The endocannabinoid system is a homeostatic regulator of neuronal activity and almost every other physiological system in the body. It has a regulatory role on pain, inflammation, memory, emotion, sleep and metabolic function.
Even though much is still yet be known about the endocannabinoid system, a PubMed search reveals more than 1500 studies and reviews have been published in this area of science. There is a growing interest in the endocannabinoid system, particularly as it presents a promising therapeutic target for a wide array of disorders.
Discovery of Endocannabinoid System
Even though d9-THC was discovered in 1964, it was after a long period of time the first receptor in Endocannabinoid System, cannabinoid receptor type 1 (CB1), was characterized. It was done so in 1988 by a team of scientists lead by Allyn Howlett and William Devane at the St. Louis University Medical School in Missouri.
The receptor is predominantly located in the central nervous system. The endocannabinoid system, largely through the action of CB1 receptors, modulates the release of neurotransmitters. This is particularly relevant for chronic pain and spasticity related diseases, in which there is an overstimulation of neurons which lead to the disease.
William Devane, and his research group at the Hebrew University, then went on to discover the first endocannabinoid in 1992. It was named Anandamide which was based on the Sanskrit word for bliss, “ananda” or आनन्द.
The second cannabinoid receptor, Cannabinoid Receptor type 2 (CB2), was discovered in 1993 at the University of Cambridge in a study lead by Sean Munro. The CB2 receptors are predominantly located in the periphery, particularly on the cells of the immune system. The CB2 receptor can play a key immunomodulatory role, especially for autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and psoriasis.
The second endocannabinoid to be discovered was 2-arachidonoylglycerol (2-AG) by a group of scientists lead by Raphael Mechoulam at the Hebrew University in 1995.
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The endocannabinoid system includes other endogenous compounds and receptors
As time passes, more knowledge is being accumulated on the endocannabinoid system. Other endogenous compounds have been found to interact with the endocannabinoid system, such as Noladin ether and virodhamine.
Thermosensitive transient receptor potential (TRP) cat-ion channels (thermo-TRPs) are receptors which govern temperature regulation. These receptors are activated by active compounds from garlic (allicin), chilli pepper (capsaicin) and peppermint (menthol).
In 1999, research led by Peter M. Zygmunt showed that anandamide activated TRPV1 channels], a receptor channel activated by capsaicin (causes the spiciness of chilli peppers). In 2013, Peter M. Zygmunt later demonstrated that 2-AG also showed activity at this receptor. Anandamide was later also found to antagonize TRP channels of melastatin type-8 (TRPM8), a receptor which is activated by low temperatures and menthol.
The third cannabinoid receptor was discovered using cloning techniques in 1999 and it was named GPR55. Much is yet to be discovered on the implications of this receptor, but it has been found that the receptor has a wide array of ligands, including both THC and CBD!
A new definition of Endocannabinoid System offered
Findings released from the Endocannabinoid Research Group in Italy showed that a large spectrum of cannabinoids had activity at the TRP channels. Henceforth they have been warped into the definition of the endocannabinoid system. As described by Vincenzo Di Marzo and Fabiana Piscitelli,
“The ensemble of endocannabinoids, endocannabinoid-like mediators, and theird several receptors and metabolic enzymes could then be defined as the “endocannabinoidome”
Recent research has demonstrated that active compounds from other plants species such as Carrot (Daucus carota), kava (Piper methyscum), New Zealand liverwort (Radula marginata), Ginger (Zingiber officinale) and Black pepper (Piper nigrum) contain compounds which interact with the endocannabinoid system.
By Abdul Rehman Mohammad, BSc