusion and the strength of evidence did not change.
October 27, 2026
The European product information of the approved medicine was reread. Added: the difference from placebo in the share of patients whose seizures were at least halved was not statistically significant. The Turkey row was corrected: cannabidiol oral solution is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency), and the unsourced information about the SGK (Social Security Institution) list was removed. The conclusion and the strength of evidence did not change.
October 22, 2026
The names of the conclusion labels were simplified: the "Benefit shown" label on this page became "Proven effect". The assessment did not change.
October 21, 2026
Newly published and previously missed clinical studies were searched for in PubMed and ClinicalTrials.gov. Study added: Thiele 2022 (GWPCARE6 open-label extension). The conclusion and the strength of evidence did not change.
Related studies: Thiele 2022 (GWPCARE6 open-label extension), published February 2022 (PMID 34957550, doi:10.1111/epi.17150, NCT02544750, no peer-reviewed publication, 3-year results only as a conference abstract: American Epilepsy Society 2022))
October 21, 2026
The full texts of the studies were reread and the information on the page was checked against its sources. Corrected: the dose titration information in the study table; drug interaction notes; the approved medicine's dosing schedule; the starting and titration summary; reported side effects. Points that could not be confirmed from the full text went down from 3 items to 1 item. The definition used to measure liver enzyme elevation was clarified. The conclusion and the strength of evidence did not change.
October 19, 2026
Page published. This first assessment reviewed 1 study.

Evidence changes across all topics