Psilocybin-assisteret psykoterapi til behandling af svær alkoholforbrugsforstyrrelse

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.

Psilocybin is administered in oral capsule form during two dosing sessions held four weeks apart. Each session occurs in a controlled clinical environment with continuous monitoring by trained study therapists. Participants receive a standardized psychotherapy protocol that includes preparatory sessions before dosing and integration sessions afterward. The randomized dosing schedule includes either 10 mg with optional escalation to 15 mg or 30 mg with optional escalation to 40 mg for the second session. All participants also receive support from a peer recovery coach and are offered ongoing outpatient addiction treatment throughout the study period.

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.

Psilocybin is administered in oral capsule form during two dosing sessions held four weeks apart. Each session occurs in a controlled clinical environment with continuous monitoring by trained study therapists. Participants receive a standardized psychotherapy protocol that includes preparatory sessions before dosing and integration sessions afterward. The randomized dosing schedule includes either 10 mg with optional escalation to 15 mg or 30 mg with optional escalation to 40 mg for the second session. All participants also receive support from a peer recovery coach and are offered ongoing outpatient addiction treatment throughout the study period.

Percent Heavy Drinking Days (PHDD) is defined as the percentage of days in which participants engage in heavy drinking, calculated using the Timeline Follow-Back (TLFB) method. Heavy drinking is defined using NIAAA criteria (≥4 drinks/day for women; ≥5 drinks/day for men). PHDD will be analyzed as a continuous outcome to compare change over time between the full-dose and low-dose psilocybin groups.

We will utilize the Patient-Rated Inventory of Side Effects to assess the frequency and severity of adverse effects.

Craving intensity elicited by alcohol-related visual cues during a standardized cue-reactivity task as measured using a visual analog scale. The scale is titled Cue induced Craving scale and is measured from 0-10, 0 being Not at all and 10 being extremely craving. A higher score indicates more craving of the substance shown.

BOLD response in the nucleus accumbens (NAcc) to alcohol-related images during craving.

BOLD response in the dorsolateral prefrontal cortex (DLPFC) during down-regulation of craving.

NAcc-DLPFC functional connectivity during alcohol cue processing.

Percentage of days with no alcohol use, based on TLFB.

Number of standard drinks consumed on days with any drinking, assessed using the Timeline Follow-Back (TLFB) method.

Blood pressure

The Mystical Experience Questionnaire (MEQ-30) is a 30-item self-report measure assessing the intensity of mystical-type experiences during a psychedelic session. Scores are calculated for Transcendence, Positive Mood, Ineffability, Mystical experience, and as a total score, with each expressed as a percentage of the maximum possible score. Higher percentages indicate more intense and complete mystical experiences.

5-dimensional Altered States of Consciousness questionnaire

Mirror Tracing Persistence Task- Assesses distress tolerance.

Number of days from first psilocybin dose to first consumption of alcohol following inpatient withdrawal treatment.

Number of days from first psilocybin dose to first heavy drinking episode, defined using NIAAA criteria.

Change in WHO alcohol risk classification categories based on self-reported alcohol consumption.

Blood biomarker of recent alcohol use measured via PEth concentration.

Urine biomarker of recent alcohol consumption measured via EtG levels.

The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) is a clinician-administered scale used to assess the severity of alcohol withdrawal symptoms. It includes 10 items evaluating symptoms such as tremor, anxiety, agitation, nausea, and hallucinations, with total scores ranging from 0 to 67. Higher scores indicate more severe withdrawal and guide clinical management and treatment decisions.

Participant expectations regarding treatment benefit measured prior to any psilocybin dosing. The Stanford Expectancy Treatment Scale (SETS) is a self-report measure assessing participants' expectations, mindset ("set"), and perceptions of the treatment context ("setting") prior to an intervention. It evaluates beliefs about treatment credibility, anticipated benefits, and the therapeutic environment. Higher scores indicate more positive expectations and a more supportive perceived setting.

Participant and clinician guesses regarding dose assignment to evaluate masking integrity.

he Penn Alcohol Craving Scale (PACS) is a 5-item self-report measure assessing the frequency, intensity, and duration of alcohol craving over the past week. Total scores range from 0 to 30. Higher scores indicate greater alcohol craving severity.

The World Health Organization Quality of Life-BREF (WHOQOL-BREF) is a self-report measure assessing overall quality of life across physical health, psychological health, social relationships, and environment. Scores are calculated for each domain and transformed to standardized scales. Higher scores indicate better perceived quality of life.

Frequency and extent of interactions with the peer recovery coach across the study period.

Self-reported attendance at Alcoholics Anonymous or other mutual-help meetings.

The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-report measure assessing depressive symptom severity over the past two weeks. Total scores range from 0 to 27. Higher scores indicate greater severity of depressive symptoms.

The Generalized Anxiety Disorder-7 (GAD-7) is a 7-item self-report measure assessing anxiety symptom severity over the past two weeks. Total scores range from 0 to 21. Higher scores indicate greater anxiety severity

The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-administered measure assessing the severity and intensity of suicidal ideation and behavior. It evaluates the presence, frequency, and lethality of suicidal thoughts and actions over specified time frames. Higher severity ratings indicate greater suicide risk and inform clinical monitoring and intervention.

Laboratory evaluation of hepatic safety using standard liver enzyme markers.

Documentation of any all-cause hospital readmissions during the follow-up period.

Baseline; Weeks 4 and 24 after the second psilocybin session

Measured using the Monetary Choice Questionnaire, which presents choices between smaller immediate rewards and larger delayed rewards. The calculated discount rate (k-value) reflects impulsive choice and reward valuation.

Measured using the Iowa Gambling Task (IGT). Participants select cards from decks with varying reward and penalty structures. Performance reflects learning from feedback and risk-sensitive decision making.

Heart rate will be measured.

Temperature will be measured.