National Institute on Drug Abuse (NIDA) clinical trials network (CTN) stimulant use disorder (StUD) task force...

Increases in morbidity and mortality associated with stimulant use disorders (StUDs) combined with limited pharmacological research and development highlight the need to explore repurposing existing medications with mechanisms of action relevant to the management of StUDs. This paper presents findings regarding a common set of symptoms common across StUDs, impulsivity and compulsivity, that offer compelling rationale to identify future interventions for evaluation in CTN trials and elsewhere.

A virtual Task Force meeting held in 2024 by the National Drug Abuse Treatment Clinical Trials Network (CTN) assembled national experts to consider pharmacological and non-pharmacological candidates for repurposing in StUD treatment. Discussion centered on evidence regarding their mechanisms of action, preclinical and clinical evidence in StUD management, and how these interventions could be further researched or applied in clinical practice.

Discussions referenced medications including: suvorexant, GLP-1 agonists, guanfacine, clavulanic acid, cariprazine, cannabidiol and psychedelics. Non-medication therapeutic strategies to consider for managing StUDs include novel neuromodulation techniques (low-intensity focused ultrasound (LIFU), photobiomodulation (tPBM)), which are believed to precisely and deeply penetrate brain tissues, targeting areas responsible for StUDs-related behaviors.

Task Force findings with high enthusiasm for possible consideration as candidate medication options for future research based on novel strategies for StUDs include suvorexant and GLP-1R agonists. Findings with less enthusiasm, but with evidence-based rationale include cariprazine, clavulanic acide, and guanfacine. Findings noted strong rationale for the promise of new neuromodulation therapies; constraints of their time-consuming nature over through multiple sessions across several weeks are challenges.

Task Force findings provide guidance for a possible pipeline of candidate therapeutic options for future research on novel strategies for treatment of StUDs. A cross-cutting theme emerged in recognition of heterogeneous behavioral phenotypes presenting challenges to recovery, suggesting that beyond understanding the mechanism of action and efficacy of each therapeutic strategy, it is important to pursue personalized medicine approaches to improve outcomes for StUDs.