Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse

The ability of ⁹-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E₁ (PGE₁) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED₅₀ in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED₅₀ range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE₁ as the nociceptive agent, 11-OH THC was equipotent to THC while 8,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.