Cannabinoid Agonists

The studies on the possible mechanism of action of derivatives of the Cannabis and, of consequence, on their own prospective therapeutic applications, endured an unexpected acceleration with the discovery of specific receptors for the THC and endogenous ligands for such proteins.

Up to now two types of receptors for the THC and its synthetic derivates have been characterized: CB1 receptor, discovered in 1990, mostly expressed in the nervous system and some peripheral tissue, and CB2 receptor, singled out for the first time in 1993 and till now identified only in the immune system cells of the mammals.

To the discovery of CB1 receptor immediately followed up, in 1992, the isolation, from the pig's brain, of the first endogenous compound in a position to tying itself selective to such protein: it was the amide formed by ethanolamin and arachidonic acid, two ubiquitous components of animal cellular membranes, called "anandamide" (from the Sanskrit word "ananda" that means "inner serenity").

Subsequently others two structural analogous of the "anandamide" were isolated still from the pig's brain, while another type of molecule, pertaining to the class of metabolic intermediates known as monoacylglycerols, was identified in peripheral tissues and set as CB2 receptor ligand: 2-arachidonoyl-glycerol (2-AG).

Afterwards anandamide and its analogous were discovered to preferentially activate CB1 receptor, while 2-AG, that it is also present in mammals brain, can indifferently activate both types of receptors for THC.

The discovery of receptors for the THC and endogenous molecules in a position to activating such proteins, simulating therefore in great part the typical Cannabis psychotropic effects, demonstrated the existence of an endogenous cannabinoid system whose physiological role is still a debate subject, and whose future study will be able to carry to the understanding of molecular mechanisms that are the base of the abuse of chemical compounds contained in the Indian hemp, and to developing, on the base of the well known therapeutic properties of such plant, new drugs high therapeutic potential for the treatment of the nervous, immune and cardiovascular system diseases.