First Demonstration That Brain CYP2D-Mediated Opiate Metabolic Activation Alters Analgesia in Vivo.

First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo.

Biochem Pharmacol. 2013 Apr 23;
Zhou K, Khokhar JY, Zhao B, Tyndale RF

The response to centrally-acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigate the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20?g propranolol or 40?g propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30mg/kg subcutaneous codeine, b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30min after 30mg/kg subcutaneous codeine, and c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine’s therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally-acting drugs. HubMed – addiction

All-cause mortality in criminal justice clients with substance use problems-A prospective follow-up study.

Drug Alcohol Depend. 2013 Apr 24;
Hakansson A, Berglund M

BACKGROUND: Mortality in previously incarcerated individuals is known to be elevated, with high proportions of drug-related deaths. However, there is less documentation of whether specific substance use patterns and other clinical characteristics predict increased mortality in the group. METHODS: This is a follow-up study of mortality and causes of death in ex-prisoners with substance use problems prior to incarceration (N=4081), who were followed during an average of 3.6 years from release from prison until death or until data were censored. Baseline predictors of mortality, derived from interviews with Addiction Severity Index (ASI) in prison, were studied in a Cox regression analysis. RESULTS: During follow-up, 166 subjects (4.1%) died. Standardized mortality ratios were 7.0 (3.6-12.2) for females and 7.7 (5.6-9.0) for males. In 84% of cases, deaths were unnatural or due to substance-related disease. Most common causes of death were accidental poisoning (27%), transport accidents (13%), poisoning/injury with undetermined intent (12%), and suicide (10%). Death was positively predicted by heroin use, overdose, and age, and negatively predicted by a history of depression. CONCLUSIONS: A vast majority of deaths after release from prison in individuals with substance use are due to violent or substance-related causes. Significant predictors identified were mainly related to patterns of drug use, and need to be addressed upon incarceration as risk factors of death. The findings have implications for referral and treatment upon release from prison. HubMed – addiction

Substance-specific environmental influences on drug use and drug preference in animals and humans.

Curr Opin Neurobiol. 2013 Apr 24;
Badiani A

Epidemiological, clinical, and preclinical evidence indicate that the setting of drug use can exert a powerful modulatory influence on drug reward and that this influence is substance-specific. When heroin and cocaine co-abusers, for example, report on the circumstances of drug use, they indicate distinct settings for the two drugs: heroin being used preferentially at home and cocaine being used preferentially outside the home. Similar results were obtained in laboratory rats. These findings will be interpreted in the light of a novel model of drug reward, based on the emotional appraisal of central and peripheral drug effects as a function of environmental context. I argue here that drug addiction research has not paid sufficient attention to the substance-specific aspects of drug abuse and this may have contributed to the present dearth of effective treatments. Pharmacological and cognitive-behavioral therapy, for example, should be tailored so as to allow the addict to anticipate, and cope with, the risks associated, in a substance-specific manner, to the different settings of drug use. HubMed – addiction

Psychiatric and Addictive Symptoms of Young Adult Female Indoor Tanners.

Am J Health Promot. 2013 Apr 26;
Heckman CJ, Cohen-Filipic J, Darlow S, Kloss JD, Manne SL, Munshi T

Abstract Purpose . Indoor tanning (IT) increases risk for melanoma and is particularly common among young adult women. IT has also been linked with some psychiatric symptoms, and frequent tanning may indicate tanning dependence (addiction) associated with endorphin release during ultraviolet radiation exposure. The objective of the current study was to investigate associations between IT, tanning dependence, and psychiatric and substance use symptoms in young adult women. Design . Cross-sectional survey and psychiatric interview. Setting . Online, except for the Mini International Neuropsychiatric Interview (MINI), which was completed over the telephone. Subjects . Participants were 306 female university students aged 18 to 25 years. Measures . MINI, Seasonal Scale Index, tanning dependence scales, reporting ever having used a tanning bed or booth with tanning lamps (single item), reporting smoking a cigarette in the last 30 days (single item). Analysis . Descriptive statistics, ?(2) analysis, multivariate logistic regression. Results . Forty-six percent of the sample reported a history of IT, and 25% were classified as tanning dependent. Multivariate logistic regression analyses showed that IT was significantly associated with symptoms of alcohol use disorders, generalized anxiety, and not having social anxiety. Tanning dependence was associated with symptoms of alcohol use disorders. Conclusion . Tanning is of concern not only for its association with skin cancer but for its association with psychiatric and substance use symptoms. Young women with certain psychological problems may seek relief from their symptoms by IT. These findings suggest that indoor tanners may benefit from health behavior and other psychosocial interventions. HubMed – addiction

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