Dietary supplements for Parkinson's disease: State of the science.

Polysubstance use disorders (having ≥2 substance use disorders (SUDs)) are associated with significant morbidity, poor treatment adherence and outcomes, and high mortality [–]. Polysubstance use disorders reflect shared neurobiological mechanisms, with addictive drugs inducing common mesolimbic dopamine adaptations that strengthen reinforcement and promote cross‑sensitization across substances [, ]. Moreover, shared developmental [–] and genetic [, , ] vulnerabilities interact with environmental factors [, ], collectively increasing risk across drug classes and sustaining persistent polysubstance use and use disorders. However, significant gaps persist in our understanding of the current prevalence, severity, and correlates of polysubstance use disorders. Existing studies’ reliance on data collected more than a decade ago, the exclusion of nicotine dependence, or a narrow focus on opioid misuse and opioid use disorder, constrain our understanding of current polysubstance use disorders and hinder the development of effective prevention and treatment strategies. In particular, the epidemiology of SUDs has evolved since researchers examined national data from 2012–2013 []. While alcohol use disorder declined during 2002–2019, drug use disorders (e.g., cannabis and methamphetamine use disorders) increased during 2015–2019 [–]. Few studies of polysubstance use disorders include nicotine [, , ], despite its widespread use among adults, common co‑use with alcohol, cannabis, and other drugs [, –], and links between nicotine dependence and persistent co‑occurring SUDs due to shared neurobiological pathways, notably dopaminergic enhancement and nicotine’s potentiating effects of other substances [, –].