INTERACTION OF CANNABIS AND GENERAL ANAESTHETIC AGENTS IN MICE

Abstract

A cannabis extract (I) (in a concentration equivalent to 10 mg Δ9‐tetrahydrocannabinol(THC)/kg) prolonged pentobarbitone anaesthesia in mice maximally 20 min to 2 h after medication. The effect was still significant after 8 h, but less than at 2 hours. The cannabis extract (I) (equivalent to 10 mg Δ9‐THC/kg) prolonged both pentobarbitone and ether anaesthesia in mice when administered 20 min before the anaesthetic. After eight consecutive daily doses of cannabis, the pentobarbitone anaesthesia was still significantly longer than a control group, while ether anaesthesia was not significantly prolonged. A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg Δ9‐THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I. Δ8‐THC, Δ9‐THC and cannabidiol prolonged pentobarbitone anaesthesia with cannabidiol being generally more active than Δ9‐THC. Cannabinol (10 mg/kg) was inactive. The effects of cannabidiol and Δ9‐THC were found to be additive, and there was a consistent trend for cannabinol to reduce the effectiveness of Δ9‐THC and cannabidiol when given in combination. Premedication with phenoxybenzamine, phentolamine, propranolol, iproniazid, protriptyline, desipramine, reserpine, α‐methyl tyrosine or parachlorophenylalanine did not affect the extract I‐induced prolongation of pentobarbitone anaesthesia. It is concluded that cannabis may affect pentobarbitone and ether anaesthesia in mice at least partially by a direct depressant effect, and that the cannabis‐induced prolongation of anaesthesia is probably unrelated to any effect on central 5‐hydroxytryptamine or catecholamine neurones. 1974 British Pharmacological Society