Precision Functional Brain Mapping in Psilocybin

NCT04501653 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 202002165GF0010787
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults.

Conditions

Psilocybin

Outcome Measures

Primary Outcomes (1)

• Functional Connectivity

  Our overall goal is to use a Functional Connectivity (very long scans to produce individual connectomes) to examine the effects of psilocybin on cortical and cortico- subcortical brain networks that could explain its rapid and sustained behavioral effects.

  1 week

Secondary Outcomes (2)

• Mystical Experiences

  1 week

• Personality Change

  1 week

Study Arms (2)

Psilocybin first

EXPERIMENTAL

Participants will receive 25 mg of psilocybin at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the control drug (methylphenidate) at their second drug exposure neuroimaging session.

Drug: Psilocybin; Drug: Methylphenidate

Methylphenidate first

ACTIVE COMPARATOR

Participants in this group will be randomized to receive 40 mg of methylphenidate at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the active comparator (psilocybin) at their second drug exposure neuroimaging session.

Drug: Psilocybin; Drug: Methylphenidate

Interventions

Psilocybin DRUG

Psilocybin is a naturally occurring psychedelic compound produced by psilocybin mushrooms, and has been shown to have antidepressant and anti-anxiety effects after one dose of 25 mg. Common side effects are slight elevations in blood pressure and heart rate. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Also known as: psilocin

Methylphenidate first; Psilocybin first

Methylphenidate DRUG

Methylphenidate is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is used as an active control for this study because it is metabolized similarly to psilocybin and has similar effects on heart rate and blood pressure. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Also known as: Metadate, Methylin, Ritalin, Concerta

Methylphenidate first; Psilocybin first

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• men and woman between 18 and 40 years of age;
• Have used a psychedelic substance within the previous 5 years but not within the last 6 months
• No active psychiatric conditions requiring treatment with psychotropic medications (may be included if psychiatric condition is stable and participant is willing to discontinue medication for 1 month prior to participation with permission from their treating provider);
• Able to provide informed consent.

You may not qualify if:

• Presence of medical conditions that may confound results of imaging study or that are contraindications to psilocybin exposure (e.g. neurological, renal, hypertension, metabolic or cardiovascular disease or pregnancy);
• No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);
• Presence of psychiatric conditions that may confound interpretation of results or that are contraindications to psilocybin exposure (e.g. major mood disorder, current substance use disorder, personal or immediate family history (parents, siblings) of any schizophrenia spectrum disorders);
• Use of psychotropic medication during the study;
• Presence of contraindications to MRI scanning (implantable devices, bone hardware, IUD).
• Prior adverse reactions to psychedelics, based on the Challenging Experiences Questionnaire administered during initial screening

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Interventions

Psilocybin; psilocin; Methylphenidate

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be aware that they are receiving either psilocybin or methylphenidate at each medication imaging session, but will not be told in what order they will receive study medication (psilocybin first versus methylphenidate first).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: Participants will undergo a baseline imaging session, followed by a blinded drug session with psilocybin 25mg, or methylphenidate (MTP) 40mg. Participants will then have a "between" imaging session without medication, followed by another medication imaging session with the agent not used in the first medication session. This will be followed by a final imaging session without medication.

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 6, 2020
• Study Start: June 1, 2021
• Primary Completion: March 19, 2023
• Study Completion: March 19, 2023
• Last Updated: October 31, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)