Tag Archives: CB(1) and CB(2) receptors

Cannabis in cancer care.

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“Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status.

Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function.

Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome.

Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics.

Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms.

Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.”

http://www.ncbi.nlm.nih.gov/pubmed/25777363

http://www.thctotalhealthcare.com/category/cancer/

Cannabinoid receptor 1 is a major mediator of renal fibrosis.

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“Chronic kidney disease, secondary to renal fibrogenesis, is a burden on public health.

There is a need to explore new therapeutic pathways to reduce renal fibrogenesis.

To study this, we used unilateral ureteral obstruction (UUO) in mice as an experimental model of renal fibrosis and microarray analysis to compare gene expression in fibrotic and normal kidneys.

The cannabinoid receptor 1 (CB1) was among the most upregulated genes in mice, and the main endogenous CB1 ligand (2-arachidonoylglycerol) was significantly increased in the fibrotic kidney.

Interestingly, CB1 expression was highly increased in kidney biopsies of patients with IgA nephropathy, diabetes, and acute interstitial nephritis. Both genetic and pharmacological knockout of CB1 induced a profound reduction in renal fibrosis during UUO. While CB2 is also involved in renal fibrogenesis, it did not potentiate the role of CB1. CB1 expression was significantly increased in myofibroblasts, the main effector cells in renal fibrogenesis, upon TGF-β1 stimulation.

The decrease in renal fibrosis during CB1 blockade could be explained by a direct action on myofibroblasts. CB1 blockade reduced collagen expression in vitro. Rimonabant, a selective CB1 endocannabinoid receptor antagonist, modulated the macrophage infiltrate responsible for renal fibrosis in UUO through a decrease in monocyte chemoattractant protein-1 synthesis.

Thus, CB1 has a major role in the activation of myofibroblasts and may be a new target for treating chronic kidney disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25760323

Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta.

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“Synthetic cannabinoids, the psychoactive components of the Cannabis sativa (marijuana) and their endogenous counterparts, act through two G protein-coupled receptors, CB1 and CB2.

The endocannabinoids are metabolized by fatty acid amide hydrolase (FAAH).

We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry.

CB1 receptor was found to be present in all layers of the membrane, with particularly strong expression in the amniotic epithelium and reticular cells and cells of the maternal decidua layer. Moderate expression was observed in the chorionic cytotrophoblasts. The expression of FAAH was the highest in amniotic epithelial cells, chorionic cytotrophoblast and maternal decidua layer.

Our results suggest that the human placenta is a likely target for cannabinoid action and metabolism. ”

http://www.ncbi.nlm.nih.gov/pubmed/12744923

Simultaneous inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) shares discriminative stimulus effects with ∆9-THC in mice.

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“Δ9 -tetrahydrocannabinol (∆9 -THC) is a cannabinoid CB1 /CB2 receptor agonist that produces therapeutic effects such as analgesia and anti-emetic effects…

Collectively, the current results show that pharmacological increases in endogenous AEA and 2-AG simultaneously through inhibition of FAAH and MAGL, respectively, mimics the discriminative stimulus effects of Δ9 -THC.”

http://jpet.aspetjournals.org/content/early/2015/02/24/jpet.115.222836.long

Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy.

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“The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist…

Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25712641

http://www.thctotalhealthcare.com/category/neuropathic-pain/

The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

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“Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others.

Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract.

These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut.

…the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field.

Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency.

The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25715910

Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

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“Vulnerability to drug addiction depends upon the interactions between the biological make-up of the individual, the environment, and age. These interactions are complex and difficult to tease apart.

Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure.

In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) have been considered a putative protective and risk factor, respectively, that can influence one’s susceptibility to continued drug abuse as well as the transition to addiction.

This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons.

Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle.

In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented.

Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.”

http://www.ncbi.nlm.nih.gov/pubmed/25714966

http://www.thctotalhealthcare.com/category/addiction/

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

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“The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins).

The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2.

These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry.

A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.”

http://www.ncbi.nlm.nih.gov/pubmed/25698968

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

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“To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by proinflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).

CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases.

Cannabinoids can suppress inflammatory cytokines…

The levels of CB1 and CB2 can be up-regulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS”

http://www.ncbi.nlm.nih.gov/pubmed/25704169

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoid signaling and liver therapeutics.

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Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

http://www.thctotalhealthcare.com/category/liver-disease/