Drug & supplement interaction

Ayahuasca + Safinamide Mesylate

Safinamide Mesylate brand name: Xadago.

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

Safinamide Mesylate falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ayahuasca and Safinamide Mesylate

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. Safinamide Mesylate 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

SEROTONERGIC DRUGS

1 of 2

Why this applies to Safinamide Mesylate

Safinamide Mesylate 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 the concern with combining ayahuasca and Xadago (safinamide). Safinamide is an MAO-B inhibitor that raises dopamine in the brain to smooth out your Parkinson's "off" times. Ayahuasca's vine compounds (harmine and harmaline) are also MAO inhibitors and can push serotonin levels up. Stacking two drugs that affect these brain chemicals can lead to too much serotonin activity at once.

The worry is serotonin syndrome, which can show up as shaking, sweating, a racing heart, confusion, fever, or a dangerous spike in blood pressure. This is based mostly on pharmacology and lab reasoning rather than a long list of real cases, so it's theoretical, but it's a combination I would not take a chance with. Please run this by your doctor or pharmacist before mixing 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

DOPAMINE AGONISTS

2 of 2

Safinamide Mesylate also falls under DOPAMINE AGONISTS.

Theoretically, ayahuasca might have additive effects when used with dopamine agonists.
Ayahuasca contains the beta-carboline constituent harmine. Animal research shows that harmine increases extracellular dopamine levels.
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 thing to keep in mind if you take Xadago (safinamide) for Parkinson's. Safinamide is an MAO-B inhibitor, and ayahuasca contains harmine, which acts as an MAO inhibitor too. On top of that, lab research suggests harmine can raise dopamine levels in the brain. So you'd potentially be stacking two things that both push dopamine and block its breakdown.

In real life, that could mean more of safinamide's dopamine-related effects, things like nausea, trouble sleeping, dizziness, involuntary movements (dyskinesia), or a spike in blood pressure. To be fair, this concern is theoretical and based mostly on animal data, not solid human studies. Still, combining two MAO-active substances is risky, so please don't try ayahuasca without first talking it through with your doctor or pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Iurlo, M., Leone, G., Schilstrom, B., Linner, L., Nomikos, G., Hertel, P., Silvestrini, B., and Svensson, H. Effects of harmine on dopamine output and metabolism in rat striatum: role of monoamine oxidase-A inhibition. Psychopharmacology (Berl) 2001;159(1 PubMed
  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 Safinamide Mesylate 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. Safinamide Mesylate)
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 Safinamide Mesylate

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Safinamide Mesylate page lists 81 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Bitter Orange (major), Brewer's Yeast (major) and Cowhage (major).

By severity: 14 major · 56 moderate · 11 minor.

Open the Safinamide Mesylate interaction page

How much people look this up

Where Ayahuasca and Safinamide Mesylate 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

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

29 days ago today
Medication Safinamide Mesylate
Top half

#856 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 Safinamide

What Is Safinamide Used For?

Brand name: Xadago

Xadago (safinamide) is used as an add-on treatment for adults with Parkinson's disease who are already taking levodopa/carbidopa and experiencing 'off' episodes — times when the medication wears off and Parkinson's symptoms return before the next dose is due.

Xadago is not used alone; it works only in combination with levodopa/carbidopa.

See full Safinamide 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 Safinamide Mesylate, 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 Safinamide Mesylate supplement interactions › Every supplement checked against Safinamide Mesylate, ranked by severity Safinamide 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 Safinamide Mesylate Together: Common Questions

Can you take Ayahuasca with Safinamide Mesylate?
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 Safinamide Mesylate?
Safinamide Mesylate 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 Safinamide Mesylate 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 Safinamide Mesylate 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.