ANALGESIC EFFECTS OF 1',1'DIMETHYLHEPTYL-DELTA(8)-THC-11-OIC ACID (CT3) IN MICE

The metabolic pathway leading to carboxylic acid derivatives of cannab inoids was discovered more than twenty years ago. While these compound s showed no cannabimimetic activity, subsequent work documented severa l biological responses both in vitro and in vivo for the THC acids. Th ese include inhibition of eicosanoid synthesis, antiedema effects, ant agonism to PAF actions, inhibition of leucocyte adhesion and anti noci ception. In this report we present data further characterizing the ana lgesic properties of the title substance which is a potent synthetic m ember of this group. CT3 was effective in the mouse hot plate assay at 48 degrees C showing an ED-50 of 4.31(3.37-5.83) mg/kg when administe red i.v (10% Cremophor EL in saline). When given by gavage in peanut o il, it resulted in 30-40% MPE (maximum possible effect) at 10 mg/kg wi th the effect persisting for up to 5 hours. A more potent response was observed in the mouse p-phenylquinone writhing test. When given i.v., it showed an ED-50 of 1.24 (0.84-1.75) mg/kg. However, no activity wa s found with oral administration either in peanut oil or Cremophor EL. At 10 mg/kg i.v., a 100% inhibition of the writhing response was seen . The mouse formalin antinociception test was also studied in animals that received CT3 (4.64 mg/kg) i.v, using three behavioral parameters for activity. The drug showed decreases in each category when compared with vehicle/formalin treated mice. The formalin effect showed a typi cal two phase, time related, response in which CT3 caused a 64% reduct ion in the early phase and a 48% reduction in the late phase in a comp osite score of nociception. Interestingly, it did not alter motor func tion in the rota rod procedure at 4.64 mg/kg i.v.