Past and current drug repurposing clinical trials to treat cognition in methamphetamine use: a scoping review of pharmacotherapy candidates

Globally, methamphetamine is one of the most widely used illicit substances. Despite this, there are no Food and Drug Administration (FDA)-approved pharmacotherapies for treating methamphetamine use disorder. Accumulating evidence suggests consistent cognitive impairments in people with methamphetamine use disorder, which are also associated with neural dysfunction. Importantly, improving cognition may be highly beneficial in reducing methamphetamine use. Indeed, there are medications that have been or are currently being assessed in clinical trials as repurposing drugs to treat methamphetamine use disorder and associated cognitive deficits. Given the known safety profiles and bioavailability, as well as established manufacturing processes, drug repurposing can bypass some steps of conventional drug discovery. This shortens the timeline from bench to bedside translation with lower cost and less risk. Hence, drug repurposing to find pharmacotherapies to treat methamphetamine use disorder should be highly encouraged. The aim of the present review is to scope all repurposed medications in past and current clinical trials in people with methamphetamine use disorder that also assess cognitive function. Medications were selected from publicly available clinical trials registration databases. Based on human and animal literature, we will describe their putative mechanism of action, pharmacological properties, and their potential to improve cognitive functioning in people who use methamphetamine. We hope this scoping review will stimulate drug repurposing and promote rigorous neuroscience-based rationale in future clinical trials to treat methamphetamine use disorder.