Psychedelics have been investigated as a treatment for alcohol use disorder since the 1950s, with over a dozen clinical trials of LSD and recent trials of psilocybin and ayahuasca. Observational studies consistently show promising results, but placebo-controlled trials have produced inconsistent outcomes and methodologies. This review characterizes foundational studies, emphasizing key design factors such as the presence of a placebo (e.g., ephedrine, dextroamphetamine, diphenhydramine, or low-dose LSD) and non-pharmacological factors like treatment setting and psychotherapy. It also examines candidate mechanisms of action through a biopsychosocial lens, spanning cellular neuroplasticity, cognitive neuroscience, subjective experience, and social connection, highlighting findings on efficacy and potential mechanisms to guide future research.
Posttraumatic stress disorder and alcohol use disorder frequently co-occur and lead to more severe symptoms, higher suicide risk, and poorer treatment outcomes. MDMA-assisted therapy shows promise; the FDA designated it a Breakthrough Therapy for PTSD based on six Phase 2 trials. This manuscript describes the design of the first open-label trial of MDMA-AT for military veterans with both PTSD and AUD, enrolling 12 participants. The study includes neuroimaging and biomarker measures to assess brain changes and neuroinflammation before and after treatment. The authors detail the complex clinical and regulatory processes involved in setting up the trial, aiming to establish standardized protocols and outcomes for future FDA approval.
Smoking cannabis acutely reduces alcohol consumption in people who drink heavily and use cannabis at least twice weekly. In a double-blind crossover trial, 157 participants were randomized to smoke cannabis cigarettes with 7.2% THC, 3.1% THC, or placebo (0.03% THC) across three days. After smoking, they were exposed to alcohol cues and given a choice to consume alcohol. Those who smoked 3.1% THC reduced alcohol consumption by 19%, and those who smoked 7.2% THC reduced it by 27%, compared to placebo. No significant effects on overall craving were found, though the higher dose reduced alcohol urge immediately after smoking. Further research on various cannabinoids is needed to inform alcohol treatment guidelines.