The RECAP2 Study: Midazolam and Psilocybin
- Conditions
- Psilocybin
- Interventions
- Registration Number
- NCT06692192
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing.
Researchers will compare different doses of psilocybin combined with midazolam or placebo to see what dose induces increased wellbeing.
Participants will:
* Receive one of four possible combinations of medications
* Undergo an MRI
* Complete questionnaires
* Undergo transcranial magnetic stimulation (TMS) and EEG
- Detailed Description
The purpose of this study is to investigate the role that inducing neuroplasticity plays in the behavioral effects of psilocybin in people with modest decrements in emotional wellbeing.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Age 18 to 70 years at screening, of any identified gender and racial/ethnic group
- Physically healthy; does not meet criteria for an exclusionary medical condition
- English-speaking (able to provide consent and complete questionnaires)
- Modest decrement in self-reported wellbeing without the presence of a DSM-5 Axis I mood or anxiety disorder
- Exclusionary DSM-5 psychiatric diagnosis and/or active suicidal ideation
- Exclusionary medical conditions
- Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
- Clinically significant electrocardiogram (ECG)
- Use of psychotropic or CNS-altering medications within 3 months of screening
- Hypertension or tachycardia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Psilocybin and IV saline Psilocybin Psilocybin (25 mg) + IV saline (placebo for midazolam) Group 3: Psilocybin and IV midazolam Psilocybin Psilocybin (1 mg/control) + IV midazolam Group 4: Psilocybin and IV saline Psilocybin Psilocybin (1 mg/control) + IV saline Group 2: Psilocybin and IV saline Saline Psilocybin (25 mg) + IV saline (placebo for midazolam) Group 3: Psilocybin and IV midazolam Midazolam Psilocybin (1 mg/control) + IV midazolam Group 4: Psilocybin and IV saline Saline Psilocybin (1 mg/control) + IV saline Group 1: Psilocybin and intravenous (IV) midazolam Psilocybin Psilocybin (25 mg) + IV midazolam Group 1: Psilocybin and intravenous (IV) midazolam Midazolam Psilocybin (25 mg) + IV midazolam
- Primary Outcome Measures
Name Time Method Change in Penn Conditional Exclusion Test (PCET) Baseline to 7 days post-dose As participants receive serial scans, they are asked to complete three different object sorting tasks based on one of three sorting principles. During the test, participants must infer the correct sorting principle based on response feedback. Once the participant achieves 10 correct responses in a row, the sorting principle shifts, and the participant must learn the new sorting principle presented by the new object sorting task. In this study, participants will be tested at baseline and again 28-days post-treatment. Perseverative errors on the PCET before and after the psychedelic experience will be measured for each participant, with fewer errors interpreted as improved cognitive flexibility.
Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS) Baseline to 7 days post-dose WEMWBS is a 14-item questionnaire in which participants describe their experience of each item. It is scored on a 5-point Likert scale, possible range of 14-70 where higher scores indicate higher levels of wellbeing.
Change in Brief Experiential Avoidance Questionnaire (BEAQ) Baseline to 7 days post-dose The BEAQ is a 15-item questionnaire assessing participants agreement with wellbeing statements. It is scored on a 6-point Likert scale, ranging from 15-90 with higher scores indicating a greater tendency towards experiential avoidance
Change in transcranial magnetic stimulation evoked potential (TEP) amplitude Baseline to 7 days post-dose TEP measures neural excitability in the stimulated region of the brain.
- Secondary Outcome Measures
Name Time Method BEAQ 28 days post-dose The BEAQ is a 15-item questionnaire assessing participants agreement with wellbeing statements. It is scored on a 6-point Likert scale, ranging from 15-90 with higher scores indicating a greater tendency towards experiential avoidance
PCET 28 days post-dose As participants receive serial scans, they are asked to complete three different object sorting tasks based on one of three sorting principles. During the test, participants must infer the correct sorting principle based on response feedback. Once the participant achieves 10 correct responses in a row, the sorting principle shifts, and the participant must learn the new sorting principle presented by the new object sorting task. In this study, participants will be tested at baseline and again 28-days post-treatment. Perseverative errors on the PCET before and after the psychedelic experience will be measured for each participant, with fewer errors interpreted as improved cognitive flexibility.
Change in Personalized Psychological Flexibility Index (PPFI) Baseline to 28 days post-dose the PPFI first asks participants to identify "an important goal that they are working on," and then, using a 7-point Likert scale, to select the rating that best describes their thoughts and feelings about that specified goal.
Change in Alternate Use Task (AUT) Baseline to 28 days post-dose The AUT is a timed assessment that asks participants to list as many alternatives uses as possible for each common object presented to them. The more alternatives listed, the better.
Change in Cognitive Control and Flexibility (CCF) questionnaire Baseline to 28 days post-dose The CCF is an 18-item questionnaire that assesses two aspects of cognitive flexibility, specific to stress and depressive symptoms. Items are rated by participants on a 7-point Likert scale. 1 = strongly disagree, 7 = strongly agree, with a score range of 18-126. The higher the overall score indicates better cognitive control and cognitive flexibility.
Change in TEP amplitude Baseline to 28 days post-dose TEP measures neural excitability in the stimulated region of the brain.
Altered States of Consciousness (ASC) questionnaire Dosing 1 day Participants will complete a selection of several questions from the ASC questionnaire that strongly associate positively or negatively with later antidepressant effect of psilocybin in patients with treatment resistant depression or capture classic features of the psychedelic experience. During the dosing session, investigator will repeatedly ask selected items from the ASC scale to get a "real time" measure of what the participants are experiencing. Each of these items will be scored separately. Higher score are indicative of a more intense psychedelic experience.
Emotional Breakthrough Inventory (EBI) Dosing 1 day The EBI is a 6-item scale that assesses the presence and severity of emotionally challenging/distressing experiences that occur during a psychedelic experience. Participants rate to what extent the statements apply to their experience by marking a single line across each scale. Scale ranges from not at all to very much so. Higher scores (more slashes toward the 'very much so' end) on the scale have been associated with enhanced well-being following psychedelic use
Psychological Insight Questionnaire (PIQ) Dosing 1 day The PIQ is a 23-item instrument designed to query self-perceived attainment of insight during a psychedelic medicine session. Items are rated on a 6-point Likert scale, 0 = no not at all and 5 = extremely. Possible scares range from 0-115, with higher scores indicating greater insight.