Effects of general anesthesia on anandamide blood levels in humans.
BACKGROUND
The endocannabinoid system includes G-protein-coupled cannabinoid receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and degradation of endocannabinoids, including the anandamide metabolizing enzyme fatty acid amide hydrolase. Endocannabinoids play an important role in the physiologic control of sleep, pain processing, and emesis. The authors therefore investigated the effects of general anesthesia on the endocannabinoid system in humans.


METHODS
The authors measured whole blood levels of anandamide in 12 patients after induction of general anesthesia with etomidate (an agent shown to have no effect on anandamide levels) and maintenance of anesthesia with the volatile agent sevoflurane as well as in 12 patients undergoing total intravenous anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the mouse brain. Anandamide levels were measured using high-performance liquid chromatography-tandem mass spectrometry at four time points (before and at 10, 20, 30, and 40 min after induction of anesthesia).


RESULTS
Patients of the sevoflurane group showed a significant decline in anandamide levels from induction of anesthesia to 40 min after induction, whereas anandamide levels in patients of the propofol group remained unchanged (type III sum of squares = 1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance).


CONCLUSIONS
General anesthesia influences the endocannabinoid system in a drug-dependent way, which may explain side effects of general anesthetics such as psychomimetic and antiemetic properties of propofol and the high incidence of postoperative nausea and vomiting after volatile anesthetics. These findings suggest new targets for anesthetic drug development.
Schelling
Gustav
G
Department of Anaesthesiology, Institute for Medical Informatics, Ludwig-Maximilians University, Munich, Germany.
Hauer
Daniela
D
Azad
Shahnaz Christina
SC
Schmoelz
Martin
M
Chouker
Alexander
A
Schmidt
Michael
M
Hornuss
Cyrill
C
Rippberger
Markus
M
Briegel
Josef
J
Thiel
Manfred
M
Vogeser
Michael
M
D000368:Aged; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001095:Arachidonic Acids / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D063388:Endocannabinoids; D005045:Etomidate; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008738:Methyl Ethers; D008875:Middle Aged; D010865:Pilot Projects; D053284:Polyunsaturated Alkamides; D015742:Propofol; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001095:Arachidonic Acids; D063388:Endocannabinoids; D008738:Methyl Ethers; D053284:Polyunsaturated Alkamides; D000077149:Sevoflurane; C078814:anandamide; D015742:Propofol; D005045:Etomidate