Zotepine

Clinical contraindication: Relative; Substantial clinical concern; the literature treats it as a reason for caution or deferral.
Best available evidence: Mechanism only
Half-life: Not recorded

Named in state rules?

CONamed

ORNot named

NMPending

Cite asPsilodex: zotepine · v2026.10.02

Clinical data and state rules are separate facts. Both are shown; neither is a decision.

01 Interaction with psilocybin

5-HT2A/D2 blockade blunts; dose-dependent QTc prolongation and lowered seizure threshold.

Human data with psilocybin: None known: no published human data with psilocybin

Evidence types on this record

ThMechanism only (theoretical)

02 Pharmacology relevant to psilocybin

3 listed · counted on reports

Blocks 5-HT2A (may blunt effects): Blocks the 5-HT2A receptor, the main receptor psilocybin acts through. Can reduce or block the psilocybin effect. Sources [5]
QT-prolonging: Lengthens the QT interval on an ECG, a measure of the heart’s electrical recovery between beats. A long QT raises the risk of a dangerous heart rhythm, more so with other QT-prolonging drugs or low potassium or magnesium. Sources [1]
Lowers seizure threshold or carries seizure risk: Makes a seizure more likely, or has been linked to seizures. Sources [2]

03 State rules

Official text governs

CO4 CCR 755-1

Named · 2.2(A)(6)–(7) · 2.5(A)(2)

Antipsychotic medications are named in rule, regardless of indication or dose. A Facilitator licensee may not provide services to a participant taking one without a referral for natural medicine services from a licensed provider, medical clearance from their medical or behavioral health provider, or a consultation and risk review with a medical or behavioral health provider. A Clinical Facilitator who does not prescribe antipsychotics within their secondary license needs clearance from, or a consultation and risk review with, such a provider.

Colorado · checked 2026-09-30

OROAR 333-333

Not named

No provision names this medication or its class.

Oregon · checked 2026-09-30

NM7.35.3 NMAC (proposed)

Pending

New Mexico's clinical rules (proposed 7.35.3 NMAC) are not final. No provision naming this medication has been found.

New Mexico · checked 2026-09-30

04 Conditions to ask about

Screening items in state rules

This medication is usually taken for a condition. State rules screen for some conditions directly, so the medication is a prompt to ask about them. Confirm with the participant; never assume a condition from the medication.

Psychotic disorder or bipolar disorder (common indications)CO 2.2(A)(6)–(7) · CO 2.5(A)(2) · OR 333-333-5050(3)(j)

05 Sources

Preston CL (ed). Stockley’s Drug Interactions, 11th ed. Pharmaceutical Press, 2016., p. 286
Preston CL (ed). Stockley’s Drug Interactions, 11th ed. Pharmaceutical Press, 2016., p. 904
Halman A, Kong G, Sarris J, Perkins D. Drug–drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol 2024;38(1):3–18.
Vollenweider FX, Vollenweider-Scherpenhuyzen MFI, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport 1998;9:3897–3902. — class finding
NIMH Psychoactive Drug Screening Program (PDSP) Ki Database, University of North Carolina. Roth BL et al. (per-entry query link; primary references in note) — 5-HT2A Ki 0.7–2.7 nM (human cloned; Schotte 1996, Richelson & Souder 2000, PDSP)

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