The RECAP2 Study: Midazolam and Psilocybin

University of Wisconsin (UW)

Status and phase: Enrolling; Phase 1

Conditions: Psilocybin

Treatments: Drug: Midazolam; Drug: Saline; Drug: Psilocybin

Study type: Interventional

Funder types: Other

Identifiers

NCT06692192

Protocol Version 12/12/2025 (Other Identifier)

A538900 (Other Identifier)

SMPH/PSYCHIATRY/PSYCHIATRY (Other Identifier)

2024-0852

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age 18 to 65 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
• Able to undergo magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS)

Exclusion criteria

• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 4 patient groups

Group 1: Psilocybin and intravenous (IV) midazolam

Experimental group

Description:

Psilocybin (25 mg) + IV midazolam

Treatment:

Drug: Psilocybin

Drug: Psilocybin

Drug: Midazolam

Group 2: Psilocybin and IV saline

Experimental group

Description:

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

Treatment:

Drug: Psilocybin

Drug: Psilocybin

Drug: Saline

Group 3: Psilocybin and IV midazolam

Experimental group

Description:

Psilocybin (1 mg/control) + IV midazolam

Treatment:

Drug: Psilocybin

Drug: Psilocybin

Drug: Midazolam

Group 4: Psilocybin and IV saline

Experimental group

Description:

Psilocybin (1 mg/control) + IV saline

Treatment:

Drug: Psilocybin

Drug: Psilocybin

Drug: Saline