NONSPECIFIC MEMBRANE-BINDING PROPERTIES OF DELTA-9-TETRAHYDROCANNABINOL AND THE EFFECTS OF VARIOUS SOLUBILIZERS

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. 1979 Royal Pharmaceutical Society of Great Britain