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articles illustrate the principle that eCB tone maintains the ECS and its neuroprotective effects without requiring a boost from cannabinergic compounds. However, if eCB tone is low, cannabis and other cannabinergic compounds can provide a re-boot to ECS function.
eCB tone is maintained by eCB receptors (CB1, CB2), their endogenous ligands, called
eCBs (Anandamide, 2-Arachidonoylglycerol), and their degradative enzymes (FAAH, MAGL). Although THC was discovered in 1964 by Dr. Raphael Mechoulam, its mechanism of action was unknown until 1988, when Allyn Howlett and associates characterized the first eCB receptor, CB1, in the brain of a rat (Devane et al. 1988).
Munro et. al. (1993) characterized a second eCB receptor, CB2, in the spleen. Large numbers of CB2 receptors are also found in immune-tissues, accounting for the immune-modulatory and anti-inflammatory effects of the ECS (Sugiura & Waku 2000; Joy, Watson & Benson 1999). Although CB2 was thought to be located mainly in peripheral tissues, it is now well established that these receptors express in CNS tissue in contexts of neuro-inflammation (Atwood & Mackie 2010).
This article focuses on the well-known ECS receptors CB1 and CB2. However, other ECS receptors are under investigation. These receptors include, but are not limited to, TRPV1 (“vanilloid receptor”), important in hyperalgesia/neuropathic pain (Costa et al. 2004), and GPR55 (“orphan receptor”), important in cancer (Hu, Ren & Shi 2011).
eCB tone is maintained by the interaction of neuro-modulatory lipids, called eCBs, with the ECS receptors described above. In some professional literature, eCBs are referred to as neurotransmitters. The first eCB, discovered in 1992 by William Devane and associates, was given the name “Anandamide” (AEA) after the Sanskrit word meaning “bliss” (Devane et al. 1992).
Although AEA does not resemble THC in structure, its effect at the CB1 receptor, such as decreased muscle spasticity and emotional modulation of pain, is identical to THC (Maccarrone et al. 2015).
Three years after the discovery of AEA, Mechoulam and associates discovered a second eCB, 2-Arachidonoylglycerol (2-AG), with activity at CB1 and CB2 receptors (Mechoulam et al. 1995). 2-AG is more abundant than AEA (Shohami et. al. 2011) and dramatically increases in the presence of traumatic brain injury, stroke, obesity, Parkinson’s disease, and multiple sclerosis (Brose 2016).