Studies on the agonistic activity of delta 9-11-tetrahydrocannabinol in mice, dogs and rhesus monkeys and its interactions with delta 9-tetrahydrocannabinol.

P M Beardsley, J A Scimeca, B R Martin

Index: J. Pharmacol. Exp. Ther. 241(2) , 521-6, (1987)

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Abstract

The present studies examine some of the pharmacological effects of delta-9 (11)-tetrahydrocannabinol (delta 9-11-THC), an analog of delta-9-tetrahydrocannabinol (delta 9-THC). In tests with mice, delta 9-11-THC was similar to but less potent than delta 9-THC in producing hypothermia, analgesia, lethality and in reducing spontaneous activity. In dogs delta 9-THC but not delta 9-11-THC produced classical cannabimimetic signs including static ataxia, hyperreflexia, prancing and tail-tuck. delta 9-11-THC did produce central nervous system depression in 9 of the 15 dogs tested but the effects were not dose-related and appeared earlier and dissipated faster than the depressive effects induced by delta 9-THC. delta 9-THC but not delta 9-11-THC produced signs of ptosis, sedation and ataxia in rhesus monkeys. delta 9-THC also suppressed operant responding completely in four of four monkeys tested whereas in one monkey delta 9-11-THC did not do so up to doses as high as 5.0 mg/kg and was 8 to 100 times less potent in doing so in the other monkeys. When monkeys were pretreated with delta 9-11-THC the doses of delta 9-THC required to produce ptosis, sedation, ataxia and operant suppression were increased. However, when mice and dogs were pretreated with delta 9-11-THC the effects of delta 9-THC were not attenuated and usually were enhanced. The pharmacological profile of delta 9-11-THC is unusual in that it seems to have cannabimimetic activity in mice, noncannabimimetic-like effects in dogs and is perhaps devoid of cannabimimetic effects in rhesus monkeys. In addition, pretreatment with delta 9-11-THC attenuates the cannabimimetic effects of delta 9-THC in rhesus monkeys but not in mice or dogs.