ABSTRACT
Tolerance occurs when a larger dose of a drug is required to achieve a given effect, or when a dose that nonnally achieves an effect is no longer sufficient to produce it. In a therapeutic context, tolerance may necessitate an increase in the dose required to achieve symptom relief. Thi s may initially increase the risk of some unwanted side effects, although tolerance may also develop to these,
Tolerance to the biological effects ofTHC has been demonstrated in cultured cells and to many behavioral and physiological effects in humans and animal species. 2, 13,21,21(30,32 The precise underlying mechanisms remain unknown, although they are believed to involve changes in cannabinoid receptor functioning,2, 11 Although the onset of tolerance is typically rapid, the rate of development depends on the effect and its duration is variable, 13,311 Tolerance is less definitive with intermittent exposure to THC,2
Jones and Benowitz studied the effects of a daily 210 mg dose of oral THC, administered in a fixed-dosing schedule to healthy male volunteers with an extensive history of cannabis use, ' l Over the 30-day study period, there was a decline in the positive etfects of intoxication, A marked deterioration in social functioning in the early days ofthe high dose regimen almost completely reversed to baseline levels by study's end, while there was similar evidence of recovery in cognitive and psychomotor performance over the course of the study,
The magnitude of both the cardiovascular and subjective responses to smoking a single "joint" decreased with the length oftime the subjects had
received a high dose of THe. After a few days of high dose THe, an increased hemt rate was replaced by a normal, and in some cases a slowed, heart rate. Self-ratings of the "high" all but disappeared in the course of the study. Georgotas and Zeidenberg reported similar tolerance to the subjective effects of cannabis in humans.21
