Changes of blood endocannabinoids during anaesthesia: A special case for fatty acid amide hydrolase inhibition by propofol?

Abstract

Aims: The aim of our study was to describe the time course of endocannabinoids during different anaesthesia protocols in more detail, and to challenge the hypothesis that propofol acts as a FAAH inhibitor. Methods: Endocannabinoids were measured during the first hour of anaesthesia in 14 women and 14 men undergoing general anaesthesia with propofol and in 14 women and 14 men receiving thiopental/sevoflurane. We also incubated whole human blood samples ex vivo with propofol and the known FAAH inhibitor oloxa and determined FAAH enzyme kinetics. Results: Plasma anandamide decreased similarly with propofol and thiopental/sevoflurane anaesthesia, and reached a nadir after 10min. Areas under the curve for anandamide (mean and 95% CI) were 53.3 (47.4, 59.2) nmoll-160min with propofol and 48.5 (43.1, 53.8) nmoll-160min with thiopental/sevoflurane (P= NS). Anandamide and propofol plasma concentrations were not correlated at any time point. Ex vivo FAAH activity was not inhibited by propofol. Enzyme kinetics (mean ± SD) of recombinant human FAAH were Km= 16.9 ± 8.8μmoll-1 and Vmax= 44.6 ± 15.8nmolmg-1min-1 FAAH without, and Km= 16.6 ± 4.0μmoll-1 and Vmax= 44.0 ± 7.6nmolmg-1min-1 FAAH with 50μmoll-1 propofol (P= NS for both). CONCLUSIONS Our findings challenge the idea that propofol anaesthesia and also propofol addiction are directly mediated by FAAH inhibition, but we cannot exclude other indirect actions on cannabinoid receptors. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.