14C-delta-tetrahydrocannabinol (14C-Δ9THC) was administered to 12 long-term marihuana smokers intravenously, orally or by inhalation, and the drug's disposition, excretion and psychologic effects compared. Over 90 per cent of the dose was absorbed after oral administration; the psychologic effects and plasma levels of metabolites of Δ9-THC peaked at three hours. After inhalation, the peak psychologic “high” ranged from 10 to 140 minutes (average peak “high” of 70 minutes), correlating well with the peak plasma levels of metabolites of Δ9-THC. The percentage of administered radioactive dose excreted in urine during the first day was similar after oral and intravenous routes, but the proportion of radioactivity recovered from feces (seven days) exceeded that in the one-day urine output. The fact that the psychologic effects in response to pharmacologic doses of ingested or inhaled 14C-Δ9-THC were temporally correlated with plasma levels of the metabolites of the drug supports the hypothesis that these metabolites are active compounds.
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