Associations Between E-cigarettes and Subsequent Cocaine Use in Adolescence: An Analysis of the UK Millennium Cohort Study.

INTRODUCTION: Nicotine exposure via early combustible cigarette smoking can prime the adolescent brain for subsequent cocaine use. However, there is limited evidence whether e-cigarette use, a nicotine delivery system that is increasingly popular among youth, is associated with later cocaine use. We examine the association between e-cigarette use by the age of 14 years and cocaine use by the age of 17 years. AIMS AND METHODS: The Millennium Cohort Study is a nationally representative sample of 18 552 9-month-old children born between September 2000 and January 2002 in the United Kingdom. Follow-up interviews and surveys were collected from children and their caregivers at modal ages 3, 5, 7, 9, 11, 14, and 17 years. Our analytic sample included 340 youth who had used e-cigarettes by age 14 years (exposure variable), matched using coarsened exact matching, to 4867 nicotine naïve youth on childhood common liability confounders and demographics measured from infancy to age 11. The outcome was cocaine use by the modal age of 17 years. RESULTS: Of the 5207 successfully matched youth, 7.6% of adolescent e-cigarette users by age 14 years used cocaine by age 17 years versus 3.1% of non-e-cigarette users. Multivariable logistic regression in the matched sample indicated that e-cigarette use by age 14 years was associated with 2.7 times higher odds of cocaine use by age 17 years (95% CI, 1.75 to 4.28). CONCLUSIONS: These findings in a UK sample showed that e-cigarette use in early adolescence is associated with higher odds of cocaine use later in adolescence, similar to risks posed by tobacco cigarette smoking. IMPLICATIONS: In this large-scale prospective cohort study (n = 5207), youth who had used e-cigarettes by the age of 14 years were matched to nicotine naïve youth on childhood common liability confounders and demographics measured from infancy to age 11 years (e.g. school engagement, risk-taking propensity, delinquency, peer and parental smoking, parental educational attainment). After matching, 7.6% of age 14 years e-cigarette users had subsequently used cocaine by the age of 17 years versus 3.1% of non-e-cigarette users. Although e-cigarettes are promoted as a strategy for nicotine-dependent users to reduce the harms of combustible cigarettes, the evidence here suggests that for nicotine naïve youth, they may increase the risk of subsequent cocaine use.

Electronic cigarette use in adolescence is associated with later cannabis use.

BACKGROUND: Research is needed to determine whether e-cigarette use during adolescence is associated with higher odds of subsequent cannabis use, net of tobacco cigarette use and childhood confounders. METHODS: Multivariable logistic regressions predicting using cannabis by age 17 based upon prospective, intergenerational data from 10,251 youth in a nationally representative UK birth cohort followed from infancy who had not used cannabis by age 14. The focal predictor is e-cigarette use by age 14 in the context of the potential confounder tobacco cigarette use. Regressions include sociodemographic background and risk factors assessed at age 11 (e.g., alcohol initiation, problem behaviors, parental and peer smoking) and during early childhood (e.g., maternal smoking during pregnancy, parental substance use). RESULTS: Youth use of e-cigarettes by age 14 was associated with 2.8 times higher odds of subsequent cannabis use by age 17 [OR 2.75; 95% CI 1.82,4.15], net of tobacco cigarette smoking and childhood confounders. Similarly, use of e-cigarettes by age 14 was associated with 2.5 times higher odds [OR 2.46; 95% CI 1.48,4.08] of frequent cannabis use at age 17 (>10 times in prior year). If youth used both e-cigarettes and tobacco cigarettes by age 14, the probabilities of cannabis initiation were 75% and of frequent use was 25% by age 17, compared to probabilities of 23% and 6%, respectively, among youth who had used neither product. CONCLUSIONS: Findings add to accumulating evidence that adolescent e-cigarette use is associated with higher odds of later cannabis initiation and frequent use, independent of tobacco cigarette use.

Adolescent Stress Reduces Adult Morphine-Induced Behavioral Sensitization in C57BL/6J Mice.

Deaths related to opioid use have skyrocketed in the United States, leading to a public health epidemic. Research has shown that both biological (genes) and environmental (stress) precursors are linked to opioid use. In particular, stress during adolescence-a critical period of frontal lobe development-influences the likelihood of abusing drugs. However, little is known about the biological mechanisms through which adolescent stress leads to long-term risk of opioid use, or whether genetic background moderates this response. Male and female C57BL/6J and BALB/cJ mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence and then tested for morphine locomotor sensitization or morphine consumption in adulthood. To examine possible mechanisms that underlie stress-induced changes in morphine behaviors, we assessed physiological changes in response to acute stress exposure and prefrontal cortex (PFC) miRNA gene expression. Adolescent stress did not influence morphine sensitization or consumption in BALB/cJ animals, and there was limited evidence of stress effects in female C57BL/6J mice. In contrast, male C57BL/6J mice exposed to adolescent CVSS had blunted morphine sensitization compared to control animals; no differences were observed in the acute locomotor response to morphine administration or morphine consumption. Physiologically, C57BL/6J mice exposed to CVSS had an attenuated corticosterone recovery following an acute stressor and downregulation of twelve miRNA in the PFC compared to control mice. The specificity of the effects for C57BL/6J vs. BALB/cJ mice provides evidence of a gene-environment interaction influencing opioid behaviors. However, this conclusion is dampened by limited locomotor sensitization observed in BALB/cJ mice. It remains possible that results may differ to other doses of morphine or other behavioral responses. Long-term differences in stress reactivity or miRNA expression in C57BL/6J mice suggests two possible biological mechanisms to evaluate in future research.

Cigarette smoke-induced alterations in blood: A review of research on DNA methylation and gene expression.

Worldwide, smoking remains a threat to public health, causing preventable diseases and premature mortality. Cigarette smoke is a powerful inducer of DNA methylation and gene expression alterations, which have been associated with negative health consequences. Here, we review the current knowledge on smoking-related changes in DNA methylation and gene expression in human blood samples. We identified 30 studies focused on the association between active smoking, DNA methylation modifications, and gene expression alterations. Overall, we identified 1,758 genes with differentially methylated sites (DMS) and differentially expressed genes (DEG) between smokers and nonsmokers, of which 261 were detected in multiple studies (≥4). The most frequently (≥10 studies) reported genes were AHRR, GPR15, GFI1, and RARA. Functional enrichment analysis of the 261 genes identified the aryl hydrocarbon receptor repressor and T cell pathways (T helpers 1 and 2) as influenced by smoking status. These results highlight specific genes for future mechanistic and translational research that may be associated with cigarette smoke exposure and smoking-related diseases. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Pharmacokinetic Profile of Spectrum Reduced Nicotine Cigarettes.

INTRODUCTION: Spectrum research cigarettes have been developed with varying nicotine content for use in studies evaluating the effects of a regulatory policy reducing the permissible nicotine content in cigarettes. This study aimed to characterize the nicotine pharmacokinetic profile of Spectrum cigarettes. METHODS: Twelve daily smokers attended four sessions and had blood nicotine, exhaled carbon monoxide, and subjective effects measured before and after smoking either a single cigarette of their preferred brand or high (10.9 mg/cigarette), medium (3.2 mg/cigarette), or low (0.2 mg/cigarette) nicotine content Spectrum research cigarettes, in a double-blind design with order counterbalanced. RESULTS: The boost in blood nicotine concentration was dose-dependent, with a boost of 0.3, 3.9, and 17.3 ng/mL for low-, medium-, and high-nicotine content Spectrum cigarettes. The high dose Spectrum had a similar nicotine boost to the "preferred brand" cigarettes (19 ng/mL). Subjects took longer puffs on the low nicotine cigarettes, but smoked these cigarettes faster than other cigarette types. High nicotine Spectrum cigarettes reduced the urge to smoke more than other cigarette types. CONCLUSIONS: This study shows that Spectrum research cigarettes produce blood nicotine absorption in a dose-dependent manner, and therefore, are appropriate for use in studies of nicotine reduction in cigarettes. IMPLICATIONS: This is the first study to determine the pharmacokinetic profile of Spectrum reduced nicotine content research cigarettes following an overnight abstinence. These data could provide evidence to regulatory agencies about the effects of reduced nicotine cigarettes when considering regulations on tobacco reduction.

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.

Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of these substances on brain gene expression. Forty-three adolescent female C57BL/6J mice were assigned to four groups. In the first phase of the experiment, adolescent mice (PND 36-41 days) were exposed to three bottles filled with water or nicotine (200 µg/ml) for 22 h a day and a single bottle of water 2 h a day for six days. In the second phase (PND 42-45 days), the 4-day Drinking-in-the-Dark paradigm consisting of access to 20% v/v ethanol or water for 2h or 4h (the last day) was overlaid during the time when the mice did not have nicotine available. Ethanol consumption (g/kg) and blood ethanol concentrations (BEC, mg %) were measured on the final day and whole brains including the cerebellum, were dissected for RNA sequencing. Differentially expressed genes (DEG) were detected with CuffDiff and gene networks were built using WGCNA. Prior nicotine exposure increased ethanol consumption and resulting BEC. Significant DEG and biological pathways found in the group exposed to both nicotine and ethanol included genes important in stress-related neuropeptide signaling, hypothalamic-pituitary-adrenal (HPA) axis activity, glutamate release, GABA signaling, and dopamine release. These results replicate our earlier findings that nicotine exposure during adolescence increases ethanol consumption and extends this work by examining gene expression differences which could mediate these behavioral effects.

[Alcohol consumption patterns and genotypes determining alcohol tolerance in Chilean university students]. / Patrones de consumo y genotipos determinantes de la tolerancia al alcohol: estudio en estudiantes universitarios de Santiago de Chile.

BACKGROUND: Alleles involved in inefficient (ADH1B2*2 and ALDH2*2) or efficient (SNP6, ADH4 gene) alcohol metabolism may influence the risk of alcoholism. Alcoholism susceptibility has been classified as protector and risk-dependence phenotypes, associated with inefficient and efficient alcohol genetic metabolizing variants, respectively. AIM: To investigate the possible association between genetic protective and risk-dependence variants and alcohol intake patterns. MATERIAL AND METHODS: Saliva DNA samples were obtained and the AUDIT (Alcohol Use Disorders Identification Test) questionnaire was applied to 210 university students aged between 18 and 25 years old. RESULTS: No statistically significant association between protective or risk-dependence genetic variants and alcohol pattern intake was detected. However, new categories of alcohol intake patterns-not included in the AUDIT questionnaire-were identified. CONCLUSIONS: No association between the protector and risk-dependence phenotypes and patterns of alcohol consumption was detected in this sample of students.

Patrones de consumo y genotipos determinantes de la tolerancia al alcohol: estudio en estudiantes universitarios de Santiago de Chile / Alcohol consumption patterns and genotypes determining alcohol tolerance in Chilean university students

Background: Alleles involved in inefficient (ADH1B2*2 and ALDH2*2) or efficient (SNP6, ADH4 gene) alcohol metabolism may influence the risk of alcoholism. Alcoholism susceptibility has been classified as protector and risk-dependence phenotypes, associated with inefficient and efficient alcohol genetic metabolizing variants, respectively. Aim: To investigate the possible association between genetic protective and risk-dependence variants and alcohol intake patterns. Material and Methods: Saliva DNA samples were obtained and the AUDIT (Alcohol Use Disorders Identification Test) questionnaire was applied to 210 university students aged between 18 and 25 years old. Results: No statistically significant association between protective or risk-dependence genetic variants and alcohol pattern intake was detected. However, new categories of alcohol intake patterns-not included in the AUDIT questionnaire-were identified. Conclusions: No association between the protector and risk-dependence phenotypes and patterns of alcohol consumption was detected in this sample of students.