Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Sponsor

Anders Fink-Jensen, MD, DMSci (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05416229

Collaborator

The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Psilocybin Drug: Lactose	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

single-centre, randomised, double-blinded, placebo-controlled, 1:1 parallel-group clinical trialsingle-centre, randomised, double-blinded, placebo-controlled, 1:1 parallel-group clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The QUANTUM Trip Trial - Psilocybin-assisted Therapy for Reducing Alcohol Intake in Patients With Alcohol Use Disorder: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin-assisted therapy 45 patients will receive a single administration of 25mg psilocybin given in a protocol of psychological support before, during and after dosing.	Drug: Psilocybin Psilocybin-assisted therapy
Placebo Comparator: Placebo-assisted therapy 45 patients will receive a single administration of placebo (lactose) given in a protocol of psychological support before, during and after dosing.	Drug: Lactose Placebo-assisted therapy

Arm

Intervention/Treatment

Experimental: Psilocybin-assisted therapy

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

Drug: Psilocybin

Psilocybin-assisted therapy

Placebo Comparator: Placebo-assisted therapy

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

Drug: Lactose

Placebo-assisted therapy

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Change in days of abstinence [Baseline to week 12]
Percentage of days without any alcohol consumption as measured by TLFB.
Change in total alcohol consumption [Baseline to week 12]
Total grams of alcohol consumed per day 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 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 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.
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.
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: 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.
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).
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.