Drug & supplement interaction

Gamma-aminobutyric Acid (gaba) + Acetaminophen, Codeine

Acetaminophen, Codeine brand names: Tylenol w/ Codeine, Tylenol No.3.

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

Gamma-aminobutyric Acid (gaba) has a minor interaction with Acetaminophen, Codeine. Theoretically, GABA might have additive sedative effects when used in conjunction with CNS depressants.

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

Gamma-aminobutyric Acid (gaba) and Acetaminophen, Codeine

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

Minor

CNS DEPRESSANTS

Why this applies to Acetaminophen, Codeine

Acetaminophen, Codeine falls under CNS DEPRESSANTS — the group Gamma-aminobutyric Acid (gaba) interacts with.

Theoretically, GABA might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Endogenous GABA has well-established relaxant effects and GABA(A) receptors have an established physiological role in sleep. However, the effects of GABA supplements are unclear, as it is unknown whether exogenous GABA crosses the blood-brain barrier. Although there have been limited reports of drowsiness or tiredness with GABA supplements, these effects have not been widely reported in clinical studies. Additionally, intravenous GABA 0.1-1 mg/kg has been shown to induce anxiety in a dose-dependent manner.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: GABA is a calming supplement, and the codeine side of Tylenol with Codeine already has its own sedating, drowsy effect (codeine is an opioid that gets turned into morphine in your body). On paper, stacking two calming things could add up to more sleepiness, dizziness, or grogginess than either alone.

That said, this is a theoretical worry. We honestly aren't sure how much swallowed GABA even reaches the brain, and real-world reports of it making people drowsy are pretty thin. So this is rated minor and unlikely. Still, if you notice you feel extra foggy or sluggish when using both, that's worth mentioning. And always check with your pharmacist or doctor before pairing GABA with any opioid product.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Cavagnini F, Invitti C, Pinto M, et al. Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Acta Endocrinol (Copenh) 1980;93:149-54.
  2. Nurnberger JI Jr, Berrettini WH, Simmons-Alling S, et al. Intravenous GABA administration is anxiogenic in man. Psychiatry Res 1986;19:113-7. PubMed
  3. Loeb C, Benassi E, Bo, GP, et al. Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients. Epilepsy Res. 1987;1:209-12 . PubMed
  4. ELLIOTT, K. A. and JASPER, H. H. Gammaaminobutyric acid. Physiol Rev. 1959;39(2):383-406.
  5. Winsky-Sommerer, R. Role of GABAA receptors in the physiology and pharmacology of sleep. Eur.J.Neurosci. 2009;29(9):1779-1794.
  6. Meldrum, B. S. GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br.J.Clin.Pharmacol. 1989;27 Suppl 1:3S-11S. PubMed
  7. Loeb, C., Marinari, U. M., Benassi, E., Besio, G., Cottalasso, D., Cupello, A., Maffini, M., Mainardi, P., Pronzato, M. A., and Scotto, P. A. Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats. Exp.Neurol. 1988;99(2):4 PubMed
  8. Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015 Oct 6;6:1520. doi: 10.3389/fpsyg.2015.01520. eCollection 2015. 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

Gamma-aminobutyric Acid (gaba) Also Interacts With Other Medications

Gamma-aminobutyric Acid (gaba) has 172 moderate, 246 minor known drug interactions in our database — the Acetaminophen, Codeine one above is one of them. If you take anything else, check it against the full list below.

Moderate 172 Minor 246 No known interaction 2,412 (incl. Acetaminophen, Codeine)
Taking anything else?

Check Another of Your Medications Against Gamma-aminobutyric Acid (gaba)

Covers the 2,830 medications we’ve checked against Gamma-aminobutyric Acid (gaba). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Codeine

This page covers Gamma-aminobutyric Acid (gaba) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine page lists 240 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 9 major · 191 moderate · 40 minor.

From our pharmacist’s overview on the Acetaminophen, Codeine page

“People usually take Tylenol No. 3 (acetaminophen with codeine) for short-term pain, often while still drinking wine with dinner or reaching for an herbal sleep aid.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Codeine interaction page

One more smart check

Taking Gamma-aminobutyric Acid (gaba) as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,760 real supplement products containing Gamma-aminobutyric Acid (gaba), each one broken down to its full ingredient list — and combination products often carry several ingredients besides Gamma-aminobutyric Acid (gaba). Your product may carry other ingredients that interact with Acetaminophen, Codeine too, on top of Gamma-aminobutyric Acid (gaba) — 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 Gamma-aminobutyric Acid (gaba) and Acetaminophen, Codeine 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-aminobutyric Acid (gaba)
Top 10%

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

29 days ago today
Medication Acetaminophen, Codeine
Top 5%

#45 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-aminobutyric Acid (gaba)

What is Gamma-aminobutyric Acid (gaba)?

Gamma-aminobutyric Acid (gaba)
  • Anxiety and stress
  • Sleep problems
  • Relaxation
  • High blood pressure
  • Mood support

GABA is a calming chemical messenger (neurotransmitter) that your body makes on its own, and it is sold as a supplement for stress, anxiety, and sleep. The science behind oral GABA supplements is limited and mixed, partly because it is unclear how much swallowed GABA actually reaches the brain. It is generally well tolerated short-term, but talk with a pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or take other medicines.

Read the full Gamma-aminobutyric Acid (gaba) monograph & all interactions
Keep checking

Other Drugs & Gamma-aminobutyric Acid (gaba)

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

0Major
172Moderate
246Minor
2,411No known interaction
172 Moderate 246 Minor 2,411 No interaction
Moderate

172 interactions

Showing 60 of 172 moderate interactions — see all 172 on the Gamma-aminobutyric Acid (gaba) page.

Minor

246 interactions

Showing 60 of 246 minor interactions — see all 246 on the Gamma-aminobutyric Acid (gaba) page.

No interaction 2,411 drugs checked — show the list

We also checked Gamma-aminobutyric Acid (gaba) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,411 medications checked with no known interaction — see the full Gamma-aminobutyric Acid (gaba) list.

See the full Gamma-aminobutyric Acid (gaba) interactions page
See every supplement checked against Acetaminophen, Codeine, 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-aminobutyric Acid (gaba) monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Codeine supplement interactions › Every supplement checked against Acetaminophen, Codeine, 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 Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Gamma-aminobutyric Acid (gaba) and Acetaminophen, Codeine Together: Common Questions

Can you take Gamma-aminobutyric Acid (gaba) with Acetaminophen, Codeine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Gamma-aminobutyric Acid (gaba) and Acetaminophen, Codeine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Acetaminophen, Codeine and Gamma-aminobutyric Acid (gaba)?

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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.