Consciousness, Psilocybin, and Well-Being

Study Overview
=================
Brief Summary
-----------------
This pilot study aims to 1) establish a dosing regimen for intravenous (IV) psilocybin that will allow the drug to be administered to asleep participants without awakening them; and 2) assess whether this dosing regimen produces a psychedelic experience.

Detailed Description
-----------------
The study intervention will be psilocybin administered by the intravenous (IV) route to sleeping and awake participants. The study will test up to two different IV administration protocols in sleeping participants. The first protocol to be tested will consist of 2 mg of psilocybin administered via IV infusion over a 2-minute period. Should this method allow participants to remain asleep for at least 1 hour post-dosing, no further dosing strategies will be evaluated. If the 2-minute IV infusion delivery method disrupts sleep, a second dosing strategy will be examined consisting of 2 mg of IV psilocybin administered over 10 minutes. Whichever dosing strategy causes the least sleep disruption will be selected for administration to awake participants. As part of the study design, some participants may also receive normal IV saline instead of IV psilocybin during the dosing session. 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 will include medically and psychiatrically healthy biological males and females of any identified gender and racial/ethnic group aged 18 to 35 years.

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

Conditions
-----------------
Healthy, Psychedelic Experiences, Sleep

Intervention / Treatment
-----------------
* Drug: Psilocybin and Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Medically healthy English-speaking 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 History of heart transplant or stroke Females with positive urine pregnancy at any time point during screening or study participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: An initial group of participants (n=5) will receive 2 mg of IV psilocybin over a 2-minute period while asleep. If participants are able to remain asleep under this protocol, a subsequent 5 participants will receive the 2-min IV infusion protocol while awake. If the 2-minute IV infusion produces an unacceptable rate of awakening in the initial 5 participants, a subsequent 5 participants will receive 2 mg of IV psilocybin over a 10-minutes period while asleep. If the 10-minute IV infusion protocol succeeds in keeping participants asleep, an additional 5 participants will receive the 10-min IV infusion protocol while awake. If the 10-minute IV infusion produces an unacceptable rate of awakening, this dosage will not be tested in awake subjects and the study will be re-evaluated.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-minute IV Psilocybin/Placebo Infusion - Asleep<br>Participants will receive 2mg of IV psilocybin over 2 minutes while asleep during an overnight visit and 10 mL of placebo (saline) over 2 minutes while asleep during another overnight visit. The order of administration will be determined by the study protocol. | Drug: Psilocybin and Saline<br>* 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). The IV placebo (saline) will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center.<br>* Other names: Psilocibin;|
| Experimental: 2-minute IV Psilocybin/Placebo Infusion - Awake<br>Participants will receive either 2mg of IV psilocybin or 10 mL of IV saline (placebo) over 2 minutes during an overnight visit while awake. | Drug: Psilocybin and Saline<br>* 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). The IV placebo (saline) will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center.<br>* Other names: Psilocibin;|
| Experimental: 10-minute IV Psilocybin/Placebo Infusion - Asleep<br>Participants will receive 2mg of IV psilocybin over 10 minutes while asleep during an overnight visit and 10 mL of placebo (saline) over 10 minutes while asleep during another overnight visit. The order of administration will be determined by the study protocol. | Drug: Psilocybin and Saline<br>* 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). The IV placebo (saline) will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center.<br>* Other names: Psilocibin;|
| Experimental: 10-minute IV Psilocybin/Placebo Infusion - Awake<br>Participants will receive either 2mg of IV psilocybin or 10 mL of IV saline (placebo) over 10 minutes during an overnight visit while awake. | Drug: Psilocybin and Saline<br>* 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). The IV placebo (saline) will be prepared under sterile conditions by the University of Wisconsin Pharmaceutical Research Center.<br>* Other names: Psilocibin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and nature of adverse events associated with the administration of a single dose of IV psilocybin while asleep or awake | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects administered IV psilocybin while asleep who remain asleep for at least 1 hour post dosing |  | 1 day | 
| Post-dosing scores on the 30-item Mystical Experiences Questionnaire (MEQ30) following administration of IV psilocybin 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. | Up to 2 days | 
| Post-dosing scores on the Emotional Breakthrough Inventory (EBI) following administration of IV psilocybin while asleep or 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. | Up to 2 days | 
| Post-dosing scores on the Psychological Insight Scale (PIS) following administration of IV psilocybin while asleep or 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 | 
| Post-dosing scores on the Ego Dissolution Inventory (EDI) following administration of IV psilocybin while asleep or 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. | Up to 2 days | 
| Post-dosing scores on the Awe Experiences Scale (AWE) following administration of IV psilocybin while asleep or 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. | Up to 2 days | 
| Post-dosing scores on the Altered States of Consciousness Questionnaire (ASC) following administration of IV psilocybin while asleep or 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. | Up to 2 days | 
| Post-dosing scores on the Challenging Experiences Questionnaire (CEQ) following administration of IV psilocybin while asleep or 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. | Up to 2 days | 
| Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) score 7 days post administration of IV psilocybin while asleep or 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sleep, Psilocybin, Psychedelics, Healthy Volunteer