Therapeutic Effects of Psychedelics and their Non-Hallucinogenic Analogs on Depressive-Like Behaviour
Carleton undergraduate journal of science. September 2, 2025 Kaylee Reid, Dhiral Kot, Argel Aguilar‐valles
Major depressive disorder affects about 280 million people globally, and many do not respond to first-line antidepressants, leading to treatment-resistant depression. Psychedelics like psilocybin show rapid antidepressant effects by enhancing neuroplasticity through 5-HT2A receptor activation, but their hallucinogenic properties limit clinical use. A non-hallucinogenic analog, 2-bromo-lysergic acid diethylamide (2-Br-LSD), may promote neuroplasticity without hallucinations, though it is unclear if hallucinatory activity is necessary for therapeutic benefit. This thesis examines both compounds in rodent models of chronic stress, hypothesizing that both will reduce depression-like behaviors by modulating mood-regulating neural circuits, aiming to assess 2-Br-LSD as a more accessible treatment for treatment-resistant depression.