In Vivo Imaging of Translocator Protein in Long-term Cannabis Users.

Importance: Cannabis is the most commonly used illicit drug in the world. Cannabinoids have been shown to modulate immune responses; however, the association of cannabis with neuroimmune function has never been investigated in vivo in the human brain. Objective: To investigate neuroimmune activation or 18-kDa translocator protein (TSPO) levels in long-term cannabis users, and to evaluate the association of brain TSPO levels with behavioral measures and inflammatory blood biomarkers. Design, Setting, and Participants: This cross-sectional study based in Toronto, Ontario, recruited individuals from January 1, 2015, to October 30, 2018. Participants included long-term cannabis users (n = 24) and non-cannabis-using controls (n = 27). Cannabis users were included if they had a positive urine drug screen for only cannabis and if they used cannabis at least 4 times per week for the past 12 months and/or met the criteria for cannabis use disorder. All participants underwent a positron emission tomography scan with [18F]FEPPA, or fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide. Main Outcomes and Measures: Total distribution volume was quantified across regions of interest. Stress and anxiety as well as peripheral measures of inflammatory cytokines and C-reactive protein levels were also measured. Results: In total, 24 long-term cannabis users (mean [SD] age, 23.1 [3.8] years; 15 men [63%]) and 27 non-cannabis-using controls (mean [SD] age, 23.6 [4.2] years; 18 women [67%]) were included and completed all study procedures. Compared with the controls, cannabis users had higher [18F]FEPPA total distribution volume (main group effect: F1,48 = 6.5 [P = .01]; ROI effect: F1,200 = 28.4 [P < .001]; Cohen d = 0.6; 23.3% higher), with a more prominent implication for the cannabis use disorder subgroup (n = 15; main group effect: F1,39 = 8.5 [P = .006]; ROI effect: F1,164 = 19.3 [P < .001]; Cohen d = 0.8; 31.5% higher). Greater TSPO levels in the brain were associated with stress and anxiety and with higher circulating C-reactive protein levels in cannabis users. Conclusions and Relevance: The results of this study suggest that TSPO levels in cannabis users, particularly in those with cannabis use disorder, are higher than those in non-cannabis-using controls. The findings emphasize the need for more complementary preclinical systems for a better understanding of the role of cannabinoids and TSPO in neuroimmune signaling.

Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.

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

Immunoregulatory Role of Cannabinoids during Infectious Disease.

Although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this drug increases susceptibility to infections because of the impact on the modulation of the immune system. Concerning the medicinal or recreational use of marijuana, its influence on the course of an infection, whether this has been caused by bacteria, viruses, parasites, and to a lesser degree, fungi, has been reported. Furthermore, there is evidence suggesting the involvement of the ECS in the control and elimination of infectious agents such as bacteria, viruses, and some protozoa; in the case of fungi, few studies are available so far. The purpose of this review is to present the existing studies related to infections and the ECS, the microbicidal effects of compounds isolated from Cannabis sativa, and the association between marijuana use and the development of rare pathologies in specific diseases.

Effect of Marijuana Use on Thyroid Function and Autoimmunity.

BACKGROUND: Marijuana is legalized for medical use in 24 states and for recreational use in 5. However, effects of marijuana use on thyroid function and autoimmunity are unknown. METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2012 to assess the effects of marijuana on thyroid function and autoimmunity in users. We included 5280 adults ages 18 to 69 years, who responded to questions related to marijuana use and had laboratory results related to thyroid parameters. Subjects were categorized as nonusers (never used), past users (used prior to 30 days ago), and recent users (used within last 30 days). Using NHANES normative cut offs for thyroid parameters, we compared recent users with nonusers and past users and calculated the odds ratios for the relative rate of clinically significant thyroid dysfunction in those groups. Multivariate logistic regression was then performed to control for confounders. RESULTS: Fifty-four percent of subjects reported lifetime cannabis use, with 15% using it recently. Univariate regression analysis showed that recent marijuana users had significantly lower frequency of elevated thyrotropin (TSH) and positive anti-thyroperoxidase antibody (TPOAb) versus nonusers/past users. After controlling for confounders, recent marijuana use remained an independent predictor for TSH <5.6 µIU/mL (odds ratio of 0.344 with 95% CI of 0.127-0.928; p = 0.04) but not for negative TPOAb. CONCLUSION: Recent marijuana use was not associated with thyroid dysfunction but was significantly associated with lower levels of TSH.