title: Effects of general anesthesia on anandamide blood levels in humans.
abstract: 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.
authors.affiliation: Department of Anaesthesiology, Institute for Medical Informatics, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.forename: Shahnaz Christina
authors.initials: SC
authors.lastname: Azad
authors.forename: Martin
authors.initials: M
authors.lastname: Schmoelz
authors.forename: Alexander
authors.initials: A
authors.lastname: Chouker
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Cyrill
authors.initials: C
authors.lastname: Hornuss
authors.forename: Markus
authors.initials: M
authors.lastname: Rippberger
authors.forename: Josef
authors.initials: J
authors.lastname: Briegel
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
mesh_terms: 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
chemical_list: 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