Neural and Physiological Correlates of Psychedelic Sub-states (i2)

Multivariate Neural and Physiological Correlates of Psychedelic Sub-states: a Within-subjects, Healthy Volunteer Study With Experience-sampling

The main purpose of this study is to gain a better understanding of the distinct mental states and physical reactions that can arise during a psychedelic experience. By repeatedly assessing the same participants in an MRI while under the effects of psilocybin, the investigators want to identify reliable brain and body reactions arising during these psychedelic experiences. It is hoped that this will provide an insight to inspire future research on psilocybin and related psychedelics as well as inform on their therapeutic action. This study will involve up to 12 healthy volunteers with previous psychedelic experience. Participants in this study will be given four doses of psilocybin, with breaks of at least seven days in between dosing visits. The first dosing visit will feature a 10 mg dose of psilocybin, which can be considerate a low to moderate dose, whereas the remaining three dosing visits will feature 25 mg psilocybin, a high dose that is consistent with the dosage chosen for several modern clinical trials with psilocybin. From the initial in-person screening visit to the final follow-up, participants will be in this study for approximately 6-12 weeks and visit the research site 5 times. The first visit will be an in-person screening visit, during which the investigators will assess participants' eligibility to be enrolled. There will be 4 subsequent visits to the scan center for dosing and magnetic resonance imaging (MRI) scanning, and there will be a final remote follow up. Each of the four dosing visits will include four periods of lying within the MRI scanner for scanning, each of these 'in-scanner' sessions will last for ~ 45 minutes. Actual scans, which are also called 'runs' last for ~ 12 mins. During these 'runs', the investigators will ask participants two brief questions about how positive or negative their current experience is every 100 seconds. They will be able to record their answers using a button box which they will be operating with their hand. One day after each dosing visit, the investigators will schedule a phone call with the participant to check how they are doing and perform an informal interview focused on their experience while under the effects of psilocybin.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers; Psychedelic Experiences; Neuroimaging
• Intervention / Treatment: Drug: Psilocybin

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lorenzo Pasquini, PhD; Phone Number: (415) 476-1000; Email: lorenzo.pasquini@ucsf.edu
• Study Contact Backup: Name: Robin Carhart-Harris, PhD; Phone Number: (415) 476-1000; Email: insight2@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California, San Francisco
      • Contact: Robin Carhart-Harris, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Have at least one previous experience with a psychedelic substance
2. Have no more than 500 previous experiences with a psychedelic substance. It will be an advantage to recruit persons to this study with ample prior experience with psychedelics and no history of responding adversely; however, an excessive history of use might signify abuse of these compounds.
3. Have no history of a severe negative response to a psychedelic e.g., severe, and enduring anxiety, depression, or psychotic symptoms
4. Are between 21 and 70 years of age
5. Are fluent in speaking and reading English
6. Can swallow pills/capsules
7. 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 and contraception over the course of the study. Adequate forms of birth control or contraception 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). Not of childbearing potential is defined as documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, and/or tubal ligation), permanently sterile by medical device such as Essure, postmenopausal, or male by birth. Contraception applies to males as well as females and male participants must not be planning sperm donation within the study period.
8. Able and willing to provide informed consent
9. Able and willing to use computers and tablets or phones to enter electronic data
10. Agree to inform the investigators within 48 hours of any new or changed medical conditions.

Exclusion Criteria:

1. Have no previous experience a psychedelic substance
2. Have a current diagnosed psychiatric disorder that, in the opinion of the study clinician interferes with activities of daily living, could impact attendance at or participation in study activities, or requires a more therapeutically structured context for psilocybin than can be provided within the constraints of this study's design.
3. Have a current or previously diagnosed psychotic disorder
4. Have a current or previously diagnosed psychiatric disorder that renders them unsuitable for the study (e.g., borderline personality disorder)
5. Have one or more immediate family members (i.e., parent or sibling) with a current or previously diagnosed psychotic disorder, e.g., schizophrenia.
6. Have a medically significant condition that renders them unsuitable for the study (e.g., cardiovascular or cerebrovascular conditions for which an acute increase in blood pressure (BP) would be clinically concerning, hepatic or renal disease, etc.).
7. Systolic and diastolic BP values of >155 SBP and >95 DBP would result in exclusion from the study.
8. Present with a QTc > 450 msec or with evidence of cardiac damage, ischemia, or heart disease.
9. Have a recent history of suicidal ideation or attempted suicide that, in the opinion of the study clinician or PI, may present a risk of suicidal or self-injurious behavior
10. Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire
11. Have used alcohol within 24 hours or other psychoactive drugs within 7 days of an Experimental Session (with the exception of the psilocybin used within this study). NB the study researchers and PI may decide to continue with procedures if a positive drug-screen result is seen for cannabis use, or the participant openly declares recent cannabis-use; however, we might consider factoring in cannabis use in subsequent analyses and would strongly discourage any further use and consider exclusion if not reassured that the participant will comply with this request.
12. Current chronic cannabis use
13. Give a positive alcohol breathalyzer test result on any study visit
14. Are currently taking any of the medications or substances listed in Appendix 1 or, in the opinion of the study clinician or PI, engage in excessive use of alcohol or recreational drugs, particularly cannabis, which is legally available in California
15. Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study
16. Have an allergy or intolerance to any of the materials contained in the drug product
17. Have any current problem which, in the opinion of the investigator or clinician, might interfere with participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin; Healthy volunteers will receive up to four doses of psilocybin separated from each other by at least one week. The first dosing session will involve 10 mg psilocybin, the remaining three dosing sessions will receive up to 25mg psilocybin.	Drug: Psilocybin; Multiple dosing of healthy volunteers with up to 25 mg psilocybin separated from each other by at least one week. Participants will be scanned before and after receiving psilocybin on each dosing day. Surveys will be performed on dosing days and after dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The WHO - Five Well-Being Index (WHO-5)	Measure of psychological well-being	Baseline (visit 0) vs 4 weeks post visit 4

Collaborators and Investigators

• Sponsor: Robin Carhart-Harris, PhD, MA
• Investigators: Principal Investigator: Robin Carhart-Harris, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 21-35696; 157762 (Other Identifier: FDA IND)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No