Cannabinoids. I. Behavioral effects.

Abstract

The effects of two new cannabinoids, nabilone and canbisol, have been compared to delta 9-tetrahydrocannabinol (delta 9-THC) and chlordiazepoxide in behavioral tests in mice, rats, dogs and rhesus monkeys. Activity of mice was measured in a photocell device. Oral doses of 5 and 10 mg/kg of delta 9-THC and 200 mg/kg of chlordiazepoxide caused only a decrease in the initial high activity. Doses of 5 and 10 mg/kg of nabilone and 2.5, 5.0 and 10 mg/kg of canbisol decreased the initial high activity but increased the subsequent low activity. In rats delta 9-THC, nabilone and canbisol, but not chlordiazepoxide, slowed muricide and intracranial self-stimulation. Chlordiazepoxide, nabilone and canbisol, but not delta 9-THC, reduced reactivity of septal-lesioned rats. At ehe dosages studied only nabilone and canbisol reduced food consumption by rats. Ataxia in dogs was detected following as little as 0.062 mg/kg of delta 9-THC, 0.032 mg/kg of nabilone and 0.004 mg/kg of canbisol when given intravenously; orally, doses of more than 0.25 mg/kg of delta 9-THC, and 0.1 mg/kg of nabilone or canbisol were necessary. Rhesus monkeys working under multiple fixed-ratio fixed-interval schedules showed an increase in rate at some dose of all three cannabinoids but higher doses reduced responding, and responding was abolished following 3.0 mg/kg of delta 9-THC or nabilone or 0.3 mg/kg of canbisol. Chlordiazepoxide increased responding at all doses studied, 3.0 to 30.0 mg/kg. Nabilone and canbisol resemble chlordiazepoxide in som tests and delta 9-THC in other tests.