Overview
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).
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.
Eligibility
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.