Clinical TrialAlcohol Use Disorder (AUD)PsilocybinPsilocybinNot yet recruiting

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

This Phase II, randomized, quadruple‑masked, parallel trial (n=36) will evaluate the safety and preliminary efficacy of psilocybin‑assisted psychotherapy in adults aged 18–65 with severe alcohol use disorder, with primary outcomes including percent heavy drinking days and adverse effects and secondary measures of cue‑induced craving and neural response by fMRI. Participants will be randomised 1:1 to a low‑dose or full‑dose psilocybin arm and will complete two supervised dosing sessions paired with a standardised psychotherapy protocol. Participants in the low‑dose arm receive oral psilocybin capsules of 10 mg at the first session with an optional escalation to 15 mg at the second session; the full‑dose arm receives 30 mg at the first session with an optional escalation to 40 mg at the second session. Dosing sessions occur in a controlled clinical setting four weeks apart with preparatory and integration sessions delivered by a dyad of trained therapists, continuous monitoring during dosing, and support from a peer recovery coach plus optional outpatient addiction treatment. Eligible participants are recruited up to 90 days after completing inpatient withdrawal management; outcomes are assessed through 48 weeks after the second dose, including percent heavy drinking days (weeks 0–24 after the first dose), adverse events at multiple post‑treatment timepoints, cue‑induced craving (baseline, 4 and 24 weeks after the second treatment), and fMRI measures one week before and one week after the second psilocybin session.

Target Enrollment
36 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This study aims to determine the safety and preliminary efficacy of psilocybin-assisted psychotherapy in improving alcohol-related outcomes among adults with severe alcohol use disorder in a a double-blind, dose-comparison concurrent control, randomized trial. Participants will undergo structured psychotherapy and will be randomized to two psilocybin sessions to receive either a full dose (30mg or 40mg) or low dose (10mg or 15mg).

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Low Dose Psilocybin

active comparator

Participants randomized to this arm receive psilocybin in capsule form at a dose of 10 mg during the first dosing session, with the option to increase to 15 mg at the second session. Doses are administered orally under direct supervision in a controlled clinical setting and paired with the same standardized psychotherapy protocol used in the high-dose arm. Participants complete two dosing sessions four weeks apart and receive ongoing support from a peer recovery coach and optional outpatient addiction treatment.

Interventions

  • Psilocybin

Full Dose Psilocybin

experimental

Participants randomized to this arm receive psilocybin in capsule form at a dose of 30 mg during the first dosing session, with the option to increase to 40 mg at the second session. Doses are administered orally under direct supervision in a controlled clinical setting and paired with a standardized psychotherapy protocol, including preparatory and integration sessions. All participants complete two dosing sessions spaced four weeks apart and receive ongoing support from a peer recovery coach and optional outpatient addiction treatment.

Interventions

  • Psilocybin30 - 40 mg
    via Oral

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • 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.

Exclusion Criteria

No exclusion criteria listed.

Study Details

Study Team

Sponsors & Collaborators

Locations

Brigham and Women's Hospital — Boston, Massachusetts, United States

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