Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Phenobarbital, Phenytoin

Phenobarbital, Phenytoin brand name: Dilantin with PB.

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

Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin

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. Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin

Phenobarbital, Phenytoin 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 big-picture concern with this combination. Phenobarbital is a barbiturate that already calms and slows down the brain, and GHB is a heavy-duty central nervous system depressant in its own right. Stack them together and those sedating effects pile up. That can mean extreme drowsiness, confusion, slurred speech, slowed or shallow breathing, and in a worst-case scenario, coma. Phenytoin (Dilantin) is mainly a seizure medicine, but combining it with GHB still adds to that overall sedation risk.

To be honest, the evidence here is mostly anecdotal, but the danger is real enough that I wouldn't take chances. Keep in mind GHB outside of a prescription is illegal and unpredictable. Please talk with your doctor or pharmacist before mixing anything like this.

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

Phenobarbital, Phenytoin 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

Let me be upfront here: GHB really isn't a true supplement. It's a controlled substance and a powerful brain depressant, and mixing it with seizure medicines like phenytoin (Dilantin) or phenobarbital raises two real concerns. First, GHB has been reported to actually trigger seizures, so it could theoretically work against the very thing your medication is trying to prevent, making breakthrough seizures more likely.

Second, phenobarbital is itself a sedating drug, and stacking it with GHB can dangerously slow your breathing and deepen sedation, which can lead to extreme drowsiness, confusion, or even stopped breathing. The evidence here is mostly anecdotal, but the risk is serious enough that I'd strongly urge you not to combine them, and please talk with your doctor or pharmacist first.

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 Phenobarbital, Phenytoin 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. Phenobarbital, Phenytoin)
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 Phenobarbital, Phenytoin

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital, Phenytoin page lists 229 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), Kava (major) and L-tryptophan (major).

By severity: 9 major · 192 moderate · 28 minor.

From our pharmacist’s overview on the Phenobarbital, Phenytoin page

“If your seizure medicine is the phenobarbital and phenytoin combination (Dilantin with PB), read this list carefully before you add any supplement. Nine of the 229 entries rate major, and most of the risk runs through two channels.”

Reviewed by 2 · Jul 18, 2026

Open the Phenobarbital, Phenytoin interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Phenobarbital, Phenytoin 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)
Top half

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

29 days ago today
Medication Phenobarbital, Phenytoin
Top 25%

#439 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
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 Phenobarbital, Phenytoin, 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 Phenobarbital, Phenytoin supplement interactions › Every supplement checked against Phenobarbital, Phenytoin, ranked by severity 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 Phenobarbital, Phenytoin Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Phenobarbital, Phenytoin?
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 Phenobarbital, Phenytoin?
Phenobarbital, Phenytoin 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 Phenobarbital, Phenytoin 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

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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.