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The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood.
There are indications that marijuana is increasingly used to alleviate symptoms and for the treatment of a variety of medical conditions both physical and psychological. The purpose of this study was to describe the health concerns and problems that prompt some adolescents to use marijuana for therapeutic reasons, and their beliefs about the risks and benefits of the therapeutic use of marijuana.
Background Increased accessibility, recreational use, and regional legalization of marijuana (cannabis) have been paralleled by widespread recognition of its serious cardiovascular complications (acute myocardial infarction, stroke, sudden death) particularly in the young. We aimed to examine trends in hospital admissions and outcomes of adults with stress cardiomyopathy (SC) in temporal relation to marijuana use. Methods and results A search of the 2003-2011 Nationwide Inpatient Sample (NIIS) database identified 33,343 admissions for SC of which 210 (0.06%) were temporally related to marijuana use. Demographics, clinical characteristics, and outcomes of marijuana users (MU) and non-marijuana users (NMU) with SC were compared. MU were younger (44±14 vs. 66±13 years), more often male (36% vs. 8%), and had lower prevalence of hypertension (38% vs. 62%), diabetes (2.4% vs. 17.6%), and hyperlipidemia (16% vs. 52%) while more often suffered from depression (33% vs. 15%), psychosis (12% vs. 4%), anxiety disorder (28% vs. 16%), alcohol use disorder (13% vs. 3%), tobacco use (73% vs. 29%), and polysubstance abuse (11% vs. 0.3%) [all p<0.001]. In addition, MU more often suffered a cardiac arrest and required placement of a defibrillator while congestive heart failure was more frequent in NMU. Logistic regression analysis on the entire database (n=71,753,900), adjusted for known risk factors for SC, identified marijuana use as an independent predictor of SC (OR=1.83; 95% CI=1.57-2.12, p<0.0001). Among MU, older age (>48 years) was a strong predictor of any major adverse cardiac event (OR=7.8; 95% CI=2.88-21.13; p<0.0001). Conclusions Marijuana use is linked to SC in younger individuals and is associated with significant morbidity despite being younger in age and having a more favorable cardiac risk factor profile in affected individuals.
Substance misuse is now encountered in settings beyond addiction specialty care, with schools a point-of-contact for student access to behavioral health services. Marijuana is a leading impetus for adolescent treatment admissions despite declining risk perception, for which the Teen Marijuana Check-Up (TMCU)-a tailored adaptation of motivational enhancement therapy-offers an efficacious service option. To bridge the knowledge gap concerning effective and affordable technical assistance strategies for implementing empirically supported services, the described trial will test such a strategy to facilitate school-based TMCU implementation.
With increases in marijuana use and legalization efforts, it is imperative to establish its impact on the developing brain. Therefore, we investigated whether exposure to marijuana alters brain derived neurotropic-factor (BDNF), given its critical role in brain development and plasticity. We then examined whether onset age of cannabis use was associated with more severe changes. A single site, cohort study following 500 urban healthy American adolescents. Changes in plasma m-BDNF levels were longitudinally assessed, and a multi-method approach was implemented to ascertain marijuana use. Multivariate and general linear model (GLM) regression modeling were utilized to test the main hypothesis, controlling for confounders.
To date, there has been little work describing the neurochemical profile of young, heavy marijuana users. In this study, we examined 27 young-adult marijuana users and 26 healthy controls using single-voxel magnetic resonance spectroscopy on a 3 T scanner. The voxel was placed in the dorsal striatum, and estimated concentrations of glutamate + glutamine, myo-inositol, taurine + glucose, total choline and total N-acetylaspartate were examined between groups. Therewere no overall group effects, but two metabolites showed group by sex interactions. Lower levels of glutamate + glutamine (scaled to total creatine) were observed in female, but not male, marijuana users compared to controls. Higher levels of myo-inositol were observed in female users compared to female non-users and to males in both groups. Findings are discussed in relation to patterns of corticostriatal connectivity and function, in the context of marijuana abuse.
Pharmacists, the most accessible of health care professionals, are well positioned to help prevent and treat substance use disorders and should prepare themselves to perform these functions. New research improves our knowledge about the pharmacological and behavioral risks of drug abuse, supports the clinical impression that drug dependence is associated with long-lasting neurochemical changes, and demonstrates effective pharmacological treatments for certain kinds of drug dependencies. The profession is evolving. Pharmacists are engaging in new practice behaviors such as helping patients manage their disease states. Collaborative practice agreements and new federal policies set the stage for pharmacists to assist in the clinical management of opioid and other drug dependencies. Pharmacists need to be well informed about issues related to addiction and prepared not only to screen, assess, and refer individual cases and to collaborate with physicians caring for chemically dependent patients, but also to be agents of change in their communities in the fight against drug abuse.At the end of this article the pharmacist will be better able to:1. Explain the disease concept of chemical dependence2. Gather the information necessary to conduct a screen for chemical dependence3. Inform patients about the treatment options for chemical dependence4. Locate resources needed to answer questions about the effects of common drugs of abuse (alcohol, marijuana, narcotics, "ecstasy", and cocaine)5. Develop a list of local resources for drug abuse treatment6. Counsel parents who are concerned about drug use by their children7. Counsel individuals who are concerned about drug use by a loved one.8. Counsel individuals who are concerned about their own drug use
Drugs of abuse could interfere with the hypothalamic-pituitary-gonadal axis, causing impaired functions of the gland and associated functions of target organs. Drugs of abuse tend to cause changes in the endocrine system, and these changes could be physiological, molecular, biochemical, genetic, and cellular.
Background: Finding social causes of a particular disease or specific health problem in groups or hidden illnesses, such as drug misuse is difficult. To estimate the population size, it should be taken into account that under enumeration usually occurs in direct estimation of population of certain high-risk groups. The present study used indirect methods to accurately estimate the population of students who have once experienced marijuana abuse. Methods: This cross sectional research was conducted on 461 students in Hamadan. Two indirect methods, the Network Scale-up (NSU) and proxy respondent method (PRM), were used. Data were analyzed by statistical tests and SPSS version 16 and Excel. Results: The mean age (standard deviation) was 22.51 (4.19 years), and the prevalence of marijuana misuse was 1.94%, 4.12%, and 2.6%, respectively, in girls and 14.57%, 12.58%, and 10.4% in boys using NSU, PRM, and direct method. Conclusion: Direct and NSU methods had higher bias than PRM, the frequency of PRM was closer to reality, and the once use prevalence of marijuana was higher in the young male population than in the female.
Drug abuse is a common and heritable set of disorders, but the underlying genetic factors are largely unknown. We conducted genome-wide association studies of drug abuse using 7 million imputed single nucleotide polymorphisms (SNPs) and insertions/deletions in African Americans (AAs; n = 3742) and European Americans (EAs; n = 6845). Cases were drawn from the Urban Health Study of street-recruited people, who injected drugs and reported abusing opioids, cocaine, marijuana, stimulants and/or other drugs 10 or more times in the past 30 days, and were compared with population controls. Independent replication testing was conducted in 755 AAs and 1131 EAs from the Genetic Association Information Network. An intronic SNP (rs9829896) in the K(lysine) acetyltransferase 2B (KAT2B) gene was significantly associated with drug abuse in AAs (P = 4.63 × 10-8 ) and independently replicated in AAs (P = 0.0019). The rs9829896-C allele (frequency = 12%) had odds ratios of 0.68 and 0.53 across the AA cohorts: meta-analysis P = 3.93 × 10-10 . Rs9829896-C was not associated with drug abuse across the EA cohorts: frequency = 36% and meta-analysis P = 0.12. Using dorsolateral prefrontal cortex data from the BrainCloud cohort, we found that rs9829896-C was associated with reduced KAT2B expression in AAs (n = 113, P = 0.050) but not EAs (n = 110, P = 0.39). KAT2B encodes a transcriptional regulator in the cyclic adenosine monophosphate and dopamine signaling pathways, and rs9829896-C was associated with expression of genes in these pathways: reduced CREBBP expression (P = 0.011) and increased OPRM1 expression (P = 0.016), both in AAs only. Our study identified the KAT2B SNP rs9829896 as having novel and biologically plausible associations with drug abuse and gene expression in AAs but not EAs, suggesting ancestry-specific effects.
The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon.
Although the incidence of cannabis abuse/dependence in Americans is rising, the neurobiology of cannabis addiction is not well understood. Imaging studies have demonstrated deficits in striatal D(2)/D(3) receptor availability in several substance-dependent populations. However, this has not been studied in currently using chronic cannabis users.
Little is known about the unique contribution of schools vs neighborhoods in driving adolescent marijuana use. This study examined the relative contribution of each setting and the influence of school and neighborhood socioeconomic status on use. We performed a series of cross-classified multilevel logistic models predicting past 30-day adolescent (N = 18 329) and young adult (N = 13 908) marijuana use using data from Add Health. Marijuana use differed by age, sex, race/ethnicity, and public assistance in adjusted models. Variance parameters indicated a high degree of clustering by school (σ2 = 0.30) and less pronounced clustering by neighborhood (σ2 = 0.06) in adolescence when accounting for both levels simultaneously in a cross-classified multilevel model. Clustering by school persisted into young adulthood (σ2 = 0.08). Parental receipt of public assistance increased the likelihood of use during adolescence (odds ratio = 1.39; 95% confidence interval: 1.19-1.59), and higher parental education was associated with increased likelihood of use in young adulthood. These findings indicate that both contexts may be promising locations for intervention.
Jacob Cohen developed two statistical measures for judging the magnitude of effects produced by an intervention, known as Cohen's d, appropriate for assessing scaled data, and Cohen's h, appropriate for assessing proportions. These have been widely employed in evaluating the effectiveness of alcohol, cigarette, marijuana, and other drug prevention efforts. I present two tests to consider the adequacy of using these statistics when applied to drug use prevention programs. I used student survey data from grades 6 through 12 (N = 1,963,964) collected by the Georgia Department of Education between 2015 and 2017 and aggregated at the school level (N = 1036). I calculated effect sizes for an imaginary drug prevention program that (1) reduced 30-day alcohol, cigarette, and marijuana prevalence by 50%; and (2) maintained 30-day prevalence at a pretest level for multiple years. While both approaches to estimating intervention effects represent ideal outcomes for prevention that surpass what is normally observed, Cohen's statistics failed to reflect the effectiveness of these approaches. I recommend including an alternative method for calculating effect size for judging program outcomes. This alternative method, Relative Reduction in Prevalence (RRP), calculates ratio differences between treatment and control group drug use prevalence at posttest and follow-up, adjusting for differences observed at pretest. RRP allows researchers to state the degree to which an intervention could be viewed as efficacious or effective that can be readily understood by practitioners.
In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.
Background: Among adolescents, cannabis use is a health concern due to associations with drug addiction and mental health disorders across the life course. It has been shown that childhood maltreatment is associated with drug addiction in adulthood. However, a better understanding of the relationship between maltreatment and drug use may improve targeted prevention and interventions. The aim of this systematic review is to describe the association between exposure to childhood maltreatment, specifically physical and sexual abuse, with adolescent cannabis use. Methods: A systematic search strategy was applied to Embase, PsycINFO, and Ovid MEDLINE(R) databases. Methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstract and title screening was performed to identify papers which reported an estimate of the association between childhood physical or sexual abuse and adolescent cannabis use. Full text screening of each paper was performed, and data were extracted and study quality assessed. Weighted means meta-analysis was performed on studies reporting odds ratios as effect estimates. Results: Of 8,780 screened articles, 13 were identified for inclusion. Eight papers received a quality rating score indicating lower risk of bias. Eleven papers reported the relationship between childhood sexual abuse and adolescent cannabis use; effect estimates ranged from AOR 0.53-AOR 2.18 (weighted mean OR 1.29, 95% CI 1.08-1.49). The relationship between childhood physical abuse and adolescent cannabis use was reported in 7 papers; effect estimates ranged from AOR 1.25-AOR 1.87 (weighted mean OR 1.39, 95% CI 1.12-1.66). Differences in the strength of the evidence were observed by the method of exposure ascertainment, and there was some evidence of differences in association by gender, age of cannabis initiation, and the severity of the abuse. Conclusions: This systematic review indicates childhood physical or sexual abuse may increase risk of adolescent-onset cannabis use. Few studies considered variation in timing of onset, or by gender. Adolescent cannabis use precedes is strongly associated with increased risk of negative mental health outcomes; further exploration of adolescent cannabis use's place on the causal pathway between childhood abuse and adult mental health problems is warranted to improve intervention.
It has been shown that 17β-estradiol (E2) hormone is an essential biological factor for increasing the sensitivity of women to drug abuse. Recent studies have shown a potential overlap between the molecular pathways of cannabinoids and ovarian hormones. The current study evaluated the interference between the marijuana and E2 effect on spatial learning and memory and the role of the G protein-coupled estrogen receptor (GPR30) in young female rats. The animals were separated into two main groups: intact-ovary and ovariectomized (OVX) rats. The latter group received intraperitoneal injections of E2, G-1 (GPR30 agonist), G-15 (GPR30 antagonist), marijuana, and different combinations of these substances for 28 days. Spatial learning and memory were evaluated by the Morris water maze (MWM) test. We also assessed the BDNF (brain-derived neurotrophic factor) concentration and the hippocampal level of GPR30. The results showed a significant reduction of spatial learning and memory in OVX rats compared to intact-ovary rats, which were restored by E2 replacement. Moreover, treatment with G-1 mimicked E2 effects on spatial learning and memory. Marijuana impaired spatial learning and memory in intact-ovary rats, while improved in OVX rats. We also found that treatment with M + E2 induced significant impairment in spatial learning and memory; however, treatment with M + G1 and M + G15 + E2 showed no significant difference. No significant differences in BDNF expression were observed in experimental groups. These results suggest that marijuana and E2 interact in their effect on spatial learning and memory in young female rats, but GPR30 seems to play no role in this interaction.
The aim of the present study was to assess the prevalence by gender of substance use and misuse in late childhood and early adolescence. A survey was conducted in 2013-2014 at primary and secondary schools of Padova, Veneto region, North-East Italy, on a sample of 171 pupils in 5th grade and 1325 in 6th to 8th grade. Among the 8th graders, more than one in three males and one in four females had experimented with smoking, and more than half the boys and nearly half the girls had experience of alcohol. In this same age group, almost two in three males and one in three females had used energy drinks, and nearly 5% of the boys had experience of marijuana and/or stimulant drugs. In addition, almost one in four of the male students in 8th grade had experimented with three of these substances. The middle school years should be identified as the first period at risk concerning the use of these drugs. Prevention programs should begin in early adolescence, focusing on delaying the use or abuse of any of the "gateway drugs."
Herbal products containing synthetic cannabinoids-initially sold as legal alternatives to marijuana-have become major drugs of abuse. Among the synthetic cannabinoids, [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)-methanone (MAM-2201) has been recently detected in herbal products and has psychoactive and intoxicating effects in humans, suggesting that MAM-2201 alters brain function. Nevertheless, the pharmacological actions of MAM-2201 on cannabinoid receptor type 1 (CB1R) and neuronal functions have not been elucidated. We found that MAM-2201 acted as an agonist of human CB1Rs expressed in AtT-20 cells. In whole-cell patch-clamp recordings made from Purkinje cells (PCs) in slice preparations of the mouse cerebellum, we also found that MAM-2201 inhibited glutamate release at parallel fiber-PC synapses via activation of presynaptic CB1Rs. MAM-2201 inhibited neurotransmitter release with an inhibitory concentration 50% of 0.36 μM. MAM-2201 caused greater inhibition of neurotransmitter release than Δ(9)-tetrahydrocannabinol within the range of 0.1-30 μM and JWH-018, one of the most popular and potent synthetic cannabinoids detected in the herbal products, within the range of 0.03-3 μM. MAM-2201 caused a concentration-dependent suppression of GABA release onto PCs. Furthermore, MAM-2201 induced suppression of glutamate release at climbing fiber-PC synapses, leading to reduced dendritic Ca(2+) transients in PCs. These results suggest that MAM-2201 is likely to suppress neurotransmitter release at CB1R-expressing synapses in humans. The reduction of neurotransmitter release from CB1R-containing synapses could contribute to some of the symptoms of synthetic cannabinoid intoxication including impairments in cerebellum-dependent motor coordination and motor learning.
Public health research has pointed to alcohol and substance abuse as the most significant public health challenges in Greenland with the negative impact on families and communities that entail, but few studies have investigated the role of problem gambling as addictive behaviour among Inuit. The objectives of the present study were to investigate (a) the association between lifetime problem gambling and harmful alcohol use as well as frequent use of marijuana and (b) the prevalence of cross-addictive behaviour among Greenland Inuit.
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