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Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)
Sponsor: Centre Hospitalier St Anne
Summary
Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects. The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit/risk ratio of psilocybin. We hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects.
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
112
Start Date
2025-10-08
Completion Date
2030-06-30
Last Updated
2025-10-07
Healthy Volunteers
No
Interventions
Psilocybin 25 mg per os
Caps of psilocybin administered orally once (V3) under medical and psychologist supervision in group 1, 2, and 3 and in an open-label setting for group 4
Trazodone 5mg
Oral preparation of trazodone administered orally once (V3) with psilocybin in Group 2
Trazodone 30 mg
Oral preparation of trazodone administered orally once (V3) with psilocybin in Groups 3 \& 4
Placebo of psilocybin
Caps of psilocybin placebo will be administered at V3 in group 4
Placebo of trazodone
A placebo of trazodone will be administered orally at V3 in group 1
Locations (1)
GHU Paris Psychiatrie and Neurosciences
Paris, France