Pharmacology and adverse effects of new psychoactive substances: synthetic cannabinoid receptor agonists

GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist.

Objective To determine whether the acute consumption of cannabis (cannabinoids) by drivers increases the risk of a motor vehicle collision. Design Systematic review of observational studies, with meta-analysis. Data sources We did electronic searches in 19 databases, unrestricted by year or language of publication. We also did manual searches of reference lists, conducted a search for unpublished studies, and reviewed the personal libraries of the research team. Review methods We included observational epidemiology studies of motor vehicle collisions with an appropriate control group, and selected studies that measured recent cannabis use in drivers by toxicological analysis of whole blood or self report. We excluded experimental or simulator studies. Two independent reviewers assessed risk of bias in each selected study, with consensus, using the Newcastle-Ottawa scale. Risk estimates were combined using random effects models. Results We selected nine studies in the review and meta-analysis. Driving under the influence of cannabis was associated with a significantly increased risk of motor vehicle collisions compared with unimpaired driving (odds ratio 1.92 (95% confidence interval 1.35 to 2.73); P=0.0003); we noted heterogeneity among the individual study effects (I2=81). Collision risk estimates were higher in case-control studies (2.79 (1.23 to 6.33); P=0.01) and studies of fatal collisions (2.10 (1.31 to 3.36); P=0.002) than in culpability studies (1.65 (1.11 to 2.46); P=0.07) and studies of non-fatal collisions (1.74 (0.88 to 3.46); P=0.11). Conclusions Acute cannabis consumption is associated with an increased risk of a motor vehicle crash, especially for fatal collisions. This information could be used as the basis for campaigns against drug impaired driving, developing regional or national policies to control acute drug use while driving, and raising public awareness.

Synthetic cannabinoids (SC) are a heterogeneous group of compounds developed to probe the endogenous cannabinoid system or as potential therapeutics. Clandestine laboratories subsequently utilized published data to develop SC variations marketed as abusable designer drugs. In the early 2000s, SC became popular as "legal highs" under brand names such as Spice and K2, in part due to their ability to escape detection by standard cannabinoid screening tests. The majority of SC detected in herbal products have greater binding affinity to the cannabinoid CB1 receptor than does Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive compound in the cannabis plant, and greater affinity at the CB1 than the CB2 receptor. In vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC, including analgesic, anti-seizure, weight-loss, anti-inflammatory, and anti-cancer growth effects. SC produce physiological and psychoactive effects similar to THC, but with greater intensity, resulting in medical and psychiatric emergencies. Human adverse effects include nausea and vomiting, shortness of breath or depressed breathing, hypertension, tachycardia, chest pain, muscle twitches, acute renal failure, anxiety, agitation, psychosis, suicidal ideation, and cognitive impairment. Long-term or residual effects are unknown. Due to these public health consequences, many SC are classified as controlled substances. However, frequent structural modification by clandestine laboratories results in a stream of novel SC that may not be legally controlled or detectable by routine laboratory tests.