Alcohol use disorder (AUD) is a widespread burden on public health across the world and constitutes a major risk factor for disability and mortality. In Denmark, approximately 15% of the population has a harmful use of alcohol and 3% fulfill the criteria for AUD and excessive consumption of alcohol cost the Danish society 1.7 billion EUR per year. Unfortunately, AUD has a chronic and progressive course and is inefficiently treated. In the 1950s through the 1960s, before the Controlled Substance Act of 1970, several studies were carried out evaluating the effects of classic psychedelics such as psilocybin and LSD on addiction. A recent meta-analysis reviewed six randomized controlled trials in AUD from the 1950-1970s (n = 536) and found odds in favor of abstinence (OR 19.6) after a single administration of LSD. Recently in 2015, a small (n=10) proof of concept study in patients with AUD evaluated the effects of psilocybin and found significant and persisting reductions in drinking days and heavy drinking days. While these preliminary results are certainly encouraging, a larger placebo-controlled study is needed to evaluate treatment efficacy of psilocybin for AUD.

The overall aim of the proposed project is therefore to evaluate the treatment efficacy of a single administration of psilocybin in patients with AUD. We hypothesize that psilocybin will reduce percentage of heavy drinking days and that these effects will be positively correlated with plasma psilocin levels and peak levels of the acute psychedelic experience in patients treated with psilocybin.

The proposed study will be conducted as a randomized, double-blinded, placebo-controlled 12-week clinical trial, in which we include 90 patients diagnosed with AUD, screened for eligibility. Patients will be randomized for a single administration of 25 mg of psilocybin vs placebo. Psilocybin is supplied by Usona Institute and is imported by a GMP approved pharmacy that will prepare opaque identical capsules of 25 mg psilocybin and placebo. As per safety guidelines, patients will be monitored the entire dosing session by staff trained in the administration of psilocybin. Patients will also attend preparation and post-session debriefing. During dosing, we will collect plasma psilocin levels in order to estimate corresponding brain serotonin 2A receptor occupancy. When the effects of psilocybin subside, patients will complete validated questionnaires characterizing the psychedelic experience. In the 12 weeks following administration, patients will complete daily alcohol logs and attend follow-up visits and data collection, including MR scanning of the brain and psychometrics.