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

NCT07360301 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2025-1861SMPH | PsychiatryProtocol Version 12/18/25
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Psychedelic Experiences; Well-Being, Psychological

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Change in Brief Experiential Avoidance Questionnaire (BEAQ): Psilocybin Awake versus Asleep

  Baseline 2 (Day 0) to post-dosing Day 29

• Change in Brief Experiential Avoidance Questionnaire (BEAQ): Psilocybin Asleep versus Placebo Asleep

  Baseline 2 (Day 0) to post-dosing Day 29

• Change in Watts Social Connectedness (WCS) Scale: Psilocybin Awake versus Asleep

  Baseline 2 (Day 0) to post-dosing Day 29

• Change in Watts Social Connectedness (WCS) Scale: Psilocybin Asleep versus Placebo Asleep

  Baseline 2 (Day 0) to post-dosing Day 29

• Persisting Effects Questionnaire (PEQ): Psilocybin Awake versus Asleep

  post-dosing Day 29

Study Arms (3)

Psilocybin While Awake, Placebo While Asleep

EXPERIMENTAL

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; Other: Saline Placebo; Drug: Clonidine

Placebo While Awake, Psilocybin While Asleep

EXPERIMENTAL

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; Other: Saline Placebo; Drug: Clonidine

Placebo While Awake, Placebo While Asleep

PLACEBO COMPARATOR

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; Drug: Clonidine

Interventions

Psilocybin DRUG

IV administration, infusion of 3.2 mg psilocybin over 10 minutes, followed by an additional 0.8 mg infused over the following 20 minutes

Also known as: intravenous psilocybin

Placebo While Awake, Psilocybin While Asleep; Psilocybin While Awake, Placebo While Asleep

Saline Placebo OTHER

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.

Placebo While Awake, Placebo While Asleep; Placebo While Awake, Psilocybin While Asleep; Psilocybin While Awake, Placebo While Asleep

Clonidine DRUG

0.2 mg of clonidine will be taken by mouth by all participants 60 minutes prior to the initial infusion on Dosing Night

Also known as: Clonidine ER

Placebo While Awake, Placebo While Asleep; Placebo While Awake, Psilocybin While Asleep; Psilocybin While Awake, Placebo While Asleep

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 45 years (inclusive) at screening, of any identified gender and racial/ethnic group
• English-speaking (able to provide consent and complete questionnaires)
• Sub-optimal self-reported wellbeing

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Tiny Blue Dot Foundation: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Psychological Well-Being

Interventions

Psilocybin; Clonidine

Condition Hierarchy (Ancestors)

Personal Satisfaction; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Charles Raison, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CoPEWell Study Contact

CONTACT

608-263-4852; copewell@psychiatry.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 22, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available beginning after publication of primary study results and following completion of data quality control and de-identification procedures.
• 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.

Locations

US (1)