Mechanism of cannabinoid incorporation in hair

Analysis of hair for the detection of illegal and therapeutic drugs has become a widely accepted alternative or complementary method to traditional urinalysis. Hair pigmentation has been shown to play a role in the incorporation of drug into hair. Drug basicity has increased the incorporation of certain basic compounds, such as cocaine, codeine, amphetamine, and phencyclidine, into pigmented hair compared to non-pigmented hair through their interactions with melanin in hair. However, the nonbasic cannabinoids should not show the same differential incorporation as do some basic drugs. We hypothesized that delta-9-tetrahydrocannabinol (THC) and 11 -nor-delta-9-tetrahydrocannabinol (THCA) incorporated into hair by a mechanism independent of melanin binding. THC and THCA in pigmented and nonpigmented hair collected from Long-Evans rats administered THC did not statistically differ. Cultured pigmented melanocytes (PM) and nonpigmented melanocytes (NPM) were employed to examine the effect of pigmentation on the influx and efflux of THC and THCA into and out of hair cell types. There was no difference in the influx of THC and THCA into PM and NPM, with the exception of THC in NPM at 15s and 150 min The efflux of THC and THCA further support the hypothesis that factor/s other than pigmentation effect cannabinoid retention in PM and NPM. There was no significant difference between the amount of THC effluxed from PM and NPM. THCA efflux from PM was significantly greater than NPM at 1,5, 30, and 60 min. Indirect immunofluorescence was used to observe sites of THC and COC (positive control) localization within the hair follicle. No fluorescence was evident in either pigmented or nonpigmented hair follicle sections at any time after a single dose of THC. After multiple administrations, THC was localized with epidermal keratins and sebaceous glands, not the melanosomes of the hair follicle. In contrast to THC, COC associated with the dense population of melanosomes in the cortex of the pigmented hair follicle. In conclusion, the data presented in this dissertation demonstrate that THC and THCA incorporate into hair by a mechanism independent of hair pigmentation, and suggest its incorporation is influenced by the indirect deposition via sebum and skin.