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NIDA Home > Publications > Director's Reports > September, 2009 Index    

Director's Report to the National Advisory Council on Drug Abuse - September, 2009

Research Findings - International Research

Effects of Modafinil on Dopamine Transporter Systems

Dr. Raka Jain of the All India Institute of Medical Sciences and a recipient of a NIDA INVEST Fellowship (19961997) and DISCA award (2006) joined Dr. Michael H. Baumann, IRP, and other colleagues to uncover key findings about modafinil, a drug that has been used off-label to treat cocaine dependence. In a recent study, the researchers examined modafinil's interaction with various receptors and transporters and compared the drug's effects to those of the indirect dopamine agonists GBR12909 and (+)-methamphetamine (METH). Results provide evidence for the involvement of dopamine transporters in the behavioral stimulant effects of modafinil. The finding that modafinil pretreatment reduced behavioral and neurochemical effects of METH support the drug's potential use as an adjunct for treating METH addiction. Zolkowska D, Jain R, Rothman RB, Partilla JS, Roth BL, Setola V, Prisinzano TE, Baumann MH. Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil. Journal of Pharmacology and Experimental Therapeutics. 2009 May;329(2):738-746. Epub 2009 Feb 5.

Publications by Former NIDA Hubert H. Humphrey Fellows

HHH Fellow: Arthur Guerra de Andrade, Brazil, 1991-1992
A high smoking prevalence has been registered among alcoholics. It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism. This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers. The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of So Paulo, Brazil. The sample comprised 155 male alcohol-dependent outpatients (52 non-smokers and 103 smokers), 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, the patients randomly received placebo, naltrexone (50mg/day) or topiramate (up to 300mg/day). Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction. Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65%, independently of the medications prescribed, using the intention-to-treat method. Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients (mean difference=7.91, p<0.01). There were no significant differences between the naltrexone group and the placebo group. The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment. Baltieri DA, Dar FR, Ribeiro PL, Andrade AG. Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients. Drug Alcohol Depend. 2009 Jul 10. [E-pub ahead of print].

HHH Fellow: Tomas Zabransky, Czech Republic, 2003-2004
The aims of this study were to report the results of a comprehensive literature search of studies of mortality among people who use amphetamines. Three electronic databases were searched (EMBASE, Medline and PsycINFO) and "grey" literature was located. Shortlists of papers were circulated to experts to ascertain whether any important papers had been missed. Papers were hand-searched to retrieve any additional relevant articles. Studies meeting inclusion criteria were prospective cohort studies examining mortality risk among dependent and problematic amphetamine users. Crude mortality rates (CMR/100PY) and standardised mortality ratios (SMRs) were the primary outcome measures considered. Data on overall mortality, and rates for specific causes of death, were of interest. 2,187 articles and 9 grey literature sources were obtained. After thorough review, 72 articles were identified as reporting on amphetamine-related mortality, 7 provided data from cohort studies of users. An additional study of Swedish military conscripts was identified by the authors during correspondence with other researchers. The geographic spread of cohorts was restricted to high income countries with the exception of one Thai study; reporting of standard parameters in mortality studies was often sparse. The estimated CMRs ranged from 0 in Australia to 2.95 (1.46-4.59) in Thailand. The Czech cohort reported the only SMR: 6.22 overall, males: 5.87, females: 7.84. Given the widespread use of amphetamines, the known non-fatal adverse effects of use and the mortality rates reported here, cohort studies investigating the morbidity and mortality associated with such drug use should be a research priority. Singleton J, Degenhardt L, Hall W, Zabransky T. Mortality among amphetamine users: A systematic review of cohort studies. Drug Alcohol Depend. 2009 Jul 22. [E-pub ahead of print].

HHH Fellow: Olga Toussova, Russia, 2001-2002
The epidemic of HIV in St. Petersburg, which is currently concentrated among injection drug users (IDUs), may be penetrating into the general population. Non-IDUs who have IDU sex partners (SP) could be potential bridges in an expanding epidemic. To investigate potential bridges, the authors accrued a convenience sample of 288 non-IDUs whose HIV diagnosis was attributed to sexual transmission and determined the proportion that had IDUs among their SP. Having IDU SP ever (lifetime) and IDU SP in the last year were the key variables for the analysis of potential bridges in this study. The interaction of gender and age was found to be a significant predictor of having lifetime IDU SP (p = 0.006, chi (2) test) and IDU SP in the last year (p = 0.05, chi (2) test): females aged 26 and younger were more likely to have both lifetime IDU SP and IDU SP in the last year. Among the group of young females, 46% reported ever having an IDU SP. Out of young women reporting ever having an IDU SP, 85% also reported at least one lifetime non-IDU SP. Among the females aged 26 or younger, a lower level of education (odds ratio [OR] = 2.7, confidence interval [CI] = 1.1-6.7), being born in St. Petersburg (OR = 2.9, CI = 1.2-7.2), and alcohol use in the last 30 days (OR = 3.5, CI = 1.3-9.6) were significant correlates for ever having had an IDU SP. Urgent efforts are necessary to expand HIV prevention to target the potential bridging population to prevent further transmission. Toussova O, Shcherbakova I, Volkova G, Niccolai L, Heimer R, Kozlov A. Potential bridges of heterosexual HIV transmission from drug users to the general population in St. Petersburg, Russia: is it easy to be a young female? J Urban Health. 2009 Jul;86 Suppl 1:121-130.

HHH Fellow: Olga Toussova, Russia, 2001-2002
The HIV epidemic that began in Russia in the mid-1990s has been concentrated mostly among drug users (DUs). Recent evidence of increasing HIV cases among non-DUs attributed to sexual behavior raises potential concern about a more generalized epidemic. The purpose of this analysis is to examine the potential for HIV transmission from DUs to their non-DU sex partners. Analyses are conducted using data collected during 2005-2008 in St. Petersburg, Russia. A total of 631 DUs were recruited into the sample with an HIV prevalence of 45%. A majority (84%) of DUs reported being sexually active in the past 6 months, and the DU status of their sex partners was reported as follows: 54% DU, 40% non-DU, and 6% unknown DU status. In 41% of partnerships with an HIV-negative or unknown status partner not known to be DU (potential bridging partnerships), the last reported intercourse was unprotected. Female DUs with potential bridging partnerships were more likely than male DUs to be younger and report homelessness and to have multiple or new sex partners. Many non-DU sex partners of DUs enrolled in the study reported new sex partners in the past 6 months (66%), unprotected intercourse at last sex (60%), and multiple sex partners in the past 6 months (48%). HIV prevalence in this group was 15% (eight out of 53). The high prevalence of HIV among DUs, their sexual contact with non-DUs, and the high-risk sexual behaviors of this potential bridging population together indicate the real potential for an increasingly generalized epidemic. The degree to which there will be further transmission from non-DU sex partners of DUs who exhibit high levels of sex risk behaviors to other non-DU sex partners deserves further study. Niccolai LM, Shcherbakova IS, Toussova OV, Kozlov AP, Heimer R. The potential for bridging of HIV transmission in the Russian Federation: sex risk behaviors and HIV prevalence among drug users (DUs) and their non-DU sex partners. J Urban Health. 2009 Jul;86 Suppl 1:131-143.

HHH Fellow: Flavio Pechansky, Brazil, 1993-1994
Brazil lacks information about driving under the influence of alcohol (DUI) originated from representative samples obtained from the general population. 333 subjects with a valid driver's license and drinking in the last 12 months were drawn from a multistaged sample of 2,346 adults from the first Brazilian Household Survey of Patterns of Alcohol Use. A multivariate analysis was conducted to understand the associations between risk factors and driving after drinking three or more drinks. The overall DUI prevalence reported in the sample was 34.7% - 42.5% among males and 9.2% among females. Being male (OR = 6.0, 95% CI 2.9-12.6), having a previous DUI accident (OR = 7.9, 95% CI 2.5-24.9), binging in the last year (OR = 2.2, 95% CI 1.03-4.5) and having an unfavorable opinion towards policies (OR = 2.9, 95% CI 1.4-6.2) remained associated with heavy drinking and driving after model adjustments. This was the first study evaluating driving under the influence of alcohol in a representative sample of the Brazilian population. The prevalence of DUI found is alarming, and possibly underestimated in the sample. Results demonstrate the need for more studies on this association and show directions towards preventive strategies for the specific high-risk group of male drivers with previous problems with alcohol and unfavorable opinions about prevention policies. Pechansky F, De Boni R, Diemen LV, Bumaguin D, Pinsky I, Zaleski M, Caetano R, Laranjeira R. Highly reported prevalence of drinking and driving in Brazil: data from the first representative household study. Rev Bras Psiquiatr. 2009 Jun;31(2):125-130.

HHH Fellow: Berna Ulu&gcaron;, Turkey 1995-1996
Recent neuroimaging studies support functional and structural alterations in the dorsolateral prefrontal cortex (DLPFC), particularly on the left side in patients with major depressive disorders (MDD). The aim of the present study was to examine the biochemical characteristics of left DLPFC as measured on proton ((1)H) magnetic resonance spectroscopy (MRS) in patients with drug-nave first-episode MDD and a healthy control group. A second aim was to assess the effect of antidepressant treatment on the metabolites of DLPFC. Short-echo single-voxel (1)H-MRS was done for the left DLPFC in 17 female drug-free MDD patients (mean age +/- SD, 30.9 +/- 6.9 years) and 13 matched control subjects (mean age +/- SD, 29.1 +/- 6.2 years) and was repeated at 8 weeks following antidepressant treatment. Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine [NAA/Cr], myoinositol [Ino]/Cr, and choline [Cho]/Cr) between patients and controls. Significant differences were detected between pre- and post-treatment Ino/Cr ratios (0.67 +/- 0.13, 0.58 +/- 0.22, P = 0.032, respectively), although there was no difference in NAA/Cr and Cho/Cr ratios. Although no significant metabolic alterations exist in female patients with drug-nave first-episode MDD as evaluated on (1)H-MRS, an increase in Ino/Cr was observed following 8-week antidepressant treatment. These findings give rise to the possibility that non-neuronal cells, particularly glial cells that are probably damaged, play a role in the action of antidepressant treatment. Kaymak SU, Demir B, O&gcaron;uz KK, Sentrk S, Ulu&gcaron; B. Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-nave female patients with first-episode major depression. Psychiatry and Clinical Neurosciences 2009 Jun;63(3):350-356.


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