Drug & supplement interaction

Psilocybin + Doxepin

Doxepin brand names: Sinequan, Doxepin, Zonalon.

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

Psilocybin has a moderate interaction with Doxepin. Theoretically, combining psilocybin with serotonergic drugs might cause additive serotonergic effects.

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

Psilocybin and Doxepin

Here is the interaction we found between these two, with the evidence behind it.

Moderate

SEROTONERGIC DRUGS

Why this applies to Doxepin

Doxepin falls under SEROTONERGIC DRUGS — the group Psilocybin interacts with.

Theoretically, combining psilocybin with serotonergic drugs might cause additive serotonergic effects.
Psilocybin has serotonin 2A (5-HT2A) receptor agonist activity. Theoretically, combining serotonergic drugs with psilocybin might increase the risk of serotonergic side effects, including serotonin syndrome. However, this interaction 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

Doxepin is a tricyclic antidepressant that, like many of these medicines, raises serotonin activity in the brain. Psilocybin (which your body turns into psilocin) also stirs up the serotonin system. So when we line them up together, the worry is that two serotonin-boosting effects could stack on top of each other.

In theory, that overlap could nudge you toward too much serotonin, called serotonin syndrome, with things like agitation, a racing heart, sweating, shivering, or muscle twitching. I want to be honest though: this is a theoretical concern based on how each works, and it has not actually been reported in people taking these together. Psilocybin also isn't a legal or approved supplement. Please don't start, stop, or change your doxepin on your own, and run any plans past your doctor or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rosenbaum D, Weissman C, Anderson T, et al. Microdosing psychedelics: Demographics, practices, and psychiatric comorbidities. J Psychopharmacol 2020;34(6):612-622. PubMed
  2. Higgins GA, Carroll NK, Brown M, et al. Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property. Front Pharmacol 2021;12:640241. PubMed
  3. Hesselgrave N, Troppoli TA, Wulff AB, Cole AB, Thompson SM. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc Natl Acad Sci U S A 2021;118(17):e2022489118. PubMed
  4. Winter JC, Rice KC, Amorosi DJ, Rabin RA. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 2007;87(4):472-80. PubMed
  5. Kometer M, Schmidt A, Bachmann R, Studerus E, Seifritz E, Vollenweider FX. Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors. Biol Psychia 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

Psilocybin Also Interacts With Other Medications

Psilocybin has 292 moderate known drug interactions in our database — the Doxepin one above is one of them. If you take anything else, check it against the full list below.

Moderate 292 No known interaction 2,538 (incl. Doxepin)
Taking anything else?

Check Another of Your Medications Against Psilocybin

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

Everything else you take

See Every Supplement That Interacts With Doxepin

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Doxepin page lists 186 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 15 major · 145 moderate · 26 minor.

From our pharmacist’s overview on the Doxepin page

“Doxepin is a sedating tricyclic prescribed for depression, anxiety, and often sleep itself, and the people taking it tend to shop the same shelf where the trouble sits. Of the 186 supplements on file, 78 deepen its drowsiness, with alcohol (beer and wine carry major, well-documented ratings) and kava the clearest examples, and I would…”

Reviewed by 2 · Jul 18, 2026

Open the Doxepin interaction page

How much people look this up

Where Psilocybin and Doxepin 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 Psilocybin
Top half

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

29 days ago today
Medication Doxepin
Top half

#1,184 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 Psilocybin

What is Psilocybin?

  • Depression
  • Anxiety (including in serious illness)
  • Substance use disorders
  • Post-traumatic stress
  • Spiritual or psychological exploration

Psilocybin is a powerful psychedelic compound found in certain mushrooms and is being studied for hard-to-treat depression, anxiety, and addiction, but it is still investigational and not an approved supplement. It is illegal in most places, can cause intense and unpredictable mental effects, and should never be used outside of a supervised clinical setting.

Read the full Psilocybin monograph & all interactions
Medication

About Doxepin (Insomnia)

What Is Doxepin (Insomnia) Used For?

Brand names: Sinequan, Doxepin, Zonalon

This product is marketed to temporarily relieve occasional trouble sleeping when it's brought on by anxiety, restlessness, stress, or sensitivity to caffeine.

It is a homeopathic remedy — meaning its claims are based on traditional homeopathic practice, not accepted medical evidence, and it has not been evaluated by the FDA for effectiveness.

See full Doxepin (Insomnia) drug information
Keep checking

Other Drugs & Psilocybin

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

0Major
292Moderate
0Minor
2,537No known interaction
292 Moderate 2,537 No interaction
Moderate

292 interactions

Showing 60 of 292 moderate interactions — see all 292 on the Psilocybin page.

No interaction 2,537 drugs checked — show the list

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

Showing the 60 most looked-up of 2,537 medications checked with no known interaction — see the full Psilocybin list.

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

Can you take Psilocybin with Doxepin?
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.
How serious is the Psilocybin and Doxepin 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 Doxepin and Psilocybin?

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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.