animals, traces ofthe drug cans till be found as long as thirty days after a single administration. Other studies inanimals have shown that the cannabinoids and/or their metabolites accumulate in the brainfollowing repeated administration. This accumulation could increase the length of time that thesecannabinoids remain in the brain and might account for such long-lasting phenomena as learningand memory impairment and also flashbacks that have been reported in long-time users ofmarijuana.On the other hand, there is no doubt that tolerance does develop to many of the effects ofTHC. In general tolerance to a drug is recognized as having developed when, after repeatedadministrations, a given dose of that drug produces less of an effect than was initially produced.Alternatively, tolerance is said to have developed when greater amounts of the drug is required toproduce the desired effects. Closely related to the event of tolerance is physical dependence.Physical dependence on a drug is said to have developed when a characteristic withdrawalsyndrome is observed when use of the drug is discontinued. Although drug dependence is alwaysassociated with tolerance, tolerance does not necessarily result in drug dependence. To accountfor the observation that many users do not get “high” when they first use the drug, the concept of“reverse tolerance” has been hypothesized. However, there is very little evidence to support thistheory. Although tolerance develops quite rapidly to many of the behavioral and physiologicaleffects of marijuana, marked physical dependence, has not been observed. Studies of the acutetoxicity of marijuana and its derivatives in animals indicate that huge doses of these drugs can beadministered without causing death. The absence of cannabis overdose reports in man indicatethat marijuana and its derivatives are relatively safe substances. One estimate says that the lethaloral dose in humans is about 4,000 ...
