RecruitingPhase 1

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

Austria85 participantsStarted 2025-11-01

Plain-language 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.

Who can participate

Age range

18 Years – 55 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Aesthetic task

Timeframe: From enrolment until the second assessment session (up to 9 weeks after enrolment)

Monetary Incentive Delay (MID) Task

Timeframe: From enrolment until the last imaging session (up to 8 weeks after enrolment)

Sexual arousal task

Timeframe: From enrolment until the last imaging session (up to 8 weeks after enrolment)

Cognitive Flexibility Inventory (CFI)

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

Intensity rating

Timeframe: From enrolment until the second medication session (up to 8 weeks after enrolment)

Warwick-Edinburgh Mental Well-being Scale (WEMWBS)

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

Beck-Depression-Inventory (BDI)

Trial details

NCT IDNCT07490353

SponsorMedical University of Vienna

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-05-31

Contact for this trial

Marie Spies, Priv.-Doz. DDr.

+43 1 40400 marie.spies@meduniwien.ac.at

View on ClinicalTrials.gov More Depression - Major Depressive Disorder trials

Plain-language summary

Who can participate

Age range

18 Years – 55 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Aesthetic task

Timeframe: From enrolment until the second assessment session (up to 9 weeks after enrolment)

Monetary Incentive Delay (MID) Task

Timeframe: From enrolment until the last imaging session (up to 8 weeks after enrolment)

Sexual arousal task

Timeframe: From enrolment until the last imaging session (up to 8 weeks after enrolment)

Cognitive Flexibility Inventory (CFI)

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

Intensity rating

Timeframe: From enrolment until the second medication session (up to 8 weeks after enrolment)

Warwick-Edinburgh Mental Well-being Scale (WEMWBS)

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

Beck-Depression-Inventory (BDI)