Adolescent Marijuana Dependence: The Role of Social Bonds and Social Learning Theory.

Using the 2017 National Survey of Drug Use and Health (NSDUH) data, this research examines the extent to which social bonds and social learning theory predict adolescent marijuana dependence. Full information maximum likelihood (FIML) for logistic regression analyses were conducted in four models to test the competing theories. The results revealed partial support for both theories, such that adolescents with stronger parental bonds and negative definitions of substance use were less likely to be dependent on marijuana, while adolescents who associated with substance using peers were more likely to be dependent on marijuana. The multi-theoretical model suggested that only the social learning theory concepts of differential association and negative definitions were significant theoretical predictors of adolescent marijuana dependence. Additional analyses revealed that first using marijuana at 14 or 15 years old was also significantly related to adolescent marijuana dependence. Implications for future research and risk prevention programs are discussed.

Prevalence of obesity among U.S. population with substance dependence.

AIM: To investigate associations between substance dependence and obesity. METHODS: Obesity (body mass index ≥ 30 kg/m2) status and the status of dependence on heroin, stimulant, marijuana, nicotine and alcohol (past-month status for nicotine and past-year status for all others) were identified from the U.S. National Survey on Drug Use and Health (NSDUH, 2015-2017) datasets. SAS Surveylogistic regression was used to estimate adjusted odds ratio (AOR) for the association between each substance dependence and obesity, adjusting for potentially confounding effects of sociodemographic factors and health condition. RESULTS: It was estimated that 10.6 % of noninstitutional U.S. residents aged 12 years or older were nicotine-dependent, 3.0 % alcohol-dependent, 1.0 % marijuana-dependent, 0.6 % stimulant-dependent, and 0.2 % heroin-dependent. Heroin-dependent individuals had 59 % lower odds of obesity relative to their non-dependent counterparts (AOR = 0.41; 95 % CI: 0.28-0.60; p < 0.0001). Lower odds of obesity were also noted for marijuana-dependent (AOR = 0.64; 95 % CI: 0.56-0.73; p < 0.0001), nicotine-dependent (AOR = 0.68; 95 % CI: 0.64-0.72; p < 0.0001) and alcohol-dependent (AOR = 0.77, 95 % CI: 0.69-0.84; p < 0.0001) individuals, but not statistically significant for stimulant-dependent individuals (AOR = 0.84; 95 % CI: 0.68-1.02; p = 0.0825). CONCLUSIONS: Heroin, marijuana, nicotine and alcohol dependence were associated with lower odds of obesity than their non-dependence counterparts. Main findings based on 2015-2017 NSDUH are consistent with findings from our prior report based on clinical trials data from National Institute on Drug Abuse Clinical Trials Network, and other epidemiological evidence in the literature. These findings can alert substance abuse treatment professionals to monitor weight change, especially among weight-concerned substance abusers.

Fronto-striatal effective connectivity of working memory in adults with cannabis use disorder.

Previous working memory (WM) studies found that relative to controls, subjects with cannabis use disorder (CUD) showed greater brain activation in some regions (e.g., left [L] and right [R] ventrolateral prefrontal cortex [VLPFC], and L dorsolateral prefrontal cortex [L-DLPFC]), and lower activation in other regions (e.g., R-DLPFC). In this study, effective connectivity (EC) analysis was applied to functional magnetic resonance imaging data acquired from 23 CUD subjects and 23 controls (two groups matched for sociodemographic factors and substance use history) while performing an n-back WM task with interleaved 2-back and 0-back periods. A 2-back minus 0-back modulator was defined to measure the modulatory changes of EC corresponding to the 2-back relative to 0-back conditions. Compared to the controls, the CUD group showed smaller modulatory change in the R-DLPFC to L-caudate pathway, and greater modulatory changes in L-DLPFC to L-caudate, R-DLPFC to R-caudate, and R-VLPFC to L-caudate pathways. Based on previous fMRI studies consistently suggesting that greater brain activations are related to a compensatory mechanism for cannabis neural effects (less regional brain activations), the smaller modulatory change in the R-DLPFC to L-caudate EC may be compensated by the larger modulatory changes in the other prefrontal-striatal ECs in the CUD individuals.

Whole genome sequence study of cannabis dependence in two independent cohorts.

Recent advances in genome wide sequencing techniques and analytical methods allow for more comprehensive examinations of the genome than microarray-based genome-wide association studies (GWAS). The present report provides the first application of whole genome sequencing (WGS) to identify low frequency variants involved in cannabis dependence across two independent cohorts. The present study used low-coverage whole genome sequence data to conduct set-based association and enrichment analyses of low frequency variation in protein-coding regions as well as regulatory regions in relation to cannabis dependence. Two cohorts were studied: a population-based Native American tribal community consisting of 697 participants nested within large multi-generational pedigrees and a family-based sample of 1832 predominantly European ancestry participants largely nested within nuclear families. Participants in both samples were assessed for Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) lifetime cannabis dependence, with 168 and 241 participants receiving a positive diagnosis in each sample, respectively. Sequence kernel association tests identified one protein-coding region, C1orf110 and one regulatory region in the MEF2B gene that achieved significance in a meta-analysis of both samples. A regulatory region within the PCCB gene, a gene previously associated with schizophrenia, exhibited a suggestive association. Finally, a significant enrichment of regions within or near genes with multiple splice variants or involved in cell adhesion or potassium channel activity were associated with cannabis dependence. This initial study demonstrates the potential utility of low pass whole genome sequencing for identifying genetic variants involved in the etiology of cannabis use disorders.

Shifting the Paradigm: Adolescent Cannabis Abuse and the Need for Early Intervention.

This article describes the increasing risks of use of marijuana and related products by adolescents. As THC content increases and methods such as "dabbing" increase frequency of use, risks of marijuana use as perceived by youth are decreasing. At a time when marijuana access is increasing nationally, a new marijuana landscape is forming in which both adolescents and treatment providers must adjust their perceptions of what was once thought of as a "harmless" drug. This article describes this new landscape, and what it may mean for adolescent drug treatment.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

The Moderating Role of Experiential Avoidance in the Relationship between Posttraumatic Stress Disorder Symptom Severity and Cannabis Dependence.

The relationship between cannabis use and posttraumatic stress disorder (PTSD) has received increased scientific scrutiny in recent years. Consistent with this research, studies provide evidence that many individuals with PTSD use cannabis to reduce negative affect and other unpleasant internal experiences associated with PTSD. However, no research to date has explored factors that may be associated with an increased likelihood of cannabis misuse among individuals with PTSD. Consequently, this study explored the moderating role of experiential avoidance (EA; defined as the tendency to engage in strategies to reduce unpleasant private experiences) in the PTSD-cannabis dependence relationship among a sample of 123 Criterion A trauma-exposed patients in residential substance abuse treatment. Moderation analyses indicated an interactive effect of PTSD symptom severity and EA on current cannabis dependence. Specifically, results revealed a conditional effect of PTSD symptom severity on cannabis dependence only when EA was average or higher, with higher levels of PTSD symptom severity associated with a greater risk of cannabis dependence. These findings are consistent with evidence that cannabis use may serve an avoidant function among some individuals with PTSD and suggest that acceptance-based behavioral approaches might be effective in targeting both cannabis use and PTSD-related impairment.

Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilone's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol's effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within-subjects, double-blind, randomized protocol. Over seven sessions, the time-dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or 'high' relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose-dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose-related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose-related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.

New Developments in Understanding and Treating Adolescent Marijuana Dependence.

BACKGROUND: Marijuana is the most commonly used illicit substance in the United States and worldwide. Marijuana use is a problem of increasing magnitude among adolescents. Use typically begins in adolescence and is associated with a variety of adverse outcomes. METHOD: This article will present an overview of trends in marijuana use, and will review the endocannabinoid system and marijuana. It will discuss recent policy developments in US and their implications, especially for adolescents. Existing treatments will be reviewed, including findings from a recent randomized double-blind trial of N-acetylcysteine, a compound that reverses the dysregulation of the glutamate system that occurs in substance dependence. CONCLUSIONS: The core treatment approaches include psychosocial interventions, sometimes in combination with each other. While a reduction in days of use is often achieved with most of these approaches, abstinence is a much more elusive goal. The evidence base for effective treatments remains inadequate especially with regard to adolescents, and there is an urgent need for more research in this area. Promising new treatments include N-acetylcysteine in conjunction with contingency management.

Characteristics of cannabis users seeking treatment in São Paulo, Brazil / Características de los fumadores de marihuana que buscan tratamiento en São Paulo, Brasil

OBJECTIVES: This article describes a sample of 160 adults selected to participate in a randomized controlled trial conducted at a specialized outpatient clinic for cannabis users in Brazil. It correlates consumption with several measures of marijuana use, comparing it with other samples. METHODS: Instruments used were the Composite International Diagnostic Interview (CIDI) and Wender Utah Rating Scale for screening and demographic data interviews, and the ASI, time-line follow back (TLFB), Marijuana Withdrawal and Marijuana Problem Scales, and Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) Checklist for cannabis dependence. RESULTS: Participants in the study were mostly single, white men; their mean age was 32.3 years. They had a mean of 15.6 years of formal education and 61.6 percent worked. The cohort started using marijuana at a mean age of 16.5 years and developed daily use by a mean age of 21 years. Subjects in the sample had used marijuana for a mean of 15 years. They used it for 92.2 percent of the 90 days prior to the interview and smoked a mean of 1.99 marijuana cigarettes per day during this period. Individuals in the group had experimented with other drugs, especially cocaine. CONCLUSIONS: Marijuana users in this sample matched the profiles of those investigated elsewhere, although they reported fewer symptoms of dependence. Marijuana users should be considered independently in substance abuse programs, because they require specific attention and treatment. Broader epidemiological studies should be conducted to determine the extent of marijuana use within the Brazilian population.

OBJETIVOS: Describir una muestra de 160 adultos seleccionados para participar en un ensayo aleatorizado controlado, realizado en una clínica ambulatoria especializada para consumidores de marihuana en Brasil. Se asoció el consumo de marihuana con varias medidas relacionadas con este hábito y se comparó con otras muestras. MÉTODOS: Se empleó la Entrevista Diagnóstica Internacional Compuesta (CIDI) y la Escala de Valoración de Wender Utah para las entrevistas de tamizaje y la obtención de datos demográficos, y el Índice de Intensidad de la Adicción (ASI), la Línea Cronológica Retrospectiva (TLFB), la Escala de Abandono de la Marihuana, la Escala de Problemas por Marihuana y la lista de comprobación para la dependencia de la marihuana del Manual Diagnóstico y Estadístico de Trastornos Mentales (DSM-III-R). RESULTADOS: La mayoría de los participantes eran hombres blancos solteros; en promedio, la edad fue de 32,3 años y el nivel de escolarización de 15,6 años; 61,6 por ciento trabajaba. Como promedio, esta cohorte comenzó a fumar marihuana a una edad de 16,5 años y llegó a consumirla diariamente a los 21. Los participantes habían consumido marihuana durante 15 años y la consumieron 92,2 por ciento de los 90 días previos a la encuesta, con un consumo diario medio en ese lapso de 1,99 cigarrillos de marihuana. Miembros del grupo habían experimentado con otras drogas, principalmente cocaína. CONCLUSIONES: Los consumidores de marihuana estudiados se ajustan a los perfiles encontrados en otras investigaciones similares, aunque manifestaron menos síntomas de dependencia. En los programas para consumidores de estupefacientes se debe considerar a los consumidores de marihuana de manera independiente, ya que necesitan atención y tratamiento específicos. Se deben emprender estudios epidemiológicos más amplios para determinar la magnitud del consumo de marihuana en la población brasileña.