Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Heavy drinking is defined as days with five drinks/60 grams of alcohol or more for men, four drinks/48 grams of alcohol or more for women. Data will be collected using the Timeline Followback Method (TLFB) which is a widely used, calendar-based retrospective measure of self-reported use of alcohol. The number of days drinking assessed is 28 days.

Total grams of alcohol consumed per day as measured by TLFB.

Percentage of days without any alcohol consumption as measured by TLFB.

PEth is formed only in the presence of alcohol and is correlated with the amount of alcohol consumed the past month. PEth concentrations will be measured by peripheral blood test.

AUDIT is a 10-item questionnaire that measures alcohol use. The score range is 0-40, with higher scores indicating a more problematic use of alcohol.

PACS is a 40-item questionnaire that measures alcohol craving severity. The score range is 0-30, with higher scores indicating more severe symptoms.

AASE is a 40-item questionnaire that measures two scales: the temptation to drink and the confidence in the ability to avoid drinking. The score range for each scale is 0-80, with higher score indicating greater temptation or confidence, respectively.

FTND is a 6-item questionnaire that measures the quantity of cigarette consumption, the compulsion to use, and dependence. The score range is 0-10, with higher scores indicating a more severe dependence.

DUDIT is an 11-item questionnaire that measures drug use. The score range is 0-44, with higher scores indication a more problematic use.

MDI is a 12-item questionnaire that measures depression severity. The score range is 0-50, with higher scores indicating greater severity.

SF-36 is a 36-item questionnaire that measures the quality-of-life. The score range is 0-100, with higher scores indicating better health status.

MAAS is a 15-item scale that measures core characteristic of mindfulness. The score range is 1-6, with higher scores indicating greater mindfulness.

AAQ is a 7-item questionnaire that measures psychological flexibility. The score range is 7-49, with higher scores indicating lesser flexibility.

The NEO-PI is a 240-item personality instrument that measures the five factors in the Five Factor Model. It consists of 30 eight-item facet scales, 6 for each of the five basic personality factors: Neuroticism (N), Extraversion (E), Openness (O), Agreeableness (A), and Conscientiousness (C), rated by use of a 5-point Likert-type scale ranging from strongly disagree to strongly agree.

PEQ is a 143-item scale aiming to assess changes in attitudes, moods, behavior, and spiritual experience

Neuroplasticity and inflammation as measured by mean concentrations of plasma serum brain-derived neurotrophic factor (BDNF) and plasma cytokines, respectively.

SDI will be regularly assessed asking the patients "how intense is the experience right now" on a 0-10 Likert scale where 0 = not intense at all, 10 = very intense.

Pharmacokinetics- and dynamics of plasma psilocin, serum BDNF and plasma cytokines, as determined by concentration-time curves of mean plasma concentrations

MEQ is a 30-item questionnaire that measures experiential aspects of psilocybin. The patients are asked to rate the items on a 6-point scale going from 0= none; not at all to 5=extreme; more than ever before in my life and stronger than 4.

5D-ASC is a 94-item questionnaire that measures experiential aspects of psilocybin. The patients are asked to rate the items by placing marks on a horizontal visual analogue scale (100 millimeters in length) going from "no, not more than usual" (on the left) to "yes, very much more than usual" (on the right).

EDI is a 8-item questionnaire that measures the experiential aspects of psilocybin. The patients are asked to rate the items by placing marks on a horizontal visual analogue scale (100 millimeters in length) going from "no, not more than usual" (on the left) to "yes, very much more than usual" (on the right).

EBI is a 6-item questionnaire that measures the experiential aspects of psilocybin. The patients are asked to rate the items by placing marks on a horizontal visual analogue scale (100 millimeters in length) going from "no, not more than usual" (on the left) to "yes, very much more than usual" (on the right).

AWE-S is a 30-item questionnaire that measures the experiential aspects of psilocybin. The patients are asked to rate the items on a 7-point scale going from 1= Strongly Disagree to 7= Strongly Agree.

The blood-oxygen-level-dependent differences between the two treatment arms with respect to resting-state functional connectivity, alcohol vs neutral cue-reactivity within mesocorticolimbic pathways and habitual vs goal-directed activity within corticostriatal pathways

We will explore the role of the music in psilocybin-assisted therapy by use of the questionnaires Experience with Music and Geneva Emotional Music Scale

We will explore the role of the music in psilocybin-assisted therapy by qualitative semi-structured interview

The Stanford Expectations of Treatment Scale is a 6 item a scale that measures positive and negative treatment expectancies using a Likert scale from 1 (strongly disagree) to 7 (strongly agree)

Patients may consent to post-trial follow-up to explore the long-term effects on drinking outcomes using TLFB adjusted for current or previous treatments since completing the trial.