Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Codeine Phosphate

Codeine Phosphate brand name: Codeine.

Major Interaction
The bottom line Major

Gamma-hydroxybutyrate (ghb) has a major interaction with Codeine Phosphate. GHB may increase the risk of serious CNS and respiratory depression.

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

Gamma-hydroxybutyrate (ghb) and Codeine Phosphate

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

Major

CNS DEPRESSANTS

Why this applies to Codeine Phosphate

Codeine Phosphate 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 codeine slow down your central nervous system. Codeine is an opioid that relaxes your brain and dampens your breathing drive, and GHB is a powerful sedative that does much the same thing. Stack them together and those calming effects can pile up. We're talking about heavy drowsiness, confusion, very slow or shallow breathing, and in a worst case, losing consciousness or stopping breathing altogether.

This combination is rated as a major concern, even though the proof so far is mostly from real-world reports rather than formal studies. Keep in mind that non-prescription GHB is dangerous and illegal on its own. Please don't pair these without talking to your doctor or pharmacist first.

References
  1. 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 Codeine Phosphate one above is one of 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.

From our Q&A

Questions About Gamma-hydroxybutyrate (ghb) or Codeine Phosphate

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 Codeine Phosphate, 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 Codeine Phosphate

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine Phosphate page lists 144 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 · 114 moderate · 23 minor.

From our pharmacist’s overview on the Codeine Phosphate page

“Codeine phosphate is an opioid painkiller and cough suppressant that slows breathing along with brain activity, and the wrong supplement can push that effect into dangerous territory. Seven of the 144 documented ingredients rate major, and nearly all of that serious risk comes from things that deepen sedation.”

Reviewed by 2 · Jul 18, 2026

Open the Codeine Phosphate interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Codeine Phosphate 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

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

29 days ago today
Medication Codeine Phosphate
Top 25%

#380 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 Codeine

What Is Codeine Used For?

Brand name: Codeine

Codeine Sulfate tablets are used for the management of mild to moderate pain in adults and adolescents when other treatments have not worked well enough or are not tolerated. It is an opioid medication, so it is only appropriate when non-opioid options are inadequate.

Because of its serious risks — including addiction, misuse, and overdose — codeine is reserved for patients who truly need an opioid. Prescribers are expected to use the lowest effective dose for the shortest time possible.

See full Codeine 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
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 Codeine Phosphate Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Codeine Phosphate?
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.
How serious is the Gamma-hydroxybutyrate (ghb) and Codeine Phosphate 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

Still Have a Question About Codeine Phosphate and Gamma-hydroxybutyrate (ghb)?

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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.