Consciousness, Psilocybin, and Well-Being

NCT05592379 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: 2022-0746A532017Protocol Version 10/2/2024233897
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy; Psychedelic Experiences; Sleep

Keywords

Sleep; Psilocybin; Psychedelics; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

• Post-dosing scores on the 30-item Mystical Experiences Questionnaire (MEQ30) following administration of psilocybin and clonidine while asleep or awake

  1 day

• Post-dosing scores on the Emotional Breakthrough Inventory (EBI) following administration of IV psilocybin either alone or in combination with clonidine while awake

  1 day

• Post-dosing scores on the Psychological Insight Scale (PIS) following administration of IV psilocybin either alone or in combination with clonidine while awake

  1 day

• Post-dosing scores on the Ego Dissolution Inventory (EDI) following administration of IV psilocybin either alone or in combination with clonidine while awake

  1 day

Study Arms (7)

Group 1A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants

EXPERIMENTAL

Participants will receive 10 mL of placebo (saline) over 2 minutes while asleep during their first overnight visit. Participants will receive 0.2 mg oral clonidine and either 2 mg of IV psilocybin or saline over 2 minutes while asleep during their second overnight visit.

Drug: Psilocybin; Drug: Clonidine; Other: Saline

Group 1B: 2-minute IV Psilocybin+Clonidine Infusion in Awake Participants

EXPERIMENTAL

If Group 1A participants can sleep 1 hour post-dosing and/or have no memory of dosing, Group 1B moves forward and participants will receive 0.2 mg clonidine and 2 mg of IV psilocybin over 2 minutes while awake.

Drug: Psilocybin; Drug: Clonidine

Group 2A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants

EXPERIMENTAL

If Group 1A participants fail to sleep 1 hour post-dose, Group 2A moves forward. Participants will receive 10 mL of placebo (saline) over 10 minutes while asleep during their first overnight visit. Participants will receive 0.2 mg oral clonidine and either 2 mg of IV psilocybin or saline over 10 minutes while asleep during their second overnight visit.

Drug: Psilocybin; Drug: Clonidine; Other: Saline

Group 2B: 10-minute IV Psilocybin+Clonidine in Awake Participants

EXPERIMENTAL

If Group 2A participants can sleep 1 hour post-dosing and/or have no memory of dosing, Group 2B moves forward and participants will receive 0.2 mg clonidine and 2 mg of IV psilocybin over 10 minutes while awake.

Drug: Psilocybin; Drug: Clonidine

Group 1C: 2-minute IV Psilocybin Alone in Awake Participants

ACTIVE COMPARATOR

If Group 1A allows for sleep 1 hour post dose, Group 1C will move forward and participants will receive 2mg of IV psilocybin over 2 minutes while awake for comparison.

Drug: Psilocybin

Group 2C: 10-minute IV Psilocybin Alone in Awake Participants

ACTIVE COMPARATOR

If Group 2A allows for sleep 1 hour post dose, Group 2C will move forward and participants will receive 2mg of IV psilocybin over 10 minutes while awake for comparison.

Drug: Psilocybin

Initial Groups 1A and 2A

EXPERIMENTAL

Participants will receive 2mg of IV psilocybin over 2 minutes or 10 minutes while asleep during an overnight visit and 10 mL of placebo (saline) over 2 minutes or 10 minutes while asleep during another overnight visit. The order of administration will be determined by the study protocol.

Drug: Psilocybin; Other: Saline

Interventions

Psilocybin DRUG

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).

Also known as: Psilocybine, Psilocibin

Group 1A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Group 1B: 2-minute IV Psilocybin+Clonidine Infusion in Awake Participants; Group 1C: 2-minute IV Psilocybin Alone in Awake Participants; Group 2A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Group 2B: 10-minute IV Psilocybin+Clonidine in Awake Participants; Group 2C: 10-minute IV Psilocybin Alone in Awake Participants; Initial Groups 1A and 2A

Clonidine DRUG

Clonidine will be administered orally in a 0.2mg dose

Group 1A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Group 1B: 2-minute IV Psilocybin+Clonidine Infusion in Awake Participants; Group 2A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Group 2B: 10-minute IV Psilocybin+Clonidine in Awake Participants

Saline OTHER

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

Also known as: Placebo

Group 1A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Group 2A: 2-minute IV Psilocybin+Clonidine / Saline in Asleep Participants; Initial Groups 1A and 2A

Eligibility Criteria

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

You may qualify if:

• Medically healthy
• English-speaking
• Live within 150 miles of Madison, WI for duration of study

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53715, United States

Location

MeSH Terms

Interventions

Psilocybin; Clonidine; Sodium Chloride

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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Charles Raison, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants may receive placebo (saline) or psilocybin during their treatment on overnight 2 but will not be told which they will receive.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo first followed by placebo+clonidine or psilocybin+clonidine in asleep healthy volunteers

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: October 24, 2022
• Study Start: November 7, 2023
• Primary Completion: February 19, 2025
• Study Completion: February 19, 2025
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)