1 Ethanol and nicotine are commonly coabused drugs. Cytochrome P450 2E1 (CYP2E1) metabolizes ethanol and bioactivates tobacco-derived procarcinogens. Ethanol and nicotine can induce hepatic CYP2E1 and we hypothesized that both centrally active drugs could also induce CYP2E1 within the brain. 2 Male rats were treated with saline, ethanol (3.0 g kg À1 by gavage) or nicotine (1.0 mg kg À1 s.c.) for 7 days. Ethanol treatment significantly increased CYP2E1 in olfactory bulbs (1.7-fold), frontal cortex (2.0-fold), hippocampus (1.9-fold) and cerebellum (1.8-fold), while nicotine induced CYP2E1 in olfactory bulbs (2.3-fold), frontal cortex (3.0-fold), olfactory tubercle (3.1-fold), cerebellum (2.5-fold) and brainstem (2.0-fold). Immunocytochemical analysis revealed that the induction was cell-type specific.3 Consistent with the increased CYP2E1 found in rat brain following drug treatments, brains from alcoholics and alcoholic smokers showed greater staining of granular cells of the dentate gyrus and the pyramidal cells of CA2 and CA3 hippocampal regions as well as of cerebellar Purkinje cells compared to nonalcoholic nonsmokers. Moreover, greater CYP2E1 immunoreactivity was observed in the frontal cortices in the alcoholic smokers in comparison to nonalcoholic nonsmokers and alcoholic nonsmokers. 4 To investigate if nicotine could contribute to the increased CYP2E1 observed in alcoholic smokers, we treated human neuroblastoma IMR-32 cells in culture and found significantly higher CYP2E1 immunostaining in nicotine-treated cells (0.1-10 nm). 5 CYP2E1 induction in the brain, by ethanol or nicotine, may influence the central effects of ethanol and the development of nervous tissue pathologies observed in alcoholics and smokers.

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We found a significantly greater frequency of the CYP2E1*1D allele among Indo-Asian Canadians (0.31), Chinese Canadians (0.19), Taiwanese (0.20), Japanese Canadians (0.18), African Americans (0.13), African Canadians (0.10) and Canadian Native Indians (0.09) compared to Caucasian Canadians (0.02). Although the power of the association study was low among some subgroups, the CYP2E1*1D genotype (subjects with at least one variant allele) was associated with alcohol as well as nicotine dependence. Specifically, Canadian Native Indians dependent on nicotine alone or alcohol alone exhibited significantly greater CYP2E1*1D frequencies compared to non-drug dependent controls, while the variant frequency among Southeast Asians dependent on nicotine was greater than their non-drug dependent counterparts. We also found that CYP2E1*1D genotype was associated with significantly greater 3-hydroxycotinine per cigarette in African Americans. The variable frequency of CYP2E1*1D among ethnic groups suggests a greater risk for diseases putatively related to CYP2E1 in some non-Caucasian ethnic groups. The association of CYP2E1*1D with alcohol and nicotine dependence suggests that CYP2E1 may contribute to the development of these dependencies.

BackgroundLimited access to Cognitive Training (CT) for people with schizophrenia (SZ) prevents widespread adoption of this intervention. Delivering CT remotely via tablets may increase accessibility, improve scheduling flexibility, and diminish patient burden.MethodsIn this reanalysis of data from a larger trial of CT, we compared two samples of individuals with SZ who chose to complete 40 h of CT either on desktop computers in the laboratory (N = 33) or remotely via iPads (N = 41). We examined attrition rates and adherence to training, and investigated whether remote iPad-based CT and in-person desktop-based CT induced significantly different improvements in cognitive and real-world functioning.ResultsThe attrition rate was 36.6%. On average, participants completed 3.06 h of CT per week. There were no significant between-group differences in attrition and adherence to CT requirements. Participants who completed iPad-based CT were significantly younger and had lower symptoms at baseline compared to participants who completed CT on the lab desktops. Controlling for age and symptom severity, rANCOVA showed that iPad-based and desktop-based CT similarly and significantly improved verbal learning and problem solving. Main effects of time, at trend level significance, were evident in global cognition, verbal memory, quality of life, and social functioning. All group by time interactions were non-significant except for verbal memory, where iPad users showed greater gains. Within-group effect sizes for changes in outcomes were in the small range.ConclusionAlthough underpowered and not randomized, this study demonstrates that delivering CT remotely to people with SZ using tablets is feasible and results in retention rates, adherence, and cognitive and functional outcome improvements that are comparable to those observed when CT is delivered in the laboratory. This has important implications in terms of scalability and dissemination of CT. These results require confirmation in larger samples.

The risk of drug dependence is determined by the interaction of drug, individual and environment. 'Pharmacogenetics' is the study of the influence of heredity on the response to drugs and their fate in the body; these studies aim to improve the understanding of inter-individual variability in drug response. The authors have applied this research approach to the study of drug metabolism and dependence. Specifically the interaction of genetically variable hepatic cytochrome P450 (CYP) enzymes and their effect on self-administration of drugs has been examined. Many drugs of abuse are substrates (e.g., amphetamines, codeine, nicotine) or inhibitors (e.g., (-)-cocaine) of polymorphic CYPs. Drug metabolism by genetically polymorphic enzymes can have significant clinical implications relating to drug toxicity, therapeutic failure, drug-drug interactions, disease susceptibility and abuse liability. There is good evidence that drug metabolism by genetically variable CYPs can influence the risk of drug dependence, the amount of drug consumed by dependent individuals and some of the toxicities associated with drug-taking behavior. It is anticipated that pharmacogenetics will be used to identify individuals at a greater risk for specific drug dependencies, provide information that can lead to novel treatment and prevention approaches as well as provide guidance for individualization of treatment choice.