Psilocybin interactions
Review the current reference classification for Psilocybin paired with medications or other agents represented in the Arcametric reference library.
Reference information only. This resource summarizes information from external sources and isn't individualized medical advice or a determination of treatment suitability.
Interactors with a reference entry
Cardiovascular
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Psilocybin and Propranolol Monitor Only
Theoretical: beta blockade may blunt heart rate and somatic anxiety during psilocybin sessions. Propranolol contraindications (asthma, bradycardia, AV block) must be screened. No direct psilocybin-propranolol studies found.
Evidence: FDA label (Inderal) + mechanistic
GLP-1/GIP Agonist
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Psilocybin and Zepbound (tirzepatide) Clinician Review
Demonstrated delayed gastric emptying with potential impact on oral psilocybin absorption. Delayed or variable onset increases risk of premature non-response conclusion and dose stacking. Nausea overlap may worsen tolerability.
Evidence: FDA label (Zepbound 2025) + mechanistic
MAOI
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Psilocybin and Phenelzine (Nardil) Absolute Contraindication
CONTRAINDICATED. MAOIs combined with psilocybin create severe serotonin syndrome risk. This combination can be fatal.
Evidence: Strassman R. DMT: The Spirit Molecule. 2001; Case reports NLM.
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Psilocybin and Tranylcypromine (Parnate) Absolute Contraindication
CONTRAINDICATED. Severe serotonin syndrome risk. Do not combine under any circumstances.
Evidence: NLM Drug Interaction Database. Clinical case reports.
Mood Stabilizer
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Psilocybin and Lithium Absolute Contraindication
Significant seizure risk (47% in observational data) from suspected synergistic excitatory neurotoxicity.
Evidence: Observational, Case series
Opioid
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Psilocybin and Oxycodone (Percocet) Monitor Only
No established contraindication. No direct pharmacodynamic overlap. Acute pain may alter subjective setting.
Evidence: Observational
SSRI/SNRI
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Psilocybin and Fluoxetine (Prozac) Strong Caution
SSRIs may significantly blunt or block the psychedelic effects of psilocybin, and the combination carries serotonin syndrome risk at higher doses.
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Psilocybin and Sertraline (Zoloft) Strong Caution
Significant reduction in psilocybin response expected. Monitor closely for serotonin syndrome.
Evidence: Journal of Psychopharmacology. 2022.
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Psilocybin and Venlafaxine (Effexor) Strong Caution
High serotonin syndrome risk. Venlafaxine (SNRI) combined with psilocybin poses greater risk than SSRI alone due to norepinephrine activity.
Evidence: NLM Drug Interaction Database. 2023.
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Psilocybin and Pristiq (desvenlafaxine) Clinician Review
Pristiq may attenuate psilocybin effects based on SSRI/SNRI survey observational data (5-HT2A receptor downregulation). Pristiq also carries label warnings for elevated BP and seizure risk. Abrupt discontinuation must not be advised.
Evidence: Gukasyan 2023 (SSRI/SNRI + psilocybin observational) + FDA label (Pristiq 2017)
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Psilocybin and Escitalopram (Lexapro) Possible Efficacy Blunting
Efficacy blunting and attenuated subjective effects from 5-HT2A receptor downregulation. Does not cause physical danger.
Evidence: Clinical trial, Meta-analysis
Return to the Drug Interaction Checker to look up a specific pair, or open the Knowledge library.