Drug & supplement interaction

Ayahuasca + Tramadol

Tramadol brand names: Ultram, Zytram XL, Qdolo.

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

Tramadol falls into 3 drug categories that Ayahuasca can interact with; the most serious is rated moderate. Theoretically, ayahuasca might increase levels of serotonin, which may have additive effects with serotonergic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ayahuasca and Tramadol

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Ayahuasca interacts with whole categories of medication. Tramadol falls into 3 of those categories, so it can interact with Ayahuasca in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SEROTONERGIC DRUGS

1 of 3

Why this applies to Tramadol

Tramadol falls under SEROTONERGIC DRUGS — the group Ayahuasca interacts with.

Theoretically, ayahuasca might increase levels of serotonin, which may have additive effects with serotonergic drugs.
In vitro and animal research shows that harmaline and harmine, constituents of ayahuasca, strongly and reversibly inhibit monoamine oxidase A and weakly inhibit monoamine oxidase B. The dimethyltryptamine and tetrahydroharmine constituents of ayahuasca have also demonstrated serotonergic activity. A case of serotonin syndrome characterized by tremors, sweating, shivering, confusion, nausea, vomiting, and disorientation has been reported in a 36-year-old male who consumed 100 mL of ayahuasca while taking fluoxetine 20 mg daily. Combining serotonergic drugs with ayahuasca might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders.
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

Here's something worth knowing about this pairing. Tramadol does more than just dull pain. It also raises serotonin levels in your brain. Ayahuasca does the same thing, partly because the vine acts like an MAO inhibitor that lets serotonin build up. Stack the two together and you can push serotonin too high, which can trigger what we call serotonin syndrome.

Watch for things like shivering, sweating, a racing heart, tremors, agitation, confusion, or nausea and vomiting. Tramadol also lowers the seizure threshold on its own, so that's an added concern here. This warning is mostly theoretical and based on pharmacology, but a real case of serotonin syndrome has happened with another serotonin drug. Please don't combine these without talking to your doctor or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kawanishi, K., Hashimoto, Y., Fujiwara, M., Kataoka, Y., and Ueki, S. Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice. J Pharmacobiodyn 1981;4(7):520-527. PubMed
  2. Herraiz, T., Gonzalez, D., Ancin-Azpilicueta, C., Aran, V. J., and Guillen, H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol 2010;48(3):839-845. PubMed
  3. Fuller, R. W., Wong, C. J., and Hemrick-Luecke, S. K. MD 240928 and harmaline: opposite selectivity in antagonism of the inactivation of types A and B monoamine oxidase by pargyline in mice. Life Sci 1986;38(5):409-412. PubMed
  4. Abdel-Fattah, A. F., Matsumoto, K., Murakami, Y., Adel-Khalek, Gammaz H., Mohamed, M. F., and Watanabe, H. Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats. Ge PubMed
  5. Bergstrom, M., Westerberg, G., and Langstrom, B. 11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies. Nucl Med Biol 1997;24(4):287-293. PubMed
  6. Gerardy, J. Effect of moclobemide on rat brain monoamine oxidase A and B: comparison with harmaline and clorgyline. Prog Neuropsychopharmacol Biol Psychiatry 1994;18(4):793-802.
  7. Sacher, J., Houle, S., Parkes, J., Rusjan, P., Sagrati, S., Wilson, A. A., and Meyer, J. H. Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study. J Psychiatry
  8. 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
  9. dos Santos RG. A critical evaluation of reports associating ayahuasca with life-threatening adverse reactions. J Psychoactive Drugs. 2013 Apr-Jun;45(2):179-88. PubMed
  10. Callaway JC, Grob CS. Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions. J Psychoactive Drugs. 1998 Oct-Dec;30(4):367-9. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Tramadol also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

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 something worth knowing about combining these two. Tramadol is a little unusual: your body has to switch it on. An enzyme called CYP2D6 converts tramadol into its more potent painkilling form. The beta-carboline compounds in ayahuasca (harmine and harmaline) may slow that same enzyme down. In theory, that could mean less of the active form is made, so your pain relief might be weaker than expected.

There's a second, bigger concern though. Ayahuasca also acts like an MAOI, and tramadol nudges up serotonin levels too. Together they raise the risk of serotonin syndrome, which can cause agitation, racing heart, sweating, tremor, and confusion. This is a serious combination. Please don't mix these without talking to your doctor or pharmacist first.

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

3 of 3

Tramadol 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

Here's the bigger picture with these two. Ayahuasca's vine compounds (the beta-carbolines) act as strong MAO inhibitors, and tramadol already raises serotonin in your brain. Combining them can push serotonin too high, which can trigger serotonin syndrome (agitation, racing heart, sweating, shaking, even seizures). Tramadol on its own can lower the seizure threshold, so that risk goes up.

On top of that, lab studies hint that ayahuasca may slow CYP3A4, one enzyme that helps clear tramadol, so the drug could build up and cause more drowsiness, nausea, or dizziness. That enzyme part is theoretical and only seen in test tubes, but the serotonin concern is real. Please don't mix these without talking to your doctor or pharmacist first.

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 Tramadol 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. Tramadol)
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.

From our Q&A

Questions About Ayahuasca or Tramadol

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Ayahuasca or Tramadol, 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 Tramadol

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol page lists 223 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), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Tramadol page

“Tramadol (Ultram, Qdolo) is an opioid, and its supplement interactions worry me more than most because the worst of them compound the drug's most dangerous effects. Alcohol and dozens of calming herbs deepen its sedation, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol interaction page

How much people look this up

Where Ayahuasca and Tramadol 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
Steady interest

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

29 days ago today
Medication Tramadol
Top half

#1,397 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
Medication

About Tramadol

What Is Tramadol Used For?

Brand names: Ultram, Zytram XL, Qdolo

Tramadol is used in adults for pain that is severe enough to need an opioid-strength medication and where non-opioid treatments haven't been enough. It's typically reserved for situations where milder options have failed or aren't expected to work.

It is not meant for everyday or long-term use unless the pain remains severe and alternatives continue to fall short. Prescribers carefully weigh the benefits against the real risks before starting tramadol.

See full Tramadol drug information
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 Tramadol, 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 Tramadol supplement interactions › Every supplement checked against Tramadol, ranked by severity Tramadol drug information › The full plain-English guide to this medication 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 Tramadol Together: Common Questions

Can you take Ayahuasca with Tramadol?
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 3 interactions listed for Ayahuasca and Tramadol?
Tramadol 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 Tramadol 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

Still Have a Question About Tramadol and Ayahuasca?

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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.