"The magnitude of the present effect, like the striking behavioral tolerance, may stem in part that, unlike other psychoactive agonist drugs, cannabinoids can be administered in very high doses. It is ironic that the magnitude of both tolerance (complete disappearance of the inhibitory motor effect) and receptor down-regulation (78%loss . . .) is so large, whereas cannabinoid dependence and withdrawal phenomena are minimal. This supports the claim that tolerance and dependence are independently mediated in the brain."

Oviedo, A., Glowa, J, and Herkenham, M. (1993), "Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study." Brain Research, 616:293-302. pg. 300.