Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study

Sponsor

Anders Fink-Jensen, MD, DMSci (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04718792

Collaborator

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

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this project is to assess the feasibility and safety of administering a single dose of psilocybin to patients diagnosed with alcohol use disorder (AUD). In addition the investigators will establish the pharmacokinetic properties of the active metabolite psilocin. This is the first step in a research project that has the overall aim to evaluate the efficacy of a single administration of psilocybin as an intervention for treatment of AUD.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder (AUD)	Drug: Psilocybin	Phase 2

Detailed Description

The investigators will evaluate the feasibility and safety of administering psilocybin to 10 patients diagnosed with AUD. Following informed consent, patients will be screened for eligibility as per in- and exclusion criteria and baseline values will be recorded as per outcome measures. All patients will receive a single administration of 25 mg of psilocybin. As per safety guidelines patients will be monitored the entire dosing session by study staff familiar with the psychedelic effects of psilocybin. In addition, the patients will meet before and after the dosing session with a psychologist connected to the study for preparation and post-session debriefing, respectively. During dosing session, the investigators will collect blood plasma psilocin levels in order to establish pharmacokinetics and an estimated brain 5-HT2AR occupancy. When the effects of psilocybin subside, the investigators will ask the patients to fill out questionnaires encapsulating the psychedelic experience. One week after drug administration the patients are required to meet for an end-of-study assessment of outcome measures including adverse events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open label studyOpen label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin 10 patients will receive a single administration of psilocybin	Drug: Psilocybin A single administration psilocybin (25mg, opaque capsule for oral ingestion). The psilocybin is synthetically manufactured under current Good Manufacturing Practices (cGMP)

Arm

Intervention/Treatment

Experimental: Psilocybin

10 patients will receive a single administration of psilocybin

Drug: Psilocybin

A single administration psilocybin (25mg, opaque capsule for oral ingestion). The psilocybin is synthetically manufactured under current Good Manufacturing Practices (cGMP)

Outcome Measures

Primary Outcome Measures

Safety: Adverse events associated with administration of psilocybin in patients diagnosed with alcohol use disorder [1 week after drug administration]
Assessment of the incidence and severity of expected and unexpected adverse events

Secondary Outcome Measures

Feasibility: Proportion of participants who complete [1 week after drug administration]
Proportion of included patients who complete the planned procedures
Pharmacokinetic parameter of psilocin: Cmax [From drug administration and 300 minutes after.]
Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data. Blood samples will be drawn with intervals of 20 minutes
Pharmacokinetic parameter of psilocin: Tmax [From drug administration to 300 minutes after.]
Tmax: Time to reach maximum concentration of plasma psilocin determined from concentrations-versus-time data. Blood samples will be drawn with intervals of 20 minutes
Pharmacokinetic parameter of psilocin: AUC [From drug administration to 300 minutes after.]
AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.
Subjective effects of psilocybin: Intensity [From drug administration to 8 hours after]
Intensity of the drug effect will be assessed with intervals of 20 minutes 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 [8 hours after drug administration]
Experiential aspects of psilocybin measured by The Mystical Experience Questionnaire (MEQ). 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: Altered States of Consciousness [8 hours after drug administration]
Experiential aspects of psilocybin measured by the 11-Dimensional Altered State of Consciousness scale (11-DASC). 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 [8 hours after drug administration]
Experiential aspects of psilocybin measured by the Awe Experience Scale. 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 [8 hours after drug administration]
Experiential aspects of psilocybin measured by the Ego Dissolution Inventory. 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).
Change in craving [Baseline and 1 week after drug administration]
Change in self-reported craving measured by the Penn Alcohol Craving Scale (PACS). The patients are asked to rate the items on a 7-point scale going from 0= Never to 6= Nearly all of the time.
Change in self-efficacy [Baseline and 1 week after drug administration]
Change in self-reported self-efficacy measured by the Alcohol Abstinence Self-efficacy (AASE). The patients are asked to rate the items on a 5-point scale going from 1= not at all to 5= extremely.
Change in mindfulness [Baseline and 1 week after drug administration]
Change in self-reported mindfulness measured by the Mindful Attention Awareness Scale (MAAS). The patients are asked to rate the items on a 6-point scale going from 1= Almost always to 6= Almost never.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age of 20-70 years (both included).
Body weight of 60-95 kg (both included).
Diagnosed with AUD according to DSM-5 criteria and alcohol dependence according to ICD-10.
Alcohol Use Disorder Identification Test (AUDIT) ≥ 15.
≥ 5 heavy drinking days.

Exclusion Criteria:

Personal or first-degree relatives with current or previous diagnosis within psychotic spectrum disorders or bipolar disorder.
History of delirium tremens or alcohol withdrawal seizures.
History of suicide attempt or present suicidal ideation.
Withdrawal symptoms at inclusion, defined as a score higher than 9 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar).
Present or former severe neurological disease including head trauma with loss of consciousness > 30 min.
Impaired hepatic function (liver transaminases > 3 times upper normal limit).
Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months.
Abnormal electrocardiogram
Impaired renal function (eGFR < 50 ml/min).
Uncontrolled hypertension (systolic blood pressure >165 mmHg, diastolic blood pressure

95 mmHg).

Pharmacotherapy against AUD including disulfiram, naltrexone, acamprosate and nalmefene or treatment with any of these compounds within 28 days prior to inclusion.
Treatment with any serotonergic medication or any use of serotonergic psychedelics within 1 month prior to inclusion.
Any other active substance use defined as a Drug Use Disorder Identification Test score > 6/2 (m/w) and substance use disorder based on investigator's clinical evaluation, except for nicotine.
Women of childbearing potential who are pregnant, breastfeeding or have intention of becoming pregnant or are not using adequate contraceptive measures considered highly effective61.
Hypersensitivity to the active substance or to any of the excipients.
Unable to speak and/or understand Danish.
Any condition that the investigator feels would interfere with trial participation.