Substance use disorders (SUDs) are heterogenous and complex, making the development of translationally predictive rodent and non-human primate models to uncover their neurobehavioral underpinnings difficult. Neuroscience-focused outcomes have become highly prevalent, and with this, the notion that SUDs are disorders of the brain embraced as a dominant theoretical orientation to understand SUD etiology and treatment. These efforts, however, have led to few efficacious pharmacotherapies, and in some cases (as with cocaine or methamphetamine), no pharmacotherapies have translated from preclinical models for clinical use. In this review and theoretical commentary, we first describe the development of animal models of SUDs from a historical perspective. We then define and discuss three logical fallacies including 1) circular explanation, 2) affirming the consequent, and 3) reification that can apply to developed models. We then provide three case examples in which conceptual or logical issues exist in common methods (i.e., behavioral economic demand, escalation, and reinstatement). Alternative strategies to refocus behavioral models are suggested for the field in an attempt to better bridge the translational divide between animal models and the clinical condition of SUDs.

Smoking rates among those who use prescribed or recreational opioids are significantly higher than the general population. Hypothesized neuropharmacological interactions between opioids and nicotine may contribute to this pattern of polysubstance use, especially during withdrawal. However, little research has examined how the withdrawal of one substance may affect the consumption of the other (i.e., cross-drug withdrawal effects). Behavioral economic demand tasks (e.g., hypothetical purchase tasks) can be used to quickly assess the value of a drug. Crowdsourcing can be a convenient tool to gain preliminary insight into different processes in substance valuation that may otherwise be impossible or prohibitively difficult to study. The purpose of the present study was to provide a preliminary examination of the effects of hypothetical withdrawal of cigarettes and opioids on the consumption of those drugs among polysubstance users. Amazon Mechanical Turk workers who reported daily smoking and at least monthly opioid use completed a series of hypothetical purchase tasks for doses of opioids and cigarettes under various withdrawal conditions. Sensitivity to the price of both drugs decreased when under withdrawal for either, indicating a higher drug value of cigarettes and opioids due to effects of cross-drug withdrawal. Nicotine and opioid dependence severity, impulsive choice, and riskiness were also positively related to drug purchasing. Public Health SignificanceThe results of this study suggest that opioid withdrawal may increase the value of cigarettes and therefore difficulty in quitting smoking, while nicotine withdrawal may similarly increase the value of opioids and difficulty in quitting opioid use. Results of this study could inform treatment development by explaining difficulties in maintaining abstinence that may arise as a function of cross-drug withdrawal effects between opioids and nicotine.

No abstract