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1.
Addict Biol ; 27(1): e13092, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467598

RESUMO

Using a federally compatible, naturalistic at-home administration procedure, the present study examined the acute effects of three cannabis flower chemovars with different tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios, in order to test whether chemovars with a higher CBD content produce different effects. Participants were randomly assigned to ad libitum administration of one of three chemovars (THC-dominant: 24% THC, 1% CBD; THC+CBD: 9% THC, 10% CBD; CBD-dominant: 1% THC, 23% CBD); 159 regular cannabis users (male = 94, female = 65) were assessed in a mobile pharmacology lab before, immediately after, and 1 h after ad libitum administration of their assigned chemovar. Plasma cannabinoids as well as positive (e.g., high, elation) and negative (e.g., paranoia and anxiety) subjective effects were assessed at each time points. Participants who used the CBD-dominant and THC + CBD chemovars had significantly less THC and more CBD in plasma samples compared to participants who used the THC-dominant chemovar. Further, the THC + CBD chemovar was associated with similar levels of positive subjective effects, but significantly less paranoia and anxiety, as compared to the THC-dominant chemovar. This is one of the first studies to examine the differential effects of various THC to CBD ratios using chemovars that are widely available in state-regulated markets. Individuals using a THC + CBD chemovar had significantly lower plasma THC concentrations and reported less paranoia and anxiety while also reporting similar positive mood effects as compared to individuals using THC only, which is intriguing from a harm reduction perspective. Further research is needed to clarify the harm reduction potential of CBD in cannabis products.


Assuntos
Canabidiol/administração & dosagem , Cannabis/química , Dronabinol/administração & dosagem , Flores/química , Adulto , Canabidiol/efeitos adversos , Canabidiol/sangue , Dronabinol/efeitos adversos , Dronabinol/sangue , Feminino , Redução do Dano , Humanos , Masculino , Pessoa de Meia-Idade
2.
Yale J Biol Med ; 95(3): 327-341, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36187412

RESUMO

Cannabis and health research continue to largely ignore the usage patterns, perceptions, and medically related use in Spanish-speaking communities. The primary aim of this study was to collect data among Spanish-speaking communities on cannabis use that specifically characterizes granular demographic information, medically motivated and recreational use patterns including potency of products, medical motivations for use, and what perceptions are held as to risks and benefits. Secondarily, exploratory analyses were made to investigate potential effects of location or acculturation status. Five hundred forty-nine individuals completed the survey, including 294 residing in the United States (US) (Mage =31.8, SD=9.72; 154 women, 137 men, 3 non-binary and self-described individuals), 174 residing outside of the US (International) (Mage =26.6, SD=8.75; 77 women, 96 men, 1 non-binary and self-described individuals), and 81 who did not report country of residence (Unknown location) (Mage =26.7, SD=7.37; 17 women, 61 men, 3 non-binary and self-described individuals). Overall use was mostly recreational, while the US group was significantly more motivated by medical or combined medical and recreational reasons than the other two groups (p=0.02). The most common reason for medical use was anxiety or depression (14% of sample). The US group also smoked or vaporized significantly more often than the other two groups and was more likely to include daily users (p<0.001). The sample generally viewed the effects of cannabis use more favorably than negatively, but there were significant differences in these views between users and non-users. The rich heterogeneity suggested by these data belies the importance of taking an equity focused approach to cannabis research and will help to improve representation in the field.


Assuntos
Cannabis , Maconha Medicinal , Adulto , Analgésicos , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários , Estados Unidos/epidemiologia
3.
Ther Drug Monit ; 43(4): 536-545, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33656464

RESUMO

BACKGROUND: Self-report questionnaires, weighing products consumed, and Δ9-tetrahydrocannabinol (THC) biomarkers are established techniques for estimating cannabis exposure. Population pharmacokinetic modeling of plasma THC and metabolite concentrations by incorporating self-reported and weighed products as covariates could improve estimates of THC exposure in regular cannabis users. METHODS: In this naturalistic study, blood samples were obtained from 36 regular smokers of cannabis for analysis of THC and its 2 metabolites at 4 time points: recruitment and during an experimental mobile laboratory assessment that included 3 time points: before, immediately after, and 1 hour after ad libitum legal market flower use. These data were analyzed using an established model of population pharmacokinetics developed from laboratory-controlled cannabis administration data. Elimination and metabolite production clearances were estimated for each subject as well as their daily THC doses and the dose consumed during the ad libitum event. RESULTS: A statistically significant correlation existed between the daily THC dose estimated by self-report questionnaire and population pharmacokinetic modeling (correlation coefficient = 0.79, P < 0.05) between the weighed cannabis smoked ad libitum and that estimated by population pharmacokinetic modeling (correlation coefficient = 0.71, P < 0.05). CONCLUSION: Inclusion of self-reported questionnaire data of THC consumption improved pharmacokinetic model-derived estimates based on measured THC and metabolite concentrations. In addition, the pharmacokinetic-derived dose estimates for the ad libitum smoking event underestimated the THC consumption compared with the weighed amount smoked. Thus, the subjects in this study, who smoked ad libitum and used cannabis products with high concentrations of THC, were less efficient (lower bioavailability) compared with computer-paced smokers of low potency, NIDA cannabis in a laboratory setting.


Assuntos
Dronabinol/farmacocinética , Fumar Maconha , Cannabis , Colorado , Humanos , Fumar Maconha/epidemiologia
4.
Anal Bioanal Chem ; 413(12): 3381-3392, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33817753

RESUMO

The endocannabinoid system (ECS) is a complex cell-signaling system. To address the growing need of analytics capturing endocannabinoid levels to investigate the ECS, we developed and validated an assay for the quantitative analysis of 14 endocannabinoids and congeners. A simple extraction using protein precipitation with acetonitrile followed by online-trapping high-performance liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS) was used to monitor the levels of 14 endocannabinoids in plasma. The assay was validated and intra-run and inter-run accuracies and imprecisions as well as matrix effects, recoveries, and sample stabilities were determined. As a proof of concept, a subset of study samples after naturalistic administration of Cannabis flower and concentrate was analyzed. With the exception of N-oleoyl dopamine and oleamide, all endocannabinoids fulfilled the predefined acceptance criteria. Reproducible recoveries and no significant matrix effects were observed. Sample stability was an issue. Analysis of the proof-of-concept study samples revealed a significantly (p = 0.006) higher concentration of docosatetraenoyl ethanolamide in concentrate users (300 ± 13 pg/mL) compared to flower users (252 ± 11 pg/mL). A robust, sensitive high-throughput assay for the quantitation of 14 endocannabinoids and congeners was successfully validated. Our study showed that it is mandatory to (A) appropriately stabilize samples and (B) separate and separately quantify 1-AG and 2-AG; otherwise, study results are unreliable. The analysis of study samples from Cannabis flower users versus Cannabis concentrate users revealed higher levels of docosatetraenoyl ethanolamide and anandamide (n.s.) in high THC concentrate users in accordance with the existing literature, supporting the validity of the assay measurements. Graphical abstract.


Assuntos
Cannabis , Cromatografia Líquida de Alta Pressão/métodos , Endocanabinoides/sangue , Espectrometria de Massas/métodos , Pressão Atmosférica , Humanos , Limite de Detecção , Estudo de Prova de Conceito , Controle de Qualidade , Reprodutibilidade dos Testes
5.
Alcohol Clin Exp Res ; 44(2): 340-353, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31803950

RESUMO

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota-gut-brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm-reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions.


Assuntos
Alcoolismo/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Canabidiol/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Alcoolismo/metabolismo , Animais , Encéfalo/metabolismo , Canabidiol/metabolismo , Canabidiol/farmacologia , Canabinoides/metabolismo , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Humanos
6.
Addict Biol ; 25(1): e12684, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370960

RESUMO

Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inability to control consumption of alcohol and other drugs as substance use disorders progress. Genetic and epigenetic factors have been associated with substance use disorders (SUDs). For example, dopamine receptor 2 (DRD2) functioning has been associated with alcohol use disorder (AUD) and related phenotypes, including correlates of executive functioning. The present study aims to explore the relationship between a continuous measure of alcohol-related problems, epigenetic markers (methylation) within the DRD2 gene, and functional connectivity within the ECN among a sample of polysubstance users. A community sample of 658 subjects, whose consumption of alcohol, nicotine, and cannabis span across a spectrum of quantity and frequency of use, were obtained across previous studies in polysubstance using populations. Resting state functional magnetic resonance imaging was analyzed to identify intrinsic connectivity networks using a priori regions of interest. Methylation measurement of functionally relevant sites within the DRD2 gene was achieved via pyrosequencing. Regression-based models, including mediation and moderation models, tested the association between DRD2 methylation, functional connectivity within intrinsic neural networks (including the ECN), and severity of alcohol problems. Results suggest that average DRD2 methylation was negatively associated with right ECN (RECN) and left ECN (LECN) connectivity, but not associated with other networks tested, and DRD2 methylation was significantly associated with alcohol problems severity. Mediation models were not supported, although moderation models suggested that connectivity between edges within the RECN moderated the relationship between DRD2 methylation and AUD severity. Results support a theoretical model in which epigenetic factors are associated with neurobiological correlates of alcohol consumption among a sample of polysubstance users.


Assuntos
Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Fumar Cigarros/fisiopatologia , Função Executiva/efeitos dos fármacos , Abuso de Maconha/fisiopatologia , Receptores de Dopamina D2/genética , Adulto , Alcoolismo/genética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Fumar Cigarros/genética , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Abuso de Maconha/genética , Metilação , Índice de Gravidade de Doença , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
7.
Value Health ; 22(11): 1289-1294, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31708066

RESUMO

The United States has witnessed enormous changes concerning the acceptance of medicinal and recreational cannabis use. Sixty-three percent of the US population has access to medicinal cannabis markets, which offer increasingly diverse and potent cannabis products. Considering the rapidly changing cultural, political, and legal landscape, the scientific literature does not adequately inform public policy, medical decision making, or harm reduction approaches. The goals of this paper are to (1) investigate the state of cannabis research on medical conditions commonly treated with cannabis, (2) review the barriers that have led to large gaps between cannabis use and available empirical data, and (3) suggest a path forward with new research designs to address these gaps. Thus, we aim to advance a more nuanced understanding of the barriers to cannabis research and suggest innovative research designs necessary for rapid development of a meaningful knowledge base.


Assuntos
Pesquisa Biomédica/organização & administração , Maconha Medicinal/uso terapêutico , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Humanos , Disseminação de Informação , Conhecimento , Maconha Medicinal/administração & dosagem , Maconha Medicinal/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Estados Unidos
8.
Addict Biol ; 24(3): 539-548, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29464814

RESUMO

Studies have identified strong associations between D2 receptor binding potential and neural responses to rewarding stimuli and substance use. Thus, D2 receptor perturbations are central to theoretical models of the pathophysiology of substance dependence, and epigenetic changes may represent one of the fundamental molecular mechanisms impacting the effects of alcohol exposure on the brain. We hypothesized that epigenetic alterations in the promoter region of the dopamine D2 receptor (DRD2) gene would be associated with cue-elicited activation of neural reward regions, as well as severity of alcohol use behavior. The current study leveraged functional neuroimaging (fMRI) during an alcohol reward paradigm (n = 383) to test associations among DRD2 promoter methylation in peripheral tissue, signal change in the striatum during the presentation of alcohol cues, and severity of alcohol use disorder (AUD). Controlling for age, DRD2 promoter methylation was positively associated with responses to alcohol cues in the right accumbens (partial r = 0.144, P = 0.005), left putamen (partial r = 0.133, P = 0.009), right putamen (partial r = 0.106, P = 0.039), left caudate (partial r = 0.117, P = 0.022), and right caudate (partial r = 0.133, P = 0.009), suggesting that DRD2 methylation was positively associated with robust activation in the striatum in response to reward cues. DRD2 methylation was also positively associated with clinical metrics of AUD severity. Specifically, controlling for age, DRD2 methylation was associated with Alcohol Use Disorders Identification Test total (partial r = 0.140, P = 0.002); Impaired Control Scale total (partial r = 0.097, P = 0.044) and Alcohol Dependence Scale total (partial r = 0.152, P = 0.001). Thus, DRD2 methylation may be a critical mechanism linking D2 receptors with functional striatal brain changes and clinical severity among alcohol users.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Receptores de Dopamina D2/metabolismo , Recompensa , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Encéfalo/metabolismo , Sinais (Psicologia) , Metilação de DNA/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Paladar/fisiologia , Adulto Jovem
9.
Am J Drug Alcohol Abuse ; 45(5): 514-526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184938

RESUMO

Background: Polymorphisms in cannabinoid receptor type 1 (encoded by CNR1) and fatty acid amide hydrolase (encoded by FAAH) have been associated with cannabis dependence, but it remains unknown whether variation within these genes influences cannabis' acute effects on affect. Objective: Conduct a secondary data analysis study to determine whether previously observed acute effects of tetrahydrocannabinol (THC) on mood was dependent upon variation in CNR1 and FAAH. Methods: A balanced placebo design was used crossing marijuana administration (i.e., 0% THC vs. 2.8% THC) with stimulus expectancy. Participants (N = 118; 64% male) provided DNA and completed the Profile of Mood States questionnaire prior to and after smoking. Haplotypes were constructed from genotyped single nucleotide polymorphisms for CNR1 (rs1049353 and rs806368) and FAAH (rs4141964, rs324420, and rs11576941); rs2023239 (CNR1) and rs6703669 (FAAH) were not part of a phased haplotype block. Analyses tested both main and interaction effects for genotype across CNR1 and FAAH, and drug, and expectancy effects. Results: THC increased levels of POMS Tension-Anxiety and Confusion-Bewilderment over and above the effects of variation in CNR1 and FAAH. Significant drug X genotype/haplotype and expectancy X genotype/haplotype interaction effects were observed for some but not all mood states [e.g., 'C' allele carriers of rs2023239 who received THC had higher levels of Anger-Hostility (ß= 0.29 (0.12), p= .02) compared to those who received placebo]. Conclusion: These preliminary findings suggest individual differences in mood states after using marijuana depend on genetic variation. Such information might be useful in understanding either motivation for use of marijuana and/or risk for associated behaviors.


Assuntos
Amidoidrolases/genética , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Receptor CB1 de Canabinoide/genética , Afeto/efeitos dos fármacos , Dronabinol/farmacologia , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Abuso de Maconha/genética , Fumar Maconha/genética , Polimorfismo de Nucleotídeo Único
10.
Alcohol Clin Exp Res ; 42(3): 531-539, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29286537

RESUMO

BACKGROUND: In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination. METHODS: We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1ß in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines. RESULTS: A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1ß. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users. CONCLUSIONS: These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets.


Assuntos
Consumo de Bebidas Alcoólicas/imunologia , Citocinas/imunologia , Uso da Maconha/imunologia , Adulto , Feminino , Humanos , Inflamação , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Masculino
11.
Am J Med Genet B Neuropsychiatr Genet ; 174(4): 458-466, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28512748

RESUMO

Although the heritability of ADHD is estimated to be high, identifying specific genetic markers remains challenging. Most studies to date have examined the genetic basis of ADHD by employing dichotomous diagnostic phenotypes, but, as ADHD symptoms tend to be phenotypically dimensional, an alternative and potentially informative approach is to examine continuous indices of inattention and hyperactivity-impulsivity symptoms. The current study aimed to identify genetic effects on dimensionally-focused adult ADHD-related phenotypes in 990 individuals of European ancestry with intentionally low levels of substance misuse to avoid confounding. The study used four complementary approaches: (1) analysis of a priori candidate loci identified in prior meta-analytic work; (2) gene-based analysis; (3) hypothesis-free genome-wide association testing; and (4) single nucleotide polymorphism (SNP) heritability via genomic-relatedness-matrix restricted maximum likelihood analysis (GREML). The GREML analysis included a bivariate model to test whether the ADHD symptom dimensions index the same genetic liability. The results revealed significant differential associations between two a priori loci and ADHD phenotypes, rs6296 in HTR1B with inattention and rs3746544 in SNAP-25 with hyperactivity-impulsivity. No significant gene-based or genome-wide associations were detected, but SNP heritability revealed that a large portion of genetic variance was accounted for by common SNPs (44%, 55%, and 59% for inattention, hyperactivity-impulsivity, and total ADHD, respectively) and substantial shared genetic variance across inattention and hyperactivity-impulsivity (86%). These findings reveal both unique and common patterns of genetic influences across dimensional ADHD-related phenotypes. More broadly, these findings reveal the value in using multiple methods to understand the genetic etiology of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Marcadores Genéticos , Predisposição Genética para Doença , Testes Genéticos/métodos , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Receptor 5-HT1B de Serotonina/genética , Proteína 25 Associada a Sinaptossoma/genética , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Feminino , Humanos , Masculino , Fenótipo , Prognóstico , Adulto Jovem
12.
Behav Genet ; 46(3): 416-30, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27098899

RESUMO

When examining the effects of prenatal exposure to maternal smoking during pregnancy (MSDP) on later offspring substance use, it is critical to consider familial environments confounded with MSDP. The purpose of this study was to examine the effect of MSDP on offspring's initial reactions to cigarettes and alcohol, which are indicators of future substance-use related problems. We tested these effects using two propensity score approaches (1) by controlling for confounding using the MSDP propensity score and (2) examining effects of MSDP across the MSDP risk distribution by grouping individuals into quantiles based on their MSDP propensity score. This study used data from 829 unrelated mothers with a reported lifetime history of smoking to determine the propensity for smoking only during their first trimester (MSDP-E) or throughout their entire pregnancy (MSDP-T). Propensity score analyses focused on the offspring (N = 1616 female twins) of a large subset of these mothers. We examined the effects of levels of MSDP-E/T on offspring initial reactions to their first experiences with alcohol and cigarettes, across the distribution of liability for MSDP-E/T. MSDP-E/T emerged as significant predictors of offspring reactions to alcohol and cigarettes, but the effects were confounded by the familial liability for MSDP. Further, the unique MSDP effects that emerged were not uniform across the MSDP familial risk distribution. Our findings underscore the importance of properly accounting for correlated familial risk factors when examining the effects of MSDP on substance related outcomes.


Assuntos
Etanol/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Pontuação de Propensão , Fumar/efeitos adversos , Adolescente , Criança , Intervalos de Confiança , Feminino , Humanos , Gravidez , Prevalência , Fatores de Risco , Adulto Jovem
13.
Behav Genet ; 46(3): 403-15, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26826031

RESUMO

Studies of maternal smoking during pregnancy (MSDP) suggest increased risk for cognitive impairment and psychiatric outcomes. However, it is uncertain whether these associations are the direct result of MSDP or related to confounding familial variables associated with MSDP. The current study employed propensity score analysis to examine the effects of MSDP on offspring EXT using data from a large sample of 979 unrelated mothers. Logistic regression models were used to determine the propensity that the offspring of these mothers were likely to be exposed to MSDP [i.e., smoked during only the first trimester (MSDP-EARLY[E]) or smoked throughout their pregnancy (MSDP-THROUGHOUT[T])] given known familial confounders. Analyses focused on the effect of MSDP-E/T on the EXT behavior in offspring of these mothers (N = 1616) were conducted across the distribution of liability for MSDP-E/T and at different levels of risk for MSDP-E/T. MSDP-E/T was associated with offspring EXT problems, but the effects were partly confounded by the familial liability for MSDP. Further, the observed effects were not consistent across all levels of the MSDP risk distribution. These findings suggest a direct association between MSDP and offspring EXT behaviors, and that varied associations observed across studies may be the result of differences in the level of familial confounders that also have an effect on offspring EXT.


Assuntos
Transtornos do Comportamento Infantil/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Gêmeos/psicologia , Adolescente , Criança , Intervalos de Confiança , Feminino , Humanos , Mães , Gravidez , Prevalência , Fatores de Risco
14.
Alcohol Clin Exp Res ; 40(8): 1633-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27388583

RESUMO

BACKGROUND: Epigenetic factors, including DNA methylation, play an important role in the etiology of alcohol use disorders (AUDs). Noncandidate-based methylome-wide studies leveraging multiple tissue types are needed in order to identify a set of CpG targets that reliably differentiate AUD patients from controls and strongly correlate across brain tissue and more commonly collected tissue types (e.g., buccal cells). METHODS: Postmortem precuneus brain tissue samples were collected from 49 alcohol-dependent (AD) cases and 47 controls (sample I), and DNA was extracted from precuneus and putamen brain tissue and buccal cells in 24 postmortem subjects (sample II). Methylation levels were analyzed at over 450,000 CpG sites in both samples. CpGs that demonstrated significant methylation differences between cases and controls were advanced for further analysis with the goal of identifying CpGs that also demonstrated consistent methylation correlations across tissue type. RESULTS: In the primary analysis, 244 hypomethylated and 188 hypermethylated CpGs met a priori criteria for both significant methylation differences between cases and controls as well as significant correlation across brain and buccal cell tissue types, employing stringent Bonferroni p-value correction. Many of these CpGs were involved in gene networks related to lipid metabolism, immune response, inflammatory response/disease, and gastro-intestinal disease. CONCLUSIONS: More than 400 CpGs demonstrated differences in methylation between AD cases and controls and showed significant correlation across tissue types. Several genes and pathways (e.g., inflammation and immune functioning) that have been previously associated with AUD were identified in the current analyses.


Assuntos
Transtornos Relacionados ao Uso de Álcool/genética , Transtornos Relacionados ao Uso de Álcool/patologia , Encéfalo/patologia , Metilação de DNA/genética , Estudo de Associação Genômica Ampla , Adulto , Ilhas de CpG/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Am J Med Genet B Neuropsychiatr Genet ; 171(7): 971-81, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26799787

RESUMO

Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the developing child, including behavioral outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD). There is substantial interest in understanding the nature of this reported association, particularly in light of more recent genetically informed studies that suggest that the SDP-ADHD link is less clear than once thought. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we use a sibling-comparison approach that controls for shared genetic and familial influences to assess the effects of SDP on ADHD symptom dimensions. ADHD was measured by both parent and teacher report on the Conners report forms and the Child Behavior Checklist/Teacher Report Form (CBCL/TRF). Results for the CBCL/TRF Total ADHD score are consistent with prior genetically informed approaches and suggest that previously reported associations between SDP and ADHD are largely due to familial confounding rather than causal teratogenic effects. However, results from the Conners parent report suggest a potentially causal effect of SDP on hyperactive/impulsive and, to a lesser extent, total ADHD symptoms; SDP results in increased parent-reported hyperactive/impulsive and total ADHD symptoms even after accounting for genetic and familial confounding factors. This suggests that the Conners assessment (parent-report) may provide a sensitive measure for use in studies examining child specific SDP effects on continuous and dimensional aspects of ADHD. © 2016 Wiley Periodicals, Inc.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Fumar/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Gravidez , Reprodutibilidade dos Testes , Fatores de Risco , Irmãos
16.
Nicotine Tob Res ; 17(5): 510-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25143294

RESUMO

INTRODUCTION: Beneficial effects of nicotine on cognitive functioning may contribute to the markedly high rates of smoking among people with schizophrenia. A reduction in the nicotine content of cigarettes to non-addictive levels is being considered as a regulatory strategy for reducing tobacco dependence in the United States. We examined whether switching to very low nicotine content (VLNC) cigarettes impairs cognitive functioning in smokers with and without schizophrenia, andwhether nicotine replacement reverses these effects. METHODS: Smokers with schizophrenia (SS, n = 29) and control smokers matched on smoking rate but without psychiatric illness (CS, n = 28) smoked usual-brand cigarettes, VLNC cigarettes while wearing 2 placebo patches (PLA), or VLNC cigarettes while wearing 2 nicotine patches totaling 42mg (NIC) for 5hr, and then completed computerized assessments of visual sustained attention, motor speed, visual working memory, processing speed, inhibitory control, and response variability. RESULTS: Across conditions, SS were slower than CS in tasks of motor speed and visual working memory, and had poorer target detectability on a visual sustained attention task. Across groups, functioning in domains of visual sustained attention, inhibitory control, processing speed, and response variability was impaired in the VLNC + PLA condition relative to the usual-brand and VLNC + NIC conditions. CONCLUSIONS: Dramatically reducing the nicotine content of cigarettes may impair cognitive functioning in heavy smokers with and without schizophrenia, but the use of nicotine replacement while smoking VLNC cigarettes may preserve cognitive functioning in these smokers.


Assuntos
Cognição/efeitos dos fármacos , Nicotina/administração & dosagem , Esquizofrenia/complicações , Abandono do Hábito de Fumar/psicologia , Fumar/psicologia , Dispositivos para o Abandono do Uso de Tabaco , Tabagismo/complicações , Adulto , Feminino , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Nicotiana , Produtos do Tabaco/efeitos adversos , Tabagismo/tratamento farmacológico , Adulto Jovem
17.
Nicotine Tob Res ; 16(6): 743-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24415586

RESUMO

INTRODUCTION: Unlike older smokers, young adult smokers frequently engage in light and intermittent smoking. It remains unclear how stable such smoking patterns are over time, as substantial variability exists between these smokers. This study identified subgroups of college student smokers based on the trajectory of their smoking frequency during the first year of college, thereby examining stability versus instability over time. We then tested if the interplay between drinking and smoking differed in the identified groups to determine the relative role drinking may play in intermittent versus more regular smoking. METHODS: Incoming college students at 3 institutions completed online biweekly surveys of their daily substance use throughout the first year of college. Students who reported smoking at least 1 cigarette during this year (n = 266) were included in analyses (70% female, 74% White). RESULTS: Group-based trajectory modeling identified 5 groups of smokers, 3 of which maintained their smoking frequency throughout the year (77%), and 2 groups of infrequent smokers showed significant trends (11% increasing, 12% decreasing). Notably, nondaily smoking was maintained at different specific frequencies (e.g., 1 vs. 3 days per week). Identified groups differed in the relationship between drinking and smoking, where cooccurrence was particularly strong among infrequent smokers, and trends in smoking quantity differed between groups. CONCLUSIONS: While there was a diversity of smoking patterns in the sample, patterns of intermittent smoking remain relatively stable for a majority of students throughout the year. Intervention messages targeting drinking and smoking should be tailored on the basis of smoking frequency.


Assuntos
Consumo de Bebidas Alcoólicas/tendências , Fumar/tendências , Estudantes/estatística & dados numéricos , Adolescente , Feminino , Humanos , Masculino , Universidades , Adulto Jovem
18.
Nicotine Tob Res ; 16(8): 1085-93, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24692670

RESUMO

INTRODUCTION: We examined the association between hostility-a personality trait reflective of negativity and cynicism toward others-and smoking in adolescents by measuring (a) several subcomponents of hostility, and (b) facial emotion processing ability, which has been previously linked to hostility. METHODS: Participants (N = 241 aged 14-19) were 95 smokers and 95 demographically matched nonsmokers as well as 51 nonmatched smokers. All participants completed the Cook-Medley (C-M) hostility scale, which provides a general hostility score and 3 component scores (cynicism, hypersensitivity, and aggressive responding), and a facial emotion processing task. This task, designed to assess emotion recognition, requires quickly identifying the emotion of faces that gradually morph from neutral to high-intensity happy, angry, or fearful. RESULTS: Independent sample t tests indicated that matched smokers scored significantly higher in cynicism and aggressive responding than nonsmokers. Among smokers, age of smoking onset was negatively correlated with general hostility and aggressive responding. All hostility scales were positively correlated with the intensity needed to recognize happy faces. Counterintuitively, smokers required a greater intensity to recognize angry faces than nonsmokers. No other relations between hostility/smoking status and facial emotion processing were observed. CONCLUSIONS: Aspects of hostility, particularly aggressive responding, may be a risk factor for early onset smoking. Although hostile participants exhibited a deficiency in their ability to recognize happiness in facial pictures, these results did not translate to differences in smoking status. This study elucidates some of the complex interrelations between hostility, emotion processing, and adolescent smoking, which may have implications for teen smoking prevention.


Assuntos
Hostilidade , Fumar/psicologia , Adolescente , Agressão , Ira , Emoções , Expressão Facial , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
19.
Psychiatry Clin Psychopharmacol ; 34(1): 82-93, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38883882

RESUMO

Cannabis use is increasingly common. There is a need for validated tools to meaningfully assess recreational, medical, and disordered cannabis use in both research and clinical contexts. Cannabis assessments were considered against pre-determined inclusion criteria within a comprehensive review. Measures were categorized as either (i) evaluating use frequency or quantity, (ii) measuring symptoms of disordered use and withdrawal, or (iii) assessing use motives, effects, and perceptions. The applications and validations for each assessment are summarized. Finally, recommendations for refining of existing measures or development of new measures are presented. The literature review resulted in 289 publications that were reviewed in detail, yielding 21 assessments that met inclusion criteria. The applications of these assessments are described here, in addition to the information about the validation studies of each assessment. Based on the complication of these tools, 5 areas of potential development are highlighted to guide future research, including (i) sensitivity to the mode of cannabis administration as well as sensitivity to (ii) potency of cannabis products alongside frequency and quantity, (iii) unit equivalence, (iv) aligning clinical measures consistently with cannabis use disorder (CUD) diagnostic criteria, and (v) creating measures specific to medical users, their motives for use, and their perceptions of therapeutic benefits or side effects. Clinicians and researchers can pragmatically benefit from this summary of validated measures of cannabis use, and future work could improve the study of and clinical care for cannabis use and CUD by pursuing one or more key areas of development described here.

20.
Drug Alcohol Rev ; 43(2): 501-511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985016

RESUMO

INTRODUCTION: Sleep problems and anxiety conditions are common comorbidities and may be influenced by cannabis and alcohol use. This study examined daily within-person variation in subjective sleep quality among individuals with anxiety symptoms after cannabis or alcohol were used alone, and after co-use. METHODS: A total of 347 individuals with intentions to use cannabis to cope with anxiety reported their cannabis and alcohol use in the previous 24 h and their previous nights' sleep quality for 30 consecutive days. Mixed-effects models examined whether the within-person daily variation in use of cannabis and alcohol (alone and co-use) was associated with subjective sleep quality. Models also examined whether daily cannabis and alcohol use associations with sleep were moderated by frequency of cannabis, alcohol and co-use during the study period. RESULTS: Compared to non-use, participants reported better sleep after cannabis-use-only and after co-use, but not after alcohol-use-only. People who more frequently use alcohol and cannabis reported sleeping better after cannabis-use-only days compared to those who use cannabis and alcohol less frequently. DISCUSSION AND CONCLUSIONS: The study's utilisation of naturalistic data among individuals with anxiety symptoms replicated previously reported experimental findings among individuals without sleep and anxiety problems that overall, cannabis is associated with higher subjective sleep quality. The results expand upon other research to suggest that more frequent use of alcohol and cannabis may moderate daily associations of cannabis use and sleep, potentially through pharmacokinetics and cross-sensitisation.


Assuntos
Cannabis , Humanos , Intenção , Qualidade do Sono , Ansiedade , Transtornos de Ansiedade , Consumo de Bebidas Alcoólicas/epidemiologia , Etanol
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