: Impact of Magnesium Adjunctive Therapy in Methamphetamine Use Disorder: Mechanisms, Neurobiological Pathways, and Therapeutic Progress

Methamphetamine use disorder (MUD) which is characterized by persistent neurochemical dysregulation, cognitive deficits, and elevated relapse rates, remains a major public health challenge. Conventional pharmacotherapies, which often insufficiently address the neuropathological underpinnings of addiction, do not point out the necessity for new and innovative, mechanism-driven interventions. Magnesium, a pleiotropic mineral with N-methyl-D-aspartate (NMDA) receptor–modulating, antioxidant, and neurotransmitter-stabilizing and regulating properties, has emerged as a promising adjunctive therapy. Recent preclinical and clinical studies highlight magnesium’s capacity to mitigate methamphetamine-induced neurotoxicity, oxidative stress, and neuroinflammation, while restoring synaptic plasticity and dopaminergic equilibrium. This review synthesizes current evidence on magnesium’s neurobiological mechanisms, evaluates translational advancements, and identifies unresolved challenges in optimizing its therapeutic application.