CNSPulse

NOVEL TARGETS AND TREATMENTS FOR STIMULANT USE DISORDERS AND DEPRESSION

Keren Bachi — The Addiction Institute of Mount Sinai; Icahn School of Medicine at Mount Sinai

2026 ASCP Annual Meeting

There are no US Food and Drug Administration (FDA)-approved pharmacotherapy options for the treatment of cocaine or methamphetamine use disorder (often referred to together as stimulant use disorder). Individuals with stimulant use disorders have often co-occurring and/or lifetime depression. There is thus an urgent need to identify other novel treatments, given that over 2 million adults in the United States suffer from these disorders, and overdose deaths involving these substances have increased exponentially over the past decade. The most recent wave of the opioid overdose epidemic has been driven, in part, by an increase in illicit stimulant use and fentanyl contamination. Challenges in treatment of stimulant disorders is also expected to worsen with the recently increasing trend of individuals receiving stimulant prescriptions accompanied by increases in prescription stimulant use disorders. To address these concerns, we propose a panel presentation comprised of individuals across the career span which will include presentations ranging from groundbreaking clinical trials, to neuroimaging with novel social-dynamic paradigm, and interventional experiments with intermittent theta burst stimulation (iTBS) and integration of CBT and TMS. Presentations include a neuroimaging study of circuit-level dysfunctions associated with social-neurobehavioral phenotype in individuals with cocaine use disorder as a foundation for advancement of social-related treatment targets (Bachi); the very first clinical trial of a glucagon-like peptide 1 (GLP-1) receptor agonist (tirzepatide, a dual GLP-1/glucose-dependent insulinotropic peptide agonist) for methamphetamine use disorder (Jha); a feasibility trial of an accelerated course of intermittent theta burst for methamphetamine use disorder (Haque); and the first pilot study of augmenting perinatal rumination-focused cognitive-behavioral therapy with repetitive transcranial magnetic stimulation to enhance antidepressant response and modulate neurocircuitry in moderate– severe MDD (Jawish). Together, these presentations will provide an overview of cutting-edge research that may further our understanding of the circuitry-mechanisms underpinning stimulant use disorders and depression and outcomes of innovative trials to provide foundation for the development of novel and effective treatments.

Learning Objective 1: Learn about mechanisms of novel potential targets for treatments of stimulant use disorders and prenatal depression.

Learning Objective 2: Learn about outcomes of recent pilot and clinical trials that examine new potential targets for treatments of stimulant use disorders and prenatal depression.

References

  1. Sahani, V., Hurd, Y.L., Bachi, K. (2022). “Neural Underpinnings of Social Stress in Substance Use Disorders.” Curr Top Behav Neurosci.
  2. Henney AE, Riley DR, Heague M, Roberts CA, Hydes TJ, Anson M, Hughes DM, Alam U, Cuthbertson DJ. (2025). Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach. Diabetes Obes Metab.
  3. Li Y, Yang B, Ma J, et al. (2024). Assessment of rTMS treatment effects for methamphetamine addiction based on EEG functional connectivity. Cogn Neurodyn, 18(5):2373–2386.
  4. Jawish, R., M. Smid, A. Gordon, K. Shangraw and B. J. Mickey (2024). “Prolonged transcranial magnetic stimulation in a pregnant patient with treatment-resistant depression: a case report.” J Med Case Rep 18(1): 512.