Synthesis and pharmacological activity of a phosphate ester of delta8-tetrahydrocannabinol

A water-soluble phosphate ester of delta8-tetrahydrocannabinol (delta8-THC) was synthesized and its pharmacological activities were examined. The cataleptogenic and thiopental sleep-potentiating effects of delta8-THC phosphate in the mouse was approximately 10 and 7% of those of delta8-THC, respectively. However this phosphate showed almost the same potency and a longer duration of hypothermic effect, as compared with delta8-THC in the mouse. The acute toxicity of this phosphate was far lower than that of delta8-THC. delta 8-THC phosphate was difficultly hydrolyzed by alkaline phosphatase or mouse liver homogenate in vitro. The mode of action of the phosphate derivative is discussed in connection with this enzymatically difficult hydrolysis.