Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Gabapentin enacarbil

Gabapentin enacarbil brand name: Horizant.

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

Gabapentin enacarbil 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 Gabapentin enacarbil

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. Gabapentin enacarbil 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 Gabapentin enacarbil

Gabapentin enacarbil 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 GHB and Horizant (gabapentin enacarbil) calm down your central nervous system. When you stack two sedating substances like these, their effects add together. That can leave you overly drowsy, dizzy, confused, or unsteady on your feet, and in a worse case it can slow your breathing to a dangerous level. GHB is especially risky because, unlike a prescription supplement, street GHB is unpredictable and has caused comas and deaths on its own.

Horizant isn't a prodrug in a way that flips this, it works directly to quiet nerve signals, so adding GHB simply piles on more sedation. This warning comes from anecdotal reports, but the potential outcome is serious enough that I'd never combine them. 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

Gabapentin enacarbil 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 things first: GHB really isn't a dietary supplement at all. It's a powerful, illegal central nervous system depressant, and mixing it with anything is risky. With Horizant (gabapentin enacarbil), there are two concerns. GHB has been reported to trigger seizures, so in theory it could work against the very thing your medicine is meant to calm down, whether that's seizures, nerve pain, or restless legs.

The bigger worry is the opposite direction: both GHB and gabapentin slow the brain down. Together they can stack up that effect, leading to heavy sedation, confusion, slowed or stopped breathing, and in serious cases coma. This is based mostly on anecdotal reports, but the danger is real. Please don't use GHB, and talk with your doctor or pharmacist about any sedating substances.

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 Gabapentin enacarbil 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. Gabapentin enacarbil)
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.

From our Q&A

Questions About Gamma-hydroxybutyrate (ghb) or Gabapentin enacarbil

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Gamma-hydroxybutyrate (ghb) or Gabapentin enacarbil, 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 Gabapentin enacarbil

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Gabapentin enacarbil page lists 105 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 · 82 moderate · 16 minor.

From our pharmacist’s overview on the Gabapentin enacarbil page

“Alcohol tops the list of supplement and food risks for gabapentin enacarbil (Horizant), a nerve pain and restless legs medicine that already slows the central nervous system. Beer and wine both carry major ratings because their sedation stacks on the drug's own, and 78 of the 105 ingredients on file act the same way, deepening drowsine…”

Reviewed by 2 · Jul 18, 2026

Open the Gabapentin enacarbil interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Gabapentin enacarbil 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

#1,235 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Gabapentin enacarbil
Top 25%

#445 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 Gabapentin

What Is Gabapentin Used For?

Brand name: Horizant

Gabapentin (brands include Neurontin, Relgaabi, Gabarone, Gralise, and Horizant) is primarily used to manage postherpetic neuralgia (PHN) — the nerve pain that lingers after a shingles outbreak — in adults. Neurontin, Relgaabi, Gabarone, and gabapentin capsules, tablets, and oral solution are also used as add-on therapy for partial onset seizures (a type of epilepsy) in adults and children aged 3 and older.

Horizant (gabapentin enacarbil extended-release tablet) has two specific approvals: treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults, and management of postherpetic neuralgia in adults. Horizant is not recommended for people who need to sleep during the day and stay awake at night. Gralise is approved only for postherpetic neuralgia and cannot be substituted for other gabapentin products due to its different release profile.

See full Gabapentin 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 Gabapentin enacarbil, 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
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Pharmacist Counseling Corner

Taking Gamma-hydroxybutyrate (ghb) and Gabapentin enacarbil Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Gabapentin enacarbil?
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 Gabapentin enacarbil?
Gabapentin enacarbil 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 Gabapentin enacarbil 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.