Drug & supplement interaction

Phenibut + Promethazine

Promethazine brand name: Phenergan.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Phenibut and Promethazine in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Phenibut and Promethazine

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Promethazine and Phenibut in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Phenibut safety at a glance

Phenibut overall Avoid Phenibut carries a high risk of dependence, dangerous withdrawal, and overdose, and is not approved as a supplement or drug in the U.S.
Pregnancy Avoid There is no safety data in pregnancy and it is a CNS depressant, so it should be avoided.
Breastfeeding Avoid It is unknown whether phenibut passes into breast milk, so it should be avoided while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Promethazine and Phenibut? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Promethazine

Interactions in our licensed database are recorded against drug classes, not just single drug names. Promethazine is filed under 4 classifications — including phenothiazines, anticholinergic drugs, photosensitizing drugs. Phenibut has documented interactions with 2 drug classes — the most serious being cns depressants (moderate) and pregabalin (lyrica) (moderate) — and none of Promethazine’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Phenibut Does Interact With Other Medications

Phenibut has 248 moderate known drug interactions in our database — Promethazine isn’t one of them. If you take anything else, check it against the full list below.

Moderate 248 No known interaction 2,582 (incl. Promethazine)
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.

What to actually watch for

No Interaction Found — But Data Suggests Phenibut and Promethazine May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 3 of them are worth acting on rather than waiting out — marked below.

  • Hallucinations / Confusion / Seizures Worth acting on Additional detail

    Phenibut

    “Orally, phenibut has been associated with aggression, agitation, altered mental status, anxiety, sedation, hallucinations, insomnia, and coma in case reports and case series. Phenibut is often used concurrently with other addictive substances, including alcohol.

    Observational research and case reports have found that the use of phenibut can lead to the rapid development of tolerance within 3 days, and that use for 3…”

    Phenibut · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 96748. 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. 96750. 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. 96753. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
    4. 101108. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
    5. 101109. Ahuja T, Mgbako O, Katzman C, Grossman A. Phenibut (β-Phenyl-γ-aminobutyric Acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Rep Psychiatry. 2018;2018:9864285.
    6. 101110. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. PubMed

    Promethazine

    Listed in the ADVERSE REACTIONS section of the FDA label for Promethazine. Read the label on DailyMed ›

  • A fast or pounding heartbeat Additional detail

    Phenibut

    “Orally, phenibut has been associated with withdrawal symptoms, including tachycardia, palpitations, and hypertension.”

    Phenibut · Natural Medicines adverse-effect record, reported in hypertension.

    6 sources cited
    1. 101108. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
    2. 101111. McCabe DJ, Bangh SA, Arens AM, Cole JB. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med. 2019;37(11):2066-2071. PubMed
    3. 104511. Tamarelli C, Hosanagar A. Phenibut use in a patient prescribed gabapentinoids (letter). Pain Med 2020; Aug 4:pnaa205. doi: 10.1093/pm/pnaa205. PubMed
    4. 106839. Esposito CM, Mandolini GM, Delvecchio G, Fiorentini A, Brambilla P. Psychomotor agitation non-responsive to treatment: a case report of phenibut withdrawal syndrome. Front Psychiatry 2021;12:688147. PubMed
    5. 112293. Martin R, Buffenstein I, Cho D, Kiyokawa M. Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium. J Clin Psychopharmacol 2023. PubMed
    6. 112294. Morris M, Espinosa J, Lucerna A, Lahr R. A case of phenibut withdrawal and treatment with baclofen. World J Emerg Med 2023;14(4):338-340. PubMed

    Promethazine

    Listed in the ADVERSE REACTIONS section of the FDA label for Promethazine. Read the label on DailyMed ›

  • Drowsiness / Anxiety or restlessness / Trouble sleeping / Nausea reported in 11.7% of FDA reports for Promethazine Additional detail

    Phenibut

    Recorded for Phenibut in the same Natural Medicines adverse-effect record shown under Hallucinations / Confusion / Seizures above.

    Promethazine

    Listed in the ADVERSE REACTIONS section of the FDA label for Promethazine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Tiredness reported in 6.6% of FDA reports for Promethazine Additional detail

    Phenibut

    Recorded for Phenibut in the same Natural Medicines adverse-effect record shown under Hallucinations / Confusion / Seizures above.

    Promethazine

    Listed in the ADVERSE REACTIONS section of the FDA label for Promethazine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Vomiting reported in 8.0% of FDA reports for Promethazine Additional detail

    Phenibut

    “Orally, phenibut has been associated with nausea and vomiting. Regular phenibut use followed by abrupt discontinuation is associated with withdrawal symptoms, including decreased appetite and nausea.”

    Phenibut · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    3 sources cited
    1. 96753. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
    2. 101110. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. PubMed
    3. 96754. Magsalin RM, Khan AY. Withdrawal symptoms after internet purchase of phenibut (beta-phenyl-gamma-aminobutyric acid HCl). J Clin Psychopharmacol. 2010 Oct;30(5):648-9.

    Promethazine

    Listed in the ADVERSE REACTIONS section of the FDA label for Promethazine, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

Showing the 10 most notable of 11 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for Phenibut but not commonly for Promethazine: dependence or withdrawal symptoms, kidney problems, reduced appetite and severe muscle breakdown.

Effects for Promethazine come from the ADVERSE REACTIONS section of its FDA label; effects for Phenibut come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 22,361 voluntary FDA FAERS reports for Promethazine that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

From our Q&A

Questions About Phenibut or Promethazine

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 Promethazine, 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 Promethazine

This page covers Phenibut only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Promethazine page lists 83 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Scopolia (major), Alfalfa (moderate) and Angel's Trumpet (moderate).

By severity: 3 major · 57 moderate · 23 minor.

From our pharmacist’s overview on the Promethazine page

“Promethazine (Phenergan) is a phenothiazine antihistamine used for allergies, nausea, and motion sickness, and it is strongly anticholinergic on its own, causing dry mouth, blurred vision, drowsiness, and constipation. That is why the 83 supplements and herbs on this list deserve real attention, starting with the three rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Promethazine 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. Even though Phenibut itself has no known interaction with Promethazine, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Phenibut and Promethazine 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

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

29 days ago today
Medication Promethazine
Steady interest

#2,102 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Phenibut reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Phenibut and Promethazine records this page draws on were last updated July 11, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
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.

Synthetic compound (not a plant part) · Powder, capsules, tablets

An interaction check asks whether these two react with each other — it does not ask whether Phenibut is a good idea for someone in your situation. Here is what our Phenibut record says about it on its own.

Phenibut: dosing

There is no established safe or standardized dose of phenibut for use as a supplement, and it is not approved as a medicine or supplement in the United States. Products sold online are unregulated, so the actual amount and purity can vary widely and be unpredictable.Because of the real risk of dependence, dangerous withdrawal, and overdose, we do not provide dosing guidance and do not recommend using phenibut. If you already use it regularly, do not stop suddenly—get medical help to taper safely.

From our Phenibut monograph — the full record covers uses, side effects and every documented interaction.

Read the full Phenibut monograph & all interactions
Medication

About Promethazine

What Is Promethazine Used For?

Brand name: Phenergan

Promethazine is used for a wide range of conditions. Tablets, oral solution, and rectal suppositories (brands including Phenergan, Promethegan, and Phenadoz) are approved for seasonal and perennial allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, hives (urticaria), angioedema, dermographism, and allergic reactions to blood or plasma. They are also used for motion sickness (both prevention and active treatment), nausea and vomiting related to anesthesia and surgery, sedation, and as a helper medication alongside pain relievers after surgery.

Promethazine hydrochloride injection (brands including Phenergan and Promethazine HCl injection) is used for many of the same purposes but is reserved for situations where oral treatment is not possible — including allergic emergencies as an adjunct to epinephrine, sedation during labor, and as an aid during certain surgical procedures such as bronchoscopy and eye surgery.

Most-Reported Side Effects for Promethazine

From FAERS, the FDA’s public side-effect reporting system (22,614 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Dependence 3,586 reports
Nausea 2,646 reports
Vomiting 1,802 reports
Fatigue 1,496 reports
Diarrhea 1,341 reports
See full Promethazine 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
248Moderate
0Minor
2,581No known interaction
248 Moderate 2,581 No interaction
Moderate

248 interactions

Showing 60 of 248 moderate interactions — see all 248 on the Phenibut page.

No interaction 2,581 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 2,581 medications checked with no known interaction — see the full Phenibut list.

See the full Phenibut interactions page
See every supplement checked against Promethazine, ranked by severity
Evidence & sources

Phenibut References

The 23 references that drive our Phenibut monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  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. Samokhvalov AV, Paton-Gay CL, Balchand K, Rehm J. Phenibut dependence. BMJ Case Rep. 2013 Feb 6;2013. Pii: bcr2012008381.
  3. 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
  4. Brunner E, Levy R. Case report of physiologic phenibut dependence treated with a phenobarbital taper in a patient being treated with buprenorphine. J Addict Med. 2017 May/Jun;11(3):239-40. PubMed
  5. Sankary S, Canino P, Jackson J. Phenibut overdose. AM J Emerg Med. 2017 Mar;35(3):516.e1-516.e2.
  6. Owen DR, Wood DM, Archer JR, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects, and acute toxicity. Drug Alcohol Rev. 2016 Sep;35(5):591-6. PubMed
  7. Magsalin RM, Khan AY. Withdrawal symptoms after internet purchase of phenibut (beta-phenyl-gamma-aminobutyric acid HCl). J Clin Psychopharmacol. 2010 Oct;30(5):648-9.
  8. Rod W, Kudryk A, Brunetti L, Sun N, Nguyen M. Phenibut withdrawal management in the setting of concomitant kratom and alcohol dependence. Critical Care Med 2018;46(1):451.
  9. Li W, Madhira B. Phenibut (beta-phenyl-gamma-aminobutyric acid) psychosis. Am J Therapeut 2017;24(5):e639-640.
  10. Joshi Y, Friend S, Jimenez B, Steiger L. Dissociative intoxication and prolonged withdrawal associated with phenibut: a case report. J Clin Psychopharmacol 2017;37(4):478-80. PubMed
  11. Zheng KH, Khan A, Espiridion ED. Phenibut addiction in a patient with substance use disorder. Cureus. 2019;11(7):e5230. PubMed
  12. Hardman MI, Sprung J, Weingarten TN. Acute phenibut withdrawal: A comprehensive literature review and illustrative case report. Bosn J Basic Med Sci. 2019;19(2):125-129. PubMed
  13. Ahuja T, Mgbako O, Katzman C, Grossman A. Phenibut (β-Phenyl-γ-aminobutyric Acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Rep Psychiatry. 2018;2018:9864285.
  14. Isoardi KZ, Kulawickrama S, Isbister GK. Severe phenibut poisoning: An adolescent case cluster. J Paediatr Child Health. 2020;56(2):330-331. PubMed
  15. McCabe DJ, Bangh SA, Arens AM, Cole JB. Phenibut exposures and clinical effects reported to a regional poison center. Am J Emerg Med. 2019;37(11):2066-2071. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Phenibut and Promethazine Together: Common Questions

Is it safe to take Phenibut with Promethazine?
We do not list a known interaction between Phenibut and Promethazine. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Phenibut and Promethazine have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
How was the Phenibut and Promethazine combination checked?
Interactions in our licensed database are recorded against drug classes. Promethazine is filed under 4 classifications, and Phenibut has documented interactions with 2 drug classes — none of Promethazine's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Phenibut interact with any other medications?
Yes. Phenibut has 248 documented drug interactions in our database — Promethazine is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Promethazine interact with any supplements?
Yes. Promethazine has documented interactions with 83 supplements in our database — Phenibut is not one of them. The Promethazine interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Phenibut monograph Uses, safety profile, and every drug interaction in one place Promethazine drug information The full plain-English guide to this medication Promethazine supplement interactions Every supplement checked against Promethazine, 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 References The 23 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Promethazine 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.