Drug & supplement interaction

Passion Flower + 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 Passion Flower can interact with; the most serious is rated moderate. Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.

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

Passion Flower and Zonisamide

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

Why Are There 2 Interactions?

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

Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam.
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: passion flower has a mild calming effect of its own, and zonisamide already tends to make people feel drowsy or foggy. Put them together and those sedating effects can stack up. You might notice more sleepiness, tiredness, trouble concentrating, dizziness, or feeling slowed down than you would from the medicine alone.

I want to be honest about the evidence here. This concern is theoretical, based on how passion flower works on calming brain chemicals, not on strong human studies with zonisamide specifically. For many people it may be no big deal, but since zonisamide is controlling seizures, please don't add or change anything on your own. Have a quick chat with your pharmacist or doctor first so they can keep an eye on how alert you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Akhondzadeh S, Naghavi HR, Shayeganpour A, et al. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther 2001;26:363-7. PubMed
  2. Speroni E., Minghetti A. Neuropharmacological activity of extracts from Passiflora incarnata. Planta Med. 1988;54:488-91.
  3. Capasso A., Sorrentino L. Pharmacological studies on the sedative and hypnotic effect of Kava kava and Passiflora extracts combination. Phytomedicine. 2005;12:39-45. PubMed
  4. 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.
  5. Soulimani, R., Younos, C., Jarmouni, S., Bousta, D., Misslin, R., and Mortier, F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997;57(1):11-20. PubMed
  6. da Cunha RS, Amorim KS, Gercina AC, et al. Herbal medicines as anxiolytics prior to third molar surgical extraction. A randomized controlled clinical trial. Clin Oral Investig. 2020. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.
Severity Minor 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 your seizure medicine. Your body partly clears zonisamide using a liver enzyme called CYP3A4. Lab studies hint that passion flower may speed that enzyme up a little, which in theory could clear zonisamide a bit faster and leave slightly less of it working in your system. Since zonisamide isn't a prodrug, faster clearance would mean a touch less effect, not more.

The honest truth is this is weak, test-tube level evidence, and the nudge looked far smaller than known strong inducers. For most people it's unlikely to cause a real problem. But because letting your seizure control slip even slightly matters, please run it by your pharmacist or neurologist before adding passion flower.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. 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

Passion Flower Also Interacts With Other Medications

Passion Flower has 247 moderate, 588 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 247 Minor 588 No known interaction 1,995 (incl. Zonisamide)
Taking anything else?

Check Another of Your Medications Against Passion Flower

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

From our Q&A

Questions About Passion Flower 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 Passion Flower 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 Passion Flower 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 Passion Flower as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2,129 real supplement products containing Passion Flower, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Passion Flower. Your product may carry other ingredients that interact with Zonisamide too, on top of Passion Flower — 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 Passion Flower 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 Passion Flower
Top 10%

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

29 days ago today
Medication Zonisamide
Top 25%

#635 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 Passion Flower

What is Passion Flower?

Passion Flower
  • Anxiety and stress
  • Trouble sleeping
  • Restlessness
  • Mild nervous tension
  • Muscle tension

Passion flower is a traditional calming herb that many people use for anxiety and sleep. Early studies hint it may help with mild anxiety and restlessness, but the evidence is limited and more research is needed. It is generally well tolerated short-term, but should be avoided in pregnancy and discussed with your pharmacist or doctor first.

Read the full Passion Flower 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 & Passion Flower

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

0Major
247Moderate
588Minor
1,994No known interaction
247 Moderate 588 Minor 1,994 No interaction
Moderate

247 interactions

Showing 60 of 247 moderate interactions — see all 247 on the Passion Flower page.

Minor

588 interactions

Showing 60 of 588 minor interactions — see all 588 on the Passion Flower page.

No interaction 1,994 drugs checked — show the list

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

Showing the 60 most looked-up of 1,994 medications checked with no known interaction — see the full Passion Flower list.

See the full Passion Flower 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
Passion Flower 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 Passion Flower and Zonisamide Together: Common Questions

Can you take Passion Flower 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 Passion Flower and Zonisamide?
Zonisamide belongs to more than one drug category, and Passion Flower 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 Passion Flower 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 Passion Flower?

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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.