Drug and Alcohol Dependence 136 (2014) 51–62

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Drug and Alcohol Dependence journal homepage: www.elsevier.com/locate/drugalcdep

Early adolescent patterns of alcohol, cigarettes, and marijuana polysubstance use and young adult substance use outcomes in a nationally representative sample夽 Howard Barry Moss b,∗ , Chiung M. Chen a , Hsiao-ye Yi a a b

Alcohol Epidemiologic Data System, CSR, Incorporated, United States National Institute on Alcohol Abuse and Alcoholism, United States

a r t i c l e

i n f o

Article history: Received 30 July 2013 Received in revised form 9 December 2013 Accepted 14 December 2013 Available online 31 December 2013 Keywords: Adolescent Alcohol Marijuana Cigarettes Polysubstance use Substance use disorders

a b s t r a c t Background: Alcohol, tobacco and marijuana are the most commonly used drugs by adolescents in the U.S. However, little is known about the patterning of early adolescent substance use, and its implications for problematic involvement with substances in young adulthood. We examined patterns of substance use prior to age 16, and their associations with young adult substance use behaviors and substance use disorders in a nationally representative sample of U.S. adolescents. Method: Using data from Wave 4 of the Add Health Survey (n = 4245), we estimated the prevalence of various patterns of early adolescent use of alcohol, cigarettes, and marijuana use individually and in combination. Then we examined the effects of patterns of early use of these substances on subsequent young adult substance use behaviors and DSM-IV substance use disorders. Results: While 34.4% of individuals reported no substance use prior to age 16, 34.1% reported either early use of both alcohol and marijuana or alcohol, marijuana and cigarettes, indicating the relatively high prevalence of this type of polysubstance use behavior among U.S. adolescents. Early adolescent use of all three substances was most strongly associated with a spectrum of young adult substance use problems, as well as DSM-IV substance use disorder diagnoses. Conclusions: This research confirms the elevated prevalence and importance of polysubstance use behavior among adolescents prior to age 16, and puts early onset of alcohol, marijuana and cigarette use into the context of use patterns rather than single drug exposures. Published by Elsevier Ireland Ltd.

1. Introduction Alcohol, tobacco and marijuana are the most commonly used drugs by adolescents in the U.S. (Johnston et al., 2013). Various studies have suggested that such substance use behavior during early adolescent development increases the risk for a variety of health issues (Aarons et al., 1999; Weinberg et al., 1998). Research has also demonstrated associations between adolescent drug use and abuse and measures of low self-esteem, depression, antisocial behavior, rebelliousness, aggressiveness, crime, delinquency, truancy, and poor school performance (Dishion and Loeber, 1985; Donovan and

夽 Supplementary material for this article can be found by accessing the online version of this paper. Please see Appendix A for more information. ∗ Corresponding author at: National Institute on Alcohol Abuse and Alcoholism, OD, 5635 Fishers Lane, Bethesda, MD 20892-9304, United States. Tel.: +1 301 402 0944; fax: +1 301 480 1726; mobile: +1 301 357 0797. E-mail address: [email protected] (H.B. Moss). 0376-8716/$ – see front matter. Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.drugalcdep.2013.12.011

Jessor, 1978; Jessor, 1987; Jessor and Jessor, 1975; Kandel, 1975; Margulies et al., 1977; Robins, 1966). Investigators have employed several liability models in order to guide efforts at prevention and risk mitigation. One such model has emphasized the specificity of effects of early use of alcohol, cigarettes, or marijuana. For example, studies have demonstrated that adolescents who begin their first regular use of alcohol at ages 11–14 have a significantly heightened risk for later progression to an alcohol disorder (Grant and Dawson, 1997; Grant et al., 2001; Hingson et al., 2006a,b). Other research has shown that early adolescent cigarette smoking initiation increases the risk of future nicotine dependence substantially (Buchmann et al., 2011; Johnson and Novak, 2009; Kendler et al., 2013; Morrell et al., 2011; Westling et al., 2012). There is also evidence that early marijuana use increases the risk for a cannabis use disorder (Ehlers et al., 2007; Gillespie et al., 2009; Perez et al., 2010; Swift et al., 2008). This approach has stimulated basic science research that addresses biobehavioral adolescent responses to these various substances in animal models in an effort to understand their subsequent potential for addiction in later life (Crews

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et al., 2007; Dinieri and Hurd, 2012; Ellgren et al., 2008, 2007; Mychasiuk et al., 2013; Spear, 2002; Spear and Varlinskaya, 2005; Weaver et al., 2012). Another model of investigation has addressed the developmental patterning of acquisition of substance use behavior, and is frequently referred to as the “gateway” hypothesis. This model suggests that adolescents, who start with the use of one class of drug, that may be socially acceptable (but not legal for adolescent use), such as alcohol and/or tobacco, may then cross over and progress on to the use other illicit substances such as cannabis, methamphetamine or cocaine (Degenhardt et al., 2009; Kandel, 1975; Kandel and Faust, 1975; Patton et al., 2005; Sartor et al., 2013; Stenbacka et al., 1993; Tarter et al., 2012; Timberlake et al., 2007; Vanyukov et al., 2012). A third body of research suggests that adolescent substance use behavior may be a manifestation of an underlying addiction-prone diathesis associated with behavioral disinhibition and conduct deviancy (Hicks et al., 2012; Iacono et al., 2008; Kirisci et al., 2013; McGue and Iacono, 2008; Tarter et al., 2003; Vanyukov and Ridenour, 2012; Vanyukov et al., 2003) and may be associated with heightened risk for a spectrum of problematic involvements with alcohol, and other drugs later in life. This latter notion is also consistent with Problem Behavior theory, which posits that some individuals possess a personality proneness, environmental proneness, and behavioral proneness to engage in multiple problem behaviors (such as delinquency, substance abuse, or criminality) that depart from social and legal norms and can result in mild social reproof, social rejection, or even incarceration (Jessor, 1987; Jessor et al., 2006). It is noteworthy that although Problem Behavior Theory tends to emphasize psychosocial factors leading to “proneness,” there is a burgeoning body of genetic evidence for both specific patterns of drug-associated risks (Agrawal and Lynskey, 2006; Batra et al., 2003; Distel et al., 2011; Ehlers et al., 2010; Gillespie et al., 2007; Horimoto et al., 2012; Li, 2003; Pickens et al., 1991; Vink et al., 2010; Wang et al., 2012), and an emerging literature reporting significant heritability for the common addiction liability diathesis (Hicks et al., 2012; Palmer et al., 2012; Vanyukov and Ridenour, 2012; Vrieze et al., 2012a,b). In this study, we use data from a nationally representative survey to examine the U.S. prevalence of various patterns of early adolescent (prior to age 16) use of alcohol, cigarettes, and marijuana individually and in combination and differences of these patterns in age, gender, and race/ethnicity among users of all three substances. We then examine the associations between early adolescent use of alcohol, cigarettes and marijuana with a spectrum of subsequent young adult substance use outcomes ranging from regular drinking and smoking behavior to binge drinking, use of illicit drugs such as cocaine and methamphetamine, to the young adult development of DSM-IV substance use disorder diagnoses. In that context, we examine the hypothesis that there is specificity of the risk of early drug use to young adult problematic involvement. That is, early alcohol drinking leads to later alcohol problems, early smoking leads to later regular smoking, and early marijuana use leads to later regular marijuana use and use of illicit drugs. Next, we examine whether risk for young adult problems with substances is related to use of specific drugs prior to age 16 or the interactive patterns of drug types, which might be a reflection of developmental patterning consistent with a “gateway” hypothesis. Then we examine whether an additive combinations of drugs used in early adolescence is associated with young adult problems with substances, a hypothesis consistent with an underlying addiction-prone diathesis. Finally, we test the hypothesis that the relationship between early drug use behaviors and problematic involvement with substances in young adulthood is mediated by the overt social deviancy of the adolescent in consistence with the notion of a diathesis driven largely by delinquency as an extreme

form of behavioral disinhibition. It is hoped that this investigation will clarify the magnitude and nature of risk of early adolescent substance use in a representative sample, and suggest a suitable prevention strategy to mitigate risk and avert substance-related problems later in life. 2. Methods 2.1. Data sources The current study draws upon the restricted-use data from Waves I (1994–1995) and IV (2008) of the National Longitudinal Study of Adolescent Health (Add Health), the largest, most comprehensive survey of adolescents ever undertaken in the United States. Add Health was designed by a nationwide team of multidisciplinary investigators from the social, behavioral, and biomedical sciences to help explain the causes of adolescent health and health behavior and the effects of multiple contexts of adolescent life, through the longitudinal follow-up, to identify developmental and health trajectories across the life course of adolescence into young adulthood, and to study how social environments and behaviors in adolescence are linked to health and achievement outcomes in young adulthood. Add Health collected data from a nationally representative sample of adolescents in grades 7 through 12 during the 1994–1995 school year and continued following them into young adulthood with four in-home interviews, most recently in 2008, when they were between ages 24 and 32. This sample selection was carried out using a stratified two-stage sampling design. At the first stage, a stratified sample of 80 high schools was selected along with 52 associated feeder schools (i.e., middle schools and junior high schools that sent graduates to these high schools), with the selection probabilities proportional to school enrolment, from a primary sampling frame of all high schools in the United States. At the second stage, a sample of adolescents was selected from these sampled schools for a 90-minute in-home interview based on the computer-assisted personal interview (CAPI) or the computer-assisted self-interview (CASI). More details on the data collection and design features of Add Health can be found elsewhere (Harris, 2011). 2.2. Case identification The response rates for Waves I and IV Add Health were 79% and 80.3%, respectively. Of the 15,701 respondents who completed the Wave IV interviews, 14,800 had a grand sample cross-sectional weight. Our analytic sample included 4245 respondents who reported having ever used alcohol (more than 2–3 times), marijuana, and cigarettes (at least one cigarette every day for 30 days) as of Wave IV, and reported their age at onset of each respective substance use. 2.3. Statistical analysis To produce nationally representative results with unbiased estimates, we conducted analyses using Stata 12 (StataCorp LP, College Station, TX), a statistical software capable of handling the design effect of Add Health and incorporating the Wave IV grand sample cross-sectional weight into its survey procedures. We presented descriptive estimates for mean or prevalence (%) along with the associated 95% confidence intervals (CIs), tested statistical significance for all pairwise comparisons, and quantified the strength of associations in terms of adjusted prevalence ratios (PR) from Poisson regression that included the variables described in the following subsections. 2.3.1. Independent variables. The independent variables pertain to early use of alcohol, marijuana, or cigarettes, where early use was defined by the onset of use prior to age 16. We identified the following 8 patterns of use with varying sample size: No Early Use (n = 1539), Early Regular Use of Cigarettes Only (n = 175), Early Use of Marijuana Only (n = 274), Early Use of Marijuana And Cigarettes (n = 137), Early Use of Alcohol Only (n = 609), Early Use of Alcohol and Cigarettes (n = 161), Early Use of Alcohol And Marijuana (n = 666), and Early Use of Alcohol, Marijuana, and Cigarettes (n = 684). These 8 patterns of use were included in the regression as 7 dummy variables corresponding to the last 7 patterns of early use with “No Early Use” as the reference category. This model can be seen as to estimate 3 main effects of early use (alcohol, marijuana, and cigarettes), 3 two-way interaction effects of early use (alcohol and marijuana, alcohol and cigarettes, and marijuana and cigarettes), and 1 three-way interaction effects of early use (alcohol and marijuana and cigarettes). 2.3.2. Covariates. Covariates or the potential confounders controlled for in regression included basic demographics, namely, age (24–26, 27, 28, 29, 30, and 31–32) from Wave IV, biologic sex (male, female) from Wave IV, and race/ethnicity (nonHispanic White, non-Hispanic Black, non-Hispanic others, and Hispanics) from Wave I. 2.3.3. Dependent variables. The dependent variables pertained to substance use and lifetime diagnoses of DSM-IV abuse and dependence of alcohol, marijuana, and other illegal drugs, with dichotomous responses (1 = Yes, 0 = No) indicating whether or not one engaged in certain substance use behavior, whether or not one met any abuse

9.2 [6.5, 12.9] [7.1, 14.3] 10.4 [4.7, 21.5] 8.3 [4.8, 13.7]

5.5 [3.4, 8.6]

[5.0, 9.1]

[1.7, 9.1] 4.07 6.87

Note: 95% confidence intervals in brackets. * The superscript i (i = 1, 2, . . ., 8) indicates a significant pairwise comparison with the pattern i (p < 0.05).

7.2 [4.6, 11.2]

7.4 [3.8, 13.9]

10.11,2

5.9 [4.0, 8.6] 5.2 [2.1, 12.6] 5.1 [3.3, 7.8] 7.1 [3.5, 13.9] 5.1 [2.1, 12.0] 7.8 [5.3, 11.3]

8.2 [4.7, 14.2]

4.31,3,7 [2.7, 6.7] 8.13,6,8 [5.3, 12.2] 3.21,3,7 [1.2, 8.0] 6.61,3 [4.4, 9.8] 8.23 [4.2, 15.6] 17.81,2,4,5,6,7,8 [11.6, 26.3] 4.41,3 [2.0, 9.4] 9.72,3,5,6,8 [7.0, 13.2]

81.11,3 [76.2, 85.2] 75.92,3 [69.6, 81.2] 84.23 [75.1, 90.3] 81.01,3 [75.5, 85.5] 74.22 [63.6, 82.6] 86.41,3,4,7 [78.6, 91.7] 75.72,3,5,8 [70.3, 80.5]

65.71,2,5,6,7,8 [56.1, 74.2]

55.4 [49.8, 60.9] 44.6 [39.1, 50.2] 61.51,2,5 [56.4, 66.3] 38.51,2,5 [33.7, 43.6] 54.0 [44.6, 63.1] 46.0 [36.9, 55.4] 53.87 [48.0, 59.5] 46.27 [40.5, 52.0] 55.3 [44.4, 65.8] 44.7 [34.2, 55.6] 44.97 [34.5, 55.8] 55.17 [44.2, 65.5] 53.97 [50.6, 57.2] 46.17 [42.8, 49.4]

54.3 [47.3, 61.2] 45.7 [38.8, 52.7]

27.81,2,5,6,7 [27.5, 28.2] 28.91,3,4,7,8 [28.5, 29.3] 28.12,4,5,6,8 [27.8, 28.4] 27.61,2,5,6,7 [27.2, 28.1] 28.43,4,7,8 [28.1, 28.8] 27.81,2,5,6 [27.4, 28.3] 28.63,4,7,8 [28.2, 29.0] 28.33,4,6,8 [28.0, 28.6]

16.01,2,3,4,6 [14.4, 17.7] 3.91,3,5,7,8 [3.1, 4.9] 14.31,2,3,4,6,8 [12.9, 15.9] 3.51,3,5,7,8 [2.8, 4.4] 5.91,2,4,5,6,7,8 [4.8, 7.4] 3.81,3,5,7,8 [3.0, 4.7] 34.42,3,4,5,6,7,8 [32.2, 6.7]

53

Weighted population distribution (%) Age (at Wave 4) Mean (years) Sex Male Female Race/ethnicity Non-Hispanic White Non-Hispanic Black Non-Hispanic others Hispanics

7 Early Use of Alcohol and Marijuana (n = 666) 6 Early Use of Alcohol and Cigarettes (n = 161) 5 Early Use of Alcohol Only (n = 609) 4 Early Use of Marijuana and Cigarettes (n = 137) 3 Early Use of Marijuana Only (n = 274) 2 Early Regular Use of Cigarettes Only (n = 175) 1 No Early Use (n = 1539)

The age, sex, and racial/ethnic distributions of our analytic sample by the pattern of early adolescent substance use are described in Table 1. At the Wave IV follow-up, the mean age of respondents in each substance use pattern category is approximately 28 years old. As can be seen, the largest percentage of individuals falls into the “No Early Use” category (n = 1539; 34.4%). However, a near equal proportion of individuals fall into the combined “Early Use of Alcohol and Marijuana” (n = 666) and the “Early Use of Alcohol, Marijuana, and Cigarettes” (n = 684) categories (total n = 1350; 34.1%), suggesting the relatively high prevalence of this type of polysubstance use among adolescents prior to age 16. Across substance use patterns, 52.4% of individuals (n = 2120) reported alcohol use before age 16, reflecting that alcohol is the most commonly used drug in the U.S. among young adolescents. However, early marijuana use was not far behind having been endorsed by 43.6% of individuals (n = 1761). Early use of cigarettes was endorsed by 29.3% (n = 1157). On average, individuals in this cohort initiated alcohol use at a younger age (15.1 years), followed by marijuana use (16.0 years), and regular cigarette use (17.0 years) (data not shown in Table 1). In terms of the gender distribution, for all categories except “Early Regular Use of Cigarettes Only,” a higher percentage of males were present in each early drug use and non-early use category. This gender discrepancy was particularly evident in the “Early Use of Alcohol and Marijuana” grouping, wherein males comprised 61.5%, and females comprised 38.5%. However, gender differences across the other categories of polysubstance use were not statistically significant. The racial/ethnic distribution of early adolescent substance use demonstrates a clear over-representation of non-Hispanic whites across all early use (and non-early use) categories. However, among minority groups, it is noteworthy that non-Hispanic blacks had a sizable presentation in “No Early Use” (9.7%), and particularly in the “Early Use of Marijuana Only” (17.8%) group, in contrast

Pattern of early onset of substance use*

3.1. Sample demographics and the prevalence of patterns of early adolescent substance use

Demographics

3. Results

Table 1 Mean age and percentage distribution of sex and race/ethnicity by early onset (age < 16) of alcohol, marijuana, or cigarette use, Add Health (Wave IV, n = 4245).

2.3.4. Mediator variable. Overt social deviancy, measured by the self-reported number of arrests before age 18, was included in the regression model as a mediator in a sensitivity analysis to assess whether or not the observed relationships between specific types of early adolescent drug use and young adult substance involvement could be completely explained by the mechanism in which specific types of early adolescent drug use increased overt social deviancy, which in turn resulted in young adult substance involvement. In the current study, the mediation effect was assessed by comparing two sets of final regression models with and without including the mediator as an additional covariate.

8 Early Use of Alcohol, Marijuana, and Cigarettes (n = 684)

criterion for the abuse diagnosis, or whether or not one met both 3+ out of the 7 dependence criteria and the clustering criterion for the dependence diagnosis. Nicotine dependence also was examined. One was considered nicotine dependence if he or she scored between 6 and 10 on the Fagerström Test for Nicotine Dependence or between 4 and 6 on the Heavy Smoking Index scale (Heatherton et al., 1989, 1991). Substance use behaviors of interest included daily smoking in the past 30 days; any alcohol use in the past 12 months, past 30 days, and past 24 h; drunkenness in the past 12 months; binge drinking (i.e., 5+ drinks for men and 4+ drinks in a row) in the past 12 months; drinking more alcohol in a period of life than now; and daily or almost daily marijuana use in the past 30 days, in addition to experiences in having taken any prescription drugs not prescribed, or in larger amounts than prescribed, or more often than prescribed, or for longer periods than prescribed, or for the feeling or experience they caused; and specifically with respect to sedatives or downers, such as barbiturates, sleeping pills, Quaalude, or Seconal; tranquilizers, such as Librium, Valium, or Xanax; stimulants or uppers, such as amphetamines, prescription diet pills, Ritalin, Preludin, or speed; and pain killers or opioids, such as Vicodin, OxyContin, Percocet, Demerol, Percodan, or Tylenol with codeine. Additional substance use outcomes were lifetime use of anabolic steroids, cocaine, crystal meth, and other types of illegal drugs than marijuana, such as LSD, PCP, ecstasy, heroin, or mushrooms; or inhalants.

18.11,2,3,4,5,6 [16.6, 19.8]

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62

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to endorsement of the “Early Use of Alcohol, Marijuana, and Cigarettes” (4.3%) group. 3.2. Young adult substance use outcomes and specific DSM-IV substance abuse and dependence diagnoses 3.2.1. Effects of patterns of early use of cigarettes, alcohol, and marijuana and their additive combinations. Table 2 shows the adjusted prevalence of young adult substance abuse behaviors according to early substance use patterns. Table 3 displays the prevalence ratio (PR), adjusted for age, gender, and race/ethnicity, of substance use behaviors according to early onset use of alcohol, marijuana, and cigarettes, with “No Early Use” as the reference category for comparison. Notably, early use of cigarettes in general was associated with reduced prevalence for young adult alcohol use. For example, “Early Regular Use of Cigarettes Only” was associated with significantly reduced prevalence for endorsing “being drunk (past 12 months)” (PR = 0.84) in young adulthood in comparison to the “No Early Use” group. The “Early Users of Marijuana Only” group was found to have significantly higher prevalence for being a daily cigarette smoker (past 30 days) (PR = 1.41), a daily or almost daily marijuana user (past 30 days) (PR = 2.37), and taking sedative not prescribed (PR = 1.43), a significantly higher prevalence for having ever using cocaine (PR = 1.44), crystal methamphetamine (PR = 1.71), and other illegal drugs than marijuana (PR = 1.29) in comparison to the “No Early Use” group. Members of the “Early Use of Alcohol Only” had significantly higher prevalence for 5+/4+ drinks in a row (i.e. binge drinking) (PR = 1.11), having drunk more alcohol than now in the past (PR = 1.19), being drunk during the last 12 months (PR = 1.07), and having ever used illegal drugs other than marijuana (PR = 1.21) than the “No Early Use” group. However, this group also had significantly lower prevalence for being a daily smoker (PR = 0.81) in comparison to the non-early users. The group that endorsed “Early Use of Marijuana and Cigarettes” showed significantly higher prevalence (PR = 1.26) for being a daily smoker (past 30 days), a daily or almost daily marijuana user (past 30 days) (PR = 2.81), and for having ever used cocaine (PR = 1.36), crystal methamphetamine (PR = 2.06), and other illegal drugs (PR = 1.34) in comparison to the “No Early Use” group. In addition, early users of marijuana and cigarettes had significantly lower prevalence for 5+/4+ drinks in a row (binge drinking) (PR = 0.81), and having been drunk during the past 12 months (PR = 0.72) in comparison to the “No Early Use” group. The “Early Use of Alcohol and Cigarettes” group reported significantly higher prevalence for using marijuana daily or almost daily in the past 30 days (PR = 3.03), having taken prescription drugs not prescribed (PR = 1.45), specifically painkillers (PR = 1.48) and having ever used other illegal drugs than marijuana (PR = 1.29) in comparison to the “No Early Use” group. The “Early Use of Alcohol and Marijuana” group reported significantly higher prevalence for having drunk more than now (PR = 1.13), using marijuana daily or almost daily in the past 30 days (PR = 1.99), taking prescription drugs that were not prescribed (PR = 1.72), specifically sedatives (PR = 1.82), tranquilizers (PR = 1.97), stimulants (PR = 2.07), pain killers (PR = 1.84), having ever used steroids (PR = 2.46), cocaine (PR = 1.62), crystal methamphetamine (PR = 2.35), and other illegal drugs than marijuana (PR = 1.67) in comparison to those who had no early drug use. Lastly, the group that endorsed “Early Use of Alcohol, Marijuana, and Cigarettes” reported significantly higher prevalence for being a daily smoker over the past 30 days (PR = 1.15), having drunk more than now in the past (PR = 1.14), taking prescription drugs not prescribed (PR = 1.60), specifically sedatives (PR = 1.88), tranquilizers (PR = 1.96), stimulants (PR = 1.89), and painkillers (PR = 1.63). In addition, they had significantly higher prevalence for having ever used cocaine (PR = 1.68), crystal methamphetamine (PR = 2.61), other illegal drugs than marijuana (PR = 1.57). Interestingly, they

also had significantly lower prevalence for having had alcohol in the last 12 months (PR = 0.93) and having been drunk (PR = 0.92) in the past 12 months compared with the “No Early Use” group. It is also noteworthy that daily smoking, alcohol, and daily marijuana use in the past 30 days, among early users of multiple substances, were not significantly higher than among single substance users. Table 5 displays the adjusted prevalence rates of ever meeting DSM-IV diagnostic criteria for specific substance use disorders in young adulthood. Table 6 compares the adjusted prevalence ratios associated with the categories of early adolescent cigarette, alcohol and marijuana use and specific DSM-IV abuse and dependence diagnoses with the “No Early Use” category. Risk for a DSM-IV alcohol abuse diagnosis was significantly associated with early alcohol use alone (PR = 1.39), Early Use of Alcohol And Marijuana (PR = 1.55), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 1.33). Risk for a DSM-IV marijuana abuse diagnosis was significantly associated with Early Use of Marijuana Only (PR = 1.55), Early Use of Alcohol And Marijuana (PR = 1.95), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 1.89). Risk for other DSMIV illegal drug abuse diagnoses were significantly associated with Early Use of Marijuana And Cigarettes (PR = 2.15), Early Use of Alcohol And Marijuana (PR = 2.42), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 2.29). Risk for a DSM-IV alcohol dependence diagnosis was significantly associated with early use of cigarettes (PR = 1.47), Early Use of Alcohol Only (PR = 1.58), Early Use of Alcohol And Marijuana (PR = 1.84), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 1.58). Risk for nicotine dependence was associated with early use of cigarettes only (PR = 1.74), Early Use of Marijuana And Cigarettes (PR = 1.89), Early Use of Alcohol and Cigarettes (PR = 1.69), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 1.74). Risk for a DSM-IV marijuana dependence disorder was associated with early use of alcohol alone (PR = 1.72), Early Use of Alcohol and Cigarettes (PR = 1.79), Early Use of Alcohol And Marijuana (PR = 2.15), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 2.47). The risk for other DSM-IV illegal drug dependence diagnoses, was associated with early regular cigarette use (PR = 1.72), early marijuana use (PR = 1.85), Early Use of Marijuana And Cigarettes (PR = 2.17), Early Use of Alcohol And Marijuana (PR = 2.66), and Early Use of Alcohol, Marijuana, and Cigarettes (PR = 3.19). 3.2.2. Specificity of effects of early drug use and their interactions on young adult substance use involvement. In an effort to examine the specificity of early use drug effects, we have tested the statistical significance of the main and interaction effects of early use of alcohol, marijuana and cigarettes on the young adults’ substance use domains displayed in Table 4. For clarity, these are summarized below by drug. 3.2.2.1. Young adult smoking. Risk for being a young adult daily smoker: There was a significant interaction effect of combined early alcohol and early cigarette use (PR = 1.25), while early marijuana and cigarette use (PR = 0.73) was associated with decreased risk. There were also main effects of early marijuana use (PR = 1.22), and early cigarette use (PR = 1.19) increasing risk, and a main effect of early alcohol use (PR = 0.83) decreasing risk. 3.2.2.2. Young adult alcohol use. Risk for having drunk alcohol in the past 12 months as a young adult: There was only a significant main effect of early use of cigarettes (PR = 0.93) that was somewhat protective. Young adult risk for having 5+/4+ drinks in a row (i.e. binge drinking): There were only significant main effects for early alcohol use somewhat increasing risk (PR = 1.09), and early cigarette use (PR = 0.90) decreasing risk.

Table 2 Adjusted prevalencea (%) of substance use as of Wave IV, according to pattern of early onset (age < 16) of alcohol, marijuana, and cigarette use, Add Health (Wave IV, n = 4.245). Substance use as of Wave IV

1 No Early Use (n = 1.539)

2 Early Regular Use of Cigarettes Only (n = 175)

3 Early Use of Marijuana Only (n = 274)

4 Early Use of Marijuana and Cigarettes (n = 137)

5 Early Use of Alcohol oNly (n = 609)

6 Early Use of Alcohol and Cigarettes (n = 161)

7 Early Use of Alcohol and Marijuana (n = 666)

8 Early Use of Alcohol, Marijuana, and Cigarettes (n = 684)

45.93,4,5,8 [42.5, 49.2]

53.43,5 [43.8, 62.9]

64.61,2,5,7,8 [57.5, 71.7]

57.91,5,7 [48.1, 67.6]

37.21,2,3,4,6,7,8 [32.2, 42.2]

57.05 [44.8, 69.2]

47.13,4,5,8 [42.6, 51.5]

52.71,3,5,7 [48.4, 57.0]

93.74,6,8 [91.8, 95.5]

89.5 [83.7, 95.3]

94.36,8 [90.4, 98.1]

85.51,5 [78.2, 92.9]

94.24,6,8 [92.0, 96.4]

84.71,3,5,7 [77.5, 91.9]

92.66,8 [89.9, 95.3]

86.81,3,5,7 [83.6, 89.9]

73.34,5 [70.1, 76.4]

66.15 [55.5, 76.6]

72.44 [63.6, 81.2]

59.51,3,5,7 [49.3, 69.7]

81.21,2,4,6,7,8 [77.4, 85.0]

68.55 [60.8, 76.2]

74.94,5 [70.3, 79.4]

70.05 [66.3, 73.8]

76.02,4,5,6,8 [72.6, 79.4]

63.61,5,7 [53.8, 73.4]

72.14,5 [63.7, 80.5]

54.71,3,5,7,8 [44.1, 65.3]

81.01,2,3,4,6,8 [76.7, 85.4]

65.61,5,7 [56.4, 74.8]

79.52,4,6,8 [75.2, 83.8]

69.81,4,5,7 [66.3, 73.4]

80.52 [77.5, 83.6]

70.01,5,7 [60.5, 79.6]

78.1 [70.4, 85.7]

72.85,7 [64.1, 81.5]

83.92,4,8 [79.9, 87.8]

75.9 [68.6, 83.2]

84.22,4,8 [80.8, 87.6]

76.15,7 [72.4, 79.9]

31.5 [27.9, 35.1]

23.05,7,8 [15.1, 31.0]

29.3 [22.6, 36.0]

33.2 [22.6, 43.9]

36.92 [29.9, 43.8]

33.8 [24.0, 43.5]

35.32 [30.3, 40.3]

34.12 [29.9, 38.4]

64.05,7,8 [60.2, 67.7]

69.8 [61.4, 78.1]

59.65,7,8 [52.1, 67.0]

58.25,7,8 [47.6, 68.8]

76.11,3,4 [71.6, 80.7]

68.1 [59.2, 77.0]

72.01,3,4 [67.3, 76.7]

72.71,3,4 [68.8, 76.6]

14.81 [9.1, 20.5]

17.51 [9.2, 25.9]

18.91,2,5 [10.2, 27.6]

12.41,8 [9.8, 15.1]

17.31,2,5,7 [13.4, 21.3]

6.23,4,6,7,8 [4.7, 7.8]

8.06,8 [2.7, 13.3]

8.66,8 [5.7, 11.5]

28.06,7,8 [24.5, 31.5]

20.43,5,6,7,8 [13.7, 27.2]

33.92,7,8 [26.6, 41.2]

32.67,8 [21.7, 43.4]

31.92,7,8 [26.8, 37.0]

40.51,2 [30.8, 50.2]

48.01,2,3,4,5 [42.9, 53.2]

44.91,2,3,4,5 [39.8, 50.0]

16.07,8 [12.6, 19.4] 15.07,8 [12.4, 17.6] 11.27,8 [8.9, 13.5] 23.66,7,8 [20.2, 27.1] 2.37 [1.3, 3.3] 35.43,4,7,8 [32.1, 38.6] 13.23,4,7,8 [10.4, 15.9]

12.23,4,7,8 [6.9, 17.4] 9.73,4,5,6,7,8 [4.2, 15.1] 9.47,8 [4.2, 14.6] 16.63,5,6,7,8 [9.9, 23.4] 3.8 [0.2, 7.3] 33.53,4,7,8 [24.4, 42.5] 18.07,8 [9.4, 26.6]

22.92,5 [16.2, 29.7] 18.62,7,8 [12.5, 24.7] 15.17 [9.1, 21.1] 27.52,7,8 [19.7, 35.3] 1.06,7,8 [-0.5, 2.5] 50.91,2,5 [42.3, 59.5] 22.61,8 [14.3, 30.8]

23.72 [13.8, 33.5] 20.92 [11.1, 30.7] 14.0 [5.4, 22.6] 22.57,8 [12.7, 32.3] 2.2 [-1.7, 6.2] 48.21,2,8 [38.8, 57.5] 27.11,5 [17.1, 37.1]

14.03,7,8 [10.6, 17.4] 17.12,7,8 [12.7, 21.6] 12.87,8 [9.1, 16.5] 27.12,7,8 [22.1, 32.1] 3.5 [1.4, 5.6] 37.23,7,8 [31.3, 43.1] 14.54,7,8 [10.3, 18.7]

17.07,8 [9.6, 24.3] 19.72,7 [11.2, 28.2] 17.3 [10.2, 24.3] 35.01,2 [25.0, 45.0] 4.43 [0.9, 8.0] 39.17,8 [29.4, 48.8] 18.17,8 [11.2, 24.9]

29.21,2,5,6 [25.0, 33.4] 29.61,2,3,5,6 [25.1, 34.1] 23.21,2,3,5 [19.2, 27.2] 43.41,2,3,4,5 [38.2, 48.6] 5.61,3 [3.3, 8.0] 57.31,2,5,6 [52.2, 62.4] 30.91,2,5,6 [25.7, 36.1]

30.11,2,5,6 [25.9, 34.2] 29.31,2,3,5 [24.7, 34.0] 21.21,2,5 [16.7, 25.6] 38.61,2,3,4,5 [33.4, 43.7] 3.33 [1.8, 4.9] 59.31,2,4,5,6 [54.7, 64.0] 34.31,2,3,5,6 [28.8, 39.9]

39.93,4,5,7,8 [35.9, 44.0]

31.83,4,5,6,7,8 [23.3, 40.4] 51.71,2,7,8 [42.4, 61.0]

53.71,2,7 [43.9, 63.5]

48.41,2,7,8 [42.8, 54.0]

51.72,7 [40.4, 63.0]

66.81,2,3,4,5,6 [62.3, 71.3]

62.51,2,3,5 [57.9, 67.2]

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62

Daily cigarette smoking (past 30 days) Had alcohol (past 12 months) 5+ (men) or 4+ (women) drinks in a row (past 12 months) Been drunk (past 12 months) Had alcohol (past 30 days) Had alcohol (past 24 h) Drank more than now Daily/almost daily marijuana use (past 30 days) Ever taken prescription drugs not prescribed Sedatives Tranquilizers Stimulants Pain killers Ever used steroid Ever used cocaine Ever used crystal meth Ever used other illegal drugs, except marijuana

Pattern of early onset of substance use*

Note: 95% confidence intervals in brackets. 1 Adjusted for sex, age, and race/ethnicity. a Adjusted for sex, age, and race/ethnicity. * Superscript i (i = 1, 2, . . ., 8) indicates a significant pairwise comparison with pattern i (p < 0.05).

55

56 Table 3 Adjusted prevalence ratioa of substance use as of Wave IV, according to pattern of early onset (age < 16) of alcohol, marijuana, and cigarette use, with “No Early Use” as the reference category for comparison, Add Health (Wave IV, n = 4.245). Substance use as of Wave IV

No Early Use (n = 1539)

Early Use of Cigarettes Only (n = 175)

Early Use of Marijuana Only (n = 274)

Early Use of Marijuana and Cigarettes (n = 137)

Early Use of Alcohol Only (n = 609)

Early Use of Alcohol and Cigarettes (n = 161)

Early Use of Alcohol and Marijuana (n = 666)

Early Use of Alcohol, Marijuana, and Cigarettes (n = 684)

Adjusted prevalence ratio

a * ** ***

1

1.16

1.41***

1.26**

0.81**

1.24

1.03

1.15*

1

0.96

1.01

0.91*

1.01

0.90*

0.99

0.93***

1

0.90

0.99

0.81*

1.11***

0.93

1.02

0.96

1

0.84*

0.95

0.72**

1.07*

0.86*

1.05

0.92*

1

0.87

0.97

0.90

1.04

0.94

1.05

0.95

1 1 1

0.73 1.09 1.28

0.93 0.93 2.37***

1.06 0.91 2.81***

1.17 1.19*** 1.38

1.07 1.06 3.03***

1.12 1.13* 1.99***

1.08 1.14** 2.78***

1

0.73

1.21

1.16

1.14

1.45**

1.72***

1.60***

1 1 1 1 1 1 1 1

0.76 0.64 0.84 0.70 1.66 0.95 1.37 0.80

1.43* 1.24 1.35 1.16 0.44 1.44*** 1.71* 1.29**

1.48 1.40 1.25 0.95 0.98 1.36** 2.06*** 1.34**

0.87 1.14 1.15 1.15 1.54 1.05 1.10 1.21*

1.06 1.31 1.54 1.48* 1.94 1.11 1.37 1.29*

1.82*** 1.97*** 2.07*** 1.84*** 2.46** 1.62*** 2.35*** 1.67***

1.88*** 1.96*** 1.89*** 1.63*** 1.45 1.68*** 2.61*** 1.57***

Adjusted for sex, age, and race/ethnicity. p < .05. p < .01. p < .001.

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62

Daily cigarette smoking (past 30 days) Had alcohol (past 12 months) 5+ (men) or 4+ (women) drinks in a row (past 12 months) Been drunk (past 12 months) Had alcohol (past 30 days) Had alcohol (past 24 h) Drank more than now Daily/almost daily marijuana use (past 30 days) Ever taken prescription drugs not prescribed Sedatives Tranquilizers Stimulants Pain killers Ever used steroid Ever used cocaine Ever used crystal meth Ever used other illegal drugs, except marijuana

Table 4 Main and interaction effectsa of early onset (age < 16) of alcohol, marijuana, and cigarette use on young adult substance use behaviors as of Wave IV, Add Health (Wave IV, n = 4245). Substance use as of Wave IV

Effect of early onset of use (adjusted prevalence ratio) Marijuana

Cigarettes

Alcohol × Maijuana

Alcohol × cigarettes

Marijuana × cigarettes

Alcohol × marijuana × cigarettes

0.83*** 1.00 1.09** 1.09*** 1.05* 1.17* 1.18*** 1.24 1.30*** 1.09 1.34*** 1.36** 1.40*** 1.85* 1.11 1.20* 1.25***

1.22*** 0.99 0.95 0.97 1.00 0.99 0.95 1.63*** 1.34*** 1.77*** 1.55*** 1.52*** 1.34*** 1.10 1.49*** 1.89*** 1.34***

1.19*** 0.93*** 0.90*** 0.85*** 0.90*** 0.94 1.00 1.46** 0.96 1.02 0.98 0.96 0.91 0.85 1.01 1.17 0.95

– – – – – – – 0.56* – – – – – – – – –

1.25* – – – – – – – – – – – – – – – –

0.73** – – – – – – – – – – – – – – – –

– – – – – – – – – – – – – – – – –

a

Adjusted for sex, age, and race/ethnicity. p < .05. ** p < .01. *** p < .001. –: The nonsignificant two-way or three-way interaction term was excluded from the model. *

Table 5 Adjusted prevalencea (%) of ever meeting DSM-IV substance abuse or dependence criteria as of Wave IV, according to pattern of early onset (age < 16) of alcohol, marijuana, and cigarette use, Add Health (Wave IV, n = 4245). Ever meeting DSM-IV substance use disorders criteria as of Wave IV

Abuse Alcohol Marijuana Other illegal drugs Dependence Alcohol Nicotine Marijuana Other illegal drugs

Pattern of early onset of substance use*

1 No Early Use (n = 1539)

2 Early Regular Use of Cigarettes Only (n = 175)

3 Early Use of Marijuana Only (n = 274)

4 Early Use of Marijuana and Cigarettes (n = 137)

5 Early Use of Alcohol Only (n = 609)

6 Early Use of Alcohol and cigarettes (n = 161)

7 Early Use of Alcohol and Marijuana (n = 666)

8 Early Use of Alcohol, Marijuana, and Cigarettes (n = 684)

37.65,7,8 [33.3, 41.9] 14.57,8 [11.3, 17.7] 9.14,7,8 [6.6, 11.5]

31.85,7,8 [22.9, 40.7] 15.17,8 [7.3, 22.9] 9.74,7,8 [4.7, 14.7]

41.97 [33.3, 50.5] 22.4 [15.2, 29.5] 14.7 [8.6, 20.8]

35.55,7,8 [25.1, 45.9] 20.8 [12.6, 29.0] 19.51,2,6 [10.9, 28.1]

52.11,2,4 [46.1, 58.1] 19.17,8 [14.1, 24.1] 10.17,8 [6.5, 13.6]

42.17 [32.7, 51.5] 18.97 [11.1, 26.7] 8.24,7,8 [3.4, 13.1]

58.31,2,3,4,6,8 [53.9, 62.7] 28.11,2,5,6 [23.7, 32.6] 22.01,2,5,6 [17.5, 26.4]

49.91,2,4,7 [44.5, 55.2] 27.31,2,5 [22.7, 32.0] 20.81,2,5,6 [17.1, 24.5]

15.65,7,8 [13.2, 18.0] 27.12,4,6,8 [24.2, 30.1] 8.45,7,8 [6.3, 10.5] 6.37,8 [4.4, 8.2]

22.9 [15.1, 30.7] 47.31,3,5,7 [38.3, 56.2] 12.18 [5.5, 18.8] 10.88 [5.8, 15.9]

14.05,7,8 [7.7, 20.2] 31.42,4,6,8 [24.6, 38.2] 13.08 [8.1, 18.0] 11.78 [6.0, 17.3]

17.97 [9.6, 26.3] 51.31,3,5,7 [39.8, 62.8] 12.88 [5.8, 19.7] 13.7 [6.2, 21.2]

24.61,3 [19.8, 29.5] 25.12,4,6,7,8 [20.5, 29.7] 14.51,8 [10.9, 18.1] 8.37,8 [5.5, 11.0]

16.07,8 [8.7, 23.3] 45.81,3,5,7 [37.2, 54.4] 15.1 [7.5, 22.6] 7.07,8 [2.7, 11.3]

28.71,3,4,6 [24.6, 32.8] 31.92,4,5,6,8 [26.5, 37.2] 18.11 [14.6, 21.5] 16.81,5,6 [13.4, 20.2]

24.71,3,6 [20.9, 28.5] 47.31,3,5,7 [42.8, 51.8] 20.71,2,3,4,5 [17.2, 24.3] 20.11,2,3,5,6 [16.5, 23.8]

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62

Daily cigarette smoking (past 30 days) Had alcohol (past 12 months) 5+ (men) or 4+ (women) drinks in a row (past 12 months) Been drunk (past 12 months) Had alcohol (past 30 days) Had alcohol (past 24 h) Drank more than now Daily/almost daily marijuana use (past 30 days) Ever taken prescription drugs not prescribed Sedatives Tranquilizers Stimulants Pain killers Ever used steroid Ever used cocaine Ever used crystal meth Ever used other illegal drugs, except marijuana

Alcohol

Note: 95% confidence intervals in brackets. a Adjusted for sex, age, and race/ethnicity. * Superscript i (i = 1, 2, . . ., 8) indicates a significant pairwise comparison with pattern i (p < 0.05). 57

1.33*** 1.89*** 2.29***

1.58*** 1.74*** 2.47*** 3.19***

1.55*** 1.95*** 2.42***

3.2.2.3. Young adult marijuana use. Risk for young adult daily marijuana use: Early marijuana use and early cigarette use had significant risk-augmenting main effects (PR = 1.63 and 1.46, respectively) on “daily marijuana use”, although a surprising protective effect was noted for the significant interaction of early use of both alcohol and marijuana (PR = 0.56). 3.2.2.4. Other drug use as a young adult. Endorsement of having taken “prescription drugs not prescribed” was predicted by risk-augmenting main effects of early use of alcohol (PR = 1.30), and marijuana (PR = 1.34). For the specific classes of prescription drugs used, “sedative use” was predicted by a main effect of early marijuana use (PR = 1.77), while “use of un-prescribed tranquilizers” was associated with main effects of both early alcohol use (PR = 1.34), and early marijuana use (PR = 1.55). “Stimulant use” was predicted by main effects of early alcohol use (PR = 1.36), and early marijuana use (PR = 1.52). The risk for use of un-prescribed “pain killers” was associated with main effects of the early alcohol use (PR = 1.40) and early marijuana use (PR = 1.34), but not any of the early drug use interactions. The risk for having ever used anabolic steroids in young adulthood was augmented by early alcohol use (PR = 1.85). While, risk for “having ever used cocaine or crystal methamphetamine” by young adulthood was only associated with early use of marijuana as a main effect (PR = 1.49 and PR = 1.89, respectively). An augmented risk for having “ever used other illegal drugs except marijuana” was associated with significant main effects of early use of alcohol (PR = 1.25) and marijuana (PR = 1.34).

1.84*** 1.17 2.15*** 2.66***

**

***

Adjusted for sex, age, and race/ethnicity. p < .05. p < .01. p < .001. *

a

1.15 1.89*** 1.52 2.17* 1.47* 1.74*** 1.44 1.72* 1 1 1 1

0.90 1.16 1.55 1.85*

1.58*** 0.92 1.72** 1.31

1.12 1.31 0.91 0.94 1.44 2.15** 0.84 1.04 1.07 1 1 1

Abuse Alcohol Marijuana Other illegal drugs Dependence Alcohol Nicotine Marijuana Other illegal drugs

Adjusted prevalence ratio

1.11 1.55* 1.62

1.39*** 1.32 1.11

Early Use of Alcohol Only (n = 609) Early Use of Marijuana and Cigarettes (n = 137) Early Use of Marijuana Only (n = 274) Early Use of Cigarettes Only (n = 175) No Early Use (n = 1539) Ever meeting DSM-IV substance use disorders criteria as of Wave IV

Risk for young adult drunkenness during the past 12 months: There were only significant main effects of early use of cigarettes (PR = 0.85), which was protective and early alcohol use (PR = 1.09), which somewhat augmenting risk. Risk for young adult consumption of alcohol in the past 30 days: There were significant main effects of early cigarettes use (PR = 0.90) associated with diminished risk and early alcohol use (PR = 1.05) somewhat augmenting risk. Risk for young adult consumption of alcohol in the past 24 h: There was significant risk-augmenting main effect item early alcohol use (PR = 1.17). Young adult risk for “having drunk more than now in the past”: There was a significant risk-augmenting main effect of early use of alcohol (PR = 1.18).

1.03 1.69*** 1.79* 1.10

Early Use of Alcohol, Marijuana, and Cigarettes (n = 684) Early Use of Alcohol and Cigarettes (n = 161)

Early Use of Alcohol and Marijuana (n = 666)

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62 Table 6 Adjusted prevalence ratioa of ever meeting DSM-IV substance abuse or dependence criteria as of Wave IV, according to pattern of early onset (age < 16) of alcohol, marijuana, and cigarette use, with “No Early Use” as the reference category for comparison, Add Health (Wave IV, n = 4245).

58

3.2.3. Specificity of effects of early drug use and their interactions on DSM-IV substance use disorder diagnoses. Table 7 displays the final regression models demonstrating a main effect of “early onset of alcohol use” on ever meeting a DSM-IV alcohol abuse (PR = 1.38) and dependence (PR = 1.47) diagnosis, and on a DSM-IV marijuana abuse (PR = 1.30) or dependence (PR = 1.57) diagnosis. “Early onset marijuana use” had a significant main effect on DSM-IV alcohol abuse (PR = 1.13), marijuana abuse (PR = 1.48) and dependence (PR = 1.32), nicotine dependence (PR = 1.16), as well as abuse and dependence on other illegal drugs (PR = 2.04 and 2.00, respectively). Early onset of cigarette use had a significant risk-augmenting main effect on nicotine dependence (PR = 1.61), while it had a protective effect on an alcohol abuse diagnosis (PR = 0.84). Curiously, the interaction of early use of both alcohol and cigarettes had a protective effect on alcohol dependence diagnoses (PR = 0.66). 3.2.4. Testing mediation by overt social deviancy of the relationships between specific types of early drug use and substance involvement in young adulthood. We employed the self-reported number of arrests prior to age 18 as a surrogate measure of overt social deviancy, and re-computed the tests of main and interaction effects of early adolescent onset of the use of cigarettes, alcohol and marijuana on

Alcohol × marijuana × Cigarettes

– – –

– – – –

Marijuana × cigarettes

– – –

– – – –

59

young adulthood measures of substance involvement while including the number of arrests in the model (Supplementary Tables 1 and 2). Significant main effects of number of arrests were found on having had alcohol in the past 30 days (p < 0.05), taken sedatives not prescribed (p < 0.0001), having ever used cocaine (p < 0.0001), and ever having used crystal methamphetamine (p < 0.005), as well as on having alcohol dependence (p < 0.01), nicotine dependence (p < 0.01), and marijuana abuse (p < 0.005) and dependence (p < 0.005). However, inclusion of arrests in the regression model did not alter the significant main effects and interactions effects of early use of alcohol, cigarettes and marijuana on young adult substance involvement measures. Thus, number of arrests, as a measure of overt social deviancy, did not fully mediate the aforementioned relationships between early adolescent substance use and young adulthood substance use outcomes.

0.66* – – – *

a

Adjusted for sex, age, and race/ethnicity. p < .05. ** p < .01. *** p < .001. Note: The non-significant two-way or three-way interaction terms were excluded from the model.

– – – – 1.12 1.16* 1.32* 2.00*** 1.47*** 0.95 1.57*** 1.29*

1.02 1.61*** 1.14 1.21

– – – – – – 0.84*** 0.98 0.99 1.13* 1.48*** 2.04*** 1.38*** 1.30* 1.17

Abuse Alcohol Marijuana Other illegal drugs Dependence Alcohol Nicotine Marijuana Other illegal drugs

Cigarettes Marijuana Alcohol

Effect of early onset of use (adjusted prevalence ratio)

Alcohol × marijuana

Alcohol × cigarettes

4. Discussion

DSM-IV substance use disorders (Wave IV)

Table 7 Main and interaction effectsa of early onset (age < 16) of alcohol, marijuana, and cigarette use on ever meeting DSM-IV substance abuse or dependence criteria as of Wave IV, Add Health (Wave IV, n = 4245).

H.B. Moss et al. / Drug and Alcohol Dependence 136 (2014) 51–62

This research confirms the elevated prevalence and importance of polysubstance use behavior among adolescents prior to age 16 (Martin et al., 1996; Slesnick et al., 2006), and puts early onset of alcohol, marijuana and cigarette use into the context of use patterns rather than single drug exposures. These data reveal the heterogeneity in the patterns of polysubstance use and support the observation that single drug experimentation is much rarer than use of multiple substances in early adolescence prior to age 16, such that non-early-use of substances is even less prevalent than early polysubstance use in various combinations. In terms of substance classes, 52.4% of respondents reported alcohol use prior to age 16, while 43.6% of respondents reported early marijuana use, and early use of cigarettes was endorsed by 29.3%. While males typically over-represented females in nearly all use patterns, females were more prevalent than males in early use of cigarettes only, suggesting that smoking prevention interventions might specifically target young females as a group at elevated risk. Another at-risk group to warrant targeted prevention interventions would be the early users of multiple substances, who appeared to have a greater diversity of drug involvements by young adulthood than early users of single substances. For instance, Table 2 shows that the prevalence of having ever taken prescription drugs not prescribed as of Wave IV is significantly higher among the early users of alcohol, marijuana, and cigarettes (44.9%), compared with early users of cigarettes only (20.4%), marijuana only (33.9%), or alcohol only (31.9%). Similarly, higher prevalence was observed at Wave IV for having ever used crystal meth and other illegal drugs besides marijuana among early users of alcohol, marijuana, and cigarettes, although their difference in having ever used cocaine was not statistically significant from early users of marijuana only. Nevertheless, the risks of several young adult substance use behaviors among early users of multiple substances were not always significantly higher than earlier single substance users. We found that the elevated risk to young adults of early alcohol, cigarette, and marijuana experimentation in terms of substance behaviors (except daily cigarette smoking and daily/almost daily marijuana use) is related to the additivity of types of substances used before age 16. For instance, because early regular use of cigarettes appeared to protect against alcohol use, including binge drinking and drunkenness (i.e., PR < 1), early users of alcohol, marijuana, and cigarettes had lower prevalence of binge drinking (70.0%) and drunkenness (69.8%) than early users of alcohol only (81.2% for binge drinking and 81.0% for drunkenness). As for the risk of daily cigarette smoking in young adulthood, early regular cigarette use was found to interact with early alcohol use (PR = 1.25) and marijuana use (PR = 0.73) differently. While early alcohol use appeared to protect against daily smoking, early

60

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alcohol use in combination with early regular cigarette use potentiated the effect of early regular cigarette use on the chance of daily cigarette smoking by 25%. By contrast, while early marijuana use appeared to increase daily cigarette smoking, early marijuana use in combination with early regular cigarette use weakened the effect of early regular cigarette use on the chance of daily cigarette smoking by 27%. Regarding the risk of daily/almost daily marijuana use in young adulthood, early marijuana use was found to interact negatively with early alcohol use (PR = 0.56). While early marijuana use appeared to increase daily/almost daily marijuana use, early marijuana use in combination with early alcohol use weakened the effect of early marijuana use on the chance of daily/almost daily marijuana use by 44%. The reasons for these significant interaction effects are not clear. We can only conjecture that early users of marijuana and cigarettes might be more likely than early users of cigarettes only to substitute marijuana for cigarettes, thereby decreasing their chance of daily cigarette smoking. Likewise, early users of both marijuana and alcohol might be more likely than early users of marijuana only to substitute alcohol for marijuana, thereby decreasing their chance of daily/almost daily marijuana use. On the other hand, alcohol use might complement cigarette smoking, thereby stimulating early regular cigarette use among early users of both alcohol and cigarettes. It is interesting to note that early marijuana use had no significant effect on alcohol use or alcohol dependence and that early regular cigarette use had no significant effect on having taken any prescription drugs not prescribed, other illegal drugs than marijuana, or drug dependence in young adulthood. Adolescents with Early Use of Alcohol And Marijuana with or without early use of cigarettes appeared to be at significantly increased risk for both abuse and dependence diagnoses under the DSM-IV schema, although early regular cigarette use among adolescents with early alcohol use somehow protected against alcohol dependence in their young adulthood. However, in terms of acquisition of a DSMIV substance use disorder, the elevated risk to young adults of early alcohol, cigarette, and marijuana experimentation is more related to the additivity of types of substances used before age 16, rather than the specific identity of the substance or specific interactions between substances. These results are consistent with the concept of a common underlying liability to problematic involvement with substances (Hicks et al., 2012; Palmer et al., 2012; Vanyukov and Ridenour, 2012). A noteworthy limitation to the interpretation of our results is that the analytical sample only included the respondents who reported having ever used alcohol (more than 2–3 times), marijuana, and cigarettes (at least 1 cigarette every day for 30 days). Thus, our sample includes both those who had used these substances after age 16, and those who had significant exposure to these substances before age 16. As a result, this study excluded adolescents who used only one or two types of these substances and hence had low-level experimental exposure to other substances (e.g., tried drinking alcohol once before age 16 or experimented with cigarettes two or three times). Therefore, this work can offer little insight into their level of risk for future problematic involvement in substances. Also, while our study supports a relationship between overt adolescent antisocial behavior (in the form of arrests before age 18) and young adult substance use outcomes, this particular measure of antisocial behavior does not fully mediate the association between early adolescent substance use behavior and young adult outcomes. Unfortunately, this study cannot address whether disinhibited personality traits such as impulsivity, sensation-seeking, rebelliousness, or aggression (Krueger et al., 2007) are more potent mediators of this developmental relationship, consistent with the common liability to addiction theory of others.

In conclusion, we have confirmed that early use of a single type of substance (before age 16) is rare among substance users in this particular cohort of U.S. adolescents followed by Add Health, and that the early use of multiple substances is more common than nonearly-use of substances. Our results do not always support a direct correspondence between the early adolescent use of a specific drug and subsequent young adult involvement or development of substance use disorders. Among young adults in the United States, unsanctioned use of prescription drugs, cocaine, crystal methamphetamine, and other illegal drugs is largely associated with the early onset of alcohol and marijuana use. In contrast, problematic involvement with alcohol is largely associated with early alcohol use and is negatively associated with early cigarettes smoking. One potential explanation for this finding is that although the purchase and use of alcohol, cigarettes, or marijuana is illegal for those under age 16 across all 50 States, the nature of the distributional networks for these substances is distinctly different and might account for the differential pathways toward young adult problems. Alcohol and tobacco are distributed through culturally accepted, legally sanctioned, and governmentally regulated outlets for adult purchases, but the distribution network for marijuana at the time of this survey was largely illegal for both adolescents and adults. Thus, early exposure to this illicit marijuana market may increase availability and offer rates for other types of illegal drugs, thereby augmenting subsequent risk for problematic involvement with these substances (Van Etten and Anthony, 1999; Wagner and Anthony, 2002). Finally, the strongest predictor of problematic involvement with substances in young adulthood is the additive effect of psychoactive substances used before age 16. Prevention programs that emphasize delayed use of an individual drug—be it alcohol, tobacco, or marijuana—could therefore yield improved outcomes by having a broader focus across multiple substances. Role of funding source This study was supported through internal funds provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). NIAAA had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The results presented and their interpretation are the author’s, and not do not represent the views of NIAAA or the National Institutes of Health. Contributors All authors materially contributed to the design, analysis, and interpretation of the data. Dr. Moss and Mr. Chiung were responsible for writing the manuscript. All authors have approved the final manuscript. Conflict of interest The authors have no actual or potential conflicts of interest including any financial, personal or other relationships that could inappropriately influence, or be perceived to influence this work. Acknowledgments This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special

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