Propofol Sedation Is Reduced by Δ9-Tetrahydrocannabinol in Mice

In Brief BACKGROUND: Δ9-Tetrahydrocannabinol (Δ9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of Δ9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between Δ9-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 Δ9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with Δ9-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 Δ9-THC alone had no sedative effects. Administration of Δ9-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 Δ9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of Δ9-THC. CONCLUSION: The results indicate a dose-dependent antagonistic interaction between Δ9-THC and propofol, and also between Δ9-THC and thiopental. IMPLICATIONS: It has been reported that propofol increases cerebral endocannabinoid concentrations. We found that the sedative effect of a low propofol concentration was abolished by 50 mg/kg delta9-tetrahydrocannabinol (D9-THC) that produced no sedation when given alone. Our results indicate a dose-dependent antagonistic interaction between D9-THC and propofol.