Category Archives: Endocannabinoid System

Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.

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“Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited.

Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication…

In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity.”

http://www.ncbi.nlm.nih.gov/pubmed/25933444

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine.

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“Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate.

Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity.

URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury.

Using confocal liver intravital microscopy, we observed that CBD reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure.

Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics.

These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/25999668

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427116/

Lipid nanoparticles as an emerging platform for cannabinoid delivery: physicochemical optimization and biocompatibility.

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“This work aims at developing and optimizing a valuable oral delivery carrier for the cannabinoid derivative CB13, which presents a high therapeutic potential in chronic pain states that respond poorly to conventional analgesics, but also shows highly unfavorable physicochemical properties.

CB13-loaded lipid nanoparticles (LNP) formulations were developed…

The LNP formulation proposed proved to be a promising carrier for the oral delivery of CB13, a cannabinoid with high therapeutic potential in chronic pain states that currently lack a valid oral treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25996463

Synthetic and endogenous cannabinoids protect retinal neurons from AMPA excitotoxicity in vivo, via activation of CB1 receptors: Involvement of PI3K/Akt and MEK/ERK signaling pathways.

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“Cannabinoids have been suggested to protect retinal ganglion cells in different models of toxicity…

These results suggest that endogenous and synthetic cannabinoids protect retinal amacrine neurons from AMPA excitotoxicity in vivo via a mechanism involving the CB1 receptors, and the PI3K/Akt and/or MEK/ERK1/2 signaling pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/25989217

Anxiety, Stress, and Fear Response in Mice with Reduced Endocannabinoid Levels.

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Disruption of the endocannabinoid system through pharmacological or genetic invalidation of cannabinoid CB1 receptors has been linked to depression in humans and depression-like behaviors in mice.

We generated and used knockout mice lacking DAGL-α (Dagla-/-) to assess the behavioral consequences of reduced endocannabinoid levels in the brain…

Our findings demonstrate that the deletion of Dagla adversely affects the emotional state of animals and results in enhanced anxiety, stress, and fear responses.”

http://www.ncbi.nlm.nih.gov/pubmed/25981172

A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.

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“We have previously shown that agonists selective for the cannabinoid receptor 2 (CB2), including O-1966, inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ graft rejection, predominantly through effects on T-cells. Current studies explored the mechanism of this immunosuppression by O-1966 using mouse spleen cells…

These data support the potential of CB2-selective agonists as useful therapeutic agents to prolong graft survival in transplant patients, and strengthens their potential as a new class of immunosuppressive agents with broader applicability.”

http://www.ncbi.nlm.nih.gov/pubmed/25980325

Endocannabinoid-mediated improvement on a test of aversive memory in a mouse model of fragile X syndrome.

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“Silencing the gene FMR1 in fragile X syndrome (FXS) with consequent loss of its protein product, FMRP, results in intellectual disability, hyperactivity, anxiety, seizure disorders, and autism-like behavior. In a mouse model (Fmr1 knockout (KO)) of FXS, a deficit in performance on the passive avoidance test of learning and memory is a robust phenotype.

We report that drugs acting on the endocannabinoid (eCB) system can improve performance on this test.

Our results indicate that the eCB system is involved in FXS and suggest that the eCB system is a promising target for treatment of FXS.”

http://www.ncbi.nlm.nih.gov/pubmed/25979787

http://www.thctotalhealthcare.com/category/fragile-x-syndrome-fxs/

Endocannabinoid and ceramide levels are altered in patients with colorectal cancer.

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“Endocannabinoids and ceramides have demonstrated growth inhibition, cell death induction and pro-apoptotic activity in cancer research.

In the present study, we describe the profiles of two major endocannabinoids, ceramides, free fatty acids and relevant metabolic enzymes in 47 pairs of human colorectal cancer tissues and adjacent non-tumor tissues…

Elevation of AEA and alteration of ceramides (C16, C24, C18, C20) may qualify as potential endogenous biomarkers and novel drug targets for colorectal cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/25975960

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

The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueduactal Grey.

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“Emerging evidence indicates the involvement of GPR55 and its proposed endogenous ligand, lysophosphatidylinositol (LPI), in nociception…

Thus, we provide the first pharmacological evidence that GPR55 activation at central levels is pronociceptive, suggesting that interfering with GPR55 signaling in the PAG may promote analgesia.”

http://www.ncbi.nlm.nih.gov/pubmed/25972448

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

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“The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer.

Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25970609