Drug & supplement interaction

Valerian + Zonisamide

Zonisamide brand names: Zonegran, Zonisade.

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

Zonisamide falls into 2 drug categories that Valerian can interact with; the most serious is rated moderate. Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Valerian and Zonisamide

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Valerian interacts with whole categories of medication. Zonisamide falls into 2 of those categories, so it can interact with Valerian in 2 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 2

Why this applies to Zonisamide

Zonisamide falls under CNS DEPRESSANTS — the group Valerian interacts with.

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and 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: zonisamide already tends to make people feel drowsy, foggy, or off-balance, and valerian is used to make you sleepy. Put them together and those calming effects can stack up. You might notice more daytime sleepiness, trouble concentrating, slower reaction time, or feeling unsteady on your feet.

I want to be honest about the science though. This concern comes mostly from lab and animal research, not strong human studies, so it's more of a 'be aware' than a 'this will definitely happen.' Zonisamide isn't a prodrug, so valerian isn't changing how your body activates it, it's just adding its own sedating effect on top. If you're thinking about valerian for sleep, check with your pharmacist or doctor first so they can keep an eye on the drowsiness.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  2. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  3. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme. In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4. However, this mild inhibition is unlikely to be clinically relevant.
Severity Minor Likelihood Possible Evidence B

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 short version: based on the studies we have, valerian doesn't meaningfully change how your body handles zonisamide. Zonisamide is partly broken down by a liver enzyme called CYP3A4, and while lab tests once hinted that valerian might slow that enzyme down, real human studies showed only a tiny effect that wasn't enough to matter in practice. Zonisamide is active on its own (not a prodrug), so even mild slowing wouldn't be expected to cause trouble.

The one thing I'd keep in mind is overlap of effects, not metabolism. Both valerian and zonisamide can make you feel drowsy or foggy, so together you might notice more sleepiness or trouble concentrating. Since zonisamide controls seizures, please check with your pharmacist or doctor before adding valerian.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Lefebvre T, Foster BC, Drouin CE, et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 2004;7:265-73.
  3. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  4. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  5. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. 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

Valerian Also Interacts With Other Medications

Valerian has 337 moderate, 564 minor 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 337 Minor 564 No known interaction 1,929 (incl. Zonisamide)
Taking anything else?

Check Another of Your Medications Against Valerian

Covers the 2,830 medications we’ve checked against Valerian. Pick one to open its full report.

From our Q&A

Questions About Valerian or Zonisamide

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Valerian or Zonisamide, 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 Zonisamide

This page covers Valerian 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

One more smart check

Taking Valerian as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2,185 real supplement products containing Valerian, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Valerian. Your product may carry other ingredients that interact with Zonisamide too, on top of Valerian — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Valerian 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 Valerian
Top 10%

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

29 days ago today
Medication Zonisamide
Top 25%

#577 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 Valerian

What is Valerian?

Valerian
  • Insomnia and poor sleep
  • Anxiety and stress
  • Restlessness
  • Muscle tension or cramps
  • Menstrual discomfort

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably for everyone. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before starting it.

Read the full Valerian 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 & Valerian

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

0Major
337Moderate
564Minor
1,928No known interaction
337 Moderate 564 Minor 1,928 No interaction
Moderate

337 interactions

Showing 60 of 337 moderate interactions — see all 337 on the Valerian page.

Minor

564 interactions

Showing 60 of 564 minor interactions — see all 564 on the Valerian page.

No interaction 1,928 drugs checked — show the list

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

Showing the 60 most looked-up of 1,928 medications checked with no known interaction — see the full Valerian list.

See the full Valerian 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
Valerian 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 Valerian and Zonisamide Together: Common Questions

Can you take Valerian 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 2 interactions listed for Valerian and Zonisamide?
Zonisamide belongs to more than one drug category, and Valerian 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 Valerian 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 Valerian?

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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.