The Relatively Unknown CB-3 and GPR55 Cannabinoid Receptors

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Although CB1 and CB2 receptors are often discussed; the lesser-known CB3 and GPR55 pose a great case for promoting medical Cannabis research.

These days, more and more folks have educated themselves about the links between specific cannabinoids, namely THC and CBD, and CB1 and CB2 receptors in the human body. However, little is mentioned in public about CB3 and GPR55 receptors and their actions. These receptors function as a gateway through which common phytocannabinoids (produced by plants) and endocannabinoids (produced by the human body, such as N-arachidonoylethanolamine, also known as anandamide, and 2-arachidonoylglycerol) can communicate with corporal systems and cause specific, desirable affects within humans. Such action is why medical Cannabis is so effective in treating a myriad of ailments. What is not so well-publicized, however, is cannabinoid activity related to two other receptors: CB3 and GPR55.

Over the past few decades, much research has been conducted that reveals the specific effects of certain cannabinoids. THC binds primarily to the CB1 receptor, resulting in not only the euphoric 'high' effect imparted by consumption of sativa-dominant strains (which are higher in THC content) but also specific medical success in treating ailments such as depression, nausea and certain types of pain. CBD actually responds to both CB1 and CB2 receptors – the latter of which controls more body-related issues, rather than having cerebral implications – allowing for the effective treatment of other types of pain, in addition to offering a muscle relaxant, sedative and anti-spasmodic effect. The efficacy of CBD in treating illnesses such as multiple sclerosis and epilepsy without resulting in a psychoactive intoxication is exactly why this type of medicine is now being widely pursued around the globe.

Cannabinoids create effects by activating or blocking what are known as G-protein-coupled receptors, often abbreviated to GPCR. One such site in the body is called GPR55, known as an 'orphan receptor', and its importance has been studied at a highly scientific level, yet the average user may not yet be aware of its existence. This is partially because, despite pharmaceutical giants GlaxoSmithKline and AstraZenica applying for a GPR55-related patent back in 2001, no peer-reviewed research supported the claim that GPR55 was indeed a cannabinoid receptor until an article was published in the British Journal of Pharmacology in 2007 [Ryberg et al]. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/]

In addition, the Ryberg findings note that “the endocannabinoid 2-arachidonoylglycerol displays more than 170 times greater potency as an agonist at GPR55 than at the CB1 or CB2 receptor and that Δ9-THC has greater efficacy (though not greater potency) as an agonist for GPR55 than for CB1 or CB2 receptors.”

A related 2007 study [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095104/?tool=pubmed] refers to GPR55 as a 'new' receptor, and states that “the main psychoactive constituent of Cannabis, Δ9-tetrahydrocannabinol, displayed greater efficacy at GPR55 than at CB1 or CB2 receptors.” This discovery from nearly a decade ago holds a significant clue for future medical Cannabis applications, as it would allow potential therapies to be more directly targeted and could also facilitate the development of better strain-matching techniques for treating specific ailments.

The study also states that, “GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by the non-psychoactive phytocannabinoid, cannabidiol.” It continues by outlining the pharmacological differences between GPR55, CB1 and CB2 receptors, pointing out that while some receptors are triggered by certain cannabinoids, others are blocked; this action reverses and/or varies, depending upon which receptor and which cannabinoid is being discussed. All of this information highlights the natural inclination of our bodies to accept cannabinoids as medicine, whether they are produced within our bodies or sourced from plants or synthetic means. Thus, cannabinoids are an effective, natural way to fix inadequacies in our systems – one that is purposeful and intended to actually help at a cellular level, rather than a simple ploy to get high, as opponents have been claiming.

Such discoveries also prove that medical Cannabis is not as straightforward as some people would prefer to believe, increasing the necessity of further study at a pharmacological level. If we are to continue promoting the efficacy of medical Cannabis, it is essential that further research is conducted, and studies such as this prove the need to do so. This helps to form a case in support of re-scheduling Cannabis and downgrading it from a Schedule I substance, so that universities, hospitals and research facilities may obtain access to and permission for medical Cannabis trials.

 

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