Previously we have conducted extensive investigations of the metabolism of radio-labeled delta 9-THC in young male volunteers. Similar information is not available at present for young females whose metabolism, excretion, and general pharmacokinetic parameters may differ from the male. No information is available on the effects of cannabinol and cannabidiol (the other major cannabinoids found in marihuana) on metabolism, excretion, and pharmacokinetics of delta 9-THC in man. CBN and CBD are normally ingested simultaneously with delta 9-THC and may compete with the latter for plasma protein and microsomal enzyme binding sites. Specifically tritium labeled delta 9-THC will be administered intravenously, orally, or by smoke inhalation to paired normal male and female subjects. Blood, urine, and feces will be collected at appropriate times. Analytical measurements include total drug, total unconjugated and conjugated delta 9-THC and metabolites, and delta 9-THC and individual metabolites. The latter determinations will be carried out by thin layer chromatography combined with scintillation counting. In this manner the percentage of the dose in each biological sample can be calculated for total drug and the individual parent drug and individual metabolites. The pharmacokinetic parameters to be measured include volume of distribution, total body clearance, urinary clearance, and biological half-lives of delta 9-THC and major metabolites for each of routes of administration to be investigated. The chemistry of certain major delta 9-THC metabolites will be further investigated. These include the nature of polar acid fraction, and studies of the nature of the conjugates excreted in the urine. Both fractions will be extensively purified, derivatized and subject to mass spectral and nuclear magnetic resonance analyses.