What does the research say?
In two large studies, patients aged 2 to 55 were assigned to groups by chance: one group received the CBD medicine in addition to their existing medicines, the other received a placebo, and neither the patients nor the doctors knew who was getting which. After 14 weeks, drop seizures had decreased by about 37–44% in the CBD groups and by 17–22% in the placebo groups.
Because people taking placebo also improved, the extra difference that can be attributed to CBD is about 17–25 percentage points. The European Medicines Agency (EMA) states that the effect has not been proven in patients who do not take the medicine clobazam, and it approves the medicine only for use together with clobazam; the US approval has no such condition. When the same studies were re-examined separately by clobazam use, CBD was also better than placebo in those not taking clobazam; the average reduction in the number of seizures was smaller in these patients, but the difference from placebo in the proportion of patients whose seizures were at least halved was similar in the two groups. Because whether patients took clobazam was not decided by chance, this comparison is not conclusive.
These results belong to the approved medicine and cannot be applied to unregulated CBD oils. Labels on market products may not be reliable; a product may contain THC or contaminants, and there are reports of increased seizures with these products. There is no controlled study of unlicensed cannabis oils in Lennox–Gastaut syndrome. A retrospective review in the US based on parent reports found a high response rate in children with LGS; but the number of children with LGS is not given in the abstract, the contents of the products had not been verified, there was no comparison group, and the response in families who had moved from another state for this treatment was twice that of families already living there. In a study following 29 people (11 with LGS) on two CBD-rich, low-THC cannabis products, no significant change in seizures was seen; this small study without a comparison group is not enough to draw any conclusion about THC-containing products.
In the extension study in which 366 patients who continued the medicine after the trial ended were followed for up to three years, the reduction in drop seizures continued. In everyday-practice data from France and Germany, the proportion of patients whose seizures were at least halved was about 44%; in two adult studies in England, this proportion was reported as 50–76%, while in a small study of children in Korea it fell to 21% at month 6. A meta-analysis that looked at children and adults separately found that age (child or adult) did not clearly change the effect. None of these studies had a comparison group, and most had manufacturer funding or authors with financial ties to the manufacturer; so they show not the size of the effect but whether it holds up in everyday practice.
Strength of evidence: ●●●● Strong evidence. Finding: Proven effect. What does this mean?
Ongoing research on this topic
Trials testing CBD for this topic on ClinicalTrials.gov: 5 under way. A trial being under way does not show that CBD works.
- NCT05044819: Phase 4, active, not recruiting, 154 participants
- NCT07728097: Phase 4, not yet recruiting, target 40 participants
- NCT06924827: Phase 4, not yet recruiting, target 25 participants
Registries in other countries also list 1 recruiting trial on this topic: other registries.
Possible side effects and drug interactions
The most common side effects were sleepiness, decreased appetite and diarrhea; these were more common at the higher dose. In one study, 14% of the CBD group and 1% of the placebo group stopped treatment because of side effects. In the other study, liver enzymes rose in 9% of those taking CBD; this risk increases markedly together with the medicine valproate. In the extension study lasting up to three years, liver enzymes rose markedly in 15% of patients, and about three quarters of them were taking valproate; in everyday-practice studies too, raised liver enzymes were seen mostly together with valproate.
CBD can slow the breakdown of some medicines in the body. It can raise the level of the active substance that clobazam is converted into in the body by about 3 times, which increases sleepiness; levels of medicines such as rufinamide and topiramate may also rise. Because seizures may 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.
| 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 |
| 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 studies and in the approved labeling, the dose is calculated as milligrams per kilogram of body weight per day. The large studies used 10 or 20 mg per kilogram per day (study dose; not a personal recommendation), and the daily amount was split into two equal parts. Under the approved labeling, the dose is adjusted slowly over weeks under a doctor's supervision; the upper limit is 20 mg per kilogram per day (study dose; not a personal recommendation). According to the labeling information, the higher dose means slightly more seizure reduction but more side effects.
The medicine is measured with a calibrated syringe, and because a fatty meal markedly increases the amount that reaches the blood, it is always taken the same way in relation to meals.
Study details (for health professionals)
In two double-blind RCTs (GWPCARE3 and GWPCARE4), prescription pure CBD added to existing medicines reduced drop seizures more than placebo over 14 weeks (about 37–44% vs. 17–22%). Because seizures also decreased in the placebo group, the absolute difference is about 17–25 points. Some patients see clear benefit and some see none. The EMA writes that efficacy has not been proven in patients not taking clobazam and restricts the approval to use with clobazam. In analyses that separated the same four RCTs by clobazam use, CBD was also better than placebo in patients not taking clobazam. For the reduction in the number of seizures, the effect was smaller in patients without clobazam (with both diseases and both doses combined, the ratio of seizure frequency vs. placebo was 0.59 with clobazam and 0.85 without; when the two doses were looked at separately, the difference was not significant in those without clobazam; manufacturer analysis, Devinsky 2020); for the proportion of patients whose seizures were at least halved, the difference from placebo was similar in the two groups (RR 1.80 and 1.85 in an independent meta-analysis; Lattanzi 2020). Because whether patients took clobazam was not decided by chance, these comparisons are not conclusive. In everyday-practice data on 92 LGS patients taking CBD without clobazam, the proportion of patients whose drop seizures were at least halved was 19% at month 3 and 30% at month 12 (Nabbout 2023; no control group, manufacturer-supported). The Stockings 2018 review in the table found CBD superior to placebo for at least halving seizures but rated the certainty of the evidence as low (GRADE); this rating was based on a search up to October 2017 and, for this outcome, on two RCTs (291 patients). Later meta-analyses combining four RCTs (Lattanzi 2018 LGS and Dravet, Lattanzi 2020) gave results in the same direction; the guide's 'Strong' rating is based on this whole body of evidence. The Cochrane review of medicines in LGS (Brigo 2021) included the two CBD studies. Because the information in the two studies' publications was not enough to calculate the response rate for all seizure types (the studies' main outcome was drop seizures), the review remained uncertain about whether CBD reduces all seizures; it did, however, find with high certainty that stopping because of side effects was more common with CBD (RR 6.62). This uncertainty comes not from a result pointing the other way but from this outcome not being reported in the studies; the guide's rating is based on drop seizures, the studies' main outcome. In a network meta-analysis comparing LGS treatments, CBD's effect on drop seizures was not significantly different from other LGS medicines such as clobazam, rufinamide and fenfluramine; high-dose clobazam was ahead in the ranking, but there are no studies comparing the medicines directly, and the comparisons are indirect (Zhu 2025). In the open-label extension of the two RCTs, the median reduction in drop seizures in 366 patients stayed between 48% and 71% for up to 156 weeks; according to the final results on ClinicalTrials.gov (a registry, not a peer-reviewed publication), 243 of the patients completed the study, and the median reduction in drop seizures over each patient's last 12 weeks in the study, including those who left early, was 59%; liver enzymes rose markedly in 15% of patients, most of whom were taking valproate (Patel 2021). Everyday-practice studies from France and Germany and two studies in adults with LGS in England point in the same direction, while in a small study of children from Korea the response decreased at month 6; these have no comparison group, and most have manufacturer funding or authors with financial ties to the manufacturer. There is no controlled study of unlicensed cannabis products in LGS. October 2026 search (PubMed, Cochrane, ClinicalTrials.gov): 2 controlled treatment studies with cannabinoids and 7 systematic reviews (one of them Cochrane) were found on this topic; these appear in the table below, together with a manufacturer-supported pooled analysis of the same studies, 10 studies without a comparison group (long-term extension, access programs, everyday practice, and unlicensed or THC-containing products), and 2 drug-level studies measuring drug interactions, mainly with clobazam (one placebo-controlled in patients with epilepsy, one in healthy volunteers). No controlled study of THC-containing products in LGS was found.
Evidence assessment: Strong (double-blind, placebo-controlled RCTs + meta-analyses)
CBD alone
The approved, purified pharmaceutical CBD reduced drop seizures as an add-on treatment in Lennox–Gastaut syndrome; this evidence does not apply to unregulated CBD oils.
Products containing THC
There is no controlled study of THC-containing products in Lennox–Gastaut syndrome. The only data come from a small observational study: in 29 people (11 with LGS) followed for at least 24 weeks on two CBD-rich, low-THC cannabis products (at most 6 mg of THC a day), no significant change in seizure frequency was seen.
Evidence: Insufficient: there is no controlled study of a THC-containing product in LGS; there is only a small observational study without a comparison group that included 11 LGS patients
Approved drug regimen
FDA (≥1 year, no clobazam requirement): start at 2.5 mg/kg twice daily (5 mg/kg/day); after 1 week, the maintenance dose is 5 mg/kg twice daily (10 mg/kg/day). If further seizure reduction is needed, increase weekly by 2.5 mg/kg twice daily up to a maximum of 10 mg/kg twice daily (20 mg/kg/day); for faster titration, increases no more often than every other day. Label: 20 mg/kg/day gives slightly more seizure reduction but more side effects. EMA (≥2 years, add-on treatment only together with clobazam): 5 mg/kg/day for 1 week, then maintenance 10 mg/kg/day; increases above 10 mg/kg/day only with an individual benefit–risk assessment and a full monitoring schedule, maximum 20 mg/kg/day. Liver impairment: moderate (Child-Pugh B) start at 1.25 mg/kg twice daily, severe (Child-Pugh C) 0.5 mg/kg twice daily. Stopping is done gradually. Source: FDA label (05/2026) §2.1–2.2, §2.5–2.6; EMA product information §4.1–4.2 (last updated in the EPAR on August 20, 2026). Turkey: Epidyolex/cannabidiol is not on the list of licensed products of TİTCK (Turkish Medicines and Medical Devices Agency) (October 16, 2026); however, on TİTCK's Foreign Active Substance List (September 28, 2026), cannabidiol oral solution (YDN02BG1099) is listed as a red-prescription medicine among those that cannot be imported without TİTCK's written approval.
Dose range in studies
In the labeling and RCTs, 10–20 mg/kg/day (split into two equal doses); in the open-label expanded access program, up to a ceiling of 25–50 mg/kg/day; in the open-label extension study, at most 30 mg/kg/day (mean 24 mg/kg/day); in everyday-practice studies in Europe and England, the median dose was mostly 10–15 mg/kg/day
Starting dose and titration
Labeling: start at 5 mg/kg/day, then 10 mg/kg/day after 1 week; if needed, increase weekly by 5 mg/kg/day up to a maximum of 20 mg/kg/day. In the RCTs, a 2-week titration (to 10 mg/kg/day in 7 days, to 20 mg/kg/day in 11 days), followed by 12 weeks of maintenance
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 |
|---|---|---|---|---|---|---|
| Devinsky 2018 (GWPCARE3) Double-blind, placebo-controlled RCT, 30 centers | 225 Lennox–Gastaut syndrome, aged 2–55 | CBD oral solution (pure CBD) | 10 or 20 mg/kg/day, 2 equal doses 2 weeks (reached 10 mg/kg/day in 7 days and 20 mg/kg/day in 11 days; CT.gov NCT02224560) | 14 weeks | Reduction in drop seizures 41.9% (20 mg) and 37.2% (10 mg), placebo 17.2%; p=0.005 and p=0.002 Side effects: Sleepiness, decreased appetite, diarrhea (more common at the higher dose). Discontinuation due to side effects: 6 at 20 mg, 1 at 10 mg. Transaminase elevation in 14 (9%) of those taking CBD | PMID 29768152, doi:10.1056/NEJMoa1714631, NCT02224560, PMID 33797076, the authors include employees of the manufacturer): the difference from placebo appeared on day 6 (nominal p = 0.008), Auvin 2023, PMID 37052803, Specchio 2025, PMID 40775196, funded by the manufacturer): the threshold at which caregivers said 'slightly improved' was about a 31% reduction in drop seizures |
| Thiele 2018 (GWPCARE4) Double-blind, placebo-controlled phase 3 RCT, 24 centers | 171 Lennox–Gastaut syndrome, aged 2–55 | Oral CBD (pure CBD) | 20 mg/kg/day 2 weeks (reached 20 mg/kg/day in 11 days; CT.gov NCT02224690) | 14 weeks | Median reduction in drop seizures 43.9% (placebo 21.8%); estimated median difference −17.21 (p=0.0135) Side effects: Side effects 86% vs. 69%: diarrhea, sleepiness, fever, decreased appetite, vomiting. Discontinuation due to side effects 14% vs. 1%. 1 death (judged unrelated to the drug) | PMID 29395273, doi:10.1016/S0140-6736(18)30136-3, NCT02224690 |
| Lattanzi 2018 (LGS and Dravet) Systematic review and meta-analysis (4 RCTs) | 550 LGS and Dravet syndrome | Pharmaceutical CBD (pure) | 10 and 20 mg/kg/day | Difference in seizure frequency vs. placebo 19.5 points (10 mg/kg/day) and 19.9 points (20 mg/kg/day). ≥50% reduction in all seizures 37.2% vs. 21.2% (20 mg; RR 1.76) Side effects: Discontinuation due to side effects 8.9% vs. 1.8% (RR 5.59); RR 6.89 at 20 mg, not significant at 10 mg | PMID 30390221, doi:10.1007/s40265-018-0992-5 | |
| Lattanzi 2020 Systematic review and meta-analysis (4 RCTs) | 714 LGS and Dravet syndrome | Pharmaceutical CBD (pure) | not reported | ≥50% response: without clobazam 29.1% vs. 15.7% (RR 1.80); with clobazam 52.9% vs. 27.8% (RR 1.85). Clobazam was not randomized; the authors warn about this | PMID 32452532, doi:10.1111/epi.16546 | |
| Stockings 2018 Systematic review (6 RCTs + 30 observational studies) | not reported Drug-resistant epilepsy; mean age 16.1 | Pharmaceutical CBD (RCTs) + various products in observational studies | 20 mg/kg/day (RCT) | ≥50% seizure reduction RR 1.74 (NNT 8); GRADE: low Side effects: Side effects RR 1.24; serious side effects RR 2.55 | PMID 29511052, doi:10.1136/jnnp-2017-317168 | |
| Brigo 2021 (Cochrane) Cochrane systematic review and meta-analysis (all seizure medicines in LGS; 11 RCTs, 2 of them CBD) | 1,277 in the review; CBD comparison 2 RCTs, 396 patients Lennox–Gastaut syndrome; children, adolescents and adults | Purified CBD oral solution (GWPCARE3 and GWPCARE4) | 10 and 20 mg/kg/day | Search up to March 2020; CBD studies 14 weeks | The response rate for all seizure types, which the review looked at, could not be calculated because the information in the two CBD studies' publications was not enough (the two studies' own main outcome was drop seizures); in its plain language summary, the review writes that it is uncertain whether CBD reduces all seizure types. Withdrawal from the study because of side effects was more common with CBD than placebo: RR 6.62 (95% CI 1.56–28.15; 82 more per 1,000 patients), high certainty of evidence (GRADE). There are no studies comparing LGS medicines directly. The review authors have no reported ties to the CBD manufacturer. Side effects: Discontinuation due to side effects RR 6.62 (95% CI 1.56–28.15; high certainty) | PMID 33825230, doi:10.1002/14651858.CD003277.pub4, Update of the 2013 Cochrane review, PMID 35322410 |
| Lattanzi 2018 (LGS meta-analysis) Systematic review and meta-analysis (2 RCTs, LGS only) | 396 Lennox–Gastaut syndrome | Pharmaceutical CBD (pure) | 10 and 20 mg/kg/day | 14 weeks (studies) | At least a halving of drop seizures in 40.0% with CBD and 19.3% with placebo (RR 2.12; 95% CI 1.48–3.03; p<0.001). At least a halving of non-drop seizures 49.4% vs. 30.4% (RR 1.62; 95% CI 1.09–2.43; p=0.018). A pooling of the same two RCTs; no new patient data. Side effects: Any side effect RR 1.24 (95% CI 1.11–1.38); stopping the drug RR 4.93 (95% CI 1.50–16.22). Significantly associated with CBD: sleepiness, decreased appetite, diarrhea, liver enzyme elevation | PMID 30132269, doi:10.1007/s40263-018-0558-9 |
| Devinsky 2020 (clobazam subgroups) The manufacturer's post hoc analysis separating 4 RCTs (GWPCARE1–4) by clobazam use and pooling them (stratified meta-analysis) | 714 (396 LGS, 318 Dravet); CBD 429 (240 with clobazam, 189 without clobazam), placebo 285 LGS (aged 2–55) and Dravet syndrome; in the LGS studies, 49% of patients were taking clobazam | Epidiolex/Epidyolex (100 mg/mL oral solution, purified CBD) | 10 and 20 mg/kg/day | 14 weeks | With both doses and both diseases combined, the ratio of seizure frequency vs. placebo was 0.59 with clobazam (95% CI 0.52–0.68) and 0.85 without clobazam (95% CI 0.73–0.98; p=0.023): on this measure, the effect was smaller without clobazam, and the dose groups were not significant individually. The OR for at least a halving, however, was similar in the two groups: 2.51 (1.69–3.71) with clobazam and 2.40 (1.38–4.16) without clobazam. In LGS, in the 20 mg/kg/day group without clobazam, seizure counts increased in more patients than with placebo. Clobazam use was not decided by chance; about two thirds of those not taking clobazam had tried and stopped clobazam before, and the authors write that this may have affected the result. All authors (7/7) were employees (5) or consultants and investigators (2) of the manufacturer; the manufacturer funded it. Side effects: Sleepiness, rash, pneumonia and aggression were more common together with clobazam; discontinuation due to side effects at 20 mg/kg/day was 13.0% with clobazam and 8.0% without | PMID 32592183, doi:10.1111/ane.13305, Gunning 2021, PMID 32969022, in LGS, the ratio of drop seizures vs. placebo was 0.70 in all patients (95% CI 0.62–0.80) and 0.56 with clobazam (0.47–0.67), OR for at least a halving 3.14 (2.04–4.81) and 3.48 (1.96–6.17), 3 of 7 authors are employees of the manufacturer, and 4 are consultants or investigators of the manufacturer |
| Zhu 2025 (network meta-analysis) Systematic review and network meta-analysis (drug and non-drug treatments in LGS; 12 RCTs) | 1,445 (CBD 235 patients, 2 RCTs) Lennox–Gastaut syndrome | Purified CBD (GWPCARE3 and GWPCARE4); comparators were fenfluramine, clobazam, rufinamide, felbamate, lamotrigine, topiramate, deep brain stimulation and corpus callosotomy | CBD 10 and 20 mg/kg/day | At least a halving of drop seizures, compared with usual treatment: CBD 10 mg/kg/day OR 2.8 (95% CI 1.4–5.7), 20 mg/kg/day OR 3.1 (1.9–5.2); clobazam 1 mg/kg/day OR 7.8, rufinamide OR 4.6, fenfluramine OR 3.0–3.5. At the top of the ranking were clobazam 1 mg/kg/day, corpus callosotomy and rufinamide; the comparisons are indirect (there are no studies comparing the medicines directly), and the authors ask that the ranking be read with caution. The authors report no conflicts of interest. Side effects: In the ranking for likelihood of side effects, CBD 20 mg/kg/day was first, followed by fenfluramine 0.7 mg/kg/day; for serious side effects, CBD 10 mg/kg/day came after lamotrigine | PMID 40078280, doi:10.3389/fphar.2025.1522543 | |
| de Oliveira 2026 (meta-analysis by syndrome and age) Systematic review and meta-analysis (developmental and epileptic encephalopathies; 5 RCTs + 41 non-randomized studies); prespecified subgroups by age and syndrome | 2,592 Developmental and epileptic encephalopathies (LGS, Dravet, Doose, CDKL5 and others); children, adults and mixed age groups | Pharmaceutical-grade (approved) CBD | Varied by study (no details in the abstract) | Search up to October 12, 2025 | Across all studies, the pooled rate of at least a halving was 49.9% (95% CI 44.9–55.0), at least a 75% reduction 26.7% (22.0–32.0), and seizure freedom 5.7% (4.0–8.0). Age (child, adult), syndrome (including LGS), dose, clobazam use and length of follow-up did not consistently change the effect; some subgroup differences that were significant rest on small groups and do not meet credibility criteria. Because most studies were uncontrolled, the pooled rates are not differences from placebo; an LGS-specific rate is not in the abstract. The authors report no conflicts of interest. Side effects: Sleepiness, decreased appetite, diarrhea, fatigue and behavior changes; liver enzyme elevation mostly together with valproate, and it resolved when the dose was lowered or the drug stopped | PMID 42185726, doi:10.1007/s40263-026-01301-z |
| Patel 2021 (GWPCARE5, LGS) Open-label extension study (those who completed GWPCARE3 and GWPCARE4); no control group | 366 (99.5% of the 368 patients who completed the RCTs) Lennox–Gastaut syndrome (children and adults) | Epidiolex/Epidyolex (100 mg/mL oral solution, plant-derived purified CBD) | Target maintenance 20 mg/kg/day; could be lowered or raised to at most 30 mg/kg/day based on response and tolerability; mean modal dose 24 mg/kg/day To 20 mg/kg/day over 2 weeks | Median 1,090 days, mean 826 days (3–1,421 days); efficacy up to 156 weeks | Over 12-week periods up to 156 weeks, the median reduction was 48–71% for drop seizures and 48–68% for total seizures. In every period, at least 87% of patients or caregivers reported improvement in overall condition. According to the final results on ClinicalTrials.gov (a registry, not a peer-reviewed publication), 243 of 366 patients completed the study (of the 123 who left, 48 at the patient's or family's request, 38 because of side effects, 12 for lack of efficacy, 11 by investigator decision); over each patient's last 12 weeks in the study (regardless of when they left; 363 patients), the median reduction was 59.4% for drop seizures (IQR −87.1 to −15.4) and 51.9% for total seizures (IQR −84.7 to −13.3). No control group, and only those who completed the first study and continued were included. Conducted by the manufacturer (GW Research); 2 of 13 authors are employees of the manufacturer, and the conflict of interest statements of the others could not be read (in the interim analysis of the same study, all 8 authors had ties to the manufacturer). Side effects: Side effects 96%, serious side effects 42%, discontinuation due to side effects 12%. Most common: seizures (39%), diarrhea (38%), fever (34%), sleepiness (29%). Liver enzymes (transaminases) >3×ULN in 55 patients (15%); 40 of them (73%) were taking valproate. In the final results in the registry, serious side effects in 157 patients (42.9%), 12 deaths (the registry does not state whether they were related to the drug) | PMID 34287833, doi:10.1111/epi.17000, NCT02224573, separate final results for LGS in the registry, posted on February 3, 2022). Interim analysis: Thiele 2019, PMID 30740695, median 38 weeks, transaminase elevation 10.1% (29 of 37 patients were taking valproate), discontinuation due to side effects 9.6% |
| Laux 2019 Open-label expanded access program (EAP), LGS/Dravet subgroup | 152 (58 Dravet, 94 LGS) LGS and Dravet syndrome | Epidiolex 100 mg/ml (pure CBD) | 2–10 mg/kg/day starting → 25–50 mg/kg/day ceiling; median 21–25 mg/kg/day in weeks 12–96 By center | Median 78.3 weeks | At week 12, a 50% reduction in major motor seizures and 44% in all seizures; consistent up to 96 weeks (no control group) Side effects: Sleepiness 30%, diarrhea 24%; 28% stopped (mostly for lack of efficacy, 20%) | PMID 31022635, doi:10.1016/j.eplepsyres.2019.03.015 |
| VanLandingham 2020 (clobazam interaction, in patients) Phase 2, double-blind, placebo-controlled, randomized (4:1) drug interaction study; not designed to measure efficacy | 20 randomized (16 CBD, 4 placebo); 13 in the drug-level analysis (10 CBD, 3 placebo) Epilepsy patients aged 18–65 with uncontrolled seizures taking a stable dose of clobazam (at most 20 mg a day); syndrome not specified | Epidiolex (100 mg/mL oral solution, purified CBD) or placebo, added to clobazam | CBD 20 mg/kg/day, 2 equal doses; clobazam 5–20 mg a day (unchanged) To 20 mg/kg/day over 10 days | 33 days (10-day dose increase, 21 days at a fixed dose) | CBD did not change the level of clobazam itself (total exposure ratio 1.1; 90% CI 0.9–1.2); the peak level of clobazam's active breakdown product N-desmethylclobazam rose 2.2-fold (90% CI 1.4–3.5) and its total exposure 2.6-fold (2.0–3.6); it did not change in those taking placebo (1.2 and 1.0). Few patients, and efficacy was not measured. The manufacturer's study; all 4 authors were employees of the manufacturer (one at the time of the study). Side effects: Side effects in 13 of 16 patients with CBD and 2 of 4 with placebo; most common were diarrhea (6/16), nausea and vomiting (3/16), sleepiness, lightheadedness and skin inflammation; 1 patient was withdrawn because of a serious side effect (seizure cluster), 1 patient left because of side effects; no deaths | PMID 32652616, doi:10.1002/jcph.1634, NCT02565108 |
| Morrison 2019 (clobazam, stiripentol and valproate interaction) Phase 1, open-label, fixed-sequence drug interaction study (in the same person, first the single drug, then with CBD) | 78 enrolled; 77 received a drug, 70 completed (12 people in the group adding CBD to clobazam; the article's results section says 13) Healthy adult volunteers (aged 18–55), the Netherlands | Epidiolex (100 mg/mL oral solution) + clobazam, stiripentol or valproate | CBD 750 mg twice daily (equivalent to the highest dose in the phase 3 studies); clobazam 5 mg, stiripentol 750 mg, valproate 500 mg twice daily After cases of rash, a 3–10-day dose increase was added to the protocol | Co-administration for 7–21 days depending on the group | CBD increased the peak level and total exposure of clobazam's active breakdown product N-desmethylclobazam about 3.4-fold (in everyone in the group); clobazam itself increased 1.2-fold. Stiripentol exposure increased 1.3–1.6-fold; the valproate level did not change. Clobazam increased CBD's active breakdown product 7-OH-CBD 1.5–1.7-fold. No placebo group. The manufacturer's study; 2 of 4 authors are employees of the manufacturer and 2 are consultants to the manufacturer. Side effects: 6 people were withdrawn because of side effects (3 when clobazam was added, 3 when valproate was added); the study was temporarily paused because of cases of rash, and no link to the drug could be established; no serious side effects or deaths | PMID 30791225, doi:10.1002/cpdd.665 |
| D'Onofrio 2020 (France, slow dose increase) Prospective, open-label, multicenter study (7 rare epilepsy centers in France; under a temporary authorization for use); no control group | 125 (62 LGS, 48 Dravet, 5 TSC, 10 other) Children aged 2–18 with drug-resistant epilepsy | Purified CBD oral solution (Epidyolex; under a temporary authorization for use) | Target of 10 mg/kg/day over at least 1 month, then at most 20 mg/kg/day; median 10, 14 and 15.5 mg/kg/day at months 1, 2 and 6 Started at 2.5 mg/kg/day and increased by 2.5 mg/kg/day each week (10 mg/kg/day in 4 weeks) | 6 months | At month 6, total seizure frequency decreased by a mean of 41% (SD 37.5); at least a halving in 28 patients (37.8%). In patients with LGS (41 patients with month 6 data), seizures decreased by a mean of 42.1% and were at least halved in 43.9%; efficacy and side effects did not differ between LGS and Dravet or between those taking and not taking clobazam. No control group; the conclusion that slow titration was better tolerated rests on an indirect comparison with earlier studies. The manufacturer is not in the funding section; 2 of 16 authors report receiving meeting fees from the manufacturer. Two of the centers (Paris Necker, Lyon) are also in Nabbout 2023; patients may partly overlap. Side effects: Side effects 48.8% (sleepiness in 26, weakness/fatigue in 20, behavior problems in 16 patients); transaminase elevation ≥3-fold in 11 patients, all taking valproate and clobazam together; 26 patients (20.8%) stopped (mostly for lack of efficacy); 1 sudden unexpected death in epilepsy | PMID 32903409, doi:10.3389/fneur.2020.00829 |
| Nabbout 2023 (use without clobazam) Retrospective chart review (the manufacturer's study GWEP20052), European early access program; no control group | 114 enrolled; 107 analyzed (92 LGS, 15 Dravet) LGS and Dravet, age ≥2; people who used CBD for at least 3 months without taking clobazam (mean age 14.5 in LGS); based on the authors' institutions, the centers were in France, England, Italy and Spain | Epidyolex (100 mg/mL oral solution) | Time-weighted mean dose 13.54 mg/kg/day in LGS | Up to 12 months | In LGS, the median change in 28-day seizure frequency over 3-month periods ranged from −6.2% to −20.9%; at least a halving of drop seizures in 19% at month 3 (69 patients) and 30% at month 12 (53 patients). The proportion staying on CBD without clobazam (LGS and Dravet together) was 94%, 80%, 69% and 63% at months 3, 6, 9 and 12. No control group. Manufacturer-supported; 2 of 12 authors are employees of the manufacturer (Jazz), and 7 more report receiving consulting fees, speaker fees or travel support from the manufacturer. Some of the French centers are also in D'Onofrio 2020; patients may partly overlap. Side effects: Side effects 31% (most commonly sleepiness, seizures, diarrhea, decreased appetite); 2 patients stopped because of side effects; liver enzyme elevation in 4 LGS patients | PMID 37331197, doi:10.1016/j.seizure.2023.05.003 |
| Strzelczyk 2025 (Germany, real-world) Retrospective, multicenter chart review (6 epilepsy centers in Germany); no control group | 202 (159 LGS, 34 Dravet, 9 TSC) LGS, Dravet and TSC; median age 18 (0.3–72); a median of 6 earlier medicines; 64.2% of those with LGS were taking clobazam | Epidyolex (100 mg/mL oral solution); through early access or by prescription (2019–2023) | Median target dose 11.1 mg/kg/day (<6 years 17.6; 6–17 years 15.2; ≥18 years 9.9) | Up to 12 months | At least a halving of total seizures in 43.3% at month 3 (194 patients) and 44.0% at month 12 (168 patients); 37.0–52.5% across age groups. Improvement in 62% by the doctor's assessment. Staying on CBD for one year (Kaplan–Meier) was 61.0% in LGS; no difference by age, syndrome or clobazam use. Seizure results are not given separately by syndrome; no control group. Funded by the manufacturer (GW/Jazz); 9 of 11 authors report receiving fees or support from the manufacturer. Side effects: Side effects 41.6%: sleepiness/apathy 20.3%, diarrhea 13.4%; liver enzyme elevation 1.0% | PMID 40650804, doi:10.1007/s40120-025-00788-w, Subanalysis of the same study in those using it together with clobazam: Strzelczyk 2025, PMID 40073826, 126 patients, 102 with LGS) |
| Elbadri 2024 (adult LGS, Birmingham) Retrospective, single-center follow-up study (England); no control group | 50 Adults aged 16 and over with LGS | Approved purified CBD (together with clobazam, per the NICE recommendation) | From 1 mg/kg/day up to 10 mg/kg/day Slow increase (from 1 to 10 mg/kg/day) | 6–24 months | At least a halving of focal and generalized seizures in 76% of patients; no one became seizure-free. At last follow-up, 94% were still on the medicine. No control group, single center. 2 of 8 authors report receiving speaker fees from the manufacturer (Jazz). Side effects: The abstract says 'well tolerated'; side effect rates are not in the abstract | PMID 38908033, doi:10.1016/j.yebeh.2024.109904 |
| Aung 2026 (adult LGS, London) Retrospective, single-center follow-up study (King's College Hospital, London); no control group | 79 Adults with LGS (median age 29); together with clobazam, per NICE | Approved purified CBD oral solution | Median 2.4 mg/kg twice daily at the start; median 5.1 at month 6 and 7.4 mg/kg twice daily at last follow-up Per the doctor | Median 41 months | At least a halving across all seizure types in 59.5% at month 6 and 67.1% at last follow-up; in 78 patients with drop seizures, 50% at month 6 and 61.5% at last follow-up. Seizure-free days per month rose from 5.7 to 12.5; seizure-related hospital admissions and injuries decreased. At last follow-up, 86% were still on the medicine. Based on caregiver diaries, no control group. The first author's research fellowship was paid by the manufacturer (Jazz), which also reviewed the article; 6 of 10 authors report financial ties to the manufacturer. Side effects: Sleepiness in 33, diarrhea in 24, abnormal liver tests in 12 patients (10/39 of those taking valproate, 2/40 of those not; none led to stopping), worsening behavior in 11; doses of other medicines were adjusted in 51 patients; 4 deaths (judged unrelated to CBD) | PMID 42798297, doi:10.1111/ene.70760 |
| Koo 2020 (Korea) Retrospective, single-center observational study (Severance Children's Hospital, Seoul); no control group | 44 (34 LGS, 10 Dravet) Children with LGS and Dravet (aged 1.2–15.8; mean 5.1); 81.8% were taking valproate | Epidiolex (purified CBD) | Started at 5 mg/kg/day and maintained at 10 mg/kg/day | 6 months | In the LGS group at month 3, seizures decreased in 52.9% of patients and were at least halved in 32.3% (23.5% seizure-free); at month 6, these figures fell to 29.4% and 20.6%. Based on caregiver report, no control group. The authors report no conflicts of interest. Side effects: Side effects 36.3%, most commonly gastrointestinal complaints (15.9%; mild liver enzyme elevation in 1 patient) and behavior changes (11.4%); no life-threatening side effects | PMID 33372424, doi:10.3346/jkms.2020.35.e427, Prospective study from the same center: Kim 2022, PMID 36062772, NCT04611438, 30 LGS + 11 Dravet): at least a halving in 26.8% at month 6, quality of life score did not change, PMID 36854341, the dose was started at 2.5–5 mg/kg/day and raised to 10 mg/kg/day over 2 weeks, and could be increased up to 20 if needed. The periods overlap (March–October 2019 and May 2019–December 2020), and the first author of Koo 2020 is also an author of Kim 2022, some patients are most likely shared |
| Press 2015 (unlicensed cannabis extracts) Retrospective chart review (single center, Colorado); based on parent report; no control group | 75 (number of patients with LGS not in the abstract) Children and adolescents with drug-resistant epilepsy (Dravet, Doose, LGS and others) | Oral cannabis extracts (unlicensed, CBD-rich; content and THC ratio not verified) | not reported (in the abstract) | not reported (in the abstract) | In the whole group, 33% of families reported a more than 50% reduction in seizures; in LGS this figure was 88.9% (Dravet 23%, Doose 0%). Response was 47% in families who had moved to Colorado for this treatment and 22% in those already living there. No improvement was seen on the EEGs of responders. No control group, product content unknown; the authors point to confounding factors and call for controlled studies. Side effects: Side effects 44%: increased seizures 13%, sleepiness/fatigue 12%; developmental regression, abnormal movements, status epilepticus requiring intubation and death were reported rarely | PMID 25845492, doi:10.1016/j.yebeh.2015.02.043 |
| Devinsky 2022 (THC-containing medical cannabis) Prospective observational study (structured monitoring in a residential care center); no control group or blinding | 29 (11 LGS) People aged 12–46 with drug-resistant epilepsy (11 LGS, 15 focal or multifocal, 3 generalized epilepsy) | Medical cannabis tablets, THC:CBD 1:20 and/or 1:50 (Columbia Care) | At most 6 mg THC a day; at the highest dose, a mean of 5.9 mg THC and 117.2 mg CBD a day (0.11 and 2.3 mg/kg/day) Up to a predefined highest dose; if the response was inadequate, patients were switched to the 1:50 product | At least 24 weeks | At the stable highest dose, convulsive seizure frequency, seizure duration, post-seizure time and rescue medicine use did not change significantly from baseline; in patients with LGS, the result was no different from the other syndromes. No difference in behavior or sleep duration. The CBD doses were much lower than in the approved medicine's studies. The company that makes the product (Columbia Care) partly funded the study. Side effects: 10 side effects in 6 patients (including vomiting, gum or nose bleeding and 1 status epilepticus), all temporary and most unrelated to the drug; 16 serious side effects in 7 patients (5 of them pneumonia), all judged unrelated to the drug; 2 patients were withdrawn from the study because of serious side effects (one for increased seizures, one for increased behavior problems) | PMID 35267245, doi:10.1002/acn3.51537 |
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%); 17% at 20 mg/kg/day, 1% at 10 mg/kg/day; >20×ULN <1%
- ALT >3×ULN with valproate: valproate+clobazam 30%, valproate alone 21%, clobazam alone 4%, neither 3% (FDA)
- Drowsiness/sedation with clobazam 46% (without clobazam 16%)
- Discontinuation due to side effects 8.9% vs. 1.8% (Lattanzi 2018, LGS and Dravet meta-analysis)
- 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)
- Long term (LGS extension study GWPCARE5, median 1,090 days): side effects 96%, serious side effects 42%, discontinuation due to side effects 12%; transaminases >3×ULN 15%, 73% of whom were taking valproate (Patel 2021)
- Weight loss: in the LGS/Dravet controlled studies, a decrease in measured weight of at least 5% from baseline was seen in 16% of those taking CBD and 8% with placebo; the decrease appeared to be dose-related (18% at 20 mg/kg/day, 9% at 10 mg/kg/day). Weight loss reported as a side effect was 3% at 10 mg/kg/day, 5% at 20 mg/kg/day and 1% with placebo. In the TSC study (25 mg/kg/day), weight loss of at least 5% was 31% 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 drugs should not be stopped on one's 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 the studies, stopping was done over ~10 days, reducing 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 meals; with a high-fat meal, Cmax increases 5-fold and AUC 4-fold. It is measured with a calibrated syringe; a household spoon is not suitable
- Unregulated (artisanal) CBD/cannabis oils do not replace 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) (total exposure 2.6-fold in a placebo-controlled study in epilepsy patients taking clobazam, VanLandingham 2020; 3.4-fold in healthy volunteers, Morrison 2019); clobazam also increases 7-OH-CBD (AUC 47%). If drowsiness occurs, lowering the clobazam dose is considered
- 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; 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 at most 2-fold may be considered based on response and tolerability
- CYP1A2 substrates (theophylline, tizanidine, caffeine): caffeine AUC increased 95%; dose reduction is considered for narrow-range medicines
- 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%)
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 right for you or your child.
- Review all the medicines being taken, especially clobazam and valproate, together for interactions.
- Plan the schedule of liver tests from the start; if there is unexplained nausea, abdominal pain, yellowing of the skin or eyes (jaundice) or dark urine, tell your doctor right away.
- Do not stop epilepsy medicines or CBD suddenly.
- If a product from the market is being considered, review its label and independent laboratory certificate of analysis (COA) together 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.
Bottom line
In Lennox–Gastaut syndrome, the approved CBD medicine is an add-on treatment option that can reduce drop seizures and is supported by good studies. It does not give the same benefit to everyone, and it requires regular monitoring. There is no evidence that CBD oils sold on the market will have the same effect.
Frequently asked questions
Does CBD oil work for Lennox–Gastaut syndrome?
When an approved, purified CBD medicine was added to existing medicines, it reduced drop seizures more than an inactive substance (placebo); the evidence for this is strong. The benefit is not the same in every patient, and this result does not apply to unregulated CBD oils.
Can CBD oil be used in children?
The approved CBD medicine has also been studied in children; it is approved from age 1 in the US and from age 2 in the European Union. It is used by decision of a pediatric neurologist and with regular liver tests. CBD oils sold on the market do not replace this medicine.
Does CBD stop seizures completely?
In the studies, seizures decreased, but in most patients they did not stop completely. In an expanded access program that followed 152 patients with LGS and Dravet syndrome, the proportion of patients in whom all seizures stopped at week 12 was 5%. In an analysis combining 46 studies (41 of them non-randomized) in severe epilepsies that include Lennox–Gastaut syndrome (developmental and epileptic encephalopathies), this proportion was about 6%; in a study of 50 adults with LGS, no one became seizure-free. Some patients saw clear benefit, while others saw none. CBD was used in addition to, not instead of, existing treatment.
What should we know if we take clobazam?
CBD can raise the level of the active substance that clobazam is converted into in the body by about 3 times; this increases sleepiness. In Europe, the medicine is in fact approved for use together with clobazam. Better results than placebo were also seen in patients not taking clobazam; the reduction in the number of seizures was smaller in some analyses, but this comparison was not made by chance assignment. If sleepiness occurs, the doctor may consider lowering the clobazam dose.
Can CBD oil be obtained with a prescription for Lennox–Gastaut syndrome in Turkey?
In Turkey, products derived from cannabis 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 at most 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 thinking of using it, talk to your doctor first.
References
Show 22 references
- Devinsky 2018 (GWPCARE3). Double-blind, placebo-controlled RCT, 30 centers. PMID 29768152, doi:10.1056/NEJMoa1714631, NCT02224560, PMID 33797076, the authors include employees of the manufacturer): the difference from placebo appeared on day 6 (nominal p = 0.008), Auvin 2023, PMID 37052803, Specchio 2025, PMID 40775196, funded by the manufacturer): the threshold at which caregivers said 'slightly improved' was about a 31% reduction in drop seizures
- Thiele 2018 (GWPCARE4). Double-blind, placebo-controlled phase 3 RCT, 24 centers. PMID 29395273, doi:10.1016/S0140-6736(18)30136-3, NCT02224690
- Lattanzi 2018 (LGS and Dravet). Systematic review and meta-analysis (4 RCTs). PMID 30390221, doi:10.1007/s40265-018-0992-5
- Lattanzi 2020. Systematic review and meta-analysis (4 RCTs). PMID 32452532, doi:10.1111/epi.16546
- Stockings 2018. Systematic review (6 RCTs + 30 observational studies). PMID 29511052, doi:10.1136/jnnp-2017-317168
- Brigo 2021 (Cochrane). Cochrane systematic review and meta-analysis (all seizure medicines in LGS; 11 RCTs, 2 of them CBD). PMID 33825230, doi:10.1002/14651858.CD003277.pub4, Update of the 2013 Cochrane review, PMID 35322410
- Lattanzi 2018 (LGS meta-analysis). Systematic review and meta-analysis (2 RCTs, LGS only). PMID 30132269, doi:10.1007/s40263-018-0558-9
- Devinsky 2020 (clobazam subgroups). The manufacturer's post hoc analysis separating 4 RCTs (GWPCARE1–4) by clobazam use and pooling them (stratified meta-analysis). PMID 32592183, doi:10.1111/ane.13305, Gunning 2021, PMID 32969022, in LGS, the ratio of drop seizures vs. placebo was 0.70 in all patients (95% CI 0.62–0.80) and 0.56 with clobazam (0.47–0.67), OR for at least a halving 3.14 (2.04–4.81) and 3.48 (1.96–6.17), 3 of 7 authors are employees of the manufacturer, and 4 are consultants or investigators of the manufacturer
- Zhu 2025 (network meta-analysis). Systematic review and network meta-analysis (drug and non-drug treatments in LGS; 12 RCTs). PMID 40078280, doi:10.3389/fphar.2025.1522543
- de Oliveira 2026 (meta-analysis by syndrome and age). Systematic review and meta-analysis (developmental and epileptic encephalopathies; 5 RCTs + 41 non-randomized studies); prespecified subgroups by age and syndrome. PMID 42185726, doi:10.1007/s40263-026-01301-z
- Patel 2021 (GWPCARE5, LGS). Open-label extension study (those who completed GWPCARE3 and GWPCARE4); no control group. PMID 34287833, doi:10.1111/epi.17000, NCT02224573, separate final results for LGS in the registry, posted on February 3, 2022). Interim analysis: Thiele 2019, PMID 30740695, median 38 weeks, transaminase elevation 10.1% (29 of 37 patients were taking valproate), discontinuation due to side effects 9.6%
- Laux 2019. Open-label expanded access program (EAP), LGS/Dravet subgroup. PMID 31022635, doi:10.1016/j.eplepsyres.2019.03.015
- VanLandingham 2020 (clobazam interaction, in patients). Phase 2, double-blind, placebo-controlled, randomized (4:1) drug interaction study; not designed to measure efficacy. PMID 32652616, doi:10.1002/jcph.1634, NCT02565108
- Morrison 2019 (clobazam, stiripentol and valproate interaction). Phase 1, open-label, fixed-sequence drug interaction study (in the same person, first the single drug, then with CBD). PMID 30791225, doi:10.1002/cpdd.665
- D'Onofrio 2020 (France, slow dose increase). Prospective, open-label, multicenter study (7 rare epilepsy centers in France; under a temporary authorization for use); no control group. PMID 32903409, doi:10.3389/fneur.2020.00829
- Nabbout 2023 (use without clobazam). Retrospective chart review (the manufacturer's study GWEP20052), European early access program; no control group. PMID 37331197, doi:10.1016/j.seizure.2023.05.003
- Strzelczyk 2025 (Germany, real-world). Retrospective, multicenter chart review (6 epilepsy centers in Germany); no control group. PMID 40650804, doi:10.1007/s40120-025-00788-w, Subanalysis of the same study in those using it together with clobazam: Strzelczyk 2025, PMID 40073826, 126 patients, 102 with LGS)
- Elbadri 2024 (adult LGS, Birmingham). Retrospective, single-center follow-up study (England); no control group. PMID 38908033, doi:10.1016/j.yebeh.2024.109904
- Aung 2026 (adult LGS, London). Retrospective, single-center follow-up study (King's College Hospital, London); no control group. PMID 42798297, doi:10.1111/ene.70760
- Koo 2020 (Korea). Retrospective, single-center observational study (Severance Children's Hospital, Seoul); no control group. PMID 33372424, doi:10.3346/jkms.2020.35.e427, Prospective study from the same center: Kim 2022, PMID 36062772, NCT04611438, 30 LGS + 11 Dravet): at least a halving in 26.8% at month 6, quality of life score did not change, PMID 36854341, the dose was started at 2.5–5 mg/kg/day and raised to 10 mg/kg/day over 2 weeks, and could be increased up to 20 if needed. The periods overlap (March–October 2019 and May 2019–December 2020), and the first author of Koo 2020 is also an author of Kim 2022, some patients are most likely shared
- Press 2015 (unlicensed cannabis extracts). Retrospective chart review (single center, Colorado); based on parent report; no control group. PMID 25845492, doi:10.1016/j.yebeh.2015.02.043
- Devinsky 2022 (THC-containing medical cannabis). Prospective observational study (structured monitoring in a residential care center); no control group or blinding. PMID 35267245, doi:10.1002/acn3.51537
Points that could not be verified from the full text
- The full texts of GWPCARE1, GWPCARE3 (NEJM) and GWPCARE4 (Lancet) could not be opened; the design, titration and results were verified using the ClinicalTrials.gov record and results, the PubMed abstract and the EMA product information. For Laux 2019, only the abstract was read
- Whether the route of importing a medicine from abroad for personal treatment with a doctor's report (TİTCK permission) has been used for Epidyolex in Turkey could not be found in an official source
- Of the studies added in the October 2026 search, only the PubMed abstract could be read for Patel 2021, Lattanzi 2018 (LGS meta-analysis), de Oliveira 2026, Nabbout 2023, Elbadri 2024 and Press 2015; for the Cochrane review in LGS (Brigo 2021), only the abstract and plain language summary are open. The PubMed and PMC (later edited) versions of this Cochrane abstract give different numbers for stopping because of side effects with CBD (RR 4.90 and 6.62); the table uses the edited version, and the current version in the Cochrane Library could not be checked because access was blocked.
Trusted sources from around the world
Show 5 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.
- NICE TA615: CBD with clobazam for Lennox–Gastaut syndromeNICE (National Institute for Health and Care Excellence, UK), English, December 2019
The UK's health technology appraisal: approved CBD, together with clobazam, in patients aged 2 and over; drop seizures are reviewed every 6 months, and the medicine is stopped if there is not at least a 30% reduction.
- CADTH: Reimbursement recommendation for CBD in Lennox–Gastaut syndromeCADTH (Canadian Agency for Drugs and Technologies in Health), English, May 2024
Canada's drug assessment agency's reimbursement recommendation for approved CBD as an add-on treatment in patients aged 2 and over with Lennox–Gastaut syndrome.
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.
On October 28, 2026, four sources found for this page during the searches for other topics were read from their primary sources. The separate final Lennox–Gastaut results on ClinicalTrials.gov for the extension study lasting up to three years (Patel 2021) were added to the table and the evidence summary: 243 of 366 patients completed the study; the median reduction in drop seizures over each patient's last 12 weeks, including those who left early, was 59%; serious side effects occurred in 157 patients, and 12 deaths were recorded (the registry does not state whether the deaths were related to the medicine). These results come from a study without a comparison group and are not a peer-reviewed publication. Weight loss figures from the US product information for the approved CBD medicine were added to the side effects list: in controlled studies, the proportion of patients whose weight decreased by at least 5% was 16% in the CBD group and 8% in the placebo group. A small, uncontrolled series of 12 patients with a Lennox–Gastaut-like picture in 15q duplication syndrome (in the same direction as the larger studies in the table) and a 2021 position paper of the Brazilian Academy of Neurology (which brings no new data and reports study results differently from their sources) were reviewed and not added to the page. The conclusion and strength of evidence did not change.
In October 2026, PubMed, Cochrane and ClinicalTrials.gov were systematically searched again (878 PubMed and 24 ClinicalTrials.gov records were reviewed; the findings were reread from primary sources in an independent check). Studies added: the Cochrane review of LGS medicines (Brigo 2021), a meta-analysis combining LGS only (Lattanzi 2018), a network meta-analysis comparing LGS treatments (Zhu 2025), a meta-analysis broken down by age and syndrome (de Oliveira 2026), a manufacturer analysis by clobazam use (Devinsky 2020), the three-year extension of the two studies (Patel 2021), two drug-level studies measuring the clobazam interaction (VanLandingham 2020, in patients; Morrison 2019, in healthy volunteers), everyday-practice studies from France, Germany and Korea (D'Onofrio 2020, Strzelczyk 2025, Koo 2020), use without clobazam (Nabbout 2023), adult LGS studies (Elbadri 2024, Aung 2026), unlicensed cannabis extracts (Press 2015) and a THC-containing product (Devinsky 2022). Added to the evidence summary: that the Cochrane review could not calculate the effect on all seizures because of insufficient data, that in patients not taking clobazam the reduction in the number of seizures was smaller and the response rate similar (the comparison was not made by chance assignment), and long-term liver data; for THC-containing products, the box and the strength of evidence were written for the first time ('Insufficient'). The two Lattanzi 2018 reviews in the table were distinguished by name. No third controlled treatment study was found. The conclusion and strength of evidence did not change.
Related studies: Brigo 2021 (Cochrane), published April 7, 2021 (PMID 33825230, doi:10.1002/14651858.CD003277.pub4, Update of the 2013 Cochrane review, PMID 35322410); Lattanzi 2018 (LGS meta-analysis), published October 2018 (PMID 30132269, doi:10.1007/s40263-018-0558-9); Devinsky 2020 (clobazam subgroups), published December 2020 (PMID 32592183, doi:10.1111/ane.13305, Gunning 2021, PMID 32969022, in LGS, the ratio of drop seizures vs. placebo was 0.70 in all patients (95% CI 0.62–0.80) and 0.56 with clobazam (0.47–0.67), OR for at least a halving 3.14 (2.04–4.81) and 3.48 (1.96–6.17), 3 of 7 authors are employees of the manufacturer, and 4 are consultants or investigators of the manufacturer); Zhu 2025 (network meta-analysis), published February 26, 2025 (PMID 40078280, doi:10.3389/fphar.2025.1522543); de Oliveira 2026 (meta-analysis by syndrome and age), published July 2026 (PMID 42185726, doi:10.1007/s40263-026-01301-z); Patel 2021 (GWPCARE5, LGS), published September 2021 (PMID 34287833, doi:10.1111/epi.17000, NCT02224573, separate final results for LGS in the registry, posted on February 3, 2022). Interim analysis: Thiele 2019, PMID 30740695, median 38 weeks, transaminase elevation 10.1% (29 of 37 patients were taking valproate), discontinuation due to side effects 9.6%); Morrison 2019 (clobazam, stiripentol and valproate interaction), published November 2019 (PMID 30791225, doi:10.1002/cpdd.665); D'Onofrio 2020 (France, slow dose increase), published August 12, 2020 (PMID 32903409, doi:10.3389/fneur.2020.00829); Nabbout 2023 (use without clobazam), published August 2023 (PMID 37331197, doi:10.1016/j.seizure.2023.05.003); Strzelczyk 2025 (Germany, real-world), published October 2025 (PMID 40650804, doi:10.1007/s40120-025-00788-w, Subanalysis of the same study in those using it together with clobazam: Strzelczyk 2025, PMID 40073826, 126 patients, 102 with LGS)); Elbadri 2024 (adult LGS, Birmingham), published August 2024 (PMID 38908033, doi:10.1016/j.yebeh.2024.109904); Aung 2026 (adult LGS, London), published October 2026 (PMID 42798297, doi:10.1111/ene.70760); Koo 2020 (Korea), published December 28, 2020 (PMID 33372424, doi:10.3346/jkms.2020.35.e427, Prospective study from the same center: Kim 2022, PMID 36062772, NCT04611438, 30 LGS + 11 Dravet): at least a halving in 26.8% at month 6, quality of life score did not change, PMID 36854341, the dose was started at 2.5–5 mg/kg/day and raised to 10 mg/kg/day over 2 weeks, and could be increased up to 20 if needed. The periods overlap (March–October 2019 and May 2019–December 2020), and the first author of Koo 2020 is also an author of Kim 2022, some patients are most likely shared); Press 2015 (unlicensed cannabis extracts), published April 2015 (PMID 25845492, doi:10.1016/j.yebeh.2015.02.043); Devinsky 2022 (THC-containing medical cannabis), published April 2022 (PMID 35267245, doi:10.1002/acn3.51537); VanLandingham 2020 (clobazam interaction, in patients), published October 2020 (PMID 32652616, doi:10.1002/jcph.1634, NCT02565108)
The reason for the difference between the 'low certainty' rating of a review in the table (Stockings 2018) and the guide's 'Strong' rating was added to the evidence summary: the review was based on two studies up to 2017, and later meta-analyses point in the same direction. The conclusion and strength of evidence did not change.
Older changes (4)
The Turkey row was corrected: the active substance of the approved CBD medicine (cannabidiol oral solution) is on the Foreign Active Substance List of TİTCK (Turkish Medicines and Medical Devices Agency) and can be imported from abroad with the agency's written approval; unsourced information about the SGK (Turkey's Social Security Institution) list was removed. The conclusion and strength of evidence did not change.
The names of the finding labels were simplified: the label "Effect proven" on this page became "Proven effect". The assessment did not change.
The full texts of the studies were reread, and the information on the page was checked against its sources. Corrected: the dose increase details in the study table; the drug interaction notes; the approved medicine's dosing schedule; the starting and titration summary. The points that could not be verified from the full text went down from 3 items to 2. The conclusion and strength of evidence did not change.
Page published. This first review examined 6 studies.