COMPLEX PHARMACOLOGY OF NATURAL CANNABINOIDS - EVIDENCE FOR PARTIAL AGONIST ACTIVITY OF DELTA(9)-TETRAHYDROCANNABINOL AND ANTAGONIST ACTIVITY OF CANNABIDIOL ON RAT-BRAIN CANNABINOID RECEPTORS

Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabinol and cannabidi ol are three important natural cannabinoids from the Marijuana plant ( Cannabis sativa). Using [S-35]GTP-gamma-S binding on rat cerebellar ho mogenate as an index of cannabinoid receptor activation we show that: Delta(9)-THC does not induce the maximal effect obtained by classical cannabinoid receptor agonists such as CP55940. Moreover at high concen tration Delta(9)-THC exhibits antagonist properties. Cannabinol is a w eak agonist on rat cerebellar cannabinoid receptors and cannabidiol be haves as an antagonist acting in the micromolar range. (C) 1998 Elsevi er Science Inc.