Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Zonisamide

Zonisamide brand names: Zonegran, Zonisade.

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

Zonisamide falls into 2 drug categories that Gamma-hydroxybutyrate (ghb) can interact with; the most serious is rated major. GHB may increase the risk of serious CNS and respiratory depression.

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

Gamma-hydroxybutyrate (ghb) and Zonisamide

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

Why Are There 2 Interactions?

Gamma-hydroxybutyrate (ghb) interacts with whole categories of medication. Zonisamide falls into 2 of those categories, so it can interact with Gamma-hydroxybutyrate (ghb) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Zonisamide

Zonisamide falls under CNS DEPRESSANTS — the group Gamma-hydroxybutyrate (ghb) interacts with.

GHB may increase the risk of serious CNS and respiratory depression.
Concomitant use of GHB with CNS depressants may increase the risk of serious CNS and respiratory depression.
Severity Major Likelihood Probable Evidence D

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 simple version: both of these slow down your brain and nervous system. Zonisamide is a seizure medicine that already causes drowsiness, dizziness, trouble concentrating, and sometimes slowed thinking. GHB is a powerful depressant on top of that. Stacked together, the calming and sedating effects can pile up, and that's the real worry here.

The combination can push you into heavy sedation, confusion, or dangerously slow, shallow breathing. The evidence on file is anecdotal, but the concern is serious enough that I wouldn't take chances. Keep in mind GHB sold outside a pharmacy is illegal and unpredictable, so its risks are high no matter what. Please loop in your doctor or pharmacist before mixing anything that affects your breathing or alertness.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Moderate

ANTICONVULSANTS

2 of 2

Zonisamide also falls under ANTICONVULSANTS.

Theoretically, GHB may reduce the effects of anticonvulsant medications.
GHB has been reported to cause seizures, and may theoretically reduce the effectiveness of anticonvulsants. Also, concomitant use of GHB with sedative anticonvulsants may increase the risk of serious CNS and respiratory depression.
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 about mixing GHB with your zonisamide (Zonegran). GHB is a serious central nervous system depressant, not a real supplement, and there are two separate worries. First, GHB has actually been reported to trigger seizures, which could work against the very thing zonisamide is doing for you and theoretically make it less effective at keeping your seizures controlled. Second, both GHB and seizure medicines can slow the brain down, so taking them together can stack up that sedation, leaving you very drowsy, confused, or in the worst case slowing your breathing dangerously.

I'll be honest, this is based on anecdotal reports rather than strong studies, but GHB itself is genuinely dangerous and controlled. Please talk with your doctor or pharmacist before combining anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  2. Stomberg MW, Knudsen K, Stomberg H, Skärsäter I. Symptoms and signs in interpreting gamma-hydroxybutyrate (GHB) intoxication - an explorative study. Scand J Trauma Resusc Emerg Med. 2014 Apr 23;22:27. PubMed
  3. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.

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

Gamma-hydroxybutyrate (ghb) Also Interacts With Other Medications

Gamma-hydroxybutyrate (ghb) has 248 major, 21 moderate, 5 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.

Major 248 Moderate 21 Minor 5 No known interaction 2,556 (incl. Zonisamide)
Taking anything else?

Check Another of Your Medications Against Gamma-hydroxybutyrate (ghb)

Covers the 2,830 medications we’ve checked against Gamma-hydroxybutyrate (ghb). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Zonisamide

This page covers Gamma-hydroxybutyrate (ghb) 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), Grapefruit (major) and Kava (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 Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb)
Steady interest

#1,265 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Zonisamide
Top 25%

#576 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 Gamma-hydroxybutyrate (ghb)

What is Gamma-hydroxybutyrate (ghb)?

  • Narcolepsy (cataplexy and excessive daytime sleepiness)
  • Sleep aid
  • Misused as a recreational 'party drug'
  • Bodybuilding/muscle building (unproven)
  • Alcohol withdrawal (in some countries)

GHB (gamma-hydroxybutyrate) is a powerful central nervous system depressant that is NOT a safe dietary supplement. In the U.S. it is a controlled substance, and only a tightly regulated prescription form (sodium oxybate) is legal for narcolepsy. Non-prescription GHB can cause coma, breathing failure, and death, and it is also a known 'date-rape' drug — it should not be taken outside of medical supervision.

Read the full Gamma-hydroxybutyrate (ghb) 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 & Gamma-hydroxybutyrate (ghb)

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

248Major
21Moderate
5Minor
2,555No known interaction
248 Major 21 Moderate 5 Minor 2,555 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Gamma-hydroxybutyrate (ghb) page.

Moderate

21 interactions

Minor

5 interactions

No interaction 2,555 drugs checked — show the list

We also checked Gamma-hydroxybutyrate (ghb) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,555 medications checked with no known interaction — see the full Gamma-hydroxybutyrate (ghb) list.

See the full Gamma-hydroxybutyrate (ghb) 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
Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb) and Zonisamide Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Zonisamide?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Gamma-hydroxybutyrate (ghb) and Zonisamide?
Zonisamide belongs to more than one drug category, and Gamma-hydroxybutyrate (ghb) 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 Gamma-hydroxybutyrate (ghb) and Zonisamide interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Zonisamide and Gamma-hydroxybutyrate (ghb)?

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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.