Drug & supplement interaction

Ayahuasca + Dextromethorphan, Guaifenesin, Phenylephrine

Dextromethorphan, Guaifenesin, Phenylephrine brand names: Albatussin Sr, Giltuss.

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

Dextromethorphan, Guaifenesin, Phenylephrine 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 Dextromethorphan, Guaifenesin, Phenylephrine

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. Dextromethorphan, Guaifenesin, Phenylephrine 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

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Why this applies to Dextromethorphan, Guaifenesin, Phenylephrine

Dextromethorphan, Guaifenesin, Phenylephrine 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

This combination cold and cough product has two pieces worth watching with ayahuasca. The dextromethorphan raises serotonin activity in the brain, and ayahuasca's vine compounds act like MAO inhibitors that let serotonin build up. Put together, that can stack too much serotonin and theoretically trigger serotonin syndrome, with shivering, sweating, agitation, fast heartbeat, tremor, nausea, or confusion. The phenylephrine is a separate concern, since MAOIs can exaggerate its blood-pressure-raising effect.

To be fair, this is based on pharmacology and case reports, not strong studies, so it's a possible risk rather than a certain one. The guaifenesin part isn't the issue here. Still, mixing these isn't worth the gamble. Please check with your pharmacist or doctor before combining them.

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

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Dextromethorphan, Guaifenesin, Phenylephrine 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 the part that matters most in this combo product: the dextromethorphan (the cough suppressant). Your liver normally uses an enzyme called CYP2D6 to clear it out. The beta-carboline compounds in ayahuasca (harmine and harmaline) can block that enzyme, so dextromethorphan could build up higher than usual. That may mean more drowsiness, dizziness, confusion, or feeling off-balance.

There's a bigger concern, though. Ayahuasca also acts like an MAOI, and mixing MAOIs with dextromethorphan can trigger serotonin syndrome (agitation, racing heart, sweating, tremor). The CYP2D6 part is so far only seen in lab studies, but I'd treat this pairing seriously. Please check with your pharmacist or doctor before combining 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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

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Dextromethorphan, Guaifenesin, Phenylephrine 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 what's going on with this combo cough and cold product (which has dextromethorphan, guaifenesin, and phenylephrine). Lab studies hint that the beta-carboline compounds in ayahuasca may slow down CYP3A4, one of the enzymes your liver uses to clear certain drugs like dextromethorphan. If that happens, more of the drug could linger in your body, which might mean stronger effects such as dizziness, drowsiness, or feeling foggy.

I'll be honest with you: this is only theoretical and based on test-tube research, not real people, so I wouldn't lose sleep over it. The bigger worry is that ayahuasca acts as an MAOI, and dextromethorphan plus an MAOI can be a genuinely dangerous mix. Please check with your pharmacist or doctor before combining 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 Dextromethorphan, Guaifenesin, Phenylephrine 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. Dextromethorphan, Guaifenesin, Phenylephrine)
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 Dextromethorphan, Guaifenesin, Phenylephrine

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan, Guaifenesin, Phenylephrine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Lithium (major) and Peyote (major).

By severity: 8 major · 148 moderate · 41 minor.

From our pharmacist’s overview on the Dextromethorphan, Guaifenesin, Phenylephrine page

“A combination cough medicine like dextromethorphan, guaifenesin, and phenylephrine (Albatussin Sr, Giltuss) deserves real care around supplements, not casual mixing. Of the 197 ingredients with an interaction on file, 8 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan, Guaifenesin, Phenylephrine interaction page

How much people look this up

Where Ayahuasca and Dextromethorphan, Guaifenesin, Phenylephrine 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

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

29 days ago today
Medication Dextromethorphan, Guaifenesin, Phenylephrine
Steady interest

#1,862 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 Dextromethorphan, Guaifenesin, Phenylephrine, 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 Dextromethorphan, Guaifenesin, Phenylephrine supplement interactions › Every supplement checked against Dextromethorphan, Guaifenesin, Phenylephrine, 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 Dextromethorphan, Guaifenesin, Phenylephrine Together: Common Questions

Can you take Ayahuasca with Dextromethorphan, Guaifenesin, Phenylephrine?
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 Dextromethorphan, Guaifenesin, Phenylephrine?
Dextromethorphan, Guaifenesin, Phenylephrine 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 Dextromethorphan, Guaifenesin, Phenylephrine 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.