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ANESTHETIC PHARMACOLOGY

Propofol Sedation Is Reduced by 9-Tetrahydrocannabinol in Mice

Philipp-Alexander Brand, MD^*, Andrea Paris, MD^*, Berthold Bein, MD, DEAA^*, Patrick Meybohm, MD^*, Jens Scholz, MD^*, Henning Ohnesorge, MD^*, and Peter H. Tonner, MD

From the *Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; and Department of Anaesthesiology and Intensive Care Medicine, Klinikum Links der Weser, Bremen, Germany.

Address correspondence and reprint requests to Dr. Philipp-Alexander Brand, Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany, Schwanenweg 21, D-24105 Kiel, Germany. Address e-mail to pabrand{at}anaesthesie.uni-kiel.de.

BACKGROUND: 9-Tetrahydrocannabinol (9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of 9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between 9-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 9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with 9-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 9-THC alone had no sedative effects. Administration of 9-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 9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of 9-THC.

CONCLUSION: The results indicate a dose-dependent antagonistic interaction between 9-THC and propofol, and also between 9-THC and thiopental.