Drug & supplement interaction

Iboga + Diphenhydramine

Diphenhydramine brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, and others.

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

Diphenhydramine falls into 2 drug categories that Iboga can interact with; the most serious is rated moderate. Theoretically, iboga might decrease the effectiveness of anticholinergic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Iboga and Diphenhydramine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Iboga interacts with whole categories of medication. Diphenhydramine falls into 2 of those categories, so it can interact with Iboga in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICHOLINERGIC DRUGS

1 of 2

Why this applies to Diphenhydramine

Diphenhydramine falls under ANTICHOLINERGIC DRUGS — the group Iboga interacts with.

Theoretically, iboga might decrease the effectiveness of anticholinergic drugs.
In vitro research shows that iboga can inhibit acetylcholinesterase and might increase acetylcholine levels. However, the constituent ibogaine does not appear to have this effect.
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 one. Diphenhydramine (Benadryl) works partly by blocking acetylcholine, a nerve-signaling chemical. That blocking action is what dries up a runny nose and makes you sleepy. In lab dish studies, Iboga seems to do the opposite, raising acetylcholine levels, so in theory it could push back against Benadryl and make it work a little less well for your allergy or sleep symptoms.

I want to be honest with you, though: this is theoretical, based only on test-tube research, and the main active part of Iboga (ibogaine) didn't show this effect. The bigger concern is Iboga itself, which is illegal in the U.S. and carries serious heart-rhythm risks. Please talk with your pharmacist or doctor before combining anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alper K, Reith ME, Sershen H. Ibogaine and the inhibition of acetylcholinesterase. J Ethnopharmacol. 2012;139(3):879-82. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

2 of 2

Diphenhydramine also falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS.

Theoretically, taking iboga with CYP2D6 inhibitors might increase the levels and clinical effects of ibogaine.
Ibogaine, the active constituent of iboga, is a substrate of CYP2D6. One pharmacokinetic study shows that taking the CYP2D6 inhibitor paroxetine prior to taking ibogaine 20 mg increases the exposure to ibogaine and its metabolite noribogaine by 2-fold when compared with ibogaine alone.
Severity Moderate Likelihood Possible Evidence B

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 key thing to understand: in this pairing, it's the Iboga that gets affected, not your Benadryl. Diphenhydramine acts as a CYP2D6 blocker, and ibogaine (the active part of Iboga) is cleared by that same CYP2D6 enzyme. So if you slow that enzyme down with diphenhydramine, the ibogaine and its byproduct can pile up. One small study saw a similar blocker roughly double ibogaine levels.

Why that matters: Iboga already carries serious risks, including dangerous heart rhythm changes, and higher levels make that worse. On top of that, both can cause heavy drowsiness and confusion. Honestly, we don't recommend Iboga at all outside of research. Please talk with your pharmacist or doctor before combining anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Henstra M, Wong L, Chahbouni A, et al. Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine. Clin Toxicol (Phila). 2017;55(6):600-602. PubMed
  2. Glue P, Winter H, Garbe K, et al. Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20?mg dose of ibogaine in healthy volunteers. J Clin Pharmacol. 2015;55(6):680-7. PubMed
  3. Rodriguez P, Urbanavicius J, Prieto JP, et al. A single administration of the atypical psychedelic ibogaine or its metabolite noribogaine induces an antidepressant-like effect in rats. ACS Chem Neurosci 2020;11(11):1661-1672. 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

Iboga Also Interacts With Other Medications

Iboga has 1 major, 500 moderate known drug interactions in our database — the Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 500 No known interaction 2,329 (incl. Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Iboga

Covers the 2,830 medications we’ve checked against Iboga. Pick one to open its full report.

From our Q&A

Questions About Iboga or Diphenhydramine

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

This page covers Iboga only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine page lists 147 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 Henbane (major).

By severity: 9 major · 119 moderate · 19 minor.

From our pharmacist’s overview on the Diphenhydramine page

“Diphenhydramine (Benadryl, Simply Sleep) is sedating by design, and most of the 147 supplements and herbal ingredients on this list lean into that. Seventy-eight are sedating substances themselves, alcohol and kava the standouts, and stacking them can slow breathing and reflexes well beyond ordinary drowsiness.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine interaction page

How much people look this up

Where Iboga and Diphenhydramine 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 Iboga
Top half

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

29 days ago today
Medication Diphenhydramine
Top 25%

#483 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 Iboga

What is Iboga?

Iboga
  • Drug and alcohol addiction
  • Opioid withdrawal
  • Spiritual and ceremonial rituals
  • Fatigue and stimulant effects
  • Mood and emotional issues

Iboga is a Central African shrub whose root bark contains ibogaine, a powerful hallucinogenic compound studied mainly for addiction. It carries serious safety risks, including dangerous heart rhythm changes and deaths, and ibogaine is illegal in the United States and many other countries. We do not recommend its use outside of tightly controlled research settings.

Read the full Iboga monograph & all interactions
Medication

About Diphenhydramine

What Is Diphenhydramine Used For?

Brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, Simply Sleep, Sominex, Diphenhydramine, Compoz, Sleep Aid, Benadryl cream, Benadryl spray, Dermamycin cream, Ziradryl, Nytol

Most oral diphenhydramine products temporarily relieve symptoms of hay fever and other upper respiratory allergies: runny nose, sneezing, itchy and watery eyes, and an itchy nose or throat. They also temporarily relieve runny nose and sneezing from the common cold.

After Bite Xtra is a topical gel. It is used for temporary relief of pain and itching from minor burns, minor cuts or scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak and poison sumac.

See full Diphenhydramine drug information
Keep checking

Other Drugs & Iboga

Browse every other medication we’ve checked against Iboga — both the ones with a known interaction and the ones without. Select any drug for the full detail.

1Major
500Moderate
0Minor
2,328No known interaction
1 Major 500 Moderate 2,328 No interaction
Major

1 interaction

Moderate

500 interactions

Showing 60 of 500 moderate interactions — see all 500 on the Iboga page.

No interaction 2,328 drugs checked — show the list

We also checked Iboga against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,328 medications checked with no known interaction — see the full Iboga list.

See the full Iboga interactions page
See every supplement checked against Diphenhydramine, 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
Iboga monograph › Uses, safety, and every drug interaction in one place Diphenhydramine supplement interactions › Every supplement checked against Diphenhydramine, ranked by severity Diphenhydramine 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 Iboga and Diphenhydramine Together: Common Questions

Can you take Iboga with Diphenhydramine?
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 Iboga and Diphenhydramine?
Diphenhydramine belongs to more than one drug category, and Iboga 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 Iboga and Diphenhydramine 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 Diphenhydramine and Iboga?

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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.