Drug & supplement interaction

Ayahuasca + Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.

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

Acetaminophen, Caffeine, Codeine falls into 2 drug categories that Ayahuasca can interact with; the most serious is rated moderate. Theoretically, ayahuasca might increase plasma concentrations of CYP2D6 substrates.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ayahuasca and Acetaminophen, Caffeine, Codeine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Ayahuasca interacts with whole categories of medication. Acetaminophen, Caffeine, Codeine falls into 2 of those categories, so it can interact with Ayahuasca in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Caffeine, Codeine

Acetaminophen, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Ayahuasca interacts with.

Theoretically, ayahuasca might increase plasma concentrations of CYP2D6 substrates.
Ayahuasca contains beta-carboline alkaloids, including harmine and harmaline. In vitro research suggests that the beta-carboline alkaloids might inhibit CYP2D6 enzymes. This effect has not been reported in humans.
Severity Moderate 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 tricky part with this combo pill. The codeine part is a prodrug, meaning it does nothing for pain until your body converts it into morphine using an enzyme called CYP2D6. Lab studies suggest the beta-carboline compounds in ayahuasca (harmine and harmaline) may block that same enzyme. If that happens, less codeine gets turned into morphine, so you might get weaker pain relief rather than more.

This is only theoretical and based on test-tube data, not real people, so I don't want to alarm you. But ayahuasca carries its own serious safety risks (it acts like an MAOI), and combining it with any medication deserves a real conversation. Please check with your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
  2. dos Santos RG. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology. J Psychoactive Drugs. 2013 Jan-Mar;45(1):68-78. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Acetaminophen, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, ayahuasca might increase plasma concentrations of CYP3A4 substrates.
Ayahuasca contains beta-carboline alkaloids. In vitro research suggests that beta-carboline alkaloids competitively inhibit CYP3A4 enzymes. This effect has not been reported in humans.
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

This combo pill contains three things, but the part to watch most is the codeine. Lab studies hint that ayahuasca's beta-carboline compounds can gently block the CYP3A4 enzyme, one of the pathways that helps clear these ingredients. If that pathway slows, levels could creep up, meaning more drowsiness, dizziness, nausea, or slowed breathing from the codeine, and possibly more jitteriness from the caffeine.

Honestly, this is only seen in test-tube research, not in real people, so the actual risk is uncertain. The bigger worry is that ayahuasca acts as an MAOI, which can react badly with opioids and caffeine on its own. Please run this by your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
  2. dos Santos RG. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology. J Psychoactive Drugs. 2013 Jan-Mar;45(1):68-78. 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

Ayahuasca Also Interacts With Other Medications

Ayahuasca has 803 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.

Moderate 803 No known interaction 2,027 (incl. Acetaminophen, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Ayahuasca

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Caffeine, Codeine

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine page lists 303 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 Ephedra (major).

By severity: 15 major · 244 moderate · 44 minor.

Open the Acetaminophen, Caffeine, Codeine interaction page

How much people look this up

Where Ayahuasca and Acetaminophen, Caffeine, 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 Ayahuasca
Top half

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

29 days ago today
Medication Acetaminophen, Caffeine, Codeine
Top 10%

#145 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 Ayahuasca

What is Ayahuasca?

Ayahuasca
  • Spiritual and ceremonial rituals
  • Depression
  • Anxiety
  • Substance use disorders
  • Personal or emotional insight

Ayahuasca is a powerful psychoactive brew that combines a DMT-containing plant with a vine that allows the DMT to take effect, causing intense hallucinations. It is illegal in many places, can trigger dangerous reactions, and is not recommended for self-use; talk to a doctor or pharmacist before considering it.

Read the full Ayahuasca monograph & all interactions
Keep checking

Other Drugs & Ayahuasca

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

0Major
803Moderate
0Minor
2,026No known interaction
803 Moderate 2,026 No interaction
Moderate

803 interactions

Showing 60 of 803 moderate interactions — see all 803 on the Ayahuasca page.

No interaction 2,026 drugs checked — show the list

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

Showing the 60 most looked-up of 2,026 medications checked with no known interaction — see the full Ayahuasca list.

See the full Ayahuasca interactions page
See every supplement checked against Acetaminophen, Caffeine, 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
Ayahuasca monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Caffeine, 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 Ayahuasca and Acetaminophen, Caffeine, Codeine Together: Common Questions

Can you take Ayahuasca with Acetaminophen, Caffeine, Codeine?
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.
Why are there 2 interactions listed for Ayahuasca and Acetaminophen, Caffeine, Codeine?
Acetaminophen, Caffeine, Codeine belongs to more than one drug category, and Ayahuasca 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 Ayahuasca and Acetaminophen, Caffeine, Codeine 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

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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.