Consciousness, Psilocybin, and Well-Being

Healthy Clinical Trial

— CoPE Pilot  

Official title:

Consciousness and Psilocybin Effects on Well-Being (The CoPE Study): Pilot Phase

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05592379
• Other study ID #: 2022-0746
• Secondary ID: A532017Protocol
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: November 7, 2023
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to identify a dosing strategy that will allow IV psilocybin to be administered to sleeping participants without awakening them.

Description:

The study intervention will be psilocybin administered by the intravenous (IV) route combined with oral clonidine (hereafter "psilocybin+clonidine") in sleeping participants and psilocybin+clonidine and psilocybin alone administered to awake participants.

The study will use an adaptive design. This design will involve testing up to two psilocybin+clonidine administration protocols in asleep and awake subjects and one of two "IV psilocybin only" administration protocols in awake participants.

The first psilocybin+clonidine protocol to be tested will consist of 2 mg of psilocybin administered via IV infusion over a 2-minute period combined with 0.2 mg oral clonidine in 2 sleeping participants (Group 1A).

• Should this method allow at least 2 participants to remain asleep for at least 1-hour post-dosing and/or to have no memory of the dosing experience upon awakening, this 2-minute IV dosing strategy (co-administered with 0.2 mg of oral clonidine) will be selected for testing in 2 to 5 awake participants (Group 1B).

• Should participants fail to remain asleep during testing of the 2-minute infusion protocol, investigators will test a second protocol that will comprise a 10-minute minute IV infusion of 2 mg psilocybin combined with 0.2 mg oral clonidine in 2 to 5 asleep participants (Group 2A).

• Should at least 2 participants remain asleep for at least 1-hour post-dosing and/or have no memory of the dosing experience upon awakening, this 10-minute IV dosing strategy (co-administered with 0.2 mg of oral clonidine) will be selected for testing in 2 to 5 awake participants (Group 2B).

• If either the 2-minute or 10-minute psilocybin infusion (plus oral clonidine) protocols allow sleep maintenance, 2 to 5 participants will receive that psilocybin infusion protocol without clonidine to evaluate any potential effect of co-administered clonidine on the acute psychedelic experience in awake participants (Group 1C for 2-minute psilocybin infusion; Group 2C for 10-minute psilocybin infusion).

In addition, all participants enrolled to receive psilocybin+clonidine while asleep will also receive normal saline via IV prior to the night they receive IV psilocybin+clonidine to accommodate them to the IV procedure. For any given participant, the protocol for delivering the normal saline will be identical to the psilocybin protocol they receive (e.g., either IV saline (10 mL) over 2 minutes or IV saline (10 mL) over 10 minute IV infusion). Participants unable to remain asleep through the IV placebo administration may be discontinued from study participation at the discretion of the study team without progressing to receive a n IV dose of IV psilocybin and oral clonidine.

Adaptive Study Design Change per Protocol Amendment Approved 5/21/24

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 23
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Medically healthy

• English-speaking

• Live within 150 miles of Madison, WI for duration of study

Exclusion Criteria:

• Current use of medications that may interact with psilocybin

• Current sleep disorder, including (but not limited to) insomnia, sleep apnea, restless legs syndrome, and/or narcolepsy

• Females with positive urine pregnancy at any time point during screening or study participation

• Current cardiac valve disease

Related Conditions & MeSH terms

• Healthy
• Psychedelic Experiences
• Sleep

Intervention

Drug:
• Psilocybin
The IV formulation of psilocybin will be prepared using bulk psilocybin that will satisfy Good Manufacturing Practice (GMP) criteria. The IV psilocybin solution will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center (PRC).
• Clonidine
Clonidine will be administered orally in a 0.2mg dose

Other:
• Saline
The IV placebo (saline) will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center.

Locations

Country	Name	City	State
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin

Sponsors (3)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Tiny Blue Dot Foundation, Usona Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and nature of adverse events associated with the administration of a single dose of IV psilocybin	Adverse events associated with the administration of a single dose of IV psilocybin administered either alone or in combination with oral clonidine in asleep and awake participants. Adverse event grading will be done using Common Terminology Criteria for Adverse Event (CTCAE)Adverse events will be graded from Grade 1-5 depending on severity. Grade 1 - mild, grade 2 - moderate, grade 3 - severe, grade 4 - Life threatening, grade 5 - Fatal. Adverse events will be collected on an Adverse Event Log throughout the study.	Up to 9 days
Secondary	Number of participants administered psilocybin plus clonidine while asleep who remain asleep for at least 1 hour post dosing and/or report no memory of the dosing experience upon awakening		1 day
Secondary	Post-dosing scores on the 30-item Mystical Experiences Questionnaire (MEQ30) following administration of psilocybin and clonidine while asleep or awake	The MEQ30 is a 30-item self-report measure developed to assess the effects of classic psychedelics in laboratory studies. It covers the major dimensions of the classic mystical experience: unity, transcendence, noetic quality, sacredness, positive mood, and ineffability/paradoxicality. The MEQ has 4 sub scales: 1) transcendence, 2) positive mood, 3) ineffability, and 4) mystical. The total possible range for each sub scale and total score is 0-100% with higher percentages indicating a larger mystical experience. Typically, a complete mystical experience is defined as scoring 60% or more on all four MEQ30 subscales.	1 day
Secondary	Post-dosing scores on the Emotional Breakthrough Inventory (EBI) following administration of IV psilocybin either alone or in combination with clonidine while awake	The EBI is a 6-item self-report scale that assesses the presence and severity of emotionally challenging/distressing experiences that occur during a psychedelic experience. The scale utilizes visual analog responses captured on a line anchored by "not at all" on one end and "very much so" on the other. Experiences queried include 1) facing emotionally difficult feelings that are usually pushed aside; 2) experiencing a resolution of a personal conflict/trauma; 3) being able to explore challenging emotions and memories; 4) having an emotional breakthrough; 5) getting a sense of closure on an emotional problem, and 6) achieving an emotional release followed by a sense of relief. The total possible range of scores for the EBI is 0-100 with higher scores indicating a greater emotional breakthrough.	1 day
Secondary	Post-dosing scores on the Psychological Insight Scale (PIS) following administration of IV psilocybin either alone or in combination with clonidine while awake	The PIS is a 6-item self-report scale that queries the acquisition of insight following a psychedelic therapy. The items are answered with visual analogue scales anchored by "no more than usually" on the left and "much more than usually" on the far right. A seventh item separately assesses self-reported behavioral change resulting from the psychedelic experience. The total possible range of scores for the PIS is 0-100 with higher scores indicating a greater psychological insight.	1 day
Secondary	Post-dosing scores on the Ego Dissolution Inventory (EDI) following administration of IV psilocybin either alone or in combination with clonidine while awake	The EDI is an 8-item self-report scale designed to measure ego-dissolution. Each item is scored on a visual analogue scale from 0 to 100 with the following statements at the lower and upper end, respectively: "No, not more than usually" and "Yes, I experienced this completely/entirely." The total possible range of scores for the EDI is 0-100 with higher scores indicating a greater ego dissolution.	1 day
Secondary	Post-dosing scores on the Awe Experiences Scale (AWE) following administration of IV psilocybin either alone or in combination with clonidine while awake	The AWE is a 30-item self-report scale that measures the state of awe. Each items is rated on a scale of 1 to 7, with 1 representing "Strongly Disagree" and 7 representing "Strongly Agree". The total possible range of scores for the AWE is 1-7 with higher scores indicating a greater awe.	1 day
Secondary	Post-dosing scores on the Altered States of Consciousness Questionnaire (ASC) following administration of IV psilocybin while either alone or in combination with clonidine while awake	The ASC is a 94-item self-report scale that assesses alterations from your normal waking consciousness. Each item is scored on a visual analogue scale from 0 to 100 with the following statements at the lower and upper end, respectively: "No, not more than usually" and "Yes, much more than usually." The total possible range of scores for the ASC is 0-100 with higher scores indicating a greater state of altered consciousness.	1 day
Secondary	Post-dosing scores on the Challenging Experiences Questionnaire (CEQ) following administration of IV psilocybin either alone or in combination with clonidine while awake	The CEQ is a 26-item questionnaire that consists of seven factors of challenging experience with psilocybin mushrooms: fear, grief, feeling of losing your sanity (insanity), feel as though you are dying (death), feelings of isolation, physiological distress, and paranoia. The CEQ uses a 6-point response scale [0: None/not at all, 1: So slight cannot decide, 2: Slight, 3: Moderate, 4: Strong; 5: Extreme (more than ever before in my life)] to indicate the degree to which a participant experiences each of a series of subjective effects during their psilocybin session. Total CEQ score is expressed as the percentage of the total possible ratings on the scale. The total possible range of scores for the CEQ is 0-5 with higher scores indicating a greater challenging experience.	1 day
Secondary	Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) score 7 days post administration of IV psilocybin either alone or in combination with clonidine while awake	The WEMWBS is a 14-item self-report scale that was designed to measure the psychological well-being of a population. The questions use a five-point Likert scale. The items are all worded positively and cover both feeling and functioning aspects of mental wellbeing. Items on the questionnaire are rated on a 5-point scale, where 1= "None of the time", 2= "rarely", 3= "some of the time", 4= "often", 5= "all the time". A total scale score is calculated by summing the 14 individual item scores. The total possible range of scores for the WEMWBS is 14-70 with higher scores indicating a greater well-being.	Up to 19 days
Secondary	World Health Organization Well-Being Index	World Health Organization Well-Being Index (WHO-5) is a 5-item survey with a total possible range of scores 0-25 where higher scores indicate increased well-being.	Up to 19 days