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Introduction to Special Issue on Tobacco and Other Substance Use Disorders: Links and Implications

The morbidity, mortality, and cost of tobacco, alcohol, and other substance use disorders is well established as is the need to develop more effective prevention and treatment strategies. Equally well established is the elevated prevalence of tobacco use in individuals with alcohol and other substance use disorders – approximately 75% of individuals being treated for alcohol use disorder (AUD) smoke cigarettes (1,2) and 47% to 88% of individuals being treated for substance use disorder (SUD) smoke, depending on the substance (1–5). Less well established is the role that: 1) tobacco/nicotine plays in establishing and maintaining AUD and other SUDs and 2) the role that non-nicotine substance use plays in establishing and maintaining tobacco use disorder (TUD). Regardless of causality, the elevated prevalence of smoking in individuals with AUD and/or other SUD (AUD/SUD) represents an important health issue that needs to be addressed; however, how best to address it depends, in part, on whether co-use plays a causal role in maintaining addiction. This special issue includes a review of research pertinent to the questions of causation and potential causal mechanisms from across the translational research spectrum. Findings that the use of nicotine/tobacco plays a causal role in establishing and maintaining addiction to alcohol and other substances, or viceversa, would have important implications for prevention and treatment. For example, if nicotine does, in fact, increase the likelihood that an individual will develop an AUD/SUD then the recent increase in nontobacco nicotine products by adolescents would have public health implications well-beyond the health consequences of the use of these products or even the potential progression to TUD, demanding more vigorous prevention efforts. Findings that tobacco/nicotine co-use moderates treatment outcomes for the primary substance for which SUD treatment is sought would indicate that co-use may be a precision-medicine-factor (6,7), which should be used to help guide treatment planning. Findings of a causal relationship in cooccurring addiction could also have significant implications for treatment development, with potentially novel therapeutic targets yielded by an understanding of underlying mechanisms. In this special issue, Dr. Richter and colleagues (8) reviewed, and contributed new data to, the epidemiological literature on the tobacco/nicotine link with other substances. They note that, while tobacco use initiation in adolescents has declined, the use of electronic cigarettes (e-cigarettes) and other electronic nicotine delivery systems has increased significantly in the past several years. Of particular concern is evidence that the use of any nicotine-containing product is associated with a greater likelihood of using and being addicted to other substances. The authors discuss the prevention and policy implications of these findings. While the epidemiological findings are consistent with a causal role for co-use in the development of addiction, the correlational nature of the data does not allow for causal determinations to be made. Thus, findings from pre-clinical research, which can establish causal relationships, are of critical import. Three papers in this special issue, by Tarren and Bartlett (9), Kohut (10), and Cross et al. (11), review pre-clinical research findings. The paper by Drs. Tarren and Bartlett (9) describes pre-clinical models being utilized to more precisely delineate the neurobiological mechanisms underlying alcohol and nicotine codependence and discusses findings suggesting a role for nicotinic acetylcholine receptors (nAChRs) in codependence. This research suggests that nicotinic receptor antagonists may offer promising therapeutic agents in the treatment of co-occurring tobacco and alcohol use disorders, an important implication given evidence that concurrent use of nicotine and alcohol may alter the effectiveness of FDA-approved medications used to treat AUD and TUD. Dr. Kohut (10) reviewed findings from animal models evaluating the