Mapping the Intervention Landscape for Methamphetamine Use Disorder: A Scoping Review of Integrated Pharmacological,Behavioral,and Neuromodulation Approaches

Abstract

Background:

The global resurgence of methamphetamine use disorder (MUD) represents a critical public health challenge, characterized by high morbidity and a lack of approved pharmacotherapies. Treatment research spans diverse domains, but a comprehensive synthesis of the scope, efficacy, and interrelationships of these approaches is lacking.

Objective:

To systematically map and synthesize the available evidence on interventions for MUD, including their efficacy, mechanisms, and the overall structure of the research landscape.

Methods:

Following the Arksey and O’Malley framework and PRISMA-ScR guidelines, we conducted a systematic search of 5 electronic databases (MEDLINE, Embase, CENTRAL, PsycINFO, CINAHL) from inception to October 2025. We included studies of any design evaluating interventions for MUD in human populations.

Results:

From 6852 screened records, 62 studies were included. Our synthesis reveals a tripartite intervention landscape: (1) Behavioral interventions, particularly contingency management (CM), demonstrate the most robust efficacy, increasing abstinence rates by 40% to 60%. (2) Pharmacological approaches show promise with combination therapy (naltrexone-bupropion and Wellbutrin), significantly increasing methamphetamine-negative urine samples versus placebo (11.4% vs 5.7%), though effect sizes are generally modest. (3) Neuromodulation, specifically repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex, consistently reduces cue-induced craving by 25% to 35%. Critical moderators of treatment response were identified, including the OPRM1 A118G polymorphism and high rates of polydrug use (up to 42% in opioid use disorder cohorts), which predicts poorer outcomes. Implementation feasibility and intervention fidelity are critical considerations, particularly for CM and pharmacotherapy adherence.

Conclusion:

Effective MUD management requires a multimodal, personalized framework. While CM remains a foundational behavioral strategy, advances in combination pharmacotherapy and neuromodulation offer new avenues for targeting core neurobiological deficits. Future research must prioritize integrated treatment platforms, implementation science to scale effective interventions like CM, and personalized strategies informed by genetics and neuroimaging.