Psilocybin Microdosing on Cognition, Mood and Quality of Life

This study is being conducted to evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences.

Inclusion Criteria: * No history of psychedelic use OR * No use within 10 years, less than or equal to 7x in life OR * No use within 5 years, less than or equal to 3x in life * Able to read, speak, and understand English * Able and willing to provide written informed consent, and willing to commit to study protocol * Women of childbearing potential must be on a highly effective birth control method * Must have smartphone compatible with mindLAMP app Exclusion Criteria: * Positive screen for recreational drugs or alcohol on test day will result in rescheduling the appointment * Current mood, developmental, or psychotic disorders (e.g., schizophrenia, affective disorders) per DSM-V * Current or past alcohol or substance use disorder per DSM-V * IQ \30 minutes or concussion in last 30 days * Any medical/neurological condition that could compromise neurocognitive performance (e.g., epilepsy, multiple sclerosis, fetal alcohol syndrome) * Anyone deemed unsafe to study personnel for any reason; e.g., suicidal ideation * Focal brain lesion seen on structural MRI * MRI contraindications (e.g., implanted metallic object, severe claustrophobia) * Clinically significant risk of suicidality, as determined by a score of 4 or higher on the suicidal ideation subscale of C-SSRS (past 6 months) or any suicidal behavior (lifetime) * Currently taking a monoamine oxidase inhibitor, tricyclic antidepressant, other non-SSRI or non-SNRI antidepressants, an antipsychotic or a mood stabilizer * Family history of schizophrenia or schizoaffective disorder (first degree relatives), or bipolar disorder type 1 (first degree relatives) * Diagnosis of arrhythmia or ongoing cardiovascular disorder * Sustained clinically relevant abnormal heart rate (resting supine heart rate \>100 bpm) or blood pressure (resting supine sustolic blood pressure (SBP) above 140mmHg or diastolic blood pressure (DBP) above 90mmHg) at screening * Clinically relevant abnormal laboratory results, 12-lead ECG, vital signs, cardiopulmonary compromise as detected by echocardiogram, or other physical findings * Presence of more than mild regurgitant lesions in any position and left ventricular ejection fraction \< 35 % * Evidence of pulmonary vascular disease demonstrated by right ventricular systolic pressure \>30mmHg * Currently taking any GLP-1 Study Discontinuation Criteria * Development of active suicidal or homicidal ideation with plan and intent * Worsening in mood symptoms, or development of psychotic symptoms that in the opinion of the investigators requires discontinuation * Development of severe or life-threatening medical condition * Psychiatric or medical hospitalization or incarceration post-screening * Adverse reaction to study drug that in the opinion of the investigators requires discontinuation (e.g. acute, clinically significant hypertension, cardiac toxicity, non-acute significant negative psychological changes)