Interaction of cannabis and general anaesthetic agents in mice

1 A cannabis extract (I) (in a concentration equivalent to 10 mg Delta(9)-tetrahydro-cannabinol(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.2 The cannabis extract (I) (equivalent to 10 mg Delta(9)-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.3 A second cannabis extract (II) with a different ratio of cannabinoids (also administered in dosage equivalent to 10 mg Delta(9)-THC/kg) failed to affect pentobarbitone anaesthesia in mice. This extract presented about 4% the dose of cannabidiol as extract I.4 Delta(8)-THC, Delta(9)-THC and cannabidiol prolonged pentobarbitone anaesthesia with cannabidiol being generally more active than Delta(9)-THC. Cannabinol (10 mg/kg) was inactive.5 The effects of cannabidiol and Delta(9)-THC were found to be additive, and there was a consistent trend for cannabinol to reduce the effectiveness of Delta(9)-THC and cannabidiol when given in combination.6 Premedication with phenoxybenzamine, phentolamine, propranolol, iproniazid, protriptyline, desipramine, reserpine, alpha-methyl tyrosine or parachlorophenylalanine did not affect the extract I-induced prolongation of pentobarbitone anaesthesia.7 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.