Psilocybin's Anti-Anhedonic Effects and Brain Network Complexity in Depression
This phase 1 study aims to evaluate the anti-anhedonic effects of Psilocybin in individuals with depression, focusing on alterations in consciousness, aesthetic experiences, and various aspects of psychological well-being.
Psilocybin (Usona Institute)
+ Risperidone 1 MG
+ MRI
Behavior+6
+ Behavioral Symptoms
+ Depression
Treatment Study
Summary
Study start date: November 1, 2025
Actual date on which the first participant was enrolled.This clinical trial aims to understand how psilocybin, a psychedelic substance, might help people with depression who experience anhedonia, or the inability to feel pleasure. It seeks to explore how psilocybin impacts the brain during hedonic (pleasure-related) experiences using functional Magnetic Resonance Imaging (fMRI). The study also investigates the role of the psychedelic experience itself in these effects, using a medication called risperidone to block the psychedelic effects of psilocybin. Participants will include both individuals with depression and anhedonia, and healthy controls. During the study, participants will take psilocybin in two separate sessions. In one session, they will also take risperidone before the psilocybin to block its psychedelic effects. Participants will undergo three MRI scans: one before the first psilocybin session, and one after each subsequent session. During each fMRI scan, participants will perform various tasks to assess the effects of psilocybin on anhedonia. The study will measure various aspects of the psychedelic experience, aesthetic experiences, depression symptoms, challenging experiences, cognitive flexibility, resilience, anhedonia, and mental well-being.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.85 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 55 Years
Range of ages for which participants are eligible to join.Healthy volunteers allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of General Psychiatry
Vienna, AustriaSee the location