The non-specific membrane binding properties of delta9-tetrahydrocannabinol and the effects of various solubilizers

The binding of [3H]delta9-tetrahydrocannabinol to crude and purified synaptosomal membrane suspended in either Krebs solution or 10 mM 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(-6)M. Binding was similar in both suspending media, and to both crude and purified synaptosomal membrane. The solubilizing agent Cremophor E.L. (8 microgram 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 x 10(-4) to 1 x 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.