Analysis of hair for drugs of abuse has increasingly been used as an alternative to traditional urinanalysis. Hair is a complex protein matrix capable of many types of interactions with drugs. Certain drugs have been shown to be preferentially incorporated into hair by pigmentation. The binding of basic drugs, like cocaine, on melanin is believed to produce a hair color effect through both ionic and non-ionic interactions. However, our present knowledge regarding the characteristics and mechanisms for the incorporation of non-basic drugs or their metabolites remains incomplete. Thus, this proposal will test the hypothesis that delta9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCA), cannabidiol (CBD) and cannabinol (CBN) incorporate into hair by a mechanism that is independent of melanin binding. This will be accomplished by completing the following specific aims: 1) Quantitate the concentrations of THC, THCA, CBD and CBN, in pigmented and non-pigmented hair using Long-Evans (LE) rats exposed, acutely or chronically, to THC, THCA, CBD or CBN. 2) Identify sites of cannabinoid localization in hair using [3H]-delta9 tetrahydrocannabinol and microautoradiography. 3) Determine major mechanisms of THC, THCA, CBD and CBN, incorporation into hair using in vitro techniques. The results of these studies will increase our understanding of cannabinoid deposition into hair, and further elucidate possible mechanisms for the incorporation of non-basic analytes into hair. This is important because the general acceptance of hair testing relies on the ability to answer questions regarding mechanisms of drug incorporation into hair.