Exploratory Study of Low Dose Psilocybin

Inclusion Criteria:

1. Ability to read and write in English
2. Between 25 and 65 years old
3. Demoralization Scale-II (DS-II) score of \> 8
4. No prior hallucinogen use or it would have been 3 years since the last use of a hallucinogen
5. Availability of a friend, family member, or other form of transportation (e.g., Uber) to drive participants home after their drug administration sessions
6. In good general health as assessed by detailed medical history interview and physical examination

Exclusion Criteria:

1. 24 years of age or younger; 66 years of age or older
2. Women who are pregnant (pregnancy status confirmed via urine pregnancy test) or breastfeeding
3. Current hypertension (exceeding 140 systolic and/or 90 diastolic at resting)
4. Use of methylphenidate or other medications for ADHD, benzodiazepines or other medications for anxiety (e.g., beta-blockers), tricyclic antidepressants, MAOIs, SSRIs, SNRIs or other medications for depression, lithium or other mood stabilizers, haloperidol or other antipsychotic medications, any medications or supplements with serotonin activity (e.g., St. John's Wort), or any other pharmacologic or biologic agent used to treat depression or anxiety (e.g., magnesium, cannabis)
5. Personal or family history (first or second degree relatives) of psychotic or bipolar I or II disorders
6. Any suicidal ideation of type 4 or type 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the 3 months prior to screening (i.e., active suicidal thought with method and intent but without a specific plan, or active suicidal thought with method, intent and plan).
7. History of head trauma, loss of consciousness, or neurological disease
8. Receiving treatment within the past 30 days for depression, anxiety, or substance use disorder
9. Participation within the past 30 days in a clinical trial for the treatment of depression, anxiety, or substance use disorder
10. Any current substance use disorder diagnosis (substance abstinence confirmed via urine drug screen)
11. History of immoderate alcohol consumption within the past 3 months per NIAAA definitions: more than 4 drinks per day or 14 drinks per week for men; more than 3 drinks per day or 7 drinks per week for women
12. Any headache disorder (i.e., migraine, tension-type headache, or cluster headache) in the past year
13. Planning to move from the Birmingham area in the next 3 months