Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study

Anders Fink-Jensen, MD, DMSci10 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Alcohol Use Disorder (AUD)

Interventions

PsilocybinDRUG

A single administration of PEX010 (psilocybin 25 mg, opaque capsule for oral ingestion). PEX010 contains psilocybin (25 mg) naturally extracted from Psilocybe cubensis mushroom fruiting bodies, manufactured under current Good Manufacturing Practices (cGMP)

Eligibility

Sex: ALLMin age: 20 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age of 20-70 years (both included). 2. Body weight of 60-95 kg (both included). 3. Diagnosed with AUD according to DSM-5 criteria and alcohol dependence according to ICD-10. 4. Alcohol Use Disorder Identification Test (AUDIT) ≥ 15. 5. ≥ 5 heavy drinking days. Exclusion Criteria: 1. Personal or first-degree relatives with current or previous diagnosis within psychotic spectrum disorders or bipolar disorder. 2. History of delirium tremens or alcohol withdrawal seizures. 3. History of suicide attempt or present suicidal ideation. 4. Withdrawal symptoms at inclusion, defined as a score higher than 9 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar). 5. Present or former severe neurological disease including head trauma with loss of consciousness \> 30 min. 6. Impaired hepatic function (liver transaminases \> 3 times upper normal limit). 7. Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months. 8. Abnormal electrocardiogram 9. Impaired renal function (eGFR \< 50 ml/min). 10. Uncontrolled hypertension (systolic blood pressure \>165 mmHg, diastolic blood pressure \>95 mmHg). 11. Pharmacotherapy against AUD including disulfiram, naltrexone, acamprosate and nalmefene or treatment with any of these compounds within 28 days prior to inclusion. 12. Treatment with any serotonergic medication or any use of serotonergic psychedelics within 1 month prior to inclusion. 13. 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. 14. Women of childbearing potential who are pregnant, breastfeeding or have intention of becoming pregnant or are not using adequate contraceptive measures considered highly effective61. 15. Hypersensitivity to the active substance or to any of the excipients. 16. Unable to speak and/or understand Danish. 17. Any condition that the investigator feels would interfere with trial participation.

Locations (1)

Psychiatric Center Copenhagen

Copenhagen, Frederiksberg, Denmark

Outcomes

Primary Outcomes

Safety: Adverse events associated with administration of psilocybin in patients diagnosed with alcohol use disorder

Assessment of the incidence and severity of expected and unexpected adverse events

Time frame: 12 week after drug administration

Secondary Outcomes

Feasibility: Proportion of participants who complete

Proportion of included patients who complete the planned procedures

Time frame: 1 week after drug administration

Pharmacokinetic parameter of psilocin: Cmax

Cmax: maximum concentration of plasma psilocin determined from concentrations-versus-time data. Blood samples will be drawn with intervals of 20 minutes

Time frame: From drug administration and 360 minutes after.

Pharmacokinetic parameter of psilocin: Tmax

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

Time frame: From drug administration to 360 minutes after.

Pharmacokinetic parameter of psilocin: AUC

AUC: Area under the plasma concentrations-versus-time curve determined using the linear trapezoidal rule.

Time frame: From drug administration to 360 minutes after.

Pharmacokinetic parameter of brain-derived neurotropic factor

Acute and subacute changes in plasma and wholeblod brain-derived neurotropic factor (BDNF)

Time frame: From drug administration to 360 minutes after and 1 week after

Pharmacokinetic parameter of cytokines

Data from ClinicalTrials.gov

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Acute and subacute changes in plasma cytokines including tumour necrosis factor alpha, interleukin-4 and 6.

Time frame: From drug administration to 360 minutes after and 1 week after

Pharmacodynamics of cardiovascular measures

Acute changes in systolic and diastolic blood pressure (mmHg)

Time frame: From drug administration to 360 minutes after

Pharmacodynamics of cardiovascular measures

Acute changes in heart rate (beats per minute)

Time frame: From drug administration to 360 minutes after

Subjective effects of psilocybin: Intensity

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.

Time frame: From drug administration to 8 hours after

Subjective effects of psilocybin: Mystical Experience

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.

Time frame: 8 hours after drug administration

Subjective effects of psilocybin: Altered States of Consciousness

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).

Time frame: 8 hours after drug administration

Subjective effects of psilocybin: Awe Experience

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.

Time frame: 8 hours after drug administration

Subjective effects of psilocybin: Ego Dissolution

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).

Time frame: 8 hours after drug administration

Change in heavy drinking days

Change in heavy drinking day, defined as consuming 60/48 g (men/women) of alcohol or more on any day, in the past 28 days as quantified by the Timeline Followback Method

Time frame: Baseline, 4, 12 and 52 weeks after drug administration

Change in drinks per day

Change in drinks per day in the past 28 days as quantified by the Timeline Followback Method

Time frame: Baseline, 4, 12 and 52 weeks after drug administration

Change in drinking days

Change in drinking days in the past 28 days as quantified by the Timeline Followback Method

Time frame: Baseline, 4, 12 and 52 weeks after drug administration

Change in alcohol use

Change in self-reported alcohol use measured by the Alcohol Use Identification Test (AUDIT). The AUDIT has 10 questions and the possible responses to each question are scored 0, 1, 2, 3 or 4, with the exception of questions 9 and 10 which have possible responses of 0, 2 and 4. The range of possible scores is from 0 to 40 where 0 indicates an abstainer who has never had any problems from alcoho

Time frame: Baseline, 12 and 52 week after drug administration

Change in craving

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.