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CBD drug interaction · Medicine group

CBD and epilepsy medicines: which interactions matter?

Prepared by: cbd.school editorial teamLast reviewed: 11 medicines, 5 warnings15 sources

Epilepsy medicines are used to prevent seizures, and many of them are broken down in the liver by enzymes. On this page you will find how CBD interacts with clobazam, valproate, stiripentol, carbamazepine, lamotrigine and other epilepsy medicines, how strong the evidence is, and what is monitored if they are used together.

What's on this page?7 sections

Medicines and the importance of their interactions

From peer-reviewed publications and drug labels: the warnings, most important first. The same warnings also appear in the interaction checker. A medicine that is not listed can still interact with CBD.

Epilepsy medicines: CBD interaction warnings
MedicineImportanceWarningSource
ClobazamHigh importanceClobazam: 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 importanceValproate 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
Rufinamide, Topiramate, Zonisamide, Eslicarbazepine, Stiripentol, Brivaracetam, Other epilepsy medicinesCautionOther 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)CautionStrong 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
Lamotrigine (Lamictal, Pinral)InformationLamotrigine: In 63 people with epilepsy taking approved CBD, lamotrigine blood levels did not change as the CBD dose went up; the European package leaflet says no dose adjustment is needed. Still tell your doctor about the medicines you take.PMID 37593907, EMA Epidyolex SmPC 4.5

Detailed pages: Clobazam and CBD · Valproate and CBD

How does the interaction happen?

CBD is broken down in the liver, mainly by the CYP2C19 and CYP3A4 enzymes and by other enzymes called UGTs. CBD moderately slows the CYP2C19 enzyme; the blood levels of medicines broken down by this enzyme may rise. The active breakdown product of clobazam (N-desmethylclobazam) is the best-known example. In healthy volunteers, however, approved CBD did not change the level of midazolam, which is broken down by CYP3A4. Breakdown products can also have their own effects. According to the US product information, when approved CBD is used regularly, the total amount in the blood of the breakdown product 7-COOH-CBD is about 40 times that of CBD itself; in the laboratory, CBD itself did not slow the UGT1A1, UGT1A4 and UGT1A6 enzymes. According to the European product information, however, 7-COOH-CBD slowed these three enzymes in the laboratory, and medicines broken down by these enzymes may need a lower dose; the product information does not include a study measuring this in humans. (FDA Epidiolex label §7.2 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5 and 5.2, PMID 32918835)

The interaction works both ways: some epilepsy medicines also affect CBD. Clobazam raises 7-OH-CBD, the active breakdown product of CBD, while stiripentol lowers it by about 30%. Strong enzyme inducers such as carbamazepine can lower the levels of CBD and 7-OH-CBD. Valproate, on the other hand, did not change the levels of CBD or its breakdown products in a clinically meaningful way. (EMA Epidyolex prescribing information 4.5 and 5.2, FDA Epidiolex label §7.1 and §12.3 (05/2026), PMID 30791225)

Not every interaction is explained by blood levels. Why liver enzymes rise more often with valproate is not known; the blood levels of neither medicine change clearly. In addition, when CBD, clobazam and other medicines that cause sleepiness are used together, sleepiness and drowsiness may increase. (EMA Epidyolex prescribing information 4.5, FDA Epidiolex label §7.3 and §7.4 (05/2026), PMID 32918835)

There are clear differences between the medicines. The interaction with clobazam was shown in controlled studies and repeated in many studies. The rise in stiripentol is small. For topiramate, rufinamide, zonisamide, eslicarbazepine and brivaracetam, the data come from open-label observation and small patient series, and not every study found the same result. No clear change was seen with medicines such as lamotrigine, lacosamide and oxcarbazepine. Almost all of these studies were done with approved CBD; the results cannot be applied directly to other CBD products. (PMID 32918835, PMID 28782097, PMID 37593907, PMID 31211851, PMID 33541771)

What do studies and official drug information say?

Each finding shows the type of evidence it rests on. A case report describes a single patient; it does not prove cause and effect.

  1. Drug-level study

    Clobazam: active breakdown product rose about 3-fold (2019)

    In healthy volunteers, approved CBD (750 mg twice a day) changed the level of clobazam itself only a little, but raised its active breakdown product N-desmethylclobazam about 3.4-fold. In a placebo-controlled study in people with epilepsy, the rise was 2.2–2.6-fold. In placebo-controlled studies, sleepiness occurred in 46% of those taking clobazam and 16% of those not taking it. Details are on the clobazam page.

    Source: PMID 30791225, PMID 32918835, PMID 26114620, FDA Epidiolex label §5.2 and §12.3 (05/2026)

  2. Controlled study

    Valproate: raised liver enzymes more common

    In the Lennox–Gastaut and Dravet syndrome studies, ALT (a blood test that shows liver cell damage) above 3 times the upper limit of normal was seen in 30% of those taking both valproate and clobazam, 21% of those taking valproate alone, 4% of those taking clobazam alone and 3% of those taking neither. The blood level of valproate did not change clearly; the cause of the rise is not known. Details are on the valproate page.

    Source: FDA Epidiolex label §5.1 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, PMID 28782097, PMID 33346789

  3. Drug-level study

    Stiripentol: level rose by 30–55% (2019, 2020)

    In healthy volunteers, approved CBD raised stiripentol's peak level by 28% and its total exposure (AUC, the total amount of medicine remaining in the blood) by 55%; in people with epilepsy the rise was smaller, at 17% and 30%. In a study of children with Dravet syndrome, no change in stiripentol level was seen. The product information recommends monitoring for stiripentol side effects when the two are used together.

    Source: PMID 30791225, PMID 32918835, PMID 29540584, FDA Epidiolex label §7.2 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5

  4. Observational study

    Topiramate, rufinamide, zonisamide, eslicarbazepine: varying results (2017, 2023)

    In an open-label study of 81 patients using approved CBD, as the CBD dose increased, topiramate and rufinamide levels rose, and in adults zonisamide and eslicarbazepine levels rose; average values stayed within the recommended range. In the final analysis of the same program, with 169 patients, the rise in topiramate persisted, while no significant change was seen in rufinamide, zonisamide and eslicarbazepine. The researchers state that the clinical importance of these changes is most likely small. In children with Dravet syndrome, topiramate levels did not change.

    Source: PMID 28782097, PMID 37593907, PMID 29540584

  5. Case series

    Brivaracetam: level rose by 95–280% in 5 patients (2019)

    In five patients who added CBD, brivaracetam levels rose by between 95% and 280%. Two patients had mild side effects, and in one the brivaracetam dose was lowered. The authors state that slowing of CYP2C19 is a possible cause and that more studies are needed.

    Source: PMID 31211851, PMID 33541771

  6. Official drug information

    Carbamazepine and strong enzyme inducers: CBD levels may fall

    Rifampin (rifampin), a strong enzyme inducer, lowered CBD levels by about 32% and the active breakdown product 7-OH-CBD by about 63% in healthy volunteers. The European product information states that other strong inducers such as carbamazepine may cause a similar fall, that CBD's effect may be reduced and that a dose adjustment may be needed. We did not find a study that directly measured CBD levels with carbamazepine. In the other direction, in 7 patients, carbamazepine levels did not change as the CBD dose increased.

    Source: FDA Epidiolex label §7.1 and §12.3 (05/2026), EMA Epidyolex prescribing information 4.5, PMID 32918835, PMID 37593907

  7. Observational study

    Lamotrigine: level did not change (2023)

    In 63 people with epilepsy using approved CBD, the blood level of lamotrigine did not change as the CBD dose increased. The European product information also states that no dose adjustment is needed with lamotrigine.

    Source: PMID 37593907, EMA Epidyolex prescribing information 4.5

  8. Observational study

    Other epilepsy medicines: no clear change for most (2023)

    In an open-label study of 169 patients, levels of levetiracetam (in children only), perampanel (in adults only) and felbamate rose as the CBD dose increased; however, these rises were inconsistent and were not clearly reflected in side-effect scores. No change was seen in the levels of lacosamide, oxcarbazepine, phenytoin, phenobarbital and clonazepam. The European product information states that no dose adjustment is needed for medicines broken down by CYP2C9, such as phenytoin. The authors stress that the findings need to be confirmed by other studies.

    Source: PMID 37593907, EMA Epidyolex prescribing information 4.5

  9. Systematic review

    Reviews: the clearest interaction is with clobazam (2020, 2021)

    A review of thirty studies found that CBD could potentially interact with many epilepsy medicines; however, for many medicines the data were based on small groups of patients. A review assessing six interaction studies of approved CBD found the likelihood of important interactions with epilepsy medicines other than clobazam to be low. In a meta-analysis of controlled studies, links with abnormal liver tests, sleepiness and pneumonia were seen only in the childhood epilepsy studies; the authors state that this may be due to interactions with clobazam and valproate.

    Source: PMID 33541771, PMID 32918835, PMID 32268347

  10. Official drug information

    Product information for approved CBD

    The European product information says that CBD's behavior in the body is complex and that it may interact with epilepsy medicines taken at the same time; it therefore recommends that CBD and the other medicines be adjusted under regular medical supervision, that side effects be monitored closely and that blood levels be measured if needed. The US product information states that sleepiness may increase with other medicines that cause sleepiness and with alcohol.

    Source: EMA Epidyolex prescribing information 4.5, FDA Epidiolex label §7.4 (05/2026)

What is monitored?

What to tell your doctor

If you are not sure whom to ask: Thinking about CBD? Which specialist should you see?

Frequently asked questions

Can I use CBD while taking an epilepsy medicine?

Make this decision together with your neurologist. Approved CBD is already a medicine used on top of other epilepsy medicines; however, sleepiness with clobazam and raised liver enzymes with valproate are seen more often. If they are used together, your doctor monitors side effects and liver tests and adjusts medicine doses if needed.

Which epilepsy medicine interactions matter most?

Clobazam and valproate. These two interactions were seen again and again in controlled studies and appear in the product information. The rise in stiripentol levels is small; the data on topiramate, rufinamide, zonisamide, eslicarbazepine and brivaracetam are weaker and inconsistent. Lamotrigine levels did not change.

Does nonprescription CBD oil cause the same interactions?

It is not known. Almost all interaction studies were done with approved CBD, and the researchers state that the results cannot be applied directly to other CBD products. A lack of data does not mean it is safe; be sure to tell your doctor about the product you use.

I take carbamazepine; will CBD's effect be reduced?

It may be. The strong enzyme inducer rifampin lowered CBD levels by about a third, and the European product information states that carbamazepine may have a similar effect. However, we did not find a study that directly measured CBD levels with carbamazepine. Your doctor decides on any dose adjustment.

Can I use diazepam nasal spray for seizures together with CBD?

In a later analysis of a phase 3 safety study, the safety and effect of diazepam nasal spray did not change in patients using CBD. Even so, the two medicines together may increase sleepiness. You can find details on diazepam and other anxiety and sleep medicines on the anxiety and sleep medicines page.

I take lamotrigine; will CBD change my lamotrigine level?

In 63 patients using approved CBD, lamotrigine levels did not change as the CBD dose increased, and the European product information states that no dose adjustment is needed. Even so, tell your doctor that you use CBD.

References

Show 15 references
  1. Morrison G, Crockett J, Blakey G, Sommerville K. A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects. Clin Pharmacol Drug Dev. 2019;8(8):1009–1031. PMID 30791225
  2. Patsalos PN et al. Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Epilepsia. 2020;61(9):1854–1868. PMID 32918835
  3. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246–1251. PMID 26114620
  4. Gaston TE et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586–1592. PMID 28782097
  5. Gaston TE et al. Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program. Epilepsia Open. 2023;8(4):1405–1412. PMID 37593907
  6. Devinsky O et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018;90(14):e1204–e1211. PMID 29540584
  7. Thiele EA et al. Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial. JAMA Neurol. 2021;78(3):285–292. PMID 33346789
  8. Klotz KA et al. Effects of cannabidiol on brivaracetam plasma levels. Epilepsia. 2019;60(7):e74–e77. PMID 31211851
  9. Gilmartin CGS et al. Interaction of cannabidiol with other antiseizure medications: A narrative review. Seizure. 2021;86:189–196. PMID 33541771
  10. Chesney E et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020;45(11):1799–1806. PMID 32268347
  11. Peters JM et al. Concomitant cannabidiol does not impact safety and effectiveness of diazepam nasal spray for seizure clusters: Post hoc analysis of a phase 3 safety study. Epilepsy Behav. 2023;144:109248. PMID 37210793
  12. FDA: Epidiolex (cannabidiol) prescribing information, section 2.5, 5.1, 5.2, 5.5, 7 and 12.3 (05/2026), DailyMed. dailymed.nlm.nih.gov
  13. EMA: Epidyolex prescribing information, section 4.4, 4.5, 4.7 and 5.2. www.ema.europa.eu
  14. Clobazam prescribing information, section 2.2 (03/2024), DailyMed. dailymed.nlm.nih.gov
  15. Valproate (divalproeks sodium) prescribing information and patient information (03/2026), DailyMed. dailymed.nlm.nih.gov

Last reviewed: . On this date, each source was opened and checked against the related sentence.