Inclusion Criteria:
1. Adults aged 21-65 who meet criteria for current DSM-5 diagnosis of AUD and PTSD as determined by the Alcohol System Checklist and CAPS-5.
2. Are either a US military Veteran or are currently employed as a first responder, including EMT, paramedic, firefighter, or law enforcement officer.
3. Report wanting to stop or decrease drinking and are willing to abstain from alcohol for the week prior to receiving any study drug.
4. Are English-speaking.
5. Must be willing to use contraception throughout the duration of the study. This applies to anyone, regardless of biological sex, who can cause pregnancy or become pregnant themselves.
6. Have a friend or family member who can pick them up and stay with them overnight after the DAS and who agrees to share contact information with the research team.
7. Have a primary care provider.
8. Have access to stable internet and either smart phone or computer.
9. Are willing to disclose medication use, supplement use, and interventions they are currently enrolled in; and commit to all study-related activities and follow-up sessions.
10. For the drug administration session, participants must be willing to reduce alcohol intake to be alcohol-free for 24 hours before DAS, fast after midnight before DAS, avoid caffeine and nicotine 2 hours before and 6-8 hours after DAS, and avoid driving for 24 hours post-DAS.
11. Must be locally accessible to the University of Washington for multiple in-person study visits.
12. Must have a friend or someone else the participant trusts to stay with them overnight for the evening following the DAS.
Exclusion Criteria:
1. A reported history of known medical conditions that would preclude safe participation in the trial, including the following:
* seizure disorder,
* coronary artery disease,
* history of arrhythmia or known valvopathy,
* heart failure,
* cerebrovascular accident,
* severe asthma
* pulmonary hypertension,
* hyperthyroidism,
* stenosing peptic ulcer,
* pyloroduodenal obstruction,
* symptomatic prostatic hypertrophy,
* bladder-neck obstruction.
2. Clinical findings on screening, including:
* significantly impaired liver function found in labs in prior 45-days or at screening
* uncontrolled hypertension (above 165/95 mmHg at screening)
* Serious ECG abnormalities measured at or within 45-days of screening (e.g., evidence of ischemia, myocardial infarction, QTc prolongation (QTc \> 0.45 seconds for men, QTc \> 0.47 seconds for women).
3. Reported history or findings on SCID-CT of known exclusionary psychiatric conditions, including schizophrenia, schizoaffective disorder, bipolar disorder type I or type II.
4. A reported history of a serious suicide attempt (SSA) in previous 12-months.
5. A reported history of a personality disorder at time of screening.
6. A reported family history of schizophrenia or schizoaffective disorder (first- or second-degree relatives), or bipolar disorder type 1 (first degree relatives).
7. Currently using SSRIs, SNRIs, MAOIs, TCAs, antipsychotics, lithium, stimulants, or other psychedelics.
8. Currently engaged in CBT, DBT, EMDR, psychoanalytic/psychodynamic therapy, MBSR, or unapproved group therapies, except for peer support groups.
9. Cognitive impairment (Folstein Mini Mental State Exam score \< 26).
10. A reported lifetime history of hallucinogen use disorder (per DSM-5).
11. A reported history of cocaine, psychostimulant, or opioid use disorder defined by DSM-5 in the past 12 months, or currently utilizing full-agonist (methadone) or partial-agonist (buprenorphine) for OUD.
12. Current or historical abuse of psychedelic/hallucinogenic substances (e.g. LSD, mushrooms/psilocybin, mescaline/peyote, MDMA, ketamine, ayahuasca, ibogaine, DMT, etc.) endorsed by participant or suspected by the Lead Investigator's clinical judgement.
13. Reported current non-medical use of cocaine, psychostimulants, psilocybin, or opioids (past 30 days).
14. A reported history of significant alcohol withdrawal (CIWA-Ar score greater than 7) or a history of severe alcohol withdrawal, including delirium tremens, withdrawal seizures or any acute hospitalization related to alcohol withdrawal. Participants presenting at screening in withdrawal may be referred for detoxification and reassessed within 30 days.
15. Serious abnormalities of complete blood count (CBC) or chemistries found at or within 45-days of screening.
16. Currently enrolled in another clinical trial of any kind.
17. Active legal problems with the potential to result in incarceration.
18. Pregnancy or lactation; or intention to become pregnant or cause pregnancy
19. Need to take medication with significant potential to interact with study medications (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants) as determined by Study Physician or Lead Investigator.
20. Allergy or hypersensitivity to psilocybin.
21. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support), or deemed not suitable for other reasons stipulated by the research team.
22. A previous diagnosis of Hallucination Perceptual Persisting Disorder (HPPD).
23. Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 3 months or 5 half-lives before enrollment or is currently enrolled in the treatment stage of an investigational study.
