Concurrent Alcohol and Tobacco Dependence

Mechanisms and Treatment

David J. Drobes, Ph.D.

People who drink alcohol often also smoke and vice versa. Several mechanisms may contribute to concurrent alcohol and tobacco use. These mechanisms include genes that are involved in regulating certain brain chemical systems; neurobiological mechanisms, such as cross-tolerance and cross-sensitization to both drugs; conditioning mechanisms, in which cravings for alcohol or nicotine are elicited by certain environmental cues; and psychosocial factors (e.g., personality characteristics and coexisting psychiatric disorders). Treatment outcomes for patients addicted to both alcohol and nicotine are generally worse than for people addicted to only one drug, and many treatment providers do not promote smoking cessation during alcoholism treatment. Recent findings suggest, however, that concurrent treatment for both addictions may improve treatment outcomes. KEY WORDS: comorbidity; AODD (alcohol and other drug dependence); alcoholic beverage; tobacco in any form; nicotine; smoking; genetic linkage; cross-tolerance; AOD (alcohol and other drug) sensitivity; neurotransmitters; brain reward pathway; cue reactivity; social AODU (AOD use); cessation of AODU; treatment outcome; combined modality therapy; literature review

lcohol consumption and tobacco ers who are dependent on nicotine Department of Health and Human use are closely linked behaviors. have a 2.7 times greater risk of becoming Services 1989). The concurrent use of A Thus, not only are people who alcohol dependent than nonsmokers both drugs by pregnant women can drink alcohol more likely to smoke (and (e.g., Breslau 1995). Finally, although also result in more severe prenatal dam- vice versa) but also people who drink the smoking rate in the general popula­ age and neurocognitive deficits in their larger amounts of alcohol tend to smoke tion has gradually declined over the offspring than use of either drug alone more cigarettes. Furthermore, patients past three decades, the smoking rate (e.g., Martin et al. 1997). Furthermore, diagnosed with dependence on one of among alcoholics has remained persis­ the combined use of alcohol and tobacco the drugs also are commonly diagnosed tently high (e.g., Hays et al. 1999). among adolescents is more predictive with dependence on the other drug Concerns about the concurrent use (e.g., Zacny 1990). In fact, smoking of alcohol and tobacco are particularly rates among alcoholics have been esti­ salient given the detrimental impact of DAVID J. DROBES, PH.D., is an associate mated to be as high as 90 percent, with this drug combination on the individ­ professor at the Moffitt Cancer Center & approximately 70 percent of alcoholics ual and on society. For instance, alcohol Research Institute, University of South smoking at least one pack of cigarettes and tobacco when used together increase Florida, Tampa, Florida. per day (National Institute on Alcohol the risk of various forms of cancer (e.g., Abuse and Alcoholism 1998). Similarly, mouth and esophageal cancer), as well Preparation of this article was supported smokers are far more likely to consume as cardiovascular disease, more than by National Institutes of Health grant alcohol than are nonsmokers, and smok­ use of either drug alone (e.g., U.S. AA–11157.

136 Alcohol Research & Health Concurrent Alcohol and Tobacco Dependence

of illicit drug use and various personal between smoking and alcoholism— alcoholism and smoking will be the and social problems among this popu­ that is, genetic factors that increase the establishment of valid and reliable lation than use of either drug alone risk for smoking also increase the risk endophenotypes for these addictive (e.g., Hoffman et al. 2001). for alcoholism and vice versa (e.g., behaviors. An endophenotype is an Given the frequent occurrence and Koopmans et al. 1997; Prescott and objective and measurable characteristic broad implications of concurrent alco­ Kendler 1995). of a person that is thought to be more hol and tobacco use, research and clini­ The relative contributions of genetic directly related to the person’s genetic cal efforts clearly must focus on people and environmental risk factors may makeup (i.e., genotype) than are typical who abuse both drugs. Over the past depend on a person’s age and gender. diagnostic categorizations (e.g., alcohol decade, interactions between alcohol Thus, one study found that the com­ abuse or dependence). Perhaps the and tobacco have indeed received bined risk for alcohol use and smoking best-established example of such an growing attention from both basic and in adolescents was primarily attributable endophenotype in the drug addiction clinical researchers. Alcohol dependence to shared environmental features (e.g., field is the P300 component of the and smoking, individually and in com­ peer influences) whereas in young event-related brain potential (ERP). bination, are complex forms of addic­ adults, this risk was significantly influ­ ERPs are brain waves elicited by a sud­ tive behavior that may be influenced by enced by genetic factors (Koopmans et den stimulus (e.g., a light or sound). a variety of genetic, neurobiological, al. 1997). Laboratory findings suggest One component of an ERP typically conditioning, and psychosocial mecha­ that reduced subjective effects of alcohol can be measured approximately 300 nisms, as described in this article. In (e.g., euphoria or sedation) among milliseconds after the stimulus occurs addition to these mechanisms, the article smokers may underlie this genetic asso­ and is therefore called the P300 signal. discusses issues related to the treatment ciation (Madden et al. 1997), particu­ It is thought to represent cognitive, or of alcoholic smokers. This overview will larly among women. attentional, processing of novel infor­ necessarily be selective; for instance, Recent molecular genetic studies have mation. This P300 signal commonly there is little mention of sociocultural attempted to identify specific genetic is reduced in size in people at risk for (e.g., economic and demographic) fac­ factors that may underlie various forms alcoholism (e.g., Porjesz et al. 1998). tors that also may contribute to con- of addictive behavior. Perhaps the Recent work has also shown that smok­ current use of alcohol and tobacco (see strongest evidence for individual genes ers may exhibit ERPs with a reduced Bobo and Husten 2000). that may contribute to both smoking P300 signal (e.g., Anokhin et al. 2000). and alcoholism involves the dopamin­ By replicating these findings and identify­ ergic reward system. Dopamine is a ing additional valid endophenotypes Mechanisms Underlying brain chemical (i.e., neurotransmitter) for alcoholism and smoking, researchers Combined Alcohol and that mediates the communication among hope to detect stronger relationships Tobacco Use brain cells in certain brain regions. between these forms of addictive behav­ Some of these brain regions play a role ior and certain genes. In addition, these in the pleasant (i.e., rewarding) effects studies may lead to a fuller understand­ Genetic Factors of drugs such as alcohol and nicotine. ing of the mechanisms through which To exert its effects, dopamine released these genes influence behavior. The importance of genetic influences by one brain cell interacts with specific on both alcoholism and smoking has protein molecules (i.e., receptors) on Neurobiological Mechanisms gained widespread recognition over the the surface of neighboring cells, and past decade. Using behavioral genetic this interaction causes a biochemical Several neurobiological mechanisms methods, such as twin and adoption reaction in those cells. Some evidence may underlie the strong relationship studies, as well as genetic epidemiologi­ suggests that certain variants of genes between alcohol and tobacco use. Both cal approaches, researchers have estab­ that regulate the activity of dopamine the ability of one drug to reduce the lished that both alcoholism and smoking or its receptors may be related to the effects of the other drug (i.e., cross- have strong heritable components (e.g., risk of excessive alcohol consumption tolerance) and the ability of one drug Prescott and Kendler 1995). In general, or smoking (e.g., Lerman et al. 1999; to increase the effects of the other drug heritability, which estimates the propor­ Li 2000). The results at this stage are (i.e., cross-reinforcement) may play tion of variability within an observed merely suggestive, but the application important roles in mediating this characteristic that can be attributed to of molecular genetic research techniques relationship (Pomerleau 1995). Such genetic factors, appears to be slightly to studies of complex behaviors such as processes could act immediately when higher for smoking-related variables alcohol and nicotine addiction is pro­ alcohol and nicotine are taken together, (e.g., smoking initiation and smoking gressing rapidly and may yield impor­ or they could involve changes in nerve persistence) than for alcoholism (e.g., tant findings within the next decade. cell function that occur over time with Heath and Madden 1995). Moreover, One development that most likely repeated usage of either one or both several researchers have indicated that a will accelerate researchers’ understand­ drugs. It is also possible that the two substantial shared genetic risk exists ing of genetic factors contributing to drugs when taken together create a

Vol. 26, No. 2, 2002 137 combined reward effect that is qualita­ supported by findings that nicotine notably the ventral tegmental area, the tively different from the effects of administration directly increases alcohol nucleus accumbens, and the prefrontal either drug taken alone. consumption in animal models; this cortex (see figure). Both alcohol and The development of tolerance (and, effect appears to be mediated through nicotine directly activate dopamine­ by extension, cross-tolerance) to both receptors for nicotine in the brain (e.g., releasing nerve cells within the ventral pleasurable and aversive drug effects is Lê et al. 2000). Similarly, earlier labora­ tegmental area, ultimately leading to thought to support the development or tory studies with humans showed that dopamine release in the nucleus accum­ maintenance of an addiction. Thus, alcohol consumption increased the bens and prefrontal cortex. These path- tolerance to pleasurable drug effects amount and rate at which participants ways appear to become sensitized with requires the user to consume increasing smoked cigarettes (e.g., Mello et al. 1980). repeated use of either drug, a process drug amounts to achieve the desired As mentioned earlier, components called neuroadaptation (e.g., Robinson rewarding effects. Conversely, tolerance of the brain signaling system involving and Berridge 1993). One theoretical to aversive drug effects enables the user the neurotransmitter dopamine may model called the incentive sensitization to experience pleasant effects while not play a role in the genetic basis for both model (Robinson and Berridge 1993) experiencing the initial aversive drug alcohol and tobacco addiction. One brain posits that stimuli which have been closely effects. Experimental evidence of cross- system that uses dopamine as a primary associated with prior drug use (e.g., tolerance between alcohol and nicotine neurotransmitter is the mesolimbic the sight of a beer bottle or a pack of comes from several lines of research. dopamine system, which has been cigarettes) gradually become more For instance, mice bred for different implicated in the motivation to obtain powerful (i.e., gain incentive salience) levels of sensitivity to certain alcohol various rewards, including alcohol and because of this sensitization. According effects (e.g., either extremely high or nicotine (e.g., Wise 1988). This system to this model, both alcohol- and nicotine- extremely low sensitivity to alcohol’s encompasses several brain regions, most associated stimuli may activate the sedative effects) exhibit corresponding changes in their behavioral and physio­ logical responses to nicotine (Collins 1990). Also, mice that chronically receive nicotine (via intravenous infu­ Prefrontal sion) or alcohol (via a liquid diet) show cortex cross-tolerance to a drug-induced decrease in body temperature when the alternate drug is given (Collins et al. 1988). Finally, in a recent study, female adolescent mice treated with alcohol for 4 days displayed cross-tolerance to nicotine’s effects on body temperature and activity when they were tested 30 days later (Lopez et al. 2001). Extending these demonstrations of cross-tolerance from animal models to the phenomenon of concurrent alcohol and nicotine dependence in humans, one could hypothesize that people who Nucleus regularly consume both alcohol and accumbens nicotine may develop dependence on both drugs more rapidly than if they Ventral consumed only one drug, because the tegmental rate of tolerance development would be area increased. Alternatively, smoking may promote alcohol consumption through an immediate (i.e., acute) form of Dopaminergic pathways in the brain, including the mesolimbic dopaminergic system, cross-tolerance. This means that smokers which consists of the ventral tegmental area, the nucleus accumbens, and the prefrontal may be able to consume more alcohol cortex. This system has been implicated in the motivation to obtain various rewards, because nicotine exerts a stimulatory including the positive reinforcement of alcohol and nicotine. effect that can directly counteract both the sedative properties of alcohol and SOURCE: Adapted from Heimer, L. The Human Brain and Spinal Cord: Functional Neuroanatomy and Dissection Guide. 2d ed. New York: Springer-Verlag, 1995. the cognitive deficits associated with alcohol intoxication. This hypothesis is

138 Alcohol Research & Health Concurrent Alcohol and Tobacco Dependence

mesolimbic dopaminergic system in holics and smokers, respectively (for a a standard dose of alcohol. The study people who frequently use both drugs, review, see Carter and Tiffany 1999). found that after the men had received thereby increasing the overall vulnera­ Several human laboratory studies a standard dose of alcohol, those who bility to an addiction in those people. suggest a role for cue conditioning in had been allowed to smoke before Another brain neurotransmitter sys­ the close association between alcohol working on the task worked harder to tem that may be involved in alcohol- use and smoking. For instance, one study obtain more alcohol than did men who tobacco interactions is the endogenous showed that the severity of nicotine had been deprived of nicotine overnight opiate system. Endogenous opiates are dependence among alcoholic smokers (Perkins et al. 2000). This effect was molecules produced naturally by the was related to the strength of alcohol not observed when the men were tested body that have effects similar to opiates cravings elicited by alcohol cues (Abrams before they had received the alcohol, (e.g., morphine). Alcohol appears to et al. 1992). Other findings have demon­ indicating that when it is combined stimulate the endogenous opiate system, strated that alcohol cues can simultane­ with alcohol consumption, nicotine which may contribute to alcohol’s plea­ ously increase smoking urges and alcohol consumption can increase the motiva­ surable effects. Clinical and laboratory- urges among alcoholic smokers (e.g., tion to drink alcohol. This interaction based studies have shown that agents that Gulliver et al. 1995; Rohsenow et al. between nicotine and alcohol consump­ block the effects of endogenous opiates 1997). Overall, laboratory findings sug­ tion was not observed in women, sug­ (i.e., opiate antagonists) can reduce alcohol gest that substantial overlap between gesting that important gender differences consumption (see Anton 2001). The alcohol and smoking cues may exist may exist with respect to pharmacolog­ effects of nicotine may also be partly in promoting drug cravings and drug ical and motivational influences on mediated through this opiate brain sys­ consumption—that is, both types of alcohol and tobacco use. tem, although studies on the effects of cues may elicit cravings and consump­ Research has not yet directly exam­ opiate antagonists on smoking behav­ tion of either drug. ined acute nicotine effects on reactivity ior and other nicotine-related responses Even the administration of alcohol to alcohol cues, nor has the combined have provided equivocal results to date. or nicotine can serve as a conditioned impact of alcohol and nicotine admin­ pharmacological or sensory cue. Accord­ istration on cue-elicited craving, drug Conditioning Mechanisms ingly, research that evaluates the effects effects, or drug consumption been of the administration of either drug on studied extensively (for a review, see It is a common observation that people responding to the other drug can help Perkins 1997). Overall, the available who drink alcohol and smoke tend to determine the role of conditioning fac­ research suggests that alcohol and nico­ engage in these behaviors in particular tors in concurrent alcohol and tobacco tine can have interactive effects on the situations (e.g., in a bar or at a party) use. For instance, several early studies motivation to consume either drug. and contemporaneously. Furthermore, demonstrated that alcohol consump­ Further research is needed to obtain a studies have confirmed that relapse to tion can promote smoking (e.g., Mello better understanding of the interactive smoking following smoking cessation is et al. 1980). Furthermore, a more effects of various pharmacological and strongly associated with alcohol consump­ recent study of nonalcoholic smokers cue manipulations on cravings for and tion (e.g., Brandon et al. 1990). These showed that cue-elicited cravings for consumption of alcohol and nicotine. observations support the hypothesis nicotine increased when the partici­ that alcohol and smoking may become pants first consumed alcohol (Burton Psychosocial Factors associated through a process called cue and Tiffany 1997). However, craving conditioning because of the frequent increases in this study were not specific Even at the earliest stages of drug use, concurrent use of the two drugs. In to smoking-related cues, which implies which often occurs during adolescence, general, conditioning models of addic­ that alcohol consumption leads to a more common psychosocial factors may pro- tion suggest that cues previously paired general increase in cravings to smoke. mote the use of both alcohol and with drug use (e.g., the sight of a liquor Finally, another laboratory study inves­ tobacco. For instance, personality char­ bottle or the smell of a lighted cigarette) tigated how hard people who had been acteristics that remain stable throughout will elicit conditioned responses, includ­ allowed to smoke or who were smoking a person’s life often have been impli­ ing cravings and associated physiological deprived would work on a computer cated as playing a role in the initiation activity. These cue-elicited cravings and task to receive alcohol.1 Each participant of both alcohol and tobacco use (e.g., physiological reactions, in turn, can was tested in two separate sessions involv­ Flay et al. 1995). These characteristics motivate ongoing drug use and increase ing either ad lib smoking or smoking may include sensation seeking, impul­ the probability of relapse among people deprivation prior to the session. During sivity, compulsiveness, and neuroticism who are abstinent (e.g., Drobes and each session, the task was performed (i.e., trait anxiety). Such a role of per­ Tiffany 1997). Numerous laboratory twice, both before and after receiving sonality characteristics in determining studies have supported this view, demon­ alcohol consumption and smoking is strating that various alcohol and smoking- not incompatible with the genetic 1The effort a person puts into the task (i.e., how hard he or related cues can elicit cravings and she works) in order to receive alcohol is considered an mechanisms discussed above. Indeed, physiological responses among alco­ indication of his or her motivation to drink. many of these personality variables are

Vol. 26, No. 2, 2002 139 themselves heritable, and the genetic logical disorders, particularly various smoking is considered a risk factor for risk for alcohol use and smoking may affective (e.g., depression) and anxiety alcohol relapse (e.g., Johnson and be mediated partly through these per­ disorders. People with such disorders Jennison 1992). Similarly, nicotine sonality traits. presumably use alcohol and tobacco to dependence and the experience of nico­ Another important psychosocial self-medicate their affective symptoms tine withdrawal appear to be more severe influence on the initiation of combined through the direct stimulatory or stress- in smokers with a history of alcohol alcohol and tobacco use stems from reducing drug effects. The order in dependence (e.g., Marks et al. 1997), family modeling. Thus, numerous stud­ which the psychological disorders and and rates of successful smoking cessation ies show that adolescents who are exposed alcohol and tobacco use develop, how- are lower among smokers with past or to older family members who smoke ever, is not always clear and may vary current alcohol problems (e.g., DiFranza and drink are more liable to engage in for different people. Thus, alcohol and and Guerrera 1990). Consequently, these behaviors than are adolescents with- tobacco use may represent a form of improvements in treatment outcomes out such family members (e.g., Bobo (maladaptive) coping with a preexisting among smoking alcoholics remain an and Husten 2000). Accordingly, com­ psychological disorder or they may pre- important challenge for the future. bined alcohol and tobacco use may cede or exacerbate the development of Until recently, treatment providers become a self-propagating cycle across psychopathology. Finally, alcohol and generally believed that smoking cessation familial generations independent of any tobacco use may be part of a broader was contraindicated during alcoholism direct genetic influence. constellation of symptoms associated treatment for several reasons. Some Other important modeling influences with the comorbid condition. Further alcoholism program philosophies con­ for alcohol use and smoking behaviors long-term studies with alcohol and sidered smoking a relatively benign are likely to be peer related. As mentioned tobacco users who exhibit or later develop problem compared with alcohol depen­ earlier, the impact of genetic factors on various forms of psychopathology may dence. Another reason was the fear that alcohol use and smoking may be some- clarify the causal pathways underlying smoking cessation would lead to poorer what less pronounced during adolescence these relationships. alcoholism treatment outcomes, either than during early adulthood (Koopmans Several other psychosocial variables by increasing the clients’ stress or decreas­ et al. 1997). This observation is consis­ have been tied theoretically or empiri­ ing the effort that clients could devote tent with findings supporting a strong cally to the risk of combined alcohol to achieving abstinence from alcohol role of parental and peer influences and tobacco use in various situations. (e.g., Bobo and Gilchrist 1983). Finally, (e.g., Hoffman et al. 2001). Furthermore, These variables include life stressors many alcoholism treatment providers both alcohol use and smoking commonly (e.g., loss of a job or a loved one), social believed that smoking serves as an serve as outlets for adolescent rebellious­ support, self-efficacy, coping skills, and effective coping tool for dealing with ness, and both behaviors are associated expectancies (i.e., expectations about alcohol cravings and with the stress with illicit drug use and other problems the effects of alcohol and tobacco on associated with alcohol withdrawal or among adolescents (Hoffman et al. 2001). behavior). These and other psychosocial protracted abstinence. Consequently, Temporary psychological states in factors most likely interact with genetic, these providers were unwilling to take otherwise mentally healthy people also biological, and conditioning mechanisms away that coping tool. may contribute to the ongoing use of in unique ways throughout each person’s Despite longstanding fears from alcohol and tobacco. For example, both history of alcohol and nicotine use, treatment providers that smoking ces­ laboratory and field studies have found including initiation, maintenance, ces­ sation would interfere with alcoholism that situational stress and negative emo­ sation, and relapse, to determine that treatment, there are several reasons to tional states (e.g., anxiety and depression) person’s risk of alcohol and nicotine anticipate that combined treatment can serve as cues that elicit alcohol or abuse and dependence. for both addictions may lead to more tobacco craving or consumption of these favorable outcomes for both drugs. drugs in active drinkers or smokers (e.g., First, at a neurobiological level, alcohol Tiffany and Drobes 1990). People also Treatment of Smoking in and nicotine act, at least in part, on the may use alcohol and nicotine to allevi­ Alcoholics same brain pathways involved in reward ate stress or tension. Indeed, both drugs and craving. Therefore, it may be advan­ exhibit extreme versatility in their abil­ For people addicted to alcohol and nico­ tageous to cease using both drugs to ity to regulate mood, in that they may tine, outcomes during treatment for reverse the effects on these pathways. be used either to help a person relax alcoholism, smoking, or both are often One important caveat here is that nico­ or to stimulate or energize the person. less favorable than for people addicted tine appears to serve an acute protective Alcohol and smoking also both fre­ to only one drug. For example, alcoholics function concerning certain neurotoxic quently serve as “social lubricants” in who smoke generally are less successful effects of alcohol withdrawal. Therefore, social situations. in achieving and maintaining sobriety extreme caution must be exercised in Rates of alcohol and tobacco con­ than are nonsmoking alcoholics (e.g., determining the optimal sequence of sumption are disproportionately high Hughes 1995). Furthermore, in alcoholics drug removal for patients desiring among people with comorbid psycho- treated for both addictions, relapse to treatment for both addictions. Second,

140 Alcohol Research & Health Concurrent Alcohol and Tobacco Dependence

as discussed above, continued smoking logical treatments that may be effective programs for people dependent on both or alcohol use may elicit or exacerbate in the treatment of alcoholism and alcohol and nicotine will be greatly craving for the other drug. Third, behav­ smoking. For instance, as mentioned enhanced if such programs are based ioral treatments based on coping-skill earlier, endogenous opioids play a role on a fundamental understanding of attainment may be more effective when in mediating alcohol’s effects, and opi­ mechanisms that promote this dual developing skills are generalized to both ate antagonist medications (e.g., nal­ addiction. Similarly, basic researchers types of addictive behavior. For instance, trexone and nalmefene) can be effective should consider the clinical phenomenol­ people may be able to obtain more for the treatment of alcoholism. Recent ogy of concurrent alcohol and tobacco practice at using coping skills if they studies have suggested that opiate path- use as a guiding force for investigating apply them to both alcohol consumption ways may also be involved in nicotine dual addictions in the laboratory. and smoking. And fourth, a treatment dependence (e.g., Pomerleau 1998). approach that encourages an overall However, the usefulness of opiate milieu of healthy lifestyle changes would antagonists as a treatment for smokers References be more generally consistent with absti­ in general or alcoholic smokers in par­ nence from both drugs. ticular remains to be determined. ABRAMS, D.B.; ROHSENOW, D.J.; NIAURA, R.S.; ET AL. Smoking and treatment outcome for alcoholics: Another reason to support concurrent Effects on coping skills, urge to drink, and drinking treatment for smoking and alcoholism rates. Behavior Therapy 23:283–297, 1992. is that more alcoholics will die from Conclusions smoking-related illnesses than from ANOKHIN, A.P.; VEDENIAPIN, A.B.; SIREVAAG, E.J.; ET AL. The P300 brain potential is reduced in alcohol-related causes (e.g., Hurt et al. Alcohol and tobacco use are highly cor­ smokers. Psychopharmacology 149:409–413, 2000. 1996). The numerous problems associ­ related behaviors. For example, people ated with smoking are well docu­ who drink are very likely to smoke and ANTON, R.F. Pharmacologic approaches to the management of alcoholism. Journal of Clinical mented, and most alcoholics entering vice versa; furthermore, people who are Psychiatry 62 (Suppl. 20):11–17, 2001. treatment are aware of these problems dependent on alcohol also are frequently and appear quite willing to receive con- dependent on nicotine. The costs of the BOBO, J.K., AND GILCHRIST, L.D. Urging the alco­ holic client to quit smoking cigarettes. Addictive current smoking cessation treatment combined use of these drugs to both Behaviors 8:297–305, 1983. (e.g., Saxon et al. 1997). Even without the individual and society are substan­ formal smoking cessation treatment, tial. Several potential mechanisms may BOBO, J.K., AND HUSTEN, C. Sociocultural influences on smoking and drinking. Alcohol Research & Health smoking rates appear to decrease and promote the combined use of alcohol 24:225–232, 2000. the motivation to quit smoking and nicotine. Although researchers have increases following successful alco­ made substantial progress in delineating BRANDON, T.H.; TIFFANY, S.T.; OBREMSKI, K.M.; AND BAKER, T.B. Postcessation cigarette use: The pro­ holism treatment (e.g., Monti et al. factors that may underlie alcohol and cess of relapse. Addictive Behaviors 15:105–114, 1990. 1995). Researchers have begun to eval­ tobacco comorbidity, several research uate the effectiveness of explicit smok­ gaps remain. For example, investigators BRESLAU, N. Psychiatric comorbidity of smoking ing cessation attempts during alco­ and clinicians still need to fully eluci­ and nicotine dependence. Behavior Genetics 25:95– 101, 1995. holism treatment as well as the impact date and consider the roles of various of such attempts on the outcome of the genetic, neurobiological, conditioning, BURTON, S.M., AND TIFFANY, S.T. The effect of alcoholism treatment (e.g., Martin et and psychosocial factors in developing alcohol consumption on craving to smoke. Addiction al. 1997). Findings to date generally do a more thorough understanding of this 92:15–26, 1997. not confirm the traditional notion that dual addiction. Important potential CARTER, B.L., AND TIFFANY, S.T. Meta-analysis of only one addiction should be treated at gender differences in how these mecha­ cue-reactivity in addiction research. Addiction 94:327– a given time. It is still too early to tell nisms operate also merit further research, 340, 1999. what treatment configuration will be as do potential differences in the treat­ COLLINS, A.C. Interactions of ethanol and nicotine most effective for smoking alcoholics. ment of male and female alcoholic at the receptor level. In: Galanter, M., ed., Recent Developments in Alcoholism: Vol. 8. Combined In concert with recent advances in smokers. Alcohol and Other Drug Dependence. New York: their understanding of neurobiological Despite long-held views that smoking Plenum Press, 1990. pp. 221–231. factors that contribute to the develop­ cessation attempts should be deferred ment and maintenance of addictive or discouraged among alcoholics under- COLLINS, A.C.; BURCH, J.B.; DE FIEBRE, C.M.; AND MARKS, M.J. Tolerance to and cross tolerance behavior, including alcoholism and going treatment, researchers have begun between ethanol and nicotine. Pharmacology, smoking, researchers have been explor­ to evaluate treatment programs designed Biochemistry, and Behavior 292:365Ð373, 1988. ing potentially useful pharmacological to address alcohol and nicotine depen­ DIFRANZA, J.R., AND GUERRERA, M.P. Alcoholism treatments that may benefit various dence simultaneously. Early results of and smoking. Journal of Studies on Alcohol 51:130– types of addiction. Because it is likely these analyses are promising, although 135, 1990. that alcohol and nicotine act at least additional research is clearly needed to DROBES, D.J., AND TIFFANY, S.T. Induction of partially through the same brain reward optimize treatment outcomes and to smoking urge through imaginal and in vivo proce­ pathways, it is reasonable to expect address important health and safety con­ dures: Physiological and self-report manifestations. some overlap in the types of pharmaco­ cerns. The development of treatment Journal of Abnormal Psychology 106:15–25, 1997.

Vol. 26, No. 2, 2002 141 FLAY, B.R.; PETRAITIS, J.; AND HU, F.B. Theory of LI, T.-K. Pharmacogenetics of responses to alcohol POMERLEAU, O.F. Endogenous opioids and triadic influence: Preliminary evidence related to and genes that influence alcohol drinking. Journal of smoking: A review of progress and problems. alcohol and tobacco use. In: Fertig, J.B., and Allen, Studies on Alcohol 61:5–12, 2000. Psychoneuroendocrinology 23:115–130, 1998. J.P., eds. Alcohol and Tobacco: From Basic Science to Clinical Practice. National Institute on Alcohol LOPEZ, M.F.; WHITE, N.M.; AND RANDALL, C.L. PORJESZ, B.; BEGLEITER, H.; REICH, T.; ET AL. Abuse and Alcoholism Research Monograph No. Alcohol tolerance and nicotine cross-tolerance in Amplitude of visual P3 event-related potential as a 30. NIH Pub. No. 95–3931. Washington, DC: adolescent mice. Addiction Biology 6:119–127, phenotypic marker for a predisposition to alcoholism: Government Printing Office, 1995. pp. 37–57. 2001. Preliminary results from the COGA Project. Alcoholism: Clinical and Experimental Research 22: MADDEN, P.A.F.; HEATH, A.C.; AND MARTIN, N.G. GULLIVER, S.B.; ROHSENOW, D.J.; COLBY, S.M.; 1317–1323, 1998. ET AL. Interrelationship of smoking and alcohol Smoking and intoxication after alcohol challenge in dependence, use and urges to use. Journal of Studies women and men: Genetic influences. Alcoholism: PRESCOTT, C.A., AND KENDLER, K.S. Genetic and on Alcohol 56:202–206, 1995. Clinical and Experimental Research 21:1732–1741, 1997. environmental influences on alcohol and tobacco dependence among women. In: Fertig, J.B., and HAYS, J.T.; SCHROEDER, D.R.; OFFORD, K.P.; ET MARKS, J.L.; HILL, E.M.; POMERLEAU, C.S.; ET AL. Allen, J.P., eds. Alcohol and Tobacco: From Basic AL. Response to nicotine dependence treatment in Nicotine dependence and withdrawal in alcoholic Science to Clinical Practice. National Institute on smokers with current and past alcohol problems. and nonalcoholic ever-smokers. Journal of Substance Alcohol Abuse and Alcoholism Research Monograph Annals of Behavioral Medicine 21:244–250, 1999. Abuse Treatment 14:521–555, 1997. No. 30. NIH Pub. No. 95–3931. Washington, DC: HEATH, A.C., AND MADDEN, P.A.F. Genetic influ­ MARTIN, J.E.; CALFAS, K.J.; PATTEN, C.A.; ET AL. Government Printing Office, 1995. pp. 59–87. ences on smoking behavior. In: Turner, J.R; Cardon, Prospective evaluation of three smoking interven­ L.R.; and Hewitt, J.K., eds. Behavior Genetic Ap­ tions in 205 recovering alcoholics: One-year results ROBINSON, T.E., AND BERRIDGE, K.C. The neural proaches in Behavioral Medicine. New York: Plenum of Project SCRAP-Tobacco. Journal of Consulting basis of drug craving: An incentive-sensitization Press, 1995. pp. 45–66. and Clinical Psychology 65:190–194, 1997. theory of addiction. Brain Research Reviews 18: 247–291, 1993. HOFFMAN, J.H.; WELTE, J.W.; AND BARNES, G.M. MELLO, N.K.; MENDELSON, J.H.; SELLERS, M.L.; Co-occurrence of alcohol and cigarette use among ROHSENOW, D.J.; MONTI, P.M.; COLBY, S.M.; ET AND KUEHNLE, J.C. Effect of alcohol and marihuana adolescents. Addictive Behaviors 26:63–78, 2001. on tobacco smoking. Clinical Pharmacology and AL. Effects of alcohol cues on smoking urges and topography among alcoholic men. Alcoholism: HUGHES, J.R. Clinical implications of the associa­ Therapeutics 27:202–209, 1980. tion between smoking and alcoholism. In: Fertig, Clinical and Experimental Research 21:101–107, J.B., and Allen, J.P., eds. Alcohol and Tobacco: MONTI, P.M.; ROHSENOW, D.J.; COLBY, S.M.; 1997. From Basic Science to Clinical Practice. National AND ABRAMS, D.B. Smoking among alcoholics dur­ ing and after treatment: Implications for models, SAXON, A.J.; MCGUFFIN, R.; AND WALKER, R.D. Institute on Alcohol Abuse and Alcoholism Research An open trial of transdermal nicotine replacement Monograph No. 30. NIH Pub. No. 95–3931. treatment strategies, and policy. In: Fertig, J.B., and therapy for smoking cessation among alcohol- and Washington, DC: Government Printing Office, Allen, J.P., eds. Alcohol and Tobacco: From Basic Science drug-dependent inpatients. Journal of Substance 1995. pp. 171–185. to Clinical Practice. National Institute on Alcohol Abuse and Alcoholism Research Monograph No. Abuse Treatment 14:333–337, 1997. HURT, R.D.; OFFORD, K.P.; CROGHAN, I.T.; ET 30. NIH Pub. No. 95–3931. Washington, DC: TIFFANY, S.T., AND DROBES, D.J. Imagery and AL. Mortality following inpatient addictions treat­ Government Printing Office, 1995. pp. 187–206. ment. Role of tobacco use in a community-based smoking urges: The manipulation of affective con- cohort. JAMA: Journal of the American Medical National Institute on Alcohol Abuse and Alcoholism tent. Addictive Behaviors 15:531–539, 1990. Association 275:1097–1103, 1996. (NIAAA). Alcohol and Tobacco. Alcohol Alert U.S. Department of Health and Human Services (No. 39). Rockville, MD: NIAAA, 1998. JOHNSON, K.A., AND JENNISON, K.M. The drinking- (DHHS). Reducing the Health Consequences of smoking syndrome and social context. International PERKINS, K.A. Combined effects of nicotine and Smoking: 25 Years of Progress. A Report of the Journal of the Addictions 27:749–792, 1992. alcohol on subjective, behavioral and physiological Surgeon General. DHHS, Public Health Service, responses in humans. Addiction Biology 2: Centers for Disease Control, Center for Chronic KOOPMANS, J.R.; VAN DOORNEN, L.J.; AND 255– 268, 1997. Disease Prevention and Health Promotion, Office BOOMSMA, D.I. Association between alcohol use on Smoking and Health. DHHS Publication No. and smoking in adolescent and young adult twins: PERKINS, K.A.; FONTE, C.; AND GROBE, J.E. Sex (CDC) 89–8411. Washington, DC: Government A bivariate genetic analysis. Alcoholism: Clinical and differences in the acute effects of cigarette smoking Printing Office, 1989. Experimental Research 21:537–546, 1997. on the reinforcing value of alcohol. Behavioural WISE, R.A. The neurobiology of craving: Implications LÊ, A.D.; CORRIGALL, W.A.; WATCHUS, J.; ET AL. Pharmacology 11:63–70, 2000. Involvement of nicotine receptors in alcohol self- for the understanding and treatment of addiction. POMERLEAU, O.F. Neurobiological interactions of administration. Alcoholism: Clinical and Experimental Journal of Abnormal Psychology 97:118–132, 1988. alcohol and nicotine. In: Fertig, J.B., and Allen, Research 24:155–163, 2000. J.P., eds. Alcohol and Tobacco: From Basic Science ZACNY, J.P. Behavioral aspects of alcohol-tobacco LERMAN, C.; CAPORASO, N.E.; AUDRAIN, J.; ET AL. to Clinical Practice. National Institute on Alcohol interactions. In: Galanter, M., ed. Recent Developments Evidence suggesting the role of specific genetic fac­ Abuse and Alcoholism Research Monograph No. in Alcoholism: Vol. 8. Combined Alcohol and Other tors in cigarette smoking. Health Psychology 18:14– 30. NIH Pub. No. 95–3931. Washington, DC: Drug Dependence. New York: Plenum Press, 1990. 20, 1999. Government Printing Office, 1995. pp. 145–158. pp. 205–219.

142 Alcohol Research & Health