Synthetic marijuana “K2” induced ITP

Immune thrombocytopenia (ITP) is a heterogeneous disease which can be primary or secondary due to other conditions such as drugs. CB2 receptors (CB2R) also have a role in the ITP pathogenesis as CB2 receptor gene (CNR2) polymorphisms are associated with chronic immune thrombocytopenia and autoimmune diseases. K2 is synthetic marijuana which acts on cannabinoid receptors that are found on immune cells and thrombocytes. Here, we present a case who presented with ITP secondary to K2 usage and was successfully treated with 1?mg/kg prednisolone. This is the first ITP case in the literature due to K2. It is important in the era of the new drugs development of the CB2R mimetics.     

Endocannabinoid system in irritable bowel syndrome and cannabis as a therapy

Irritable bowel syndrome (IBS) global burden is underestimated despite its high prevalence. It’s a gastrointestinal disease having obscure pathophysiology with multiple therapies yet unsatisfactory remedies. The Endocannabinoid system (ECS) of our body plays a key role in maintaining normal physiology of the gastrointestinal tract as well as involves abnormalities including functional diseases like IBS. This review highlights the importance of the Endocannabinoid system, its connections with the normal gastrointestinal functions and abnormalities like IBS. It also discusses the role of cannabis as medical therapy in IBS patients. A literature search for articles related to endocannabinoids in IBS and medical cannabis in PubMed and Google Scholar was conducted. The studies highlighted the significant participation of ECS in IBS. However, the breach in obtaining the promising therapeutic model for IBS needed further investigation in ECS and uncover other treatments for IBS. This review summarizes ECS, highlights the relationship of ECS with IBS and explores cannabis as a potential therapy to treat IBS.     

What we know and do not know about the cannabinoid receptor 2 (CB2)

It has been well appreciated that the endocannabinoid system can regulate immune responses via the cannabinoid receptor 2 (CB2), which is primarily expressed by cells of the hematopoietic system. The endocannabinoid system is composed of receptors, ligands and enzymes controlling the synthesis and degradation of endocannabinoids. Along with endocannabinoids, both plant-derived and synthetic cannabinoids have been shown to bind to and signal through CB2 via G proteins leading to both inhibitory and stimulatory signals depending on the biological process. Because no cannabinoid ligand has been identified that only binds to CB2, the generation of mice deficient in CB2 has greatly expanded our knowledge of how CB2 contributes to immune cell development and function in health and disease. In regards to humans, genetic studies have associated CB2 with a variety of human diseases. Here, we review the endocannabinoid system with an emphasis on CB2 and its role in the immune system.     

隔三七饼灸对佐剂诱导型RA大鼠脊髓AST大麻素受体及P38MAPK表达的影响及机制探讨

目的:探讨隔三七饼灸对佐剂诱导型类风湿性关节炎(RA)大鼠脊髓星形胶质细胞(AST)大麻素受体及促分裂原活化蛋白激酶(P38MAPK)表达的影响及作用机制。方法:采用足垫部皮下注射弗式完全佐剂(FAC)复制RA大鼠模型,将大鼠随机分为假手术组、隔三七饼灸治疗组(艾灸组)、模型组和红外线照射(TDP)治疗组(TDP组),每组10只,艾灸组取内膝眼、外膝眼、血海、足三里穴,予以隔三七饼灸治疗,每次每穴灸五壮,隔日1次,10次为1个疗程;TDP组予以TDP照射治疗,每次30分钟,隔日1次,10次为1个疗程;模型组、假手术组平行饲养,只在鼠板上固定而不作其他处理。在造模成功后、治疗一个疗程后分别观察记录踝关节疼痛试验评分、热痛阈和机械性痛阈,并采用免疫组织化学技术,观察大麻素受体CB1、CB2在脊髓背角的表达及P38MAPK在脊髓AST内表达。结果:造模后,与假手术组比较,模型组、艾灸组和TDP组大鼠的疼痛试验评分显著升高(P<0.01),热痛阈和机械痛阈显著降低(P<0.01);治疗1个疗程后,与模型组比较,艾灸组和TDP组的疼痛试验评分和P38MAPK的表达降低(P<0.01,P<0.05),热痛阈、机械痛阈以及CB1、CB2表达升高(P<0.01,P<0.05);与TDP组比较,艾灸组的疼痛试验评分和P38MAPK的表达明显降低(P<0.05),热痛阈、机械痛阈以及CB1、CB2表达明显升高(P<0.05)。结论:隔三七饼灸对RA大鼠产生的疼痛有良好的改善作用,能增强脊髓大麻素受体CB1、CB2表达,抑制P38MAPK的表达,其机制可能是艾灸通过调控脊髓大麻素受体CB1、CB2的表达,抑制P38MAPK的通路而对佐剂性关节炎产生镇痛作用。     

Physiological evidence of a postsynaptic inhibition of the tail flick reflex by a cannabinoid receptor agonist

Current evidence indicates that cannabinoids are antinociceptive and this effect is in part mediated by spinal mechanisms. Anatomical studies have localized cannabinoid CB₁ receptors to pre- and postsynaptic sites within the spinal cord. However, behavioural tests have not clearly indicated the relative importance of each of these sites. In this study, the tail flick test was used as a model of acute pain in the rat to determine the site of action of WIN 55,212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), a synthetic cannabinoid receptor agonist. WIN 55,212-2 (3 mg/kg, i.p.) increased the latency of tail withdrawal from a noxious radiant heat source, indicating it is antinociceptive in this model. Using the same paradigm, WIN 55,212-2 was then tested against the synaptically-induced nociceptive hypersensitivity in response to noxious thermal stimulation of the tail (hot water tail immersion). WIN 55,212-2 blocked this hypersensitivity, confirming a spinal site of action of the cannabinoid receptor agonist. Further, WIN 55,212-2 blocked the nociceptive hypersensitivity induced by intrathecal administration of substance P. As substance P acts on postsynaptic tachykinin NK1 receptors in the dorsal horn of the spinal cord, the data are interpreted to suggest that WIN 55,212-2 expressed its anti-hypersensitivity effects at least partially via a postsynaptic site of action; the data do not rule out a presynaptic site of action. This study suggests that cannabinoids may induce analgesia via a postsynaptic site of action in the spinal cord, as well as the possibility that they may interact with substance P signaling.     

Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat–an animal model of attention deficit hyperactivity disorder

Rationale  Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking. Objective  To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a “normal” genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB₁ cannabinoid receptor and (2) on putative changes by WIN in blood pressure. Methods  WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats. Results  In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB₁-mediated and not related to blood pressure. Conclusion  The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.     

Investigation of endocannabinoid modulation of conditioned responding evoked by a nicotine CS and the Pavlovian stimulus effects of CP 55,940 in adult male rats

Rationale  The cannabinoid CB₁ receptor antagonist/inverse agonist rimonabant (SR 141716) has been shown to block reinforcing and rewarding effects of nicotine. Research has not investigated whether the cannabinoid system is involved in the interoceptive stimulus effects of nicotine functioning as a conditional stimulus (CS). Objective  We examined the effects of rimonabant and the CB_1/2 receptor agonist, CP 55,940, on responding evoked by a nicotine CS in rats. Additionally, we determined whether CP 55,940 functioned as a CS or a Pavlovian positive drug feature Materials and methods  Pavlovian discrimination training involved intermixed nicotine (0.2 mg base/kg) and saline sessions with intermittent access to water only on nicotine. Antagonism tests with rimonabant (0.1-3 mg/kg) and substitution tests with CP 55,940 (0.003–0.1 mg/kg) followed. An effective dose of CP 55,940 was tested against the nicotine generalization curve. A separate group received CS training with CP 55,940 (0.01 mg/kg). Two other groups were trained using CP 55,940 (0.01 or 0.03 mg/kg) as a positive drug feature in which a brief light CS signaled access to water only on CP 55,940 sessions Results  Rimonabant blocked nicotine-evoked responding. CP 55,940 partially substituted for nicotine and enhanced responding to lower nicotine doses. Overall, CP 55,940 did not acquire control of conditioned responding in either Pavlovian drug discrimination task Conclusions  The cannabinoid system was involved in the CS effects of nicotine. This finding is counter to the operant drug discrimination research with nicotine as a discriminative stimulus, warranting further research into this possible dissociation.     

大麻素Ⅱ型受体在尖锐湿疣和Ⅰ级宫颈上皮内瘤变组织中的表达

目的：探讨大麻素Ⅱ型受体（CB2）在正常宫颈组织、宫颈尖锐湿疣（CA）和Ⅰ级宫颈上皮内瘤变（CINⅠ）中的表达规律和意义。方法：采用免疫组织化学方法分别检测正常宫颈组织、宫颈CA皮损、CINⅠ组织中CB2受体的表达情况。结果：CB2受体在正常宫颈组织、宫颈CA皮损、CINⅠ组织中均有表达,CINⅠ组织中CB2受体表达水平明显高于宫颈CA皮损,两组CB2受体表达水平均明显高于对照组。结论：CB2受体的表达可能与宫颈尖锐湿疣和宫颈上皮内瘤变的发生发展相关。     

内源性大麻素系统抗胶质瘤的作用机制

内源性大麻素系统是近年来研究较为深入的一个脂质信号和神经调节系统，广泛参与了体内一些生理或病理过程的调节。大量的研究表明，内源性大麻素系统及其相关药物能在体内外实验中抑制胶质瘤的生长，深入研究内源性大麻素系统抗胶质瘤的作用机制对改善胶质瘤的化疗效果具有重要的临床意义。     

Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model

BackgroundMany inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.ObjectiveIn order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation.MethodsThe effects of selected compounds on FcεRI-induced histamine and β-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited.ResultsWe found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine.ConclusionOur results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.