Neurobiology and systems physiology of the endocannabinoid system.

Abstract

“Endocannabinoids are synthesised from lipid precursors, are released from postsynaptic neurons in an activity-dependent way, and act as retrograde signalling messengers on specific G (i)-protein-coupled cannabinoid (CB (1)) receptors on presynaptic terminals. Hence, endocannabinoids are in a strategic position to regulate transmitter release. CB (1)-receptors are abundant on GABAergic, glutamatergic and dopaminergic synapses and play an essential role in a variety of cognitive processes and in the control of behaviour. The endocannabinoid system is not only the target of the psychoactive components of the hemp plant (tetrahydrocannabinol from hashish and marijuana) but has also been exploited for drugs acting as agonists (e.g. dronabinol) or antagonists (e.g. rimonabant) of the CB (1)-receptor. The former drugs exert orexigenic effects and can be used for the mitigation of anorexia e.g. in cancer patients, but have also been used for the treatment of multiple sclerosis. The latter have been used to treat adipositas. The role of the endocannabinoid system in the development of drug dependence has been discussed controversially, but recent evidence suggests that chronic stimulation of the endocannabinoid system may facilitate drug dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/19434559

The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation.

Abstract

“The endocannabinoid signalling system includes: (1) at least two G-protein-coupled receptors, known as the cannabinoid CB(1) and CB(2) receptors and discovered following studies on the mechanism of action of Delta(9)-tetrahydrocannabinol, the major psychoactive principle of the hemp plant Cannabis sativa; (2) the endogenous agonists at these receptors, known as endocannabinoids, of which anandamide and 2-arachidonoylglycerol are the best known; and (3) proteins and enzymes for the regulation of endocannabinoid levels and action at receptors. The endocannabinoid system is quite widespread in mammalian tissues and cells and appears to play a pro-homeostatic role by being activated following transient or chronic perturbation of homeostasis, and by regulating in a local way the levels and action of other chemical signals. Compounds that selectively manipulate the action and levels of endocannabinoids at their targets have been and are being developed, and represent templates for potential new therapeutic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/19559360

An introduction to the endocannabinoid system: from the early to the latest concepts

Abstract

“A rather complex and pleiotropic endogenous signalling system was discovered in the late 1990s, starting from studies on the mechanism of action of Delta(9)-tetrahydrocannabinol, the major psychoactive principle of the hemp plant Cannabis sativa. This system includes: (1) at least two G-protein-coupled receptors, known as the cannabinoid CB(1) and CB(2) receptors; (2) the endogenous agonists at these receptors, known as endocannabinoids, of which anandamide and 2-arachidonoylglycerol are the best known; and (3) proteins and enzymes for the regulation of endocannabinoid levels and action at receptors. The number of the members of this endocannabinoid signalling system seems to be ever increasing as new non-CB(1) non-CB(2) receptors for endocannabinoids, endocannabinoid-related molecules with little activity at CB(1) and CB(2) receptors, and new enzymes for endocannabinoid biosynthesis and degradation are being identified every year. The complexity of the endocannabinoid system and of its physiological and pathological function is outlined in this introductory chapter, for a better understanding of the subsequent chapters in this special issue.”

http://www.ncbi.nlm.nih.gov/pubmed/19285257

Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (review).

Journal Cover

“The medicinal properties of extracts from the hemp plant Cannabis sativa have been known for centuries but only in the 90s membrane receptors for the Cannabis major principle were discovered in mammalian cells. Later on the endogenous ligands for the cannabinoid receptors were identified and the term ‘endocannabinoid system’ was coined to indicate the complex signaling system of cannabinoid receptors, endogenous ligands and the enzymes responsible for their biosynthesis and inactivation.

The ‘endocannabinoid system’ is involved in a broad range of functions and in a growing number of pathological conditions.

There is increasing evidence that endocannabinoids are able to inhibit cancer cell growth in culture as well as in animal models.

Most work has focused on the role of endocannabinoids in regulating tumor cell growth and apoptosis and ongoing research is addressed to further dissect the precise mechanisms of cannabinoid antitumor action. However, endocannabinoids are now emerging as suppressors of angiogenesis and tumor spreading since they have been reported to inhibit angiogenesis, cell migration and metastasis in different types of cancer, pointing to a potential role of the endocannabinoid system as a target for a therapeutic approach of such malignant diseases.

The potential use of cannabinoids to retard tumor growth and spreading is even more appealing considering that they show a good safety profile, regarding toxicity, and are already used in cancer patients as palliatives to stimulate appetite and to prevent devastating effects such as nausea, vomiting and pain.”  http://www.ncbi.nlm.nih.gov/pubmed/17342320

https://www.spandidos-publications.com/or/17/4/813

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Cannabinoids in the treatment of cancer.

“Cannabinoids, the active components of the hemp plant Cannabis sativa, along with their endogenous counterparts and synthetic derivatives, have elicited anti-cancer effects in many different in vitro and in vivo models of cancer. While the various cannabinoids have been examined in a variety of cancer models, recent studies have focused on the role of cannabinoid receptor agonists (both CB(1) and CB(2)) in the treatment of estrogen receptor-negative breast cancer. This review will summarize the anti-cancer properties of the cannabinoids, discuss their potential mechanisms of action, as well as explore controversies surrounding the results.”

http://www.ncbi.nlm.nih.gov/pubmed/19442435