Phase I
Conditions
Keywords
psilocybin, psychedelic, cognition, learning, healthy volunteers
Brief summary
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.
Interventions
1 dose of psilocybin 25 mg oral capsule
DRUGInactive Placebo (Usona Institute)
1 dose of Microcrystalline Cellulose (MCC) 25 mg capsule
Sponsors
Brown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reinforcement Learning and Abstraction Task | During dosing session and 1 day after the dosing session | 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. |
| Belief Updating Task | 1 day before dosing, during dosing, and 1 day after the dosing session | Custom computer-based behavioral task in which participants must dynamically adjust predictions on each trial. This task measures trial to trial belief updating. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Altered States of Consciousness Questionnaire (ASC) | During dosing session | Measure of subjective experience. |
| Mystical Experience Questionnaire (MEQ) | During dosing session | Measure of mystical type experiences |
| Psychological Insight Questionnaire (PIQ) | During dosing session | Measure of psychological insight |
| Emotional Breakthrough Inventory (EBI) | During dosing session | Measure of emotional breakthrough |
| Challenging Experience Questionnaire (CEQ) | During dosing session | Measure of challenging subjective experiences |
| Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) | 1 day before dosing, 1 day after dosing, and 1 week after dosing | Measure of general wellbeing |
| Clinician Administered Dissociative States Scale (CADSS) | 1 day before dosing, during dosing, 1 day after dosing, 3 days after dosing, and 1 week after dosing | Measure of dissociative experiences |
| Barcelona Music Reward Questionnaire (BMRQ) | From baseline to 1 week after dosing | Measure of music reward experiences |
| Geneva Emotional Music Scale, 9-item version (GEMS-9) | During dosing session, 1 day after dosing | Measure of music experiences |
| Modified Stanford Expectations of Treatment Scale (SETS) | 1 day before dosing session | Measure of expectancy about psychological changes from psilocybin |
| Bang Blinding Index | 1 day after dosing | Measure of blinding integrity |
| Custom Rapport Questions | 1 day after dosing | Measure of rapport with study team |
| Subjective intensity and valence | During dosing session | Periodic measurements of subjective intensity and valence |
| Subjective insight | During dosing session | Participant-triggered measurements of subjective insight experiences |
| Semi-structured interviews | 1 day after dosing session | 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. |
| Columbia Suicide Severity Rating Scale (C-SSRS) | From baseline to 1 week after dosing | Measure of suicidal ideation during every study visit |
| Incidence of Adverse Events | From baseline to 1 week follow up | Monitoring for adverse events, including misuse monitoring |
| Feasibility and Acceptability | From baseline to 1 week after dosing | Percentage of full study completion; percentage of tasks and questionnaires completed per participant; semi-structured interview questions to assess tolerability of the study procedures |
Countries
United States
Outcome results
None listed