Drug & supplement interaction

Psilocybin + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

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

Psilocybin has a moderate interaction with Fluoxetine. 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 Fluoxetine

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Fluoxetine

Fluoxetine 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

Here's the basic idea: Prozac (fluoxetine) raises serotonin activity in your brain, and psilocybin (turned into psilocin in your body) tinkers with a serotonin receptor too. So putting them together means you're hitting the same system from two angles. On paper, that could add up and raise the odds of too much serotonin, which can show up as agitation, a racing heart, sweating, shivering, muscle twitching, or, in the worst cases, serotonin syndrome.

I want to be honest about the evidence, though. This is a theoretical concern based on how both act, not something actually reported in people. Fluoxetine isn't a prodrug here, so the worry is simply additive effects. Fluoxetine also lingers in the body for weeks after stopping. Bottom line, never mix these without talking to 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 Fluoxetine 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. Fluoxetine)
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.

From our Q&A

Questions About Psilocybin or Fluoxetine

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

This page covers Psilocybin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluoxetine page lists 163 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 127 moderate · 28 minor.

From our pharmacist’s overview on the Fluoxetine page

“Grapefruit is the surprise at the top of fluoxetine's (Prozac) supplement list. In large amounts it can stretch the QT interval, the electrical pause between heartbeats, and fluoxetine, a widely prescribed antidepressant, can do the same, raising the odds of a dangerous rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Fluoxetine interaction page

How much people look this up

Where Psilocybin and Fluoxetine 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

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

29 days ago today
Medication Fluoxetine
Top 5%

#41 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 Fluoxetine

What Is Fluoxetine Used For?

Brand names: Prozac, Sarafem

Fluoxetine treats several mental health conditions. Most fluoxetine products are labeled for major depressive disorder (MDD), obsessive compulsive disorder (OCD), bulimia nervosa (binge-eating and vomiting behaviors) and panic disorder, with or without agoraphobia (fear of open or crowded places).

Some uses are product-specific. Fluoxetine delayed-release capsules are labeled only for major depressive disorder. Prozac capsules and fluoxetine capsules are also labeled to be used together with olanzapine for depressive episodes linked to Bipolar I Disorder and for treatment resistant depression. Fluoxetine alone is not approved for those two uses.

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

Can you take Psilocybin with Fluoxetine?
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 Fluoxetine 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 Fluoxetine 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.