Drug & supplement interaction

Cannabidiol (cbd) + Phenobarbital

Phenobarbital brand names: Phenobarbital, Solfoton, Luminal.

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

Phenobarbital falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Phenobarbital

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Phenobarbital falls into 4 of those categories, so it can interact with Cannabidiol (cbd) in 4 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 4

Why this applies to Phenobarbital

Phenobarbital 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 simple version: phenobarbital already works by calming activity in the brain. CBD, especially in higher doses, can be a little sedating on its own. Put the two together and those calming effects may stack up. That could mean feeling more drowsy, foggy, dizzy, or unusually tired than you'd expect from your phenobarbital dose alone.

I want to be honest about how strong this concern is. This interaction is mostly theoretical, based on how these substances behave rather than solid head-to-head studies, so it may never cause you a problem. Still, since both touch the same system, it's worth a quick chat with your pharmacist or doctor before adding CBD. Please don't stop or adjust your phenobarbital on your own.

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) INDUCERS

2 of 4

Phenobarbital 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 keep in mind with this pairing: it's the CBD that gets affected here, not your phenobarbital. Phenobarbital is a strong inducer, meaning it revs up certain liver enzymes (including CYP2C19), and CBD happens to be cleared by that same enzyme. So taking them together can speed up how fast you break down CBD, leaving less of it in your system and possibly making it work less well.

I'll be honest, this one is theoretical, based on how the drugs behave in the lab rather than proven in people. Your phenobarbital should keep doing its job normally. If you do use CBD for a specific reason, just loop in your pharmacist or doctor first, since phenobarbital itself is a powerful medicine you never want to adjust on your own.

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

3 of 4

Phenobarbital 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 know about this pairing: it's the phenobarbital affecting the CBD, not the other way around. Phenobarbital is a strong enzyme booster (it revs up a liver enzyme called CYP3A4), and CBD is partly cleared by that same enzyme. So when you take them together, your body may break down the CBD faster, which can leave you with lower CBD levels and a weaker effect than you'd expect.

To be honest, this is a theoretical concern based on how the drugs behave, not on solid human studies, so I wouldn't lose sleep over it. Phenobarbital itself should keep working normally. Still, if you're using CBD for a real reason and it doesn't seem to do much, that's worth mentioning. Please check with your pharmacist or doctor before combining them, especially since phenobarbital is a serious seizure and sedative medicine.

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

4 of 4

Phenobarbital 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 if you're using CBD alongside phenobarbital. Your liver uses an enzyme called CYP2B6 to help break this medicine down. In lab (test tube) studies, CBD appears to slow that enzyme. If the same thing happens in people, phenobarbital could clear a bit more slowly and build up in your system.

Since phenobarbital is a barbiturate that quiets brain activity, higher-than-usual levels could mean more drowsiness, grogginess, dizziness, or slowed breathing. I want to be honest, though: this is only a theoretical concern based on lab work, and it hasn't actually been reported in real patients. Still, because phenobarbital is a powerful seizure and sedative drug, it's worth a quick chat with your pharmacist or doctor before combining the two.

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 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)
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.

From our Q&A

Questions About Cannabidiol (cbd) or Phenobarbital

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabidiol (cbd) or Phenobarbital, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Phenobarbital

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital page lists 174 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 Henbane (major).

By severity: 10 major · 143 moderate · 21 minor.

Open the Phenobarbital interaction page

How much people look this up

Where Cannabidiol (cbd) and Phenobarbital 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

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

29 days ago today
Medication Phenobarbital
Steady interest

#1,944 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
Medication

About Phenobarbital

What Is Phenobarbital Used For?

Brand names: Phenobarbital, Solfoton, Luminal

Phenobarbital tablets and oral solutions are used to treat generalized and partial seizures and as a sedative. Phenobarbital Sodium injection is used as a long-term anticonvulsant for generalized tonic-clonic and focal seizures, for emergency control of acute convulsive episodes (including status epilepticus), for sedation, short-term treatment of insomnia, and as a preanesthetic. It is also used in pediatric patients as an anticonvulsant and sedative, including before and after surgery.

Sezaby (phenobarbital injection, intravenous) is specifically indicated for the treatment of neonatal seizures in term and preterm infants. It is not approved for use in adolescents or adults.

See full Phenobarbital drug information
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, 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 supplement interactions › Every supplement checked against Phenobarbital, ranked by severity Phenobarbital drug information › The full plain-English guide to this medication 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 Together: Common Questions

Can you take Cannabidiol (cbd) with Phenobarbital?
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 4 interactions listed for Cannabidiol (cbd) and Phenobarbital?
Phenobarbital 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 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

Still Have a Question About Phenobarbital and Cannabidiol (cbd)?

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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.