The endocannabinoid signalling system: Implications for anaesthesia and the pain clinic

Abstract

Δ 9 -Tetrahydrocannabinol ( Δ 9 THC) is the major psychoactive ingredient of the plant Cannabis sativa that has been extensively used by humans for over 4000 years for both therapeutics and economic growth. Until a decade ago, the effects of Δ 9 THC were frequently attributed to non-specific alterations in membrane structure, based on its high lipophilicity, a theory similar to that proposed a century ago (by Meyer and Overton) for anaesthetics. Recent evidence identified a distinct protein receptor site (cannabinoid receptor, CB1) in the human brain activated not only by Δ 9 THC, but also by two endogenously produced lipid compounds, anandamide and 2-arachidonylglycerol. The cannabinoid has been subsequently tested in a plethora of in vitro, in vivo and clinical (to lesser extent) assays that revealed interesting features of their pharmacology and physiological roles. Cannabinoids have the potential to interact with a number of drugs that are used in clinical anaesthetic practice, while in turn anaesthetic agents may produce their effects through modulation of the endocannabinoid signalling system. Herein, we briefly review the discovery, pharmacological actions and putative physiological functions of endocannabinoids. We then discuss some of these finding in relation to anaesthesia in order to identify therapeutic potentials, highlight specific problems and stimulate further debate.