Drug & supplement interaction

Ayahuasca + Lidocaine

Lidocaine brand names: Xylocaine, Dilocaine, Lidoject-1, Xylocaine MPF, Nervocaine, and others.

Moderate Interaction
The bottom line Moderate

Lidocaine 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 Lidocaine

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. Lidocaine 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 Lidocaine

Lidocaine 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 idea behind this pairing. Lidocaine is partly cleared by a liver enzyme called CYP2D6, and the beta-carboline compounds in ayahuasca (harmine and harmaline) may slow that enzyme down. If lidocaine is broken down more slowly, more of it could linger in your body. With higher levels, you might notice signs like dizziness, numbness or tingling around the mouth, ringing in the ears, drowsiness, or in rare cases an irregular heartbeat.

I want to be honest about the strength of this, though. So far this is only seen in lab (test tube) studies, not in real people, so it's theoretical. The numbing creams and patches you buy over the counter put very little lidocaine into your blood, so the risk there is low. Still, given ayahuasca's other serious effects, please talk with your doctor or pharmacist before combining anything.

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

Lidocaine 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 idea behind this pairing. Lidocaine is partly cleared by a liver enzyme called CYP3A4. Ayahuasca contains beta-carboline compounds that may slow that enzyme down. If lidocaine clears more slowly, a bit more could build up in your body. Lidocaine is not a prodrug, so blocking this enzyme would tend to strengthen its effects, not weaken them.

I want to be honest about the evidence, though. This is only seen in lab dishes, never confirmed in people, so it's largely theoretical. Most over-the-counter lidocaine is a cream or patch on the skin, where very little reaches your bloodstream. Bigger concerns with ayahuasca itself remain. Still, please run any combination past your pharmacist or doctor 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 Lidocaine 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.

Everything else you take

See Every Supplement That Interacts With Lidocaine

This page covers Ayahuasca only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Lidocaine page lists 145 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Fever Bark (major), Grapefruit (major), St. John's Wort (major), 1,3-dmaa (moderate) and Acacia Rigidula (moderate).

By severity: 3 major · 111 moderate · 31 minor.

From our pharmacist’s overview on the Lidocaine page

“Lidocaine (Xylocaine) deserves genuine care on this page, and I would learn its three major-rated entries first. Grapefruit and St.”

Reviewed by 2 · Jul 18, 2026

Open the Lidocaine interaction page

How much people look this up

Where Ayahuasca and Lidocaine 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

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

29 days ago today
Medication Lidocaine
Steady interest

#1,701 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 Lidocaine Transdermal Patch

What Is Lidocaine Transdermal Patch Used For?

Brand names: Xylocaine, Dilocaine, Lidoject-1, Xylocaine MPF, Nervocaine, Lidoject-2, Duo-Trach Kit, Octocaine, Lidoderm, Ztlido

Lidocaine skin patches are applied directly to the painful area to treat post-herpetic neuralgia (PHN) — the persistent burning or aching nerve pain that can remain after a shingles outbreak.

Lidoderm (lidocaine patch 5%) and ZTlido (lidocaine topical system 1.8%) are both indicated for this use in adults. Note that despite their different strengths, one ZTlido topical system provides equivalent lidocaine exposure to one Lidoderm patch.

See full Lidocaine Transdermal Patch 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 Lidocaine Together: Common Questions

Can you take Ayahuasca with Lidocaine?
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 Lidocaine?
Lidocaine 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 Lidocaine 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.