rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use...

Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.