Drug & supplement interaction

Phenibut + Methadone

Methadone brand name: Dolophine.

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

Phenibut has a moderate interaction with Methadone. Theoretically, phenibut might increase the risk of sedation and respiratory depression when taken with CNS depressants.

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

Phenibut and Methadone

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Methadone

Methadone falls under CNS DEPRESSANTS — the group Phenibut interacts with.

Theoretically, phenibut might increase the risk of sedation and respiratory depression when taken with CNS depressants.
Phenibut has been associated with sedation and respiratory depression in several case reports, especially when taken at high doses.
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 simple version: both phenibut and methadone calm down your central nervous system. Methadone is a powerful opioid that already slows your breathing and makes you drowsy. Phenibut adds its own sedating, GABA-boosting effect on top of that. Stack the two and you could get dangerously deep sedation, very slow or shallow breathing, and trouble waking up. With a long-acting drug like methadone, that risk can sneak up hours later.

I want to be honest that this concern comes from theory and case reports, not large studies, but the danger is real enough that I wouldn't take chances. Phenibut isn't an approved product, and we don't recommend it. Please talk with your doctor or pharmacist before combining anything with methadone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Downes MA, Berling IL, Mostafa A, Grice J, Roberts MS, Isbister GK. Acute behavioural disturbance associated with phenibut purchased via an internet supplier. Clin Toxicol (Phila). 2015;53(7):636-8. PubMed
  2. O'Connell CW, Schneir AB, Hwang JQ, Cantrell FL. Phenibut, the appearance of another potentially dangerous product in the United States. Am J Med. 2014 Aug;127(8):e3-4. PubMed
  3. Sankary S, Canino P, Jackson J. Phenibut overdose. AM J Emerg Med. 2017 Mar;35(3):516.e1-516.e2.
  4. Graves JM, Dilley J, Kubsad S, Liebelt E. Notes from the field: phenibut exposures reported to poison centers - United States, 2009-2019. MMWR Morb Mortal Wkly Rep 2020;69(35):1227-8. 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

Phenibut Also Interacts With Other Medications

Phenibut has 247 moderate known drug interactions in our database — the Methadone one above is one of them. If you take anything else, check it against the full list below.

Moderate 247 No known interaction 2,583 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Phenibut

Covers the 2,830 medications we’ve checked against Phenibut. Pick one to open its full report.

From our Q&A

Questions About Phenibut 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 Phenibut 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 Phenibut 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

One more smart check

Taking Phenibut as Part of a Dietary Supplement Product? Check It for Interactions

We hold 41 real supplement products containing Phenibut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phenibut. Your product may carry other ingredients that interact with Methadone too, on top of Phenibut — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Phenibut 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 Phenibut
Top half

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

29 days ago today
Medication Methadone
Top half

#1,071 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 Phenibut

What is Phenibut?

Phenibut
  • Anxiety and stress
  • Insomnia and sleep problems
  • Stress relief
  • Mood and focus
  • Reducing alcohol withdrawal symptoms (unproven)

Phenibut is a synthetic, lab-made central nervous system depressant—not a natural herb—that some people use for anxiety and sleep, but it carries a serious risk of tolerance, dependence, and dangerous withdrawal. It is not an approved medication or dietary supplement in the United States, and we do not recommend its use. Talk to a doctor or pharmacist about safer, proven options for anxiety or sleep.

Read the full Phenibut 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 & Phenibut

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

0Major
247Moderate
0Minor
2,582No known interaction
247 Moderate 2,582 No interaction
Moderate

247 interactions

Showing 60 of 247 moderate interactions — see all 247 on the Phenibut page.

No interaction 2,582 drugs checked — show the list

We also checked Phenibut against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,582 medications checked with no known interaction — see the full Phenibut list.

See the full Phenibut 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
Phenibut 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 Phenibut and Methadone Together: Common Questions

Can you take Phenibut 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.
How serious is the Phenibut 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 Phenibut?

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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.