Consciousness and Psilocybin Effects on Well-Being: The CoPEWell Study

University of Wisconsin (UW)

Status and phase: Not yet enrolling; Phase 1

Conditions: Psychedelic Experiences; Well-Being, Psychological

Treatments: Other: Saline Placebo; Drug: Psilocybin; Drug: Clonidine

Study type: Interventional

Funder types: Other

Identifiers

NCT07360301

Protocol Version 12/18/25 (Other Identifier)

2025-1861

SMPH | Psychiatry (Other Identifier)

Details and patient eligibility

About

This study is exploring how psilocybin (a psychedelic drug) may improve mood and wellbeing. Many people report feeling better after taking psilocybin, but it is not clear why. The CoPEWell study will test whether these improvements come from the psychedelic experience itself (the "trip") or from direct effects on the brain. To study this, up to 120 participants will be enrolled to receive psilocybin either while awake or asleep and can expect to be on study for up to 4 months.

Full description

Primary Objectives:

1. To evaluate the effect of psilocybin on wellbeing when administered while awake vs. while asleep

2. To evaluate the effect of psilocybin on wellbeing administered while asleep vs. placebo administered while asleep

   Secondary Objectives:

3. To evaluate the effect of psilocybin on psychological flexibility when administered while awake vs. while asleep

4. To evaluate the effect of psilocybin on psychological flexibility administered while asleep vs. placebo administered while asleep

5. To evaluate the effect of psilocybin on social connectedness when administered while awake vs. while asleep

6. To evaluate the effect of psilocybin on social connectedness administered while asleep vs. placebo administered while asleep

7. To evaluate the effect on wellbeing/life satisfaction/purpose/meaning explicitly ascribed to psilocybin administered while awake vs. while asleep

8. To evaluate the effect on wellbeing/life satisfaction/purpose/meaning explicitly ascribed to psilocybin administered while asleep vs. saline placebo administered while asleep

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age 18 to 45 years (inclusive) at screening, of any identified gender and racial/ethnic group
• Physically healthy; does not meet criteria for an exclusionary medical condition
• No exclusionary sleep condition
• English-speaking (able to provide consent and complete questionnaires)
• Sub-optimal self-reported wellbeing

Exclusion criteria

• Exclusionary DSM-5 psychiatric diagnosis and/or active suicidal ideation
• Exclusionary medical conditions or sleep 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: Double Blind

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120 participants in 3 patient groups, including a placebo group

Psilocybin While Awake, Placebo While Asleep

Experimental group

Description:

Participants in this group will receive psilocybin by intravenous (IV) infusion while awake and placebo (saline) by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.

Treatment:

Drug: Clonidine

Drug: Psilocybin

Other: Saline Placebo

Placebo While Awake, Psilocybin While Asleep

Experimental group

Description:

Participants in this group will receive placebo (saline) by intravenous (IV) infusion while awake and psilocybin by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.

Treatment:

Drug: Clonidine

Drug: Psilocybin

Other: Saline Placebo

Placebo While Awake, Placebo While Asleep

Placebo Comparator group

Description:

Participants in this group will receive placebo (saline) by intravenous (IV) infusion while awake and placebo by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.

Treatment:

Drug: Clonidine

Other: Saline Placebo