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Research CB2 receptor proliferation as an anti-inflammatory response in the brain

herbivore21

Well-Known Member
Welcome to our first scientific research topic in the Cannabis Research section.

I draw on the following article for the CB2 related mechanisms that we discuss in this thread (this link is fortunately available to all of you to read in full text - I will try to use such articles wherever possible): http://www.academia.edu/1897039/Cannabinoid_CB2_receptors_in_human_brain_inflammation

We should always start these topics with definitions of key terms. I want to start by defining key concepts to this discussion. I should note that whilst I have used wikipedia articles here, wikipedia should only be used as a source when you can confirm that what you have found at wikipedia is supported by scholarly research evidence. The following definitions check out in this sense, and so I share them here.

Upregulation: "The process, in the regulation of gene expression, in which the number, or activity of receptors increases in order to increase sensitivity [to a relevant receptor agonist - agonists are any compound which binds with that receptor to stimulate corresponding activity]." (Source: Wiktionary)

In Vivo: "Studies that are in vivo those in which the effects of various biological entities are tested on whole, living organisms, usually animals, including humans, and plants as opposed to a partial or dead organism, or those done in vitro, i.e., in a laboratory environment" (Source: Wikipedia)

In Vitro: "In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines have traditionally been done in test tubes, flasks, Petri dishes, etc., and since the onset of molecular biology, involve techniques such as the omics. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms. In contrast, in vivo studies are those conducted in animals, including humans, and whole plants." (Source: Wikipedia)

In this thread, I wanted to raise a fascinating finding of a recent body of research literature.

It seems that CB2 receptors, when activated stimulate a reduction in pro-inflammatory molecules in human and animal brains (most of the research at this stage is in vitro, see p. 278 of the source linked at the top of this post). This can be understood as an anti-inflammatory mechanism of action that results from activation/binding at the CB2 receptor.

CB2 receptors are found throughout the brain, gut and at other sites in the human body and in assorted parts of the bodys of various animals. Endocannabinoids that bind with and stimulate activity at the CB2 receptors include (but are not necessarily limited to) 2-AG and AEA (aka anandamide). Phytocannabinoids that stimulate the CB2 receptor include CBD, CBC and to a lesser extent, THC (which is a weaker agonist of the receptor than CBD, for example). Another terpenoid/cannabinoid (yes, this is a cannabinoid, because it acts on a cannabinoid receptor) that acts on the CB2 receptor is Beta-Caryophyllene - the compound responsible for the black pepper-like smell and taste in many cannabis varieties.

Consider the following quote:

"As pointed out by Maresz et al. (2005), the upregulation of cannabinoid CB2 receptors also takes place in vivo, and seems to be triggered by chronic inflammatory conditions." (pp. 278-279)

What is being said here, is that when ongoing inflammation occurs in the body (particularly the brain) in a living animal (namely humans in our case), the body appears to respond by creating more CB2 receptor sites in that region of the body, which can then be activated by endogenous cannabinoids (not to mention plant derived cannabinoids with similar receptor affinities!), which can lead to the abovementioned reduction in pro-inflammatory molecules.

I am sure you all reading now can see obvious implications for cannabis as medicine, especially in individuals who suffer from endocannabinoid deficiencies (examples include people with Fragile X syndrome, who can experience a mutation at the Neurologin-3 gene which prevents their body from synthesizing this crucial precursor to endocannabinoids like 2-AG and AEA - these people may benefit from substituting with phytocannabinoids to promote the above anti-inflammatory response).

Isn't cannabis a wonderful thing? Please feel free to ask questions and discuss any thoughts you might have on this one.

Thanks for reading, I hope this was as interesting for you to read as it was for me to write!
 
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