Action of Δ9-tetrahydrocannabinol on membrane-bound monoamine oxidase activity

In vivo administration (ip) of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) to adult rats under acute conditions (10 and 50 mg/kg) produced a dose-dependent stimulation of monoamine oxidase (MAO; monoamine: O₂ oxidoreductase (deaminating), EC 1.4.3.4) activity in blood platelets and in mitochondrial preparations of hypothalamus and heart. Chronic treatment (10 mg/kg/day for 15 consecutive days) produced a smaller stimulating effect on MAO activity of these tissues. In vitro treatment with Δ⁹-THC produced (1) a stimulatory effect in hypothalamic MAO up to a concentration of 4 μg/mg of protein, (2) an inhibitory effect on heart MAO, and (3) a slight though not insignificant inhibitory effect on platelet MAO. Kinetic studies of in vivo and in vitroΔ⁹-THC-treated enzyme (MAO) are discussed on the basis of K_m and V_max values obtained from Linewwaver-Burk plots. When KSCN, KNO₃, and urea were used, they produced a significant inhibitory effect on MAO activity in all these tissues, even in the presence of Δ⁹-THC, indicating that a characteristic interaction between membrane-bound MAO and Δ⁹-THC can be disrupted by these chaotropic agents.