The RECAP2 Study: Midazolam and Psilocybin

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

Participants invited to participate in the 28-day open label follow-up phase will:

1. Fully complete all activities associated with the randomized phase, including the virtual Day 84 assessment, before being approached about participation in the open label phase.
2. Participants who meet stopping criteria during the randomized phase are not eligible to enroll in the open label phase.
3. Participants who withdraw from the randomized phase are not eligible to enroll in the open label phase.
4. Enrollment into the open label phase must occur in the following sequence:

   1. participants who have fully completed the randomized phase are screened for eligibility;
   2. eligible participants meet with the study team and provide informed consent for the open label phase;
   3. baseline eligibility is reassessed to confirm that participation in the open label phase remains appropriate and safe.

The Principal Investigator may decline or defer open-label enrollment when unresolved concerns make participation unsafe or scientifically inappropriate.