Bogdan Szukalski

Układ endokannabinoidowy: charakterystyka, działanie i perspektywy zastosowań klinicznych

The endocannabinoid system: general view, function and perspectives of clinical applications. The endocannabinoid system is a lipid signalling system which has important regulatory function throughout the body. The main endocannabinoids are small molecules derived from arachidonic acid: N-arachidonoylethanolamide (anandamide-AEA), 2-arachidonoylglycerol (2-AG), 2-arachidonylglycerol ether (naladin, 2-AGE), O-arachidonoylethanolamide (virodhamine) and N-arachidonoyldopamine (NADA). They bind to a family of G-protein coupled receptors, of which CB1 receptor is densily distributed in areas of brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Endocannabinoids are produced and released "on demand" from lipid precursors in a receptor-dependent manner and serve as retrograde signalling messengers in GABA-ergic and glutamatergic synapses. They are transported into cells by a specific uptake system and degraded by two well-characterized enzymes: the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAG). Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers and potent selective inhibitors of endocannabinoids degradation. These new tools have opened up new strategies in the treatment of pain, obesity and neurological diseases, including multiple sclerosis.