Tag Archives: cannabinoid receptors

A Cannabinoid CB1 Receptor Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with no Psychoactive Effects.

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“The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states.

However, therapeutic applications of Δ9-tetrahydrocannabinol (THC) and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects…

These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26052038

Targeting cannabinoid receptors as a novel approach in the treatment of graft-versus-host disease: evidence from an experimental murine model.

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“Allogeneic hematopoietic cell transplantation (HCT) is widely used to treat patients with life-threatening malignant and nonmalignant hematological diseases. However, allogeneic HCT often is accompanied by severe and lethal complications from graft-versus-host disease (GVHD)…

Cannabinoids, the active ingredients found in Cannabis sativa, have been shown to exhibit a wide range of pharmacological properties. Studies from our laboratory and elsewhere have suggested that cannabinoids exhibit potent anti-inflammatory properties and therefore can be used to treat autoimmune and inflammatory diseases.

Cannabinoids have been shown to inhibit tumor cell growth and angiogenesis, suggesting their potential use in the treatment of gliomas, prostate and breast cancers, and malignancies of immune origin.

Δ9-Tetrahydrocannabinol (THC) is one of the most extensively investigated ingredients found in cannabis. THC activates both CB1 and CB2, thereby mediating both psychotropic and anti-inflammatory properties.

Inasmuch as our previous studies suggested that THC exhibits anti-inflammatory and immunosuppressive properties, we tested the possibility of its use in treating GVHD in a parent → F1 model. We hereby demonstrate for the first time that administration of THC during allogeneic transplantation can significantly suppress GVHD…

Our results demonstrate for the first time that targeting cannabinoid receptors may constitute a novel treatment modality against acute GVHD.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164345/

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells.

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“Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression.

Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts…

Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection.”

http://www.ncbi.nlm.nih.gov/pubmed/26034207

Primary Macrophage Chemotaxis Induced by Cannabinoid Receptor 2 Agonists Occurs Independently of the CB2 Receptor.

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“Activation of CB2 has been demonstrated to induce directed immune cell migration. However, the ability of CB2 to act as a chemoattractant receptor in macrophages remains largely unexplored…

Taken together our results conclusively demonstrate that CB2 is not a chemoattractant receptor for murine macrophages. Furthermore we show for the first time that JWH133, HU308, L-759,656 and L-759,633 have off-target effects of functional consequence in primary cells and we believe that our findings have wide ranging implications for the entire cannabinoid field.”

http://www.ncbi.nlm.nih.gov/pubmed/26033291

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

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“We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size…

We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia…”

http://www.ncbi.nlm.nih.gov/pubmed/26032254

http://www.thctotalhealthcare.com/category/stroke-2/

Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.

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Cannabinoid CB1 receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail…

In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis.”

http://www.ncbi.nlm.nih.gov/pubmed/26024113

http://medical-dictionary.thefreedictionary.com/chemotaxis

Cannabinoid receptor CB1 regulates STAT3 activity and its expression dictates the responsiveness to SR141716 treatment in human glioma patients’ cells.

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“Herein we show that a majority of human brain tumor samples and cell lines over-expressed cannabinoid receptor CB1 as compared to normal human astrocytes (NHA), while uniformly expressed low levels of CB2. This finding prompted us to investigate the therapeutic exploitation of CB1 inactivation by SR141716 treatment, with regard to its direct and indirect cell-mediated effects against gliomas…

These results indicate that CB1 and STAT3 participate in a new oncogenic network in the complex biology of glioma and their expression levels in patients dictate the efficacy of the CB1 antagonist SR141716 in multimodal glioma destruction.

CB1 is implicated in the regulation of cellular processes linked to survival, proliferation, invasion and angiogenesis in several physio-pathological conditions. We shed light on previously unrecognized molecular mechanism of CB1-mediated modulation of human glioma progression and provide the first and original demonstration of CB1-STAT3 axis as a new target and predictor biomarkers of the benefit from specific therapies.

Indeed CB1 antagonism capable of tumoral cell division’ control while making the glioma immunovisible and engaging the immune system to fight it may represent a hopeful alternative to other established chemotherapeutics.

Because different aspects of glioma biology have been separately targeted with very limited success, we speculate that CB1 inhibitors which enclose in the same molecule cytotoxic potential and high activity to boost competent immune surveillance mechanisms, at a degree that seems to be correlated to the levels of CB1 immunoreactivity, might have profound implications for exploring new therapeutic anti-glioma actions.”

http://www.ncbi.nlm.nih.gov/pubmed/26008966

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

Prenatal elevation of endocannabinoids corrects the unbalance between dopamine systems and reduces activity in the Naples High Excitability rats.

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“Several evidences suggest that endocannabinoids exert a neurotrophic effect on developing mesencephalic dopamine neurons.

Since an altered mesocorticolimbic system seems to underlie hyperactivity and attention deficit in clinical and animal studies of attention deficit hyperactivity disorder(ADHD), prenatal elevation of anandamide has been induced…

The data suggest a corrected unbalance between the two dopamine systems that apparently leads to reducedhyperactivity and modified scanning times in this animal model of ADHD.

This, in turn, might open new strategies in the treatment of a subset of ADHD cases.”

http://www.ncbi.nlm.nih.gov/pubmed/12732229

Association between cannabinoid receptor gene (CNR1) and childhood attention deficit/hyperactivity disorder in Spanish male alcoholic patients

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“The CB1 receptor is encoded by the CNR1 gene (6q14–q15), which is known to carry a nine-allele microsatellite polymorphism containing repeats of a single trinucleotide, ATT, which localizes to the 3’UTR of the gene and has been related to drug dependency states in Caucasian populations.

Moreover, a link has been found between this polymorphism and the properties of the event-related wave p300, some studies having suggested that p300 variations might function as a marker for an underlying, hereditary, predisposition to alcoholism.

Moreover, a direct relationship has been found between p300 wave fluctuations and attention deficit/hyperactivity disorder (ADHD). In recent years, the relationship between ADHD and addictions has been stressed. ADHD has been linked to the malfunctioning of catecholaminergic systems, which also play a fundamental role in the brain’s rewarding system.

These data suggest that the link between the cannabinoid system and the p300 wave could be related to some aspects of ADHD.

In this study, we found a quantitative relationship between the largest-sized alleles of the CNR1 gene and the presence of ADHD during childhood in Spanish male alcoholic patients…

To the best of our knowledge, this is the first study relating the CNR1-gene polymorphisms with ADHD in alcoholic patients.

These data are consistent with the fact that the cannabinoid system is known to affect dopaminergic transmission, with the malfunctioning of the dopaminergic system being regarded as a potential physiopathological cause of ADHD. Further studies are needed to determine the functional basis of the observed association.”

http://www.nature.com/mp/journal/v8/n5/full/4001278a.html

Subtypes of attention deficit-hyperactivity disorder (ADHD) and cannabis use.

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“The current study examined the association between subtypes of attention-deficit/hyperactivity disorder (ADHD) and cannabis use within a sample of 2811 current users.

When asked about the ADHD symptoms they have experienced when not using cannabis, a higher proportion of daily users met symptom criteria for an ADHD diagnoses of the subtypes that include hyperactive-impulsive symptoms than the inattentive subtype.

For nondaily users, the proportions of users meeting symptom criteria did not differ by subtype.

These results have implications for identifying which individuals with ADHD might be more likely to self-medicate using cannabis. Furthermore, these findings indirectly support research linking relevant cannabinoid receptors to regulatory control.”

http://www.ncbi.nlm.nih.gov/pubmed/24093525