Drug & supplement interaction

Gamma-hydroxybutyrate (ghb) + Oxycodone, Naloxone

Oxycodone, Naloxone brand name: Targiniq ER.

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

Oxycodone, Naloxone 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 Oxycodone, Naloxone

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. Oxycodone, Naloxone 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 Oxycodone, Naloxone

Oxycodone, Naloxone 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 big picture: Targiniq ER (oxycodone with naloxone) is an opioid painkiller, and opioids already slow down your breathing and your brain. GHB is a strong sedative that does the very same thing. Stacking two heavy central nervous system depressants like these is a dangerous combination. They don't cancel out, they add up.

Together they could push you into deep sedation, dangerously slow or shallow breathing, and even coma or death. This isn't a subtle chemistry quirk, it's two drugs piling on the same effect. The evidence here is mostly anecdotal, but the risk is real and serious enough that I'd urge you not to combine them. Please talk with your doctor or pharmacist before doing anything.

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

NALOXONE (Narcan)

2 of 2
Theoretically, naloxone may antagonize the effects of GHB.
Theoretically, naloxone may antagonize the effects of GHB, but anecdotally, naloxone is not effective for treating GHB poisoning.
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

Let me set the record straight on this combination. Targiniq ER pairs oxycodone (a strong opioid painkiller) with a small amount of naloxone, the same opioid-blocker found in Narcan. The interaction on file says that, in theory, naloxone might counteract some of GHB's effects. But here's the honest part: this is based only on weak, anecdotal reports, and in real life naloxone does not reliably reverse GHB poisoning. GHB works mainly through GABA-B receptors, not opioid receptors, so the naloxone in your medicine isn't a safety net against GHB.

The bigger concern is that GHB and oxycodone are both heavy central nervous system depressants. Together they can cause dangerous sedation, slowed or stopped breathing, and unresponsiveness. GHB is not a safe supplement to take at all. Please talk with your pharmacist or doctor before combining anything with this medication.

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

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 Oxycodone, Naloxone 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. Oxycodone, Naloxone)
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.

Everything else you take

See Every Supplement That Interacts With Oxycodone, Naloxone

This page covers Gamma-hydroxybutyrate (ghb) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Oxycodone, Naloxone page lists 145 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: 8 major · 114 moderate · 23 minor.

From our pharmacist’s overview on the Oxycodone, Naloxone page

“Targiniq ER combines the opioid oxycodone with naloxone for around-the-clock pain, and because opioids can dangerously slow breathing once sedation stacks up, the 145 supplements on file here deserve genuine respect, above all the eight rated major. The largest group, 78 ingredients, layers drowsiness onto the opioid's own, with alcoho…”

Reviewed by 2 · Jul 18, 2026

Open the Oxycodone, Naloxone interaction page

How much people look this up

Where Gamma-hydroxybutyrate (ghb) and Oxycodone, Naloxone 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

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

29 days ago today
Medication Oxycodone, Naloxone
Top 25%

#548 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
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 Oxycodone, Naloxone, 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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Taking Gamma-hydroxybutyrate (ghb) and Oxycodone, Naloxone Together: Common Questions

Can you take Gamma-hydroxybutyrate (ghb) with Oxycodone, Naloxone?
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 Oxycodone, Naloxone?
Oxycodone, Naloxone 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 Oxycodone, Naloxone 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.