Tag Archives: target

The cannabinoid receptor 2 is involved in acute rejection of cardiac allografts.

Posted on by
Reply

“Acute rejection of cardiac allografts is a major risk factor limiting survival of heart transplant recipients. Rejection is triggered by dendritic cell (DC) mediated activation of host T cells, amongst others CD4+ T helper (TH)1- and TH17 cells.

The cannabinoid receptor 2 (CB2) is an important modulator of cellular immune responses…

These results demonstrate that CB2 modulates in vitro cytokine responses via DCs and directly via its influence on TH1/TH17 differentiation.

These findings and the fact that allograft rejection is enhanced in Cnr2-/- mice suggest that CB2 may be a promising therapeutic target in organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/25744392

Intact cannabinoid CB1 receptors in the Alzheimer’s disease cortex.

Posted on by
1

“The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer’s disease (AD). Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function.

 Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD.”

http://www.ncbi.nlm.nih.gov/pubmed/21034788

Enhancement of endocannabinoid neurotransmission through CB1 cannabinoid receptors counteracts the reinforcing and psychostimulant effects of cocaine.

Posted on by
Reply

Abstract

“Cannabinoids, in contrast to typical drugs of abuse, have been shown to exert complex effects on behavioural reinforcement and psychomotor function. We have shown that cannabinoid agonists lack reinforcing/rewarding properties in the intracranial self-stimulation (ICSS) paradigm and that the CB1 receptor (CB1R) agonist WIN55,212-2 attenuates the reward-facilitating actions of cocaine. We sought to determine the effects of the endocannabinoid neurotransmission enhancer AM-404 (1, 3, 10, 30 mg/kg) on the changes in ICSS threshold and locomotion elicited by cocaine and extend the study of the effects of WIN55,212-2 (0.3, 1, 3 mg/kg) on cocaine-induced hyperlocomotion. AM-404 did not exhibit reward-facilitating properties, and actually increased self-stimulation threshold at the highest dose. Cocaine significantly reduced self-stimulation threshold, without altering maximal rates of responding. AM-404 (10 mg/kg) attenuated this action of cocaine, an effect which was reversed by pretreatment with the selective CB1R antagonist SR141716A. WIN55,212-2 decreased locomotion at the two highest doses, an effect that was blocked by SR141716A; AM-404 had no effect on locomotion. Cocaine caused a significant, dose-dependent increase in locomotion, which was reduced by WIN55,212-2 and AM-404. SR141716A blocked the effects of WIN55,212-2 and AM-404 on cocaine-induced hyperlocomotion. SR141716A alone had no effect on ICSS threshold or locomotion. These results indicate that cannabinoids may interfere with brain reward systems responsible for the expression of acute reinforcing/rewarding properties of cocaine, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for the treatment of psychostimulant addiction and pathological states associated with psychomotor overexcitability.”

http://www.ncbi.nlm.nih.gov/pubmed/18377702

An endocannabinoid hypothesis of drug reward and drug addiction.

Posted on by
Reply

Abstract

“Pharmacologic treatment of drug and alcohol dependency has largely been disappointing, and new therapeutic targets and hypotheses are needed. There is accumulating evidence indicating a central role for the previously unknown but ubiquitous endocannabinoid physiological control system (EPCS) in the regulation of the rewarding effects of abused substances. Thus an endocannabinoid hypothesis of drug reward is postulated. Endocannabinoids mediate retrograde signaling in neuronal tissues and are involved in the regulation of synaptic transmission to suppress neurotransmitter release by the presynaptic cannabinoid receptors (CB-Rs). This powerful modulatory action on synaptic transmission has significant functional implications and interactions with the effects of abused substances. Our data, along with those from other investigators, provide strong new evidence for a role for EPCS modulation in the effects of drugs of abuse, and specifically for involvement of cannabinoid receptors in the neural basis of addiction. Cannabinoids and endocannabinoids appear to be involved in adding to the rewarding effects of addictive substances, including, nicotine, opiates, alcohol, cocaine, and BDZs. The results suggest that the EPCS may be an important natural regulatory mechanism for drug reward and a target for the treatment of addictive disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/18991888

The role of the endocannabinoid system in the control of energy homeostasis

Posted on by
Reply

Abstract

“The endocannabinoid system has recently emerged as an important regulator of energy homeostasis, involved in the control of both appetite and peripheral fat metabolism. We briefly review current understanding of the possible sites of action and cellular mechanisms involved in the central appetitive and peripheral metabolic effects of endocannabinoids. Studies in our laboratory, using leptin-deficient obese rodents and CB1 cannabinoid receptor (CB1)-deficient mice, have indicated that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in brain areas involved in appetite control, including the hypothalamus, limbic forebrain and amygdala. CB1-/- mice are lean and are resistant to diet-induced obesity (DIO) despite similar energy intake to wild-type mice with DIO, suggesting that CB1 regulation of body weight involves additional peripheral targets. Such targets appear to include both adipose tissue and the liver. CB1 expressed in adipocytes has been implicated in the control of adiponectin secretion and lipoprotein lipase activity. Recent findings indicate that both endocannabinoids and CB1 are present in the liver and are upregulated in DIO. CB1 stimulation increases de novo hepatic lipogenesis through activation of the fatty acid biosynthetic pathway. Components of this pathway are also expressed in the hypothalamus where they have been implicated in the regulation of appetite. The fatty acid biosynthetic pathway may thus represent a common molecular target for the central appetitive and peripheral metabolic effects of endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/16570103

Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity.

Posted on by
Reply

Abstract

“Obesity, an ever-increasing problem in the industrialized world, has long been a target of research for a cure or, at least, control of its expansion. In the search for treatment, the recently discovered endocannabinoid system has emerged as a new target for controlling obesity and its associated conditions. The endocannabinoid system plays an important role in controlling weight and energy balance in humans. This system is activated to a greater extent in obese patients, and the specific blockage of its receptors is the aim of rimonabant, one of the most recent drugs created for the treatment of obesity. This drug acts as a blockade for endocannabinoid receptors found in the brain and peripheral organs that play an important role on carbohydrate and fat metabolism. Clinical studies have confirmed that, when used in combination with a low calorie diet, rimonabant promotes loss in body weight, loss in abdominal circumference, and improvements in dyslipidemia. Rimonabant is also being tested as a potential anti-smoking treatment since endocannabinoids are related to the pleasurable effect of nicotine. Thus, rimonabant constitutes a new therapeutic approach to obesity and cardiovascular risk factors. Studies show effectiveness in weight loss; however, side effects such as psychiatric alterations have been reported, including depression and anxiety. These side effects have led the FDA (Food and Drug Administration) to not approve this drug in the United States. For a more complete evaluation on the safety of this drug, additional studies are in progress.”

http://www.ncbi.nlm.nih.gov/pubmed/19443932