Characterization of a novel non-hallucinogenic psilocybin derivative for alcohol use disorder

Abstract The use of psychedelic molecules in the treatment of alcohol/substance abuse and mental health disorders is one of the most controversial topics in modern society. This skepticism is due to its historic recreational use for hallucinogenic effects and potential for abuse. However, recent investigations specifically around psilocybin and derivatives reveal increasing evidence for their therapeutic use in mental health, neurocognitive, and substance abuse disorders. Safe and effective treatments for each of the aforementioned ailments require greater attention as we progress as a society. We have performed detailed structure-activity relationship analyses of various tryptamine analogs to probe their biological properties and develop effective treatments with reduced hallucinogenic properties. This proposal provides a detailed plan to further develop a more selective serotonergic-targeting, non- hallucinogenic psilocybin derivative for alcohol use disorders with promising preliminary efficacy in alcohol preferring mice that surpass the activity of psilocin over a 60-day dosing period.