Endocannabinoid system in health and sickness

Endogeni kanabinoidni sustav čini skupina receptora u organizmu sisavaca, njihovih liganada, enzima koji sudjeluju u stvaranju endogenih kanabinoida, kao i njihovoj razgradnji. Endokanabinoidni sustav posreduje brojne fiziološke učinke te igra važnu ulogu u različitim patološkim procesima. U ovom radu opisana je fiziološka funkcija endokanabinoidnog sustava, posebnosti endokanabinoidnih receptora i njihovih liganada, njihova uloga u različitim patofiziološkim procesima, farmakološke mogućnosti manipulacije tim sustavom te potencijalne terapijske indikacije. Danas znamo da je endokanabinoidni sustav uključen u modulaciju nocicepcije, upalnih procesa, apetita, sna, termogeneze, imunosnog odgovora, kognitivnih funkcija, a vjerojatno i drugih fizioloških funkcija i patoloških stanja. To govori da je proces otkrivanja raznih staničnih, fizioloških i farmakoloških procesa uzrokovanih agonizmom ili antagonizmom kanabinoidnih receptora još uvijek aktualan i istraživačima zanimljiv. Distribucija receptora u organizmu ostavlja puno mogućnosti za farmakološku manipulaciju. Raznolikost liganada za kanabinoidne receptore, od endogenih do egzogenih, biljnih i sintetskih kanabinoida (tetrahidrokanabinol, kanabidiol, kanabivarin; nabilon, dronabinol i mnogi drugi) također proširuje spektar potencijalnih terapijskih pristupa za razne indikacije; od kojih su neke već utvrđene i odobrene (mučnina i povraćanje kod kemoterapije i radioterapije, gubitak apetita i tjelesne mase kod AIDS-a), dok su druge još uvijek nedovoljno istražene. Usprkos svim saznanjima o mogućim koristima manipulacije endokanabinoidnim sustavom, možemo zaključiti da smo ipak daleko od cilja. Potrebna su daljnja pretklinička istraživanja kako bismo dobili još bolji uvid u fiziološke i patološke procese koji su pod većim ili manjim utjecajem endokanabinoidnog sustava, ali i dobro dizajnirana klinička ispitivanja kako bi se utvrdio farmakološki profil potencijalnih novih molekula s djelovanjem na endokanabinoidni sustav.Endogenous cannabinoid system is comprised of a number of receptors, their ligands, and enzymes with a function in synthesis and degradation of endogenous cannabinoids. Endocannabinoid system is a part of many physiological mechanisms and plays a role in various pathological processes. This paper describes the physiological function of endocannabinoid systems, intricacies of endocannabinoid receptors and their ligands, their role in various pathophysiological processes, pharmacological options in manipulation of the system and potential indications for therapy. Nowadays we know that the endocannabinoid system is a part of nociception modulation, inflammation processes, appetite, sleep, thermogenesis, immune responses, cognitive functions and probably a slew of other physiological functions and pathological conditions. This goes to show that the discovery process of various cellular, physiological and pharmacological mechanisms is very much alive and of great interest to scientists. Distribution of cannabinoid receptors in the human body provides a lot of possibilities for pharmacological manipulation. A variety of cannabinoid receptor ligands, from endogenous to exogenous, natural and synthetic cannabinoids (tetrahydrocannabinol, cannabidiol, cannabivarin; nabilon, dronabinol and many others) also increases the spectrum of possible therapeutic approaches for various indications, some of which are already established and approved (nausea and vomiting in cancer patients undergoing chemotherapy or radiotherapy, loss of appetite and body mass in AIDS patients), while others are still insufficiently researched. Despite all findings of possible benefits of the endocannabinoid system, we can conclude we are far from the goal. Further pre-clinical trials are necessary to get a better picture of physiological and pathological processes that are more or less influenced by the endocannabinoid system, as well as well-designed clinical trials to determine the pharmacological profiles of potential new molecules that influence the endocannabinoid system