Synthetic Cannabinoid

BACKGROUND: The cannabinoid receptor 2 (CB2R) is primarily expressed in immune tissues and implicated in immune regulation. In models of inflammatory diseases, modulation of CB2R alters function of immune cells and affects the progression of disease. We therefore believe that CB2R modulation could be a promising therapy for inflammatory diseases. In humans, the nonsynonymous mutation Q63R, the most common variant of the CB2 receptor, has been found to be associated with multiple diseases, including idiopathic arthritis, obesity, and celiac diseases...

Achievements of supercritical fluid chromatography with mass spectrometric detection made in the field of forensic science during the last decade are reviewed. The main topics include analysis of traditional drugs of abuse (e.g. cannabis, methamphetamine) as well as new psychoactive substances (synthetic cannabinoids, cathinones and phenethylamines), doping agents (anabolic steroids, stimulants, diuretics, analgesics etc.) and chemical warfare agents. Control of food authenticity, detection of adulteration and identification of toxic substances in food are also pointed out...

Synthetic cannabinoids (spice), which are used frequently worldwide, are more potent than herbal compounds and also have more side effects in comparison. A 23-year-old male was admitted to the emergency unit with altered consciousness. There was no sign of trauma, and his medical history did not reveal any chronic illness. Computed tomography revealed a large frontal hematoma extending to the ventricular system. The outcomes of cerebral angiography were consistent with multiple intracranial arterial stenoses (MIAS) which can also be seen after cannabis usage...

With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function...

Continued diversification and use of new psychoactive substances (NPS) across Europe remains a public health challenge. The study describes health and social consequences of recent NPS use as reported in a survey of marginalised, nightlife and online NPS users in the Netherlands, Hungary, Portugal, Ireland, Germany and Poland ( n  = 3023). Some respondents were unable to categorise NPS they had used. Use of ' herbal blends ' and ' synthetic cannabinoids obtained pure ' was most reported in Germany, Poland and Hungary, and use of ' branded stimulants ' and ' stimulants/empathogens/nootropics obtained pure ' was most reported in the Netherlands...

The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings. Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors. Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting...

Lipocalin-type prostaglandin D synthase (L-PGDS; EC:5.3.99.2) is an enzyme with dual functional roles as a prostaglandin D2 -synthesizing enzyme and as an extracellular transporter for diverse lipophilic compounds in the cerebrospinal fluid (CSF). Transport of hydrophobic endocannabinoids is mediated by serum albumin in the blood and intracellularly by the fatty acid binding proteins, but no analogous transport mechanism has yet been described in CSF. L-PGDS has been reported to promiscuously bind a wide variety of lipophilic ligands and is among the most abundant proteins found in the CSF...

EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 on major drug-metabolizing enzymes, cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were evaluated in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry (LC-MS/MS)...

This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects...

The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown...

MAM-2201 is a fluorinated naphthoylindole synthetic cannabinoid with potent psychoactive properties that has been detected as an active ingredient in herbal incense blends. To gain a greater understanding of MAM-2201 metabolism and to compare the metabolic fate in humans with those in animals, the metabolism of MAM-2201 in human, mouse, and rat hepatocytes was investigated using liquid chromatography-high-resolution mass spectrometry combined with targeted and non-targeted metabolite profiling approaches. Nineteen phase I metabolites (M1-M19) reported previously in human liver microsomes and 13 novel metabolites were identified in human, mouse, and rat hepatocytes: one phase I metabolite (M20) and 12 phase II metabolites including six glucuronides (G1-G6), one sulfate (S1), and five glutathione (GSH) conjugates (GS1-GS5) of MAM-2201 metabolites...

Priapism is a urological emergency that needs early intervention and may lead to irreversible cavernosal damage. Ischaemic priapism is the most common type, which is frequently idiopathic and commonly associated with haematological diseases, medications or recreational drugs. Synthetic cannabinoids (SCs) have been increasingly used all over the world, particularly among young-adult population. SCs can cause severe adverse effects on several organ systems. However, there are no studies in the literature which have stated the possible relationship between using of SCs and priapism...

Several molecularly imprinted polymers (MIPs) have been synthesized for the first time using various synthetic cannabinoids (JWH007, JWH015 and JWH098) as template molecules. Ethylene dimethacrylate (EDMA) was used as a functional monomer for all cases. Similarly, divinylbenzene (DVB) and 2,2'-azobisisobutyronitrile (AIBN) were used as cross-linker and initiator, respectively. The prepared MIPs have been fully characterized and evaluated as new selective adsorbents for micro-solid phase extraction (μ-SPE) of synthetic cannabinoids in urine...

INTRODUCTION: Cannabis sativa L. (cannabis) is utilised as a therapeutic and recreational drug. With the legalisation of cannabis in many countries and the anticipated regulation of potency that will accompany legalisation, analytical testing facilities will require a broadly applicable, quantitative, high throughput method to meet increased demand. Current analytical methods for the biologically active components of cannabis (phytocannabinoids) suffer from low throughput and/or an incomplete complement of relevant phytocannabinoids...

The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response...

To further elucidate the metabolism of CUMYL-4CN-BINACA, a new synthetic cannabinoid with a cyano group, and to evaluate biomarkers, we incubated the substance in human hepatocytes and analysed nine authentic urine specimens. We also quantified CUMYL-4CN-BINACA and cyanide in blood and provide comprehensive data on the seven autopsy cases, five determined CUMYL-4CN-BINACA intoxications. For metabolite elucidation, CUMYL-4CN-BINACA was incubated with pooled human hepatocytes up to 5 h, urine samples were analysed with and without enzymatic hydrolysis...

In the last years cannabinoid type 2 receptors (CB2R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB2R are devoid of psychoactive effect typically observed for CB1R ligands. Taking advantage of our recent studies on a class of pyridazinone 4-carboxamides, further structural modifications on pyridazinone core were explored to better investigate the structure-activity relationships for this promising scaffold with the aim to develop potent CB2R ligands. In binding assays two of the new synthetized compounds (2 and 22) showed high CB2R affinity, with Ki values of 2...

Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score...

BACKGROUND: Synthetic cannabinoids are the largest group of new psychoactive substances monitored by the European Monitoring Center of Drugs and Drug Addiction. The rapid proliferation of novel analogs makes the detection of these new derivatives challenging and has initiated considerable interest in the development of so-called "untargeted" screening strategies to detect these compounds. METHODS: We developed new, stable bioassays in which cannabinoid receptor activation by cannabinoids led to recruitment of truncated β-arrestin 2 (βarr2) to the cannabinoid receptors, resulting in functional complementation of a split luciferase, allowing readout via bioluminescence...

It is now incontrovertible that heavy use of cannabis increases the risk of psychosis. There is a dose-response relationship and high potency preparations and synthetic cannabinoids carry the greatest risk. It would be wise to await the outcome of the different models of legalisation that are being introduced in North America, before deciding whether or not to follow suit. Declaration of interest None.