DXM

DXM was introduced in 1958 as the first non-opioid cough suppressant and remains the most used OTC antitussive worldwide. At therapeutic doses (10-30 mg), it effectively suppresses cough via NMDA antagonism in the medulla. At supratherapeutic doses (100-700+ mg), it produces dose-dependent dissociative, hallucinogenic, and euphoric effects that mimic classical dissociatives like ketamine and PCP. Recent research has explored DXM's potential as a rapid-acting antidepressant, with the DXM-bupropion combination (Auvelity) receiving FDA approval for major depressive disorder. CYP2D6 polymorphism significantly affects DXM metabolism and subjective effects, with poor metabolizers experiencing prolonged and intensified effects. Evidence for long-term cognitive effects of recreational use remains limited but concerning, and DXM-induced psychosis has been documented and treated with atypical antipsychotics.