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5. The accute effects of cannabis intoxication
5.2 Toxic dose levels
THC appears to be the component of cannabis which has the highest direct toxicity in all animals so far tested. The toxic effects of cannabis are mediated through its effects on neural systems. The cause of death in experimental animals is almost invariably apnoea or cardiac arrest, if apnoea is prevented (Rosencrantz, 1983). Due to the development of tolerance, toxic doses depend upon the amount by which they exceed the customary dose. In contrast to the increase in toxic dose typical of many drugs when moving from primates to lower animals, it appears that phylogenetically higher animals are less susceptible to the acute toxicity of THC. Thus, the dose of THC which kills 50 per cent of animals (LD50) when administered intravenously is 40mg/kg in the rat but 130mg/kg in the dog and monkey (Rosencrantz, 1983).
For obvious ethical reasons there is no experimental evidence to determine a lethal dose in humans. Nor is there any clinical evidence, since there have been no reported cases of death attributable to cannabis in the world medical literature (Blum, 1984; Nahas, 1984). Extrapolation from the animal evidence suggests that the lethal human dose of THC is at least as high as, and probably higher than, that observed in the monkey. If this is so, then the toxic dose of THC in a 65kg adult would be 8.45kg.
A number of non-fatal toxic reactions occur in humans with higher than normal doses. The tachycardia almost invariably produced in acute intoxication, combined with the sensory alterations and increased tremor commonly reported, probably contribute to the affective components of these reactions. CNS and respiratory depression are noted with high doses, which in severe overdose may be life-threatening (Rosencrantz, 1983). These effects are, of course, more dangerous to those with pre-existing cardiac irregularities. Because of the large effective to lethal dose ratio in humans (probably in excess of 1:1000 in non-tolerant users) the risk of experiencing severe toxic effects of cannabis is limited by the aversive psychotropic effects of high doses, which usually lead to cessation of use before the onset of dangerous physical consequences.