One Is Not Enough: Understanding and Modeling Polysubstance Use

Abstract

Substance use disorder (SUD) is a chronic, relapsing disease with a highly multifaceted pathology that includes (but is not limited to) sensitivity to drug-associated cues, negative affect, and motivation to maintain drug consumption. SUDs are highly prevalent, with 35 million people meeting criteria for SUD. While drug use and addiction are highly studied, most investigations of SUDs examine drug use in isolation, rather than in the more prevalent context of comorbid substance histories. Indeed, 11.3% of individuals diagnosed with a SUD have concurrent alcohol and illicit drug use disorders. Furthermore, having a SUD with one substance increases susceptibility to developing dependence on additional substances. For example, the increased risk of developing heroin dependence is twofold for alcohol misusers, threefold for cannabis users, 15fold for cocaine users, and 40-fold for prescription misusers. Given the prevalence and risk associated with polysubstance use and current public health crises, examining these disorders through the lens of co-use is essential for translatability and improved treatment efficacy. The escalating economic and social costs and continued rise in drug use has spurred interest in developing preclinical models that effectively model this phenomenon. Here, we review the current state of the field in understanding the behavioral and neural circuitry in the context of co-use with common pairings of alcohol, nicotine, cannabis, and other addictive substances. Moreover, we outline key considerations when developing polysubstance models, including challenges to developing preclinical models to provide insights and improve treatment outcomes.

Identifying Patterns of Association and Transition in the Use of Addictive Substances over Five Decades in the United States

“…27-29 While increasing complexity of substance use has the potential of leading to addiction and progressively poor health sequelae among the users, it is particularly important to include in any analysis of this phenomenon the various demographic and dynamic factors underlying the challenge. 30,31…”

Commentary: “Ockham’s Razor” Doesn’t Apply to “Opioid” Overdose Death

“…The understanding of the nature and extent of POD is hindered by inaccuracies in the data collected and used to describe these deaths. For example, studies on Substance Use Disorder (SUD) frequently exclude those with a history of multiple drug use [17]. Many of the studies use surveys and patient questionnaires to ascertain patterns of drug use.…”

<p>The Polysubstance Overdose-Death Crisis</p>

“…13,14 Polysubstance users also frequently use cocaine and amphetamines, and 74% of cocaine and 80% of methamphetamine users also use other substances. 15 However, reports of the true extent of use are highly variable; for example, the range of those using cocaine and alcohol is reported to be 37% to 96%. 15 This large variability illustrates the complexity in polysubstance abuse and overdose patterns.…”

“…15 However, reports of the true extent of use are highly variable; for example, the range of those using cocaine and alcohol is reported to be 37% to 96%. 15 This large variability illustrates the complexity in polysubstance abuse and overdose patterns. Those who abuse "fentalogues" (illicit fentanyl and its analogs, eg, alfentanil, carfentanil, and sufentanil) 16 tend to have even greater incidence of polysubstance abuse than do abusers of other substances, albeit many victims of overdoses due to fentalogues are unaware of taking this class of drugs.…”