Pilot Study on the Effects of Psilocybin on Belief Updating and Insight Formation

The primary aim of this phase I mechanistic pilot study is to evaluate the effects of psilocybin on aspects of cognition in healthy adult volunteers. Up to 24 participants will receive a single dose of either psilocybin or inert placebo, and they will be asked to complete several computer-based behavioral tasks measuring features of learning, belief updating, and abstraction. Participants will also complete measures of subjective experience and expectancy, as well as semi-structured interviews at follow up, to assess whether experience correlates with behavior. This is a Voluntary Submission.

Study Overview

• Status: Not yet recruiting
• Conditions: Phase I
• Intervention / Treatment: Drug: Psilocybin (Usona Institute); Drug: Inactive Placebo (Usona Institute)

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Brown University School of Public Health
      • Contact: Eric A. Miller, M.D.; Email: eric_miller@brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. be at least 18 years old at time of signing informed consent
2. be fluent in speaking and reading English
3. be able to swallow pills (capsules)
4. agree to use highly effective birth control for at least one month prior to enrollment, and for the duration of study enrollment, whether male or female assigned at birth. Acceptable methods include: copper or hormonal coil intrauterine device (IUD), implanted or injected hormonal method, documented permanent sterilization, documented not able to become pregnant, or oral/intravaginal/transdermal hormones plus a barrier contraception. Two forms of contraception are required with any barrier method or with any oral, intravaginal, or transdermal hormonal method due to these methods not being considered highly effective alone. Abstinence alone is not an acceptable contraceptive method for this study.
5. be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a clinical interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine laboratory tests
6. agree to inform investigators within 48 hours of any new medical conditions, treatments, or procedures
7. agree to refrain from using any psychoactive or recreational drugs, including cannabis, for the duration of study enrollment (with the exception of limited alcohol, nicotine, and caffeine as below)
8. agree to refrain from drinking alcohol within 24 hours of all experimental sessions
9. agree to consume approximately the same amount of caffeine and nicotine as on a usual day before experimental sessions, but to not consume any nicotine or caffeine closer than 1 hour prior to the scheduled dosing time. If the participant does not routinely consume caffeine or nicotine, they must agree not to do so for the duration of the study.
10. agree to refrain from taking any "as needed" or "over the counter" medications (e.g., medications for pain, insomnia, or allergies) within 24 hours of all experimental sessions, unless previously approved by a study physician
11. agree to store their phone and car keys in a locked storage locker for the duration of the experimental dosing session, and agree to stay on site for at least 6 hours after drug administration and until a physician agrees they are safe to leave the premises
12. be able to identify two trusted support people (e.g. friend or family member, at least age 18 years of age), who are willing and able to serve as an emergency contact, and to pick the participant up and transport them home after the dosing session. One of these will be designated the primary support person, and the second will be backup to pick the person up in the event that the primary becomes unavailable.
13. agree to not drive a motor vehicle or heavy machinery for 24 hours after the dosing session
14. have used a classical psychedelic (5-HT2A agonist, such as psilocybin, LSD, DMT, 5-MeO-DMT, ayahuasca, mescaline) at least once in lifetime without clinically significant adverse effects

Exclusion Criteria:

1. have used any psychedelic, hallucinogen, or entactogen, including 3,4-methylenedioxymethamphetamine (MDMA) and ketamine/esketamine, but not including cannabis, within the past 3 months
2. unwilling or unable to stop using cannabis a minimum of one week prior to enrollment and to refrain from cannabis use for the duration of the study enrollment, to be tested with urine drug screens
3. currently pregnant (as indicated by a positive urine pregnancy test assessed at intake and before the drug session), nursing, intending to become pregnant within 3 months of enrollment, intending to father a child within 3 months of enrollment, intending to donate sperm or eggs within 3 months of enrollment, or not practicing a highly effective means of birth control as noted in the Inclusion Criteria.
4. history of traumatic brain injury, or history of seizure disorder in adulthood
5. history of any clinically significant cardiovascular condition, or condition that could make receiving the study drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, uncontrolled hypertension, coronary artery disease, heart failure, stroke, myocardial infarction, artificial heart valve, aneurism, or clinically significant arrhythmia. Uncontrolled hypertension is defined here as repeated blood pressure readings of >= 140 mmHg systolic or >= 90 mmHg diastolic.
6. baseline QTc > 450 milliseconds (QTc is defined as the QT interval corrected for heart rate, either machine-read or manually over-read)
7. current poorly controlled or insulin dependent diabetes mellitus (type I or type II)
8. current clinically significant respiratory condition (supplemental oxygen requirement, or requiring hospitalization within the last year)
9. current clinically significant liver or biliary disease, including recent laboratory abnormalities (AST or ALT > 3x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN or direct bilirubin < 35%), or based on the presence of ascites, encephalopathy, jaundice, esophageal varices, or coagulopathy
10. clinically significant renal disease, including but not limited to CKD stage 3 or greater
11. history of ever meeting Diagnostic and Statistical Manual, version 5 (DSM-5) criteria for any schizophrenia spectrum disorder, bipolar spectrum disorder, major depressive disorder with psychotic features, or any other psychotic disorder, including substance-induced psychotic disorders ever in lifetime
12. have a first or second-degree relative with history of schizophrenia spectrum disorder, bipolar spectrum disorder, major depressive disorder with psychotic features, or other psychotic disorder including substance-induced psychotic disorders ever in lifetime
13. clinically significant suicide risk, as determined by clinician judgment and the C-SSRS. Participants will be excluded if any current active suicidal ideation, including intent to kill oneself or preparatory behavior, or a lifetime history of suicide attempts including aborted or interrupted.
14. history within last 5 years of inpatient psychiatric hospitalization for any reason
15. lifetime history of hallucinogen persisting perception disorder
16. current or history within the last 1 year of meeting DSM-5 criteria for an alcohol or substance use disorder, excluding caffeine and nicotine; or a lifetime history of hallucinogen use disorder
17. a positive urine drug screen or alcohol breathalyzer test result on any study visit, or unwillingness to provide these tests
18. history of antisocial personality disorder, borderline personality disorder, or narcissistic personality disorder
19. taking a primary psychoactive medication on a regular basis within 3 months of study participation, including but not limited to antidepressants (SSRIs, SNRIs, NDRIs, MAOIs, TCAs), antipsychotics, mood stabilizers, anxiolytics, stimulants, or sedative-hypnotics
20. current clinically significant episode of any other psychiatric disorder, including but not limited to a current episode of major depressive disorder, anxiety disorder, trauma- or stressor-related disorder, obsessive-compulsive disorder, neurodevelopmental disorder, and personality disorder that is not in full remission
21. any other current problem which, in the opinion of study clinicians, might pose an unacceptable risk to participant or staff safety and/or significantly interfere with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin; Psilocybin 25 mg oral capsule	Drug: Psilocybin (Usona Institute); 1 dose of psilocybin 25 mg oral capsule
Placebo Comparator: Inert Placebo; Microcrystalline cellulose 25 mg oral capsule	Drug: Inactive Placebo (Usona Institute); 1 dose of Microcrystalline Cellulose (MCC) 25 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcement Learning and Abstraction Task	Custom computer-based behavioral task requiring participants to complete a series of puzzles to complete game levels. This task requires working memory and reinforcement learning, and it also includes a measure of state abstraction.	During dosing session and 1 day after the dosing session
Belief Updating Task	Custom computer-based behavioral task in which participants must dynamically adjust predictions on each trial. This task measures trial to trial belief updating.	1 day before dosing, during dosing, and 1 day after the dosing session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Altered States of Consciousness Questionnaire (ASC)	Measure of subjective experience.	During dosing session
Mystical Experience Questionnaire (MEQ)	Measure of mystical type experiences	During dosing session
Psychological Insight Questionnaire (PIQ)	Measure of psychological insight	During dosing session
Emotional Breakthrough Inventory (EBI)	Measure of emotional breakthrough	During dosing session
Challenging Experience Questionnaire (CEQ)	Measure of challenging subjective experiences	During dosing session
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)	Measure of general wellbeing	1 day before dosing, 1 day after dosing, and 1 week after dosing
Clinician Administered Dissociative States Scale (CADSS)	Measure of dissociative experiences	1 day before dosing, during dosing, 1 day after dosing, 3 days after dosing, and 1 week after dosing
Barcelona Music Reward Questionnaire (BMRQ)	Measure of music reward experiences	From baseline to 1 week after dosing
Geneva Emotional Music Scale, 9-item version (GEMS-9)	Measure of music experiences	During dosing session, 1 day after dosing
Modified Stanford Expectations of Treatment Scale (SETS)	Measure of expectancy about psychological changes from psilocybin	1 day before dosing session
Bang Blinding Index	Measure of blinding integrity	1 day after dosing
Custom Rapport Questions	Measure of rapport with study team	1 day after dosing
Subjective intensity and valence	Periodic measurements of subjective intensity and valence	During dosing session
Subjective insight	Participant-triggered measurements of subjective insight experiences	During dosing session
Semi-structured interviews	Brief semi-structured interviews exploring several pre-specified themes, including tolerability, changes in cognition, subjective insight experiences, experience of music, and other subjective experiences from the dosing session.	1 day after dosing session
Columbia Suicide Severity Rating Scale (C-SSRS)	Measure of suicidal ideation during every study visit	From baseline to 1 week after dosing
Incidence of Adverse Events	Monitoring for adverse events, including misuse monitoring	From baseline to 1 week follow up
Feasibility and Acceptability	Percentage of full study completion; percentage of tasks and questionnaires completed per participant; semi-structured interview questions to assess tolerability of the study procedures	From baseline to 1 week after dosing

Collaborators and Investigators

• Sponsor: Brown University

Publications and helpful links

General Publications

• Lehnert L, Littman ML, Frank MJ. Reward-predictive representations generalize across tasks in reinforcement learning. PLoS Comput Biol. 2020 Oct 15;16(10):e1008317. doi: 10.1371/journal.pcbi.1008317. eCollection 2020 Oct.
• Nassar MR, Wilson RC, Heasly B, Gold JI. An approximately Bayesian delta-rule model explains the dynamics of belief updating in a changing environment. J Neurosci. 2010 Sep 15;30(37):12366-78. doi: 10.1523/JNEUROSCI.0822-10.2010.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: September 8, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 14, 2026

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: cognition; learning; healthy volunteers; psilocybin; psychedelic
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: STUDY00001310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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