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RecruitingPhase 1

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

NCT07490353 · Medical University of Vienna

Recruiting
Status
Accepting participants
Phase 1
Phase
85
Target enrolment
1
Study sites
Outside the US

What it is testing

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.

Summary as written by the trial’s own sponsor and published on ClinicalTrials.gov API v2. It is the sponsor’s description, reproduced unedited, not an assessment by this site.

What counts as success

Primary outcome measures

  • Aesthetic task

    Measured over From enrolment until the second assessment session (up to 9 weeks after enrolment)

  • Monetary Incentive Delay (MID) Task

    Measured over From enrolment until the last imaging session (up to 8 weeks after enrolment)

  • Sexual arousal task

    Measured over From enrolment until the last imaging session (up to 8 weeks after enrolment)

  • Cognitive Flexibility Inventory (CFI)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Intensity rating

    Measured over From enrolment until the second medication session (up to 8 weeks after enrolment)

  • Warwick-Edinburgh Mental Well-being Scale (WEMWBS)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Beck-Depression-Inventory (BDI)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Montgomery-Åsberg Depression Rating Scale (MADRS)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Dimensional Anhedonia Rating Scale (DARS)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Aesthetic Experiences Scale (AES)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Temporal Experience of Pleasure Scale (TEPS)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • Barcelona Music Reward Questionnaire (BMRQ)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

  • 5-Dimensional Altered States of Consciousness Rating (5D-ASC)

    Measured over From enrolment until the second medication session (up to 8 weeks after enrolment)

  • Mystical Experience Questionnaire (MEQ30)

    Measured over From enrolment until the second medication session (up to 8 weeks after enrolment)

  • Challenging Experience Questionnaire (CEQ)

    Measured over From enrolment until the second medication session (up to 8 weeks after enrolment)

  • Connor-Davidson Resilience Scale (CD-RISC)

    Measured over From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)

A trial succeeds or fails on its primary outcome, declared in advance. Everything else it reports is secondary by definition.

Who can take part

Eligibility, as published

18 Years to 55 Years
Ages
All
Sex
Accepted
Healthy volunteers
Inclusion criteria: All participants: * General health based on medical history, physical examination, blood draw, and electrocardiogram * Age 18 to 55 years * Right-handedness (due to potential lateralization effects of left-handed subjects) * Willingness and competence to sign the informed consent form * Normal BMI weight range (18.5-24.9) Specific to healthy subjects: * Psychiatric health based on structured clinical interview for DSM-5 (SCID) * No concomitant medication Specific to anhedonia patients: * Major depressive episode (first or recurrent) based on structured clinical interview for DSM-5 (SCID) and ICD-10 * Fulfilling the ICD-10 diagnostic criterion of anhedonia * No concomitant medication, specifically also free of antidepressants or other psychopharmaceuticals (for at least 2 weeks, 5 weeks for fluoxetin) Exclusion criteria: All participants: * Current or history of neurological disease * Current medical illness requiring treatment * Pregnancy or current breastfeeding * Current or former substance dependency * Any contraindication for MRI * Failure to comply with the study protocol or to follow the instruction of the investigating team * Failure to confirm effective use of contraception in females at least 8 weeks before and after study participation each * First-degree relative with bipolar disorder or schizophrenia Specific to healthy subjects: \- Psychiatric diagnosis Specific to anhedonia patients: \- Psychiatric comorbidities excluding anxiety disorders and/or obsessive-compulsive disorders

Where

1 study site

FacilityCityRegionCountry
Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of General PsychiatryViennaState of ViennaAustria

On the registry

Contact the trial directly

This site does not enrol anyone and is not involved in this trial. To ask about taking part, use the sponsor’s own contact details on the official registry record, which is also where the most current version of everything above lives.

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NCT07490353 on ClinicalTrials.gov →

Last updated in the registry 2026-03-24. Registry records change; this page reflects the data build of 2026-08-25.

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Substance

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