The RECAP2 Study: Midazolam and Psilocybin

NCT06692192 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 2024-0852A538900SMPH/PSYCHIATRY/PSYCHIATRYProtocol Version 12/12/2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Conditions

Psilocybin

Keywords

sub-optimal wellbeing

Outcome Measures

Primary Outcomes (4)

• Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS)

  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.

  Baseline to 7 days post-dose

• Change in Brief Experiential Avoidance Questionnaire (BEAQ)

  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

  Baseline to 7 days post-dose

• Change in Probabilistic Reversal Learning (PRL)

  Participants are presented with two stimuli or options and learn which one is more likely to be associated with a reward based on feedback after each trial. After a certain number of trials, the reward contingencies are reversed, meaning the previously advantageous option becomes less likely to be rewarded, and vice versa. The task assesses how quickly and effectively individuals can adapt to these changes in reward contingencies. Researchers analyze various performance metrics, such as the speed of reversal, the number of errors, and the patterns of choices (e.g., win-stay, lose-shift).

  Baseline to 7 days post-dose

• Change in transcranial magnetic stimulation evoked potential (TEP) amplitude

  TEP measures neural excitability in the stimulated region of the brain.

  Baseline to 7 days post-dose

Secondary Outcomes (7)

• Change in WEMWBS

  Baseline to 28 days post-dose

• Change in BEAQ

  Baseline to 28 days post-dose

• Change in PRL

  Baseline to 28 days post-dose

• Change in TEP amplitude

  Baseline to 28 days post-dose

• Altered States of Consciousness (ASC) questionnaire

  Dosing 1 day

Study Arms (4)

Group 1: Psilocybin and intravenous (IV) midazolam

EXPERIMENTAL

Psilocybin (25 mg) + IV midazolam

Drug: Psilocybin; Drug: Midazolam

Group 2: Psilocybin and IV saline

EXPERIMENTAL

Psilocybin (25 mg) + IV saline (placebo for midazolam)

Drug: Psilocybin; Drug: Saline

Group 3: Psilocybin and IV midazolam

EXPERIMENTAL

Psilocybin (1 mg/control) + IV midazolam

Drug: Psilocybin; Drug: Midazolam

Group 4: Psilocybin and IV saline

EXPERIMENTAL

Psilocybin (1 mg/control) + IV saline

Drug: Psilocybin; Drug: Saline

Interventions

Psilocybin DRUG

25mg of psilocybin

Also known as: Psilocybine, Psilocibin

Group 1: Psilocybin and intravenous (IV) midazolam; Group 2: Psilocybin and IV saline

Midazolam DRUG

The goal of the midazolam dosing regimen is to induce amnesia of the psychedelic experience without inducing over-sedation during the dosing session.

Group 1: Psilocybin and intravenous (IV) midazolam; Group 3: Psilocybin and IV midazolam

Saline DRUG

Saline will be administered as a placebo for midazolam

Group 2: Psilocybin and IV saline; Group 4: Psilocybin and IV saline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years at screening, of any identified gender and racial/ethnic group
• 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
• Able to undergo magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Vail Health Foundation: collaborator

Study Sites (1)

UW School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Interventions

Psilocybin; Midazolam; Sodium Chloride

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Benzodiazepines; Benzazepines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Charles Raison, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

RECAP Study Contact

CONTACT

608-263-4852; recap2@psychiatry.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2024
• First Posted: November 18, 2024
• Study Start: August 7, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)