Interaction of cannabinoids with pentobarbital in rats

Abstract

The effect of cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), Δ 8-tetrahydrocannabinol ( Δ 8-THC), and Δ 9-tetrahydrocannabinol ( Δ 9-THC) on the in vivo metabolism of [ 14C]pentobarbital ( 14C-P) was investigated in rats. The cannabinoids were administered ip (20 mg/kg) 30 min prior to either oral or iv treatment with 14C-P. When 14C-P was given po, the 14C blood concentrations were initially depressed and later elevated by CBG and CBD, increased by Δ 8-THC and Δ 9-THC and unaffected by CBN. When 14C-P was injected iv, the blood 14C values were elevated by CBD and unchanged by CBG, Δ 8-THC or Δ 9-THC. Urinary excretion of total 14C and the metabolites of P was decreased by CBD, CBG and Δ 8-THC during the first 6 hr following treatment. The effect of CBD on the blood concentration and urinary excretion of 14C was dose-related. In rats treated with CBD + P, the liver and serum concentrations of P metabolites were significantly lower and the liver, serum and brain concentrations of unmetabolized P were significantly higher than in P-treated rats. Pentobarbital induction and sleeping times were potentiated by CBD and Δ 9-THC and antagonized by CBG. It was concluded that CBD delayed P metabolism, CBG decreased the rate of P absorption and excretion. Δ 8-THC and Δ 9-THC decreased elimination of P and CBN had little effect on P absorption, metabolism or excretion. The effect of CBD + P on sleeping time was correlated with brain P concentrations.