Tag Archives: cannabinoid receptors

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

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“Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo.

RESULTS:

CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells… In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer.

CONCLUSIONS:

CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.”

http://www.ncbi.nlm.nih.gov/pubmed/24373545

The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers.

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“The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypicalcannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system.

Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies.

Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis.

Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed.”

http://www.ncbi.nlm.nih.gov/pubmed/24369462

Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia.

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“The interactions between the cannabinoid and opioid systems for pain modulation are reciprocal. However, the role and the importance of the cannabinoid system in the antinociceptive effects of opioids remain uncertain. We studied these interactions with the goal of highlighting the involvement of the cannabinoid system in morphine-induced analgesia.

In both phases of the formalin test, intra paw and intrathecal morphine produced similar antinociceptive effects in C57BL/6, cannabinoid type 1 and type 2 receptor wildtype (respectively cnr1WT and cnr2WT) mice. In cnr1 and cnr2 knockout (KO) mice, at the dose used the antinociceptive effect of intra paw morphine in the inflammatory phase of the formalin test was decreased by 87% and 76%, respectively. Similarly, the antinociceptive effect of 0.1 μg spinal morphine in the inflammatory phase was abolished in cnr1KO mice and decreased by 90% in cnr2KO mice. Interestingly, the antinociceptive effect of morphine in the acute phase of the formalin test was only reduced in cnr1KO mice. Notably, systemic morphine administration produced similar analgesia in all genotypes, in both the formalin and the hot water immersion tail flick tests.

Because the pattern of expression of the mu opioid receptor (MOP), its binding properties and its G protein coupling remained unchanged across genotypes, it is unlikely that the loss of morphine analgesia in the cnr1KO and cnr2KO mice is the consequence of MOP malfunction or downregulation due to the absence of its heterodimerization with either the CB1 or the CB2 receptors, at least at the level of the spinal cord.”

http://www.ncbi.nlm.nih.gov/pubmed/24365460

Endocannabinoid signalling in neuronal migration.

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“The endocannabinoid (eCB) system consists of several endogenous lipids, their target CB1 and CB2 receptors and enzymes responsible for their synthesis and degradation. The most abundant eCB in the central nervous system (CNS), 2-arachidonoyl glycerol (2-AG), triggers a broad range of signalling events by acting on CB1, the most abundant G protein-coupled receptor in the CNS. The eCB system regulates many physiological processes including neurogenesis, axon guidance and synaptic plasticity. Recent studies have highlighted an additional important role for eCB signalling in neuronal migration, which is crucial to achieve the complex architecture and efficient wiring of the CNS. Indeed, eCB signalling controls migration both pre- and post-natally, regulating interneuron positioning in the developing cortex and hippocampus and the polarized motility of stem cell-derived neuroblasts. While these effects may contribute to cognitive deficits associated with cannabis consumption, they also provide potential opportunities for endogenous stem cell-based neuroregenerative strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/24361301

Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies

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“This review summarises in vitro and in vivo findings relating to the influence of cannabinoid ligands on bone metabolism and argues in favour of the exploitation of cannabinoid receptors as targets for both anabolic and anti-resorptive therapy for treatment of complex multifaceted bone diseases such as osteoporosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001217/

The promise and dilemma of cannabinoid therapy: lessons from animal studies of bone disease.

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“The endocannabinoid system plays an important role in numerous physiological processes and represents a potential drug target for diseases ranging from brain disorders to cancer…

In the aging skeleton, CB1 deficiency causes accelerated osteoporosis characterized mainly by a significant reduction in bone formation coupled to enhanced adipocyte accumulation in the bone marrow.

A similar acceleration of bone loss was also reported in aging CB2-deficient mice but found to be associated with enhanced bone turnover.

This perspective describes the role of cannabinoid ligands and their receptors in bone metabolism and highlights the promise and dilemma of therapeutic exploitation of the endocannabinoid system for treatment of bone disorders.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868875/

Spinal gene expression profiling and pathways analysis of a CB2 agonist (MDA7)-targeted prevention of paclitaxel-induced neuropathy.

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“Patients receiving paclitaxel often develop peripheral neuropathies. We found that a novel selective cannabinoid CB2 receptor agonist (MDA7) prevents paclitaxel-induced mechanical allodynia in rats and mice…

The preventive effect of MDA7 on paclitaxel-induced peripheral allodynia in rats may be associated with genes involved in signal pathways in central sensitization, microglial activation, and neuroinflammation in the spinal cord.”

http://www.ncbi.nlm.nih.gov/pubmed/24361916

The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington’s disease and in striatal tissue from Huntington’s disease patients.

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“Transcriptional dysregulation is a major pathological feature of Huntington’s disease (HD). The goal of this study was to understand how p65/RelA co-regulated genes, specifically those of the cytokine and endocannabinoid systems, were affected in HD. p65/RelA levels were lower in human HD tissue and R6/2 HD mice, as were the levels of the type 1 cannabinoid receptor (CB1), IL-1β, IL-8, CCL5, GM-CSF, MIP-1β, and TNFα, all of which may be regulated by p65/RelA. Activation of p65/RelA restored CB1 and CCL5 expression in STHdh cell models of HD. Therefore, p65/RelA activation may normalize the expression of some genes in HD.”

http://www.ncbi.nlm.nih.gov/pubmed/24360910

The agonist binding mechanism of human CB2 receptor studied by molecular dynamics simulation, free energy calculation and 3D-QSAR studies.

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“CB2-selective agonists have drawn attention in drug discovery, since CB2 becomes a promising target for the treatment of neuropathic pain without psychoactive or other CNS-related side effects…

A combinational exploration of both CoMFA steric and potential contour maps for CB2 affinities and the MD studied interaction modes sheds light on the structural requirements for CB2 agonists and serves as a basis for the design of novel CB2 agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/24358778

Cannabis Finds Its Way into Treatment of Crohn’s Disease.

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“In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases.

In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn’s disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions.”

http://www.ncbi.nlm.nih.gov/pubmed/24356243

“In their prospective study, Naftali et al. used THC-free Cannabis as placebo with no other cannabinoids present. However, we should consider that also other ingredients of Cannabis, such as cannabidiol, cannabigerol, and tetrahydrocannabivarine (THCV), all of them non-psychotropic components of Cannabis, have proven antiinflammatory effects in experimental intestinal inflammation. Their actions partly involve non-CB receptor mechanisms via, for instance, peroxisome proliferator-activated receptors (PPAR) and transient receptor potential cation channels subfamily V receptors (TRPV) and should be regarded as additive beneficial effects of Cannabis in the improvement of colitis in addition to THC-mediated effects.

 …an 8-week treatment with THC-rich Cannabis caused a decrease of the Crohn’s disease activity index (CDAI) in 90% of patients without producing significant side effects…

In summary, in agreement with the ancient use of Cannabis in intestinal disturbances and one decade of animal research, Cannabis was shown in a clinical trial to reduce symptoms in patients with CD. This elegant translation should be followed by larger trials confirming these results and by trials establishing the involved mechanisms to open a promising direction for future treatment of IBD.”

Full-text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076530/