Targeting Cutaneous Cannabinoid Signaling in Inflammation – A “High”-way to Heal?

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“The endocannabinoid system (ECS) is a recently emerging complex regulator of multiple physiological processes. It comprises several endogenous ligands (e.g. N-arachidonoylethanolamine, a.k.a. anandamide [AEA], 2-arachidonoylglycerol [2-AG], palmitoylethanolamide [PEA], etc.), a number of endocannabinoid (eCB)-responsive receptors (e.g. CB1 and CB2, etc.), as well as enzymes and transporters involved in the synthesis and degradation of the eCBs.

Among many other tissues and organs, various members of the ECS were shown to be expressed in the skin as well. Indeed, AEA, 2-AG, CB1 and CB2 together with the major eCB-metabolizing enzymes (e.g. fatty acid amide hydrolase [FAAH], which cleaves AEA to ethanolamine and pro-inflammatory arachidonic acid) were found in various cutaneous cell types. Importantly, the eCB-tone and cannabinoid signaling in general appear to play a key role in regulating several fundamental aspects of cutaneous homeostasis, including proliferation and differentiation of epidermal keratinocytes, hair growth, sebaceous lipid production, melanogenesis, fibroblast activity, etc.

Moreover, appropriate eCB-signaling through CB1 and CB2 receptors was found to be crucially important in keeping cutaneous inflammatory processes under control.

Collectively, these findings (together with many other recently published data) implied keratinocytes to be “non-classical” immune competent cells, playing a central role in initiation and regulation of cutaneous immune processes, and the “c(ut)annabinoid” system is now proven to be one of their master regulators.

Another recently emerging, fascinating possibility to manage cutaneous inflammation through the cannabinoid signaling is the administration of phytocannabinoids (pCB). Cannabis sativa contains over 100 different pCBs, the vast majority of which have no psychotropic activity, and usually possess a “favorable” side-effect profile, which makes these substances particularly interesting drug candidates in treating several inflammation-accompanied diseases.

With respect to the skin, we have recently shown that one of the best studied pCBs, (−)-cannabidiol (CBD), may have great potential in managing acne, an inflammation-accompanied, extremely prevalent cutaneous disease.

Collectively, in light of the above results, both increase/restoration of the homeostatic cutaneous eCB-tone by FAAH-inhibitors and topical administration of non-psychotropic pCBs hold out the promise to exert remarkable anti-inflammatory actions, making them very exciting drug candidates, deserving full clinical exploration as potent, yet safe novel class of anti-inflammatory agents.”

http://www.ebiomedicine.com/article/S2352-3964(17)30003-8/fulltext

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Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.

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

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Melissa Etheridge: Pot changed my life, singer advocates legalization of marijuana

WPTV Melissa Etheridge
 

“My friends have always told me that rock stardom was wasted on me.

To them it seemed that being a rock star was a free ticket to debauchery. It was sex, drugs and rock ‘n’ roll, and I was only taking advantage of two. Drugs were not a part of my rock ‘n’ roll lifestyle. I wasn’t even much of a drinker. I have never thrown up from being over intoxicated.

What kind of rock star is that? I had certainly encountered drugs during the ’80s, mostly cocaine, but nothing about grinding my teeth and rambling on about myself appealed to me. During the ’90s, I smoked an occasional joint. Those were usually fun social occasions. My work was a drug-free zone.

Then in 2004, I was diagnosed with breast cancer. The chemotherapy that was prescribed was called “dose dense”: a harsher, stronger chemo than the usual because I had the benefit of not having to work during the treatment. My close friends told me that, as an alternative, medical marijuana was a natural way to help with the excruciating side effects of chemo.

It worked. The entire experience changed my life. It opened my mind to a new way of thinking about my body, my health and the future.

This herb, this weed that is so strong it grows wild by the side of the road, has always been with us. In ancient times it was highly regarded and has even been found in tombs. It has even been put forth from some biblical scholars that Jesus may have used cannabis oil to heal.

Now, this herb, marijuana, is at center of a debate within our society….

More: http://www.wptv.com//dpp/entertainment/melissa-etheridge-pot-changed-my-life-singer-advocates-legalization-of-marijuana

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