Publications

Cannabidiol (CBD) has been shown to be a selective inactivator of cytochromes P450 (P450s) 2C and 3A in the mouse and, like many P450 inactivators, it can also induce P450s after repeated administration. The inductive effects of CBD on mouse hepatic P450s 2B, 3A, and 2C were determined using cDNA probes, polyclonal antibodies, and specific functional markers. P450 2B10 mRNA was increased markedly after repeated CBD administration and correlated well with increased P450 2B immunoquantified content and functional activity. On the other hand, although the 2-fold increase in P450 3A mRNA detected after repeated CBD administration was consistent with the increased immunoquantified P450 3A protein content, the lack of an observable increase in P450 3A-specific functional activity suggested subsequent inactivation of the induced P450 3A. Repeated CBD treatment increased P450 2C mRNA content 2-fold, but did not increase either the P450 2C immunoquantified content or its functional activity. The effect of CBD treatment on the ability of tetrahydrocannabinol (THC) to induce P450 2B was also determined. A THC dose that did not induce P450 2B significantly was administered alone or in combination with a CBD dose that markedly inactivated P450s 2C- and 3A but submaximally increased P450 2B functional activity. The combination of THC and CBD did not increase P450 2B-catalyzed activity significantly over that observed after CBD treatment alone. Thus, prior CBD-mediated P450 inactivation does not appear to increase the ability of THC to induce P450 2B. To further characterize the relationship between P450 inactivation and induction, several structurally diverse CBD analogs with varying P450 inactivating potentials were tested for their ability to induce P450 2B. At least one CBD analog that is an effective P450 inactivator failed to induce P450 2B, while at least one CBD analog that is incapable of inactivating P450 was found to be a very good P450 2B inducer. It therefore appears that inherent structural features of the CBD molecule rather than its ability to inactivate P450 determine P450 2B inducibility. The complex effects of CBD treatment on P450 inactivation and induction have the potential to influence the pharmacological action of many clinically important drugs known to be metabolized by these various P450s. The mechanism of CBD-mediated P450 induction remains to be elucidated but does not appear to be related to CBD-mediated P450 inactivation.

We surveyed varsity athletes (N = 1,328) in 16 California colleges about their patterns of spit (smokeless) tobacco (ST) use, related habits, reasons for use, and preferred methods for quitting. Prevalence of use was analyzed by sport and demographic characteristics, and patterns of use in players using snuff exclusively, using chewing tobacco exclusively, and those using both were compared. Odds ratios and 95% confidence intervals were calculated, adjusting for ethnic group. Prevalence was highest in Whites (44%) and Native Americans (48%) and lowest in African Americans (11%), and higher in varsity baseball (52%) than varsity football players (26%), in players attending rural colleges, and among those who ever smoked cigarettes or used alcohol. Forty-one percent of ST users initiated regular use during their high school years. Athletes who used snuff exclusively used it more intensively and for more years than those who used chewing tobacco exclusively. Snuff users indicated a greater perceived need for ST, but also were more ready to quit. These data suggest ST programs with prevention and cessation components are appropriate for high school as well as college athletes. Such interventions should focus on baseball players, distinguish snuff from chewing tobacco users in planning quit strategies, integrate intervention programs for cigarette smoking and alcohol consumption, provide training in refusal skills, and attempt to change social norms in support of ST use by integrating popular peers and significant others (e.g., wives/girlfriends) to endorse nonuse of ST.