Responses to oral Delta(9)-tetrahydrocannabinol in frequent and infrequentmarijuana users

It is known that an individual's drug use history affects the quality of su bjective effects experienced following administration of several clinically used psychoactive drugs such as barbiturates, diazepam, and morphine. Howe ver, it is not known whether drug use history also affects responses to the rapeutic cannabinoids such as Delta(9)-THC. Tnt current experiment compared the subjective and behavioral effects of oral Delta(9)-THC in two groups o f volunteers: frequent users (FREQ; ii = 11), who reported using marijuana at least 100 times, and infrequent users (INF: n = 10) who reported using m arijuana 10 or fewer times. Subjects participated in three sessions during which they received Delta(9)-THC (7.5 and 15 mg) and placebo. They complete d subjective effects questionnaires for 5 h following administration. In th e FREQ group, the lower dose (7.5 mg) increased ratings of "feel drug," rel ative to placebo, whereas it had no effect in the INF group. In contrast, a t the higher dose (15 mg), ratings of "feel drug" were lower in the FREQ gr oup than in the INF group, suggestive of tolerance. In addition, the INF gr oup reported greater sedative effects than the FREQ group following the hig her dose of Delta(9)-THC, again suggesting tolerance to Delta(9)-THC's seda tive effects. These findings demonstrate that marijuana use history may aff ect the subjective effects of oral Delta(9)-THC, but that the influence of drug use history depends on the dose of drug administered. These findings m ay have implications for the clinical use of Delta(9)-THC and other cannabi noids. (C) 1999 Elsevier Science Inc.