NCT07490353

Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects

Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects: A Randomized, Open-Label, Cross-Over Functional Magnetic Resonance Imaging Trial

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 85 (estimated)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The goal of this clinical trial is to systematically categorize potential prohedonic effects of psilocybin in patients with anhedonia in depression. The main questions it aims to answer are: Primary Objectives 1. Systematically categorize prohedonic effects (antianhedonic effects in patients with anhedonia in depression, increase in well-being in all participants). 2. Test effects of psilocybin on brain network complexity measures during the hedonic experience using fMRI as a correlate for prohedonic (anti-anhedonic and well-being increasing) effects. 3. Elucidate relevance of the psychedelic experience to these effects (clinical, behavioral, and imaging) in a pharmacological challenge using the 5-HT2A/D2 antagonist risperidone and extensive characterization of the psychedelic experience. Secondary Objectives 4. Test the differential effects of the psychedelic experience on fMRI paradigms measuring symptoms shown to be altered in anhedonia, more specifically reward processing and sexual arousal. 5. Test the relevance of neuroplasticity (BDNF) and inflammatory parameters to anti-anhedonic, well-being promoting, and brain network dynamic complexity effects. 6. Test the effects of the psychedelic experience on BDNF and inflammatory parameters. Researchers will compare the effects of psilocybin in two separate sessions (one with psilocybin alone, one with co-administration of risperidone) in both patients with depression and anhedonia and healthy control participants. Participants will: * Take 25 mg of psilocybin p.o. in two sessions, in one of the two sessions they will take 1 mg risperidone p.o. before ingestion of psilocybin, to block psilocybin's acute psychedelic effects. * Undergo 3 MRI sessions, one before the first psilocybin session ('baseline') and one session each on the day after each respective psilocybin session. * Perform a variety of tasks during each fMRI session to asses the treatment's effects on anhedonia.

Conditions

• Depression - Major Depressive Disorder
• Anhedonia

Interventions

Type	Name	Description
DRUG	Psilocybin (Usona Institute)	Participants will recieve two doses of Psilocybin 25 mg to be taken orally over the course of the study.
DRUG	Risperidone 1 MG	30 minutes before administration of psilocybin in one of the sessions to inhibit acute psychedelic effects
DIAGNOSTIC_TEST	MRI	Over the course of the study, participants will undergo three MRI measurement sessions. * M1 (baseline, before treatment) * M2 \& M3 (one day after each psilocybin session)

Timeline

• Start date: 2025-11-01
• Primary completion: 2028-05-31
• Completion: 2028-05-31
• First posted: 2026-03-24
• Last updated: 2026-03-24

Locations

1 site across 1 country: Austria