The Effects of SKF 525-A on the Analgesic and Barbiturate-Potentiating Activity of Δ9-Tetrahydrocannabinol in Mice and Rats

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Abstract
Δ9-Tetrahydrocannabinol (THC) markedly potentiated barbital Na sleeping time in mice and rats. The magnitude and duration of this effect were markedly enhanced when the animals were pretreated with SKF 525-A, a nonspecific inhibitor of liver microsomal enzymes responsible for drug metabolism. Moreover, depending on the method and species of animal used, THC was found to be one half (mouse hot plate), one third (mouse tail flick), and one eighth (rat tail flick) as potent an analgesic as morphine SO4. However, pretreatment with SKF 525-A significantly potentiated the analgesic activity in mice. These data suggest that intact THC and not necessarily a metabolite(s) is principally responsible for the CNS depressant and analgesic effects observed.