Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Brief Summary

Note: The trial is only eligible for citizens of Denmark. The purpose of this project is to assess the treatment efficacy of a single high dose of psilocybin administered within a protocol of psychological support to patients diagnosed with alcohol use disorder (AUD).

Intervention / Treatment

single-centre, randomised, double-blinded, placebo-controlled, 1:1 parallel-group clinical trial
  • Psilocybin (DRUG)
    Psilocybin-assisted therapy
  • Maltodextrin (DRUG)
    Placebo-assisted therapy

Condition or Disease

  • Alcohol Use Disorder

Phase

  • Phase 2
  • Study Design

    Study type: INTERVENTIONAL
    Status: Recruiting
    Study results: No Results Available
    Age: 20 Years to 70 Years
    Enrollment: 90 (ESTIMATED)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Sep 01, 2023 ESTIMATED
    Primary Completion: Nov 01, 2024 ESTIMATED
    Completion Date: Nov 01, 2025 ESTIMATED
    Study First Posted: Jun 13, 2022 ACTUAL
    Last Updated: Aug 22, 2023

    Sponsors / Collaborators

    Responsible Party: Anders Fink-Jensen, MD, DMSci

    To establish efficacy, we will investigate a single dose of psilocybin versus placebo in a randomised, double-blinded, placebo-controlled 12 weeks clinical trial. 90 patients, aged 20-70 years, diagnosed with alcohol use disorder and treatment seeking will be recruited from the community via advertisement and referrals from general practitioners and hospital units. The psilocybin or placebo is administered within a protocol of psychological support before, during and after the dosing. Outcome assessments will be carried out one, four, eight- and 12 weeks post dosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes include 1) phosphatidyl-ethanol as an objective biomarker for alcohol consumption 2) plasma psilocin, the active metabolite, to establish a possible therapeutic range and 3) the acute subjective drug experience as a possible predictor of treatment outcome. Furthermore, we will investigate the neurobiological underpinnings of the possible treatment effects by use of functional magnetic resonance brain imaging one week post dosing.

    Participant Groups

    • 45 patients will receive a single administration of 25mg psilocybin given in a protocol of psychological support before, during and after dosing.

    • 45 patients will receive a single administration of placebo (lactose) given in a protocol of psychological support before, during and after dosing.

    Eligibility Criteria

    Sex: All
    Minimum Age: 20
    Maximum Age: 70
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Bodyweight of 50-110 kg
    * AUD according to DSM-5 criteria and alcohol dependence according to ICD-10.
    * AUD Identification Test (AUDIT) ≥ 15.
    * ≥ 5 heavy drinking days in the past 28 days prior to inclusion.

    Exclusion Criteria:

    * Current or previously diagnosed with any psychotic disorder or bipolar affective disorder.
    * Immediate family member with a diagnosed psychotic disorder.
    * History of delirium tremens or alcohol withdrawal seizures.
    * History of suicide attempt or present suicidal ideation at screening.
    * Withdrawal symptoms at screening (\>nine on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) (43).
    * Present or former severe neurological disease including trauma with loss of consciousness \> 30 min.
    * Impaired hepatic function (alanine transaminase \>210/135 units/l men/women)
    * Cardiovascular disease defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris, myocardial infarction within the last 12 months or uncontrolled hypertension (systolic blood pressure \>165 mmHg, diastolic blood pressure \>95 mmHg).
    * Present or former abnormal QTc (\>450/470 ms men/women).
    * Treatment with disulfiram, naltrexone, acamprosate and nalmefene within 28 days of inclusion.
    * Treatment with any serotonergic medication or drugs within one month prior inclusion.
    * Any oOther active substance use disorders (except nicotine) defined as a Drug Use Disorder Identification Test score \>six/two (men/women) and investigator's clinical evaluation.
    * Women who are pregnant, breastfeeding, or intend to become pregnant or are not using adequate contraceptive measures considered highly effective (44).
    * Unable to speak or understand Danish.
    * Any other condition that the clinician estimates can interfere with trial participation.

    This clinical trial is recruiting

    Are you interested in participating in this trial or others? We'd love to help.

    Primary Outcomes
    • 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
    • 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

    Other Outcomes
    • 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.

    More Details

    NCT Number: NCT05416229
    Other IDs: PSILO4ALCO-TRIAL
    Study URL: https://clinicaltrials.gov/study/NCT05416229
    Last updated: Sep 29, 2023