Drug & supplement interaction

Cannabidiol (cbd) + Phenobarbital, Phenytoin

Phenobarbital, Phenytoin brand name: Dilantin with PB.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Phenobarbital, Phenytoin falls into 7 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might have additive effects if used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions7
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Phenobarbital, Phenytoin

These two interact in 7 distinct ways. Each one is explained separately below.

Why Are There 7 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Phenobarbital, Phenytoin falls into 7 of those categories, so it can interact with Cannabidiol (cbd) in 7 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 7

Why this applies to Phenobarbital, Phenytoin

Phenobarbital, Phenytoin falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.

Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
Preliminary clinical research, case reports, and animal studies suggest that high dose cannabidiol has sedative and hypnotic effects. Theoretically, concomitant use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist of pairing CBD with this combo product (phenobarbital plus phenytoin): the main worry is added drowsiness. Phenobarbital is a barbiturate that already calms the brain, and higher doses of CBD can have their own sedating, sleepy effect. Stack the two and you may feel more tired, foggy, dizzy, or unsteady on your feet than usual.

To be fair, this is a theoretical concern based mostly on pharmacology and early reports, not firm proof. There can also be a separate twist: phenobarbital and phenytoin speed up liver enzymes and may lower CBD levels, while CBD can nudge phenytoin levels in some people. Since phenytoin is fussy about its blood level, don't start, stop, or change anything on your own. Please loop in your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
  2. Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
  3. Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
  4. Perez-Vilar S, Karami S, Long K, Leishear K. Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021. Clin Toxicol (Phila) 2022. PubMed
Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

2 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP2C19.
Research shows that cannabidiol inhibits CYP2C19. In clinical studies and case reports, cannabidiol use resulted in significant increases in the serum levels of topiramate, methadone, citalopram, omeprazole, and N-desmethylclobazam, the primary active metabolite of clobazam. These chemicals are metabolized by CYP2C19. Concomitant use of cannabidiol with CYP2C19 substrates may increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Probable Evidence A

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know if you take phenytoin (Dilantin) or phenobarbital and you're thinking about CBD. Your liver uses an enzyme called CYP2C19 to help clear these seizure medicines, and CBD slows that enzyme down. When it's slowed, the drug can build up in your blood, and these two are narrow therapeutic index medicines, meaning the gap between a helpful level and a too-high level is small.

If levels creep up, you might notice more drowsiness, dizziness, unsteady walking, slurred speech, or eye-movement problems. This isn't a guess either, good clinical studies back up CBD's effect on this enzyme. Please don't start, stop, or change anything on your own. Loop in your doctor or pharmacist first, since blood-level checks may be worth doing.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  4. Devinsky O, Marsh E, Friedman D, et la. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8.
  5. Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015 Aug;56(8):1246-51. PubMed
  6. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  7. Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021. PubMed
  8. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  9. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP2C9.
In vitro and animal research shows that cannabidiol inhibits CYP2C9. In human studies, cannabidiol has been associated with an increase in plasma levels of topiramate and losartan, CYP2C9 substrates. Concomitant use of cannabidiol with CYP2C9 substrates may increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Probable Evidence A

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the practical concern with combining CBD and phenytoin (and to a lesser degree phenobarbital). Your liver uses an enzyme called CYP2C9 to help clear phenytoin out of your body. CBD can slow that enzyme down, so phenytoin may build up higher than usual. Phenytoin is a narrow-therapeutic-index drug, meaning the gap between a helpful level and a toxic one is small, so even modest increases matter.

If levels climb, you might notice dizziness, unsteadiness, slurred speech, double vision, or unusual drowsiness. Please don't start, stop, or change anything on your own. Loop in your doctor or pharmacist first. They can check a phenytoin blood level and adjust your dose safely if you and they decide CBD is worth using.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  4. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  5. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
  6. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 2C19 (CYP2C19) INDUCERS

4 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C19 (CYP2C19) INDUCERS.

Theoretically, CYP2C19 inducers might decrease cannabidiol levels.
Cannabidiol is a substrate of CYP2C19 enzymes. Theoretically, drugs that induce CYP2C19 enzymes might decrease the levels and effects of cannabidiol.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to notice with this pair: the medicine is doing something to the CBD, not the other way around. Both phenobarbital and phenytoin (the Dilantin part) are known to rev up liver enzymes, including CYP2C19, which is one of the pathways your body uses to break down CBD. So in theory, taking them together could speed up how fast you clear the CBD, leaving lower levels and possibly less benefit from it.

I want to be honest that this is theoretical, based on how the drugs behave on paper, not from solid human studies. Your seizure medicine effect shouldn't change much here. Still, since CBD itself can nudge phenytoin levels in some people, it's worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
Moderate

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES

5 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2C8.
In vitro research shows that cannabidiol inhibits CYP2C8. However, this interaction has yet to be reported in humans. Until more is known, use with caution. Theoretically, concomitant use of cannabidiol with CYP2C8 substrates might increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: in lab dishes, CBD has been shown to slow down an enzyme called CYP2C8, and both phenobarbital and phenytoin can be processed in part by that enzyme. The thinking is that if CBD blocks it, these medicines might clear a little more slowly and build up in your body. With phenytoin especially, that matters because it's a narrow therapeutic index drug, meaning the gap between a helpful dose and a toxic one is small. Higher levels could mean things like drowsiness, unsteady walking, slurred speech, or eye-twitching (nystagmus).

That said, this is only a theoretical concern from test-tube work, never actually confirmed in people. So don't panic, but do loop in your pharmacist or doctor before adding CBD, since these seizure meds are too important to guess with.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

6 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might decrease cannabidiol levels.
Cannabidiol is a substrate of CYP3A4 enzymes. Theoretically, drugs that induce CYP3A4 enzymes might reduce the levels and effects of cannabidiol.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the key thing to understand: in this pairing, it's the medicine affecting the supplement, not the other way around. Both phenobarbital and phenytoin are strong 'revvers' of a liver enzyme called CYP3A4, which is one of the pathways that breaks down CBD. So if you're taking either of these seizure medicines, your body may clear CBD faster, leaving you with lower CBD levels and possibly less of whatever benefit you were hoping for.

I'll be honest, this is a theoretical concern based on how the drugs behave, not something proven in real patients. It's also worth noting the reverse: CBD can nudge phenytoin levels up, and phenytoin is a finicky, narrow-window drug. Please loop in your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

7 of 7

Phenobarbital, Phenytoin also falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES.

Theoretically, cannabidiol might increase levels of drugs metabolized by CYP2B6.
In vitro research shows that cannabidiol inhibits CYP2B6. However, this interaction has yet to be reported in humans. Until more is known, use with caution. Theoretically, concomitant use of cannabidiol with CYP2B6 substrates might increase the risk for adverse effects from these substrates.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for this combo. Your body uses several liver enzymes to clear phenobarbital and phenytoin, and one of them is called CYP2B6. In lab (test tube) studies, CBD appears to slow that enzyme down. If that played out in real life, these seizure medicines could clear a little more slowly and build up, which might mean more side effects like drowsiness, dizziness, unsteady walking, slurred speech, or feeling foggy.

I want to be straight with you though: this is theoretical and hasn't actually been reported in people yet. Phenytoin in particular has a narrow safe range, so even small shifts can matter. Please don't change anything on your own. Loop in your pharmacist or doctor, especially since they can check a phenytoin blood level if needed.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Maeda C, Yamamoto I, Watanabe K. Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Forensic Toxicol 2011;29:117-24. DOI
  2. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Phenobarbital, Phenytoin one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Phenobarbital, Phenytoin)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Phenobarbital, Phenytoin

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital, Phenytoin page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 9 major · 192 moderate · 28 minor.

From our pharmacist’s overview on the Phenobarbital, Phenytoin page

“If your seizure medicine is the phenobarbital and phenytoin combination (Dilantin with PB), read this list carefully before you add any supplement. Nine of the 229 entries rate major, and most of the risk runs through two channels.”

Reviewed by 2 · Jul 18, 2026

Open the Phenobarbital, Phenytoin interaction page

How much people look this up

Where Cannabidiol (cbd) and Phenobarbital, Phenytoin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Cannabidiol (cbd)
Top half

#492 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Phenobarbital, Phenytoin
Steady interest

#1,957 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Keep checking

Other Drugs & Cannabidiol (cbd)

Browse every other medication we’ve checked against Cannabidiol (cbd) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

We also checked Cannabidiol (cbd) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) interactions page
See every supplement checked against Phenobarbital, Phenytoin, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Cannabidiol (cbd) monograph › Uses, safety, and every drug interaction in one place Phenobarbital, Phenytoin supplement interactions › Every supplement checked against Phenobarbital, Phenytoin, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Cannabidiol (cbd) and Phenobarbital, Phenytoin Together: Common Questions

Can you take Cannabidiol (cbd) with Phenobarbital, Phenytoin?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 7 interactions listed for Cannabidiol (cbd) and Phenobarbital, Phenytoin?
Phenobarbital, Phenytoin belongs to more than one drug category, and Cannabidiol (cbd) interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Cannabidiol (cbd) and Phenobarbital, Phenytoin interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.