Hebrew University of Jerusalem; THE ENDOCANNABINOID SYSTEM

R.Mechoulam

The endocannabinoid system was unknown 15 years ago. Now we are aware of the
existence of 2 well defined cannabinoid receptors, with a few more in various stages of
discovery. Two endogenous cannabinoids, anandamide and 2-AG, have been found in the
brain and the periphery, and several more are being looked into. The enzymes associated
with their biosynthesis and degradation have been described. Hundreds of publications on
the actions of the endocannabinoid system have appeared.
Do they have a common denominator?
I would like to propose that the endocannabinoid system is part of the general protective
system of the mammalian body. We are all aware that the immune system is our guardian
against protein attacks, such as those caused by microorganisms. But certainly not all
potential damages are due to proteins. Neurodegenerative diseases, cancers, physical
traumas and many others are examples of non-protein attacks. The immune system is
certainly involved in the reactions of the body to the physiological changes that take place.
But the mammalian body has numerous other strategies to avoid or reduce damage. The
endocannabinoid system is known to react swiftly in cases of brain trauma, to affect cancer
cell proliferation, to be involved in damage control in numerous neurological diseases  –
multiple sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, ALS.
Tourette's disease, epilepsy.  Recent data indicates that it affects osteoporosis. And it is
certainly involved in the reaction of the body to cancer. Research on many of these
protective mechanisms has only started.  
 Like the immune system, the endocannabinoids may cause damage if they come to dinner
uninvited. In some cases enhancement of neurological damage has been noted.
An enormous amount of work has to be done before we can establish conclusively that the
central task of the endocannabinoid system is a protective one. Theories serve as catalysts
for novel ideas. And sometimes they are even correct.