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Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis., (© 2022. The Author(s).)

Adolescence and early adulthood are crucial periods of neurodevelopment characterised by functional, structural, and cognitive maturation, which helps prepare young people for adulthood. This systematic review of longitudinal studies aims to delineate neural predictors from neural consequences of cannabis and illicit substance use, as well as investigate the potential for the developing brain (at ages 10-25 years) to recover after damage. Five databases were searched to yield a total of 38 eligible studies, with some assessing multiple outcome techniques, including 22 neuroimaging, two neurophysiological, and 22 neuropsychological findings. High-quality evidence suggested that delayed or irregular neurodevelopment in executive functioning, particularly emotional perception, might predispose young people to higher frequency substance use. There was evidence of functional, structural, and cognitive deficits proceeding substance use, with harm potentially dependent on the frequency of use and recovery potentially dependent on the duration of use. Identifying aberrant neurodevelopment in young people is crucial for preventing substance use-related harm., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Aspects of the canonical stress response differ in stimulant, opioid, and alcohol users relative to controls, and dysregulated responses to stress may contribute to continued use of these drugs. Little prior research has focused on stress responses in regular cannabis smokers. We assessed responses to a standardized laboratory social stress assay (the Trier Social Stress Task; TSST) in regular cannabis smokers (CANs) compared with controls (CONs)., Methods: Healthy, non-treatment-seeking adult CANs (⩾4×/week; smoking cannabis as usual) and demographically matched CONs completed the TSST. Outcome measures were subjective mood, heart rate, and salivary cortisol., Results: Nineteen CANs (1 female) and 20 CONs (2 female) participated; groups were matched on trauma exposure, sex, race, and age. CANs smoked cannabis 6.4 ± 1.1 days/week. Eight CANs and one CON smoked tobacco cigarettes daily. Overall, the TSST produced expected increases in anxiety, negative mood states, cortisol, and heart rate. CANs had blunted subjective response to stress relative to CONs, but they did not differ in physiological (cortisol and cardiovascular) stress responding., Conclusion: These results indicate that CANs have blunted mood responses to social stress, but normative physiological stress responding. Observed differences could be due to residual effects of cannabis, reluctance to endorse negative mood states, or to issues related to identifying (i.e., emotional identification) or feeling (i.e., interoception) stress-related affective states. Further research is warranted to characterize the mechanisms of these differences and assess implications for daily functioning and treatment outcomes.

Cannabis sativa is the most widely used illicit drug in the world. Its main psychoactive component is delta-9-tetrahydrocannabinol (THC), one of over 100 phytocannabinoid compounds produced by the cannabis plant. THC is the primary compound that drives cannabis abuse potential and is also used and prescribed medically for therapeutic qualities. Despite its therapeutic potential, a significant subpopulation of frequent cannabis or THC users will develop a drug use syndrome termed cannabis use disorder. Individuals suffering from cannabis use disorder exhibit many of the hallmarks of classical addictions including cravings, tolerance, and withdrawal symptoms. Currently, there are no efficacious treatments for cannabis use disorder or withdrawal symptoms. This makes both clinical and preclinical research on the neurobiological mechanisms of these syndromes ever more pertinent. Indeed, basic research using animal models has provided valuable evidence of the neural molecular and cellular actions of cannabis that mediate its behavioral effects. One of the main components being central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system. Back-translational studies have provided insight linking preclinical basic and behavioral biology research to better understand symptoms observed at the clinical level. This narrative review aims to summarize major research elucidating the molecular, cellular, and behavioral manifestations of cannabis/THC use that play a role in cannabis use disorder and withdrawal., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Background: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin., Aims: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users., Methods: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use)., Results: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort., Conclusions: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.

Purpose of Review: Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) is a disease complex with enormous societal burden and yet the pathogenesis of LUTS/BPH is poorly understood. We set out to review the literature on the relationship between depression, marijuana usage, and erectile dysfunction (ED) to LUTS/BPH., Recent Findings: LUTS/BPH has independent associations with depression as well as with ED. In each case, the causality and mechanistic relationship is unknown. The impact of marijuana, as it increasingly pervades the general population, on the disease complex of LUTS/BPH is not well studied but recent results support short-term benefit and long-term caution. Depression, a form of central nervous dysfunction, and ED, which is likely mediated via endothelial dysfunction, are independently associated with LUTS/BPH. The presence of cannabinoid receptors in urologic organs, coupled with recent population studies, supports a modulatory effect of marijuana on voiding although an enormous knowledge gap remains.

Cannabis is one of the world's most widely used recreational drugs and the second most commonly smoked substance. Research on cannabis and the lungs has been limited by its illegal status, the variability in strength and size of cannabis cigarettes (joints), and the fact that most cannabis users also smoke tobacco, making the effects difficult to separate. Despite these difficulties, the available evidence indicates that smoking cannabis causes bronchitis and is associated with changes in lung function. The pattern of effects is surprisingly different from that of tobacco. Whereas smoking cannabis appears to increase the risk of severe bronchitis at quite low exposure, there is no convincing evidence that this leads to chronic obstructive pulmonary disease. Instead, cannabis use is associated with increased central airway resistance, lung hyperinflation and higher vital capacity with little evidence of airflow obstruction or impairment of gas transfer. There are numerous reports of severe bullous lung disease and pneumothorax among heavy cannabis users, but convincing epidemiological data of an increased risk of emphysema or alveolar destruction are lacking. An association between cannabis and lung cancer remains unproven, with studies providing conflicting findings., (© 2020 Society for the Study of Addiction.)

Purpose Cannabis is widely used for medicinal and recreational purposes. Studies have evaluated its health benefits and consequences, although there is limited work on its effects on the auditory system. In this exploratory study, we evaluate the effects of cannabis smoking on early auditory evoked potentials. Method We investigated auditory brainstem response (ABR) and electrocochleography waveforms in 18 cannabis smokers (44% women, 54% men; M age = 23.06 years, range: 21-28 years) and 19 nonsmoker controls (63% women, 37% men; M age = 23.74 years, range: 21-33 years). Threshold ABRs were recorded using rarefaction clicks at a rate of 17.7/s from 80 dB nHL to Wave V threshold. Resulting amplitudes and latencies for Waves I, III, and V were compared via independent-samples t tests. Electrocochleograms obtained with 90 dB nHL (7.1/s) alternating clicks were assessed for summating and compound action potentials, which were compared between groups using independent-samples t tests. Results ABR Wave I amplitudes were significantly lower in smokers ( M = 0.14 μV, SD = 0.11) compared to nonsmokers ( M = 0.21 μV, SD = 0.10, p = .039) at 80 dB nHL. Wave V latencies were significantly delayed in smokers at 80 dB nHL. Wave I and III latencies did not differ significantly between the two groups. Summating potential/compound action potential ratios were significantly elevated in smokers ( M = 0.30, SD = 0.04) versus nonsmokers ( M = 0.21, SD = 0.05, p = .042). Conclusion We identified significant differences in electrophysiological outcomes between cannabis smokers and nonsmokers. Cannabis smoking may have a subtle neurotoxic effect on the auditory system. Larger confirmatory studies are warranted.

Background: Studies indicate that female cannabis users progress through the milestones of cannabis use disorder (CUD) more quickly than male users, likely due to greater subjective craving response in women relative to men. While studies have reported sex-related differences in subjective craving, differences in neural response and the relative contributions of neural and behavioral response remain unclear., Methods: We examined sex-related differences in neural and behavioral response to cannabis cues and cannabis use measures in 112 heavy cannabis users (54 females). We used principal component analysis to determine the relative contributions of neural and behavioral response and cannabis use measures., Results: We found that principal component (PC) 1, which accounts for the most variance in the dataset, was correlated with neural response to cannabis cues with no differences between male and female users (p = 0.21). PC2, which accounts for the second-most variance, was correlated with subjective craving such that female users exhibited greater subjective craving relative to male users (p = 0.003). We also found that CUD symptoms correlated with both PC1 and PC2, corroborating the relationship between craving and CUD severity., Conclusions: These results indicate that neural activity primarily underlies response to cannabis cues and that a complex relationship characterizes a convergent neural response and a divergent subjective craving response that differs between the sexes. Accounting for these differences will increase efficacy of treatments through personalized approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: Heroin smokers have high rates of COPD, respiratory morbidity, hospital admission, and mortality. We assessed the natural history of symptoms and lung function in this population over time., Methods: A cohort of heroin smokers with COPD was followed for 18 to 24 months. At baseline and follow-up, respiratory symptoms were measured by the Medical Research Council Dyspnea Scale (MRC) and the COPD Assessment Tool (CAT), and postbronchodilator spirometry was performed. Frequency of health-care-seeking episodes was extracted from routine health records. Parametric, nonparametric, and linear regression models were used to analyze the change in symptoms and lung function over time., Results: Of 372 participants originally recruited, 161 were assessed at follow-up (mean age, 51.0 ± 5.3 years; 74 women [46%]) and 106 participants completed postbronchodilator spirometry. All participants were current or previous heroin smokers, and 122 (75.8%) had smoked crack. Symptoms increased over time (MRC score increased by 0.48 points per year, P < .001; CAT score increased by 1.60 points per year, P < .001). FEV 1 declined annually by 90 ± 190 mL (P < .001). This deterioration was not associated with change in tobacco or heroin smoking status or use of inhaled medications., Conclusions: Heroin smokers experience a high and increasing burden of chronic respiratory symptoms and a decline in FEV 1 that exceeds the normal age-related decline observed among tobacco smokers with COPD and healthy nonsmokers. Targeted COPD diagnostic and treatment services hosted within opiate substitution services could benefit this vulnerable, relatively inaccessible, and underserved group of people., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose Cannabis is a widely used drug both medically and recreationally. The aim of this study was to determine if cannabis smoking is associated with changes in auditory function, as measured by behavioral hearing thresholds and/or distortion product otoacoustic emissions (DPOAEs). Method We investigated hearing thresholds and 2f 1 -f 2 DPOAEs in 20 cannabis smokers and 20 nonsmokers between 18 and 28 years old. Behavioral thresholds were obtained from 0.25 to 16 kHz. DPOAEs were measured using discrete tones between f 2 of 0.5 and 19.03 kHz using an f 2 /f 1 ratio of 1.22 and L 1 /L 2 = 65/55 dB SPL. Thresholds and DPOAE amplitudes were compared between groups using linear mixed-effects models with sex and frequency as predictors. Results Behavioral thresholds in smokers did not differ significantly between smokers and nonsmokers (all p s > .05). Although not significant, long-term smokers exhibited poorer thresholds than short-term smokers and nonsmokers. Smokers generally exhibited lower DPOAE amplitudes than nonsmokers, although the differences were not significant. Male smokers had significantly poorer DPOAE amplitudes than male nonsmokers in the low frequencies (f 2 ≤ 2 kHz; p = .0245). Conclusion Results indicate that smoking cannabis may negatively alter the function of outer hair cells in young men. This subtle cochleopathology is evident in the absence of measurable differences in behavioral hearing thresholds between cannabis smokers and nonsmokers.

Background: Animal models of addiction suggest that the transition from incentive-driven drug use to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and neural cue reactivity in striatal circuits; however, these studies were not able to separate addiction-related from exposure-related adaptations., Methods: To differentiate the adaptive changes, the current functional magnetic resonance imaging study examined behavioral and neural cue reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a nonusing reference group (n = 44)., Results: Irrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striatal frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal striatal reactivity and decreased striatal limbic coupling during cue exposure. An exploratory analysis revealed that higher ventral caudate neural cue reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in nondependent users., Conclusions: Taken together, the current findings suggest that exaggerated responses of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Cannabis use has been shown to affect processing of emotional facial expressions as measured by the P1 and P3 event-related potential (ERP) components. These components have been shown to be related to emotion processing in particular attention to emotion. Previous research also indicates that there are sex differences in how cannabis effects males and females as well as how they process emotion. This study examined the relationship between the effects of residual cannabis use and sex differences in 144 participants (F = 80) in a facial expression emotion processing task. Both the P1 and P3 ERP components were compared in male and female participants in noncannabis user, casual cannabis user, and heavy cannabis user groupings. The task involved implicitly, explicitly, and empathically identifying emotional expressions (angry, happy, neutral, and fearful) in male and females faces. There were differences between males and females in both the P1 and P3 ERP in relation to cannabis use. Males had a larger P1 than females with cannabis use and a smaller P3. Differences in the P1 were observed in both positive and negative emotion and between tasks in relation to cannabis use patterns. Differences in the P3 were seen in heavy male users for empathy happy and casual male users implicit angry when compared to females. These differences highlight the important of considering sex differences in regard to the effects of cannabis, in particular in emotion processing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Lisano, JK, Smith, JD, Mathias, AB, Christensen, M, Smoak, P, Phillips, KT, Quinn, CJ, and Stewart, LK. Performance and health-related characteristics of physically active men using marijuana. J Strength Cond Res 33(6): 1659-1669, 2019-The influence of chronic marijuana use on the performance and health of physically active individuals has yet to be fully elucidated. The purpose of this study was to explore pulmonary function, aerobic and anaerobic fitness, strength, serum testosterone, cortisol, C-reactive protein (CRP), Δ-9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-Δ-9-tetrahydrocannabinol (THC-COOH), and 11-hydroxy-Δ-9-tetrahydrocannabinol (THC-OH) concentrations in a physically active population either using or not using marijuana. Healthy, physically active males (N = 24) were compared based on their marijuana-use status: marijuana users (MU; n = 12) and nonusers (NU; n = 12). Statistical analysis (p = 0.05) revealed no difference between groups for age, body mass, body mass index, body fat, forced expiratory volume in 1 second percentage, VO2max, anaerobic power output, strength measures, testosterone, or cortisol concentrations. Although not statistically significant, MU showed a trend to fatigue to a greater percentage of absolute power output than NU from the beginning to the end of the Wingate Anaerobic Power Assessment (p = 0.08, effect size = 0.75). C-reactive protein in MU (1.76 ± 2.81 mg·L) and NU (0.86 ± 1.49 mg·L) was not significantly different (p = 0.60) but placed MU at moderate risk and NU at low risk for cardiovascular disease. Anaerobic fatigue was the only performance variable to show a trend for difference between groups. These results suggest that marijuana use in physically active males may not have significant effects on performance; however, it may be linked to elevated concentrations of CRP which place users at a higher risk for cardiovascular disease.

Background: The pharmacokinetic-pharmacodynamic relationship between whole blood δ-9-tetrahydrocannabinol (THC) and driving risk is poorly understood., Methods: Fifteen chronic cannabis consumers (1-2 joints/day; CC) and 15 occasional cannabis consumers (1-2 joints/week; OC) of 18 to 34 years of age were included. A pharmacokinetic study was conducted with 12 blood samplings over a 24-h period before and after controlled random inhalation of placebo or 10 mg or 30 mg of THC. THC and metabolites were quantified using LC-MS/MS. Effects on reaction time by psychomotor vigilance tests and driving performance through a York driving simulator were evaluated 7 times. A pharmacokinetic-pharmacodynamic analysis was performed using R software., Results: Whole blood peak THC was 2 times higher in CC than in OC for a same dose and occurred 5 min after the end of consumption. THC remained detectable only in CC after 24 h. Despite standardized consumption, CC consumed more available THC from each cigarette regardless of dose. Maximal effect for reaction time was dose- and group-dependent and only group-dependent for driving performance, both being decreased and more marked in OC than in CC. These effects were maximal around 5 h after administration, and the duration was longer in OC than in CC. A significant pharmacokinetic-pharmacodynamic relationship was observed only between T max for blood THC and the duration effect on mean reciprocal reaction time., Conclusions: Inhalation from cannabis joints leads to a rapid increase in blood THC with a delayed decrease in vigilance and driving performance, more pronounced and lasting longer in OC than in CC. ClinicalTrials.gov Identifier: NCT02061020., (© 2019 American Association for Clinical Chemistry.)

Background: Growing evidence shows cannabis use is associated with lower rates of metabolic dysregulation. Despite cannabis impacting each sex differently, few studies have examined the metabolic profile of male and female cannabis users separately. Our aim was to investigate sex differences in the impact of cannabis use on metabolic syndrome in adults with psychotic illness., Method: Data from 1078 men and 735 women interviewed in the second Australian national survey of psychosis were analyzed using multiple logistic regression to model separately, for each sex, the influence of no, occasional and frequent past-year cannabis use on metabolic syndrome, adjusting for potential covariates including antipsychotic medication, smoking, and physical activity., Results: The proportion of women and men with metabolic syndrome was 58.1% and 57.6% respectively. Unadjusted analyses showed frequent cannabis use was associated with significantly lower odds of metabolic syndrome for both sexes. In adjusted analyses, the association between metabolic syndrome and frequent cannabis use remained significant for men (AOR = 0.49, 95% CI = 0.31-0.78), but not for women (AOR = 0.68, 95% CI = 0.37-1.24). Frequent cannabis use was associated with lower odds of abdominal obesity, hypertension and elevated triglyceride levels in men only., Conclusions: The differences we found suggest cannabinoid regulation of energy balance may be sex-dependent and highlight the importance of examining cannabis use in men and women separately. At the same time, the negative association between cannabis and psychosis onset and relapse should not be dismissed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Treatment for substance use disorders has traditionally been abstinence-oriented, but evaluating the merits of low-level cannabis use as potential treatment endpoint may identify benefits that are clinically relevant for treatment-seeking individuals who do not attain abstinence. This study explores if reduction in cannabis use to a lower level of use is related to improved physical health, mental health, and perceived cognitive functions. Study participants with a history of problematic cannabis use (n = 111) completed assessments. Regression models were used to explore the relationship between past 30-day cannabis use levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days per week, and heavy use [22%] defined as 4 or more days of use per week) and functional status in physical health, mental health, and cognition. Compared to heavy users, both abstinent and low-use individuals were similarly associated with better global health, appetite, and depression outcomes. Abstinent users also reported improved sleep, anxiety, and self-reported cognitive functioning relative to heavy users. Thus, reduction in cannabis use to lower levels is associated with beneficial outcomes important to health and other areas of functioning in individuals with problematic cannabis use.

Background: Occasional recreational stimulant (amphetamine and cocaine) use is an important public health problem among young adults because 16% of those who experiment develop stimulant use disorder. This study aimed to determine whether behavioral and/or neural processing measures can forecast the transition from occasional to problematic stimulant use., Methods: Occasional stimulant users completed a Risky Gains Task during functional magnetic resonance imaging and were followed up 3 years later. Categorical analyses tested whether blood oxygen level-dependent (BOLD) responses differentiated occasional stimulant users who became problem stimulant users (n = 35) from those who desisted from stimulant use (n = 75) at follow-up. Dimensional analyses (regardless of problem stimulant user or desisted stimulant use status; n = 144) tested whether BOLD responses predicted baseline and follow-up stimulant and marijuana use., Results: Categorical results indicated that relative to those who desisted from stimulant use, problem stimulant users 1) made riskier decisions after winning feedback; 2) exhibited lower frontal, insular, and striatal BOLD responses to win/loss feedback after making risky decisions; and 3) displayed lower thalamic but greater temporo-occipital BOLD responses to risky losses than to risky wins. In comparison, dimensional results indicated that lower BOLD signals to risky choices than to safe choices in frontal, striatal, and additional regions predicted greater marijuana use at follow-up., Conclusions: Taken together, blunted frontostriatal signals during risky choices may quantify vulnerability to future marijuana consumption, whereas blunted frontostriatal signals to risky outcomes mark risk for future stimulant use disorder. These behavioral and neural processing measures may prove to be useful for identifying ultra-high risk individuals prior to onset of problem drug use., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: There is evidence that regular cannabis use has negative effects on sleep health. Relative to HIV- populations, HIV + individuals consistently report greater sleep impairments. The number of HIV + individuals reporting frequent cannabis use, often to treat sleep issues, has significantly increased recently. It is unknown, however, if HIV status moderates the association between cannabis use and sleep health. The current study, therefore, examines these associations in a sample of HIV + and HIV- adults., Methods: HIV + and HIV- (N = 107) individuals completed one laboratory visit. Participants completed a 30-day drug use history questionnaire quantifying consumption of cannabis, cigarettes, and alcohol, and a sleep health questionnaire. To verify substance use and HIV status, participants completed a urine toxicology screening and serology testing., Results: HIV + individuals demonstrated lower sleep health than HIV- individuals. Linear regressions indicated that HIV status moderated the association between total 30-day cannabis consumption and sleep health; cannabis consumption was negatively associated with sleep health in HIV-, but not HIV + individuals. This interactive effect was significant after examining cigarette/alcohol use, depression symptoms, and demographic variables as covariates., Conclusions: These results corroborate studies demonstrating an inverse relationship between sleep health and cannabis consumption. This study also suggests that factors other than cannabis may be associated with lower sleep health in HIV + individuals. Emerging studies suggest that inflammation may mediate effects of cannabis on HIV infection. Future studies examining this mechanism are warranted to understand cannabis further and sleep in HIV + individuals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The recent legalization of recreational marijuana use in some parts of the world, the discovery of new indications for the clinical application of cannabis, and the acceptance of the use of cannabis in practice has been paralleled by extensive research on the active components of cannabis and the endocannabinoid system within the human body. In this review, we evaluate the available evidence on cannabis and its constituents and the application of this evidence in clinical practice, focusing particularly on the liver and liver diseases. Constituents of cannabis, such as cannabidiol and Δ-tetrahydrocannabinol, have shown anti-inflammatory, antioxidant, and hepatoprotective effects both in in vitro and clinical studies, and appear to have potential in the symptom management and treatment of various liver diseases that were previously considered difficult to manage conservatively. In addition, the manipulation of the inherent endocannabinoid response system has found favor in many clinical fields and has generated considerable research and clinical interest. Moreover, evidence with regard to the adverse effects of marijuana use in liver diseases is weak, which has led to raise a question on the prior rules, with regard to a denial of liver transplantation to marijuana users. All in all, the recent trends in research, clinical experiences, as well as the legislature, has opened up new avenues towards the widespread clinical application of cannabis and its derivatives as well as modifiers of the components of the endocannabinoid system. More research is required to fully exploit these new evidences.

Marijuana or Cannabis is extensively used as a recreational substance globally. Case reports have reported cardiac arrhythmias immediately following recreational marijuana use. However, the burden of arrhythmias in hospitalized marijuana users have not been evaluated through prospective or cross-sectional studies. Therefore, we planned to measure temporal trends of the frequency of arrhythmias in hospitalized marijuana users using National Inpatient Sample (NIS) database in the United States., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A generally undesired effect of cannabis smoking is a reversible disruption of short-term memory induced by delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. However, this paradigm has been recently challenged by a group of scientists who have shown that THC is also able to improve neurological function in old animals when chronically administered at low concentrations. Moreover, recent studies demonstrated that THC paradoxically promotes hippocampal neurogenesis, prevents neurodegenerative processes occurring in animal models of Alzheimer's disease, protects from inflammation-induced cognitive damage and restores memory and cognitive function in old mice. With the aim to reconcile these seemingly contradictory facts, this work will show that such paradox can be explained within the framework of hormesis, defined as a biphasic dose-response., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse., Methods: 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood., Results: Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse., Conclusion: We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Alcohol, nicotine, and cannabis are among the most commonly used drugs. A prolonged and combined use of these substances can alter normal brain wiring in different ways depending on the consumed cocktail mixture. Brain connectivity alterations and their change with time can be assessed using functional magnetic resonance imaging (fMRI) because of its spatial and temporal content. Here, we estimated dynamic functional network connectivity (dFNC) as derived from fMRI data to investigate the effects of single or combined use of alcohol, nicotine, and cannabis. Data from 534 samples were grouped according to their substance use combination as controls (CTR), smokers (SMK), drinkers (DRN), smoking-and-drinking subjects (SAD), marijuana users (MAR), smoking-and-marijuana users (SAM), marijuana-and-drinking users (MAD), and users of all three substances (ALL). The DRN group tends to exhibit decreased connectivity mainly in areas of sensorial and motor control, a result supported by the dFNC outcome and the alcohol use disorder identification test. This trend dominated the SAD group and in a weaker manner MAD and ALL. Nicotine consumers were characterized by an increment of connectivity between dorsal striatum and sensorimotor areas. Where possible, common and separate effects were identified and characterized by the analysis of dFNC data. Results also suggest that a combination of cannabis and nicotine have more contrasting effects on the brain than a single use of any of these substances. On the other hand, marijuana and alcohol might follow an additive effect trend. We concluded that all of the substances have an impact on brain connectivity, but the effect differs depending on the dFNC state analyzed.

Objective: To evaluate the serum leptin levels in cannabis smokers., Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit., Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008). When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039)., Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms., Methods: Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05)., Results: Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001)., Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

The regular use of cannabis generates pronounced cognitive disorders, especially in users who begin before the age of 15-16. However, less is known about the impact of regular cannabis on visual function, especially in the case of early onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system, like the thalamus and primary cortex, which might originate sensory disorders. Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users with late onset of cannabis use (after 16 years old), cannabis users with early onset". We used a constant method which allowed us to control for biased responses. Stimuli were presented at high and low spatial frequencies and in both static and dynamic conditions (8Hz). As contrast sensitivity is measured behaviorally based on an explicit response and could thus be impacted by attentional or vigilance disorders, participants' attention and vigilance were carefully monitored by means of the D2 test, CPT-AX for attention and pupillography for vigilance. Cannabis users with early onset were significantly impaired only at low spatial frequency. This effect was independent of response bias, vigilance and attention. These results show for the first time that early cannabis use impacts contrast sensitivity at low spatial frequency., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Cannabis is one of the most commonly used illicit drugs in the United States and is considered to have several adverse health effects. There is evidence suggesting that its recreational use is associated with both increased cardio- and cerebrovascular events. Recently, multiple cases of ischemic and hemorrhagic strokes associated with cannabis use were reported in the literature (Goyal et al., 2017). It has been suggested that cannabis can affect cerebral auto-regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. However, hemorrhagic strokes, which are often seen with sympathomimetic illicit drugs (e.g. cocaine and amphetamines), have rarely been reported due to cannabis. Many cellular mechanisms within non-ischemic tissue post stroke may be augmented by heavy cannabis use. Here, we describe a rapid development of hemorrhage following thrombolytic therapy in a patient with heavy cannabis use with an ischemic stroke., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this review, we provide an overview of the relationship between cannabis use and the development of schizophrenia, using both animal and human studies. We further discuss the potential neural mechanism that may mediate the relationship between cannabis use and schizophrenia symptoms. We finally provide clinical implications and future studies that can further elucidate the relationship between cannabis and schizophrenia.

Background and Objectives: Marijuana use has become more widely accepted in the United States and has been legalized in many areas. Although it is biologically plausible that marijuana could affect kidney function, epidemiologic data are lacking., Design, Setting, Participants, & Measurements: We conducted a cohort study among young adults with preserved eGFR ( i.e. , eGFR≥60 ml/min per 1.73 m 2 ) using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. At scheduled examinations occurring every 5 years and starting at study year 10 (calendar years, 1995-1996), cystatin C was collected over a 10-year period, and urine albumin-to-creatinine ratio was collected over a 15-year period. We investigated the cross-sectional association between current and cumulative marijuana use (in marijuana-years; one marijuana-year equals 365 days of marijuana use) and eGFR by cystatin C (eGFR cys ) at year 10. In longitudinal analyses, we investigated the association between cumulative marijuana use and eGFR cys change and rapid (≥3%/year) eGFR cys decline over two 5-year intervals and prevalent albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) over a 15-year period., Results: Past or current marijuana use was reported by 83% (3131 of 3765) of the cohort, and the mean eGFR cys was 111 ml/min per 1.73 m 2 at year 10. Over the following 10 years, 504 had rapid eGFR cys decline, and over the following 15 years, 426 had prevalent albuminuria. Compared with no use, daily current use and ≥5 marijuana-years of cumulative use were associated with lower eGFR cys at year 10: -4.5% (95% confidence interval, -8.1 to -0.7%; P =0.02) and -3.0% (95% confidence interval, -5.6 to -0.4%; P =0.03), respectively. Marijuana use was not significantly associated with eGFR cys change, rapid eGFR cys decline, or prevalent albuminuria., Conclusions: Although we identified a modest cross-sectional association between higher marijuana exposure and lower eGFR cys among young adults with preserved eGFR, our findings were largely null and did not demonstrate a longitudinal association between marijuana use and eGFR cys change, rapid eGFR cys decline, or prevalent albuminuria., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017&#95;08&#95;24&#95;CJASNPodcast&#95;17&#95;10.mp3., (Copyright © 2017 by the American Society of Nephrology.)

Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of "shared risk factors" between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893-902).

Cannabis, like the mythic shape-shifter, presents in various guises, morphing with the perspective and context of the observer. Arguments about cannabis are confused by a myriad of debates-medical, social, ethical and political-as if a single conceptual umbrella can capture the variety and granularity of marijuana-related issues. This paper responds to marijuana use as it is commonly practised by youth in Australia. It has little to say about synthetic cannabinoids, specific medicinal cannabinoids, or medicinal properties of marijuana. We address those adolescents genetically and environmentally vulnerable to mental illness, with specific emphasis on indigenous and neurodevelopmentally impaired young people who show patterns of usage and response very different to adults and more resilient members of the population. Specifically, the practice of mixing tobacco with marijuana by aboriginal youth, and the resultant coalition of dependencies, will likely presage a rise in pulmonary and central nervous system pathology over the coming decades. Aboriginal youth begin using earlier, persist longer, and take greater quantities of cannabis than non-indigenous youth. This paper recommends practical interventions to reduce the multiple health consequences of chronic cannabis use in young people, especially indigenous young people., (Copyright © 2016. Published by Elsevier Ltd.)

Introduction: There have been suggestions of hypofrontality in cannabis users. To understand cannabis-related differences in decisional processes, Janis and Mann's conflict model of decision making was applied to recreational cannabis smokers who varied in their alcohol use and level of psychological distress., Method: An online sample of recreational substance users (114 male, 119 female) completed the Melbourne Decision Making Questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), Kessler's Psychological Distress Scale (K10), and the Severity of Dependence Scale (SDS) for cannabis., Results: Multivariate analysis of variance examined self-reported decision-making styles as a function of gender, recent cannabis use, risky alcohol consumption, and levels of psychological distress. Psychological distress was associated with lower decisional self-esteem and higher levels of procrastination and buck-passing. There were gender differences associated with cannabis use. Female cannabis users reported higher levels of hypervigilance, while male cannabis users reported lower levels of buck-passing., Conclusions: Although there was little indication of an avoidant decisional style in cannabis users, the results suggest that cannabis affects decisional processes, contributing to panic in females and impulsivity in males.

Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Background and Objective: Peripheral airway involvement in asthma remains poorly understood. We investigated impulse oscillometry (IOS) measures of peripheral airway function in a population-based birth cohort., Methods: Pre- and post-bronchodilator spirometry and IOS measures of respiratory resistance and reactance were measured in 915 participants at age 38 years., Results: Current asthma was associated with impairments in both spirometry and IOS parameters. These impairments were greater in men and in those with childhood persistent asthma. Spirometry and IOS values for those whose asthma was in remission were not different to non-asthmatic participants. There were significant changes in IOS in both asthmatic and non-asthmatic participants after bronchodilator, but between-group differences persisted. Higher BMIs were associated with impairments in IOS but not spirometry. Cumulative tobacco use was associated with spirometric airflow obstruction in both sexes, whereas cannabis use was associated with impairments in IOS in women. Despite higher lifetime exposure, there were few associations between cannabis and IOS in men., Conclusion: Asthma is associated with abnormalities in IOS measures of peripheral airway dysfunction. This association is stronger in men and in those with asthma persisting since childhood. Tobacco and cannabis use are associated with different patterns of spirometry and IOS abnormalities and may affect the bronchial tree at different airway generations with differences in susceptibility between sexes., (© 2017 Asian Pacific Society of Respirology.)

Background: Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes., Methods: Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ 9 -tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg)., Results: Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization., Conclusions: All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments., (Published by Elsevier B.V.)

Purpose: There is increasing use of marijuana among young adults and more states in the United States are legalizing medical marijuana use. A number of studies have revealed both the beneficial and harmful effects of marijuana to the human system. Despite some beneficial effects, studies have shown marijuana to have a lot of deleterious effects on the visual system, which subsequently reduces the quality of eyesight. The aim of this study was to investigate if heavy marijuana smoking is associated with a poor quality of eyesight compared with light/no use of marijuana., Methods: The National Longitudinal Survey of Youths (NLSY79), a nationally representative sample of 12,686 young men and women surveyed in 1979 to 2010 was used for this study. The quality of eyesight of 1304 heavy marijuana users was compared with 1304 respondents with light or no marijuana use. The t test, multivariate and weighted logistic regression were used in the data analysis., Results: There was no statistically significant difference in the self-reported quality of eyesight among heavy marijuana smokers compared with youths who never used marijuana or are light marijuana users. Among heavy marijuana smokers, males and high school graduates have decreased odds of reporting a poor quality of eyesight, whereas blacks have increased odds of reporting a poor quality of eyesight., Conclusions: The self-reported quality of eyesight among marijuana users can aid clinicians and other health practitioners facilitate the development of sex-, racial/ethnic-, and educational level-informed prevention and early intervention programs and also help characterize public opinions regarding cannabis, which are particularly relevant given the ongoing debate concerning the medicalization and legalization of cannabis in the United States.

The effects of residual cannabis use on emotional expression recognition and the P3 event-related potential in participants who scored highly for subclinical depression were investigated. Comparisons were made between participants who were classified as depressed or nondepressed cannabis users, depressed non-cannabis users and controls who neither used cannabis nor were characterized as being depressed. In an emotional expression recognition task, participants were asked to respond to faces depicting happy, angry, fearful, and neutral faces either implicitly, explicitly, or empathically. Residual cannabis use and mood was shown to modulate the P3 event related potential during the task. There was a significant reduction in the P3 amplitude between depressed and nondepressed participants. Residual cannabis use further reduced the P3 amplitude with the greatest deficits being associated with cannabis users who scored highly for subclinical depression. These effects were greatest for explicit and empathic processing of faces depicting negative emotions. We conclude from our study that cannabis and mood state interact to reduce the amplitude of the P3 which has been associated with attention to emotion.

Background: Experimental research has shown that nutrition influences behavioral deviance., Objectives: The current project addresses the impact of nutrition on problem alcohol and drug use in a nationally representative sample of US adults., Methods: The study relies on the daily dietary nutrition data and the substance use measures in the 2007-2008 National Health and Nutrition Examination Survey., Results: The findings generally show that macronutrients increase the odds of substance use and micronutrients decrease the odds of substance use, especially among females. In addition, nutrient imbalance is a particularly strong predictor of substance use for both males and females. Depression partially accounts for the relationship between dietary nutrition consumption and substance use., Conclusions: Nutrition represents a promising extension of the biosocial perspective in substance use disorders.

This systematic review focuses on respiratory effects of inhalational marijuana. The systematic review of the literature was conducted using a comparative method between 2 researchers. Abstracts were reviewed for inclusion of respiratory effects related to inhalational marijuana. Relevant abstracts were collected, and full text articles were retrieved for review. Articles were removed if they did not contain burning marijuana; were animal studies; or were editorials, systematic reviews, commentaries, non-English language, or non-respiratory-related articles. Forty-eight articles were collected and categorized by respiratory effects. In particular, lung cancer, bullous emphysema/COPD, and other respiratory symptoms were the primary categories. Articles were noted by study population country, sample size, age distribution, and findings that were pertinent to respiratory health. The research indicates that there is a risk of lung cancer from inhalational marijuana as well as an association between inhalational marijuana and spontaneous pneumothorax, bullous emphysema, or COPD. A variety of symptoms have been reported by inhalational marijuana smokers, including wheezing, shortness of breath, altered pulmonary function tests, cough, phlegm production, bronchodilation, and other symptoms. It is important to stay current with research findings to educate patients on this smoking behavior., (Copyright © 2016 by Daedalus Enterprises.)

Background: Cannabis use is associated with an attention-dependent deficit in prepulse inhibition of the startle reflex (PPI). The aim of the current study was to investigate startle habituation in cannabis users and healthy controls during two attentional tasks., Methods: Auditory startle reflex was recorded from orbicularis oculi muscle while participants (12 controls and 16 regular cannabis users) were either attending to or ignoring 100 dB startling pulses. Startle habituation was measured as the absolute reduction in startle magnitude on block 2 (last nine trials) vs. block 1 (first nine trials)., Results: Startle habituation with moderate effect sizes was observed in controls and cannabis users only while they were ignoring the startling pulses but not while they were attending to them. Similar results were also observed in controls (lifetime non-users of cannabis) and cannabis users with lifetime cannabis use disorders (CUD)., Conclusion: Startle habituation appears to depend on selective attention but not on cannabis use. Startle habituation was present when attention was directed away from auditory startling pulses in healthy controls and cannabis users. Such a similar pattern of results in both groups suggests that at least a trend exists towards presence of startle habituation regardless of cannabis use or CUD in otherwise healthy members of the general population.

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes.

Background: Incentive salience is a multidimensional construct that includes craving, drug value relative to other reinforcers, and implicit motivation such as attentional bias to drug cues. Laboratory cue reactivity (CR) paradigms have been used to evaluate marijuana incentive salience with measures of craving, but not with behavioral economic measures of marijuana demand or implicit attentional processing tasks., Methods: This within-subjects study used a new CR paradigm to examine multiple dimensions of marijuana's incentive salience and to compare CR-induced increases in craving and demand. Frequent marijuana users (N=93, 34% female) underwent exposure to neutral cues then to lit marijuana cigarettes. Craving, marijuana demand via a marijuana purchase task, and heart rate were assessed after each cue set. A modified Stroop task with cannabis and control words was completed after the marijuana cues as a measure of attentional bias., Results: Relative to neutral cues, marijuana cues significantly increased subjective craving and demand indices of intensity (i.e., drug consumed at $0) and Omax (i.e., peak drug expenditure). Elasticity significantly decreased following marijuana cues, reflecting sustained purchase despite price increases. Craving was correlated with demand indices (r's: 0.23-0.30). Marijuana users displayed significant attentional bias for cannabis-related words after marijuana cues. Cue-elicited increases in intensity were associated with greater attentional bias for marijuana words., Conclusions: Greater incentive salience indexed by subjective, behavioral economic, and implicit measures was observed after marijuana versus neutral cues, supporting multidimensional assessment. The study highlights the utility of a behavioral economic approach in detecting cue-elicited changes in marijuana incentive salience., (Published by Elsevier Ireland Ltd.)

Objective: Preclinical studies have reported acute cardiovascular effects of cannabis, including a dose-dependent increase in blood pressure (BP), whereas orthostatic hypotension may follow as a result of decreased vascular resistance. In case reports, evidence links cannabis with acute cardiovascular events in young and middle-aged adults. Here, we offer epidemiologic estimates on cannabis use and BP levels association from the US National Health and Nutrition Examination Surveys 2005-2012 (n = 12 426)., Methods: Computer-assisted self-interviews assessed cannabis use. BP was determined by an average of up to four measurements taken during a single examination. Regression modeling was used to examine cannabis use and BP association., Results: Recently active cannabis use was associated with increase in SBP (β = 1.6; 95% confidence interval: 0.6, 2.7) in the age-sex-adjusted model. Additional covariate adjustment did not affect the positive association. No association between cannabis use and DBP was detected., Conclusion: A modest association between recent cannabis use and SBP was detected among a relatively large nationally representative sample of US adults. With the legalization of cannabis, there is a need for preclinical, clinical and prospective population-based research on the cardiovascular effects of cannabis use., Competing Interests: There is no conflict of interest to disclose.

Background: Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep., Objectives: This study sought to determine if past-year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships., Methods: Data were collected from 41 emerging adult (ages 18-25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past-year substance use, and length of cannabis abstinence., Results: Greater past-year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a nonsignificant trend level, such that participants with the higher cannabis use and depressive symptoms reported the more impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality., Conclusions: This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users., Competing Interests: Financial Disclosures The authors report no relevant financial conflicts.

Background: The medical and recreational use of marijuana is now legal in some parts of the United States; the health effects are unknown. We aimed to evaluate associations between recent marijuana use and exhaled nitric oxide (eNO) and pulmonary function., Methods: We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey in the years 2007 to 2012. We examined associations between marijuana use and eNO, FEV1, FVC, the FEV1/FVC ratio, and forced expiratory flow (midexpiratory phase) (FEF25%-75%) by weighted linear regression., Results: In the study population, there were 4,797 never users, 4,084 past marijuana users, 555 participants who used marijuana 5 to 30 days before the examination, and 891 participants who used marijuana 0 to 4 days before the examination. Current marijuana use in the past 4 days was associated with 13% lower eNO (95% CI, -18% to 8%). FVC was higher in past users (75 mL; 95% CI, 38-112) and current users in the past 5 to 30 days (159 mL; 95% CI, 80-237) and in users within 0 to 4 days of the examination (204 mL; 95% CI, 139-270) compared with never users. All associations remained unchanged and statistically significant in sensitivity analyses excluding current and past tobacco users., Conclusions: Current marijuana use was associated with lower levels of eNO and higher FVC. The lower eNO in marijuana smokers suggests that short-term exposure to marijuana may, like tobacco, acutely affect the pulmonary vascular endothelium and impair airflow through the small airways., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)