Drug & supplement interaction

Ayahuasca + Nortriptyline

Nortriptyline brand names: Pamelor, Nortriptyline, Aventyl, Allegron.

Moderate Interaction
The bottom line Moderate

Nortriptyline 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 Nortriptyline

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. Nortriptyline 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 Nortriptyline

Nortriptyline 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 nortriptyline. Nortriptyline is a tricyclic antidepressant that raises serotonin and norepinephrine in your brain. Ayahuasca does two worrying things at once: its vine compounds (harmine and harmaline) act like MAO inhibitors, and its DMT adds its own serotonin activity. Stacking these on top of nortriptyline could push serotonin too high.

When serotonin climbs too far, you can get serotonin syndrome, with shaking, sweating, fast heartbeat, agitation, confusion, and nausea. This warning is mostly theoretical and based on pharmacology plus one case report with a different drug, but the potential reaction is serious enough that I would not take the chance. Please talk with your doctor or pharmacist before mixing these.

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 2

Nortriptyline 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 gist: your body relies on a liver enzyme called CYP2D6 to break down nortriptyline. Lab studies suggest the beta-carboline compounds in ayahuasca (harmine and harmaline) can block that enzyme. If it's blocked, nortriptyline may clear out more slowly and build up in your blood, which can mean more of its usual side effects, like a dry mouth, constipation, drowsiness, dizziness on standing, and at higher levels, an irregular or racing heartbeat.

I want to be honest, though: this comes from test-tube research, not from people, so it's theoretical for now. But there's a bigger concern. Ayahuasca also acts as an MAOI, and mixing MAOIs with a tricyclic like nortriptyline can be genuinely dangerous. Please don't combine these without talking to your doctor or pharmacist first.

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 Nortriptyline one above is among them. If you take anything else, check it against the full list below.

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 Nortriptyline

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 Nortriptyline, 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 Nortriptyline

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nortriptyline page lists 198 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Henbane (major), Lithium (major), Scopolia (major) and 1,3-dmaa (moderate).

By severity: 4 major · 150 moderate · 44 minor.

Open the Nortriptyline interaction page

How much people look this up

Where Ayahuasca and Nortriptyline 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

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

29 days ago today
Medication Nortriptyline
Top 25%

#344 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 Nortriptyline

What Is Nortriptyline Used For?

Brand names: Pamelor, Nortriptyline, Aventyl, Allegron

Nortriptyline is approved to relieve symptoms of depression. This applies to nortriptyline hydrochloride capsules, nortriptyline hydrochloride oral solution, and Pamelor capsules — all used for the same core indication.

The label notes that depression arising from within the body (endogenous depression) may respond better than other types of depression, though all of these products are indicated for the broader relief of depressive symptoms.

See full Nortriptyline 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
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
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

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Pharmacist Counseling Corner

Taking Ayahuasca and Nortriptyline Together: Common Questions

Can you take Ayahuasca with Nortriptyline?
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 Nortriptyline?
Nortriptyline 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 Nortriptyline 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 Nortriptyline 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.