Recruiting
Phase 1

Psilocybin with Midazolam

Sponsor:

University of Wisconsin, Madison

Code:

NCT06692192

Conditions

Psilocybin

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Psilocybin

Psilocybin

Midazolam

Saline

Study Details

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

Study ID

NCT06692192

Start date

Aug 7, 2025

Status verified date

Mar, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

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

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Group 1: Psilocybin and intravenous (IV) midazolam

Psilocybin (25 mg) + IV midazolam

experimental: Group 2: Psilocybin and IV saline

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

experimental: Group 3: Psilocybin and IV midazolam

Psilocybin (1 mg/control) + IV midazolam

experimental: Group 4: Psilocybin and IV saline

Psilocybin (1 mg/control) + IV saline

Interventions

Psilocybin

25mg of psilocybin

Psilocybin

1mg of psilocybin

Midazolam

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

Saline

Saline will be administered as a placebo for midazolam

Primary outcome measure

  • Change in Warwick-Edinburgh Mental wellbeing Scale (WEMWBS) [ Time Frame: Baseline to 7 days post-dose ]
  • Change in Brief Experiential Avoidance Questionnaire (BEAQ) [ Time Frame: Baseline to 7 days post-dose ]
  • Change in Probabilistic Reversal Learning (PRL) [ Time Frame: Baseline to 7 days post-dose ]
  • Change in transcranial magnetic stimulation evoked potential (TEP) amplitude [ Time Frame: Baseline to 7 days post-dose ]

Central Contacts and Locations

Central contacts

RECAP Study Contact

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

Locations

UW School of Medicine and Public Health

Recruiting

Madison, Wisconsin, United States, 53792

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

Aug 13, 2026

Last verified

Mar, 2026

Keywords

  • sub-optimal wellbeing

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-08-13.