Examining racial differences in smoking outcomes among smokers enrolled in an intravenous nicotine infusion study

Smoking remains the leading cause of preventable death in the United States. (Surgeon General, 2014, Forouzanfar et al., 2016) While a large volume of research on smoking has accumulated since the report of the Surgeon General on smoking and health declared that smoking causes lung cancer and heart disease almost 60 years ago, (Bayne-Jones, 1964) the vast majority of studies have been conducted in samples in which the majority or totality of participants identified as White or Caucasian. Currently, Black individuals who smoke are experiencing a disproportionately higher burden of smoking-related morbidity and mortality, compared to White individuals who smoke, (Haiman et al., 2006) including higher rates of lung cancer and mortality, even when the number of cigarettes smoked per day is comparable between races. (Haiman et al., 2006).

Previous research has identified several smoking- and nicotine-related differences between individuals who self-report as Black or White. For example, among people who smoke, Black individuals report smoking fewer cigarettes per day (CPD) than White individuals, (Kabat et al., 1991, Giovino et al., 1994) yet smoke more intensively as determined by higher cotinine levels, greater nicotine intake, and higher carbon monoxide levels even after smoking the same number of cigarettes. (Caraballo et al., 1998, Wagenknecht et al., 1990, Clark et al., 1996, St. Helen et al., 2013, Perez-Stable et al., 1998) Further, Black individuals report having greater difficulty quitting smoking than White individuals (Trinidad et al., 2011) despite no differences in the severity of withdrawal. (Robinson et al., 2014) The rate of nicotine clearance (assessed with the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine)), is slower in Black individuals than White individuals, (Perez-Stable et al., 1998) likely due to functional variants of the nicotine-metabolizing enzyme, CYP2A6. (Liakoni et al., 2019, Nakajima et al., 2006) Black individuals are also more likely than White individuals to smoke mentholated cigarettes, which further decreases the rate of nicotine clearance by inhibition of CYP2A6. (Benowitz et al., 2004) Variations in NMR may be clinically relevant. Studies suggest NMR differentially affects the drive to smoke, measured by CPD, across race; however, NMR and CPD are more tightly linked in prior studies in White compared to Black smokers. (Ross et al., 2016, Ho et al., 2009, Schnoll et al., 2014, Liakoni et al., 2020, Allenby et al., 2016) The NMR is also shown to modulate the severity of nicotine dependence, withdrawal severity, urges to smoke, and subjective and physiological responses to nicotine, but the results have been inconsistent across studies. (Liakoni et al., 2019, Lerman et al., 2006, Lerman et al., 2015, Sofuoglu et al., 2012) Overall, a better understanding of these differences across race, and what systemic factors may have influenced them, may help to explain higher morbidity and mortality from tobacco smoking experienced by Black individuals who smoke.

The present study examined differences in both smoking- and -nicotine-related characteristics in a sample balanced for White and Black participants who enrolled in an intravenous nicotine infusion study. The strength of a nicotine infusion study is that it eliminates much of the individual variability of nicotine intake which happens during smoking, even across individuals who use the same cigarette brand. (Zacny et al., 1987, Ahijevych and Gillespie, 1997, Eissenberg et al., 1999) The outcomes included baseline smoking characteristics as well as self-report and physiological responses to nicotine infusion. Based on the previous studies reporting slower clearance of nicotine in Black individuals compared to White individuals, we hypothesized that individuals in the self-reporting Black group, compared to those in the self-reporting White group, would report less severe urges to smoke and less severe withdrawal following overnight abstinence from smoking, and have blunted subjective and physiological responses to intravenous nicotine. Given the recognized sex differences in smoking behaviors, (Perkins et al., 2006, Pogun and Yararbas, 2009,, DeVito et al., 2014) and racial differences in rates of nicotine clearance (measured by NMR), (Perez-Stable et al., 1998) exploratory analyses were also conducted controlling for sex and NMR to evaluate their impact on these smoking outcomes.

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