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

NCT06626139 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-38706
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

well-being; psilocybin; psychedelic; neuroimaging; healthy volunteers

Outcome Measures

Primary Outcomes (4)

• Challenging Experience Questionnaire (CEQ) subscales score

  The Challenging Experience Questionnaire is designed to measure challenging psychological experiences associated with the acute effects of psilocybin. For this study, the combined score across four our of its seven subscales will be used as a primary outcome: Fear, Insanity, Isolation, and Paranoia, excluding Grief, Physical Distress, and Death subscales. Scaled scores range from 0 to 100. Higher scores indicate higher levels of challenging experience (worse outcome).

  Eight hours post-dose.

• Change in Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score from Baseline to 28 days post-dose

  The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) was developed to enable the monitoring of mental wellbeing in the general population and the evaluation of projects, programmes and policies which aim to improve mental wellbeing. Scores range form 14 to 70. Higher scores indicate higher levels of mental well-being (better outcome).

  Baseline to 28 days post-dose.

• Change in Watts Connectedness Scale (WCS) scores from Baseline to 28 days post-dose

  The WCS is a 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. Scores range from 0 to 100. Higher scores indicate higher levels of connectedness (better outcome).

  Baseline to 28 days post-dose.

• Emotional Breakthrough Inventory (EBI) score

  The Emotional Breakthrough Inventory was developed to assess emotional breakthrough, an important and distinct component of the acute psychedelic experience. Scores range from 0 to 100. Higher scores indicate higher levels of emotional breakthrough (better outcome).

  Eight hours post-dose.

Secondary Outcomes (9)

• Changes in resting state BOLD activity viafunctional magnetic resonance imaging (fMRI)

  Baseline to 28 days post-dose.

• Changes in BOLD activity during emotional processing via functional magnetic resonance imaging (fMRI)

  Baseline to 28 days post-dose.

• Changes in white matter organization via magnetic resonance imaging (MRI)

  Baseline to 28 days post-dose.

• Structural brain changes via magnetic resonance imaging (MRI)

  Baseline to 28 days post-dose.

• Acute Lempel Ziv Complexity (LZC) via Electroencephalography (EEG)

  Pre-dose; 2, 4, and 6 hours post-dose

Study Arms (4)

Psilocybin C1

EXPERIMENTAL

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.

Drug: Psilocybin; Behavioral: Context 1

Psilocybin C2

EXPERIMENTAL

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.

Drug: Psilocybin; Behavioral: Context 2

Placebo C1

PLACEBO COMPARATOR

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.

Behavioral: Context 1; Drug: Placebo

Placebo C2

PLACEBO COMPARATOR

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.

Behavioral: Context 2; Drug: Placebo

Interventions

Psilocybin DRUG

Healthy participants will receive up to 25 mg psilocybin.

Psilocybin C1; Psilocybin C2

Context 1 BEHAVIORAL

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

Placebo C1; Psilocybin C1

Context 2 BEHAVIORAL

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

Placebo C2; Psilocybin C2

Placebo DRUG

Healthy participants will receive an inactive placebo.

Placebo C1; Placebo C2

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between 21 and 70 years of age
• Are fluent in speaking and reading English
• Are able to swallow pills/capsules
• 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.
• Able and willing to provide informed consent
• Able and willing to use computers and tablets or phones to enter electronic data
• Agree to inform the investigators within 48 hours of any new or changed medical conditions.
• Have an identified support person
• 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.
• Willing to provide contact details for a friend or family member, should there be an inability to make direct contact with the participant

You may not qualify if:

• Participants will be excluded if they:
• 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
• Have a medically significant condition that renders the person unsuitable for the study
• Give a positive alcohol breathalyzer test result on any study visit
• Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study
• Present with a exceeding 450 msec or with evidence of cardiac damage, ischemia, or heart disease.
• Have received an investigational drug within 30 days of the screening visit
• Have an allergy or intolerance to any of the materials contained in either drug product or setting components, such as certain scents.
• Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.)
• Have any current problem which, in the opinion of the investigator or clinician, might interfere with participation.

Sponsors & Collaborators

• Robin Carhart-Harris, PhD, MA: lead

Study Sites (1)

UCSF Mission Bay

San Francisco, California, 94158, United States

RECRUITING

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Robin Carhart-Harris, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Jennifer Mitchell, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hannes Kettner, MSc

CONTACT

4158495452; setandsetting@ucsf.edu

Avery Ostrand, MSc

CONTACT

avery.ostrand@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Research staff will be masked in reference to the Drug condition but not the Context condition. Participants will be briefed only on the Context condition they are randomized to, and masked in reference to Drug condition.
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 2 x 2 Factorial Design Factor 1: Drug (Psilocybin vs Placebo) Factor 2: Context (Context 1 vs Context 2)

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 3, 2024
• Study Start: October 20, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)