Functional brain connectomes reflect acute and chronic cannabis use.

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.

Neuropsychological and neurophysiological predictors and consequences of cannabis and illicit substance use during neurodevelopment: a systematic review of longitudinal studies.

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.

Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings.

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.

Marijuana, Alcohol, and ED: Correlations with LUTS/BPH.

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.

Responses to social evaluative stress in regular cannabis smokers.

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.

Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

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.

Cannabis use disorder and the lungs.

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.

An Exploratory Study of Early Auditory Evoked Potentials in Cannabis Smokers.

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.

Sex-related differences in subjective, but not neural, cue-elicited craving response in heavy cannabis users.

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.

Screening Heroin Smokers Attending Community Drug Clinics for Change in Lung Function: A Cohort Study.

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). FEV1 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 FEV1 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.

Behavioral Hearing Thresholds and Distortion Product Otoacoustic Emissions in Cannabis Smokers.

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 2f1-f2 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 f2 of 0.5 and 19.03 kHz using an f2/f1 ratio of 1.22 and L1/L2 = 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 ps > .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 (f2 ≤ 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.

The effects of sex and residual cannabis use on emotion processing: An event-related potential study.

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).

Cue Reactivity in the Ventral Striatum Characterizes Heavy Cannabis Use, Whereas Reactivity in the Dorsal Striatum Mediates Dependent Use.

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.

Consumo de marihuana: análisis autobiográfico de caso paradigmático entre un adolescente consumidor y un no consumidor / Marijuana consumption: autobiographical analysis of a paradigmatic case between a consumer adolescent and a non-consumer

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Effect of Smoked Cannabis on Vigilance and Accident Risk Using Simulated Driving in Occasional and Chronic Users and the Pharmacokinetic-Pharmacodynamic Relationship.

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.

Performance and Health-Related Characteristics of Physically Active Males Using Marijuana.

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.

Sex differences in the cardiometabolic health of cannabis users with a psychotic illness.

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.

Reduction in Cannabis Use and Functional Status in Physical Health, Mental Health, and Cognition.

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.

Differential relationships between cannabis consumption and sleep health as a function of HIV status.

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.

Cannabis in liver disorders: a friend or a foe?

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.