Does Psilocybin Change Synaptic Density in Amnestic Mild Cognitive Impairment

Exclusion Criteria

• •An individual who meets any of the following criteria will be excluded from participation in this clinical trial:
• •1. Unwilling or incapable to consent to the study
• •2. Unstable medical or any concomitant major medical or neurological illness, including presence of a relative or absolute contraindication to psilocybin, i.e. a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
• •3. History of head trauma resulting in loss of consciousness \> 30 minutes that required medical attention.
• •4. DSM-5 diagnosis, with active symptoms in the last three months, of major depression; lifetime diagnosis of bipolar disorder; intellectual disability; Alzheimer's Disease; or a psychotic disorder
• •5. DSM-5 substance dependence (except caffeine) within 12 months of entering the study
• •6. Anticonvulsant, antidepressant, antipsychotic, mood stabilizer, opioid, or benzodiazepine use
• •7. Use of serotonergic psychedelic drugs within the past 10 years
• •8. Positive urine drug screen at the screening visit
• •9. Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks
• •10. Acute suicidal or homicidal ideation
• •11. Receiving treatment with medications such as levetiracetam that blocks SV2a binding, and/or inability to discontinue the following medications before study drug dosing: inhibitors of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A9 and (UGT)1A10, and ALDH inhibitors and alcohol dehydrogenase (ADH) inhibitors.
• •12. Exceeding allowed annual radiation exposure levels (20 mSv), as outlined by our PET Centre guidelines
• •13. Having completed multiple PET scans in the past, such that participation in this study would cause participant to exceed lifetime limit (8 PET scans)
• •14. Metal implants or pacemaker precluding an MRI scan or other contraindications to MRI (e.g., claustrophobia)
• •15. Female with childbearing potential\*, pregnancy (as confirmed by a negative pregnancy test) or breastfeeding
• •16. Active gender affirming hormonal treatment
• •17. Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant.
• •18. Allergies to hydroxypropyl methylcellulose \*A woman/female or person who is not of childbearing potential is considered to be postmenopausal after at least 12 months without menstruation. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Females/people of childbearing potential are those who have experienced menarche and do not meet the criteria for women not of childbearing potential.