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Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Primary Purpose

Alcohol Use Disorder

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Psilocybin
Maltodextrin
Sponsored by
Anders Fink-Jensen, MD, DMSci
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Use Disorder focused on measuring psilocybin, alcohol dependence, addiction, randomized controlled trial, brain imaging

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Psychiatric Center Copenhagen, Frederiksberg HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Psilocybin-assisted therapy

Placebo-assisted therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in percentage of heavy drinking days
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 total alcohol consumption
Total grams of alcohol consumed per day as measured by TLFB.
Change in days of abstinence
Percentage of days without any alcohol consumption as measured by TLFB.
Change in phosphatidyl-ethanol (PEth)
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)
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
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
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)
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)
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)
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)
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)
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)
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=
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)
PEQ is a 143-item scale aiming to assess changes in attitudes, moods, behavior, and spiritual experience
Neuroplasticity and inflammation
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)
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
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)
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)
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)
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)
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)
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
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

Full Information

First Posted
May 30, 2022
Last Updated
August 22, 2023
Sponsor
Anders Fink-Jensen, MD, DMSci
Collaborators
The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet
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1. Study Identification

Unique Protocol Identification Number
NCT05416229
Brief Title
Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2023 (Anticipated)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anders Fink-Jensen, MD, DMSci
Collaborators
The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder
Keywords
psilocybin, alcohol dependence, addiction, randomized controlled trial, brain imaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
single-centre, randomised, double-blinded, placebo-controlled, 1:1 parallel-group clinical trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Psilocybin-assisted therapy
Arm Type
Experimental
Arm Description
45 patients will receive a single administration of 25mg psilocybin given in a protocol of psychological support before, during and after dosing.
Arm Title
Placebo-assisted therapy
Arm Type
Placebo Comparator
Arm Description
45 patients will receive a single administration of placebo (lactose) given in a protocol of psychological support before, during and after dosing.
Intervention Type
Drug
Intervention Name(s)
Psilocybin
Intervention Description
Psilocybin-assisted therapy
Intervention Type
Drug
Intervention Name(s)
Maltodextrin
Intervention Description
Placebo-assisted therapy
Primary Outcome Measure Information:
Title
Change in percentage of heavy drinking days
Description
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.
Time Frame
Baseline to week 12
Secondary Outcome Measure Information:
Title
Change in total alcohol consumption
Description
Total grams of alcohol consumed per day as measured by TLFB.
Time Frame
Baseline to week 12
Title
Change in days of abstinence
Description
Percentage of days without any alcohol consumption as measured by TLFB.
Time Frame
Baseline to week 12
Title
Change in phosphatidyl-ethanol (PEth)
Description
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.
Time Frame
Baseline to week 12
Title
Change in Alcohol Use Disorders Identification Test (AUDIT)
Description
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.
Time Frame
Baseline to week 12
Title
Change in Penn Alcohol Craving Scale (PACS) score
Description
PACS is a 40-item questionnaire that measures alcohol craving severity. The score range is 0-30, with higher scores indicating more severe symptoms.
Time Frame
Baseline to week 12
Title
Change in Alcohol Abstinence Self-efficacy Scale (AASE) score
Description
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.
Time Frame
Baseline to week 12
Title
Change in Fagerstrom Test for Nicotine Dependence (FTND)
Description
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.
Time Frame
Baseline to week 12
Title
Change in Drug Use Disorders Identification Test (DUDIT)
Description
DUDIT is an 11-item questionnaire that measures drug use. The score range is 0-44, with higher scores indication a more problematic use.
Time Frame
Baseline to week 12
Title
Change in Major Depression Inventory (MDI)
Description
MDI is a 12-item questionnaire that measures depression severity. The score range is 0-50, with higher scores indicating greater severity.
Time Frame
Baseline to week 12
Title
Change in Short-Form 36 (SF-36)
Description
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.
Time Frame
Baseline to week 12
Title
Change in Mindful Attention Awareness Scale (MAAS)
Description
MAAS is a 15-item scale that measures core characteristic of mindfulness. The score range is 1-6, with higher scores indicating greater mindfulness.
Time Frame
Baseline to week 12
Title
Change in Acceptance and Action Questionnaire (AAQ)
Description
AAQ is a 7-item questionnaire that measures psychological flexibility. The score range is 7-49, with higher scores indicating lesser flexibility.
Time Frame
Baseline to week 12
Title
Change in NEO-Personality Inventory (NEO-PI=
Description
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.
Time Frame
Baseline to week 12
Title
Persisting Effects Questionnaire (PEQ)
Description
PEQ is a 143-item scale aiming to assess changes in attitudes, moods, behavior, and spiritual experience
Time Frame
Week 12
Title
Neuroplasticity and inflammation
Description
Neuroplasticity and inflammation as measured by mean concentrations of plasma serum brain-derived neurotrophic factor (BDNF) and plasma cytokines, respectively.
Time Frame
Baseline to week 12
Title
Subjective effects of psilocybin: Subjective Drug Intensity (SDI)
Description
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.
Time Frame
0-6 hours post dosing
Title
Pharmacokinetics- and dynamics of psilocybin
Description
Pharmacokinetics- and dynamics of plasma psilocin, serum BDNF and plasma cytokines, as determined by concentration-time curves of mean plasma concentrations
Time Frame
0 - 6 hours post dosing
Title
Subjective effects of psilocybin: Mystical Experience Questionnaire (MEQ)
Description
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.
Time Frame
Completed once the effects are fully subsided or at least 6 hours after dosing
Title
Subjective effects of psilocybin: 5-Dimensional Altered State of Consciousness scale (5D-ASC)
Description
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).
Time Frame
Completed once the effects are fully subsided or at least 6 hours after dosing
Title
Subjective effects of psilocybin: Ego Dissolution Inventory (EDI)
Description
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).
Time Frame
Completed once the effects are fully subsided or at least 6 hours after dosing
Title
Subjective effects of psilocybin: Emotional Breakthrough Inventory (EBI)
Description
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).
Time Frame
Completed once the effects are fully subsided or at least 6 hours after dosing
Title
Subjective effects of psilocybin: Awe Experience Scale (AWE-S)
Description
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.
Time Frame
Completed once the effects are fully subsided or at least 6 hours after dosing
Title
Brain imaging
Description
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
Time Frame
1 week post dosing
Other Pre-specified Outcome Measures:
Title
Role of the Music I
Description
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
Time Frame
before and after dosing
Title
Role of the Music II
Description
We will explore the role of the music in psilocybin-assisted therapy by qualitative semi-structured interview
Time Frame
week 4
Title
Treatment expectancies
Description
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)
Time Frame
Baseline
Title
Optional long-term follow-ups
Description
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.
Time Frame
week 26 and week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mathias E Jensen, MD
Phone
+45 61634663
Email
mathias.ebbesen.jensen.01@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Anders Fink-Jensen, Professor
Phone
+45 22755843
Email
anders.fink-jensen@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Fink-Jensen, Professor
Organizational Affiliation
Psychiatric Center Copenhagen, Frederiksberg Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Psychiatric Center Copenhagen, Frederiksberg Hospital
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathias E Jensen, MD, PhD
Phone
+4561634663
Email
mathias.ebbesen.jensen.01@regionh.dk
First Name & Middle Initial & Last Name & Degree
Anders C Fink-Jensen
Phone
+45 38647072
Email
anders.fink-jensen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification.
IPD Sharing Time Frame
Immediately following publication. No end date.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal.
Citations:
PubMed Identifier
36241352
Citation
Jensen ME, Stenbaek DS, Juul TS, Fisher PM, Ekstrom CT, Knudsen GM, Fink-Jensen A. Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial). BMJ Open. 2022 Oct 14;12(10):e066019. doi: 10.1136/bmjopen-2022-066019.
Results Reference
derived

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Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

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