Drug & supplement interaction

Cannabidiol (cbd) + Zonisamide

Zonisamide brand names: Zonegran, Zonisade.

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

Zonisamide falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Zonisamide

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Zonisamide falls into 3 of those categories, so it can interact with Cannabidiol (cbd) in 3 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 3

Why this applies to Zonisamide

Zonisamide 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: both CBD and zonisamide can have a calming, sleepy effect on your brain. When you put them together, those effects may stack up. So you might feel more drowsy, dizzy, foggy, or slowed down than you'd expect from either one alone. Zonisamide already tends to cause tiredness, trouble concentrating, and dizziness for some people, and CBD could add to that.

I want to be honest about the strength of this: it's based mostly on how these compounds behave in theory, not on strong studies in people, and it's mainly a concern at higher CBD doses. Still, since you're managing seizures, it's worth a quick chat with your doctor or pharmacist before combining them, so they can watch how you feel.

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 3A4 (CYP3A4) SUBSTRATES

2 of 3

Zonisamide also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Cannabidiol may increase levels of drugs that are metabolized by CYP3A4.
In vitro and animal research shows that cannabidiol inhibits CYP3A4. In human studies and case reports, cannabidiol has been associated with an increase in plasma levels of the CYP3A4 substrates zonisamide, tacrolimus, everolimus, citalopram, midazolam, and methadone.
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 short version: CBD can slow down one of the liver enzymes (CYP3A4) that helps clear zonisamide from your body. When that enzyme is working slower, zonisamide can build up to higher levels than usual. This isn't just a theory, studies in people have actually shown CBD nudging zonisamide levels up.

What that can feel like is more of zonisamide's usual side effects, things like drowsiness, dizziness, trouble concentrating, loss of appetite, or feeling unsteady. That doesn't mean you can't use both, plenty of people on seizure meds use CBD. But please loop in your neurologist or pharmacist first so they can watch your levels and your symptoms, and never adjust your seizure medicine on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Ebisawa J, Okushima Y, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88(15-16):730-6. PubMed
  2. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  3. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  4. 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
  5. Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. PubMed
  6. Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. PubMed
  7. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  8. 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
  9. 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
  10. 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
  11. 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

ZONISAMIDE (Zonegran)

3 of 3
Cannabidiol might increase zonisamide levels.
In clinical research, concomitant administration of cannabidiol and zonisamide, a cytochrome P450 3A4 (CYP3A4) substrate, is associated with a modest increase in plasma levels of zonisamide. Zonisamide levels stayed within the normal range and did not require dose adjustment. However, caution should be exercised when cannabidiol and zonisamide are taken together.
Severity Moderate Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

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

Here's the gist: your body uses an enzyme called CYP3A4 to help clear zonisamide, and CBD can slow that enzyme down a bit. The result is that zonisamide can build up slightly in your blood. The good news is that in actual clinical research, this bump was modest, levels stayed in the normal range, and people generally did not need a dose change.

Still, it's worth keeping an eye out. If you add CBD, watch for more of zonisamide's usual side effects creeping up, things like drowsiness, dizziness, trouble concentrating, loss of appetite, or feeling unsteady. Since CBD product strength varies a lot, I'd loop in your pharmacist or doctor before combining the two so they can keep tabs on how you're feeling.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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

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 Zonisamide 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. Zonisamide)
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 Zonisamide

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zonisamide page lists 206 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 Grapefruit (major).

By severity: 9 major · 157 moderate · 40 minor.

From our pharmacist’s overview on the Zonisamide page

“Zonisamide (Zonegran, Zonisade) keeps seizures under control, which means anything that shifts its blood level or stacks extra sedation on top deserves real respect, and nine of the 206 supplement ingredients on file rate major. Two big themes run through nearly everything here.”

Reviewed by 2 · Jul 18, 2026

Open the Zonisamide interaction page

How much people look this up

Where Cannabidiol (cbd) and Zonisamide 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

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

29 days ago today
Medication Zonisamide
Top half

#1,179 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 Zonisamide

What Is Zonisamide Used For?

Brand names: Zonegran, Zonisade

Zonisamide is used as add-on therapy — meaning it is combined with other seizure medications, not used alone — to treat partial seizures (seizures that start in one part of the brain) in adults with epilepsy. Zonegran (capsule) and generic zonisamide capsules are approved for adults with epilepsy.

Zonisade (oral suspension) is approved as add-on therapy for partial-onset seizures in adults and in patients 16 years of age and older.

See full Zonisamide 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 Zonisamide, 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 Zonisamide supplement interactions › Every supplement checked against Zonisamide, ranked by severity Zonisamide 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 Zonisamide Together: Common Questions

Can you take Cannabidiol (cbd) with Zonisamide?
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 3 interactions listed for Cannabidiol (cbd) and Zonisamide?
Zonisamide 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 Zonisamide 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 Zonisamide 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.