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

Eligibility Criteria

• 1. Are between 21 and 70 years of age
• 2. Are fluent in speaking and reading English
• 3. Are able to swallow pills/capsules
• 4. 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.
• 5. Able and willing to provide informed consent
• 6. Able and willing to use computers and tablets or phones to enter electronic data
• 7. Agree to inform the investigators within 48 hours of any new or changed medical conditions.
• 8. Have an identified support person
• 9. 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.
• 10. Willing to provide contact details for a friend or family member, should there be an inability to make direct contact with the participant
• 1. 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
• 2. Have a current or previously diagnosed psychotic disorder or bipolar disorder
• 3. Have a previously diagnosed psychiatric disorder that renders the person unsuitable for the study (e.g., personality disorder)
• 4. Have one or more immediate family members with a current or previously diagnosed psychotic disorder (such as schizophrenia) or bipolar disorder
• 5. Have a medically significant condition that renders the person unsuitable for the study (e.g., cardiovascular or cerebrovascular conditions for which an acute increase in blood pressure would be clinically concerning, hepatic or renal disease, etc.)
• 6. Have a history of suicidal ideation or attempted suicide in the past year that, in the opinion of the study clinician or PI, may present a risk of suicidal or self-injurious behavior
• 7. Have a wellbeing score on the WHO-5 higher than 65 points
• 8. Have used a moderate-to-high dose of a psychedelic substance on more than 10 occasions in the past five years and/or have used a moderate-to-high dose of a psychedelic within the last 6 months.
• 9. Give a positive alcohol breathalyzer test result on any study visit
• 10. Have used cocaine, stimulants (other than nicotine and caffeine), amphetamines, cannabis, ecstasy, opiates, sedatives, pain pills, sleeping pills, or other psychoactive drugs within 7 days of an Experimental Session
• 11. A positive urine drug screen to any of the above prior to an Experimental Session, which warrants exclusion based on concerns that it may compromise safety or confound outcomes
• 12. 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 drugs of abuse
• 13. Are breastfeeding, or have a positive pregnancy test at screening or at any point during the course of the study
• 14. Have a recent history of suicidal ideation or attempted suicide (ahead of dosing session), as assessed through the screening interview and specifically with the C-SSRS and/or PHQ-9
• 15. Systolic and diastolic BP values exceeding 139 SBP and exceeding 89 DBP and heart rate exceeding 90 bpm would result in exclusion from the study.
• 16. Present with a exceeding 450 msec or with evidence of cardiac damage, ischemia, or heart disease.
• 17. Have received an investigational drug within 30 days of the screening visit
• 18. Have an allergy or intolerance to any of the materials contained in either drug product or setting components, such as certain scents.
• 19. Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire.
• 20. Are using any dietary supplements or drugs with potentially concerning drug-drug interaction (e.g., SSRIs, MAO-Is, TCAs, lithium, serotonin-acting dietary supplements such as St. John's wort)
• 21. Have any current problem which, in the opinion of the investigator or clinician, might interfere with participation.