Does Psilocybin Require Psychedelic Effects to Treat Depression?
Status:
Not yet recruiting
Trial end date:
2026-02-01
Target enrollment:
Participant gender:
Summary
Psilocybin, the chemical component of "magic mushrooms", has been administered with
psychotherapy in several randomized clinical trials (RCTs) showing large and sustained
antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have
been shown to be blocked by administration of serotonin (5HT)2A receptor antagonists such as
risperidone.
The purpose of this "double dummy" proof-of-concept trial is to evaluate whether psilocybin's
antidepressant effects are dependent on its psychedelic effects. Sixty participants with
treatment-resistant depression will be randomly assigned to one of three groups: 1)
Psilocybin 25 mg plus risperidone 1 mg; 2) Psilocybin 25 mg plus placebo; and 3) Placebo plus
risperidone 1 mg. The investigator's hypothesize that the combination of psilocybin and
risperidone will be well tolerated, safe, and will block the psychedelic effects of
psilocybin in patients diagnosed with treatment-resistant depression.