Endocannabinoid signaling in innate and adaptive immunity.

“The immune system can be modulated and regulated not only by foreign antigens but also by other humoral factors and metabolic products, which are able to affect several quantitative and qualitative aspects of immunity.

Among these, endocannabinoids are a group of bioactive lipids that might serve as secondary modulators, which when mobilized coincident with or shortly after first-line immune modulators, increase or decrease many immune functions.

Most immune cells express these bioactive lipids, together with their set of receptors and of enzymes regulating their synthesis and degradation.

In this review, a synopsis of the manifold immunomodulatory effects of endocannabinoids and their signaling in the different cell populations of innate and adaptive immunity is appointed, with a particular distinction between mice and human immune system compartments.”

http://www.ncbi.nlm.nih.gov/pubmed/25585882

Endocannabinoid System

Wiley

“The endocannabinoid system (ECS) is defined as the signalling system composed of: (1) the two G‐protein‐coupled receptors known as cannabinoid receptors of type‐1 and ‐2 (CB1 and CB2); (2) the two most studied endogenous agonists of such receptors, the endocannabinoids anandamide (N‐arachidonoyl‐ethanolamine) and 2‐AG (2‐arachidonoyl‐glycerol); (3) enzymes and other proteins regulating the tissue levels of endocannabinoids; and (4) enzymes and other proteins that, together with endocannabinoids, regulate the activity of cannabinoid receptors.

A key role of the ECS is emerging in the control not only of central and peripheral nervous system functions, but also of most aspects of mammalian physiology, including energy intake, processing and storage, the immune response, reproduction and cell fate.

The ECS is also subject to dysregulation, and this seems to contribute to the symptoms and progress of several diseases. Hence, the possibility of developing new therapies starting from our increasing knowledge of the ECS is discussed.”

http://www.els.net/WileyCDA/ElsArticle/refId-a0023403.html

http://www.thctotalhealthcare.com/category/endocannabinoid-system/

Interaction of cannabinoid receptor 2 and social environment modulates chronic alcohol consumption.

“Genetic and environmental factors contribute nearly with equal power to the development of alcoholism. Environmental factors, like negative life events or emotionally disruptive conditions initiate and promote alcohol drinking and relapse.

The endocannabinoid system is involved in hedonic control and modulates stress reactivity. Furthermore, chronic alcohol drinking alters endocannabinoid signalling, which in turn influences the stress reactivity.

Recently it has been shown that CB2 receptor activity influences stress sensitivity and alcohol drinking. We hypothesised that CB2 receptors influence the impact of environmental risk factors on alcohol preference and consumption. Therefore, in this study we investigated the alcohol-drinking pattern of wild type and CB2 deficient animals under single and group housing conditions using different alcohol drinking models, like forced drinking, intermittent forced drinking and two-bottle choice paradigms.

Our data showed that CB2 receptor modulates alcohol consumption and reward.

Interestingly, we detected that lack of CB2 receptors led to increased alcohol drinking in the intermittent forced drinking paradigm under group housing conditions.

Furthermore, we found that CB2 knockout mice consumed more food and that their body weight gain was modulated by social environment.

On the base of these data, we conclude that social environment critically affects the modulatory function of CB2 receptors especially in alcohol intake.

These findings suggest that a treatment strategy targeting CB2 receptors may have a beneficial effect on pathologic drinking particularly in situations of social stress and discomfort.”

Propagation through alginate encapsulation of axillary buds of Cannabis sativa L. — an important medicinal plant

“Cannabis sativa L. (Cannabaceae) is an important medicinal plant well known for its pharmacologic and therapeutic potency…

These plants are selected to be used in mass cultivation for the production of biomass as a starting material for the isolation of THC as a bulk active pharmaceutical.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550375/

http://www.thctotalhealthcare.com/category/thc-delta-9-tetrahydrocannabinol/

 

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

“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.

“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.

“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].

“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

Drugs of abuse and parkinson’s disease.

“The term “drug of abuse” is highly contextual. What constitutes a drug of abuse for one population of patients does not for another. It is therefore important to examine the needs of the patient population to properly assess the status of drugs of abuse. The focus of this article is on the bidirectional relationship between patients and drug abuse. In this paper we will introduce the dopaminergic systems of the brain in Parkinson’s and the influence of antiparkinsonian drugs upon them before discussing this synergy of condition and medication as fertile ground for drug abuse. We will then examine the relationship between drugs of abuse and Parkinson’s, both beneficial and deleterious. In summary we will draw the different strands together and speculate on the future merit of current drugs of abuse as treatments for Parkinson’s disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25816790

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

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

“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