Effects of Δ⁸-tetrahydrocannabinol and its active metabolites on metabolic disposition of pentobarbital in the mouse

Effects of Δ⁸-tetrahydrocannabinol (Δ⁸-THC), 11-hydroxy-Δ⁸-THC and 11-oxo-Δ⁸-THC on metabolic disposition of pentobarbital in plasma, brain and liver of mice were studied. By pretreatments of mice with these cannabinoids (5 mg/kg, i.v.), the tissue concentrations of pentobarbital at 30 min after the i.p. injection (40 mg/kg) were not changed as compared with the control, although elimination of pentobarbital from the tissue in mice pretreated with cannabinoids were slower than those of the control mice. Pentobarbital concentration in brain at the time of awakening was 0.149 (control), 0.102 (Δ⁶-THC), 0.073 (11-hydroxy-Δ⁸-THC) or 0.064 μmoles/g (11-oxo-Δ⁸-THC). The result suggests that 11-hydroxy-Δ⁸-THC and 11-oxo-Δ⁸-THC possess a greater activity to the central nervous sytem than Δ⁸-THC.