Nicotine &Nicotine Tobacco & Research Tobacco Research Advance Access published July 25, 2014
Original Investigation
Drug Use, Abuse, and Dependence and the Persistence of Nicotine Dependence Renee D. Goodwin PhD, MPH1,2, Christine E. Sheffer PhD3, Hayley Chartrand MA4, Joanna Bhaskaran BSc (Hons)4, Carl L. Hart PhD5,6, Jitender Sareen4,7,8, James Bolton4,7,8 1Department of Psychology, Queens College and Graduate Center, City University of New York, Flushing, NY; 2Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; 3Sophie Davis School of Biomedical Education, City University of New York, New York, NY; 4Department of Psychology, University of Manitoba, Winnipeg, Manitoba, Canada; 5Department of Psychology, Columbia University, New York, NY; 6Department of Psychiatry, Columbia University, New York, NY; 7Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada; 8Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
Received July 29, 2013; accepted June 11, 2014
Abstract Introduction: Illicit drug use and nicotine dependence (ND) frequently cooccur. Yet, to date, very few studies have examined the role of alcohol and illicit drug use in ND persistence. The objectives of this study were to investigate the relationships between specific classes of drug use, abuse, and dependence and the persistence of ND over time among adults in the United States. Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a national survey of 34,653 U.S. adults interviewed in 2001–2002 and reinterviewed 3 years later. Logistic regression analyses were used to investigate the relations between various classes of drug use, abuse, and dependence among adults with ND at Wave 1 and odds of persistent ND at Wave 2. Analyses were adjusted for differences in demographic characteristics, mood and anxiety disorders, alcohol use disorders, and other substance use disorders. Results: Lifetime drug use was not associated with significantly increased likelihood of persistent ND. Sedative abuse was associated with increased odds of nicotine persistence, but no other types of drug abuse were predictive of ND persistence, after adjusting for demographics, mood/anxiety, alcohol use disorders. All types of drug dependence were associated with persistence of ND; the strongest associations emerged between opioid and tranquilizer dependence and persistent ND while the associations between cannabis and cocaine dependence were no longer significant after adjusting for mood/anxiety disorders. Conclusions: Clinicians should take care to evaluate the presence and/or a history of drug dependence among patients seeking treatment for smoking cessation. These data suggest that a history of substance dependence predicts increased vulnerability to persistent ND.
Introduction The prevalence of smoking among individuals who use illicit drugs remains remarkably high despite dramatic decreases in the prevalence among other groups. Consequently, the tobacco-related mortality rate among those with substance use disorders (SUDs) is twice that of the general population and greater than the mortality rate from all other drugs combined (Hurt et al., 1996; Mokdad, Marks, Stroup, & Gerberding, 2004). Nicotine, the major psychoactive drug in tobacco, shares similar addictive biochemical and behavioral processes with illicit drugs (US Department of Health and Human Services, 2011) suggesting a close relationship between drug and nicotine dependence, but the nature of this relationship is
likely to be multifaceted and remains unclear. Understanding the long-term persistence of nicotine dependence among individuals who use drugs has implications for the identification of new therapeutic targets in treatment of nicotine dependence and drug use, as well as the development of policies that support abstinence in this group. There is a well-documented relationship between cigarette smoking and drug use (Belanger et al., 2011). A large number of studies have documented links between smoking and initiation of drug use conceptualizing smoking as a “gateway” to harder drug use (Belanger et al., 2011; Biederman et al., 2006; Gray et al., 2011; Kandel, 2002; Log et al., 2011; Timberlake et al., 2007). In contrast, relativity little is known about associations among drug use and the persistence of smoking, which
doi:10.1093/ntr/ntu115 © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: [email protected].
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Corresponding Author: Renee D. Goodwin, PhD, MPH, 65-30 Kissena Boulevard, Flushing, Queens 11367, USA. Telephone: 718-997-3247; Fax: 718 -997-3257; E-mail: [email protected]
Drugs and persistence of nicotine dependence
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and drug use, we hypothesized that drug use of all types and severities would be associated with persistent nicotine dependence, consistent with the maintenance of an impaired dopaminergic reward system and sensitization of the common pathway for addiction. The prevalence of smoking is strongly associated with factors other than drug use including age, sex, and income (Agrawal et al., 2008; Barbeau et al., 2004; Centers for Disease Control and Prevention, 2011; Fagan, Shavers, Lawrence, Gibson, & O’Connell, 2007; Fagan, Shavers, Lawrence, Gibson, & Ponder, 2007; Fagan, Augustson, et al., 2007; Ferguson, Bauld, Chesterman, & Judge, 2005; Reid, Hammond, Boudreau, Fong, & Siahpush, 2010; Wetter et al., 2005) as well as anxiety, mood, and alcohol use disorders (Grant, Stinson, Dawson, et al., 2004; Grant, Stinson, Hasin, et al., 2004; Moylan, Jacka, Pasco, & Berk, 2012; Strong et al., 2010).
Methods Data Sources and Sample The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (Grant et al., 2009; Grant, Stinson, Dawson, et al., 2004) is a nationally representative longitudinal survey of the adult noninstitutionalized, civilian population of the 50 U.S. States conducted by the U.S. Census Bureau under the direction of the National Institute on Alcohol Abuse and Alcoholism. Wave 1 was conducted in 2001–2002 with a sample of 43,093 respondents age 18 and over (Grant, Moore, Shephard, & Kaplan, 2003), Wave 2 was a 3-year prospective follow-up comprising 34,653 of the Wave 1 respondents, representing a response rate of 86.7% of eligible respondents (Grant & Kaplan, 2005). In combination with the Wave 1 response rate of 81%, the cumulative response rate for Wave 2 is 70.2%. Trained lay interviewers with at least 5 years of experience conducted face-to-face assessments using computer-assisted software. Informed consent was obtained from all participants before beginning the interviews. Detailed descriptions of methodology, sampling, and weighting procedures have been reported elsewhere (Grant & Kaplan, 2005; Grant et al., 2003). For this study, the sample consisted of individuals who met criteria for past-year nicotine dependence at Wave 1 and who also responded to the Wave 2 survey (n = 4,017). Measures Diagnoses were assessed with the AUDADIS-IV. This instrument was specifically designed for experienced lay interviewers and was developed to advance measurement of drug use and mental disorders in large-scale surveys. Nicotine dependence was assessed in a unique module separate from the assessment of other drug use. To that end, the AUDADIS-IV used an extensive list of over 40 questions to assess nicotine dependence and obtains extensive information on time frames of nicotine use and dependence. Diagnoses were made according to the DSM-IV criteria (Schmitz et al., 2003). Criteria for nicotine dependence include 3/7 of the following: (a) the need for more nicotine to achieve desired effect; (b) that the subject meets the criteria for nicotine withdrawal syndromes; (c) the use of tobacco by the subject more than the subject intended; (d) the persistent desire or unsuccessful efforts to cut down on nicotine use; (e) the great deal of time spent using tobacco (e.g., chain smoking); (f) the
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is noteworthy because this group appears to be particularly susceptible to tobacco-related death and disease. Nicotine dependence has a significant and complex role in the incidence, progression, and maintenance of drug use, abuse, and dependence. Four times as many individuals who smoke report illicit drug use than nonsmokers (22.1% vs. 4.9%) (US Department of Health and Human Services, 2011). Drug users tend to start smoking tobacco at a younger age, continue smoking for longer periods of time, and be more nicotine dependent than smokers in the general population (Agrawal, Sartor, Pergadia, Huizink, & Lynskey, 2008; de Dios, Vaughan, Stanton, & Niaura, 2009; Myers & Kelly, 2006; Richter, Ahluwalia, Mosier, Nazir, & Ahluwalia, 2002). While nicotine dependence appears to slow the progression from use to dependence for cocaine and opioids users (Sartor, 2014), individuals with SUDs who are treated for nicotine dependence are more likely to achieve long-term abstinence from drugs than those who are not treated for nicotine dependence (McCarthy, Collins, & Hser, 2002; Prochaska, Delucchi, & Hall, 2004). Nonetheless, there is little understanding of the long-term relationship between nicotine dependence and drug use among individuals in the general population. SUDs exist on a spectrum from mild to severe but are often chronic in nature characterized by a repeated relapse and remittance (American Psychiatric Association 2013; Koob & Le Moal, 1997). The occasional but limited use of a drug is clinically distinct from escalated drug use and the impulsive/ compulsive qualities that have been used to characterize a SUD, formerly recognized as drug abuse or drug dependence (Barbeau, Krieger, & Soobader, 2004; Belanger et al., 2011). Despite diverse initial processes, animal and human imaging studies indicate that drugs of abuse and nicotine produce common dopaminergic effects in the ventral tegmental area of the midbrain and the nucleus accumbens in the limbic forebrain (Biederman et al., 2006). As individuals move from occasional use to a severe substance disorder, current conceptual frameworks indicate that common neurological pathways are engaged as the motivation to use a drug shifts from positive reinforcement to negative reinforcement and automaticity (Barbeau et al., 2004; Belanger et al., 2011; Biederman et al., 2006). Evidence suggests that persistent exposure to drugs of abuse and nicotine appears to cause an impaired dopaminergic response to reward and a sensitization of the dopamine system that can last long after drug administration is discontinued in some individuals. Given these common pathways, the neuroplasticity that supports the development and maintenance of drug and/or nicotine dependence in certain individuals might, hypothetically, begin with and/or be maintained by any drug or nicotine use in vulnerable individuals (e.g., adolescents, genetically vulnerable individuals; Centers for Disease Control and Prevention, 2011; de Dios et al., 2009; Fagan, Augustson, et al., 2007). In this way, drug use might have a synergistic role in incidence, progression, and maintenance of nicotine dependence. We used the National Epidemiological Survey on Alcohol and Related Conditions to understand the role of drug use and drug use disorders in the persistence of nicotine dependence. We modeled the persistence of nicotine dependence at Wave 2 among individuals who were nicotine dependent at Wave 1 and who reported a lifetime history of sedative, tranquilizer, opioid, cannabis, or cocaine use, abuse, or dependence. Given the highly significant comorbidity between nicotine dependence
Nicotine & Tobacco Research
Statistical Analyses Of people diagnosed with past-year nicotine dependence at Wave 1 (n = 4,017), multiple logistic regressions were used to examine the relationship between past-year nicotine dependence persistence at Wave 2 and Wave 1 lifetime drug use, abuse, and dependence. Specific drug use disorders (use, abuse, and dependence) for five types of drugs were the predictor variables (e.g., sedative, tranquilizer, opioid, cannabis, and/or cocaine). Past-year Wave 2 nicotine dependence persistence was the outcome variable. An alpha level of .05 was used to determine statistical significance for all analyses. For each of the analyses, we conducted three separate models: (a) unadjusted, (b) adjusting for significant sociodemographics (i.e., age, sex, ethnicity, income), (c) adjusting for any mood or anxiety disorder, (d) adjusting for alcohol abuse or dependence, and (e) adjusting for other SUDs (except the index substance). All statistical analyses were conducted using Software for Survey Data Analyses (Research Triangle Institute, 2009) using the appropriate statistical weights and stratification variables provided by the NESARC to ensure the representativeness of the data to the U.S. population. The Taylor Series Linearization method was used in the SUDAAN software system (Research Triangle Institute, 2009) to perform the necessary estimation of design-based standard errors to reflect the complex multistage sampling design of the NESARC.
Results Demographic Differences Among Those With and Without Persistent Nicotine Dependence Among adults with nicotine dependence at Wave 1, those who also had nicotine dependence at Wave 2 were more likely to be male, older, and lower income, compared with those who no longer met criteria for ND at Wave 2 (see Table 1). Those with persistent ND were more likely to have any anxiety disorders, any mood disorders, and alcohol use disorders, compared with those who had ND at Wave 1 but not Wave 2. Drug Use and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, neither a lifetime history of sedative (adjusted odds ratio [AOR] = 1.15, 95% confidence interval [CI] = 0.86–1.53), tranquilizer (AOR = 1.16, 95% CI = 0.84–1.59), cannabis (AOR = 1.08, 95% CI = 0.88–1.32), opioid (AOR = 1.07 95% CI = 0.82–1.39), or cocaine use (AOR = 1.22, 95% CI = 0.90–1.65) were associated with significantly increased odds of nicotine dependence persistence at Wave 2 (data not shown; available on request). Drug Abuse and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, a lifetime history of any substance abuse, sedative, and tranquilizer abuse were associated with significantly increased likelihood of persistent nicotine dependence (see Table 2). The association between sedative and tranquilizer abuse and persistence remained significant after adjustment for demographics and other SUDs, but were no longer significant after adjusting for any mood or anxiety disorder; tranquilizer abuse was no longer associated with persistence after adjusting for any other substance abuse. The association between any substance abuse and persistence was no longer significant after adjusting for mood or anxiety disorders and alcohol use problems. Cannabis, opioid, and cocaine abuse were not significantly associated with persistence of nicotine dependence. Cannabis abuse did become significantly associated with persistence of nicotine dependence after adjusting for demographics. Drug Dependence and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, a lifetime history of any substance dependence, sedative, tranquilizer, opioid, cannabis, and cocaine dependence were associated with significantly increased odds of nicotine dependence at Wave 2 (see Table 3). The strongest associations emerged between opioid dependence and ND persistence, followed by tranquilizer dependence, and the sedative dependence. The relationships between any substance dependence, tranquilizer dependence, and opioid dependence remained significant, though the strength of these associations were slightly attenuated after adjusting for demographics and other mood/anxiety, alcohol, and substance dependence. Adjustment for mood/ anxiety disorders did the most to decrease the strength of these associations—relative to demographics, alcohol, and other substance dependence—though the associations still remained significant. The association between sedative dependence and ND persistence was no longer significant after adjusting for
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necessity to give up activities in favor of nicotine use; and (g) the continued use despite recurrent physical or psychological problems likely to have been caused by nicotine use. Nicotine dependence was assessed in the previous 12-month period at Wave 1 and then in the previous 12-month period at Wave 2 (to determine whether the nicotine dependence was persistent or remitted). The reliability and validity of the nicotine dependence diagnosis was assessed elsewhere (Grant et al., 2003) The AUDADIS-IV was also used to generate diagnoses for drug use, abuse, and dependence. The variables for drug use used in this study included: sedative (e.g., sleeping pills, barbiturates) use, tranquilizer (e.g., Valium, muscle relaxants) use, opioid (e.g., Codeine, Demerol) use, cannabis use, and cocaine use. For drug abuse, the variables consisted of sedative abuse, tranquilizer abuse, opioid abuse, cannabis abuse, and cocaine abuse. Finally, for drug dependence the variables were sedative dependence, tranquilizer dependence, opioid dependence, cannabis dependence, and cocaine dependence. Diagnoses were categorical; in order to receive a particular diagnosis, participants must have endorsed the minimum number of symptoms required by the DSM-IV. Individual lifetime abuse and dependence variables at Wave 1 were created for each drug based on combining the past-year with prior-to-past-year abuse/dependence variables for each drug. In this study, an aggregate “any mood disorder” variable was created that was comprised of one or more of the following lifetime disorders at Wave 1: major depression, dysthymia, mania, and hypomania. Any anxiety disorder encompassed one or more of the following disorders at Wave 1: panic with agoraphobia, panic without agoraphobia, social phobia, specific phobia, and generalized anxiety disorder. Demographic variables consisted of sex (male, female), ethnicity (White, Black, Latino or Hispanic, and Other), age (18–29 years, 30–44 years, 45–64 years, and 65+ years), marital status (married and not married), education (0–11 years, 12 years, 13–15 years, and 16+ years), and urbanicity (urban, suburban, and rural).
Drugs and persistence of nicotine dependence Table 1. Associations Between Baseline Sociodemographics, Mood, Anxiety, and Alcohol Use Disorders and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017) Yes nicotine dependence persistence; N = 2,505; n (%)
763 (55.9) 749 (44.1)
1,126 (51.1) 1,379 (48.9)
469 (34.2) 525 (35.2) 421 (25.3) 97 (5.3)
559 (25.0) 926 (36.7) 896 (33.8) 124 (4.6)
253 (16.5) 518 (35.6) 651 (42.8) 90 (5.2)
498 (18.9) 844 (35.0) 1,043 (41.6) 120 (4.5)
401 (20.3) 359 (22.9) 413 (30.6) 339 (26.1)
780 (24.6) 591 (22.8) 617 (27.3) 517 (25.3)
680 (54.8) 832 (45.2)
1,127 (55.6) 1,378 (44.4)
0.14 (1)
995 (77.9) 247 (8.6) 193 (7.5) 77 (6.0) 413 (26.5) 547 (33.1) 829 (57.2)
1,774 (80.6) 389 (8.1) 224 (5.2) 118 (6.1) 878 (35.6) 1,123 (44.1) 1,495 (62.0)
2.38 (3)
χ2 (df) 5.40 (1)*
10.78 (3)***
0.88 (3)
2.95 (3)*
20.38 (1)*** 23.83 (1)*** 4.98 (1)*
Note. aPercentages are column percents. For example, among those with Wave 2 past-year nicotine dependence persistence, 51.1% were male. *p < .05, ***p < .001. other substance dependence. Cocaine and cannabis dependence was associated with ND persistence, though these associations were no longer significant after adjusting for mood/ anxiety, alcohol, and other SUDs.
Discussion There are three key findings of this study. First, substance use (in the absence of disorder) does not appear to be associated with ND persistence. Second, substance abuse is marginally associated with persistence of ND, and that most of these associations are due to confounding and do not remain significant after adjustment with the exception of sedative abuse. Third, a history of substance dependence (in particular opioid and tranquilizer dependence) is associated with increased likelihood of persistence of ND over a period of 3 years, compared with those without a lifetime history of substance dependence. Cocaine and cannabis dependence were significantly predictive of ND persistence, but these associations appeared to be largely due to confounding with demographics, mood/anxiety, alcohol, and other substance dependence. These results have considerable implications given the fact that tobacco is among the most important public health issues
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in the United States. In the ongoing effort to reduce the damaging effect of tobacco, this study underscores drug dependence as a key therapeutic target in the clinical management of individuals who smoke. Clinicians, policy makers, and user advocates should likewise address tobacco use in drug treatment and in harm reduction interventions. Drug dependence of all types was associated with increased likelihood of persistent nicotine dependence. These associations remained significant after adjusting for demographics and mood and anxiety disorders with the exception of cannabis and cocaine dependence. The strongest association was again between tranquilizer dependence and nicotine dependence. Unexpectedly, the strongest and most persistent link was between opioid and tranquilizer dependence and persistent nicotine dependence. Tranquilizers are thought to relieve anxiety; as such it is somewhat surprising that it is one class of drug use associated with persistent nicotine dependence, which is strongly associated with anxiety as well. The reason for this link cannot be determined from these data. It could be that individuals prone to anxiety need both tranquilizers and tobacco use to manage these feelings. It is also conceivable that there is some sort of casual relationship between the two or that tranquilizer use weakens the resolve to quit smoking. It could also be that people who continue to be dependent smokers have
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Sex Male Female Age 18–29 years 30–44 years 45–64 years 65+ years Education 0–11 years 12 years 13–15 years 16+ years Household income $0–19,999 $20,000–34,999 $35,000–59,999 $60,000+ Marital status Married Not married Race/ethnicity White Black Hispanic Other Any anxiety disorder Any mood disorder Any alcohol abuse/dependence
No nicotine dependence persistence; N = 1,512; n (%)a
27 (23.3) 25 (24.8) 51 (35.9) 268 (33.9) 72 (34.1) 307 (34.0)
89 (76.7) 80 (75.2) 96 (64.1) 515 (66.1) 166 (65.9) 617 (66.0)
Yes nicotine dependence persistence; N = 2,505; n (%) 2.00 (1.14–3.51)* 1.85 (1.09–3.14)* 1.07 (0.67–1.72) 1.22 (0.99–1.49) 1.17 (0.82–1.65) 1.22 (1.00–1.48)*
OR nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.95 (1.11–3.43)* 1.90 (1.12–3.22)* 1.15 (0.73–1.81) 1.37 (1.11–1.69)** 1.22 (0.86–1.73) 1.38 (1.12–1.69)**
AOR-1 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.70 (0.97–2.98) 1.53 (0.90–2.61) 0.94 (0.59–1.50) 1.15 (0.94–1.41) 1.11 (0.78–1.56) 1.14 (0.93–1.39)
AOR-2 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.88 (1.07–3.30)* 1.74 (1.02–2.96)* 1.01 (0.62–1.63) 1.16 (0.94–1.42) 1.09 (0.77–1.55) 1.16 (0.95–1.41)
AOR-3 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI)
1.83 (1.02–3.27)* 1.68 (0.95–2.97) 0.93 (0.57–1.54) 1.18 (0.94–1.47) 1.05 (0.73–1.52) N/A
AOR-4 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI)
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10 (17.0) 9 (14.8) 10 (14.6) 64 (28.9) 42 (26.6) 103 (26.7)
39 (83.0) 35 (85.2) 41 (85.4) 156 (71.1) 114 (73.4) 257 (73.3) 2.95 (1.32–6.59)** 3.47 (1.52–7.94)** 3.55 (1.56–8.07)** 1.50 (1.00–2.27) 1.68 (1.07–2.65)* 1.72 (1.23–2.39)**
3.11 (1.34–7.18)** 3.58 (1.53–8.40)** 3.43 (1.51–7.82)** 1.79 (1.18–2.71)** 1.67 (1.06–2.62)* 1.90 (1.36–2.66)***
2.35 (1.03–5.37)* 2.73 (1.17–6.39)* 2.81 (1.24–6.34)* 1.26 (0.83–1.90) 1.40 (0.89–2.20) 1.43 (1.02–2.00)*
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2.79 (1.25–6.23)* 3.27 (1.42–7.51)** 3.33 (1.46–7.60)** 1.42 (0.93–2.17) 1.57 (1.00–2.48) 1.63 (1.16–2.30)**
2.12 (0.91–4.91) 2.59 (1.12–6.01)* 2.63 (1.12–6.19)* 1.29 (0.85–1.97) 1.47 (0.93–2.32) N/A
Note. AOR-1 = adjusted odds ratios (adjusted for age, sex, and income); AOR-2 = adjusted odds ratios (adjusted for any mood disorder and any anxiety disorder); AOR-3 = adjusted odds ratios (adjusted for any alcohol abuse or dependence); AOR-4 = adjusted odds ratios (adjusted for any other substance abuse); CI = confidence interval; OR = unadjusted odds ratios. aPercentages are row percents. For example, among those with Wave 1 sedative dependence, 83.0% had Wave 2 past-year nicotine dependence persistence. *p < .05, **p < .01, ***p < .001.
Sedative dependence Tranquilizer dependence Opioid dependence Cannabis dependence Cocaine dependence Any substance dependence
Category of substance dependence
OR nicotine dependence AOR-1 nicotine AOR-3 nicotine AOR-4 nicotine Yes nicotine No nicotine persistence (reference dependence persistence AOR-2 nicotine dependence dependence persistence dependence persistence dependence dependence group: no nicotine (reference group: no persistence (reference group: (reference group: no (reference group: no persistence; persistence; dependence persistence) nicotine dependence No nicotine dependence nicotine dependence nicotine dependence N = 1,512; n (%)a N = 2,505; n (%) (95% CI) persistence) (95% CI) persistence) (95% CI) persistence) (95% CI) persistence) (95% CI)
Table 3. Associations Between Substance Dependence and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017)
Note. AOR-1 = adjusted odds ratios (adjusted for age, sex, and income); AOR-2 = adjusted odds ratios (adjusted for any mood disorder and any anxiety disorder); AOR-3 = adjusted odds ratios (adjusted for any alcohol abuse or dependence); AOR-4 = adjusted odds ratios (adjusted for any other substance abuse); CI = confidence interval; OR = unadjusted odds ratios. aPercentages are row percents. For example, among those with Wave 1 sedative abuse, 76.7% had Wave 2 past-year nicotine dependence persistence. *p < .05, **p < .01.
Sedative abuse Tranquilizer abuse Opioid abuse Cannabis abuse Cocaine abuse Any substance abuse
Category of substance abuse
No nicotine dependence persistence; N = 1,512; n (%)a
Table 2. Associations Between Substance Abuse and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017)
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Drugs and persistence of nicotine dependence
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nicotine dependence. As continued smoking is the leading preventable cause of death in the United States, understanding the factors that contribute to difficulty in successful quitting are critical to developing more effective smoking cessation strategies. With the exception of a small number of unique interventions, addressing drug dependence in a smoking cessation treatment program is not routine. Our results indeed suggest that more programs that address all type drug dependence, including nicotine—simultaneously are needed in order for cessation to be successful for any one drug. We have seen from several recent studies that this is true of alcohol (that those who contribute to smoke when they stop drinking are more likely to relapse). This study suggests the same is likely to be true for drug dependence.
Funding Preparation of this article was supported by research grants from the Manitoba Health Research Council (Dr. JB), a Manitoba Health Research Council Chair Award (Dr. JS), Canadian Institutes of Health Research New Investigator Awards (Dr. JB #113589; Dr. JS #152348), a University of Manitoba Graduate Fellowship and a Manitoba Graduate Scholarship (Ms. HC), and a University of Manitoba Graduate Fellowship (Ms. JB). The funding sources had no role in the design and conduct of the study; no role in the collection, management, analysis, and interpretation of data; and no role in the preparation, review, and approval of the manuscript.
Declaration of Interests None declared.
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higher levels of anxiety due to intense withdrawal symptoms that thus prompts increased tranquilizer use. The strength of this relationship—among those who use tranquilizers and those who are dependent on tranquilizers—suggests further investigation into this relationship since it may be useful in developing a better understanding of the etiology of both nicotine dependence and dependence on tranquilizers. This is also important given that benzodiazepines are the most prescribed psychotropic medications in the United States and that there has been a recent rise in nonprescription use and abuse of tranquilizers such as Xanax and other benzodiazepines (Greenblatt, Harmatz, & Shader, 2011). As these have increased as drugs of abuse and drug sales in recent years, their potential role in relation to tobacco smoking is even more salient. While the relationship between cannabis use/abuse/dependence has received considerably more attention toward thinking that quitting one is harder because they have a similar route of administration, these data would suggest that indeed route of administration is unlikely to be the primary factor since drugs with different routes of administration were more strongly linked with persistent nicotine dependence than those that were similar (cannabis). These results (i.e., that dependence on multiple drugs are linked) are not surprisingly, as twin and genetically informed studies have suggested there may be a common vulnerability to dependence (on any drug) (Young, Rhee, Stallings, Corley, & Hewitt, 2006). We cannot determine the pathways underlying these associations based on this study. But what it does suggest is that dependence on drugs, or misuse of prescription drugs, may be a contributing factor to persistent dependence on nicotine. Somewhat surprisingly, we did not find significant relations between drug abuse, with the exception of sedatives, and persistent nicotine dependence. There is a well-documented relationship between smoking and drug abuse (Belanger et al., 2011). A large number of studies have documented links between smoking and drug use initiation conceptualizing smoking as a “gateway” to harder drug use (Belanger et al., 2011; Biederman et al., 2006; Gray et al., 2011; Kandel, 2002; Log et al., 2011; Timberlake et al., 2007) In contrast, relativity little is known about abuse of drugs and whether this is related to persistence of dependent smoking. Based on these results, abuse of drugs does not appear linked substantially with likelihood of ongoing dependence on nicotine. Study limitations should be considered when interpreting our findings. First, we only had data on two time points that are 3 years apart and therefore had a limited ability to look prospectively at the interrelationships between drug use and drug use disorders and nicotine dependence over time. Future studies that can look at this over numerous time points in the life course are needed next. Second, it is not possible to draw conclusions regarding causality or the mechanism of these relationships based on these findings. Future animal studies, human drug administration studies and possibility studies in humans using techniques such as Ecological Momentary Analysis will be needed to understand the way the use of each drug and nicotine influence each other in micro and macro level analyses. Finally, while the NESARC is a large sample, the cell size of some of our subanalyses was somewhat low and made it difficult to reliably control for all confounders. To our knowledge, this is the first study to prospectively investigate the relations between a range of specific types of drug use and persistence of nicotine dependence over time. Overall, it appears that drug use is not associated with the persistence of
Nicotine & Tobacco Research Log, T., Hartz, I., Handal, M., Tverdal, A., Furu, K., & Skurtveit, S. (2011). The association between smoking and subsequent repeated use of prescribed opioids among adolescents and young adults–a population-based cohort study. Pharmacoepidemiology and Drug Safety, 20, 90–98. doi:10.1002/pds.2066 McCarthy, W. J., Collins, C., & Hser, Y.-I. (2002). Does tobacco smoking affect drug abuse treatment? Journal of Drug Issues, 32, 61–79. doi:10.1177/002204260203200103 Mokdad, A. H., Marks, J. S., Stroup, D. F., & Gerberding, J. L. (2004). Actual causes of death in the United States, 2000. The Journal of the American Medical Association, 291, 1238–1245. doi:10.1001/jama.291.10.1238 Moylan, S., Jacka, F. N., Pasco, J. A., & Berk, M. (2012). Tobacco smoking, nicotine dependence and anxiety disorders: A systematic review of population-based, epidemiological studies. BMC Medicine, 10, 123. doi:10.1186/1741-7015-10-123 Myers, M., & Kelly, J. (2006). Tobacco smoking among adolescents with alcohol and other drug use problems. Alcohol Research & Health, 29, 221–7. Prochaska, J. J., Delucchi, K., & Hall, S. M. (2004). A metaanalysis of smoking cessation interventions with individuals in substance abuse treatment or recovery. Journal of Consulting and Clinical Psychology, 72, 1144–1156. doi:10.1037/0022-006X.72.6.1144 Reid, J. ., Hammond, D., Boudreau, C., Fong, G., & Siahpush, M. (2010). Socioeconomic disparities in quit intentions, quit attempts, and smoking abstinence among smokers in four western countries: Findings from the International Tobacco Control Four Country Survey. Nicotine & Tobacco Research, 12(Suppl.), S20–S33. doi:10.1093/ntr/ntq051 Richter, K. P., Ahluwalia, H. K., Mosier, M. C., Nazir, N., & Ahluwalia, J. S. (2002). A population-based study of cigarette smoking among illicit drug users in the United States. Addiction (Abingdon, England), 97, 861–869. Sartor, C. E., Kranzler, H. R., & Gelernter, J. (2014). Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic, psychiatric, and childhood risk factors. Addictive Behaviors, 39, 473–479. doi:10.1016/j.addbeh.2013.10.021 Schmitz, N., Kruse, J., & Kugler, J. (2003). Disabilities, quality of life, and mental disorders associated with smoking and nicotine dependence. American Journal of Psychiatry, 160, 1670–1676. doi:10.1176/appi.ajp.160.9.1670 Strong, D. R., Cameron, A., Feuer, S., Cohn, A., Abrantes, A. M., & Brown, R. A. (2010). Single versus recurrent depression history: Differentiating risk factors among current US smokers. Drug and Alcohol Dependence, 109, 90–95. doi:10.1016/j.drugalcdep.2009.12.020 Timberlake, D. S., Haberstick, B. C., Hopfer, C. J., Bricker, J., Sakai, J. T., Lessem, J. M., & Hewitt, J. K. (2007). Progression from marijuana use to daily smoking and nicotine dependence in a national sample of U.S. adolescents. Drug and Alcohol Dependence, 88, 272–281. doi:10.1016/j. drugalcdep.2006.11.005 US Department of Health and Human Services. (2011). Results from the 2010 National Survey on Drug Use and Health: Summary of national findings. Rockville, MD: Substance Abuse and Mental Health Services Administration. Wetter, D. W., Cofta-Gunn, L., Irvin, J. E., Fouladi, R. T., Wright, K., Daza, P., Mazas, C., ... Gritz, E. R. (2005). What accounts for the association of education and smoking cessation? Preventive Medicine, 40, 452–460. doi:10.1016/j. ypmed.2004.07.001 Young, S. E., Rhee, S. H., Stallings, M. C., Corley, R . P., & Hewitt, J. K. (2006). Genetic and environmental vulnerabilities underlying adolescent substance use and problem use: General or specific? Behavior Genetics, 36, 603–615. doi:10.1007/s10519-006-9066-7
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Fagan, P., Augustson, E., Backinger, C. L., O’Connell, M. E., Vollinger, R. E., Jr., Kaufman, A., & Gibson, J. T. (2007). Quit attempts and intention to quit cigarette smoking among young adults in the United States. American Journal of Public Health, 97, 1412–1420. doi:10.2105/AJPH.2006.103697 Fagan, P., Shavers, V. L., Lawrence, D., Gibson, J. T., & O’Connell, M. E. (2007). Employment characteristics and socioeconomic factors associated with disparities in smoking abstinence and former smoking among U.S. workers. Journal of Health Care for the Poor and Underserved, 18(4 Suppl.), 52–72. doi:10.1353/hpu.2007.0119 Fagan, P., Shavers, V., Lawrence, D., Gibson, J. T., & Ponder, P. (2007). Cigarette smoking and quitting behaviors among unemployed adults in the United States. Nicotine & Tobacco Research, 9, 241–248. doi:10.1080/14622200601080331 Ferguson, J., Bauld, L., Chesterman, J., & Judge, K. (2005). The English smoking treatment services: One-year outcomes. Addiction (Abingdon, England), 100(Suppl. 2), 59– 69. doi:10.1111/j.1360-0443.2005.01028.x Grant, B. F., Goldstein, R. B., Chou, S. P., Huang, B., Stinson, F. S., Dawson, D. A., Saha, T. D., ... Compton, W. M. (2009). Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: Results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. Molecular Psychiatry, 14, 1051–1066. doi:10.1038/mp.2008.41 Grant, B. F., Kaplan, K., Moore, T., & Kimball, J. (2007). 2005 Wave 2 national epidemiologic survey on alcohol and related conditions: Source and accuracy statement. National Institute on Alcohol Abuse and Alcoholism. Bethesda, MD. Grant, B. F., Moore, T. C., & Kaplan, K. (2003). Source and accuracy statement: Wave 1 national epidemiologic survey on alcohol and related conditions (NESARC). National Institute on Alcohol Abuse and Alcoholism. Bethesda, MD. Grant, B. F., Stinson, F. S., Dawson, D. A., Chou, S. P., Ruan, J. W., & Pickering, R. P. (2004). Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry, 61, 361–368. doi:10.1001/archpsyc.61.4.361 Grant, B. F., Stinson, F. S., Hasin, D. S., Dawson, D. A., Chou, S. P., & Anderson, K. (2004). Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican Americans and non-Hispanic whites in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry, 61, 1226–1233. doi:10.1001/archpsyc.61.11.1107 Gray, K. M., Riggs, P. D., Min, S.-J., Mikulich-Gilbertson, S. K., Bandyopadhyay, D., & Winhusen, T. (2011). Tobacco and cannabis use trajectories among adolescents in treatment for attention-deficit/hyperactivity disorder and substance use disorders. Drug and Alcohol Dependence, 117, 242–247. doi:10.1016/j.drugalcdep.2011.02.005 Greenblatt, D. J., Harmatz, J. S., & Shader, R. I. (2011). Psychotropic drug prescribing in the United States: Extent, costs, and expenditures. Journal of Clinical Psychopharmacology, 31, 1–3. doi:10.1097/ JCP.0b013e318209cf05 Hurt, R. D., Offord, K. P., Croghan, I. T., Gomez-Dahl, L., Kottke, T. E., Morse, R. M., & Melton, L. J. (1996). Mortality following inpatient addictions treatment. Role of tobacco use in a community-based cohort. The Journal of the American Medical Association, 275, 1097–1103. Kandel, D. (2002). Stages and pathways of drug involvement: Examining the gateway hypothesis. Cambridge, England: Cambridge University Press. Koob, G. F., & Le Moal, M. (1997). Drug abuse: Hedonic homeostatic dysregulation. Science, 278, 52–58.
Original Investigation
Drug Use, Abuse, and Dependence and the Persistence of Nicotine Dependence Renee D. Goodwin PhD, MPH1,2, Christine E. Sheffer PhD3, Hayley Chartrand MA4, Joanna Bhaskaran BSc (Hons)4, Carl L. Hart PhD5,6, Jitender Sareen4,7,8, James Bolton4,7,8 1Department of Psychology, Queens College and Graduate Center, City University of New York, Flushing, NY; 2Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; 3Sophie Davis School of Biomedical Education, City University of New York, New York, NY; 4Department of Psychology, University of Manitoba, Winnipeg, Manitoba, Canada; 5Department of Psychology, Columbia University, New York, NY; 6Department of Psychiatry, Columbia University, New York, NY; 7Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada; 8Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
Received July 29, 2013; accepted June 11, 2014
Abstract Introduction: Illicit drug use and nicotine dependence (ND) frequently cooccur. Yet, to date, very few studies have examined the role of alcohol and illicit drug use in ND persistence. The objectives of this study were to investigate the relationships between specific classes of drug use, abuse, and dependence and the persistence of ND over time among adults in the United States. Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a national survey of 34,653 U.S. adults interviewed in 2001–2002 and reinterviewed 3 years later. Logistic regression analyses were used to investigate the relations between various classes of drug use, abuse, and dependence among adults with ND at Wave 1 and odds of persistent ND at Wave 2. Analyses were adjusted for differences in demographic characteristics, mood and anxiety disorders, alcohol use disorders, and other substance use disorders. Results: Lifetime drug use was not associated with significantly increased likelihood of persistent ND. Sedative abuse was associated with increased odds of nicotine persistence, but no other types of drug abuse were predictive of ND persistence, after adjusting for demographics, mood/anxiety, alcohol use disorders. All types of drug dependence were associated with persistence of ND; the strongest associations emerged between opioid and tranquilizer dependence and persistent ND while the associations between cannabis and cocaine dependence were no longer significant after adjusting for mood/anxiety disorders. Conclusions: Clinicians should take care to evaluate the presence and/or a history of drug dependence among patients seeking treatment for smoking cessation. These data suggest that a history of substance dependence predicts increased vulnerability to persistent ND.
Introduction The prevalence of smoking among individuals who use illicit drugs remains remarkably high despite dramatic decreases in the prevalence among other groups. Consequently, the tobacco-related mortality rate among those with substance use disorders (SUDs) is twice that of the general population and greater than the mortality rate from all other drugs combined (Hurt et al., 1996; Mokdad, Marks, Stroup, & Gerberding, 2004). Nicotine, the major psychoactive drug in tobacco, shares similar addictive biochemical and behavioral processes with illicit drugs (US Department of Health and Human Services, 2011) suggesting a close relationship between drug and nicotine dependence, but the nature of this relationship is
likely to be multifaceted and remains unclear. Understanding the long-term persistence of nicotine dependence among individuals who use drugs has implications for the identification of new therapeutic targets in treatment of nicotine dependence and drug use, as well as the development of policies that support abstinence in this group. There is a well-documented relationship between cigarette smoking and drug use (Belanger et al., 2011). A large number of studies have documented links between smoking and initiation of drug use conceptualizing smoking as a “gateway” to harder drug use (Belanger et al., 2011; Biederman et al., 2006; Gray et al., 2011; Kandel, 2002; Log et al., 2011; Timberlake et al., 2007). In contrast, relativity little is known about associations among drug use and the persistence of smoking, which
doi:10.1093/ntr/ntu115 © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: [email protected].
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Corresponding Author: Renee D. Goodwin, PhD, MPH, 65-30 Kissena Boulevard, Flushing, Queens 11367, USA. Telephone: 718-997-3247; Fax: 718 -997-3257; E-mail: [email protected]
Drugs and persistence of nicotine dependence
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and drug use, we hypothesized that drug use of all types and severities would be associated with persistent nicotine dependence, consistent with the maintenance of an impaired dopaminergic reward system and sensitization of the common pathway for addiction. The prevalence of smoking is strongly associated with factors other than drug use including age, sex, and income (Agrawal et al., 2008; Barbeau et al., 2004; Centers for Disease Control and Prevention, 2011; Fagan, Shavers, Lawrence, Gibson, & O’Connell, 2007; Fagan, Shavers, Lawrence, Gibson, & Ponder, 2007; Fagan, Augustson, et al., 2007; Ferguson, Bauld, Chesterman, & Judge, 2005; Reid, Hammond, Boudreau, Fong, & Siahpush, 2010; Wetter et al., 2005) as well as anxiety, mood, and alcohol use disorders (Grant, Stinson, Dawson, et al., 2004; Grant, Stinson, Hasin, et al., 2004; Moylan, Jacka, Pasco, & Berk, 2012; Strong et al., 2010).
Methods Data Sources and Sample The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (Grant et al., 2009; Grant, Stinson, Dawson, et al., 2004) is a nationally representative longitudinal survey of the adult noninstitutionalized, civilian population of the 50 U.S. States conducted by the U.S. Census Bureau under the direction of the National Institute on Alcohol Abuse and Alcoholism. Wave 1 was conducted in 2001–2002 with a sample of 43,093 respondents age 18 and over (Grant, Moore, Shephard, & Kaplan, 2003), Wave 2 was a 3-year prospective follow-up comprising 34,653 of the Wave 1 respondents, representing a response rate of 86.7% of eligible respondents (Grant & Kaplan, 2005). In combination with the Wave 1 response rate of 81%, the cumulative response rate for Wave 2 is 70.2%. Trained lay interviewers with at least 5 years of experience conducted face-to-face assessments using computer-assisted software. Informed consent was obtained from all participants before beginning the interviews. Detailed descriptions of methodology, sampling, and weighting procedures have been reported elsewhere (Grant & Kaplan, 2005; Grant et al., 2003). For this study, the sample consisted of individuals who met criteria for past-year nicotine dependence at Wave 1 and who also responded to the Wave 2 survey (n = 4,017). Measures Diagnoses were assessed with the AUDADIS-IV. This instrument was specifically designed for experienced lay interviewers and was developed to advance measurement of drug use and mental disorders in large-scale surveys. Nicotine dependence was assessed in a unique module separate from the assessment of other drug use. To that end, the AUDADIS-IV used an extensive list of over 40 questions to assess nicotine dependence and obtains extensive information on time frames of nicotine use and dependence. Diagnoses were made according to the DSM-IV criteria (Schmitz et al., 2003). Criteria for nicotine dependence include 3/7 of the following: (a) the need for more nicotine to achieve desired effect; (b) that the subject meets the criteria for nicotine withdrawal syndromes; (c) the use of tobacco by the subject more than the subject intended; (d) the persistent desire or unsuccessful efforts to cut down on nicotine use; (e) the great deal of time spent using tobacco (e.g., chain smoking); (f) the
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is noteworthy because this group appears to be particularly susceptible to tobacco-related death and disease. Nicotine dependence has a significant and complex role in the incidence, progression, and maintenance of drug use, abuse, and dependence. Four times as many individuals who smoke report illicit drug use than nonsmokers (22.1% vs. 4.9%) (US Department of Health and Human Services, 2011). Drug users tend to start smoking tobacco at a younger age, continue smoking for longer periods of time, and be more nicotine dependent than smokers in the general population (Agrawal, Sartor, Pergadia, Huizink, & Lynskey, 2008; de Dios, Vaughan, Stanton, & Niaura, 2009; Myers & Kelly, 2006; Richter, Ahluwalia, Mosier, Nazir, & Ahluwalia, 2002). While nicotine dependence appears to slow the progression from use to dependence for cocaine and opioids users (Sartor, 2014), individuals with SUDs who are treated for nicotine dependence are more likely to achieve long-term abstinence from drugs than those who are not treated for nicotine dependence (McCarthy, Collins, & Hser, 2002; Prochaska, Delucchi, & Hall, 2004). Nonetheless, there is little understanding of the long-term relationship between nicotine dependence and drug use among individuals in the general population. SUDs exist on a spectrum from mild to severe but are often chronic in nature characterized by a repeated relapse and remittance (American Psychiatric Association 2013; Koob & Le Moal, 1997). The occasional but limited use of a drug is clinically distinct from escalated drug use and the impulsive/ compulsive qualities that have been used to characterize a SUD, formerly recognized as drug abuse or drug dependence (Barbeau, Krieger, & Soobader, 2004; Belanger et al., 2011). Despite diverse initial processes, animal and human imaging studies indicate that drugs of abuse and nicotine produce common dopaminergic effects in the ventral tegmental area of the midbrain and the nucleus accumbens in the limbic forebrain (Biederman et al., 2006). As individuals move from occasional use to a severe substance disorder, current conceptual frameworks indicate that common neurological pathways are engaged as the motivation to use a drug shifts from positive reinforcement to negative reinforcement and automaticity (Barbeau et al., 2004; Belanger et al., 2011; Biederman et al., 2006). Evidence suggests that persistent exposure to drugs of abuse and nicotine appears to cause an impaired dopaminergic response to reward and a sensitization of the dopamine system that can last long after drug administration is discontinued in some individuals. Given these common pathways, the neuroplasticity that supports the development and maintenance of drug and/or nicotine dependence in certain individuals might, hypothetically, begin with and/or be maintained by any drug or nicotine use in vulnerable individuals (e.g., adolescents, genetically vulnerable individuals; Centers for Disease Control and Prevention, 2011; de Dios et al., 2009; Fagan, Augustson, et al., 2007). In this way, drug use might have a synergistic role in incidence, progression, and maintenance of nicotine dependence. We used the National Epidemiological Survey on Alcohol and Related Conditions to understand the role of drug use and drug use disorders in the persistence of nicotine dependence. We modeled the persistence of nicotine dependence at Wave 2 among individuals who were nicotine dependent at Wave 1 and who reported a lifetime history of sedative, tranquilizer, opioid, cannabis, or cocaine use, abuse, or dependence. Given the highly significant comorbidity between nicotine dependence
Nicotine & Tobacco Research
Statistical Analyses Of people diagnosed with past-year nicotine dependence at Wave 1 (n = 4,017), multiple logistic regressions were used to examine the relationship between past-year nicotine dependence persistence at Wave 2 and Wave 1 lifetime drug use, abuse, and dependence. Specific drug use disorders (use, abuse, and dependence) for five types of drugs were the predictor variables (e.g., sedative, tranquilizer, opioid, cannabis, and/or cocaine). Past-year Wave 2 nicotine dependence persistence was the outcome variable. An alpha level of .05 was used to determine statistical significance for all analyses. For each of the analyses, we conducted three separate models: (a) unadjusted, (b) adjusting for significant sociodemographics (i.e., age, sex, ethnicity, income), (c) adjusting for any mood or anxiety disorder, (d) adjusting for alcohol abuse or dependence, and (e) adjusting for other SUDs (except the index substance). All statistical analyses were conducted using Software for Survey Data Analyses (Research Triangle Institute, 2009) using the appropriate statistical weights and stratification variables provided by the NESARC to ensure the representativeness of the data to the U.S. population. The Taylor Series Linearization method was used in the SUDAAN software system (Research Triangle Institute, 2009) to perform the necessary estimation of design-based standard errors to reflect the complex multistage sampling design of the NESARC.
Results Demographic Differences Among Those With and Without Persistent Nicotine Dependence Among adults with nicotine dependence at Wave 1, those who also had nicotine dependence at Wave 2 were more likely to be male, older, and lower income, compared with those who no longer met criteria for ND at Wave 2 (see Table 1). Those with persistent ND were more likely to have any anxiety disorders, any mood disorders, and alcohol use disorders, compared with those who had ND at Wave 1 but not Wave 2. Drug Use and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, neither a lifetime history of sedative (adjusted odds ratio [AOR] = 1.15, 95% confidence interval [CI] = 0.86–1.53), tranquilizer (AOR = 1.16, 95% CI = 0.84–1.59), cannabis (AOR = 1.08, 95% CI = 0.88–1.32), opioid (AOR = 1.07 95% CI = 0.82–1.39), or cocaine use (AOR = 1.22, 95% CI = 0.90–1.65) were associated with significantly increased odds of nicotine dependence persistence at Wave 2 (data not shown; available on request). Drug Abuse and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, a lifetime history of any substance abuse, sedative, and tranquilizer abuse were associated with significantly increased likelihood of persistent nicotine dependence (see Table 2). The association between sedative and tranquilizer abuse and persistence remained significant after adjustment for demographics and other SUDs, but were no longer significant after adjusting for any mood or anxiety disorder; tranquilizer abuse was no longer associated with persistence after adjusting for any other substance abuse. The association between any substance abuse and persistence was no longer significant after adjusting for mood or anxiety disorders and alcohol use problems. Cannabis, opioid, and cocaine abuse were not significantly associated with persistence of nicotine dependence. Cannabis abuse did become significantly associated with persistence of nicotine dependence after adjusting for demographics. Drug Dependence and Persistence of Nicotine Dependence Among adults with nicotine dependence at Wave 1, a lifetime history of any substance dependence, sedative, tranquilizer, opioid, cannabis, and cocaine dependence were associated with significantly increased odds of nicotine dependence at Wave 2 (see Table 3). The strongest associations emerged between opioid dependence and ND persistence, followed by tranquilizer dependence, and the sedative dependence. The relationships between any substance dependence, tranquilizer dependence, and opioid dependence remained significant, though the strength of these associations were slightly attenuated after adjusting for demographics and other mood/anxiety, alcohol, and substance dependence. Adjustment for mood/ anxiety disorders did the most to decrease the strength of these associations—relative to demographics, alcohol, and other substance dependence—though the associations still remained significant. The association between sedative dependence and ND persistence was no longer significant after adjusting for
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necessity to give up activities in favor of nicotine use; and (g) the continued use despite recurrent physical or psychological problems likely to have been caused by nicotine use. Nicotine dependence was assessed in the previous 12-month period at Wave 1 and then in the previous 12-month period at Wave 2 (to determine whether the nicotine dependence was persistent or remitted). The reliability and validity of the nicotine dependence diagnosis was assessed elsewhere (Grant et al., 2003) The AUDADIS-IV was also used to generate diagnoses for drug use, abuse, and dependence. The variables for drug use used in this study included: sedative (e.g., sleeping pills, barbiturates) use, tranquilizer (e.g., Valium, muscle relaxants) use, opioid (e.g., Codeine, Demerol) use, cannabis use, and cocaine use. For drug abuse, the variables consisted of sedative abuse, tranquilizer abuse, opioid abuse, cannabis abuse, and cocaine abuse. Finally, for drug dependence the variables were sedative dependence, tranquilizer dependence, opioid dependence, cannabis dependence, and cocaine dependence. Diagnoses were categorical; in order to receive a particular diagnosis, participants must have endorsed the minimum number of symptoms required by the DSM-IV. Individual lifetime abuse and dependence variables at Wave 1 were created for each drug based on combining the past-year with prior-to-past-year abuse/dependence variables for each drug. In this study, an aggregate “any mood disorder” variable was created that was comprised of one or more of the following lifetime disorders at Wave 1: major depression, dysthymia, mania, and hypomania. Any anxiety disorder encompassed one or more of the following disorders at Wave 1: panic with agoraphobia, panic without agoraphobia, social phobia, specific phobia, and generalized anxiety disorder. Demographic variables consisted of sex (male, female), ethnicity (White, Black, Latino or Hispanic, and Other), age (18–29 years, 30–44 years, 45–64 years, and 65+ years), marital status (married and not married), education (0–11 years, 12 years, 13–15 years, and 16+ years), and urbanicity (urban, suburban, and rural).
Drugs and persistence of nicotine dependence Table 1. Associations Between Baseline Sociodemographics, Mood, Anxiety, and Alcohol Use Disorders and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017) Yes nicotine dependence persistence; N = 2,505; n (%)
763 (55.9) 749 (44.1)
1,126 (51.1) 1,379 (48.9)
469 (34.2) 525 (35.2) 421 (25.3) 97 (5.3)
559 (25.0) 926 (36.7) 896 (33.8) 124 (4.6)
253 (16.5) 518 (35.6) 651 (42.8) 90 (5.2)
498 (18.9) 844 (35.0) 1,043 (41.6) 120 (4.5)
401 (20.3) 359 (22.9) 413 (30.6) 339 (26.1)
780 (24.6) 591 (22.8) 617 (27.3) 517 (25.3)
680 (54.8) 832 (45.2)
1,127 (55.6) 1,378 (44.4)
0.14 (1)
995 (77.9) 247 (8.6) 193 (7.5) 77 (6.0) 413 (26.5) 547 (33.1) 829 (57.2)
1,774 (80.6) 389 (8.1) 224 (5.2) 118 (6.1) 878 (35.6) 1,123 (44.1) 1,495 (62.0)
2.38 (3)
χ2 (df) 5.40 (1)*
10.78 (3)***
0.88 (3)
2.95 (3)*
20.38 (1)*** 23.83 (1)*** 4.98 (1)*
Note. aPercentages are column percents. For example, among those with Wave 2 past-year nicotine dependence persistence, 51.1% were male. *p < .05, ***p < .001. other substance dependence. Cocaine and cannabis dependence was associated with ND persistence, though these associations were no longer significant after adjusting for mood/ anxiety, alcohol, and other SUDs.
Discussion There are three key findings of this study. First, substance use (in the absence of disorder) does not appear to be associated with ND persistence. Second, substance abuse is marginally associated with persistence of ND, and that most of these associations are due to confounding and do not remain significant after adjustment with the exception of sedative abuse. Third, a history of substance dependence (in particular opioid and tranquilizer dependence) is associated with increased likelihood of persistence of ND over a period of 3 years, compared with those without a lifetime history of substance dependence. Cocaine and cannabis dependence were significantly predictive of ND persistence, but these associations appeared to be largely due to confounding with demographics, mood/anxiety, alcohol, and other substance dependence. These results have considerable implications given the fact that tobacco is among the most important public health issues
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in the United States. In the ongoing effort to reduce the damaging effect of tobacco, this study underscores drug dependence as a key therapeutic target in the clinical management of individuals who smoke. Clinicians, policy makers, and user advocates should likewise address tobacco use in drug treatment and in harm reduction interventions. Drug dependence of all types was associated with increased likelihood of persistent nicotine dependence. These associations remained significant after adjusting for demographics and mood and anxiety disorders with the exception of cannabis and cocaine dependence. The strongest association was again between tranquilizer dependence and nicotine dependence. Unexpectedly, the strongest and most persistent link was between opioid and tranquilizer dependence and persistent nicotine dependence. Tranquilizers are thought to relieve anxiety; as such it is somewhat surprising that it is one class of drug use associated with persistent nicotine dependence, which is strongly associated with anxiety as well. The reason for this link cannot be determined from these data. It could be that individuals prone to anxiety need both tranquilizers and tobacco use to manage these feelings. It is also conceivable that there is some sort of casual relationship between the two or that tranquilizer use weakens the resolve to quit smoking. It could also be that people who continue to be dependent smokers have
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Sex Male Female Age 18–29 years 30–44 years 45–64 years 65+ years Education 0–11 years 12 years 13–15 years 16+ years Household income $0–19,999 $20,000–34,999 $35,000–59,999 $60,000+ Marital status Married Not married Race/ethnicity White Black Hispanic Other Any anxiety disorder Any mood disorder Any alcohol abuse/dependence
No nicotine dependence persistence; N = 1,512; n (%)a
27 (23.3) 25 (24.8) 51 (35.9) 268 (33.9) 72 (34.1) 307 (34.0)
89 (76.7) 80 (75.2) 96 (64.1) 515 (66.1) 166 (65.9) 617 (66.0)
Yes nicotine dependence persistence; N = 2,505; n (%) 2.00 (1.14–3.51)* 1.85 (1.09–3.14)* 1.07 (0.67–1.72) 1.22 (0.99–1.49) 1.17 (0.82–1.65) 1.22 (1.00–1.48)*
OR nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.95 (1.11–3.43)* 1.90 (1.12–3.22)* 1.15 (0.73–1.81) 1.37 (1.11–1.69)** 1.22 (0.86–1.73) 1.38 (1.12–1.69)**
AOR-1 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.70 (0.97–2.98) 1.53 (0.90–2.61) 0.94 (0.59–1.50) 1.15 (0.94–1.41) 1.11 (0.78–1.56) 1.14 (0.93–1.39)
AOR-2 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI) 1.88 (1.07–3.30)* 1.74 (1.02–2.96)* 1.01 (0.62–1.63) 1.16 (0.94–1.42) 1.09 (0.77–1.55) 1.16 (0.95–1.41)
AOR-3 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI)
1.83 (1.02–3.27)* 1.68 (0.95–2.97) 0.93 (0.57–1.54) 1.18 (0.94–1.47) 1.05 (0.73–1.52) N/A
AOR-4 nicotine dependence persistence (reference group: no nicotine dependence persistence) (95% CI)
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10 (17.0) 9 (14.8) 10 (14.6) 64 (28.9) 42 (26.6) 103 (26.7)
39 (83.0) 35 (85.2) 41 (85.4) 156 (71.1) 114 (73.4) 257 (73.3) 2.95 (1.32–6.59)** 3.47 (1.52–7.94)** 3.55 (1.56–8.07)** 1.50 (1.00–2.27) 1.68 (1.07–2.65)* 1.72 (1.23–2.39)**
3.11 (1.34–7.18)** 3.58 (1.53–8.40)** 3.43 (1.51–7.82)** 1.79 (1.18–2.71)** 1.67 (1.06–2.62)* 1.90 (1.36–2.66)***
2.35 (1.03–5.37)* 2.73 (1.17–6.39)* 2.81 (1.24–6.34)* 1.26 (0.83–1.90) 1.40 (0.89–2.20) 1.43 (1.02–2.00)*
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2.79 (1.25–6.23)* 3.27 (1.42–7.51)** 3.33 (1.46–7.60)** 1.42 (0.93–2.17) 1.57 (1.00–2.48) 1.63 (1.16–2.30)**
2.12 (0.91–4.91) 2.59 (1.12–6.01)* 2.63 (1.12–6.19)* 1.29 (0.85–1.97) 1.47 (0.93–2.32) N/A
Note. AOR-1 = adjusted odds ratios (adjusted for age, sex, and income); AOR-2 = adjusted odds ratios (adjusted for any mood disorder and any anxiety disorder); AOR-3 = adjusted odds ratios (adjusted for any alcohol abuse or dependence); AOR-4 = adjusted odds ratios (adjusted for any other substance abuse); CI = confidence interval; OR = unadjusted odds ratios. aPercentages are row percents. For example, among those with Wave 1 sedative dependence, 83.0% had Wave 2 past-year nicotine dependence persistence. *p < .05, **p < .01, ***p < .001.
Sedative dependence Tranquilizer dependence Opioid dependence Cannabis dependence Cocaine dependence Any substance dependence
Category of substance dependence
OR nicotine dependence AOR-1 nicotine AOR-3 nicotine AOR-4 nicotine Yes nicotine No nicotine persistence (reference dependence persistence AOR-2 nicotine dependence dependence persistence dependence persistence dependence dependence group: no nicotine (reference group: no persistence (reference group: (reference group: no (reference group: no persistence; persistence; dependence persistence) nicotine dependence No nicotine dependence nicotine dependence nicotine dependence N = 1,512; n (%)a N = 2,505; n (%) (95% CI) persistence) (95% CI) persistence) (95% CI) persistence) (95% CI) persistence) (95% CI)
Table 3. Associations Between Substance Dependence and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017)
Note. AOR-1 = adjusted odds ratios (adjusted for age, sex, and income); AOR-2 = adjusted odds ratios (adjusted for any mood disorder and any anxiety disorder); AOR-3 = adjusted odds ratios (adjusted for any alcohol abuse or dependence); AOR-4 = adjusted odds ratios (adjusted for any other substance abuse); CI = confidence interval; OR = unadjusted odds ratios. aPercentages are row percents. For example, among those with Wave 1 sedative abuse, 76.7% had Wave 2 past-year nicotine dependence persistence. *p < .05, **p < .01.
Sedative abuse Tranquilizer abuse Opioid abuse Cannabis abuse Cocaine abuse Any substance abuse
Category of substance abuse
No nicotine dependence persistence; N = 1,512; n (%)a
Table 2. Associations Between Substance Abuse and Subsequent Nicotine Dependence Persistence Among Those With Past-Year Nicotine Dependence at Baseline (n = 4,017)
Nicotine & Tobacco Research
Drugs and persistence of nicotine dependence
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nicotine dependence. As continued smoking is the leading preventable cause of death in the United States, understanding the factors that contribute to difficulty in successful quitting are critical to developing more effective smoking cessation strategies. With the exception of a small number of unique interventions, addressing drug dependence in a smoking cessation treatment program is not routine. Our results indeed suggest that more programs that address all type drug dependence, including nicotine—simultaneously are needed in order for cessation to be successful for any one drug. We have seen from several recent studies that this is true of alcohol (that those who contribute to smoke when they stop drinking are more likely to relapse). This study suggests the same is likely to be true for drug dependence.
Funding Preparation of this article was supported by research grants from the Manitoba Health Research Council (Dr. JB), a Manitoba Health Research Council Chair Award (Dr. JS), Canadian Institutes of Health Research New Investigator Awards (Dr. JB #113589; Dr. JS #152348), a University of Manitoba Graduate Fellowship and a Manitoba Graduate Scholarship (Ms. HC), and a University of Manitoba Graduate Fellowship (Ms. JB). The funding sources had no role in the design and conduct of the study; no role in the collection, management, analysis, and interpretation of data; and no role in the preparation, review, and approval of the manuscript.
Declaration of Interests None declared.
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higher levels of anxiety due to intense withdrawal symptoms that thus prompts increased tranquilizer use. The strength of this relationship—among those who use tranquilizers and those who are dependent on tranquilizers—suggests further investigation into this relationship since it may be useful in developing a better understanding of the etiology of both nicotine dependence and dependence on tranquilizers. This is also important given that benzodiazepines are the most prescribed psychotropic medications in the United States and that there has been a recent rise in nonprescription use and abuse of tranquilizers such as Xanax and other benzodiazepines (Greenblatt, Harmatz, & Shader, 2011). As these have increased as drugs of abuse and drug sales in recent years, their potential role in relation to tobacco smoking is even more salient. While the relationship between cannabis use/abuse/dependence has received considerably more attention toward thinking that quitting one is harder because they have a similar route of administration, these data would suggest that indeed route of administration is unlikely to be the primary factor since drugs with different routes of administration were more strongly linked with persistent nicotine dependence than those that were similar (cannabis). These results (i.e., that dependence on multiple drugs are linked) are not surprisingly, as twin and genetically informed studies have suggested there may be a common vulnerability to dependence (on any drug) (Young, Rhee, Stallings, Corley, & Hewitt, 2006). We cannot determine the pathways underlying these associations based on this study. But what it does suggest is that dependence on drugs, or misuse of prescription drugs, may be a contributing factor to persistent dependence on nicotine. Somewhat surprisingly, we did not find significant relations between drug abuse, with the exception of sedatives, and persistent nicotine dependence. There is a well-documented relationship between smoking and drug abuse (Belanger et al., 2011). A large number of studies have documented links between smoking and drug use initiation conceptualizing smoking as a “gateway” to harder drug use (Belanger et al., 2011; Biederman et al., 2006; Gray et al., 2011; Kandel, 2002; Log et al., 2011; Timberlake et al., 2007) In contrast, relativity little is known about abuse of drugs and whether this is related to persistence of dependent smoking. Based on these results, abuse of drugs does not appear linked substantially with likelihood of ongoing dependence on nicotine. Study limitations should be considered when interpreting our findings. First, we only had data on two time points that are 3 years apart and therefore had a limited ability to look prospectively at the interrelationships between drug use and drug use disorders and nicotine dependence over time. Future studies that can look at this over numerous time points in the life course are needed next. Second, it is not possible to draw conclusions regarding causality or the mechanism of these relationships based on these findings. Future animal studies, human drug administration studies and possibility studies in humans using techniques such as Ecological Momentary Analysis will be needed to understand the way the use of each drug and nicotine influence each other in micro and macro level analyses. Finally, while the NESARC is a large sample, the cell size of some of our subanalyses was somewhat low and made it difficult to reliably control for all confounders. To our knowledge, this is the first study to prospectively investigate the relations between a range of specific types of drug use and persistence of nicotine dependence over time. Overall, it appears that drug use is not associated with the persistence of
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