Studies on the interactions of copper and cannabis

The action of copper (CuSO4, 5 mg/kg, oral) on selected neuropharmacological actions of cannabis resin (CI, oral) was studied on albino rats and mice. Copper potentiated the barbiturate hypnosis-potentiating activity of CI in albino rats and mice and had no effect on hypothermic activity in albino rats. Single doses of copper partially inhibited tolerance to barbiturate hypnosis-potentiation activity and markedly delayed the development of tolerance to hypothermic activity of CI. Oral as well as i.c.v. copper (CuSO4, 0.1 microgram) in single dose antagonised the tolerance to hypothermic activity of cannabis or THC for one to two weeks. Copper-CI interaction could be antagonised by penicillamine. Zinc (ZnSO4, 5 mg/kg, oral) had an action similar to that of copper in antagonising the development of tolerance to the hypothermic activity of CI, but magnesium (MgSO4, 5 mg/kg, i.p.) was devoid of any such action. Studies indicate that, although copper has no significant neuropharmacological action, it interacts with CI activity, especially in tolerant rats, in effects on hypothermia. The site of action of copper is possibly the hypothalamus, where it inhibits the processes of tolerance development to CI on the noradrenergic neurone.