Consciousness, Psilocybin, and Well-Being (CoPE Pilot)

University of Wisconsin (UW)

Status and phase: Completed; Phase 1

Conditions: Healthy; Psychedelic Experiences; Sleep

Treatments: Drug: Clonidine; Other: Saline; Drug: Psilocybin

Study type: Interventional

Funder types: Other

Identifiers

NCT05592379

Protocol Version 10/2/2024 (Other Identifier)

233897 (Other Identifier)

A532017 (Other Identifier)

2022-0746

Details and patient eligibility

About

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

Full description

The study commenced with 1 subject receiving 2 mg IV infusion of psilocybin over 2 minutes and 2 subjects receiving 2 mg IV infusion of psilocybin over 10 minutes. Subsequently, the pre-treatment of 0.2 mg of clonidine was added.

This design involves testing up to two psilocybin+clonidine administration protocols in asleep and awake subjects and one of two "IV psilocybin only" administration protocols in awake subjects.

The updated protocol entails 2 mg of psilocybin administered via IV infusion combined with 0.2 mg oral clonidine in sleeping subjects. If either the 2-minute or 10-minute psilocybin infusion (plus oral clonidine) protocols allow sleep maintenance, up to 5 subjects will, while awake, receive the same psilocybin infusion protocol administered to sleeping subjects, including clonidine. Subsequently, this same infusion protocol may be administered without clonidine, to evaluate any potential effect of co-administered clonidine on the acute psychedelic experience in awake subjects (Group 1C for 2-minute psilocybin infusion; Group 2C for 10-minute psilocybin infusion), should a significant effect of clonidine on the awake psychedelic experience be suspected. For individual subjects that are dosed first while asleep and then up to twice while awake, each of their visits will be separated by a minimum of two weeks and will include psychosocial support through integration sessions following each dosing visit.

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

Enrollment: 6 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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6 participants in 7 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin

Other: Saline

Drug: Clonidine

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

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin

Drug: Clonidine

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

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin

Other: Saline

Drug: Clonidine

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

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin

Drug: Clonidine

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

Active Comparator group

Description:

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.

Treatment:

Drug: Psilocybin

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

Active Comparator group

Description:

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.

Treatment:

Drug: Psilocybin

Initial Groups 1A and 2A

Experimental group

Description:

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.

Treatment:

Drug: Psilocybin

Other: Saline