Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs.

The tetrahydrocannabinols from marihuana were found to have moderate analgesic activity in mice by the hot-plate test (sc administration). Of the several metabolites of these two compounds tested, only the 11-hydroxy derivatives were more potent than the parent compounds. Analogs 1 and 2 (9-demethyl relatives which cannot be metabolized to 11-hydroxy compounds), both of which produce a pharmacological profile generally similar to that of delta8- and delta9-THC, were analgesically inert. This suggests that metabolism to 11-hydroxy congeners may be necessary for the mediation of analgesic activity in the mouse hot-plate test but not for other pharmacologic effects produced by these substances which we have examined.