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October 26, 2005
2:00:00 PM - 3:30:00 PM
Room C301
Propofol Activates the Endocannabinoid System in Humans
Gustav Schelling, M.D., Ph.D., Daniela Hauer, M.S., Cyrill Hornuss, M.D., Josef Briegel, M.D., Ph.D., Michael Vogeser, M.D., Ph.D.
Anaesthesiology, Ludwig-Maximilians University, Muenchen, Germany
Introduction: Anandamide (arachidonyl ethanolamide, ANA) is regarded as one of the most important endogenous cannabinoids acting as a ligand on cannabinoid CB1 and CB2 receptors. The biologic activity of ANA is terminated through degradation, which occurs by means of fatty acid amide hydrolase (FAAH). Propofol has recently been shown to inhibit FAAH in mice after i.p. administration that resulted in an increase of brain anandamide content (1). If the endocannabinoid system is involved in humans undergoing general anesthesia with propofol has, to our knowledge, never been studied. We measured anandamide levels in patients during general anesthesia with a volatile agent and in patients receiving total intravenous anesthesia with propofol to test the hypothesis that the use of propofol results in higher systemic anandamide levels and thus in an activation of the endocannabinoid system.

Methods: We developed a method to measure anandamide in whole venous blood using HPLC and tandem mass spectrometry. The inter-assay coefficient of variation of this method is <5%. Using this technique in healthy volunteers, a median whole blood anandamide concentration of 9.7 ug/L was found (range 8.2-11.0 ug/L) (2). We then determined anandamide levels in 12 patients after induction of general anesthesia using etomidate (an agent shown to have no effect on anandamide (1)) and maintenance of anesthesia with sevoflurane and in 12 patients undergoing total intravenous anesthesia with propofol. Anandamide levels were measured at 4 time points (before induction, 10 min post-intubation, 20 min post-intubation and at 40 min post-intubation). There were no significant differences regarding patient or clinical data (including duration of surgery, type of surgical procedure or dosage and type of other drugs administered during anesthesia and surgery) between the two groups.

Results: Patients from the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min post-induction whereas anandamide levels in patients from the propofol group moderately increased or remained unchanged (type III sum of squares = 72.8, F = 6.8, p =0.02, repeated measure ANOVA, s. Figure).

Conclusion: Propofol is known to reduce postoperative nausea and vomiting (PONV), shows postoperative mood alterations and is associated with a higher incidence of dreaming compared to other general anesthetics. The data from this study suggest that propofol activation of the endocannabinoid system, presumably by inhibition of ANA degradation via FAAH, may contribute to these unique properties of propofol. The decline in ANA levels seen in the sevoflurane group could also be a mechanism leading to PONV in patients undergoing general anesthesia with a volatile agent.

(1) Br J Pharmacol 2003 Jul;139(5):1005-13.

(2) Clinical Biochemistry. In press 2005.[figure1]

Anesthesiology 2005; 103: A675
Figure 1