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PsilodexMedication × psilocybin
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Psychotropics
Brand names
Desyrel, Oleptro
Reviewed 2026-10-01

Trazodone

Clinical contraindication
None listed
No clinical contraindication identified.
Best available evidence
Case reports
Also: other psychedelic, mechanism only.
Half-life
Not recorded
Named in state rules?
CONot named
ORNot named
NMPending
Cite asPsilodex: trazodone · v2026.10.02

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

01 Interaction with psilocybin

CR · XP · Th

5-HT2A blockade at usual doses blunts effects. In a published case, nightly trazodone 200 mg (last dose under 12 h before 25 mg psilocybin) left no psychedelic effects while a rapid antidepressant response still occurred. Lower doses occupy fewer 5-HT2A receptors, but some blunting is expected. As an in-session anxiolytic it tends to mute the experience rather than calm it. With LSD, more than 3 weeks of an SSRI or trazodone reduced or eliminated the response in 28 of 32 people (Bonson 1996).

Human data with psilocybin
Case reports or surveys only
Evidence types on this record
CRCase reports or online surveys
XPHuman data with another classic psychedelic (e.g. LSD), not psilocybin; named in the text
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 [1]
Sedating or CNS depressant
Slows the central nervous system: drowsiness, slower reactions and impaired coordination, and slowed breathing at high doses. Effects add with other sedating substances. Sources [1]
Serotonergic
Increases serotonin activity, for example by blocking its reuptake or releasing it. Psilocybin acts on serotonin receptors, so effects can add together. With antidepressant use, the psilocybin response can be weaker. Sources [1]

03 State rules

Official text governs
CO4 CCR 755-1
Not named

No provision names this medication or its class.

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

None linked

No condition named in state rules is linked to this medication.

05 Sources

3
  1. Trazodone — prescribing information · FDA label (DailyMed)
  2. Rosenblat JD, et al. Antidepressant effects of psilocybin in the absence of psychedelic effects. Am J Psychiatry 2023 (letter).
  3. Bonson KR, Buckholtz JW, Murphy DL. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology 1996;14:425–436. — LSD; 28/32 decreased or eliminated

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