title: Propofol sedation is reduced by delta9-tetrahydrocannabinol in mice.
abstract: BACKGROUND
  Delta9-tetrahydrocannabinol (Delta9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of Delta9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between Delta9-THC and propofol in terms of sedation and analgesia.
  
  
  METHODS
  Sedation was monitored by a rota-rod and analgesia by tail-flick latencies. Twenty mice received intraperitoneal injections of 50 mg/kg Delta9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with Delta9-THC and thiopental or Intralipid.
  
  
  RESULTS
  Injection of 50 mg/kg propofol caused a rapid onset of sedation with a minimum of 24 s on the rota-rod. Fifty mg/kg Delta9-THC alone had no sedative effects. Administration of Delta9-THC significantly reduced the sedative effect of propofol to at least 60 s on the rota-rod (P < 0.001). After increasing the propofol dose to 100 mg/kg in the presence of Delta9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of Delta9-THC.
  
  
  CONCLUSIONS
  The results indicate a dose-dependent antagonistic interaction between Delta9-THC and propofol, and also between Delta9-THC and thiopental.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany. pabrand@anaesthesie.uni-kiel.de
authors.forename: Philipp-Alexander
authors.initials: PA
authors.lastname: Brand
authors.forename: Andrea
authors.initials: A
authors.lastname: Paris
authors.forename: Berthold
authors.initials: B
authors.lastname: Bein
authors.forename: Patrick
authors.initials: P
authors.lastname: Meybohm
authors.forename: Jens
authors.initials: J
authors.lastname: Scholz
authors.forename: Henning
authors.initials: H
authors.lastname: Ohnesorge
authors.forename: Peter H
authors.initials: PH
authors.lastname: Tonner
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D015742:Propofol / Q000037:antagonists & inhibitors*; D013874:Thiopental / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000700:Analgesics; D063385:Cannabinoid Receptor Modulators; D006993:Hypnotics and Sedatives; D005680:gamma-Aminobutyric Acid; D013759:Dronabinol; D013874:Thiopental; D015742:Propofol