Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Phentermine, Topiramate

Phentermine, Topiramate brand name: Qsymia.

Major Interaction
The bottom line Major

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

Gamma-hydroxybutyrate (ghb) and Phentermine, Topiramate

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

Why Are There 3 Interactions?

Gamma-hydroxybutyrate (ghb) interacts with whole categories of medication. Phentermine, Topiramate falls into 3 of those categories, so it can interact with Gamma-hydroxybutyrate (ghb) in 3 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 3

Why this applies to Phentermine, Topiramate

Phentermine, Topiramate 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 thing to know about pairing GHB with Qsymia (phentermine and topiramate). GHB is a strong brain and nervous system depressant, meaning it slows things down. The topiramate part of Qsymia also has its own calming, sedating effects on the brain. Put the two together and those slowing-down effects can stack up.

When that happens, you could get unusually drowsy, dizzy, confused, or foggy, and in a serious case your breathing could slow down dangerously. The phentermine part is a stimulant, but it doesn't reliably cancel out GHB's dangers. Honestly, GHB outside of medical supervision is risky on its own. This warning is based mostly on anecdotal reports, but the concern is real. Please talk with your doctor or pharmacist before mixing anything like this.

References
  1. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Moderate

ANTICONVULSANTS

2 of 3

Phentermine, Topiramate 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

First, a real safety note: GHB sold outside of a doctor's care is dangerous and illegal, so I'd steer clear of it entirely. With Qsymia, there are two concerns worth knowing. The topiramate piece can help control seizures in some people, and GHB has been linked to causing seizures, so in theory it could work against that calming effect. This is based only on scattered, anecdotal reports, not strong studies, so the evidence here is weak.

The bigger worry is the overlap in drowsiness. GHB is a heavy nervous-system depressant, and stacking it with anything sedating can deepen sleepiness, slow your breathing, and in worst cases cause coma. Please don't combine these, and talk with your pharmacist or doctor before changing anything.

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.
Moderate

TOPIRAMATE (Topamax)

3 of 3
Topiramate might increase the levels and clinical effects of GHB.
Concomitant use of GHB with topiramate might increase the blood levels and adverse effects of GHB. In one case report, a female regularly taking prescription GHB (sodium oxybate, Xyrem) 4.5 grams twice nightly for nocturnal headaches and insomnia experienced a worsening cluster headache requiring hospitalization after initiating treatment with topiramate 25 mg, 5 hours prior to the GHB dose. Symptoms included confusion, muscle jerking, miosis, and coma, with recovery within a few hours. Plasma levels of GHB were 2.5-fold higher than when GHB was given alone. Potential mechanisms might include decreased GHB breakdown, increased absorption, and/or increased activity.
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 key thing to know: Qsymia contains topiramate, and topiramate appears to push GHB levels up in your body. The likely reason is that topiramate slows how GHB is broken down and may increase how much you absorb, so the GHB sticks around longer and hits harder. In one real case, a woman taking prescription GHB (Xyrem) saw her GHB blood levels jump about 2.5 times higher after starting topiramate, leading to confusion, muscle jerking, pinpoint pupils, and even a coma before she recovered.

This is a one-case report, so the evidence is thin, but the danger of GHB is real and serious. Non-prescription GHB is not a safe supplement and can stop your breathing. Please talk with your doctor or pharmacist before combining anything like this with your Qsymia.

References
  1. Weiss T, Müller D, Marti I, Happold C, Russmann S. Gamma-hydroxybutyrate (GHB) and topiramate--clinically relevant drug interaction suggested by a case of coma and increased plasma GHB concentration. Eur J Clin Pharmacol. 2013 May;69(5):1193-4. 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

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 Phentermine, Topiramate one above is among them. If you take anything else, check it against the full list below.

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 Phentermine, Topiramate

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phentermine, Topiramate page lists 125 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: 7 major · 101 moderate · 17 minor.

From our pharmacist’s overview on the Phentermine, Topiramate page

“Alcohol is the single biggest hazard on this page. Beer and wine both carry major-rated interactions with Qsymia (phentermine and topiramate), because topiramate already slows the nervous system and drinking deepens that sedation.”

Reviewed by 2 · Jul 18, 2026

Open the Phentermine, Topiramate interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Phentermine, Topiramate 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

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

29 days ago today
Medication Phentermine, Topiramate
Top 25%

#608 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
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
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

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Pharmacist Counseling Corner

Taking Gamma-hydroxybutyrate (ghb) and Phentermine, Topiramate Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Phentermine, Topiramate?
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 3 interactions listed for Gamma-hydroxybutyrate (ghb) and Phentermine, Topiramate?
Phentermine, Topiramate 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 Phentermine, Topiramate 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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