Investigating the Interaction of Psilocybin and Context of Its Administration in Healthy Volunteers

NCT ID: NCT06626139

Last Updated: 2025-03-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-20
• Study Completion Date: 2028-11-30

Brief Summary

One hundred twenty healthy participants, ages 21 to 70, who experience moderate-to-lower-than-average mental well-being will be evenly randomized into four different study arms, using a 2x2 factorial design. Depending on the study arm, participants will either receive an inactive placebo or up to 25mg psilocybin (oral dose), in one of two set and setting conditions; drug administration contexts that are predicted to modulate drug effects.

The purpose of this study is to evaluate any interaction effects between an oral dose of psilocybin and the surrounding context (set and setting).

Detailed Description

Recent research posits that psychedelic medicine is best employed as a combination treatment, i.e., as drug x psychological support or psychotherapy referred to for simplicity as 'psychedelic therapy'. It is assumed that positive outcomes via psychedelic therapy critically depend on a synergistic relationship between drug-induced brain and mind plasticity and supportive contextual factors (Carhart-Harris et al., 2018; Carhart-Harris and Friston, 2019). These contextual factors have been referred to as 'set and setting' (Leary et al., 1963) or 'extrapharmacological'- highlighting elements beyond the drug that contribute to relevant outcomes (Hartogsohn, 2016).

The proposed experiment is a double-blind, randomized between-subjects 2 x 2 factorial study in 120 volunteers who experience low psychological well-being at baseline and have limited prior experience with psychedelics (1:1:1:1, n = 30 per condition). The main aim of the study is to assess the contribution of a select number of pre-defined contextual variables (both 'set' and 'setting') on the nature and trajectory of effects linked to a single dosing session with either psilocybin (oral, 25mg) or placebo (oral, inert).

The study will have four primary outcomes, two pertaining to mental health, namely: changes in psychological well-being - as measured via the Warwick-Edinburgh Mental Wellbeing Scales (WEMWBS), from baseline to 4 weeks post dosing session (primary endpoint) and changes in the Watts Connectedness Scale (WCS) at consistent timepoints. The two primary outcomes indexing the quality of the acute experience will be: Emotional Breakthrough - measured via mean scores on the Emotional Breakthrough Inventory (EBI), and Challenging experience (CE) - defined and measured here as scores on the following four sub-factors of the Challenging Experience Questionnaire (CEQ): fear, insanity, isolation, and paranoia.

Conditions

Healthy Participants With Lower-than-average Mental Well-being

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Psilocybin C1

Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Healthy participants will receive up to 25 mg psilocybin.

Context 1

Intervention Type: BEHAVIORAL

Drug administration will take place in a context (Context 1) that is expected to modulate acute and post-acute drug effects.

Psilocybin C2

Following screening and a baseline assessment visit, healthy volunteers will receive one dose of up to 25mg psilocybin in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Healthy participants will receive up to 25 mg psilocybin.

Context 2

Intervention Type: BEHAVIORAL

Drug administration will take place in a context (Context 2) that is expected to modulate acute and post-acute drug effects.

Placebo C1

Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 1) that is hypothesized to modulate acute and post-acute drug effects.

Group Type: PLACEBO_COMPARATOR

Context 1

Intervention Type: BEHAVIORAL

Drug administration will take place in a context (Context 1) that is expected to modulate acute and post-acute drug effects.

Placebo

Intervention Type: DRUG

Healthy participants will receive an inactive placebo.

Placebo C2

Following screening and a baseline assessment visit, healthy volunteers will receive one dose of an inactive placebo in a context (Context 2) that is hypothesized to modulate acute and post-acute drug effects.

Group Type: PLACEBO_COMPARATOR

Context 2

Intervention Type: BEHAVIORAL

Drug administration will take place in a context (Context 2) that is expected to modulate acute and post-acute drug effects.

Placebo

Intervention Type: DRUG

Healthy participants will receive an inactive placebo.

Interventions

Psilocybin

Healthy participants will receive up to 25 mg psilocybin.

Intervention Type: DRUG

Context 1

Drug administration will take place in a context (Context 1) that is expected to modulate acute and post-acute drug effects.

Intervention Type: BEHAVIORAL

Context 2

Drug administration will take place in a context (Context 2) that is expected to modulate acute and post-acute drug effects.

Intervention Type: BEHAVIORAL

Placebo

Healthy participants will receive an inactive placebo.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants will be considered for inclusion if they:

1. Are between 21 and 70 years of age

2. Are fluent in speaking and reading English

3. Are able to swallow pills/capsules

4. If able to become pregnant, must be non-lactating, have a negative pregnancy test at study entry and prior to each Experimental Session and must agree to an adequate form of birth control over the course of the study. Adequate forms of birth control include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Unable to become pregnant is defined as documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and/or tubal ligation), permanently sterile by medical device such as Essure, postmenopausal, or assigned male sex at birth.

5. Able and willing to provide informed consent

6. Able and willing to use computers and tablets or phones to enter electronic data

7. Agree to inform the investigators within 48 hours of any new or changed medical conditions.

8. Have an identified support person

9. For those dosed with psilocybin, their prior consent to be accompanied home (or to an otherwise safe destination) by a support person, chosen by them - ahead of time, or by a member of the study team.

10. Willing to provide contact details for a friend or family member, should there be an inability to make direct contact with the participant

Exclusion Criteria

Participants will be excluded if they:

1. Have a current diagnosed psychiatric disorder that, in the opinion of the study clinician or PI, renders to person psychologically unstable or unduly vulnerable, or interferes with activities of daily living, or could impact attendance at or participation in study activities

2. Have a medically significant condition that renders the person unsuitable for the study

3. Give a positive alcohol breathalyzer test result on any study visit

4. A positive urine drug screen to any excluded substances prior to an Experimental Session, which warrants exclusion based on concerns that it may compromise safety or confound outcomes

5. Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study

6. Systolic and diastolic BP values exceeding 139 SBP and exceeding 89 DBP and heart rate exceeding 90 bpm would result in exclusion from the study.

7. Present with a exceeding 450 msec or with evidence of cardiac damage, ischemia, or heart disease.

8. Have received an investigational drug within 30 days of the screening visit

9. Have an allergy or intolerance to any of the materials contained in either drug product or setting components, such as certain scents.

10. Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.)

11. Have any current problem which, in the opinion of the investigator or clinician, might interfere with participation.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Robin Carhart-Harris, PhD, MA

OTHER

Sponsor Role: lead

Responsible Party

Robin Carhart-Harris, PhD, MA

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robin Carhart-Harris, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Jennifer Mitchell, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Mission Bay

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Hannes Kettner, MSc

Role: CONTACT

setandsetting@ucsf.edu

4158495452

Avery Ostrand, MSc

Role: CONTACT

avery.ostrand@ucsf.edu

Facility Contacts

Kate Allison, BSc

Role: primary

kate.allison@ucsf.edu

Hannes Kettner, MSc

Role: backup

hannes.kettner@ucsf.edu

4158495452

Other Identifiers

23-38706

Identifier Type: -

Identifier Source: org_study_id