ne, did not alter respiration. Our findings suggest that the CB2 cannabinoid agonist LY2828360 may provide CB2-mediated protection against fentanyl-induced respiratory depression, a detrimental and unwanted side effect of opioid use and abuse.Objectives High levels of morbidity and mortality associated with injection drug use continue to represent a significant public health challenge in many settings worldwide. Previous studies have shown an association between cannabis use and decreased risk of some drug-related harms. We sought to evaluate the association between high-intensity cannabis use and the frequency of injection drug use among people who inject drugs (PWID). Methods The data for this analysis were collected from three prospective cohorts of PWID in Vancouver, Canada, between September 2005 and May 2018. Generalized linear mixed-effects models were used to analyze the association between daily cannabis use and the frequency of injecting illegal drugs (i.e., self-reported average number of injections per month). Results Among the 2,619 active PWID, the frequency of injection drug use was significantly lower among people who use cannabis daily compared with people who use it less than daily (adjusted odds ratio [AOR]=0.84, 95% confidence interval [CI] 0.73-0.95). Sub-analyses indicated that this effect was restricted to the frequency of illegal opioid injection (AOR=0.78, 95% CI 0.68-0.90); the association between daily cannabis use and the frequency of illegal stimulant injection was not significant (AOR=1.08, 95% CI 0.93-1.25). Discussion The findings from these prospective cohorts suggest that people who use cannabis daily were less likely to report daily injection of illegal drugs compared with people who use it less than daily. These results suggest the potential value of conducting experimental research to test whether controlled administration of cannabinoids impacts the frequency of illegal opioid injection among PWID.Introduction Cannabis smoke contains carcinogens similar to tobacco, in addition to compounds with antitumor activity. Cannabis use reduces the risk of obesity and cannabinoids inhibit chronic inflammation, known causes of cancer. The net effect of Cannabis use on cancer risk is not known. Objective To examine the association between Cannabis use and cancer risk in the United States. Methods Identify and analyze published data on cancer risk in Cannabis users. Results A total of 55 data points, consisting of risk ratios of cancer in Cannabis users and nonusers, were identified from 34 studies. Of these, 5 did not contain data essential for inclusion in the meta-analysis. The remaining data showed a nonsignificant trend to an association with reduced risk (relative risk [RR]=0.90, p>0.06, N=50) although heterogeneity is high (I2=72.4%). Sunitinib purchase Removal of data with high risk of selection bias (defined as those from North Africa and those that failed to adjust for tobacco) and data with high risk of performance bias (defined as those with fewer than 20 cases or controls among Cannabis users) resulted in an RR 1, although this was not significant and had a negligible effect size (RR=1.12, p=0.3, Hedges g=0.02). Following removal of testicular cancers the remaining data showed a decrease in risk (RR=0.87, p less then 0.025, N=41). Cancers of the head and neck showed a negative association with cancer risk (RR=0.83, p less then 0.05), with a large effect size (Hedges g=0.55), but high heterogeneity (I2=79.2%). RR did not reach statistical significance in the remaining cancer site categories (lung, testicular, obesity-associated, other). The data are consistent with a negative association between Cannabis use and nontesticular cancer, but there is low confidence in this result due to high heterogeneity and a paucity of data for many cancer types.Introduction Legalization of medicinal cannabis around the world has led to an increase in the use of commercial cannabis-based products in the community. These cannabis-based products are being used in combination with conventional drugs to treat a variety of health conditions. Moreover, recreational cannabis-based products may be used in combination with other drugs. In this setting, there is increased potential for drug-drug interactions (DDIs) involving commercial cannabis-based products. Since DDIs can lead to serious adverse events, drug regulatory bodies require that every investigational drug be evaluated for DDI potential at metabolic enzymes and transporters. However, this seldom occurs for cannabis-based products due to legislation in many jurisdictions allowing a direct pathway to market. This study aimed to examine the inhibitory potential of three commercially available cannabis-based products at human ATP-binding cassette (ABC) and solute-carrier (SLC) transporters. Materials and Methods Three based products did not inhibit ABCB1, ABCC2, SLC47A1, SLC47A2, or SLC22A8 transporters. Discussion Novel findings were that the cannabis-based products inhibited ABCB11, SLC22A6, SLC22A1, SLC22A2, SLCO1B1, and SLCO1B3 (although modestly in most instances). Spectrum Yellow and Tweed Argyle potently inhibited ABCG2, and future in vivo DDI studies could be conducted to assess whether cannabis products affect the pharmacokinetics of medications that are ABCG2 substrates.Background Recently increased access to cannabis products in the United States has been associated with increased rates of driving after cannabis use. Although numerous studies indicate that cannabis impairs psychomotor and neurocognitive functions that can affect driving ability, the determination of cannabis-impaired driving risk is complicated by the extent to which frequent cannabis users develop tolerance to THC's subjective, cognitive, and psychomotor effects, and by the fact that there is no validated behavioral or biological marker of recent cannabis use or cannabis-related impairment. This study examined the psychomotor impairment-related effects experienced by frequent cannabis users in Colorado after naturalistic consumption of smoked cannabis, both immediately and 1 h postuse. Results were then validated in a smaller replication sample from Washington state. Methods In the primary Colorado study, participants (n=70) used the DRUID® mobile app, a brief measure of psychomotor and cognitive domains that are sensitive to the effects of cannabis.