Serotonergic psychedelic treatment for obesity and eating disorders: potential expectations and caveats for emerging studies

The authors of this cautious exploratory overview write: "There has been a substantial growth in private clinics and registered clinical trials employing serotonergic psychedelics for various psychiatric illnesses, including substance use disorder1,2 and major depressive disorder.3–6 Classical psychedelics include lysergic acid diethylamide (LSD), mescaline, psilocybin, and dimethyltryptamine (DMT), the latter 3 naturally occurring in some plant, fungal and animal species. Psychedelics are one of the oldest recreational drugs used ritually by ancient cultures, but the discovery in the 1940s of the psychoactive effects of LSD fueled a huge boom in clinical studies of psychedelics.7 Psychedelic-assisted psychotherapy showed apparent promise in the treatment of disorders including depression, anxiety, anorexia nervosa and alcoholism, and psychedelics were increasingly employed in psychiatry as late as 1970.7 However, following widespread recreational use and their subsequent classification as a Schedule I drug in 1967, open medicinal use screeched to a halt, and clinical studies of psychedelics were nearly absent until the mid 2000s …... Given the potential direct and indirect effects of psychedelic treatment on food intake, there is a lot of excitement for its use as a novel therapeutic. However, in addition to the challenges with psychedelic clinical trials outlined in Box 1, several considerations should be noted when designing clinical trials for the treatment of obesity. First, there is a strong need for completion of well-controlled clinical trials to determine efficacy of this potential treatment, given the paucity in current evidence. Second, it will be important to assess the potential for adverse events, such as serotonin syndrome, which may occur when psychedelics are taken alongside serotonergic medications used to treat comorbid depression. Third, given comorbid hypertension and cardiovascular disease in people living with obesity, particular caution should be taken with those taking high doses of serotonergic compounds. Finally, as with all individuals undergoing psychedelic therapy, there is a small risk of overwhelming distress during a drug reaction or a lasting psychotic reaction, which occurs more often in people with a family history of psychosis. Thus, carefully conducted research that considers the unique effects of psychedelics on brain and behavioural plasticity will inform the treatment of various disorders, including obesity."

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