What happens when you take cbd with clobazam?
Clobazam is a benzodiazepine used widely for hard-to-treat epilepsy, particularly Lennox-Gastaut and Dravet syndromes. The combination with cannabidiol (CBD) is common because both drugs treat the same rare epilepsies, and the interaction between them is one of the best-documented in this field. Here is the sequence:
- Clobazam forms an active metabolite. The body converts clobazam into N-desmethylclobazam (N-CLB), an active metabolite that builds up to levels higher than the parent drug and is responsible for much of clobazam's sedative effect.
- N-CLB is cleared by the enzyme CYP2C19. Under normal conditions this enzyme keeps N-CLB levels in a reasonable range.
- CBD blocks CYP2C19. Cannabidiol is a potent inhibitor of this enzyme, slowing the clearance of N-CLB so the metabolite accumulates.
- N-CLB levels rise substantially. In the FDA Epidiolex interaction study, adding CBD raised N-desmethylclobazam exposure substantially, with a smaller rise in clobazam itself.
- Sedation increases. Higher N-CLB levels translate into more drowsiness, drooling, low muscle tone, unsteadiness, and confusion in a meaningful fraction of patients.
Why is this important?
This is one of the most clinically relevant CBD interactions, and the Epidiolex label addresses concurrent clobazam use directly because so many patients take both drugs for the same conditions. Without anticipating the interaction, patients can develop excessive sleepiness, low muscle tone, drooling, unsteadiness, and confusion within days to weeks of starting CBD. In small children with refractory epilepsy, this sedation is easily mistaken for worsening neurological status, a postictal state, or a new illness.
There are a few wrinkles worth knowing. The rise in N-CLB is gradual because the metabolite has a long half-life, so sedation may not peak until a week or two after starting CBD, often well past a routine follow-up visit. CYP2C19 activity also varies by genetics; people who naturally clear the metabolite slowly start with higher N-CLB levels and may notice stronger effects. The interaction is also somewhat bidirectional, with clobazam mildly increasing CBD exposure.
What should you do?
This interaction is best managed by the prescribing neurologist or epileptologist, not by self-adjustment. Use the following schedule.
Before any change: Tell the prescriber about all CBD use, including over-the-counter hemp products, before starting or escalating either drug. Ask whether the clobazam dose should be lowered when CBD is added, and whether your center monitors clobazam and N-desmethylclobazam blood levels.
Every day during the overlap: Take both medicines exactly as prescribed. Watch for sedation signs: excessive sleepiness or prolonged napping, slurred speech, increased drooling, unsteady gait or new clumsiness, behavioral change, or loss of appetite. Be cautious with other things that add to sedation, such as opioids, other benzodiazepines, alcohol, and gabapentin or pregabalin.
After a dose change: Pay special attention in the first one to two weeks after starting or increasing CBD, since sedation peaks late. Report any of the warning signs promptly rather than waiting for the next routine visit. Do not stop or change either medicine on your own; dose adjustments should be planned with the prescriber, who may also use blood-level monitoring to balance seizure control against oversedation.
Which specific products are affected?
The interaction has been formally characterized for pharmaceutical Epidiolex (cannabidiol oral solution) with clobazam (sold as Onfi, Sympazan oral film, Frisium, Tapclob, and various generics). The same mechanism applies to consumer CBD products such as tinctures, oils, gummies, capsules, and vapes. With consumer products the magnitude depends on the amount of CBD and on bioavailability, which varies widely, so the effect may be smaller in absolute terms but is still real. Full-spectrum and broad-spectrum hemp extracts contain the same cannabidiol and behave the same way. THC-containing cannabis products add their own sedating effect and should be treated as additive. All clobazam products share the same metabolic pathway, so the interaction applies regardless of brand.
The science behind it
The interaction is established at the regulatory, clinical, and mechanistic levels.
- FDA Epidiolex Prescribing Information (2024). The label reports that coadministration of cannabidiol with clobazam substantially increases N-desmethylclobazam exposure via CYP2C19 inhibition and advises considering a clobazam dose reduction if clobazam-related adverse reactions appear. (accessdata.fda.gov)
- Geffrey AL et al., Epilepsia 2015;56(8):1246-1251 (PMID 26114620). A prospective pharmacokinetic study in children with refractory epilepsy taking clobazam found that adding CBD raised N-desmethylclobazam levels markedly and was associated with somnolence, prompting clobazam dose reductions in several patients.
- Anderson LL et al., Epilepsia 2019 (PMC6900043). Preclinical work supports both a pharmacokinetic interaction (raised N-CLB) and a pharmacodynamic component, consistent with the clinical picture of increased sedation.
Together these sources confirm the direction, mechanism, and clinical importance of the interaction.
Frequently Asked Questions
Is it ever safe to take CBD with clobazam?
Yes, but only under a prescriber's supervision. Many patients take Epidiolex and clobazam together by design; the key is anticipating the interaction with a planned clobazam dose adjustment and monitoring rather than combining them without medical input.
How quickly does the interaction appear?
Sedation tends to build gradually and may not peak until a week or two after starting or increasing CBD, because the active metabolite N-desmethylclobazam has a long half-life. This delay is why problems often surface after a clinic visit.
Will over-the-counter CBD oil cause the same problem?
It can. Consumer CBD products work through the same enzyme inhibition. The size of the effect depends on how much CBD is absorbed, which varies a lot between products, but the interaction is real and should be disclosed to your prescriber.
What are the warning signs of too much sedation?
Excessive sleepiness, slurred speech, increased drooling, an unsteady or clumsy gait, behavioral changes, and loss of appetite. In children these can be mistaken for worsening illness, so report them promptly.
Should I just stop the clobazam if I feel sedated?
No. Do not stop or change clobazam on your own; abrupt benzodiazepine changes carry their own risks. Contact the prescriber, who can adjust the dose safely and, if needed, check blood levels.
Does CBD interact with other seizure medicines too?
CBD can affect the levels of several other medicines through liver enzymes, so the same principle applies: tell your prescriber about all CBD use and review the full medication list with your doctor or pharmacist.
Key takeaways
- CBD inhibits CYP2C19, raising levels of clobazam's active metabolite N-desmethylclobazam and increasing sedation.
- Severity is high: this is one of the most clinically important and best-documented CBD drug interactions.
- Manage it with the prescribing neurologist, not by self-adjustment; expect a planned clobazam dose reduction and possible blood-level monitoring.
- Watch for excessive sleepiness, drooling, slurred speech, and unsteadiness, especially in the first one to two weeks after starting or increasing CBD.
- Over-the-counter hemp CBD products carry the same risk; disclose all CBD use to your prescriber.
- Review any change to either medicine with your doctor or pharmacist first.