Propofol sedation is reduced by delta9-tetrahydrocannabinol in mice.
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.
Brand
Philipp-Alexander
PA
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany. pabrand@anaesthesie.uni-kiel.de
Paris
Andrea
A
Bein
Berthold
B
Meybohm
Patrick
P
Scholz
Jens
J
Ohnesorge
Henning
H
Tonner
Peter H
PH
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
D000700:Analgesics; D063385:Cannabinoid Receptor Modulators; D006993:Hypnotics and Sedatives; D005680:gamma-Aminobutyric Acid; D013759:Dronabinol; D013874:Thiopental; D015742:Propofol