Molecular dynamics study of differential effects of serotonin-2A-receptor (5-HT2AR) modulators
bioRxiv Preprint Server March 27, 2025 Jordy Peeters, Dimitri de Bundel, Kenno Vanommeslaeghe preprint
Activating the serotonin-2A receptor can produce antidepressant effects, but also risks hallucinations. Recent work suggests that using weak partial agonists or very low doses might separate these effects. Computer simulations of the receptor bound to different drugs show that modest activation may yield only antidepressant benefits, while excessive activation causes hallucinations. This finding points to a possible drug development strategy: administering a sufficiently weak partial agonist could provide therapeutic effects without hallucinogenic side effects, avoiding the abuse and narrow dosing problems of microdosing.