Category Archives: Endocannabinoid System

Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing.

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“An immunomodulatory role for the endocannabinoid system in gastrointestinal inflammatory disorders has been proposed and this study sought to determine the location of both cannabinoid receptors in human colon and to investigate epithelial receptor function.

The location of CB1 and CB2 receptors in human colonic tissue was determined by immunohistochemistry…

Cannabinoids enhanced epithelial wound closure…

CONCLUSIONS:

CB1 receptors are expressed in normal human colon and colonic epithelium is responsive biochemically and functionally to cannabinoids. Increased epithelial CB2-receptor expression in human inflammatory bowel disease tissue implies an immunomodulatory role that may impact on mucosal immunity.”

http://www.ncbi.nlm.nih.gov/pubmed/16083701

Cannabinoid receptor type 2 is time-dependently expressed during skin wound healing in mice.

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“Dynamic localization of CB2R and quantitative analysis of CB2R mRNA during skin wound healing in mice were performed…

In conclusion, dynamic distribution and expression of CB2R suggest that CB2R is involved in modulating macrophages and myofibroblasts in response to inflammatory event and repair process in mouse skin wound healing, and CB2R is available as a marker for wound age determination.”

http://www.ncbi.nlm.nih.gov/pubmed/22814434

The cannabinoid receptor type 2 is time-dependently expressed during skeletal muscle wound healing in rats.

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“The expression of the cannabinoid receptor type 2 (CB2R) was investigated by immunohistochemistry, Western blotting, and RT-PCR during wound healing of contused skeletal muscle in rats with attempt of its applicability to skeletal muscle wound age estimation…

In conclusion, dynamic distribution and expression of CB2R suggest that CB2R be involved in modulating macrophages in response to inflammatory event in rat skeletal muscle wound healing and CB2R be available as a marker for wound age determination.”

[Expression of cannabinoid receptor I during mice skin incised wound healing course].

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“To investigate the expression of cannabinoid receptor I (CB1R) during mice skin incised wound healing course and time-dependent changes of CB1R in wound age determination…

The control group showed a low expression of CB1R detected mainly in epidermis, hair follicles, sebaceous gland and dermomuscular layer. CB1R expression was undetectable in neutrophils in the wound specimens from 6h to 12h post-injury.

The positive bands of CB1R were observed in all time points of the wound healing course…

CONCLUSION:

CB1R is activated during the wound healing course. The expression of CB1R is found in mononuclear cells, which could be involved in inflammation reaction. CBIR is observed in fibroblastic cells, which could participate in the wound healing. CB1R may be a potentially useful marker for determination of wound healing age.”

http://www.ncbi.nlm.nih.gov/pubmed/20967946

New Approaches in the Design and Development of Cannabinoid Receptor Ligands: Multifunctional and Bivalent Compounds.

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“Since the identification of the endocannabinoid system, two G protein-coupled receptors (GPCRs) of this complex system were identified and characterized: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R).

In addition to orthosteric and subsequently allosteric ligands, new strategies have been used to target CBRs.

Bivalent ligands and multifunctional ligands acting at diverse biological targets have been designed, synthesized, and characterized for both CBRs. Due to their altered receptor binding and pharmacological profiles, they are interesting tools to explore CBR functions and their interactions with other physiological systems.

Moreover, this approach may bear therapeutic advantages in the therapy of CBR-related disorders, especially multifactorial diseases.

Promising prospects include anorectics with fewer side effects, analgesics with decreased tolerance, and therapeutics with multiple pharmacological activities for the treatment of cancer, inflammation, multiple sclerosis, Huntington’s and Alzheimer’s diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25820617

Changes in the endocannabinoid signaling system in CNS structures of TDP-43 transgenic mice: relevance for a neuroprotective therapy in TDP-43-related disorders.

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“Because of their neuroprotective properties, cannabinoids are being investigated in neurodegenerative disorders, mainly in preclinical studies. These disorders also include amyotrophic lateral sclerosis (ALS), a degenerative disease produced by the damage of the upper and lower motor neurons leading to muscle denervation, atrophy and paralysis.

The studies with cannabinoids in ALS have been conducted exclusively in a transgenic mouse model bearing mutated forms of human superoxide dismutase-1, the first gene that was identified in relation with ALS.

The present study represents the first attempt to investigate the endocannabinoid system in an alternative model, the transgenic mouse model of TAR-DNA binding protein-43 (TDP-43), a protein related to ALS and also to frontotemporal dementia…

In conclusion, our data support the idea that the endocannabinoid signaling system, in particular the CB2 receptor, may serve for the development of a neuroprotective therapy in TDP-43-related disorders. We are presently engaged in pharmacological experiments to investigate this possibility.”

http://www.ncbi.nlm.nih.gov/pubmed/25819934

http://www.thctotalhealthcare.com/category/amyotrophic-lateral-sclerosis-als-lou-gehrigs-disease/

2-AG promotes the expression of conditioned fear via cannabinoid receptor type 1 on GABAergic neurons.

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“The contribution of two major endocannabinoids, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), in the regulation of fear expression is still unknown. We analyzed the role of different players of the endocannabinoid system on the expression of a strong auditory-cued fear memory in male mice by pharmacological means…

Our findings suggest that increased AEA levels mediate acute fear relief, whereas increased 2-AG levels promote the expression of conditioned fear primarily via CB1 on GABAergic neurons.”

http://www.ncbi.nlm.nih.gov/pubmed/25814137

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Cannabinoids to treat spinal cord injury.

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“Spinal Cord Injury (SCI) is a devastating condition for which there is no standard treatment beyond rehabilitation strategies. In this review, we discuss the current knowledge on the use of cannabinoids to treat this condition.

The endocannabinoid system is expressed in the intact spinal cord, and it is dramatically upregulated after lesion. Endogenous activation of this system counteracts secondary damage following SCI, and treatments with endocannabinoids or synthetic cannabinoid receptor agonists promote a better functional outcome in experimental models.

The use of cannabinoids in SCI is a new research field and many questions remain open. Here, we discuss caveats and suggest some future directions that may help to understand the role of cannabinoids in SCI and how to take advantage of this system to regain functions after spinal cord damage.”

http://www.ncbi.nlm.nih.gov/pubmed/25805333

http://www.thctotalhealthcare.com/category/spinal-cord-injury/

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

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“In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse.

This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/25801289

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

The Medicinal Chemistry of Cannabinoids.

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“The endocannabinoid system (ECS) comprises the two well characterized Gi/o -protein coupled receptors (CB1, CB2), their endogenous lipid ligands and the enzymes involved in their biosynthesis and biotransformation.

Drug discovery efforts relating to the ECS have been focused mainly on the two cannabinoid receptors and the two endocannabinoid deactivating enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL).

This review provides an overview of cannabinergic agents used in drug research and those being explored clinically.”

 http://www.ncbi.nlm.nih.gov/pubmed/25801236