Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-55
SponsorMedical University of Vienna
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
Current or history of neurological disease
Current medical illness requiring treatment
Pregnancy or current breastfeeding
Current or former substance dependency
Trial design
Design model
Crossover
Treatments tested in this trial
Psilocybin (Usona Institute)
DrugParticipants will recieve two doses of Psilocybin 25 mg to be taken orally over the course of the study.
Risperidone 1 MG
Drug30 minutes before administration of psilocybin in one of the sessions to inhibit acute psychedelic effects
MRI
Diagnostic testOver the course of the study, participants will undergo three MRI measurement sessions. * M1 (baseline, before treatment) * M2 \& M3 (one day after each psilocybin session)
Treatment groups
85 Participants
are divided into 2 treatment groupsGroup A: Psilocybin first, psilocybin + risperidone secondExperimental treatment 3 interventions
Group B: Psilocybin + risperidone first, psilocybin secondExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Aesthetic task
This task is designed to evoke and probe the nature and extent of the aesthetic experience. Two sets of stimuli will be presented. Each set consists of 20 pieces of self-selected music with 10 pieces inducing highly hedonic experiences and 10 neutral pieces. After stimulus presentation, subjects will rate how aesthetically moving the experience was, whether they experienced chills, and what the valence of the experience was on a Likert scale.
Time frame
From enrolment until the second assessment session (up to 9 weeks after enrolment)2
Monetary Incentive Delay (MID) Task
The MID task is established to evoke and assess reward and punishment, which are centrally involved in anhedonia. The task observes several stages of reward processing, i.e., reward prediction, anticipation and reward consumption. The aim of the paradigm is to maximize gain and avoid loss by fast reaction upon presentation of a target stimulus. A trial starts with the presentation of a cue, indicating the potential gain or loss (e.g., -1€, +3€). After a variable delay of for instance 3-5 seconds the target stimulus is shown, and subjects press a button as fast as possible. If the reaction is within a given time limit the amount is gained or loss avoided. Otherwise, the amount is not gained or lost. Each button press is followed by immediate feedback, showing the outcome and the accumulated amount of money.
Time frame
From enrolment until the last imaging session (up to 8 weeks after enrolment)3
Sexual arousal task
This task has been implemented by our group to assess changes to sexual arousal, a central and burdensome, yet often understudied, component of anhedonia. During this task, subjects are presented images intended to be sexually arousing and are instructed to denote the extent to which they find the image arousing.
Time frame
From enrolment until the last imaging session (up to 8 weeks after enrolment)4
Cognitive Flexibility Inventory (CFI)
The CFI is a 20-item self-report measure to assess two aspects of cognitive flexibility: the adaptive ability to perceive multiple alternative explanations for life occurrences and the ability to generate multiple alternative solutions to difficult situations, as well as having an internal locus of control, or the tendency to perceive difficult situations as somewhat controllable.
Time frame
From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)Secondary outcomes
1
Cytokine panel
Changes in proinflammaotry cytokines, suchz as interleukin 6 and tumor necrosis factor alpha, which have been associated with depression and anhedonia, assessed via Legendplex cytokine panel
Time frame
From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)2
Brain-derived neurotrophic factor (BDNF) concentration
Changes in blood markers which have been associated with depression and anhedonia, assessed via BDNF concentration.
Time frame
From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)3
Neural activity
Neural activity during MID and sexual arousal task, assessed via fMRI measurement.
Time frame
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)4
Brain network dynamic complexity
Brain complexity measures during the hedonic experience assessed with fMRI, as assesed via integrated information decomposition and BOLD variability
Time frame
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)Other outcomes
1
Side effect monitoring
Prior to discharge at each session, subjects will be asked to report any and all adverse events they experienced and common side effects will explicitly be asked about. The most common side effects include anxiety, nausea, headache, and fatigue which are highly likely to be self-limiting or can be easily treated if necessary.
Time frame
From enrolment until the last follow-up session (expected at about 12 weeks after enrolment)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Medical University of Vienna
Lead sponsor
University of Vienna
Collaborator
Source ClinicalTrials.gov