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.

This study is being conducted to evaluate the effects of 30 days of intermittently microdosed psilocybin in a parallel arm double-blind manner on mood, cognition, subjective well-being and structural/functional MRI compared to placebo, using validated psychological assessments and cognitive tests. 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.

Demonstrating significant results in a population of healthy psychedelic non-users will establish a strong precedent for studying the effects of microdosing psychedelics in patient populations, such as those with treatment-resistant depression. Showing that microdosing minimizes risk of adverse outcomes with psychedelic treatment while maintaining beneficial effects would provide useful information relevant to clinical research in psychedelic-assisted psychotherapy. In addition to investigating claims that microdosing psychedelics may improve cognition and mood, this study also aims to test the hypothesis that these effects including those measurable at a brain level may persist beyond the course of the 30 days of the study. There are few to no studies that assessed the longevity of psychedelic effects on the majority of the above measures, so the proposed study may further establish the longer-term benefits of microdosing. The use of structural and functional magnetic resonance imaging (fMRI) will elucidate the mechanisms by which microdosing may be exerting its effects on mood and cognition. Because this is a relatively understudied area, information gleaned from this study will provide service in informing the field in general.

Inclusion Criteria:

• No history of psychedelic use
• 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

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 <70 on the Weschler Abbreviated Scale of Intelligence
• Serious medical, neuro-ophthalmological, or neurological illness (e.g., cancer, seizure disorders, encephalopathy)
• Current pregnancy, breastfeeding, or ineffective birth control methods
• History of head trauma with loss of consciousness lasting >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)