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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 (Δ9-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.

Significance The endocannabinoid system has a modulatory role in brain reward and cognitive processes. It has been hypothesized that repeated interference with endocannabinoid signaling (e.g., through abuse of cannabis or synthetic cannabinoids) can remodel the adolescent brain and make it respond differently to more addictive substances, such as cocaine. In the present study, we demonstrate that a history of synthetic cannabinoid exposure in adolescent animals results in distinct molecular and epigenetic changes following initial exposure to cocaine. These changes were pronounced in the prefrontal cortex and associated with an enhanced response to cocaine’s stimulatory effects. The prefrontal cortex is a brain region that still undergoes maturation in adolescence and its dysfunction contributes to the development of addictions., 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.

Background : Traditionally, medial maxillectomy was performed through lateral rhinotomy or mid facial degloving approach for inverted papilloma. Endoscopic medial maxillectomy, since reported first in 1992, has advanced tremendously and has been advocated by a number of authors for the fact that it prevents the morbidity of open approach with a similar recurrence rate. We present our experience of endoscopic medial maxillectomy for sinonasal inverted papilloma. Aims and Objective: To highlight the treatment of inverted papilloma through transnasal endoscopic approach. Methods: This study is a retrospective chart review of 18 patients out of 23 patients of which 5 were lost on follow-up with inverted papilloma who were treated during the last 2 years. Preoperative diagnosis was made on histopathological examination and Krouse staging in CT scans of paranasal sinus was used to estimate the extent of the disease. Then, surgical approach was decided. Post-operative follow up was done by performing direct nasal endoscopy. All patients were followed up for a minimum period of 1 year. Results : Among the 18 patients who underwent endoscopic medial maxillectomy, sex (male : female) ratio were 1.25: 1, age ranged from 24 yrs to 69 yrs with average being 41.7 yrs. According to Krouse staging, 2 patients were in Stage I, 9 patients in Stage II and 7 patients in Stage III. The laterality of the lesion was more on the right. The commonest site of attachment was found to be the lateral wall of nose. The average duration of hospital stay was 4 days. The commonest complication was nasal crusting and the recurrence rate was 11.11%. Conclusion : This work confirms the results described in recent literature and further supports transnasal endoscopic surgery to manage inverted papilloma. Journal of BP Koirala Institute of Health Sciences , Vol. 1, No. 1, 2018, Page: 20-24

Summary: 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. : Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1) known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine. Keywords: drug use, addiction, cannabis, marijuana, cocaine, epigenetics, eIF2a, CREB, GADD34, gateway drugs

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.

Background: Pediatric age group comprises the important fraction of hospital admissions in our health care settings and it is the major challenge to address in the developing countries like ours. This study was carried out to find out the significant epidemiological trends and disease patterns of the admitted children in a pediatric ward.Methods: This retrospective study was carried out by reviewing hospital records of the patients admitted in the pediatric ward from July 2015 to January 2016 in Gandaki Medical College Teaching Hospital. The disease pattern was analyzed on the basis of age, sex, final diagnosis of the disease, duration of hospital stay and months of admission.Results: Among the 1348 admitted children during the study period, majority were males (65%) and below five years (74%). Lower respiratory tract infections (30%), enteric fever (10%) and acute gastroenteritis (7.7%) were the three major causes for admission. The mean days of hospital stay was 4.43 and maximum number of children was admitted during August/September.Conclusion: Infectious diseases are the major cause for morbidity and more were during the rainy season.J-GMC-N | Volume 11 | Issue 01 | January-June 2018, Page: 61-63

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.

Key Points Question What are the patterns of association between parental and adolescent medical prescription opioid use and misuse in the US? Findings In this nationally representative cross-sectional study of 15 200 parent-adolescent dyads from the National Survey on Drug Use and Health, controlling for other factors, parental medical prescription opioid use within the past year was associated with adolescent medical prescription opioid use and misuse, whereas parental misuse was not. Meaning These findings suggest that reducing opioid prescribing by physicians and educating families about medication use practices that restrict the availability of prescription opioids to adolescents in the home could be important targets for reducing adolescent prescription opioid misuse., This cross-sectional study examines the associations between parental and adolescent prescription opioid medical use and misuse among parent and adolescent dyads in the National Survey on Drug Use and Health., 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.

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.

BACKGROUND: Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in rat dorsal striatum and incubation of Meth craving. Here we used viral constructs to study the causal role of dorsal striatal HDAC5 in this incubation. METHODS: In Exp. 1 (over-expression), we injected adeno-associated virus (AAV) bilaterally into dorsal striatum to express either GFP (control) or a mutant form of HDAC5 (mHDAC5), which strongly localized to the nucleus. After training rats to self-administer Meth (10 days, 9 h/d), we tested the rats for relapse to Meth seeking on withdrawal days 2 and 30. In Exp. 2 (knockdown), we injected AAV bilaterally into dorsal striatum to express either a short hairpin RNA against luciferase (shLUC, control) or against HDAC5 (shHDAC5). After training rats to self-administer Meth, we tested the rats for relapse on withdrawal days 2 and 30. We also measured gene expression of other HDACs and potential HDAC5 downstream targets. RESULTS: We found that HDAC5 overexpression in dorsal striatum increased Meth seeking on withdrawal day 30 but not day 2. In contrast, HDAC5 knockdown in dorsal striatum decreased Meth seeking on withdrawal day 30 but not day 2; this manipulation also altered other HDACs (Hdac1 and Hdac4) and potential HDAC5 targets (Gnb4 and Suv39h1). CONCLUSIONS: Results demonstrate a novel role of dorsal striatal HDAC5 in incubation of Meth craving. These findings also set up future work to identify HDAC5 targets that mediate this incubation.

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 epidemiology of drug use in the general population includes two distinct streams of research. The more common stream measures consumption patterns by asking individuals whether (and how frequently) they have ever used specific classes of drugs. The second stream measures the extent of problematic drug use by asking individuals about behaviors and symptoms that would meet the criteria for a substance use disorder. This chapter presents data on the epidemiology and phenomenology of substance use disorders from comparative and developmental perspectives, focusing on DSM-5 definitions, prevalence for types of drugs and by age, gender, and race/ethnicity, comorbidity with psychiatric disorders, and developmental stages.

Prior alcohol use increases vulnerability to cocaine addiction by promoting degradation of HDAC4 and HDAC5., 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 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.

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.

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.

The dentate gyrus (DG) of the hippocampus is critical for spatial memory and is also thought to be involved in the formation of drug-related associative memory. Here, we attempt to test an aspect of the Gateway Hypothesis, by studying the effect of consecutive exposure to nicotine and cocaine on long-term synaptic potentiation (LTP) in the DG. We find that a single injection of cocaine does not alter LTP. However, pretreatment with nicotine followed by a single injection of cocaine causes a substantial enhancement of LTP. This priming effect of nicotine is unidirectional: There is no enhancement of LTP if cocaine is administrated prior to nicotine. The facilitation induced by nicotine and cocaine can be blocked by oral administration of the dopamine D1/D5 receptor antagonist (SKF 83566) and enhanced by the D1/D5 agonist (SKF 38393). Application of the histone deacetylation inhibitor suberoylanilide hydroxamic acid (SAHA) simulates the priming effect of nicotine on cocaine. By contrast, the priming effect of nicotine on cocaine is blocked in genetically modified mice that are haploinsufficient for the CREB-binding protein (CBP) and possess only one functional CBP allele and therefore exhibit a reduction in histone acetylation. These results demonstrate that the DG of the hippocampus is an important brain region contributing to the priming effect of nicotine on cocaine. Moreover, both activation of dopamine-D1 receptor/PKA signaling pathway and histone deacetylation/CBP mediated transcription are required for the nicotine priming effect in the DG.

Objectives Child maltreatment is a global public health problem. There is limited information about this problem in low-income countries. We aimed to document the prevalence and factors associated with physical punishment of children less than 14 years of age in Nepal. Study design Population-based cross-sectional study. Methods We conducted an in-depth analysis using data from the Nepal Multiple Indicator Cluster Survey, a nationally representative multi-stage-stratified cluster sampling survey. Data were collected from 13,000 households in 520 sample enumeration areas. We assessed prevalence of physical punishment and different child violence related acts on 5081 children aged 3–14 years for whom complete information on all acts and attitude towards violence was available. Logistic regression was used to investigate the association between physical punishment of child and factors such as household and maternal demographics. Results Our results suggested violence is common across Nepal, with data showing one in every second child is physically punished. One in every third (33%) of children were spanked, hit or slapped on the bottom, 25% were hit or slapped on the face and approximately 3% were beaten up hard. Odds of facing physical punishment were higher among children aged 3–5 years (odds ratio [OR] 2.9, 95% confidence interval [CI]: 2.0–4.3), aged 6–8 years (OR 2.8, 95% CI: 2.2–3.7), engaged in child labour activities (OR 1.4, 95% CI: 1.1–1.7), with mother that accepted wife beating by husband is justified (OR 1.2, 95% CI: 1.1–1.4), whose father is currently abroad (OR 1.5, 95% CI: 1.2–1.9) and whose father is away from home but in the same country (OR 1.60, 95% CI: 1.1–2.3). The risk was also higher among children living in households that believe physical punishment of children is necessary (OR 3.5, 95% CI: 2.9–4.3) and from lower caste/indigenous (dalit/janajati) ethnicity (OR 1.3, 95% CI: 1.1–1.7). Those less likely to experience physical punishment included female children (OR 0.7, 95% CI: 0.6–0.9) and children with an older mother (34–49 years; OR 0.5, 95% CI: 0.3–0.9). Conclusions Our results suggest that physical punishment of children is common across Nepal with varying severity. Prevention efforts should focus on designing and promoting interventions that support parents to adapt alternative forms of parenting practices.

While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during adolescence is associated with deficits in working memory, attention, and auditory processing, as well as increased impulsivity and anxiety. Finally, recent animal studies suggest that nicotine has a priming effect that increases addiction liability for other drugs. The evidence that nicotine adversely affects fetal and adolescent development is sufficient to warrant public health measures to protect pregnant women, children, and adolescents from nicotine exposure.

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.

The age Crossover Hypothesis, first suggested by Geronimus et al. (1993) in a study of smoking by pregnant women, describes the reversal in the prevalence of drug use among whites and African Americans over the life cycle. In adolescence, the prevalence of lifetime and current use is higher among whites than African Americans. At some point in adulthood, the pattern is reversed: prevalence becomes higher among African Americans than whites. This pattern has been repeatedly observed. However, with rare exceptions, most of what is known about racial/ethnic differences in life cycle differences in patterns of drug use is based on separate adolescent and adult samples.

To identify patterns and correlates of developmental trajectories of DSM-IV nicotine dependence criteria from adolescence to early adulthood.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.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).Trajectories of dependence criteria constitute an advantageous phenotype for research and intervention over static summaries of smoking behaviors.

Background An ongoing debate regarding the nature of nicotine dependence (ND) is whether the same instrument can be applied to measure ND among adults and adolescents. Using a hierarchical item response model (IRM), we examined evidence for a common continuum underlying ND symptoms among adults and adolescents. Method The analyses are based on two waves of interviews with subsamples of parents and adolescents from a multi-ethnic longitudinal cohort of one thousand and thirty-nine 6–10th graders from the Chicago Public Schools (CPS). Adults and adolescents who reported smoking cigarettes the last 30 days prior to waves 3 and 5 completed three common instruments measuring ND symptoms and one item measuring loss of autonomy. Results A stable continuum of ND, first identified among adolescents, was replicated among adults. However, some symptoms, such as tolerance and withdrawal, differed markedly across adults and adolescents. The majority of mFTQ items were observed within the highest levels of ND, the NDSS items within the lowest levels, and the DSM-IV items were arrayed in the middle and upper third of the continuum of dependence severity. Loss of autonomy was positioned at the lower end of the continuum. We propose a ten-symptom measure of ND for adolescents and adults. Conclusions Despite marked differences in the relative severity of specific ND symptoms in each group, common instrumentation of ND can apply to adults and adolescents. The results increase confidence in the ability to describe phenotypic heterogeneity in ND across important developmental periods.

Background Age crossover describes the age-related reversal in prevalence of current cigarette smoking among non-Hispanic whites and African-Americans, with prevalence higher among whites than African-Americans in adolescence but lower in adulthood. Prior studies have examined smoking patterns in separate adolescent and adult samples and have not sought to identify factors that could account for crossover. We conducted analyses using national samples to identify factors that account for crossover and estimate their impact on crossover age. Methods Analyses are based on national samples of lifetime smokers 12–49 years old in the 2006-2008 aggregated National Surveys on Drug Use and Health ( N = 61, 757) ( SAMHSA, 2007–2009 ) and on multiple birth cohorts followed over 21 cross-sectional surveys. Results We identified crossover for cigarette smoking in the US population at about age 29. Crossover is partially explained by differences between whites and African-Americans in education and marital status, and more weakly by the opposite impact of age of smoking onset on persistence of smoking in the two groups. Controlling for smoking history, education and social role participation would raise crossover in current smoking by more than 14 years. Rates of current smoking among lifetime smokers at four different age categories in multiple birth cohorts followed from ages 12–17 to 35 and over in 21 surveys spanning 24 years confirm the age-related patterns observed cross-sectionally. Conclusion Age crossover for current smoking appears among whites and African-Americans. Efforts targeted toward improving educational levels of young people would have the strongest impact in decreasing persistent smoking, especially among African-Americans.

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.

Much more is known about the etiology of smoking than nicotine dependence (ND) in adolescence. Several studies have compared the characteristics of dependent and non-dependent adolescent smokers (Audrain-McGovern et al., 2007; DiFranza et al., 2007a; Hu, Davies, & Kandel, 2006; Kandel, Hu, Griesler, & Schaffran, 2007; Karp, O'Loughlin, Hanley, Tyndale, & Paradis, 2006). To our knowledge, no study has tested a causal model of adolescent ND to specify the role of important risk and protective factors. We apply a developmental socialization framework to document the impact of individual psychosocial characteristics and proximal contextual variables on ND in adolescence.

Using the theoretical model of nicotine dependence (ND) operationalized within the Diagnostic and Statistical Manual of Mental Disorder, fourth Edition (DSM-IV: American Psychiatric [American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC]) as a frame of reference, we used methods based in item response theory to link alternative instruments assessing adolescent nicotine dependence severity to a common latent continuum. A multi-ethnic cohort of 6th–10th graders selected from the Chicago Public Schools (CPS) completed five household interviews over 2 years. Youth who reported at least some cigarette use in the last 30 days prior to the interviews at waves W3–W5 completed measures of DSM-IV ND, the Modified Fagertrom Tolerance Questionnaire (mFTQ: Prokhorov et al., 1998 ) and the Nicotine Dependence Syndrome Scale (NDSS: Shiffman et al., 2004 ), yielding samples of 253, 241, and 296 respondents at W3–W5, respectively. Confirmatory factor analysis supported a primary dimension of ND. Each instrument’s items had complementary and stable relationships to ND across multiple waves of assessment. By aligning symptoms along a common latent ND continuum, we evaluated the consistency of symptoms from different instruments that target similar content. Further, these methods allowed for the examination of the DSM-IV as a continuous index of ND, evaluation of the degree of heterogeneity in levels of ND within groups above and below diagnostic thresholds, and the utility of using the pattern or particular DSM-IV symptoms that led to each score in further differentiating levels of ND. Finally, we examined concurrent validity of the ND continuum and levels of current of smoking at each wave of assessment.

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 to 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.

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.

The Gateway Hypothesis describes how tobacco or alcohol use precedes marijuana and other illicit drug use. We review the epidemiological data, explore the underlying molecular mechanisms in mice and discuss the societal implications of the hypothesis, including the use of e-cigarettes by young people. Conclusion Our mouse model identifies biological processes underlying the hypothesis, showing that nicotine is a gateway drug that exerts a priming effect on cocaine through increased global acetylation in the striatum.

This study examined gender differences in posttraumatic stress disorder (PTSD) symptoms and symptom factors in the total U.S. active duty force. Data were drawn from the 2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel including 17,939 men and 6751 women from all services. The results indicated that women expressed more distress than men across almost all the symptoms on the PTSD Checklist except for hypervigilance. Women also scored significantly higher on all four factors examined: Re-experiencing, Avoidance, Emotionally Numb, Hyperarousal. More women than men were distressed by combat experiences that involved some type of violence, such as being wounded, witnessing or engaging in acts of cruelty, engaging in hand-to-hand combat, and, to a lesser extent, handling dead bodies. Men who had been sexually abused had a greater number of symptoms and were consistently more distressed than women on individual symptoms and symptom factors.

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. Methods 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.

Objective To investigate the extent to which adolescents in the community with current substance use disorders (SUD) experience co-occurring psychiatric disorders. Method Diagnostic data were obtained from probability samples of 401 children and adolescents, aged 14 to 17 years, and their mothers/caretakers, who participated in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Results The rates of mood and disruptive behavior disorders are much higher among adolescents with current SUD than among adolescents without SUD. Comparison with adult samples suggests that the rates of current comorbidity of SUD with psychiatric disorders are the same among adolescents as adults, and lower for lifetime disruptive disorders/antisocial personality disorder among adolescents than adults. Conclusions The high rate of coexisting psychiatric disorders among adolescents with SUD in the community needs to be taken into account in prevention and treatment programs.

Event history analysis was applied to monthly life and drug histories of a representative community sample of 706 marijuana users, followed from ages 15–16 to 34–35, to investigate factors associated with cessation of marijuana use from adolescence to adulthood. In addition to age and gender, the most important determinants of cessation are the phenomenology of marijuana use, social role participation, depressive symptoms and deviance. Frequent users, those who started using early and those who use illicit drugs other than marijuana are more likely to continue their marijuana use. Using marijuana for social reasons accelerates cessation, using to change one's mood reduces cessation. Becoming pregnant and a parent is the most important social role leading to marijuana cessation for women. There is also a very important experimental effect of the interview itself on the reported timing of a cessation. The effect of a social context favorable to marijuana use appears to reflect selection rather than social influence.

We previously reported that maternal prenatal smoking had a significant effect on adolescent daughters' smoking, especially current smoking. Using a longitudinal sample of 187 mother-child dyads, we examine the role of child behavior problems in potentially explaining this effect. Maternal smoking during pregnancy is associated with higher levels of child behavior problems, particularly among girls. Childhood behavior problems increase the likelihood of lifetime smoking among daughters but do not explain the effect of prenatal maternal smoking on their current smoking. Maternal smoking in pregnancy, especially heavy use of a pack or more a day, retains a unique effect on girls' current smoking with controls for current maternal smoking, child behavior problems, and maternal monitoring of the child. The effect of maternal prenatal smoking is suggestive of a biological component, which may have direct or indirect influences on adolescent smoking. The small number of cases in the study calls for the replicat...

The association between levels of marijuana use and last year dependence is investigated in a nationally representative sample of adolescents and adults, who used marijuana within the last year (n = 9284). Data are aggregated from three surveys (1991-1993) of the National Household Survey on Drug Abuse. A proxy measure of DSM-IV dependence criteria was developed from self-reported symptoms of dependence and drug-related problems. Both frequency and quantity of marijuana use within the last year are linearly associated with the logit of the probability of being dependent on marijuana. The associations vary significantly by age but not gender. Adolescents are dependent at a lower frequency and quantity of use than adults: the differences diverge as level of use increases. Twice as many adolescents as adults who used marijuana near-daily or daily within the last year were identified as being dependent (35% versus 18%). Frequency and quantity of use each retained a unique effect on dependence, but frequency appeared to be more important than quantity in predicting last year dependence. These results provide insight into the processes underlying the age and sex differentials observed in the prevalence of marijuana dependence. The implications of the findings for the epidemiology of marijuana use and dependence are discussed.