The goal of this laboratory study is to establish whether and which microdoses of psilocybin are safe to administer at home to healthy participants. Eligible participants will be given ascending doses of psilocybin trihydrate and a single, interspersed, randomized placebo on separate days in double-blind fashion. The participants will be asked to complete questionnaires and undergo safety assessments.
This study aims to enroll 20 healthy participants who will complete all study procedures. Participants will undergo a standard screening procedure. Baseline measures will be completed before the first dose. Participants will then be given ascending doses of psilocybin trihydrate (1.2 mg, 2.0 mg, 3.0 mg, and 4.2 mg) and a single, interspersed, randomized placebo on separate days in double-blind fashion at the research site. A 1 mg dose of psilocybin anhydrate is equivalent to a 1.19 mg dose of psilocybin trihydrate (used in this study). For each session, participants will be assessed with criteria for the safety of home dosing. If any dose meets criteria for at-home dosing, and a lower dose did not fail these criteria, that dose will be identified as the safe dose for the given participant. After administration of all doses of psilocybin to all participants, if a safe at-home dose was identified for all participants, that will be considered the highest safe dose for at-home administration to be used for future studies. Visit summary: Initial screening: Medical and psychological screening (Approx. 4 hours though portions of this may be completed remotely). Dosing sessions: There will be 5 double-blind laboratory dosing sessions involving administration of ascending doses of psilocybin and a single, interspersed, randomized placebo dose. Baseline questionnaires will be completed on the day of the first dosing visit, and safety assessments will be administered during and at the end of each session.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
20
Microdoses of psilocybin trihydrate will be administered to participants (1.2 mg, 2.0 mg, 3.0 mg, and 4.2 mg).
Participants will receive a capsule identical in appearance to the active drug that contains an inactive substance.
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RECRUITINGSystolic and Diastolic Blood pressure (mmHg)
Blood pressure will be measured at 60, 120, 180, and 240 minutes. A dose will be deemed safe for home dosing if participants do not have elevations in blood pressure beyond threshold values; systolic blood pressure \> 150 mmHg, diastolic blood pressure \> 90mmHg) at any timepoint.
Time frame: Baseline, 1-4 hours post dose
Heart rate in beats per minute (bpm)
Heart rate will be measured at 60, 120, 180, and 240 minutes. A dose will be deemed safe for home dosing if participants do not have elevations in heart rate beyond threshold value of \> 110 bpm
Time frame: Baseline; 1-4 hours post dose
Field sobriety testing
The standardized battery of field sobriety tests includes: The Walk-and-Turn (W\&T), One-Leg Stand (OLS), Horizontal Gaze Nystagmus (HGN). A dose will be deemed safe for home dosing if participants pass field sobriety testing at time of expected peak psilocybin effects. The cumulative amount of clues observed across these tasks (out of a possible 22 clues) will be reported.
Time frame: Baseline; 90 minutes post dose
Number of participants with normal or abnormal psychological status as assessed by a psychiatric mental status exam
The Psychiatric Mental Status Exam will be a clinical interview identical to that performed by psychiatrists in daily clinical practice and will assess and document the participant's mood, affect, thought process (including the presence of formal thought disorder), paranoia, delusions, hallucinations, other perceptual alterations, speech (including rate, volume, prosody, whether or not speech is pressured), suicidal thoughts, and orientation to person, place and time. A dose will be deemed safe for home dosing if there is no evidence of abnormal psychological status on a psychiatric mental status exam performed by a blinded study psychiatrist. There is no formal scoring rubric for this outcome. A psychiatrist will use their clinical judgment to evaluate whether a participant has normal or abnormal psychological status based on a clinical interview.
Time frame: 120 minutes post dose
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Driving Performance as assessed by The Systems Technology, Inc. Simulation (STISIM) Drive® M4000-R Console
The STISIM Drive® M4000-R Console system will be used to assess driving performance, a state-of-the-art technology that has been independently validated to reflect real-world driving conditions. Specific driving outcomes include: lateral control (i.e., SDLP), longitudinal control (i.e., standard deviation of speed (SDSP), mean speed, number of speed exceedances), total accidents (sum of number of collisions, pedestrians hit, etc.), total rule violations (sum of number of missed stop signs, illegal turns, etc.), and distance to lead vehicles. Scores range from 0 to no upper limit. Higher scores represent higher magnitude of driving impairment.
Time frame: Baseline; 60 minutes post dose