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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Psychedelic Experiences; Well-Being, Psychological
• Intervention / Treatment: Drug: Psilocybin; Other: Saline Placebo; Drug: Clonidine

Detailed 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

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: CoPEWell Study Contact; Phone Number: 608-263-4852; Email: copewell@psychiatry.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin While Awake, Placebo While Asleep; 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.	Drug: Psilocybin; IV administration, infusion of 3.2 mg psilocybin over 10 minutes, followed by an additional 0.8 mg infused over the following 20 minutes; Other Names: intravenous psilocybin; Other: Saline Placebo; IV administration, placebo will be 20 mL of saline drawn up aseptically into the same sized (30 mL) syringe as is used for the active drug.; Drug: Clonidine; 0.2 mg of clonidine will be taken by mouth by all participants 60 minutes prior to the initial infusion on Dosing Night; Other Names: Clonidine ER
Experimental: Placebo While Awake, Psilocybin While Asleep; 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.	Drug: Psilocybin; IV administration, infusion of 3.2 mg psilocybin over 10 minutes, followed by an additional 0.8 mg infused over the following 20 minutes; Other Names: intravenous psilocybin; Other: Saline Placebo; IV administration, placebo will be 20 mL of saline drawn up aseptically into the same sized (30 mL) syringe as is used for the active drug.; Drug: Clonidine; 0.2 mg of clonidine will be taken by mouth by all participants 60 minutes prior to the initial infusion on Dosing Night; Other Names: Clonidine ER
Placebo Comparator: Placebo While Awake, Placebo While Asleep; 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.	Other: Saline Placebo; IV administration, placebo will be 20 mL of saline drawn up aseptically into the same sized (30 mL) syringe as is used for the active drug.; Drug: Clonidine; 0.2 mg of clonidine will be taken by mouth by all participants 60 minutes prior to the initial infusion on Dosing Night; Other Names: Clonidine ER

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) score: Psilocybin Awake versus Asleep	WEMWBS is a 14-item survey scored on a 5 point likert scale. The total range in scores is from 14 to 70 where higher scores indicate better mental wellbeing. Reported here for psilocybin administered while awake to psilocybin administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29
Change in Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) score: Psilocybin Asleep versus Placebo Asleep	WEMWBS is a 14-item survey scored on a 5 point likert scale. The total range in scores is from 14 to 70 where higher scores indicate better mental wellbeing. Reported here for psilocybin administered while asleep to and placebo administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brief Experiential Avoidance Questionnaire (BEAQ): Psilocybin Awake versus Asleep	BEAQ is 15-item survey scored on a 6 point likert scale. The total range is scores if from 15 to 90 where higher scores indicating greater avoidance. Reported here for psilocybin administered while awake to psilocybin administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29
Change in Brief Experiential Avoidance Questionnaire (BEAQ): Psilocybin Asleep versus Placebo Asleep	BEAQ is 15-item survey scored on a 6 point likert scale. The total range is scores if from 15 to 90 where higher scores indicating greater avoidance. Reported here for psilocybin administered while asleep to placebo administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29
Change in Watts Social Connectedness (WCS) Scale: Psilocybin Awake versus Asleep	WCS is a 19-item survey scored on a visual analog scale. Scores are reported from 0-100 where higher scores interpreted to be more connectedness to others. Reported here for psilocybin administered while awake to psilocybin administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29
Change in Watts Social Connectedness (WCS) Scale: Psilocybin Asleep versus Placebo Asleep	WCS is a 19-item survey scored on a visual analog scale. Scores are reported from 0-100 where higher scores interpreted to be more connectedness to others. Reported here for psilocybin administered while asleep to placebo administered while asleep.	Baseline 2 (Day 0) to post-dosing Day 29
Persisting Effects Questionnaire (PEQ): Psilocybin Awake versus Asleep	PEQ-15 is a 15-item survey in which initial items are rated on an 8-point scale ranging from "no more than routine, everyday experiences" to "the single most meaningful experience of my life." Remaining items are rated on a 7-point scale ranging from strong negative change to strong positive change. Higher scores indicate more positive persisting effects. Reported here for psilocybin administered while asleep to psilocybin administered while asleep.	post-dosing Day 29
Persisting Effects Questionnaire (PEQ): Psilocybin Asleep versus Placebo Asleep	PEQ-15 is a 15-item survey in which initial items are rated on an 8-point scale ranging from "no more than routine, everyday experiences" to "the single most meaningful experience of my life." Remaining items are rated on a 7-point scale ranging from strong negative change to strong positive change. Higher scores indicate more positive persisting effects. Reported here for psilocybin administered while asleep to psilocybin administered while asleep.	post-dosing Day 29

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Tiny Blue Dot Foundation
• Investigators: Principal Investigator: Charles Raison, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Personal Satisfaction; Psychological Well-Being; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Alkaloids; Imidazoles; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Imidazolines; Psilocybin; Clonidine
• Other Study ID Numbers: 2025-1861; Protocol Version 12/18/25 (Other Identifier: UW Madison); SMPH | Psychiatry (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) will be made available to qualified researchers for research purposes. Data will be shared in accordance with applicable funder requirements, institutional policies, and regulatory obligations, including deposition in a designated data repository when required. Otherwise, data will be shared upon reasonable request following publication of primary study results, subject to institutional review and approval.
• IPD Sharing Time Frame: Data will be available beginning after publication of primary study results and following completion of data quality control and de-identification procedures.
• IPD Sharing Access Criteria: Access will be granted to qualified investigators for scientifically valid research proposals, subject to review and approval by the study team and the University of Wisconsin-Madison, and execution of a data use agreement as required.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No