Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Primary Outcomes

• Change in percentage of heavy drinking days Baseline to week 12

  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.

Secondary Outcomes

• Change in total alcohol consumption Baseline to week 12

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

• Change in days of abstinence Baseline to week 12

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

• Change in phosphatidyl-ethanol (PEth) Baseline to week 12

  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.

• Change in Alcohol Use Disorders Identification Test (AUDIT) Baseline to week 12

  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.

• Change in Penn Alcohol Craving Scale (PACS) score Baseline to week 12

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

• Change in Alcohol Abstinence Self-efficacy Scale (AASE) score Baseline to week 12

  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.

• Change in Fagerstrom Test for Nicotine Dependence (FTND) Baseline to week 12

  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.

• Change in Drug Use Disorders Identification Test (DUDIT) Baseline to week 12

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

• Change in Major Depression Inventory (MDI) Baseline to week 12

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

• Change in Short-Form 36 (SF-36) Baseline to week 12

  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.

• Change in Mindful Attention Awareness Scale (MAAS) Baseline to week 12

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

• Change in Acceptance and Action Questionnaire (AAQ) Baseline to week 12

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

• Change in NEO-Personality Inventory (NEO-PI= Baseline to week 12

  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.

• Persisting Effects Questionnaire (PEQ) Week 12

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

• Neuroplasticity and inflammation Baseline to week 12

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

• Subjective effects of psilocybin: Subjective Drug Intensity (SDI) 0-6 hours post dosing

  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 psilocybin 0 - 6 hours post dosing

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

• Subjective effects of psilocybin: Mystical Experience Questionnaire (MEQ) Completed once the effects are fully subsided or at least 6 hours after dosing

  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.

• Subjective effects of psilocybin: 5-Dimensional Altered State of Consciousness scale (5D-ASC) Completed once the effects are fully subsided or at least 6 hours after dosing

  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).

• Subjective effects of psilocybin: Ego Dissolution Inventory (EDI) Completed once the effects are fully subsided or at least 6 hours after dosing

  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).

• Subjective effects of psilocybin: Emotional Breakthrough Inventory (EBI) Completed once the effects are fully subsided or at least 6 hours after dosing

  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).

• Subjective effects of psilocybin: Awe Experience Scale (AWE-S) Completed once the effects are fully subsided or at least 6 hours after dosing

  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.

• Brain imaging 1 week post dosing

  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

Other Outcomes

• Role of the Music I before and after dosing

  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

• Role of the Music II week 4

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

• Treatment expectancies Baseline

  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)

• Optional long-term follow-ups week 26 and week 52

  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.