Using an established alcohol self-administration paradigm (Anton et al. 2004
; O’Malley et al. 2002
), we found that transdermal nicotine replacement increased the latency to the first drink and consequently appeared to reduce the number of drinks consumed during a 2-h self-administration period, compared to 6 h of nicotine deprivation (i.e., placebo patch), in heavy drinking daily smokers. Although not significantly different, during the active patch condition, a larger proportion of subjects declined all drinks within each hour. When drinks were chosen, however, the number of sips taken per drink, time between sips, and time between drinks were similar for the active and placebo conditions. Thus, we conclude that active nicotine replacement compared to placebo replacement delayed the onset of consumption. Although subjects on nicotine patch compared to placebo patch consumed fewer drinks in the time allotted, it is not possible to determine whether this effect would be maintained, enhanced, or reduced if the time period in which drinks could be chosen was not constrained.
Our drinking outcomes are consistent with Acheson et al. (2006)
findings with women. Although Acheson et al. (2006)
did not evaluate latency to drink, our results regarding reduced drinking (which are secondary to latency to drink) were similar. However, their study found that nicotine patch increased alcohol consumption in males, whereas we found that nicotine patch also reduced drinking by men. A number of procedural differences between the two studies may account for the differential findings. Acheson et al. (2006)
examined light-smoking social drinkers and subjects were tested in small groups, whereas our subjects were heavier drinkers and smokers and were tested individually. In the Acheson et al. (2006)
study, the self-administration phase commenced while the blood alcohol levels produced by the priming drink were ascending, while our self-administration phase began when the blood alcohol levels were descending. Alcohol–nicotine interactions have been shown to be sensitive to ascending and descending limb effects (King and Epstein 2005
; McKee et al. 2006
; Mitchell et al. 1995
), and others have demonstrated that medication effects are sensitive to the interval between the priming drink and the self-administration phase (Anton et al. 2004
). Additional work is needed to delineate how nicotine replacement interacts with temporal effects of the priming drink on inhibiting or promoting further alcohol consumption.
In the period before the priming drink, we found that active nicotine patch in comparison to 6 h of nicotine deprivation (i.e., placebo patch) attenuated tobacco craving for negative reinforcement, consistent with prior research (e.g., Tiffany et al. 2000
). We also found increases in systolic blood pressure and heart rate consistent with the effects of transdermal nicotine replacement on cardiovascular responses (Zevin et al. 1998
). Nicotine withdrawal scores, as measured by the MNWS, were minimal after 6 h of cigarette deprivation and were not influenced by nicotine patch condition (see Pickworth et al. 1996
Our results suggest that treatment with the nicotine patch alters subjective and physiological responses to a standard dose of alcohol. Specifically, after the priming drink, the subjective effects of alcohol (e.g., intoxication ratings) were lower when subjects received active compared to placebo transdermal nicotine replacement. After consuming the priming drink, heart rate was increased and skin temperature was decreased by active nicotine patch. These results are consistent with prior studies which have examined the single and combined effects of alcohol and nicotine on cardiovascular responses (Benowitz et al. 1986
; Michel and Battig 1989
; Perkins et al. 1995
). Pre-alcohol differences in tobacco craving persisted with transdermal nicotine replacement attenuating craving for both positive and negative reinforcement. These findings are counter to those produced by Kouri et al. (2004)
after overnight tobacco abstinence. It is difficult to make cross-study comparisons, as Kouri et al. (2004)
used stronger alcohol priming doses (0.4, 0.7 g/kg) and removed subjects who failed to have craving responses (2 subjects of 12 total subjects) from the analyses. However, others have demonstrated that nicotine replacement and smoked tobacco resulted in lowered intoxication ratings (Madden et al. 1995
; Perkins et al. 1995
) and lowered tobacco craving (Mintz et al. 1991
) after a fixed dose of alcohol.
During the alcohol self-administration period, alcohol craving was found to decrease, while craving for tobacco increased irrespective of patch condition. Active nicotine patch increased stimulation scores as well as heart rate during this period. Others have found that nicotine replacement can attenuate some of the sedating effects produced by alcohol (Perkins et al. 1995
We also conducted exploratory analyses to investigate potential mechanisms underlying any alterations in drinking behavior. Alcohol craving at the end of the priming drink period was negatively associated with latency to consume alcohol and positively associated with the number of drinks consumed in both the nicotine and placebo patch conditions, supporting prior findings (O’Malley et al. 2002
). Additionally, we found that higher tobacco craving for both positive and negative reinforcement was associated with reduced latency to consume alcohol in the placebo patch condition, but not in the nicotine patch condition. Thus, after 6 h of nicotine deprivation, higher tobacco craving responses seen in the placebo patch condition during the priming drink period may underlie the shorter latency to consume alcohol. Similarly, Epstein et al. (2007)
found that tobacco craving for positive reinforcement was associated with blood alcohol levels. While our findings are suggestive of possible mechanisms underlying the initiation of drinking behavior, it should be noted that given our limited sample size, we were unable to conduct a full mediational analysis (see Baron and Kenny 1986
This study has several limitations. First, the sample size was modest and only generalizeable to the population of heavy-drinking daily smokers. Although our sample size was comparable to other laboratory studies examining the effect of nicotine replacement on alcohol responses (e.g., Acheson et al. 2006
; Barrett et al. 2006
; Perkins et al. 1995
), our analyses for gender comparisons were under-powered. Second, only a single priming dose was investigated. However, we have found that an alcohol dose designed to raise BALs by 0.03 g/dl is effective in priming drinking behavior (see O’Malley et al. 2002
; Krishnan-Sarin et al. 2007
). In the current study, we demonstrated that this priming dose was sensitive to the effects of transdermal nicotine on at least delaying further drinking behavior. Third, no alternative beverage was provided during the self-administration phase, and it is unknown whether reductions in alcohol consumption during the transdermal nicotine replacement condition were specific to alcohol. Fourth, only a single dose of transdermal nicotine replacement was investigated. However, the 21-mg/day dose is the dose of transdermal nicotine replacement most commonly used and most likely to be used by heavy drinkers attempting smoking cessation. Nonetheless, from a mechanistic standpoint, it would be worthwhile to conduct a dose-ranging study of transdermal nicotine replacement in this population of heavy-drinking smokers. Further, we did not include a placebo alcohol condition. As a result, we cannot determine whether the observed effects were a product of transdermal nicotine replacement or transdermal nicotine replacement interacting with alcohol. However, our results for the priming drink period (i.e., cardiovascular responses, subjective alcohol effects) were consistent with the only prior study to incorporate an active and placebo alcohol dose to examine the effect of nicotine replacement on responses to a fixed dose of alcohol (Perkins et al. 1995
). Finally, the duration of the session limited our ability to determine whether nicotine also decreases alcohol consumption once it has been initiated or whether the primary effect of nicotine is to delay the initiation of drinking.
In summary, we found that transdermal nicotine, compared to 6 h of nicotine deprivation, reduced subjective and physiological responses to a single alcohol drink, increased latency to initiate drinking, and consequently appeared to decrease the amount of alcohol subsequently consumed. It is possible that nicotine reduced the effects of nicotine deprivation on drinking. Some studies find that nicotine deprivation increases drinking behavior (e.g., Palfai et al. 2000
), and theories of behavioral choice (Vuchinich and Tucker 1988
) suggest that nicotine deprivation may increase the incentive value for alcohol because of the lack of availability of nicotine. In support of this hypothesis, subjects who reported greater tobacco craving in the placebo patch condition exhibited shorter latencies to drink. In addition, because alcohol consumption is a known precipitant of smoking relapse, it is conceivable that nicotine replacement could further facilitate smoking cessation by reducing or delaying drinking. Future laboratory and clinical studies should examine the effect of other smoking cessation pharmacotherapies on alcohol drinking to better understand the value of these treatments for this population of treatment-resistant smokers.