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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Psilocybin (Usona Institute)
  Participants will recieve two doses of Psilocybin 25 mg to be taken orally over the course of the study.
• Препарат Risperidone 1 MG
  30 minutes before administration of psilocybin in one of the sessions to inhibit acute psychedelic effects
• Диагностический тест 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)

Первичные конечные точки

• Aesthetic task [Срок оценки: From enrolment until the second assessment session (up to 9 weeks after enrolment)]
• Monetary Incentive Delay (MID) Task [Срок оценки: From enrolment until the last imaging session (up to 8 weeks after enrolment)]
• Sexual arousal task [Срок оценки: From enrolment until the last imaging session (up to 8 weeks after enrolment)]
• Cognitive Flexibility Inventory (CFI) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Intensity rating [Срок оценки: From enrolment until the second medication session (up to 8 weeks after enrolment)]
• Warwick-Edinburgh Mental Well-being Scale (WEMWBS) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Beck-Depression-Inventory (BDI) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Montgomery-Åsberg Depression Rating Scale (MADRS) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Dimensional Anhedonia Rating Scale (DARS) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Aesthetic Experiences Scale (AES) [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]

Вторичные конечные точки (4)

• Cytokine panel [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Brain-derived neurotrophic factor (BDNF) concentration [Срок оценки: From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)]
• Neural activity [Срок оценки: Over the course of the three MRI sessions (3-14 days after enrolment, 1 day after the first medication session, 6 weeks after the second measurement)]
• Brain network dynamic complexity [Срок оценки: Over the course of the three MRI sessions (3-14 days after enrolment, 1 day after the first medication session, 6 weeks after the second measurement)]

Критерии участия

Критерии включения

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)

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австрия · 1 центр

• Medical University of Vienna, Department of Psychiatry and Psychotherapy, Division of Gene — Vienna

Идентификаторы

NCT: NCT07490353 · PSY-NIL-0016 · 2024-519265-22-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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