The non-specific membrane binding properties of ΔA9-tetrahydrocannabinol and the effects of various solubilizers

Abstract

Abstract The binding of [3H]δ9-tetrahydrocannabinol to crude and purified synaptosomal membrane suspended in either Krebs solution or 10mM sodium phosphate buffer was examined. The membrane/buffer partition coefficient was found to be 12 500, and was constant over a free concentration range of 10−8 to 10−6m. Binding was similar in both suspending media, and to both crude and purified synaptosomal membrane. The solubilizing agent Cremophor E.L. (8 μg ml−1) decreased the partition coefficient by one-half, and by greater than 99 % at 0.4 mg ml−1. Similar effects were observed with Tween 80, while ethanol caused a maximum decrease of 60%. Membrane concentrations of THC were calculated at various effective concentrations reported in the literature, and were within the range predicted by the Meyer-Overton rule of anaesthesia. An apparent non-specific interaction with neuronal membranes and effective membrane concentrations of the order 2 times 10−1 to 1 times 10−2 mol kg−1 suggests THC may exert some of its effects by a mechanism analogous to the general anaesthetics, and thus may be classified as a partial anaesthetic.