Search

Little is known about the natural history of drug dependence. This article describes the development and predictors of DSM-IV nicotine dependence in adolescence when tobacco use is initiated. In a two-stage design, a survey was administered to 6th-10th graders in the Chicago Public Schools to select a cohort of adolescents. Household interviews were conducted with adolescents five times and with one parent (predominantly mothers) three times over 2 years. The analytical sample includes 353 youths, who started using tobacco within 12 months preceding Wave 1 or between Waves 1-5. Survival analysis estimated latency to individual DSM-IV nicotine dependence criteria and the full dependence syndrome. Twenty-five percent of youths experienced the syndrome within 23 months of tobacco use onset. Tolerance, impaired control and withdrawal were experienced most frequently. Youths who developed full dependence experienced their first symptom faster after tobacco use onset than those who experienced only one criterion through the end of the observation period. Cox proportional hazards models estimated the importance of time-constant and time-varying sociodemographic, tobacco and other drug use, parental and peer smoking, social psychological and biological risk factors for experiencing the first criterion and the full syndrome. Pleasant initial sensitivity to tobacco and number of cigarettes smoked the prior month predicted both outcomes. Parental dependence predicted the full syndrome. Significant covariates were generally the same across gender and racial/ethnic subgroups. The predictive significance of the initial smoking experience and parental dependence highlight the potential importance of genetic factors in the etiology of nicotine dependence. [ABSTRACT FROM AUTHOR]

Objectives. We describe the epidemiology of smoking behaviors in a national young adult sample and identify common and unique demographic, social, and psychological correlates of daily smoking and lifetime and current nicotine dependence by race/ethnicity.Methods. Data are from the National Longitudinal Survey of Adolescent Health, wave III. Dependence was measured by the Revised Fagerström Test for Nicotine Dependence. Logistic regressions were estimated.Results. Hispanic ethnicity, low education, parental and peer smoking, novelty seeking, early age of smoking onset, and pleasurable initial smoking experiences are significantly correlated with daily smoking and lifetime nicotine dependence. Depressive symptoms are uniquely associated with lifetime and current dependence. Few factors are highly associated with current dependence. Initial sensitivity to smoking has a significantly greater impact on daily smoking than on dependence. Correlates of smoking behaviors are mostly common across racial/ethnic groups, although parental and peer smoking are significant for Whites and Hispanics but not for African Americans.Conclusions. There are more common than unique correlates of each smoking stage and across racial/ethnic groups. Primary prevention and interventions addressing the factors tested could be uniform for most chronic smokers irrespective of dependence status and race/ethnicity. [ABSTRACT FROM AUTHOR]

We examine the association between education and smoking by women in the population, including smoking during pregnancy, and identify risk factors for smoking and the consequences of smoking in pregnancy for children's smoking and behavioral problems. Secondary analyses of four national data sets were implemented: The National Survey of Drug Use and Health (2006), the National Longitudinal Survey of Youth (1979-2004); the National Longitudinal Survey of Adolescent Health (Wave III); National Health and Nutrition Examination Survey (2005-2006). The lower the level of education, the greater the risk of being a current smoker, smoking daily, smoking heavily, being nicotine dependent, starting to smoke at an early age, having higher levels of circulating cotinine per cigarettes smoked, and continuing to smoke in pregnancy. The educational gradient is especially strong in pregnancy. Educational level and smoking in pregnancy independently increase the risk of offspring smoking and antisocial and anxious/depressed behavior problems. These effects persist with control for other covariates, except maternal age at child's birth, which accounts for the impact of education on offspring smoking and anxious/depressed behavior problems. Women with low education should be the target of public health efforts toward reducing tobacco use. These efforts need to focus as much on social conditions that affect women's lives as on individual level interventions. These interventions would have beneficial effects not only for the women themselves but also for their offspring. [ABSTRACT FROM AUTHOR]

The regular use of cannabis during adolescence has been associated with a number of negative life outcomes, including psychopathology and cognitive impairments. However, the exact molecular mechanisms that underlie these outcomes are just beginning to be understood. Moreover, very little is known about the spatio-temporal molecular changes that occur following cannabinoid exposure in adolescence. To understand these changes, we exposed mid-adolescent male rats to a synthetic cannabinoid (WIN 55,212-2 mesylate; WIN) and, following drug abstinence through late adolescence, we subjected the synaptosomal fractions of the prefrontal cortex (PFC) to proteomic analyses. A total of N = 487 differentially expressed proteins were found in WIN-exposed animals compared to controls. Gene ontology analyses revealed enrichment of terms related to the gamma-aminobutyric acid (GABA)-ergic neurotransmitter system. Among the top differentially expressed proteins was the synaptic Ras GTPase-activating protein 1 (SYNGAP1). Using Western blotting experiments, we found that the WIN-induced upregulation of SYNGAP1 was spatio-temporal in nature, arising only in the synaptosomal fractions (not in the cytosol) and only following prolonged drug abstinence (not on abstinence day 1). Moreover, the SYNGAP1 changes were found to be specific to WIN-exposure in adolescence and not adulthood. Adolescent animals exposed to a natural cannabinoid (Δ 9 -tetrahydrocannabinol; THC) were also found to have increased levels of SYNGAP1 in the PFC. THC exposure also led to a pronounced upregulation of SYNGAP1 in the amygdala, but without any changes in the dorsal striatum, hippocampus, or nucleus accumbens. To our knowledge, this is the first study to uncover a link between cannabinoid exposure and changes in SYNGAP1 that are spatio-temporal and developmental in nature. Future studies are needed to investigate the putative role of SYNGAP1 in the negative behavioral consequences of cannabis use in adolescence.

The effects of social isolation on an individual's behavior is an important field of research, especially as public health officials encourage social distancing to prevent the spread of pandemic disease. In this study we evaluate the effects of social isolation on physical activity in mice. Utilizing a pixel-based tracking system, we continuously monitored the movement of isolated mice compared with paired cage mates in the home cage environment. We demonstrate that mice that are socially isolated dramatically decrease their movement when separated from their cage mate, and especially in the dark cycle, when mice are normally most active. When isolated mice are re-paired with their original cage mate, this effect is reversed, and mice return to their prior levels of activity. These findings suggest a close link between social isolation and physical activity, and are of particular interest in the wake of coronavirus disease 2019, when many are forced into isolation. Social isolation may affect an individual's overall activity levels in humans too, which may have unintended effects on health that deserve further consideration., (© 2020 Wiley Periodicals LLC.)

Importance: Limited information is available regarding the association between parental and adolescent medical prescription opioid use and misuse in the US., Objective: To examine the associations between parental and adolescent prescription opioid medical use and misuse., Design, Setting, and Participants: This cross-sectional, nationally representative study included 15 200 parent-adolescent dyads from the annual 2015-2017 National Survey on Drug Use and Health. Data were collected from January 6, 2015, to December 20, 2017, and analyzed from October 4, 2019, to October 15, 2020., Exposures: Parental past 12-month exclusive medical prescription opioid use and any misuse (ie, using without a prescription or in any way not directed by a physician)., Main Outcomes and Measures: Adolescent past 12-month medical prescription opioid use or misuse. Multivariable regressions estimated associations between parental and offspring medical prescription opioid use or misuse, controlling for sociodemographic and psychosocial variables., Results: Respondents included 9400 mother-child and 5800 father-child dyads in the same household; children were aged 12 to 17 years (52.8% male; mean [SD] age, 14.5 [1.7] years). Controlling for other factors, parental medical prescription opioid use was associated with adolescent prescription opioid medical use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.06-1.53) and misuse (aOR, 1.53; 95% CI, 1.07-2.25), whereas parental misuse was not. Parental medical prescription stimulant use was associated with adolescent medical prescription opioid use (aOR, 1.40; 95% CI, 1.02-1.91). Parental marijuana use (aOR, 1.84; 95% CI, 1.13-2.99), parent-adolescent conflict (aOR, 1.26; 95% CI, 1.05-1.52), and adolescent depression (aOR, 1.75; 95% CI, 1.26-2.44) were associated with adolescent prescription opioid misuse. Adolescent delinquency (aOR, 1.55; 95% CI, 1.38-1.74) and perceived schoolmates' drug use (aOR, 2.87; 95% CI, 1.95-4.23) were also associated with adolescent misuse and more weakly with medical use (aORs, 1.13 [95% CI, 1.05-1.22] and 1.61 [95% CI, 1.32-1.96], respectively)., Conclusions and Relevance: Youth use of prescription opioids is in part a structural/environmental issue. The findings of this study suggest that parental medical prescription opioid use is associated with offspring prescription opioid use, whereas parental misuse is not. Restricting physicians' opioid prescribing to parents is a crucial public health goal. In addition, parents could be educated on the risks of their prescription opioid use for offspring and on practices to mitigate risk, including safe medication storage and disposal. Screening for parental prescription opioid use could be part of pediatric practice. Addressing adolescent mental health could also reduce adolescent prescription opioid misuse.

A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals., (Copyright © 2020 Drisaldi, Colnaghi, Levine, Huang, Snyder, Metzger, Theis, Kandel, Kandel and Fioriti.)

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological evidence demonstrating that cannabinoids can also alter the brain's initial molecular and epigenetic response to cocaine. Here, we utilized a multiomics approach (epigenomics, transcriptomics, proteomics, and phosphoproteomics) to characterize how the rat brain responds to its first encounter with cocaine, with or without preexposure to the synthetic cannabinoid WIN 55,212-2 (WIN). We find that in adolescent (but not in adult) rats, preexposure to WIN results in cross-sensitization to cocaine, which correlates with histone hyperacetylation and decreased levels of HDAC6 in the prefrontal cortex (PFC). In the PFC, we also find that WIN preexposure blunts the typical mRNA response to cocaine and instead results in alternative splicing and chromatin accessibility events, involving genes such as Npas2 Moreover, preexposure to WIN enhances the effects of cocaine on protein phosphorylation, including ERK/MAPK-targets like gephyrin, and modulates the synaptic AMPAR/GluR composition both in the PFC and the nucleus accumbens (NAcc). PFC-NAcc gene network topological analyses, following cocaine exposure, reveal distinct top nodes in the WIN preexposed group, which include PACAP/ADCYAP1. These preclinical data demonstrate that adolescent cannabinoid exposure reprograms the initial behavioral, molecular, and epigenetic response to cocaine., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Objectives. To characterize prescription opioid medical users and misusers among US adults. Methods. We used the 2016-2017 National Surveys on Drug Use and Health to compare medical prescription opioid users with misusers without prescriptions, misusers of own prescriptions, and misusers with both types of misuse. Multinomial logistic regressions identified substance use characteristics and mental and physical health characteristics that distinguished the groups. Results. Among prescription opioid users, 12% were misusers; 58% of misusers misused their own prescriptions. Misusers had higher rates of substance use than did medical users. Compared with with-prescription-only misusers, without-and-with-prescription misusers and without-prescription-only misusers had higher rates of marijuana use and benzodiazepine misuse; without-and-with-prescription misusers had higher rates of heroin use. Compared with without-prescription-only misusers, without-and-with-prescription and with-prescription-only misusers had higher rates of prescription opioid use disorder. Most misusers, especially with-prescription-only misusers, used prescription opioids to relieve pain. Misusers were more likely to be depressed than medical users. Conclusions. Prescription opioid misusers who misused both their own prescriptions and prescription opioid drugs not prescribed to them may be most at risk for overdose. Prescription opioid misuse is a polysubstance use problem.

Background: To date, intergenerational patterns of nonmedical prescription opioid (NMPO) use have not been examined. We investigate the association between parental and adolescent NMPO use in the United States., Methods: Data are from 35 000 parent-child dyads with an adolescent aged 12 to 17 years from the 2004-2012 nationally representative National Surveys on Drug Use and Health. Using multivariable logistic regression models, we estimated the association between self-reported parental and adolescent lifetime NMPO use, controlling for parental and adolescent use of other drugs, attitudes about drug use, parental and adolescent psychosocial risk factors, and sociodemographic characteristics., Results: Controlling for other factors, parental NMPO use was associated with adolescent NMPO use (adjusted odds ratio [aOR] 1.30; 95% confidence interval [CI] 1.09-1.56). Mothers' use had a stronger association with adolescent use than fathers' use (aOR 1.62 [95% CI 1.28-2.056] versus aOR 0.98 [95% CI 0.74-1.24]). Associations between parental and adolescent NMPO use did not differ by adolescent sex or race and/or ethnicity. Parental lifetime smoking, low monitoring, and parent-adolescent conflict were uniquely associated with adolescent NMPO use (aOR 1.19-1.24) as were adolescent smoking, marijuana use, depression, delinquency, and perceived schoolmates' drug use (aOR 1.25-1.71). Perceived risk of drug use and religiosity were associated with lower rates of adolescent NMPO use (aOR 0.77-0.93). Use among older adolescents was higher than among younger adolescents (aOR 1.27; 95% CI 1.21-1.34)., Conclusions: Parent-based interventions targeted at adolescent NMPO use should address parental NMPO use and smoking and promote positive parenting., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Cannabis use is typically initiated during adolescence and is a significant risk factor for the development of cocaine use in adulthood. However, no preclinical studies have examined the effects of adolescent cannabinoid exposure on cocaine dependence in adulthood using the escalation model of cocaine self-administration and the assessment of negative emotional states. In the present study, we found that exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN) in adolescence produced irritability-like behavior and psychomotor cross-sensitization to cocaine in adolescence. In adulthood, rats were allowed to self-administer cocaine. The acquisition of cocaine self-administration was lower in rats with adolescent WIN exposure compared with controls. However, both WIN-exposed and control rats escalated their cocaine intake at the same rate, had similar responding under a progressive-ratio schedule of reinforcement, and had similar psychomotor responses to cocaine. Interestingly, the increase in irritability-like behavior that was previously observed in adolescence after WIN exposure persisted into adulthood. Whether the persisting increase in irritability-like behavior after WIN exposure has translational relevance remains to be studied. In summary, these results suggest that psychoactive cannabinoid exposure during adolescence is unlikely to have a major effect on the escalation of cocaine intake or the development of compulsive-like responding per se in adulthood in a rat model of cocaine self-administration. However, whether the persisting irritability-like behavior may predispose an individual to mood-related impairments in adulthood or predict such impairments warrants further investigation.

Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials., Methods: Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs., Results: Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans., Conclusions: NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference. Long-term, but not short-term, alcohol consumption promotes proteasome-mediated degradation of the nuclear histone deacetylases HDAC4 and HDAC5 in the nucleus accumbens, a brain region critical for reward-based memory. Decreased nuclear HDAC activity results in global H3 acetylation, creating a permissive environment for cocaine-induced gene expression. We also find that selective degradation of HDAC4 and HDAC5, facilitated by the class II-specific HDAC inhibitor MC1568, enhances compulsive cocaine self-administration. These results parallel our previously reported findings that the gateway drug nicotine enhances the behavioral effects of cocaine via HDAC inhibition. Together, our findings suggest a shared mechanism of action for the gateway drugs alcohol and nicotine, and reveal a novel mechanism by which environmental factors may alter the epigenetic landscape of the reward system to increase vulnerability to cocaine addiction.

Background: Prescription opioid (PO) overdose deaths increased sharply over the last decade. Changes in PO deaths in combination with other psychoactive substances may provide a partial explanation., Methods: PO deaths from the National Multiple-Cause-of-Death Files for 2002-03 (N=15,973) and 2014-15 (N=41,491) were analyzed. We calculated (1) changes in proportions of deaths in combination with benzodiazepines, antidepressants, heroin, alcohol, cocaine between the two periods, and (2) proportions of increase in deaths attributable to each substance among PO and synthetic opioids other than methadone (SO-M) deaths, by age, gender, race/ethnicity., Results: Between 2002-03 and 2014-15, PO deaths increased 2.6 times; SO-M deaths 5.6 times, especially for ages 18-34, males, African-Americans. For PO deaths, most frequent combinations at both periods were with benzodiazepines; for SO-M, benzodiazepines, antidepressants in 2002-03, heroin, benzodiazepines in 2014-15. The largest increases occurred in combination with heroin among all PO (4.6% to 15.4%, change ratio=3.3[95%CI=3.1-3.6]), but especially SO-M deaths (1.2% to 24.5%, change ratio=21.3[95%CI=15.0-30.3]). Deaths involving cocaine decreased among PO, increased among SO-M deaths. One-fifth of increased PO or SO-M deaths were attributable to any of the five substances. Increased PO deaths were equally attributable to benzodiazepines and heroin; deaths attributable to heroin were higher among ages 18-49, males, and non-Hispanic whites. Increased SO-M deaths were attributable mostly to heroin among all groups., Conclusions: Increased PO overdose deaths over the last decade may be partially explained by increased deaths in combination with other psychoactive substances. Use of other substances should be considered in efforts toward reducing prescription opioid overdoses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To estimate age-related patterns in nonmedical prescription opioid (NMPO) use in the US population and disorder among past-year users at ages 12-34 between 2002 and 2014, controlling for period and birth-cohort effects., Methods: Data are from 13 consecutive cross-sectional National Surveys on Drug Use and Health (N=542,556). Synthetic longitudinal cohorts spanning ages 12-34 were created and an age-period-cohort analysis was implemented based on the Intrinsic Estimator algorithm., Results: In every birth cohort, past-year NMPO use increases during adolescence, peaks at ages 18-21, decreases through ages 30-34; disorder among past-year users increases from ages 18-21 through 30-34. Use at ages 12-34 decreased from the 1984-87 birth cohorts to more recently-born cohorts. Peak prevalence of use at ages 18-21 has also decreased, and the rates of increase from ages 14-17 to ages 18-21 are slowing down. Disorder at ages 18-34 increased from the 1976-79 to 1992-95 cohorts, but decreased at ages 12-17 from the 1992-95 to the most recently-born 2000-02 cohorts. The years 2010-2014 were characterized by lower NMPO use but higher disorder than 2002-2009., Conclusions: Increasing NMPO disorder among users aged 18-34 warrants concern. However, declining NMPO use among 12-34 year-olds, a declining rate of increase from adolescence to early adulthood, and a suggestive decline in disorder among the most recent adolescent cohorts may forecast a potential reduction in the public health crisis associated with NMPO drugs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To examine whether the drug behavior of adults from different birth cohorts is shaped by adolescent drug experiences and whether adult prevalence of marijuana and cocaine use depends on adolescent cigarette or alcohol use prevalence., Methods: We analyzed 18 birth cohorts comprising 8th, 10th, and 12th graders, sampled from 1991 to 2008, from Monitoring the Future, an annual nationally representative cross-sectional survey of high school students in the United States (n = 864 443)., Results: Within cohorts, lifetime rates of 8th and 10th grade cigarette use were significantly associated with subsequent lifetime rates of marijuana and cocaine use, controlling for trends in use and social norms toward drug use. Each percent increase (or decrease) in 8th and 10th grade smoking was associated with an 8% increase (or decrease) in prevalence of later marijuana use and 14% to 23% increase (or decrease) in prevalence of later cocaine use. Relationships were consistent by gender and race/ethnicity., Conclusions: Prevalences of smoking in 8th and 10th grade and of marijuana and cocaine use in 12th grade are associated. Public health campaigns should focus on early stages of adolescence, when drug use habits are forming.

Introduction: To examine the prospective associations of Diagnostic and Statistical Manual of Mental Disorders nicotine dependence (ND) and other individual and parental factors in adolescence on self-reported health symptoms in early adulthood., Methods: Multiethnic prospective longitudinal cohort of adolescents from grades 6-10 and a parent (N = 908) from the Chicago Public Schools. Adolescents were interviewed five times at 6-month intervals (Waves 1-5) and once 4.5 years later (Wave 6). Parents were interviewed annually three times (W1, W3, W5). Multivariate regressions estimated prospective associations of Diagnostic and Statistical Manual of Mental Disorders ND, other individual and familial risk factors in adolescence (mean age 16.6) on physical health symptoms in early adulthood (mean age 21.3), controlling for health symptoms in adolescence., Results: Levels of health symptoms declined from adolescence to early adulthood, except among dependent smokers. Nicotine dependent adolescents reported more health symptoms as young adults than nonsmokers and nondependent smokers, especially if depressed. ND and health symptoms in adolescence were the strongest predictors of health in early adulthood. These two adolescent factors, depression, and the familial factors of parental ND, depression and health conditions, each independently predicted health symptoms in young adulthood. Females reported more symptoms than males., Conclusions: There is continuity of health status over time. ND, depression, and parental factors in adolescence contribute to poor health in early adulthood. The findings highlight not only the role of adolescent behavior, but the importance of the family in the development of young adult health. Reducing smoking, particularly ND, and depression among adolescents and parents will decrease physical health burden., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We examined associations between parental and adolescent smoking and nicotine dependence in the United States., Methods: We used data from the 2004 to 2012 National Survey on Drug Use and Health, which ascertained smoking behaviors of 1 parent and 1 adolescent aged 12 to 17 years in 35 000 dyads. We estimated associations between parental and adolescent smoking behaviors, adjusted for covariates., Results: Parental current dependence was strongly associated with adolescents' lifetime smoking (adjusted odds ratio [AOR] = 2.96; 95% confidence interval [CI] = 2.47, 3.55), whereas parental current nondependent smoking (AOR = 2.26; 95% CI = 1.92, 2.67) and former smoking (AOR = 1.51; 95% CI = 1.31, 1.75) were less strongly associated. Only parental nicotine dependence was associated with adolescent nicotine dependence (AOR = 1.66; 95% CI = 1.00, 2.74). Associations between parental and adolescent smoking did not differ by race/ethnicity. Parents' education, marital status, and parenting and adolescents' mental health, beliefs about smoking, perception of schoolmates' smoking, and other substance use predicted adolescent smoking and dependence., Conclusions: Reducing parental smoking would reduce adolescent smoking. Prevention efforts should encourage parental smoking cessation, improve parenting, address adolescent mental health, and reinforce adolescents' negative beliefs about smoking.

Aims: To examine the inter-relationships between cigarette consumption and DSM-IV nicotine dependence (ND) criteria from smoking onset in adolescence up to 7 years later, adjusting for alcohol consumption and DSM-IV alcohol dependence (AD) criteria., Design: A cohort drawn from grades 6-10 in an urban school system was interviewed five times at 6-month intervals (waves 1-5) and 4.5 years later (wave 6). A parent was interviewed three times., Setting: Chicago, Illinois., Participants: Recent smokers (n = 409)., Measurements: Structured household interviews ascertained number of cigarettes smoked, DSM-IV ND symptoms, drinks consumed, DSM-IV AD symptoms, and selected covariates. Reciprocal prospective associations between number of cigarettes smoked and ND criteria, controlling for time-varying alcohol consumption and dependence criteria, were examined with cross-lagged models., Findings: Reciprocal associations between number of cigarettes smoked and ND criteria were both significant. Cigarette consumption had stronger associations with later ND [β = 0.25, 95% confidence interval (CI) = 0.17-0.32] than dependence had with later cigarette consumption (β = 0.09, 95% CI = 0.01-0.16). Alcohol and cigarette consumption influenced each other; AD scores were associated with later ND scores but not the reverse. Reports of pleasant initial experiences from smoking were associated positively with cigarette consumption and ND the first year after smoking onset; later smoking onset was negatively associated with cigarette consumption the seventh year after onset; parental ND predicted cigarette consumption and ND throughout., Conclusions: In adolescent smokers, higher cigarette consumption predicts later severity of DSM-IV nicotine dependence more than the reverse. Smoking and drinking also influence each other mutually over time., (© 2014 Society for the Study of Addiction.)

In human populations, there is a well-defined sequence of involvement in drugs of abuse, in which the use of nicotine or alcohol precedes the use of marijuana, which in turn, precedes the use of cocaine. The term "Gateway Hypothesis" describes this developmental sequence of drug involvement. In prior work, we have developed a mouse model to study the underlying metaplastic behavioral, cellular and molecular mechanisms by which exposure to one drug, namely nicotine, affects the response to another drug, namely cocaine. We found that nicotine enhances significantly the changes in synaptic plasticity in the striatum induced by cocaine (Levine et al., 2011). Here we ask: does the metaplastic effect of nicotine on cocaine also apply in the amygdala, a brain region that is involved in the orchestration of emotions and in drug addiction? We find that pretreatment with nicotine enhances long-term synaptic potentiation (LTP) in response to cocaine in the amygdala. Both short-term (1 day) and long-term (7 days) pre-exposure to nicotine facilitate the induction of LTP by cocaine. The effect of nicotine on LTP is unidirectional; exposure to nicotine following treatment with cocaine is ineffective. This metaplastic effect of nicotine on cocaine is long lasting but reversible. The facilitation of LTP can be obtained for 24 but not 40 days after cessation of nicotine. As is the case in the striatum, pretreatment with Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, simulates the priming effect of nicotine. These results provide further evidence that the priming effect of nicotine may be achieved, at least partially, by the inhibition of histone acetylation and indicate that the amygdala appears to be an important brain structure for the processing of the metaplastic effect of nicotine on cocaine. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'., (Published by Elsevier Ltd.)

Background: To identify patterns and correlates of developmental trajectories of DSM-IV nicotine dependence criteria from adolescence to early adulthood., Methods: The analytical sample of lifetime smokers (N=877) is from a longitudinal cohort of 6th-10th graders drawn from an urban school system. Subjects were interviewed 5 times at 6-month intervals and once 4.5 years later. Growth mixture models were estimated to identify trajectories of DSM-IV nicotine dependence criteria over ages 12-23., Results: A four-class solution fitted the data best: No dependence criteria (class 1, 32.0%); early onset/chronic course (class 2, 26.1%); early onset/remission (class 3, 15.4%); late onset (class 4, 26.5%). There appeared to be three critical periods. At ages 12-15, symptoms increased rapidly. As of age 16, the early onset/chronic class stabilized at high levels of symptoms, the early onset/remission class started its symptomatic decline, and the late onset class experienced a sharp increase in symptoms. At age 20, there was a convergence in the prevalence of symptoms experienced at high (classes 2 and 4) and low levels (classes 1 and 3). Extensiveness of smoking and marijuana use were associated with higher baseline levels of nicotine dependence criteria. Anxiety disorders were associated with all three symptomatic trajectories. Parental smoking and nicotine dependence were associated specifically with the early/chronic class, while pleasant initial sensitivity and earlier onset ages of cigarette and marijuana use characterized the two early onset classes (2 and 3)., Conclusions: Trajectories of dependence criteria constitute an advantageous phenotype for research and intervention over static summaries of smoking behaviors., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

In human populations, cigarettes and alcohol generally serve as gateway drugs, which people use first before progressing to marijuana, cocaine, or other illicit substances. To understand the biological basis of the gateway sequence of drug use, we developed an animal model in mice and used it to study the effects of nicotine on subsequent responses to cocaine. We found that pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward. Locomotor sensitization was increased by 98%, conditioned place preference was increased by 78%, and cocaine-induced reduction in long-term potentiation (LTP) was enhanced by 24%. The responses to cocaine were altered only when nicotine was administered first, and nicotine and cocaine were then administered concurrently. Reversing the order of drug administration was ineffective; cocaine had no effect on nicotine-induced behaviors and synaptic plasticity. Nicotine primed the response to cocaine by enhancing its ability to induce transcriptional activation of the FosB gene through inhibition of histone deacetylase, which caused global histone acetylation in the striatum. We tested this conclusion further and found that a histone deacetylase inhibitor simulated the actions of nicotine by priming the response to cocaine and enhancing FosB gene expression and LTP depression in the nucleus accumbens. Conversely, in a genetic mouse model characterized by reduced histone acetylation, the effects of cocaine on LTP were diminished. We achieved a similar effect by infusing a low dose of theophylline, an activator of histone deacetylase, into the nucleus accumbens. These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking increases the risk of becoming dependent on cocaine, consistent with our data from mice. If our findings in mice apply to humans, a decrease in smoking rates in young people would be expected to lead to a decrease in cocaine addiction.

Aims: To examine bidirectional influences of onset of psychiatric disorders and nicotine dependence among adolescent smokers., Design: A prospective longitudinal cohort of adolescents and mothers drawn from a large city school system. Adolescents were interviewed five times and mothers three times over 2 years., Setting: Chicago, Illinois., Participants: Subsample of adolescent smokers (n = 814)., Measurements: Selected DSM-IV psychiatric disorders, nicotine dependence and selected risk factors were ascertained., Findings: Among lifetime smokers, 53.7% experienced at least one nicotine dependence criterion; 26.1% full dependence; 14.1% experienced an anxiety disorder, 18.8% a mood disorder and 29.5% a disruptive disorder. Nicotine dependence and psychiatric disorders were comorbid: nicotine-dependent youths had higher rates of individual and multiple disorders than those not dependent. Controlling for other covariates, mood disorder and nicotine dependence did not predict each other; anxiety disorder predicted nicotine dependence. Bidirectional influences were observed for disruptive disorder and nicotine dependence. Predictors of onset of full nicotine dependence included earlier onset age of tobacco use, high initial pleasant sensitivity to tobacco, alcohol and illicit drug use, abuse and dependence and parental nicotine dependence. Predictors of psychiatric disorder onset included gender, race/ethnicity, other psychiatric disorders, illicit drug abuse or dependence and parental depression and delinquency., Conclusions: Initial pleasant experiences of smoking are predictive of later development of nicotine dependence. There may be reciprocal influences between disruptive disorder and development of nicotine dependence in adolescence, and intergenerational transmission of parental nicotine dependence and psychopathology., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

Aims: To determine whether there is a sequence in which adolescents experience symptoms of nicotine dependence (ND) as per the DSM-IV., Design: A two-stage design was implemented to select a multi-ethnic target sample of adolescents from a school survey of 6th-10th graders from the Chicago Public Schools. The cohort was interviewed at home five times with structured computerized interviews at 6-month intervals over a 2-year period., Participants: Subsample of new tobacco users (n = 353) who had started to use tobacco within 12 months prior to wave 1 or between waves 1 and 5. MEASUREMENTS AND STATISTICAL METHODS: Monthly histories of DSM-IV symptoms of ND were obtained. Log-linear quasi-independence models were estimated to identify the fit of different cumulative models of progression among the four most prevalent dependence criteria (tolerance, impaired control, withdrawal, unsuccessful attempts to quit), indexed by specific symptoms, by gender and race/ethnicity., Findings: Pathways varied slightly across groups. The proportions who could be classified in a progression pathway not by chance ranged from 50.7% to 68.8%. Overall, tolerance and impaired control appeared first and preceded withdrawal; impaired control preceded attempts to quit. For males, tolerance was experienced first, with withdrawal a minor path of entry; for females withdrawal was experienced last, tolerance and impaired control were experienced first. For African Americans, tolerance by itself was experienced first; for other groups an alternative path began with impaired control., Conclusions: The prevalence and sequence of criteria of ND fit our understanding of the neuropharmacology of ND. The order among symptoms early in the process of dependence may differ from the severity order of symptoms among those who persist in smoking.

Objective: To examine prospectively the comorbidity of DSM-IV psychiatric disorders and nicotine dependence in adolescence., Method: A multiethnic sample (N = 1,039) of adolescents from grades 6 to 10 in the Chicago public schools (mean age 14.1 years) was interviewed at home five times, and mothers were interviewed three times over a 2-year period (2003-2005). Completion rates at each wave were 96% of the initial sample. Selected DSM-IV psychiatric disorders were ascertained from youths and mothers about youths at two annual waves with the NIMH Diagnostic Interview Schedule for Children, Version IV-Y and IV-P; DSM-IV symptoms of nicotine dependence were ascertained from youths at every wave using a measure developed for adolescents., Results: Psychiatric disorders most often preceded the onset of the first criterion of nicotine dependence. Prospective associations between psychiatric disorders and nicotine dependence were examined through logistic regressions. After controlling for comorbid disorders, it was found that lifetime disruptive disorder significantly predicted the onset of a nicotine dependence criterion (adjusted odds ratio 2.1). Early onset of any psychiatric disorder increased this risk. Other predictors included novelty seeking and extensiveness of smoking. By contrast, nicotine dependence did not predict the onset of a psychiatric disorder; significant predictors included the youths' prior other psychiatric disorders, novelty seeking, and parental depression and antisocial behavior., Conclusions: Nicotine dependence does not seem to contribute to the onset of psychiatric disorders, whereas disruptive disorder is an important etiologic factor for nicotine dependence in adolescence.

We describe the nature and predictors of developmental trajectories of symptoms of DSM-IV nicotine dependence in adolescence following smoking initiation. Data are from a longitudinal cohort of 324 new smokers from grades 6-10 in the Chicago Public Schools, interviewed 5 times at 6-month intervals. Monthly data on DSM-IV symptoms of nicotine dependence were available for 36 months. Growth mixture modeling was applied to the monthly histories to identify trajectories of DSM-IV criteria of nicotine dependence. A four-class solution best fitted the data: no DSM criterion (47.7%); early onset/chronic course (19.8%); early onset/remission (17.3%); late onset (15.2%). Blunt use prior to cigarette use was associated with the three symptomatic trajectories. Conduct disorder and prior heavy smoking were associated with Class 2 (chronic). Conduct disorder differentiated Class 2 from Class 4 (late onset), while pleasant initial sensitivity to the first tobacco experience was associated with Classes 2 and 3 (remit) and differentiated Class 2 from Class 4. Novelty seeking characterized Class 3. Parental dependence differentiated chronicity (Class 2) from remission (Class 3) among those who developed symptoms early. Being Hispanic reduced membership in Classes 3 and 4, and being male for Class 3. The data highlight the importance of parental nicotine dependence as a risk factor for early and sustained nicotine dependence by the offspring, pleasant initial sensitivity and conduct disorder for early onset of dependence, and blunt use prior to smoking for all trajectories. The factors important for onset of dependence are not necessarily the same as those for sustained course.

Extent and sources of inconsistency in self-reported cigarette smoking between self-administered school surveys and household interviews was examined in two longitudinal multiethnic adolescent samples, the urban Transition to Nicotine Dependence in Adolescence (TND) (N = 832) and the National Longitudinal Study of Adolescent Health (Add Health) (N = 4,414). Inconsistency was defined as a positive report of smoking in school followed by a negative report in the household. Smoking questions were ascertained with paper-and-pencil instruments (PAPI-SAQ) in school in both studies, and computer-assisted personal interviewing (CAPI) in TND but audio computer-assisted self-interviewing (ACASI) in Add Health in the household. In TND, 23.5 percent of youths who reported smoking lifetime and 20.4 percent of those who reported smoking the last 12 months in the school survey reported in the household never having smoked; in Add Health, the latter was 8.6 percent. Logistic regressions identified five common correlates of inconsistency across the two studies: younger age, ethnic minority status, lesser involvement in deviant activities, having nonsmoking parents and friends. In TND, interviewing of youth and parent by the same interviewer increased inconsistent reporting. Matching the definition of inconsistent reporting and the age, gender and race/ethnic distributions of TND on an urban Add Health subsample reduced the predicted rate of inconsistency in TND. The estimated bias attributable to CAPI compared with ACASI methodology did not reach significance in the aggregated matched samples suggesting that irrespective of administration mode, household interviews decrease reporting of smoking, especially among younger, minority and more conventional youths embedded in a social network of nonsmokers.

Nicotine metabolism has been hypothesized to affect patterns of smoking. The recent development of a noninvasive measure of nicotine metabolism, the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine), makes it possible to examine the association between rate of nicotine metabolism and smoking behavior in the general population. This US study examined group differences in the ratio measured in urine and the association between the ratio and multiple measures of smoking behavior and nicotine dependence in a large, national representative sample of young adults. The sample included 900 daily smokers aged 18-26 years from wave III (2001-2002) of the National Longitudinal Survey of Adolescent Health. Nicotine dependence was measured by using the Fagerström Test for Nicotine Dependence. Females had higher nicotine metabolite ratios than males; Whites and Hispanics had higher nicotine metabolite ratios than African Americans or Asians. This finding is consistent with those from laboratory studies of older smokers based on intravenous infusion of nicotine. No significant association was found between the nicotine metabolite ratio and number of cigarettes smoked per day or nicotine dependence. The availability of a noninvasive measure makes possible systematic testing of causal hypotheses generated by laboratory studies in the general population.

The present study examined the extent and sources of discrepancies between self-reported cigarette smoking and salivary cotinine concentration among adolescents. The data are from household interviews with a cohort of 1,024 adolescents from an urban school system. Histories of tobacco use in the last 7 days and saliva samples were obtained. Logistic regressions identified correlates of three inconsistent patterns: (a) Pattern 1-self-reported nonsmoking among adolescents with cotinine concentration above the 11.4 ng/mg cutpoint (n = 176), (b) Pattern 2-low cotinine concentration (below cutpoint) among adolescents reporting having smoked within the last 3 days (n = 155), and (c) Pattern 3-high cotinine concentration (above cutpoint) among adolescents reporting not having smoked within the last 3 days (n = 869). Rates of inconsistency were high among smokers defined by cotinine levels or self-reports (Pattern 1 = 49.1%; Pattern 2 = 42.0%). Controlling for other covariates, we found that reports of nonsmoking among those with high cotinine (Pattern 1) were associated with younger age, having few friends smoking, little recent exposure to smokers, and being interviewed by the same interviewer as the parent and on the same day. Low cotinine concentration among self-reported smokers (Pattern 2) was negatively associated with older age, being African American, number of cigarettes smoked, depth of inhalation, and exposure to passive smoke but positively associated with less recent smoking and depressive symptoms. High cotinine concentrations among self-reported nonsmokers was positively associated with exposure to passive smoke (Pattern 3). The data are consonant with laboratory findings regarding ethnic differences in nicotine metabolism rate. The inverse relationship of cotinine concentration with depressive symptoms has not previously been reported. Depressed adolescent smokers may take in smaller doses of nicotine than nondepressed smokers; alternatively, depressed adolescents may metabolize nicotine more rapidly.

Objectives: We sought to identify individual and contextual predictors of adolescent smoking initiation and progression to daily smoking by race/ethnicity., Methods: We used data from the National Longitudinal Study of Adolescent Health to estimate the effects of individual (adolescent, family, peer) and contextual (school and state) factors on smoking onset among nonsmokers (n = 5374) and progression to daily smoking among smokers (n = 4474) with multilevel regression models., Results: Individual factors were more important predictors of smoking behaviors than were contextual factors. Predictors of smoking behaviors were mostly common across racial/ethnic groups., Conclusions: The few identified racial/ethnic differences in predictors of smoking behavior suggest that universal prevention and intervention efforts could reach most adolescents regardless of race/ethnicity. With 2 exceptions, important contextual factors remain to be identified.

Aims: To identify and compare predictors of adolescent smoking initiation and persistence among African American, Hispanic and White adolescents in a longitudinal national sample., Design: The sample includes 1537 mother-child dyads from the National Longitudinal Survey of Youth (NLSY). Family, youth, peer and sociodemographic risk and protective factors were analyzed., Findings: White adolescents reported the highest rates of smoking initiation and persistence; African Americans and Hispanics the lowest. Multivariate analyses revealed mostly common and few ethnic-specific predictors of smoking initiation and persistence. For initiation, maternal current smoking, child age, child problem behavior, and perceived peer pressure to smoke were predictive across ethnic groups; female gender and ineffective parenting were predictive among Whites only. For persistence, child age, child problem behavior and perceived scholastic competence were predictive across ethnic groups; negative mood was predictive among Whites only., Conclusions: More common than unique factors predict smoking initiation and persistence among adolescents of different ethnicity. However, the power to detect ethnicity-by-predictor interactions with respect to persistence was low. Social factors are more important for smoking initiation, whereas individual factors are more important for persistence, although child problem behaviors are common determinants both of initiation and persistence. With few exceptions, universal anti-smoking interventions should be targeted to youths of different ethnicity.

Background: Comorbidity of dependence on single and multiple drugs with psychiatric syndromes was examined in national samples from the National Household Survey on Drug Abuse (NHSDA)., Methods: Subjects are adults from the l994, l995 and l996 NHSDA surveys. Proxy measures of drug dependence in the last year were constructed from five dependence symptoms that approximated DSM-IV criteria. Measures of patterns of concurrent dependence on cigarettes, alcohol and illicit drugs were constructed. Fallible indicators of a major depressive episode and any anxiety disorder (generalized anxiety disorder, agoraphobia and panic attack) were based on scales measuring symptoms during the last year. Comorbidity was estimated by adjusted odds ratios., Results: Probable drug dependent individuals have higher rates of psychiatric syndromes. Rates of psychiatric syndromes were similar for those uniquely dependent on alcohol, cigarettes or illicit drugs (adjusted odds ratios approximately 2.0). Rates almost doubled for those dependent on both an illicit and a licit drug., Conclusions: Individuals uniquely dependent on a single drug class experience similar rates of psychiatric morbidity. All those dependent on illicit drugs experience higher rates of psychiatric syndromes. This reflects the additive association of dependence on legal and illegal drugs with psychiatric disorders and the increased rates of dependence on a legal drug among those dependent on an illicit drug. Individuals with multiple dependencies on legal and illegal drugs have the highest need for mental health services.

Rates of nicotine dependence vary in different sociodemographic groups in the population. These group differences remain to be understood. The objective of this study is to specify the relationship between cigarette consumption and nicotine dependence and whether group differences are explained by quantity smoked or differential sensitivity to nicotine. The data used derived from National Household Surveys on Drug Abuse (1991-1993), multistage area probability samples of the US population 12 years old and over, and anonymous structured household interviews, considering subjects who were last-month smokers (12,550 White, 4903 Black, 4839 Hispanic). The main outcome measure was last-year nicotine dependence based on symptoms of dependence and drug-related problems approximating DSM-IV dependence criteria. Rates are higher among females than males, Whites than minorities and the lowest among older adults. Dependence rates increase sharply up to half a pack of cigarettes smoked per day. At higher quantities, the increased risk for dependence is minimal. The higher rate of dependence among females than males results from a greater number of symptoms at the same quantity smoked. The similarity of adolescent and middle-adult rates results from the fact that adolescents smoke significantly fewer cigarettes than adults, but experience higher rates of dependence at the same levels of use. Although adults 50 and over are the heaviest smokers, they experience the lowest rates of dependence because of hypothesized lower sensitivity to increased quantity of nicotine intake. The higher rates among Whites than Blacks appear to result from heavier smoking and greater sensitivity to nicotine effects. It was concluded that adolescents, women and Whites are particularly vulnerable to becoming dependent on nicotine. Group-specific thresholds may be more appropriate criteria than an absolute threshold to define the risk for nicotine dependence.

Objective: Taxonomies of alcoholism and antisocial behaviors based on developmental course converge on two-group classifications that emphasize early and late onset. Typologies for users of illicit drugs remain to be developed. This article proposes a developmental taxonomy of marijuana users., Method: Cluster analysis was applied to a representative community sample of 708 (364 male, 344 female) marijuana users followed from adolescence to age 34-35. The Ward method, followed by relocation, was used to classify marijuana users into different types based on age of onset, chronicity of heavy use and persistence of use. ANOVA and logit analyses were utilized to describe the cluster solution and examine the correlates of cluster membership., Results: Four marijuana use clusters were identified: early onset-heavy use, early onset-light use, mid onset-heavy use and late onset-light use. The groups differed from each other in degree of involvement in marijuana and other drugs, sociodemographic and lifestyle characteristics. The majority of those with early onset did not become heavily involved in marijuana. Unique factors were associated with membership in each group. Factors differentiating early from mid-onset heavy use included association with marijuana-using peers and having had a mental disorder. Peer delinquency was an additional factor differentiating early initiators who became heavy users from those who did not., Conclusions: A simple two-type classification fails to take into account the heterogeneity of early and late onset groups. By itself, early onset into marijuana will not lead to problematic use or rapid progression into the use of other drugs. Motivation underlying use and dysfunctional behaviors are associated with the development of problematic drug use and dependence.

Objectives: The purpose of this study was to specify the effect of prenatal fetal exposure to maternal cotinine and testosterone on daughters' smoking in adolescence and adulthood., Methods: Longitudinal causal models were estimated among 240 White mother-daughter pairs from the Child Health and Development Study. Mothers and daughters were reinterviewed when daughters were aged 15 to 17 years, and daughters were interviewed at 27 to 30 years of age. Blood samples were obtained from both parents during pregnancy and from adult daughters., Results: Testosterone and smoking were positively correlated among mothers during their pregnancy and among adult daughters. Maternal prenatal cotinine had no direct effect on daughters' smoking; self-reported smoking in pregnancy did have a direct effect. Smoking among daughters during adolescence was determined by maternal prenatal testosterone and self-reported maternal smoking during pregnancy and postnatally. Smoking among adult daughters reflected chronic smoking since adolescence and the continuing effect of postnatal maternal smoking. Prenatal maternal testosterone affected adult daughters' testosterone., Conclusions: Estimates of the impact of prenatal maternal smoking depend on the measure of smoking. Prenatal testosterone exposure is a previously unrecognized risk factor for smoking among female offspring.

Objective: To extend findings from several independent reports of an association between maternal smoking during pregnancy and attention-deficit hyperactivity disorder, conduct disorder, and substance abuse in the offspring., Method: This is a 10-year longitudinal study of offspring assessed at 3 points in time into adulthood. Fifty offspring of mothers who reported smoking at least 10 cigarettes almost daily during pregnancy and 97 offspring of mothers who reported never smoking during pregnancy were studied. Psychiatric diagnosis in offspring was assessed blind to parental diagnosis., Results: There was a greater than 4-fold increased risk of prepubertal-onset conduct disorder in boys and a greater than 5-fold increased risk of adolescent-onset drug dependence in girls whose mothers smoked 10 or more cigarettes almost daily during pregnancy. These findings could not be explained by maternal substance abuse during pregnancy, parental psychiatric diagnosis, family risk factors, prenatal and early developmental history of offspring, postnatal maternal smoking, or smoking in the offspring., Conclusions: Maternal smoking during pregnancy may have a long-term effect on specific psychopathology in offspring. The underlying pathophysiology of nicotine on the fetus requires study. The findings suggest the importance of programs aimed at smoking prevention and cessation in women during pregnancy.