Methamphetamine Use Disorder: Current Status and Future Perspectives

Methamphetamine (METH) is a powerful psychostimulant associated with severe physical, neurological, and psychiatric health consequences. As of 2021, the United States is witnessing a resurgence of METH abuse, with rising overdose death rates and increased prevalence, especially among individuals aged 26 and older. Despite this urgent public health crisis, METH use disorder (MUD) remains a challenging condition to treat because there are currently no FDA-approved medications specifically indicated for its management.

The current standard of care for MUD relies heavily on non-pharmacological behavioral interventions. Among these, Contingency Management (CM) has demonstrated the most consistent efficacy in reducing drug use and improving treatment retention by providing tangible incentives for abstinence. Other approaches, including Cognitive-Behavioral Therapy (CBT), the Matrix Model, and even digital tools like the reSET mobile application, are also utilized to help patients develop coping mechanisms and identify triggers for relapse. More recently, neurostimulation techniques such as Repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) have emerged as potential treatments to address executive dysfunction and cravings by targeting the dorsolateral prefrontal cortex.

Historically, pharmacotherapy for MUD has been a major area of failed clinical research. Researchers have investigated various dopaminergic, serotonergic, and glutamatergic agents, but none have proven consistently effective for routine clinical use. The lack of success is largely attributed to the complex, chronic nature of MUD, the heterogeneity of METH-using populations, and neurobiological adaptations—such as decreased dopamine D2 receptor availability—that persist in chronic users. However, a significant breakthrough emerged with a Phase III trial demonstrating that the combination of oral bupropion and injectable naltrexone can safely and effectively reduce METH use and cravings in adults with moderate or severe MUD.