The long-term objective of this project is to characterize how psilocybin affects visual perception and the brain's representation of the visual environment. It is known that psilocybin alters aspects of visual perception, but the underlying brain mechanisms contributing to these effects are poorly understood. The proposed work will address these questions in a large, diverse sample of healthy human subjects by using functional magnetic resonance imaging (fMRI) to measure the brain's responses to visual stimuli. The proposed research will document which brain areas mediate the effects of psilocybin. The technique of fMRI will be employed to measure brain activity in different brain areas while subjects are performing a visual perceptual task.
Are ≥21 years of age at time of Informed Consent Form signing
Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations.
Are able to swallow capsules.
Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study.
Breastfeeding, have a positive pregnancy test at screening or at any point during the course of the study, or unwilling to practice birth control during participation in the study.
Have a current psychiatric disorder, general medical condition, or other problem or abnormality that, in the opinion of the study clinician or PI, could compromise safety, render them unsuitable for the study, or would make them unable to comply with study activities.
Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire.
Uncontrolled hypertension (Systolic BP>139mmHG or Diastolic BP>89mmHG) or tachycardia (average HR>90bpm) averaged over at least two measurements.
Crossover
Psilocybin
DrugThe effects of different doses of psilocybin (0 - 14 mg) will be compared.
Amplitude and pattern of fMRI cortical responses
Functional magnetic resonance imaging (fMRI) responses to visual stimuli will be recorded.
Perceptual measurements
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0-14 mg) on participants' abilities to update prior expectations based on new information. Specifically, paired t-tests will be used to contrast perceptual measures collected at MRI scan sessions.
Voxelwise modeling
Voxelwise modeling results will be quantified by measuring the amount of variance in fMRI responses to presentation of stimuli that is accounted for by the model in each voxel. Cross-validation using held-out data will be used to assess possible overfitting and to facilitate unbiased interpretations. Model weights associated with each parameter will be contrasted between the effects of doses of psilocybin (0-14 mg) and quantified for individual brain areas using paired t-tests and appropriate corrections for multiple comparisons.
Participant-reported Subjective Effects
Within-subject inferential statistical testing will be used to assess the effects of doses of psilocybin (0 - 14 mg) on subjective effects. Specifically, paired t-tests and between-group effect sizes with 95% confidence intervals will be used to contrast patient-reported outcomes (MEQ-30, ChEQ, 11D-ASC and POMS-SF), corrected for multiple comparisons.
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