Drug & supplement interaction

Gamma Butyrolactone (gbl) + Methadone

Methadone brand name: Dolophine.

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

Methadone falls into 2 drug categories that Gamma Butyrolactone (gbl) can interact with; the most serious is rated moderate. Theoretically, concomitant use of GBL with CNS depressants may potentiate respiratory and CNS depression.

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

Gamma Butyrolactone (gbl) and Methadone

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

Why Are There 2 Interactions?

Gamma Butyrolactone (gbl) interacts with whole categories of medication. Methadone falls into 2 of those categories, so it can interact with Gamma Butyrolactone (gbl) 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 Methadone

Methadone falls under CNS DEPRESSANTS — the group Gamma Butyrolactone (gbl) interacts with.

Theoretically, concomitant use of GBL with CNS depressants may potentiate respiratory and CNS depression.
GBL is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of CNS depressants with GHB may cause 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 straight-talk safety note: GBL isn't a real supplement. It's a toxic solvent your body turns into GHB, a heavy sedative, and it's illegal to use in people. So my honest advice is simple: don't take it, especially alongside methadone.

Here's the concern. Methadone is already a strong opioid that slows your breathing and your brain. GHB does the very same thing through GABA signaling. Stack the two and those slowing effects can pile up, leading to deep drowsiness, confusion, dangerously slow or shallow breathing, and in a worst case, coma. The evidence here is mostly anecdotal and theoretical, but the risk with two heavy nervous-system depressants is real enough to take seriously. Please talk with your doctor or pharmacist before mixing anything with methadone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Important message for health professionals: Report serious adverse events associated with dietary supplements containing GBL, GHB or BD. Food and Drug Administration, Rockville, MD. August 25, 1999. Available at: http://vm.cfsan.fda.gov/~dms/mwg
  2. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  3. Product information for Xyrem. Jazz Pharmaceuticals, Inc. Palo Alto, CA. March 2022.
Moderate

NARCOTIC DRUGS

2 of 2

Methadone also falls under NARCOTIC DRUGS.

Theoretically, concomitant use of GBL with narcotic drugs may potentiate respiratory and central nervous system (CNS) depression.
GBL is metabolized to gamma-hydroxybutyrate (GHB). Concomitant use of narcotic drugs with GHB may cause serious CNS and respiratory depression. In one case report, concurrent use of GHB and heroin was fatal.
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, the most important thing: GBL isn't a supplement at all. It's a toxic industrial solvent that your body turns into GHB, a heavy-duty sedative, and it's illegal to sell or take. So my real advice is to steer clear of it completely.

Here's the danger when you mix it with methadone. Both substances calm down the brain and slow your breathing. Methadone already carries a serious risk of slowed, shallow breathing on its own, and stacking GHB on top of it can push that much further, leading to deep sedation, unresponsiveness, dangerously slow breathing, or worse. A reported case of GHB combined with another opioid was fatal. The evidence here is anecdotal, but the risk is real enough that I'd never take the chance. Please talk with your doctor or pharmacist about safe options.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Important message for health professionals: Report serious adverse events associated with dietary supplements containing GBL, GHB or BD. Food and Drug Administration, Rockville, MD. August 25, 1999. Available at: http://vm.cfsan.fda.gov/~dms/mwg
  2. Anon. Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. JAMA 1991;265:447-8. DOI
  3. Ferrara SD, Tedeschi L, Frison G, Rossi A. Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication. J Forensic Sci 1995;40:501-4. DOI
  4. 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 Butyrolactone (gbl) Also Interacts With Other Medications

Gamma Butyrolactone (gbl) has 270 moderate known drug interactions in our database — the Methadone one above is among them. If you take anything else, check it against the full list below.

Moderate 270 No known interaction 2,560 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Gamma Butyrolactone (gbl)

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

From our Q&A

Questions About Gamma Butyrolactone (gbl) or Methadone

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 Butyrolactone (gbl) or Methadone, 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 Methadone

This page covers Gamma Butyrolactone (gbl) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methadone page lists 223 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: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Methadone page

“If you take methadone, choose your supplements with genuine care. Of the 223 ingredients on this page, most either add to methadone's sedating effect or change how fast your body clears it, which can push its blood level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Methadone interaction page

How much people look this up

Where Gamma Butyrolactone (gbl) and Methadone 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 Butyrolactone (gbl)
Steady interest

#1,219 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Methadone
Top 25%

#535 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 Butyrolactone (gbl)

What is Gamma Butyrolactone (gbl)?

Gamma Butyrolactone (gbl)
  • Recreational intoxication and euphoria
  • Relaxation and sedation
  • Sleep aid (misused)
  • Bodybuilding/muscle building claims (unproven)
  • Industrial solvent and cleaner

Gamma butyrolactone (GBL) is a toxic industrial solvent, not a dietary supplement, and the body converts it into GHB, a powerful and dangerous sedative. It is illegal to sell or possess for human use in the United States, has no proven medical or supplemental benefit, and can cause coma, seizures, and death. Do not take GBL — if you are seeking help for sleep, anxiety, or substance use, talk to a doctor or pharmacist.

Read the full Gamma Butyrolactone (gbl) monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment and cannot be managed adequately with other options. It is available in several forms for this use, including oral solution, oral tablets, oral concentrate, and injectable forms (intravenous, intramuscular, and subcutaneous). Injectable methadone is not approved for outpatient pain treatment — it is reserved for hospitalized patients unable to take oral medication.

Methadone is also used for the detoxification and maintenance treatment of opioid addiction (dependence on heroin or other morphine-like drugs). Oral forms — including tablets, dispersible tablets (such as Methadose Dispersible and DISKETS), and oral concentrates (such as Methadone Hydrochloride Intensol™, Methadose, and others) — are approved for this use. By law, methadone for opioid addiction treatment must be dispensed only by certified opioid treatment programs. Injectable methadone is not approved for outpatient addiction treatment.

See full Methadone drug information
Keep checking

Other Drugs & Gamma Butyrolactone (gbl)

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

0Major
270Moderate
0Minor
2,559No known interaction
270 Moderate 2,559 No interaction
Moderate

270 interactions

Showing 60 of 270 moderate interactions — see all 270 on the Gamma Butyrolactone (gbl) page.

No interaction 2,559 drugs checked — show the list

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

Showing the 60 most looked-up of 2,559 medications checked with no known interaction — see the full Gamma Butyrolactone (gbl) list.

See the full Gamma Butyrolactone (gbl) interactions page
See every supplement checked against Methadone, 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 Butyrolactone (gbl) monograph › Uses, safety, and every drug interaction in one place Methadone supplement interactions › Every supplement checked against Methadone, ranked by severity Methadone 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 Butyrolactone (gbl) and Methadone Together: Common Questions

Can you take Gamma Butyrolactone (gbl) with Methadone?
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 Gamma Butyrolactone (gbl) and Methadone?
Methadone belongs to more than one drug category, and Gamma Butyrolactone (gbl) 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 Butyrolactone (gbl) and Methadone 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 Methadone and Gamma Butyrolactone (gbl)?

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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.