Herb & supplement monograph

Psilocybin Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS ·Updated July 2026

What is this page for?

First and foremost: how Psilocybin interacts with medications. The heart of this page is the interaction list — every drug Psilocybin is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Psilocybin is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

Check Psilocybin against your medication

Add one medication

✓ Supplement

Psilocybin

1 Your medication

Start typing any prescription or over-the-counter drug name.

Reviewed by licensed pharmacists Sourced from Natural Medicines

On this page

Psilocybin Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Psilocybin drug interaction appears moderate, with no severe interactions identified but real reasons for caution with certain medication types. None of the listed interactions are rated major, yet all of them are rated moderate, so the concerns are worth understanding rather than dismissing.

Interactions deserving the most attention

The best-supported concern involves stimulant drugs. Psilocybin itself stimulates the central nervous system, so adding it to a stimulant may increase side effects, and this interaction has stronger backing than the others. The second concern involves serotonergic drugs, such as many antidepressants. Psilocybin acts on serotonin receptors, so in theory combining it with these medicines could raise serotonin activity too far, a problem called serotonin syndrome. That risk remains theoretical and has not been reported in people, but the potential outcome is serious enough to take seriously.

What the rest of the list means

The long list of nearly three hundred medications looks alarming, but it mostly reflects two broad drug categories rather than hundreds of separate proven problems. Much of the concern is based on how psilocybin works in the body rather than on documented harm, and the serotonin-related risk in particular has not actually been seen in humans.

Check your medications against Psilocybin

Based on HelloPharmacist’s Psilocybin interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Psilocybin

293 medications have a known interaction with Psilocybin, graded by severity. Select any drug for the full evidence-based detail.

Don’t want to scroll the list? Just ask.

Tell us the medications you take and we’ll check each one against Psilocybin using our pharmacist-reviewed interaction data.

AI summaries are generated from our Psilocybin interaction data for education only — always confirm with your pharmacist. How we use AI

2,830 drugs

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
Probable. 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.
Possible. 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
Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
Each drug listed above links to the full report for that exact Psilocybin combination — clinical detail, likelihood, evidence level, and citations.
Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

The big picture

The kinds of drugs Psilocybin affects

Every type of medication (drug category) Psilocybin is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 2 drug categories Psilocybin interacts with

Serotonergic DrugsStimulant Drugs

Serotonergic Drugs

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.

Likelihood Possible Evidence D

Stimulant Drugs

Theoretically, concomitant use of psilocybin with stimulant drugs might increase stimulant adverse effects.
Due to the central nervous system (CNS) stimulant effects of psilocybin, concomitant use with stimulant drugs may increase the risk of adverse effects.

Likelihood Probable Evidence D

Monograph

Psilocybin: Uses, Safety & Side Effects

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Reviewed July 2026 ·

The bottom line

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.

Part used: Psilocybin is a compound found in certain mushrooms (often called 'magic mushrooms')
Common forms: Dried mushrooms, capsules, isolated/synthetic psilocybin (used in clinical trials)

People commonly use it for

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

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance

OverallBest avoided

Psilocybin is a controlled substance with powerful mind-altering effects and is not a safe or legal dietary supplement.

PregnancyInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full pregnancy detail

BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Jump to a section

Overview

Psilocybin is a naturally occurring psychedelic compound found in certain types of mushrooms, often called 'magic mushrooms.' These mushrooms grow in many parts of the world. When eaten, the body converts psilocybin into another compound called psilocin, which causes changes in mood, thinking, and perception.

Psilocybin has a long history of use in some traditional and spiritual ceremonies. More recently, scientists have studied purified or lab-made psilocybin as a possible treatment for certain mental health conditions, given in carefully controlled clinical settings alongside therapy.

It is important to know that psilocybin is not a dietary supplement you can safely or legally buy. In most countries and U.S. states it is a controlled (illegal) substance, and the doses and purity of mushrooms can vary widely.

How it works

After it is eaten, psilocybin is changed in the body into psilocin. Psilocin acts on certain serotonin receptors in the brain (mainly the 5-HT2A receptor). Serotonin is a brain chemical involved in mood and perception.

By acting on these receptors, psilocin is thought to temporarily change how different parts of the brain communicate with each other. Researchers believe this may allow more flexible thinking and shifts in mood, which could be why it is being studied for depression and other conditions.

Much of this understanding comes from laboratory studies, brain imaging, and small clinical trials. The exact way psilocybin might help mental health conditions is still being researched.

Effectiveness

Does Psilocybin work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by Dr. Brian Staiger, PharmD.

Evidence overview · 17 uses evaluated

1 Possibly effective 16 Insufficient evidence

How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.

2Likely EffectiveGood evidence, though not yet conclusive.

3Possibly EffectiveSome evidence suggests a benefit.

4Possibly IneffectiveSome evidence it may not help.

5Likely IneffectiveFairly strong evidence it doesn’t help.

6IneffectiveStrong evidence it doesn’t work.

7Insufficient Reliable Evidence to RateToo little research to say either way.

Possibly Effective Depression