Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder

To be eligible, individuals must be:

* English speaking adults between ages 18 and 65
* Diagnosis of DSM5 AUD, severe
* Completion of inpatient withdrawal management (i.e. "detox") for AUD within 90 days of enrollment
* Amenable to attending all psychotherapy and study visits at BWH CCI
* Able to identify an individual who can act as points of contact during the trial
* Have a friend or family member who can bring the participant home after the psilocybin sessions and stay overnight

Individuals with any of the following will be excluded:

* Any personal history of a psychotic disorder (schizophrenia, schizoaffective disorder, brief psychotic disorder, delusional disorder, schizophreniform disorder, substance-induced psychotic disorder or major depression with psychotic features) or any bipolar-spectrum disorder
* Participants with a family history of first-degree relatives with psychotic disorder or bipolar-spectrum disorder
* Participants who have a significant suicide risk as defined by current suicidal ideation (Columbia-Suicide Severity Rating Scale (C-SSRS) score 2 to 5) and/or recent (within the past 6 months) active suicidal ideation (C-SSRS score 4 or 5)
* Participants who have a history of significant or serious adverse reaction to classic psychedelics
* Homicidality within the last six months
* History of DSM5 hallucinogen use disorder
* Positive blood alcohol level at screening
* Need for inpatient withdrawal management for alcohol at the time of screening
* Current DSM5 opioid, cocaine, stimulant or sedative/hypnotic use disorder
* Systolic blood pressure persistently above 165mmHg during screening
* History of hypersensitivity to psilocybin
* Use of psilocybin or other psychedelics with 5-HT2B activity in the prior 12 months
* Significant EKG abnormalities including QTc prolongation defined as \>450 ms for men and women, or a diagnosis or family history of Long QT syndrome.
* History of any cardiac valvulopathy that raises the risk for participation as determined by the cardiology consultant
* History of intracranial mass or bleed, seizure disorder other than alcohol withdrawal seizures, liver cirrhosis, renal failure, obstructive lung disease requiring supplemental oxygen, hyperthyroidism, narrow-angle glaucoma, uncontrolled cardiac arrythmias, heart failure
* History of head trauma, stroke, or myocardial infarction in one year prior to enrollment.
* Expected to require surgical treatment at any point during the trial
* Liver dysfunction with LFTs \> 3x upper normal limit at screening and Total bilirubin \> 2.5x the upper normal limit
* MRI contraindications (other ferromagnetic implants, body weight greater than 550 lbs., etc.)
* Pregnant or breastfeeding
* High risk for adverse emotional or behavioral reaction based on the opinion of the study investigators such as evidence of a personality disorder
* Currently taking medications with serotonergic activity (other than SSRIs/SNRIs); inhibitors of UGT1A9, UGT1A10, MAO, and aldehyde or alcohol dehydrogenase; antipsychotics (e.g., first and second generation); mood stabilizers (e.g., lithium, valproic acid); or significant inhibitors of UGT enzymes that metabolize psilocin
* Selective serotonergic reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors are allowed if participants have been on stable doses of the medication(s) for at least 30 days prior to enrollment.