Metabolic studies of delta-9-tetrahydrocannabinol in cancer patients

The metabolism of oral delta-9-tetrahydrocannabinol (THC) was studied in nine patients with gastrointestinal neoplasms receiving chemotherapy regimens containing 5-FU and semustine. Plasma levels of THC and its metabolites 11-OH-delta-9-THC (11-OH-THC) and 11-nor-9-carboxy-delta-9-THC (C-THC) were measured. Plasma levels of THC and its metabolites were quite variable among the patients studied. Plasma levels of THC and 11-OH-THC tended to peak at the same time; the C-THC levels peaked later and lasted much longer than the others. Mean half-lives of THC, 11-OH-THC, and C-THC were estimated to be 1.5, 2.1, and 4.4 hours, respectively. Multiple doses of THC did not produce a significant additive effect on the plasma concentrations of the biologically active metabolites THC and 11-OH-THC. No correlation between antiemetic effect or cannabinoid toxicity and plasma levels of the three metabolites could be made in this small number of patients.