Monthly Archives: July 2013

Activation of spinal cannabinoid cb2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.

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“The role of spinal cannabinoid systems in neuropathic pain of streptozotocin-induced diabetic mice was studied…

 … A low dose of WIN-55,212-2  significantly recovered the tail-flick latency in streptozotocin-induced diabetic mice… The selective cannabinoid CB2 receptor agonist L-759,656 also dose-dependently recovered the tail-flick latency in streptozotocin-induced diabetic mice…

 These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23892011

The Hypocretin/Orexin Receptor-1 as a Novel Target to Modulate Cannabinoid Reward.

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“Although there is a high prevalence of users who seek treatment for cannabis dependence, no accepted pharmacologic treatment is available to facilitate and maintain abstinence.

 The hypocretin/orexin system plays a critical role in drug addiction, but the potential participation of this system in the addictive properties of cannabinoids is unknown.

 We investigated…  studies were performed to evaluate dopamine extracellular levels in the nucleus accumbens after acute Δ9-tetrahydrocannabinol administration..

… role of Hcrtr-1 in the reinforcing and motivational properties of WIN55,212-2 (THC) was confirmed…

CONCLUSIONS:

These findings demonstrate that Hcrtr-1 modulates the reinforcing properties of cannabinoids, which could have a clear therapeutic interest.”

http://www.ncbi.nlm.nih.gov/pubmed/23896204

Hepatic Cannabinoid Receptor Type 1 Mediates Alcohol-Induced Regulation of Bile Acid Enzyme Genes Expression Via CREBH.

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“In this study, we have investigated the effect of alcohol exposure on hepatic bile acid homeostasis and elucidated the mediatory roles of Cb1r and Crebh in this process.

We found that alcohol exposure or Cb1r-agonist 2-AG treatment increases hepatic bile acid synthesis and serum ALT, AST levels in vivo along with significant increase in Crebh gene expression and activation.

 Alcohol exposure activated Cb1r, Crebh, and perturbed bile acid homeostasis…

 Overall, our study demonstrates a novel regulatory mechanism of hepatic bile acid metabolism by alcohol via Cb1r-mediated activation of Crebh, and suggests that targeting Crebh can be of therapeutic potential in ameliorating alcohol-induced perturbation of bile acid homeostasis.”

http://www.ncbi.nlm.nih.gov/pubmed/23894352

Palmitoylethanolamide: From endogenous cannabimimetic substance to innovative medicine for the treatment of cannabis dependence.

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“Palmitoylethanolamide (PEA) is a fatty acid amide showing some pharmacodynamic similarities with Δ9-tetrahydrocannabinol, the principal psychoactive compound present in the cannabis plant.

Like Δ9-tetrahydrocannabinol, PEA can produce a direct or indirect activation of cannabinoid receptors.

 Furthermore, it acts as an agonist at TRPV1 receptor.

The hypothesis is that PEA has anti-craving effects in cannabis dependent patients, is efficacious in the treatment of withdrawal symptoms, produces a reduction of cannabis consumption and is effective in the prevention of cannabis induced neurotoxicity and neuro-psychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23896215

Anandamide deficiency and heightened neuropathic pain in aged mice.

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“Damaging of peripheral nerves may result in chronic neuropathic pain for which the likelihood is increased in the elderly. We assessed in mice if age-dependent alterations of endocannabinoids contributed to the heightened vulnerability to neuropathic pain at old age.

We assessed nociception, endocannabinoids and the therapeutic efficacy of R-flurbiprofen in young and aged mice in the spared nerve injury model of neuropathic pain.

 R-flurbiprofen was used because it is able to reduce neuropathic pain in young mice in part by increasing anandamide.

Aged mice developed stronger nociceptive hypersensitivity after sciatic nerve injury than young mice.

This was associated with low anandamide levels in the dorsal root ganglia, spinal cord, thalamus and cortex, which further decreased after nerve injury…”

 More: http://www.ncbi.nlm.nih.gov/pubmed/23597506

Analysis of THCA synthase gene expression in cannabis: A preliminary study by real-time quantitative PCR.

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“In this paper we describe analyses performed by Real-Time Reverse-Transcriptase Polymerase Chain Reaction (real-time RT-PCR) on RNA of 12 samples, carried out for forensic purposes to investigate a correlation between tetrahydrocannabinol (THC) concentration in Cannabis and the tetrahydrocannabinol acid synthase (THCAS) gene expression. Samples were obtained from an experimental cultivation of declared potency Cannabis variety seeds and from seizures. The Rubisco gene and the 26S ribosomal RNA gene were used as internal control genes for their constant expression and stability. As results we found minor gene expression in samples from leaves of young plants. Further, grouping results for cannabis samples with similar characteristics, we have found an increased relative expression in samples with the highest percentage of THC coming from seized sample and adult plants.”

http://www.ncbi.nlm.nih.gov/pubmed/23890639

[So called ((soft)) drugs: cannabis and the amotivational syndrome].

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“… there is a minority of problematic cannabis users.

 There is a scientific consensus to claim that cannabis induces a state of dependence in a small proportion of users.

Severe abuse of cannabis can also lead to cognitive impairments, especially on memory, although these effects usually improve after the cessation of cannabis use.

The statistical link between cannabis use and the development of psychotic disorders is more worrying, although the causal nature of this relationship remains controversial.

 Finally, a chronic abuse of cannabis is reputed to induce an amotivational syndrome, mainly characterized by a state of apathy.

Although the symptoms of the amotivational syndrome are in keeping with some clinical observations, it remains difficult to ascertain whether this clinical picture is causally produced by cannabis abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/23888577

Police custody following driving under the influence of cannabis: A prospective study.

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“We hypothesized that drug intoxication while driving could correspond to specific medical conditions of the detainees. Our objective was to evaluate medical features and addictive behaviours of suspected drug drivers and to collect data regarding assaults or injuries in these individuals.

We conducted a prospective study of suspected drug driving arrestees, who were compared to drink drivers or persons aged over 18 detained for other reasons. Data collected concerned persons’ characteristics, reported assaults, and observed injuries…

  Cannabis-only users accounted for 201 of 205 drug drivers (98%).

Suspected drug driving arrestees had good overall health rating.

Drug drivers were younger than controls and requested more rarely medical examination.

 They were rarely involved in addiction treatment and reported assaults or presented traumatic injuries less often than drink drivers and controls.

 Drug drivers were less often alcohol abusers than controls.

 Their opinion on custody was better than that of controls and they were considered unconditionally fit for detention more frequently.

 We conclude that arrested drug drivers were young, healthy, and infrequently reported assaults or presented traumatic injuries, which does not put them in a high risk medical condition…”

http://www.ncbi.nlm.nih.gov/pubmed/23890621

Controlling 2-arachidonoylglycerol metabolism as an anti-inflammatory strategy.

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“The endocannabinoid system is implicated in, and regulates, several physiological processes, ranging from food intake and energy balance to pain and inflammation.

 2-Arachidonoylglycerol (2-AG) is a full agonist at the cannabinoid receptors which classically mediate its effects. The activity of this bioactive lipid is dependent on its endogenous levels, which are tightly controlled by several hydrolases, monoacylglycerol lipase and α/β-hydrolase domain 6 and 12.

 Moreover, 2-AG is also a substrate of cyclooxygenase-2, and this reaction leads to the formation of prostaglandin glycerol esters, the effects of which remain to be fully elucidated.

 In this review we discuss the multiple mechanisms by which 2-AG controls inflammation and the therapeutic potential of 2-AG metabolism inhibitors.”

http://www.ncbi.nlm.nih.gov/pubmed/23891880

The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.

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“Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C.

Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy.

More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects.

Compounds able to target selectively the peripheral CB1 receptors are under evaluation.

In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research.

Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/23890208