Blood levels do not predict behavioral or physiological effects of Δ⁹-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure.
Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ(9)-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving. However, because marked tolerance develops to behavioral effects of THC, the applicability of a particular threshold of blood THC as an index of impairment in people with different patterns of use remains unclear. Studies relevant to this issue are difficult to accomplish in humans, as prior drug exposure is difficult to control. Here, effects of THC to decrease rectal temperature and operant response rate compared to levels of THC and its metabolites were studied in blood in two groups of monkeys one received intermittent treatment with THC (0.1 mgkg i.v. every 3-4 days) and another received chronic THC (1 mgkg12 h s.c.) for several years. In monkeys with intermittent THC exposure, a single dose of THC (3.2 mgkg s.c.) decreased rectal temperature and response rate. The same dose did not affect response rate or rectal temperature in chronically exposed monkeys, indicative of greater tolerance. In both groups, blood levels of THC peaked 20-60 min post-injection and had a similar half-life of elimination, indicating no tolerance to the pharmacokinetics of THC. Notably, in both groups, the behavioral effects of THC were not apparent when blood levels were maximal (20-min post-administration). These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure.