Clinical trial NCT04718792: Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study
Official title: Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder (AUD)
Keywords: psilocybin
alcohol use disorder
psychedelics
addiction
pharmacokinetics
psilocin
feasibility
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
Collaborators: name: The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet
First posted: 2021-01-22
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label study
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Adverse events associated with administration of psilocybin in patients diagnosed with alcohol use disorder
timeFrame: 12 week after drug administration
Secondary outcomes:
measure: Feasibility: Proportion of participants who complete
timeFrame: 1 week after drug administration
measure: Pharmacokinetic parameter of psilocin: Cmax
timeFrame: From drug administration and 360 minutes after.
measure: Pharmacokinetic parameter of psilocin: Tmax
timeFrame: From drug administration to 360 minutes after.
measure: Pharmacokinetic parameter of psilocin: AUC
timeFrame: From drug administration to 360 minutes after.
measure: Pharmacokinetic parameter of brain-derived neurotropic factor
timeFrame: From drug administration to 360 minutes after and 1 week after
measure: Pharmacokinetic parameter of cytokines
timeFrame: From drug administration to 360 minutes after and 1 week after
measure: Pharmacodynamics of cardiovascular measures
timeFrame: From drug administration to 360 minutes after
measure: Pharmacodynamics of cardiovascular measures
timeFrame: From drug administration to 360 minutes after
measure: Subjective effects of psilocybin: Intensity
timeFrame: From drug administration to 8 hours after
measure: Subjective effects of psilocybin: Mystical Experience
timeFrame: 8 hours after drug administration
measure: Subjective effects of psilocybin: Altered States of Consciousness
timeFrame: 8 hours after drug administration
measure: Subjective effects of psilocybin: Awe Experience
timeFrame: 8 hours after drug administration
measure: Subjective effects of psilocybin: Ego Dissolution
timeFrame: 8 hours after drug administration
measure: Change in heavy drinking days
timeFrame: Baseline, 4, 12 and 52 weeks after drug administration
measure: Change in drinks per day
timeFrame: Baseline, 4, 12 and 52 weeks after drug administration
measure: Change in drinking days
timeFrame: Baseline, 4, 12 and 52 weeks after drug administration
measure: Change in alcohol use
timeFrame: Baseline, 12 and 52 week after drug administration
measure: Change in craving
timeFrame: Baseline, 1 week, 4 week, 12 and 52 week after drug administration
measure: Change in self-efficacy
timeFrame: Baseline, 1 week, 4 week, 12 and 52 week after drug administration
measure: Change in mindfulness
timeFrame: Baseline, 1 week, 4 week, 12 and 52 week after drug administration
measure: Change in psychological flexibility
timeFrame: Baseline, 1 week, 4 week, 12 and 52 week after drug administration
measure: Change in depressive symptoms
timeFrame: Baseline, 1 week, 4 week, 12 and 52 week after drug administration
measure: Expectancy to treatment
timeFrame: Baseline
measure: Persisting Effects
timeFrame: 4, 12 and 52 weeks after drug administration
measure: Change in personality traits
timeFrame: Baseline and Week 12 after drug administration
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Psychiatric Center Copenhagen
state: Frederiksberg
Study officials:
affiliation: Professor
name: Anders Fink-Jensen, Professor
role: PRINCIPAL_INVESTIGATOR
References: