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CORK Bibliography: Cocaine

140 citations. January 2009 to present

Prepared: September 2009

Ahmadi J; Kampman K; Oslin D; Pettinati H; Dackis C; Sparkman T. Predictors of treatment outcome in outpatient cocaine and alcohol dependence treatment. American Journal on Addictions 18(1): 81-86, 2009. (22 refs.)

We examined the ability of several baseline variables to predict treatment outcome in a pharmacotherapy trial that included 164 participants who were both cocaine- and alcohol-dependent and were selected for a randomized, double-blind, placebo-controlled study. Predictor variables included results from the baseline Addiction Severity Index (ASI), initial Urine Drug Screen results, cocaine and alcohol craving and cocaine and alcohol withdrawal symptoms at the start of treatment. Successful treatment was defined as four continuous weeks of self-reported cocaine abstinence verified by urine drug screens. In respect to demographic characteristics, there were no significant differences between patients who achieved four weeks of abstinence from cocaine and those who did not. Baseline variables that most consistently predicted cocaine abstinence included initial urine drug screen (UDS) results, the initial Cocaine Selective Severity Assessment (CSSA) scores, and initial self-reported cocaine use in past 30 days, whereas cocaine craving, cocaine composite scores, alcohol craving, alcohol withdrawal symptoms, and alcohol composite scores did not. The results of this study suggest that cocaine dependence severity in general, and initial UDS results, the CSSA scores and frequency of recent cocaine use in particular, have a significant impact on treatment outcome in the treatment of cocaine-dependent patients with comorbid alcoholism. Initial UDS results and CSSA scores are very useful predictors of treatment outcome and could be used as stratifying variables in outpatient cocaine and alcohol medication trials.

Anderson AL; Reid MS; Li SH; Holmes T; Shemanski L; Slee A et al. Modafinil for the treatment of cocaine dependence. Drug and Alcohol Dependence 104(1-2): 133-139, 2009. (27 refs.)

Aim: Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. Methods: This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. Results: The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine (p = 0.02), and a reduction in craving (p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p < 0.02). Conclusions: These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Bagner DM; Sheinkopf SJ; Miller-Loncar C; LaGasse LL; Lester BM; Liu J et al. The effect of parenting stress on child behavior problems in high-risk children with prenatal drug exposure. Child Psychiatry & Human Development 40(1): 73-84, 2009. (31 refs.)

Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large sample of children (n = 1,388) with prenatal cocaine exposure and a comparison sample unexposed to cocaine. Of the 607 dyads, 221 were prenatally exposed to cocaine and 386 were unexposed to cocaine. Selection was based on the presence of a stable caregiver at 4 and 36 months with no evidence of change in caregiver between those time points. Results: Parenting stress at 4 months significantly predicted child externalizing behavior at 36 months. These relations were unaffected by cocaine exposure suggesting the relationship between parenting stress and behavioral outcome exists for high-risk children regardless of drug exposure history. Conclusions: These results extend the findings of the relationship between parenting stress and child behavior to a sample of high-risk children with prenatal drug exposure. Implications for outcome and treatment are discussed.

Basurto FZ; Montes JMG; Cubos PF; Santed FS; Rios FL; Moreno AM. Validity of the self-report on drug use by university students: Correspondence between self-reported use and use detected in urine. Psicothema 21(2): 213-219, 2009. (26 refs.)

The purpose of this work was to determine the validity of a self-report on recent drug use (cocaine and cannabis) in a sample of university students of both sexes and to explore the role of attitudes toward substance use as related to this report. The subjects (506) were volunteers aged 17-35 years (who received an economic incentive) recruited at the University of Almeria (Spain). The results were analyzed on the basis of correspondence between the self-report of recent use and a urine test. Three logistic regression analyses between self-reported use and attitudes toward drugs were also performed. The results show that the convergent validity of the self-report of drug use and the urine test is quite satisfactory, with percentages of agreement varying from .89 to .98 and Kappa of .66 and .56 for cannabis and cocaine, respectively. Sensitivity of the self-report is 57.1% (cocaine) and 91.8% (cannabis), and specificity is 99.4% (cocaine) and 89.6% (cannabis). The differences found in correspondence between the two substances are discussed with regard to self-reported attitudes on drug use.

Baum MK; Rafie C; Lai S; Sales S; Page B; Campa A. Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users. Journal of Acquired Immune Deficiency Syndromes 50(1): 93-99, 2009. (32 refs.)

Background: HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. Methods: A prospective, 30-month, longitudinal Study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4(+) cell count, and viral load were performed every 6 months. Results: Crack-cocaine users were 2.14 times [95% confidence interval (Cl): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to <= 200 cells/mL, independent of antiretroviral use. Viral load over 30 months was significantly higher in crack users (P = 0.315, P = 0.037) independent of highly active antiretroviral therapy (HAART) over time. The only multidrug combination that significantly increased the risk of disease progression was crack cocaine with marijuana (hazard ratio = 2.42; 95% CI: 1.042 to 5.617, P = 0.04). Of those on HAART. a significantly lower proportion of crack-cocaine users versus nonusers had controlled viral load (P < 0.001). suggesting lower medication adherence, whereas crack-cocaine users not on HAART showed a greater risk for HIV disease progression than nonusers (hazard ratio = 3.946; 95% CI: 1.049 to 14.85, P = 0.042). Conclusions: Crack-cocaine use facilitates HIV disease progression by reducing adherence in those on HAART and by accelerating 9 disease progression independently of HAART.

Behar JM; Lindsay AC; McEwan JR. Cocaine-induced myocardial infarction: Not your average acute coronary syndrome. British Journal of Hospital Medicine 70(2): 108-109, 2009. (13 refs.)

This is a case report of a 31 year old woman who presented to an ER complaining of chest pains. Only 15 hours post-admission did she acknowledge being a regular cocaine user, who had smoked cocaine as well as injecting cocaine into the femeral artery the previous night, after which she experienced severe chest pain. Coronary angiopgraphy revelaed a thrombus in the proximal left anterior descending artery. The discussion summarizes the basis for cardiovascular problems in response to cocaine use, diagnostic issues, and clinical management and how cocaine-induced myocardial infarction requires different management than other acute coronary syndromes.

Bellis MA; Hughes K; Calafat A; Juan M; Schnitzer S. Relative contributions of holiday location and nationality to changes in recreational drug taking behaviour: A natural experiment in the Balearic Islands. European Addiction Research 15(2): 78-86, 2009. (35 refs.)

Aim: To examine the contributions of international holiday resorts and visitors' nationality to recruitment, relapse into, and escalation in frequency of recreational drug use. Methods: Retrospective design surveying British, German and Spanish (n = 3,003) holidaymakers aged 16-35 visiting Ibiza or Majorca (Spain). Results: Individuals' drug use in international resorts was related to use at home, holiday destination and nationality. While visiting Ibiza, 7.2% of British tourists tried ecstasy for the first time with similar recruitment amongst Spanish (8.6%) but not Germans (1.8%) or those visiting Majorca (0.8, 1.5 and 1.2%, respectively). Recruitment into cocaine use was associated with being Spanish, male, visiting Ibiza and drunkenness. One in 5 British holidaymakers visiting Ibiza tried at least one new drug. British and Spanish were most likely to relapse into using a drug after at least 12 months' abstinence; 6.8% of British (1.3% German, 2.9% Spanish) relapsed into using at least one drug. Across nationalities, substance use frequency increased on holiday. Conclusions: International nightlife resorts are major sources of recruitment, relapse and escalation in drug use. Such resorts contribute to the international spread of drug cultures but have been largely ignored as settings for interventions to tackle drugs.

Berg T; Lundanes E; Christophersen AS; Strand DH. Determination of opiates and cocaine in urine by high pH mobile phase reversed phase UPLC-MS/MS. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences 877(4): 421-432, 2009. (33 refs.)

A fast and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of opiates (morphine, codeine, 6-monoacetylmorphine (6-MAM), pholcodine. oxycodone, ethylmorphine), cocaine and benzoylecgonine in urine has been developed and validated. Sample preparation was performed by solid phase extraction (SPE) on a mixed mode cation exchange (MCX) cartridge. For optimized chromatographic performance with repeatable retention times, narrow and symmetrical peaks, and focusing of all analytes at the Column inlet at gradient start, a basic mobile phase consisting of 5 mM ammonium bicarbonate, pH 10.2, and methanol (MeOH) was chosen. Positive electrospray ionization (ESI+) MS/MS detection was performed with a minimum of two multiple reaction monitoring (MRM) transitions for each analyte. Deuterium labelled-internal standards were used for six of the analytes. Between-assay retention time repeatabilities (n = 10 series, 225 injections in total) had relative standard deviation (RSD) values within 0.1-0.6%. Limit of detection (LOD) and limit of quantification (LOQ) values were in the range 0.003-0.051 mu M (0.001-0.02 mu g/mL) and 0.01-0.16 mu M (0.003-0.06 mu g/mL), respectively. The RSD values of the between-assay repeatabilities of concentrations were <= 10% at five concentration levels for all analytes, except for pholcodine. Specificity was investigated by determination of the retention times of 96 drugs and internal standards in total. Co-eluting compounds were in all cases separated by the MS/MS detection. No or only minor matrix effects were observed. Total run time, including injection and equilibration time was 5.7 min. The method has been routinely used at the Norwegian Institute of Public Health (NIPH) since August 2007 for qualitative detection of opiates, cocaine and benzoylecgonine in more than 2000 urine samples with two replicates of each sample.

Beynon CM. Drug use and ageing: Older people do take drugs! (editorial). Age and Ageing 38(1): 8-10, 2009. (12 refs.)

While usually perceived as behaviour of the young, use of illicit drugs by people aged 50 and over is increasing in Europe and the USA. This increase largely reflects the ageing of general populations, and people who use drugs continuing to do so as they age. For those people dependent upon drugs [usually users of opiates (heroin) and stimulants (cocaine, crack cocaine and amphetamine)], the last 30 years has seen the advent of effective treatment and harm minimisation initiatives and, coupled with general advances in medicine, has increased the life expectancy of these drug users. Drug use by older people presents unique problems; biological systems and processes alter naturally across the life course and the effect of concurrent drug use on some of these systems is not well understood. The natural progression of certain diseases means that symptoms only manifest in older age and the lives of older drug users are likely to be characterised by considerable levels of morbidity. Further work is needed on the epidemiology of drug use by older people---a group of people who currently represent a hidden and vulnerable population.

Blazer DG; Wu LT. The epidemiology of substance use and disorders among middle aged and elderly community adults: National Survey on Drug Use and Health. American Journal of Geriatric Psychiatry 17(3): 237-245, 2009. (20 refs.)

Objective: To estimate the prevalence, distribution, and correlates of drug use among middle aged and elderly persons in the United States and to compare with alcohol use in this age group. Setting: The 2005 and 2006 National Surveys oil Drug Use and Health. Participants: A total of 10,953 subjects age 50 years and older (6,717 subjects age 50-64 years and 4,236 subjects age 65+ years). Measurements: Social and demographic variables detailed assessment of alcohol and drug use and disorders (marijuana, cocaine, inhalants, hallucinogens, methamphetamine, and heroin), major depression, and self-rated health. Results: Nearly 60% of subjects used alcohol during the past year, 2.6% marijuana, and 0.41% cocaine. Both alcohol and drug use were far more frequent in subjects age 50-64 years and among men. Drug use, in contrast to alcohol use, was not associated with education but was more common among those not married and those with major depression. The prevalence of drug abuse or dependence in the 50+ age group was very low (only 0-33% for any abuse or dependence, 0.12% for marijuana abuse or dependence, and 0.18% for cocaine abuse or dependence). Nevertheless, the use of marijuana approached 4% in the 50-64 age group in comparison with 0.7% in the 65+ age group. Conclusions: Drug use is not prevalent, although use is much more common in the middle aged, suggesting that prevalence may rise substantially in the 65+ age group as the younger cohort ages.

Bohnert ASB; Bradshaw CP; Latkin CA. A social network perspective on heroin and cocaine use among adults: Evidence of bidirectional influences. Addiction 104(7): 1210-1218, 2009. (46 refs.)

While several studies have documented a relationship between initiation of drug use and social network drug use in youth, the direction of this association is not well understood, particularly among adults or for stages of drug involvement beyond initiation. The present study sought to examine two competing theories (social selection and social influence) in the longitudinal relationship between drug use (heroin and/or cocaine) and social network drug use among drug-experienced adults. Three waves of data came from a cohort of 1108 adults reporting a life-time history of heroin and/or cocaine use. Low-income neighborhoods with high rates of drug use in Baltimore, Maryland. Participants had weekly contact with drug users and were 18 years of age or older. Drug use data were self-report. Network drug use was assessed through a social network inventory. Close friends were individuals whom the participant reported seeing daily or rated as having the highest level of trust. Structural equation modeling indicated significant bidirectional influences. The majority of change in network drug use over time was due to change in the composition of the network rather than change in friends' behavior. Drug use by close peers did not influence participant drug use beyond the total network. There is evidence of both social selection and social influence processes in the association between drug use and network drug use among drug-experienced adults.

Boulmay B; Lottenherg R. Cocaine abuse complicating acute painful episodes in sickle cell disease. Southern Medical Journal 102(1): 87-88, 2009. (8 refs.)

We report three sickle cell patients with recent cocaine abuse who presented with typical symptoms of vaso-occlusion rapidly progressing to major organ dysfunction. Our experience suggests cocaine abuse is a risk factor for major complications of a sickle cell painful episode. Enhanced clinical and laboratory surveillance for organ dysfunction is indicated if a history of cocaine abuse is elicited. Evidence of organ failure should lead to consideration of early aggressive interventions such as transfusion therapy.

Brugal MT; Pulido J; Toro C; de la Fuente L; Bravo MJ; Ballesta R et al. Injecting, sexual risk behaviors and HIV infection in young cocaine and heroin users in spain. European Addiction Research 15(3): 171-178, 2009. (44 refs.)

Aim: To evaluate differences between young cocaine users and heroin users (HUs) regarding the prevalence of sexual and injection risk behavior, and HIV, HCV and HBV infection. Methods: Two community cohorts were recruited in Madrid, Barcelona and Seville; 720 cocaine users, of whom 586 had never used heroin (CUs), and 991 HUs were interviewed. Dried blood spot samples were tested. Results: CUs were less marginalized socially than HUs. Only 0.9% had ever injected versus 64.3%; none had ever injected with borrowed syringes versus 25%; 2.2% had an injecting steady partner in the last 12 months versus 24.9%; 4.8% had ever traded sex versus 16.0%. However, 31.0 versus 12.7% had unprotected sex with more than two occasional partners in the last 12 months; 45.0 versus 21.9% had sniffed through tubes used by more than 10 persons. Only 32.3% knew their HIV status versus 80.3%; 0.4 versus 18.1% were HIV positive; 0.9 versus 51.9% were HCV positive, and 1.5 versus 17.0% were HBV positive. Conclusions: The intense cocaine epidemic has hitherto had little impact on either HIV, HBV or HCV in Spain. However, surveillance should be intensified given the high percentage of CUs having unprotected sex with occasional partners.

Brunt TM; Rigter S; Hoek J; Vogels N; van Dijk P; Niesink RJM. An analysis of cocaine powder in the Netherlands: Content and health hazards due to adulterants. Addiction 104(5): 798-805, 2009. (38 refs.)

Aims: To report on trends in the content and adulterants present in street cocaine ( powder) in the Netherlands and to describe the associated health hazards. Design and participants Drug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users' experiences with the samples received. Measurements and analysis Linear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fisher's exact test. Findings There has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects. Conclusions An increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.

Cabanas JG; Brice JH; Woodward K. An unrecognized presentation of cocaine-associated pneumomediastinum in the prehospital setting. Prehospital Emergency Care 13(3): 384-387, 2009. (18 refs.)

Cocaine abuse is associated with a significant number of emergency medical services (EMS) calls and emergency department visits every year. The medical complications of recreational cocaine use are diverse, involving almost any body organ, and vary greatly according to the substance used and the route by which is taken. Previous reports have associated cocaine abuse with serious pulmonary complications, including barotrauma. The occurrence of barotrauma is directly related to the way cocaine is consumed. The majority may manifest clinically with subcutaneous emphysema, chest pain, and neck pain. We report a case of cocaine-induced pneumomediastinum in the prehospital environment that masqueraded as an allergic reaction. Prehospital providers should be alert for clinical manifestations suggestive of barotrauma in cocaine users.

Cerny EH; Cerny T. Vaccines against nicotine. (review). Human Vaccines 5(4): 200-205, 2009. (38 refs.)

Medications against any dependence-inducing drug face a dilemma: if they are efficient, they will induce withdrawal symptoms and the patient is likely to stop taking his medication. Anti-drug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting rather with the drug in the blood than with a receptor in the brain, the vaccines are, in addition, free of side effects due to central interaction. For drugs like nicotine interacting with different types of receptors in many organs, this is a further advantage. There are three reasons that anti drug vaccines have first been developed against nicotine. Firstly, in most parts of the world 20 to 50% of the adult population smoke and any smoking cessation treatment will have an important impact on public health and be commercially a very attractive product. The second reason are the smokers themselves, who would like to quit in significant numbers and who have shown good compliance for any form of treatment. Thirdly, the quantities of cocaine or heroine taken by dependant persons are higher than the quantity of nicotine per cigarette, which makes an anti nicotine vaccine the easier vaccine project. Three anti nicotine vaccines are today in an advanced stage of clinical evaluation. We report here how those vaccines work, on the progress of the trials and future developments to expect. Results show that the efficiency of the vaccines is directly related to the antibody levels of the probates, a fact which will help to optimize further the vaccine effect. We expect the vaccines to appear on the market during a time window between 2009 and 2011.

Chae SM; Covington CY. Biobehavioral outcomes in adolescents and young adults prenatally exposed to cocaine: Evidence from animal models. Biological Research for Nursing 10(4): 318-330, 2009. (83 refs.)

Cocaine has been a popular illicit drug among drugusing pregnant women over the last three decades. Prenatal cocaine exposure (PCE) has significant effects on children's development throughout early childhood. Very few human studies, however, report the effects of PCE on adolescent or early-adult development. As knowledge about early childhood effects in human children was informed by animal studies, this review considers the effects of PCE on behavioral outcomes in adolescent and young adult animals and provides potential guidance for research in human children. Animal models prenatally exposed to cocaine manifest play deficits, decreased social interaction, and increased aggression during competition in adolescence and young adulthood. Altered behavioral adaptation after stress exposure, including hormonal response change, is also evident. Attention deficits are reported in adult offspring with PCE, not only in a novel environment, but also in a final task session, indicating effects of PCE on transition and maintenance of attention. Animal studies support that PCE effects may extend beyond early childhood and continue to adolescence and adulthood. Additionally, some studies highlight that behavioral changes in offspring with PCE born without teratogenesis remain latent and reveal themselves during adulthood when animals are under stress conditions. Based on the evidence from animal models, well-designed human studies are needed to elucidate the effects of PCE on older human children. Research models that combine behavioral measures with stressful challenges may hold potential in discerning a longer term influence 4 PCE.

Chao C; Jacobson LP; Jenkins FJ; Tashkin D; Martinez-Maza O; Roth MD et al. Recreational drug use and risk of Kaposi's sarcoma in HIV- and HHV-8-coinfected homosexual men. AIDS Research and Human Retroviruses 25(2): 149-156, 2009. (50 refs.)

Experimental data suggested that exposure to recreational drugs might adversely affect antitumor immunity, which led us to examine the hypothesis that use of marijuana, cocaine, poppers, and amphetamines might increase the risk of Kaposi's Sarcoma (KS) in HIV- and HHV-8-coinfected homosexual men. We analyzed data prospectively collected from the Multicenter AIDS Cohort Study (MACS) between 1984 and 2002. Among the 1335 HIV- and HHV-8-coinfected white men, 401 KS cases were identified. Multivariable Cox regression models were used to estimate the effects of time-varying recreational drug use on KS risk adjusting for potential confounders. The effects of both recent use (6 months prior) of recreational drugs and lagged exposure (i.e., use from 3 and 5 years prior) were examined. We did not observe any clear association with KS for recent use of any of the four drugs. In the analyses using lagged exposures, KS risk was associated with use of poppers 3-5 years prior [hazard ratio (HR) 3 years prior 1.27, 95% CI (0.97-1.67), HR5 years prior 1.46 (1.01-2.13)]. However, no clear dose-response relationship was observed. These findings do not support a biological association between use of these substances and KS development in HIV- and HHV-8-coinfected homosexual men.

Chen CY; Storr CL; Anthony JC. Early-onset drug use and risk for drug dependence problems. Addictive Behaviors 34(3): 319-322, 2009. (20 refs.)

There is substantial evidence that alcohol, tobacco, and cannabis dependence problems surface more quickly when use of these drugs starts before adulthood, but the evidence based on other internationally regulated drugs (e.g., cocaine) is meager. With focus on an interval of up to 24 months following first drug use, we examine drug-specific and age-specific variation in profiles of early-emerging clinical features associated with drug dependence. Based upon the United States National Surveys on Drug Use and Health (NSDUH) conducted in 2000-2002, the risk of experiencing drug dependence problems was robustly greater for adolescent recent-onset users of cocaine, psychostimulant drugs other than cocaine, analgesics, anxiolytic medicines. inhalants drugs, and cannabis, as compared to adult recent-onset users (odds ratio = 1.5-4.3, p<0.05). This was not the case for the NSDUH hallucinogens group (e.g., LSD). The adolescent onset associated excess risk was not constant across all clinical features. Our evidence suggests promoting earlier detection and interventions, as well as greater parent and peer awareness of drug dependence clinical features that may develop early among young people who have just started using drugs.

Chen SC; Jang MY; Wang CS; Tsai KB; Chuang SH; Chen HC et al. Cocaine-related vasculitis causing scrotal gangrene. Annals of Pharmacotherapy 43(2): 375-378, 2009. (17 refs.)

OBJECTIVE: To describe a case of possible cocaine-related vasculitis resulting in gangrene of the scrotum and review the literature on cocaine-related vascular complications. CASE SUMMARY: A 22-year-old male presented with fever, painful swelling of the right scrotum, and a blackened ulcerated lesion on the right scrotum 3 hours after smoking crack cocaine. Blood and urine cultures and serologic tests were negative, and the D-dimer level was normal. Echocardiogram showed no evidence of vegetation and results of a chest X-ray were normal, Despite treatment for presumptive orchitis with intravenous levofloxacin 750 mg/day, the ulcerated lesion of the right scrotum progressed the next day. The patient received debridement of the necrotic tissue and pathology revealed some degenerated vessels with fibrinoid deposits and inflammatory infiltrates, suggestive of vasculitis. No further tenderness and swelling of the scrotum occurred and the patient was discharged after 10 days. When he returned for follow-up, the wound had healed completely. DISCUSSIONS: Cocaine-related vascular complications, including ischemic stroke, myocardial infarction, and peripheral occlusive disease, all of which have various possible mechanisms, are of Clinical importance. Vasculitis is one of the mechanisms of vascular complications associated with cocaine use. According to the Naranjo probability scale, cocaine was the possible causative agent of the patient's vasculitis, which led to scrotum gangrene. To our knowledge, this is the first report in the literature of scrotum gangrene developing after crack cocaine was smoked. CONCLUSIONS: This case report describes a rare occurrence of gangrene of the scrotum associated with cocaine smoking, which is consistent with cocaine's potent vasoconstrictive activity. Cocaine abuse has the potential to cause clinically significant ischemic events anywhere in the body, independent of the method of administration.

Chiriboga CA; Starr D; Kuhn L; Wasserman GA. Prenatal cocaine exposure and prolonged focus attention. Developmental Neuroscience 31(1/2): 149-158, 2009. (66 refs.)

In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development of systems implicated in modulating attention. To determine whether prenatal cocaine exposure affects infant attention, we assessed visual recognition memory and focused attention during free play. We enrolled at birth 380 infants, 113 cocaine exposed, using multiple biomarkers to assess drug exposure. Behavior was videotaped and coded off-line for sustained looking time (i.e. focused attention), banging and intrusion. Prenatal cocaine exposure was not associated with visual recognition memory, but was significantly associated with longer sustained looking times (average focused attention) at ages 6 months (p = 0.02) and 12 months (p = 0.04) in analyses that adjusted for variables, including maternal intelligence, education, depressive scores and other exposures (alcohol, tobacco and marijuana). Cocaine-exposed infants at age 12 months also spent significantly less time in banging activity (p = 0.02) after adjusting for confounding variables. This finding was not explained through cocaine effects on motor development, neurological findings or time spent in focused attention. Prenatal cocaine exposure was significantly associated with longer periods of sustained looking or focused attention in infancy, a finding that could interpreted as a measure of poor processing efficiency, or alternatively as precocious maturation of attentional systems. Either interpretation has implications for later cognitive development. Lower banging activity among cocaine exposed was not explained through cocaine effects on motor development or neurological findings, suggesting that activity level itself is diminished in these infants. Whether focused attention findings impact long term development awaits further study.

Chopra MP; Landes RD; Gatchalian KM; Jackson LC; Buchhalter AR; Stitzer ML et al. Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine. Experimental and Clinical Psychopharmacology 17(4): 226-236, 2009. (37 refs.)

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030). while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Ciorba A; Bovo R; Prosser S; Martini A. Considerations on the physiopathological mechanism of inner ear damage induced by intravenous cocaine abuse: Cues from a case report. Auris Nasus Larynx 36(2): 213-217, 2009. (12 refs.)

Objective: Aim of the following paper is to discuss about the possible etiopathogenctic mechanisms of inner car damage induced by cocaine abuse. Unfortunately the data concerning this topic are very limited; the authors are then presenting a literature review, also discussing the clinical presentation and the possible therapeutical approach of a clinical case of bilateral Sudden sensorineural hearing loss following i.v. injection of cocaine. Patients: Case report. Intervention: A strictly audiological evaluation has been performed, in order to identify the cochlear lesion site(s) and to provide the best medical treatment. Conclusions: To our knowledge, this is the first report of acute cocaine intoxication with sudden bilateral hearing loss. Further studies are required in order to understand the effects of these substances oil the inner car cells and metabolism.

DeFulio A; Donlin WD; Wong CJ; Silverman K. Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: A randomized controlled trial. Addiction 104(9): 1530-1538, 2009. (46 refs.)

Context: Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. Objective: To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Design: Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. Setting: A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Intervention: Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Main outcome measure: Cocaine-negative urine samples at monthly assessments across 1 year of employment. Results: During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60-8.69]. Conclusions: Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments for drug dependence. Work-places could serve as therapeutic agents in the treatment of drug dependence by arranging long-term employment-based contingency management programs.

Dembo R; Sullivan C. Cocaine use and delinquent behavior among high-risk youths: A growth model of parallel processes. Journal of Child & Adolescent Substance Abuse 18(3): 274-301, 2009. (87 refs.)

We report the results of a parallel-process, latent growth model analysis examining the relationships between cocaine use and delinquent behavior among youths. The study examined a sample of 278 justice-involved juveniles completing at least one of three follow-up interviews as part of a National Institute on Drug Abuse-funded study. The results of our analysis of the cocaine use and delinquency parallel-process model highlighted that these phenomena are mutually related experiences over time. Particularly noteworthy is the significant, positive relationship between cocaine trend and delinquency trend: as the rate of change in cocaine use increases, a corresponding change occurs in engaging in delinquent behavior. Implications for policy and intervention service needs are discussed.

Draus PJ; Carlson RG. "The Game Turns on You:" Crack, sex, gender, and power in small-town Ohio. Journal of Contemporary Ethnography 38(3): 384-408, 2009

Exchanges of sex for crack cocaine have received much attention from public health researchers and ethnographers of substance abuse. These exchanges are often viewed as one-dimensional relationships in which men use their access to crack cocaine and women's dependence on the drug to exploit them sexually. Drawing on in-depth interview data gathered during three years of research conducted in central Ohio, this article examines the relationship between sexual behavior and crack cocaine use from both male and female perspectives. Bourdieu's concept of fields is then applied to illuminate the relational dimensions of gender, sex, and power within this local crack-cocaine using scene, while also illustrating the domination inherent in most scenarios involving crack-for-sex exchange. Implications for possible interventions based on this analysis are also discussed.

Epstein DH; Schmittner J; Umbricht A; Schroeder JR; Moolchan ET; Preston KL. Promoting abstinence from cocaine and heroin with a methadone dose increase and a novel contingency. Drug and Alcohol Dependence 101(1-2): 92-100, 2009. (43 refs.)

To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 x 3 (dose x contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. The were randomly assigned to methadone dose (70 or 100 mg/day, double-blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or "split"). The "split" contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was "split" between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin. cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine Study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The split 100 mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required.

Farrer LA; Kranzler HR; Yu Y; Weiss RD; Brady KT; Anton R et al. Association of variants in MANEA with cocaine-related behaviors. Archives of General Psychiatry 66(3): 267-274, 2009. (51 refs.)

Context: Cocaine dependence (CD) and related behaviors are highly heritable, but no genetic association has been consistently demonstrated. A recent genome-wide study of drug dependence identified an association between cocaine-induced paranoia (CIP) and a single-nucleotide polymorphism (SNP) in the alpha-endomannosidase (MANEA) locus in a family-based sample of European Americans and African Americans. Objective: To conduct a comprehensive genetic association study of the MANEA locus with CD and CIP. Design: Genome-wide association study. Setting: Four university hospitals. Participants: A total of 3992 individuals from 2 family-based and 2 case-control samples. Intervention: Participants were classified as having CD or CIP or as a control using the Semi- Structured Assessment for Drug Dependence and Alcoholism. They were genotyped for 11 SNPs spanning MANEA and its surrounding region. Main Outcome Measure: Association of CD and CIP with individual SNPs and haplotypes. Results: Cocaine-induced paranoia was associated with 6 SNPs in the European American families and 9 SNPs in the African American families. The strongest evidence in the total sample of families was observed in 3 markers located in the promoter and 3' untranslated regions (P < .001). The association of MANEA SNPs with CD in both family samples was much weaker. In the African American case-control sample, multiple markers were significantly associated with CIP and CD; CIP and CD were also significantly associated with a 2-SNP haplotype in the European American case-control sample. The A allele of the 3' untranslated region SNP rs9387522 was associated with increased risk of CIP in all 4 data sets. Conclusions: Our findings suggest that CD and associated behaviors may involve biological pathways not typically thought to be associated with brain metabolism.

Ford JD; Gelernter J; Devoe JS; Zhang W; Weiss RD; Brady K et al. Association of psychiatric and substance use disorder comorbidity with cocaine dependence severity and treatment utilization in cocaine-dependent individuals. Drug and Alcohol Dependence 99(1-3): 193-203, 2009. (74 refs.)

The relations among psychiatric and substance dependence disorders and treatment utilization are of interest both for their clinical management and for health services. We examined these relations using six self-reported indices of cocaine dependence severity and three self-reported measures of treatment utilization and self-help group participation for cocaine dependence. The sample consisted of dyads: namely, a cocaine-dependent adult proband (N=449) and a cocaine-dependent sibling (N=449). Psychiatric and substance use disorders were assessed with the semi-structured Assessment for Drug Dependence and Alcoholism. We controlled for the nesting within families of proband-sibling dyads and for demographic features using generalized estimating equation linear and logistic regression analyses. We found that psychiatric disorders were associated with an increased likelihood of cocaine dependence treatment or self-help group participation, but with only one of six indices of cocaine dependence severity. Bipolar disorder and antisocial personality disorder were associated with greater past heavy cocaine use, and with utilizing self-help but not treatment. Major depressive disorder and posttraumatic stress disorder were associated with treatment utilization and overall services utilization, respectively. The presence of other substance use disorders (SUDs) was the strongest correlate of cocaine dependence severity. Results suggest that co-occurring substance dependence and psychiatric disorders warrant attention in cocaine dependence assessment, treatment, and self-help.

Freeborn BA. Arrest Avoidance: Law Enforcement and the Price of Cocaine. Journal of Law & Economics 52(1): 19-40, 2009. (22 refs.)

Contrary to one goal of drug law enforcement, cocaine prices decreased between the years 1986 and 2000. This paper discusses how arrest avoidance behavior may affect cocaine consumer and dealer response to law enforcement. Dealers avoid arrest by making quick and easy sales; thus, pure-gram price is negatively related to dealer enforcement. Consumers avoid arrest by accepting high prices rather than searching for lower prices. Thus, pure-gram price is positively related to consumer enforcement. Because the implications from arrest avoidance conflict with traditional models of how enforcement should affect prices, I also empirically examine the relationship. Using purchase-level data from the Drug Enforcement Administration and legal penalty data, I find a negative, significant relationship between dealer enforcement and pure-gram price and a positive, significant relationship between consumer enforcement and pure-gram price. Both are consistent with the intuition of arrest avoidance.

Garcia-Bournissen F; Moller M; Nesterenko M; Karaskov T; Koren G. Pharmacokinetics of disappearance of cocaine from hair after discontinuation of drug use. Forensic Science International 189(1-3): 24-27, 2009. (13 refs.)

Methods that employ detection of drugs of abuse in hair are important for monitoring compliance with drug abstinence. Understanding the mechanisms and timeline of drug disappearance from hair is critical for clinical and forensic application of hair testing. We aimed to evaluate the kinetics of disappearance of cocaine and its metabolite, benzoylecgonine (BE), from hair after discontinuation of drug use. Methods: The Motherisk laboratory at the Hospital for Sick Children in Toronto routinely receives hair samples for toxicology analysis. Cocaine and BE hair results were obtained from the Motherisk Database for calculation of half-life of these compounds in hair. Subjects were included in the study if they had gradually decreasing concentrations of cocaine and/or BE in sequential hair samples, with higher levels in the 1-3 cm distal segments (i.e. earlier in time) and low or non-measurable levels in the segment closest to the scalp (i.e. closer to the date of sampling). Elimination half-life of cocaine and BE in hair was calculated using standard kinetics calculations. The study was anonymous, and received ethics approval by the Ethics Review Board of our institution. Results: 137 subjects met the inclusion criteria for the study. The median half-life of cocaine in hair was 1.5 months (95% Cl 1.2-1.8) in females and 1.5 months (95% Cl 1.1-1.8) in males. The median half-life of BE was 1.5 months (95% Cl 1.1-2) in females and 1.5 months (95% CI 0.8-1.8) in males. Half lives of cocaine or BE were not statistically different between males and females (Mann-Whitney U-test; P = 0.93 for cocaine, P = 0.99 for BE). Half lives of cocaine and BE were strongly correlated (Spearman rank rho = 0.73: P < 0.001). Conclusion: Cocaine and BE could be detected in hair of former drug users for several months after abstinence. The calculated half-life of over 1 month for cocaine implies that, assuming first order elimination, approximately 3-4 months have to pass for hair testing to become negative in the segment proximal to the scalp. This finding should be incorporated in interpreting compliance with abstinence of former drug users, and suggests that caution has to be exerted when evaluating potential breaches of abstinence.

Garcia-Rodriguez O; Secades-Villa R; Higgins ST; Fernandez-Hermida JR; Carballo JL; Perez JME et al. Effects of voucher-based intervention on abstinence and retention in an outpatient treatment for cocaine addiction: A randomized controlled trial. Experimental and Clinical Psychopharmacology 17(3): 131-138, 2009. (26 refs.)

The aims of this study were to assess whether voucher magnitude improved cocaine abstinence and retention in an Outpatient treatment for cocaine dependence, and to determine the effectiveness of a contingency management intervention in a European cultural context. A randomized controlled trial was conducted in which 96 participants who were randomly assigned to I of 3 treatment conditions in a community setting: standard outpatient treatment, community reinforcement approach (CRA) plus low monetary value vouchers (each point earned was equivalent to 0.125(sic), US$ 0.18), and CRA plus high monetary value vouchers (each point was worth 0.25(sic), US$ 0.36). In the standard treatment group, mean percentage of cocaine-negative samples was 88.45%, versus 96.09% in the CRA plus low-vouchers group, and 97.07% in the CRA plus high-vouchers group. Retention rate at 6 months was 36.5% in the standard treatment group, 53.3% in the CRA plus low-vouchers group, and 69.0% in the CRA plus high-vouchers group. The CRA plus vouchers groups obtained better results than the standard program. This study showed that treating cocaine addiction by combining CRA with vouchers was more effective than standard treatment in community outpatient programs in Spain.

Godlaski TM; Butler L; Heron M; Debord S; Cauvin L. A qualitative exploration of engagement among rural women entering substance user treatment. Substance Use & Misuse 44(1): 62-83, 2009. (57 refs.)

A semistructured interview was administered to a purposive sample of 12 rural women early in substance misuser treatment in a gender specific, intensive outpatient treatment program from March 2001 through March 2003. The interview used open-ended questions about the women's state of mind before entering treatment, the experiences that helped them feel more comfortable with treatment, the experiences that caused them some discomfort in treatment, and any changes they would recommend to the program content or process in an attempt to gain understanding about factors that might facilitate a subjective comfort and engagement with the treatment experience. In approaching treatment, the women almost uniformly expressed a mixture of anxiety about the requirements of treatment and cynicism about its effectiveness. Although aware of the content and structure of the treatment program, the women focused on interpersonal experiences as the critical factors in their level of comfort once in treatment. The most frequently mentioned factors adding to comfort with the treatment experience were the welcoming, accepting, and non-judgmental attitudes of the staff; having their perceptions of their problems taken seriously by the treatment staff; being with other women who shared much of their experiences; and a respectful and generally positive attitude on the part of both the staff and the patients. The only factor that consistently caused some of the women discomfort in treatment was a difficulty in trusting that some of the other women in treatment would keep the matters discussed in group sessions confidential. The women were not completely satisfied with the program content and structure, but this seemed of very little importance to them in relation to their experience of comfort with their tience.

Goel RK. Cigarette prices and illicit drug use: is there a connection? Applied Economics 41(9): 1071-1076, 2009. (14 refs.)

Using cross-sectional data from the United States, this study examines the effects of cigarette prices on the use of marijuana and illicit drugs (including marijuana, cocaine, heroin, inhalants, hallucinogens or any prescription drugs for nonmedical use). Five primary contributions of this work are: First, it provides evidence on the cross-relation between cigarettes and marijuana and illicit drugs. Second, besides the 'standard' control variables used in demand studies (namely, price, education and income), we also control for the influence of employment status and health insurance coverage. Third, this research provides new evidence on the price elasticity of cigarette demand for a recent time period. Fourth, the data used in this study are the latest available. Five, based on our results, implications for drug use policy are provided. Several key points may be noted from our results: (i) Cigarette demand seems to have become elastic in recent years. This is in contrast to findings in earlier years; (ii) Consumers seem to view cigarettes and marijuana as substitutes and cigarettes and illicit drugs as substitutes. (iii) Greater consumer income increases illegal drug use, but does not seem to have a significant impact on smoking and marijuana use; (iv) The unemployment rate and health insurance converge do not seem to significantly affect smoking or drug use; and (v) Policymakers should pay attention to the cross effects among drugs in framing drug use policies.

Goldstein RZ; Alia-Klein N; Tomasi D; Carrillo JH; Maloney T; Woicik PA et al. Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction. Proceedings of the National Academy of Sciences of the United States of America 106(23): 9453-9458, 2009. (51 refs.)

Anterior cingulate cortex (ACC) hypoactivations during cognitive processing characterize drug addicted individuals as compared with healthy controls. However, impaired behavioral performance or task disengagement may be crucial factors. We hypothesized that ACC hypoactivations would be documented in groups matched for performance on an emotionally salient task. Seventeen individuals with current cocaine use disorders ( CUD) and 17 demographically matched healthy controls underwent functional magnetic resonance imaging during performance of a rewarded drug cue-reactivity task previously shown to engage the ACC. Despite lack of group differences in objective or subjective task-related performance, CUD showed more ACC hypoactivations throughout this emotionally salient task. Nevertheless, intensity of emotional salience contributed to results: (i) CUD with the largest rostroventral ACC [Brodmann Area (BA) 10, 11, implicated in default brain functionl hypoactivations to the most salient task condition (drug words during the highest available monetary reward), had the least task-induced cocaine craving; (ii) CUD with the largest caudal-dorsal ACC (BA 32) hypoactivations especially to the least salient task condition (neutral words with no reward) had the most frequent current cocaine use; and (iii) responses to the most salient task condition in both these ACC major subdivisions were positively intercorrelated in the controls only. In conclusion, ACC hypoactivations in drug users cannot be attributed to task difficulty or disengagement. Nevertheless, emotional salience modulates ACC responses in proportion to drug use severity. Interventions to strengthen ACC reactivity or interconnectivity may be beneficial in enhancing top-down monitoring and emotion regulation as a strategy to reduce impulsive and compulsive behavior in addiction.

Goldstein RA; DesLauriers C; Burda A; Johnson-Arbor K. Cocaine: History, social implications, and toxicity: A review. (review). Seminars in Diagnostic Pathology 26(1): 10-17, 2009. (44 refs.)

The amount of positive cocaine results in all urban emergency department are staggering. The ages of use are becoming more common in older age groups. Most of these patients have underlying, medical conditions, including end-stage renal disease (on hemodialysis) and heart and lung disease. Most of their visits to the emergency department are for cocaine exacerbation of underlying chronic condition, adding exponentially to health care dollars. This article describes the history and pharmacology of illicit cocaine use.

Gonzalez-Saiz F; Domingo-Salvany A; Barrio G; Sanchez-Niubo A; Brugal MT; de la Fuente L et al. Severity of Dependence Scale as a diagnostic tool for heroin and cocaine dependence. European Addiction Research 15(2): 87-93, 2009. (28 refs.)

Aims: Our aim was to further assess the Severity of Dependence Scale (SDS) validity and to identify the cut-off score for a DSM-IV diagnosis of heroin and cocaine dependence through a cross-sectional survey in Barcelona, Spain. Methods: The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was used as the gold standard. 146 young (18-30 years old) heroin users were recruited from outside the healthcare context, 135 of whom were also current cocaine users. SDS scores were correlated to quantity, frequency and length of drug use. Results: The SDS cut-off point at which there was optimal discrimination of a DSM-IV diagnosis presence was found to be 3 (i.e., a score of 3 or more) for heroin dependence and 4 for cocaine dependence. Conclusions: The study gives further support to SDS dimensional properties and to its validity for rapid assessment of current heroin and cocaine dependence.

Greaves A; Best D; Day E; Foster A. Young people in coerced drug treatment: Does the UK Drug Intervention Programme provide a useful and effective service to young offenders? Addiction Research & Theory 17(1): 17-29, 2009. (31 refs.)

Although clear relationships have been identified between dependent drug use and crime, the relationship is less evident in young offenders, particularly for less physically dependent users. This study investigated a sample of young drug-using offenders (aged 18-24; n = 36) accessing drug treatment through the criminal justice system in Birmingham, UK, using structured interviews for the collection of both qualitative and quantitative data. It identified high levels of heroin dependence, with frequency of use linked to both acquisitive crime and willingness to engage in treatment. The relationship between crack cocaine use and offending was less clear with more client ambivalence regarding desire to stop using the drug. Whilst most praised their treatment, and their workers, substitute prescribing was less positively endorsed. The study offers some support for diverting young dependent opiate users from criminal justice services into drug treatment, but presents a less positive prognosis for primary stimulant users.

Green CE; Moeller FG; Schmitz JM; Lucke JF; Lane SD; Swann AC et al. Evaluation of heterogeneity in pharmacotherapy trials for drug dependence: A bayesian approach. American Journal of Drug and Alcohol Abuse 35(2): 95-102, 2009. (48 refs.)

Aims: Difficulty identifying effective pharmacotherapies for cocaine dependence has led to suggestions that subgroup differences may account for some of the heterogeneity in treatment response. Well-attested methodological difficulties associated with these analyses recommend the use of Bayesian statistical reasoning for evaluation of salient interaction effects. Methods: A secondary data analysis of a previously published, double-blind, randomized controlled trial examines the interaction of decision-making, as measured by the Iowa Gambling Task, and citalopram in increasing longest sustained abstinence from cocaine use. Results: Bayesian analysis indicated that there was a 99% chance that improved decision-making enhances response to citalopram. Given the strong positive nature of this finding, a formal, quantitative Bayesian approach to evaluate the result from the perspective of a skeptic was applied. Conclusions: Bayesian statistical reasoning provides a formal means of weighing evidence for the presence of an interaction in scenarios where conventional, Frequentist analyses may be less informative. [Supplementary materials are available for this article. Go to the publisher's online edition of The American Journal of Drug and Alcohol Abuse for the following free supplemental resource: Appendix 1].

Grov C; Kelly BC; Parsons JT. Polydrug use among club-going young adults recruited through time-space sampling. Substance Use & Misuse 44(6): 848-864, 2009

Though some researchers have indicated club drug users are more likely to be polydrug users, there remains little known about the prevalence and specific combinations of the substances they use. Between 2004 and 2006, and using time-space sampling, a stratified sample of 400, 18-29-year-old New York City club-going, drug-using young adults were recruited into the Club Drugs and Health Project. Most participants (91.7%) had engaged in polydrug usage and 1,670 combinations of drugs were reported. Ecstasy (86.6% of users) and cocaine (85.7% of users) were the two most-frequently reported club drugs used in combination with other substances. In terms of poly-club drug combinations, ecstasy appeared to be the universal compliment as this drug was most often cited in combinations with other club drugs (specifically ecstasy + ketamine, ecstasy + cocaine, ecstasy + gamma hydroxybutyrate or GHB). Other frequently cited drug combinations included cocaine and marijuana, ecstasy and marijuana, LSD and marijuana, and cocaine and alcohol. These data highlight the need to develop drug health-education and prevention messages targeted at polydrug usage.

Hadjizacharia P; Green DJ; Plurad D; Chan LS; Law J; Inaba K; Demetriades D. Cocaine use in trauma: Effect on injuries and outcomes. Journal of Trauma, Injury, Infection and Critical Care 66(2): 491-494, 2009. (15 refs.)

Background: It has been reported that cocaine is associated with trauma patients at epidemic proportions. However, the injury patterns, complications, and mortality in cocaine test-positive trauma patients are not well known. Methods: Retrospective review of all trauma patients with toxicology screen at a Level I trauma center between January 2002 and December 2005. A total of 1,096 patients were positive for cocaine but no other substances of abuse or alcohol. Nine hundred eighty-five patients of these cocaine test-positive patients were matched to a pool of 4,846 toxicology test-negative patients admitted during the same period with respect to age (<= 18, 19-55, >55 years), gender, mechanism (blunt, penetrating), Injury Severity Score (ISS < 16, 16-25, >25), head Abbreviated Injury Score (AIS <3, >= 3), chest AIS (<3, >= 3), abdominal AIS (<3, >= 3), and extremity AIS (<3, >= 3). Matched pairs of binary outcomes were analyzed using McNemars, and continuous data were tested using the Wilcoxon signed-ranks test. Results: The two groups had similar injury patterns and there was no difference in surgical procedures between cocaine test-positive and toxicology test-negative patients. Overall, there was no difference in mortality between the cocaine and test-negative patients (6.5% vs. 6.2%; p = 0.81), or between cocaine and test-negative patients with an ISS <16 (1.4% vs. 1.5%; p = 1.00), ISS 16 to 25 (13% vs. 12%; p = 1.00), and ISS >25 (59% vs. 54%; p = 0.70). The overall incidence of complications was 4% in cocaine patients and 3.6% in test-negative patients (p = 0.72), although the incidence of pneumonia was significantly higher in the cocaine test-positive patients (p = 0.04). Conclusion: Cocaine abuse in trauma patients is concerning. This study did not show a difference in mortality or length of intensive care unit stay between cocaine positive and negative patients. However, there was a significantly higher incidence of pneumonia in cocaine positive patients. Implementation of effective prevention strategies may help reduce cocaine related victims of trauma.

Haile CN; Kosten TR; Kosten TA. Pharmacogenetic treatments for drug addiction: Cocaine, amphetamine and methamphetamine. (review). American Journal of Drug and Alcohol Abuse 35(3): 161-177, 2009. (280 refs.)

Background: Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. Objectives: To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. Methods: We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. Results: We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3'-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. Conclusions: Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a 'protected' phenotype. Scientific Significance: Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.

Hakansson A; Schlyter F; Berglund M. Characteristics of primary amphetamine users in Sweden: A criminal justice population examined with the Addiction Severity Index. European Addiction Research 15(1): 10-18, 2009. (70 refs.)

Background/Aims: Characteristics of primary amphetamine, heroin and cocaine users were compared in a criminal justice population. Methods: 7,085 clients with suspected or reported substance use were studied using the Addiction Severity Index. Variables separating amphetamine, heroin and cocaine users were analyzed in stepwise logistic regression. Results: There were considerably more primary amphetamine users (n = 1,396) than heroin (n = 392) and cocaine (n = 119) users. Amphetamine users were older, a more rural population, and less likely to be non-Nordic immigrants. Compared with heroin, amphetamine use was associated with older age, Nordic origin, nonurban residence, memory/concentration problems, parental alcohol problems, and less history of other opioid use, overdose and detoxification. Compared with cocaine, amphetamine use was associated with older age, Nordic origin, nonurban residence, injecting, tobacco and institution treatment. Overlap of drug use between groups was relatively uncommon. Conclusion: This pattern of amphetamine use, common among Swedish criminals, has relatively distinct boundaries from heroin and cocaine use, commonly involves injecting, and differs from other countries. Psychiatric problems and alcohol heredity were common, and evidence-based treatment for amphetamine users is needed. The connection between amphetamine use and criminal behavior is insufficiently understood and should be further addressed.

Haney M. Self-administration of cocaine, cannabis and heroin in the human laboratory: Benefits and pitfalls. (review). Addiction Biology 14(1): 9-21, 2009. (106 refs.)

The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs.

Hanlon CA; Wesley MJ; Porrino LJ. Loss of functional specificity in the dorsal striatum of chronic cocaine users. Drug and Alcohol Dependence 102(1/3): 88-94, 2009. (76 refs.)

Background: Although research into the effects of cocaine has focused on the ventral striatum, recent reports have identified a significant role for the dorsal striatum. Given the importance of the dorsal striatum in motor control, the purpose of the present study was to investigate potential sensorimotor deficits among cocaine users and the functional basis of these deficits within the striatum. Methods: Functional magnetic resonance imaging data were collected from 14 right-handed, non-treatment seeking chronic cocaine users and 14 age and gender matched controls during performance of two finger-sequencing paradigms that differentially activate the caudate (internally-guided) and the putamen (externally-guided) interleaved with blocks of rest. The total percent signal change in the dorsal striatum and the contribution of the left and right caudate and putamen were calculated and compared across groups and tasks. Results: Significant deficits in sensorimotor control were observed in cocaine users for both motor tasks, with the most severe impairments present during internally-guided movements. Cocaine users lacked the typical functional segregation observed in the dorsal striatum of the control subjects. The total percent signal change in the dorsal striatum was not significantly different between the groups, but cocaine users activated significantly less contralateral caudate and putamen for internally-guided versus externally-guided movements, respectively. Conclusion: These data provide clear evidence that chronic cocaine users have significant motor performance deficits that are accompanied by disrupted processing within the dorsal striatum. These data suggest the effects of cocaine extend beyond the confines of the motivational domains of the ventral striatum.

Hansen NB; Cavanaugh CE; Vaughan EL; Connell CM; Tate DC; Sikkema KJ et al. The influence of personality disorder indication, social support, and grief on alcohol and cocaine use among HIV-positive adults coping with AIDS-related bereavement. AIDS and Behavior 13(2): 375-384, 2009. (58 refs.)

Substance use is prevalent among HIV-positive adults and linked to a number of adverse health consequences; however little is known about risk and protective factors that influence substance use among HIV-positive adults coping with AIDS-related bereavement. Using structural equation modeling (SEM), male gender, diagnostic indications of antisocial and borderline personality disorders (PD), and grief severity were tested as risk factors, and social support as a protective factor, for alcohol and cocaine use among a diverse sample of 268 HIV-positive adults enrolled in an intervention for AIDS-related bereavement. Results indicated that the hypothesized model fit the study data. Male gender, PD indication, and social support had direct effects on substance use. PD had significant indirect effects on both alcohol and cocaine use, mediated by social support, but not by grief. Finally, both PD and social support had significant, but opposite, effects on grief. Implications for intervention and prevention efforts are discussed.

Havens JR; Stoops WW; Leukefeld CG; Garrity T; Carlson RG; Falck R et al. Prescription opiate misuse among rural stimulant users in a multistate community-based study. American Journal of Drug and Alcohol Abuse 35(1): 18-23, 2009. (26 refs.)

Objectives: The purpose of the current analysis was to examine the factors associated with prescription opiate misuse among stimulant users from rural counties in Arkansas, Kentucky, and Ohio (N = 714). Methods: Multiple logistic regression was utilized to determine the independent correlates of recent (prior 6 months) prescription opiate misuse. Results: More than half of participants (53.2%) reported prescription opiate misuse in the previous 6 months. Other drug use (heroin, cocaine, methamphetamine, and marijuana) and anxiety (Adjusted Odds Ratio: 2.04, 95% Confidence Interval: 1.60, 2.59) were independently associated with prescription opiate misuse. Chronic pain and other health indicators were not associated with prescription opiate misuse after adjustment for covariates. Conclusions: Results indicate that illicit drug involvement and psychiatric symptoms may be driving the high rates of prescription opiate misuse among rural stimulant users. These findings have implications for the provision of treatment in resource-deprived rural areas.

Hay G; Gannon M; MacDougall J; Eastwood C; Williams K; Millar T. Capture-recapture and anchored prevalence estimation of injecting drug users in England: National and regional estimates. Statistical Methods in Medical Research 18(4): 323-339, 2009. (42 refs.)

Capture-recapture (C-RC) using four data sources, one of which accounted for 81% of captured injectors, and multiple indicator methods (MIM) were used to obtain national, regional and local estimates of the prevalence of injecting drug use among opiate and/or crack cocaine users in England. Persons aged 15 to 64 years, in contact with health and/or criminal justice services during 2005/2006, and known to be using opiates and/or crack cocaine and injecting drugs were included in the C-RC analysis. The MIM analysis included indicators relating to drug treatment, drug-related deaths, population density and drug offences. There were an estimated 130,000 opiate and/or crack cocaine users who injected drugs in 2005/06 (95% confidence interval 125,800 to 137,000), corresponding to 3.9 per thousand of the population aged 15 to 64 years (95% confidence interval 3.8-4.1). Regional variation in the prevalence of injecting was evident, ranging from 6.1 per thousand of the population aged 15-64 years in Yorkshire and the Humber (95% confidence interval 5.6 to 6.6) to 2.3 per thousand in the East of England (95% confidence interval 1.8 to 2.9). Application of gender and age-group distributions for treated injecting drug users (IDUs) to the prevalence estimates suggested that there were 97,200 male injectors (95% confidence interval 61,500 to 67,000). The prevalence estimates provide a basis from which numbers of current IDUs infected with hepatitis C virus (HCV) can be approximated.

Hedden SL; Malcolm RJ; Latimer WW. Differences between adult non-drug users versus alcohol, cocaine and concurrent alcohol and cocaine problem users. Addictive Behaviors 34(3): 323-326, 2009. (9 refs.)

Concurrent drug use is a serious public health concern with significant morbidity and mortality associated with the combined use of alcohol and cocaine. Multinomial logistic regression was used to assess differences between non-drug users and alcohol, cocaine and concurrent problem users incorporating data from the 2005 National Survey on Drug Use and Health. Results demonstrated that alcohol and cocaine use is associated with mental health disturbance, other drug use and adverse social consequences. Furthermore, concurrent users were more likely to report cigarette and marijuana use as well as lifetime STDs and arrest for breaking the law. Study results have implications for planning prevention and treatment services differentially for alcohol, cocaine and concurrent users and support the need for more intense resources allocated to the prevention and treatment of the concurrent use of alcohol and cocaine.

Hedden SL; Whitaker D; Floyd L; Latimer WW. Gender differences in the prevalence and behavioral risk factors of HIV in South African drug users. AIDS and Behavior 13(2): 288-296, 2009. (33 refs.)

South Africa continues to be the global epicenter of HIV infection. Further, extensive gender disparities in HIV infection exist with females four times as likely to be infected with HIV/AIDS as males (UNAIDS, AIDS epidemic update, 2006; WHO, Epidemiological fact sheets on HIV/AIDS and sexually transmitted infections, 2006). A cross-sectional collection of drug users recruited in the Pretoria region of South Africa (N = 385) was used to model HIV infection as a function of sexual risk behaviors and drug use as modified by gender. Receiving money from illicit sources and knowing someone with AIDS were loosely associated with HIV. Gender interactions were observed for age, cocaine use and condom use. Gender stratified analyses revealed that males who used condoms, were younger and tested negative for cocaine use were less likely to test positive for HIV. Findings suggest that males may have more control of risk behaviors and support the need for gender specific prevention strategies.

Heinz AJ; Wu J; Witkiewitz K; Epstein DH; Preston KL. Marriage and relationship closeness as predictors of cocaine and heroin use. Addictive Behaviors 34(3): 258-263, 2009. (33 refs.)

Marriage has been cited as a protective factor against drug use, but the relationship between marriage and drug use has not been explored longitudinally during addiction treatment. The current study assessed individual trajectories of substance use during treatment as a function of marital status and perceived closeness of the marital relationship. A parallel-process growth model was used to (I) estimate the rate of change in percentage of cocaine-positive and heroin-positive urine samples, and (2) examine the relationship between marital status and drug use trajectories over 35 weeks, during and after treatment. Percent days of use for both drugs were lowest for married participants across all time points. Among married participants. reporting a close relationship with one's partner predicted less cocaine and heroin use. These findings suggest that being married and having a close relationship with one's spouse are associated with better outcomes over time. The causal nature of the association is suggested by previous research that has demonstrated the effectiveness of couples therapy as an adjunct to methadone maintenance.

Heshmati M. Cocaine-induced LTP in the ventral tegmental area: New insights into mechanism and time course illuminate the cellular substrates of addiction. Journal of Neurophysiology 101(6): 2735-2737, 2009. (13 refs.)

Previous work has shown that a single dose of cocaine can produce long-term potentiation (LTP) of the glutamatergic synapses received by dopamine neurons in the ventral tegmental area (VTA). This and other plastic changes in the brain's reward circuitry have been suggested to underlie addiction. A recent study has provided new insights into cocaine-induced LTP, showing that it begins 3-5 h after exposure, requires activation of a dopamine D-5/NMDA receptor cascade, and can be evoked by cocaine application directly to the VTA.

Hester R; Garavan H. Neural mechanisms underlying drug-related cue distraction in active cocaine users. Pharmacology, Biochemisty and Behavior 93(3, Special Issue): 270-277, 2009. (82 refs.)

Human drug dependence routinely features a difficulty with disengaging attention from drug-related stimuli, a symptom previously shown to be predictive of relapse during treatment. We examined the neural mechanisms underlying this attentional bias in cocaine users. varying working memory (WM) load to reflect the demands imposed by ruminative craving thoughts. Sixteen active users of cocaine were administered a WM task that manipulated the requirement for selective attention by varying the background contents, cocaine-related or neutral, upon which a recall probe item was shown. Behavioural and fMRI data were collected. Cocaine users had significantly poorer attentional control under high WM demands, suffering both increased response times and reduced recall accuracy, with this effect more pronounced for cocaine stimuli (when compared to neutral stimuli). The presence of background cocaine stimuli was associated with increases in occipital cortex activity, consistent with increased visual processing of the irrelevant stimuli for these trials. In addition, the cocaine stimuli were associated with increased right prefrontal activity with those participants with higher levels of right prefrontal activity having lower levels of attentional bias. Cocaine users under high cognitive demands had difficulty modulating the neural mechanisms underlying cognitive control which appear necessary for restricting the visual processing of task-irrelevant, but salient drug-related. stimuli, a finding that may be relevant to identifying those at most risk of relapse.

Huang DK; Liu C; Huang MK; Chien CS. Simultaneous determination of morphine, codeine, 6-acetylmorphine, cocaine and benzoylecgonine in hair by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Communications in Mass Spectrometry 23(7): 957-962, 2009. (31 refs.)

A fast and sensitive liquid chromatography/triple quadrupole tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous determination of morphine, codeine, 6-acetylmorphine (6-AM), cocaine and benzoylecgonine (BE) in hair. Pulverized hair samples were extracted with methanol, and a 50 mu L supernatant aliquot was injected into the LC/MS/MS system. Chromatography was performed with an XBridge (TM) phenyl column (3.5 mu m particle size, 4.6 X 150 mm), and the mobile phase was composed of methanol and 10 mM ammonium acetate adjusted to pH 4.00 with 99% formic acid (95:5, v/v). A separation run with isocratic elution was completed in 10 min at a flow rate of 500 mu L/min. Positive electrospray ionization and multiple reaction monitoring (MRM) with one precursor ion/product ion transition were used for the identification of each analyte. Deuterated analogues as internal standards were used for quantification and qualification. Linearity was established in the concentration range of 100-3000 pg/mg. The limits of detection were 10 pg/mg for morphine, codeine and 6-AM; and 1 pg/mg for cocaine and BE. The precision and accuracy were determined by spiking hair samples at six concentration levels. For all analytes, the relative standard deviations of intra- and inter-day precision were 0.1-6.3% and 1.5-10.6%, respectively. The accuracy ranged from 92.7 to 109.7%. The validated LC/MS/MS method was successfully applied to the analysis of 79 authentic hair samples.

Hyman SM; Sinha R. Stress-related factors in cannabis use and misuse: Implications for prevention and treatment. (review). Journal of Substance Abuse Treatment 36(4): 400-413, 2009

We examined the role of stress as a risk factor and motivation for cannabis use/misuse. A systematic review of studies gathered from PsychINFO and MEDLINE databases was conducted. Findings suggest that cannabis is commonly used as a stress-coping strategy. Negative life events, trauma, and maladaptive coping were all related to consumption. Cannabis use for stress-coping purposes was most evident when examining chronic as compared with experimental use. Although many individuals may be able to use cannabis without consequences, there appears to be a subset of individuals who experience greater life stress and who may be more likely to use for stress-coping purposes. These individuals may be at greatest risk for addiction. Chronic use may potentiate stress-related motivation to use/abuse cannabis and is associated with decision-snaking deficits and alterations in brain-stress pathways that may exacerbate compulsive drug seeking and sensitize individuals to stress-related drug use. Overall, stress-coping interventions and harm reduction focused on reducing the amount ingested may facilitate prevention and recovery efforts.

Ingsathit A; Woratanarat P; Anukarahanonta T; Rattanasiri S; Chatchaipun P; Wattayakorn K et al. Prevalence of psychoactive drug use among drivers in Thailand: A roadside survey. Accident Analysis and Prevention 41(3): 474-478, 2009. (24 refs.)

The objective of this study was to determine the prevalence of psychoactive drug and alcohol use among general drivers and predictors of the drug use in Thailand. One thousand six hundred and thirty-five motor vehicle drivers were randomly selected from five geographical regions of Thailand between December 2005 and May 2006. The prevalence of psychoactive drugs was determined using urine tests by gas chromatography/mass spectrometry (GC/MS). Among 1635 drivers, 5.5% were tested positive for breath alcohol with 2% having a level exceeding the legal limit (>= 50 mg%). Psychoactive drug was presented in 158 (9.7%) urine samples for drug analysis. The top 3 most frequently detected licit drugs were antihistamines (2.0%), sedative cough suppressant (0.7%) and benzodiazepines (0.2%). Illicit drugs detected included amphetamine (1.8%), cannabis (1.1%), mitragynine (Kratom) (0.9%) and morphine (0.1%). Only type of driver (commercial/non-commetcial) was a significant predictor with psychoactive drug use. The prevalence of psychoactive drug use among drivers not involved in road crashes in Thailand was not as low as an earlier study in Europe using objective measurements, particularly among commercial drivers. However, for illicit drugs, the prevalence detected in this study was lower than those of earlier studies from high-income countries.

Jackson IT; Kelly C; Bello-Rojas G. Palatal fistulae resulting from cocaine abuse. Annals of Plastic Surgery 62(1): 67-69, 2009. (13 refs.)

Cocaine fistulae require repair with well-vascularized material. In the technique used this is accomplished by closure of the nasal layer by delayed palatal flaps and the oral layer with a tongue flap. Three cases are presented.

Johnson MB; Voas RA; Miller BA; Holder HD. Predicting drug use at electronic music dance events: Self-reports and biological measurement. Evaluation Review 33(3): 211-225, 2009. (16 refs.)

Most information on the prevalence of drug use comes from self-report surveys. The sensitivity of such information is cause for concern about the accuracy of self-report measures. In this study, self-reported drug use in the last 48 hr is compared to results from biological assays of saliva samples from 371 young adults entering clubs. The relationship between self-reports and drug presence in oral fluid was determined for three substances as follows: cocaine, marijuana, and amphetamine. Forty-one percent of the participants with drugs detected in their oral fluids reported no use in the last 48 hr. The significance of these results is discussed.

Joya X; Papaseit E; Civit E; Pellegrini M; Vall O; Garcia-Algar O et al. Unsuspected exposure to cocaine in preschool children from a Mediterranean city detected by hair analysis. Therapeutic Drug Monitoring 31(3): 391-395, 2009. (29 refs.)

We used hair testing to investigate the prevalence of unsuspected exposure to cocaine in a group of preschool children presenting to an urban pediatric emergency department without signs or symptoms suggestive of exposure. Hair samples were obtained from 90 children between 18 months and 5 years of age attending the emergency room of Hospital del Mar in Barcelona, Spain. In 85 cases, hair samples from the accompanying parent were also provided. The samples were analyzed for the presence of cocaine and benzoylecgonine by gas chromatography-mass spectrometry which also determined opiates and amphetamines. Parental sociodemographics, possible drug history, and information on the child's features were recorded. Hair samples from 21 children (23.3%) were positive for cocaine (concentration range 0.3-5.96 ng/mg of hair) with 1 sample also positive for 3,4-methylenedioxymethamphetamine and another for opiates. In 88% of the positive cases, cocaine was also found in the hair of the accompanying parent (15 of 17 matched parent-child hair samples). Parental sociodemographics were associated neither with children's exposure to cocaine nor with somatometry of children at birth. However, the behavioral patterns with potential harmful effects for the child's health (eg, tobacco smoking, cannabis, benzodiazepines and/or antidepressants use, and shorter breast-feeding time) were significantly higher in the parents of exposed children. A statistically higher percentage of exposed children were in the lower weight percentile group compared with the nonexposed children. In the light of these results, we advocate general hair screening to disclose exposure to cocaine and other drugs of abuse in children from risky environments, which could provide the basis for specific social and health interventions.

Kalivas PW. The manifest destiny of cocaine research. (editorial). Neuropsychopharmacology 34(5): 1089-1090, 2009. (6 refs.)

Kelly SM; Schwartz RP; O'Grady KE; Mitchell SG; Reisinger HS; Peterson JA et al. Gender differences among In- and out-of-treatment opioid-addicted individuals. American Journal of Drug and Alcohol Abuse 35(1): 38-42, 2009. (22 refs.)

Objective: Gender differences were explored among 355 in- and out-of-treatment opioid-addicted adults in Baltimore. Methods: Addiction Severity Index and other variables were compared among: 1) in-treatment women vs. out-of-treatment women; 2) out-of-treatment: women vs. men; and, 3) in-treatment: women vs. men. Results: Analysis indicated that in-treatment and out-of-treatment women worked less and used more cocaine than their male counterparts (ps .01). Moreover, out-of-treatment women used heroin and cocaine more often, spent more money on drugs, earned more illegal income, and had fewer treatments than in-treatment women (ps .01). Conclusions: Findings indicate greater severity of drug and employment problems of opioid-addicted women and underline the need for gender-specific drug-treatment services.

Kinsey BM; Jackson DC; Orson FM. Anti-drug vaccines to treat substance abuse. (review). Immunology and Cell Biology 87(4): 309-314, 2009. (53 refs.)

Substance abuse is a growing world-wide problem. The big four drugs of abuse that might lend themselves to immunotherapy are nicotine, cocaine, morphine/heroin and methamphetamine. Tobacco abuse has a well-known enormous impact on major chronic cardiovascular and pulmonary diseases, while the last three, aside from their neuropsychological effects, are illegal, leading to crime and incarceration as well as the transmission of viral diseases. Having an efficient vaccine that would generate antibodies to sequester the drug and prevent its access to the brain could go a long way toward helping a motivated addict quit the addiction. This review will discuss what has been done to bring such vaccines to human use, and what the challenges are for the future of this promising intervention.

Ko MC; Narasimhan D; Berlin AA; Lukacs NW; Sunahara RK; Woods JH. Effects of cocaine esterase following its repeated administration with cocaine in mice. Drug and Alcohol Dependence 101(3): 202-209, 2009. (18 refs.)

Background: A bacterial cocaine esterase (CocE) produces robust protection and reversal of cocaine toxicity. The aim of this study was to investigate how effectiveness of CocE was changed following its repeated administration together with cocaine. Methods: Cocaine toxicity was quantified by measuring the occurrence of convulsions and lethality in mice. Immunologic responses of CocE were determined using ELISA. In the protection experiment, i.v. CocE 0.3 mg was given 1 min before a lethal dose of i.p. cocaine 180 mg/kg. In the rescue experiment, i.v. CocE 0.3 mg was given 1 min after the occurrence of convulsions elicited by i.p. cocaine 100 mg/kg. In both treatment paradigms, four trials were conducted in the same animals with a 2-week interval. Results: CocE retained its effectiveness to protect or rescue mice during the first two trials and these mice did not show an immune response. In contrast, CocE's effectiveness was gradually reduced in the last two trials, accompanied by 10- and 100-fold increases in anti-CocE antibody titers. Nevertheless, effectiveness of CocE could be partially recovered by increasing the dose of CocE. In addition, escalating the dose of CocE from the minimum effective dose for repeated administration could also retain CocE's effectiveness longer and slow the production of anti-CocE antibodies. Conclusions: These results indicate that CocE is a weak antigen and it can maintain its protective and rescuing ability initially against cocaine-induced toxicity. Decreased effectiveness of CocE following repeated use can be partially improved by adjusting the dose and frequency of CocE treatment.

Kreek MJ; Zhou Y; Butelman ER; Levran O. Opiate and cocaine addiction: from bench to clinic and back to the bench. (review). Current Opinion in Pharmacology 9(1): 74-80, 2009. (62 refs.)

This review primarily focuses on our recent findings in bidirectional translational research on opiate and cocaine addictions. First, we present neurobiological and molecular studies on endogenous opioid systems (e.g. proopiomelanocortin, mu opioid receptor, dynorphin, and kappa opioid receptor), brain stress-responsive systems (e.g. orexin, arginine vasopressin, V1b receptor, and corticotropin-releasing factor), hypothalamic-pituitary-ad renal axis, and neurotransmitters (especially dopamine), in response to both chronic cocaine or opiate exposure and to drug withdrawal, using several newly developed animal models and molecular approaches. The second aspect is human molecular genetic association investigations including hypothesis-driven studies and genome-wide array studies, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy.

Kuhns JB; Wilson DB; Maguire ER; Ainsworth SA; Clodfelter TA. A meta-analysis of marijuana, cocaine and opiate toxicology study findings among homicide victims. (review). Addiction 104(7): 1122-1131, 2009. (47 refs.)

To synthesize the results of marijuana, cocaine and opiate drug toxicology studies of homicide victims and examine variation in results across person and setting characteristics. A meta-analysis of 18 independent studies identified from an extensive review of 239 published articles that met the inclusion criteria of reporting marijuana, cocaine and/or opiate toxicology test results for homicide victims. A total of 28 868 toxicology test results derived from 30 482 homicide victims across five countries were examined. On average, 6% of homicide victims tested positive for marijuana, 11% tested positive for cocaine, and 5% tested positive for opiates. The proportion of homicide victims testing positive for illicit drugs has increased over time. Age had a strong curvilinear relationship with toxicology test results, but gender differences were not apparent. Hispanic and African American homicide victims were more likely to test positive for cocaine; Caucasians were most likely to test positive for opiates. Cocaine use appeared to be related to increased risk of death from a firearm and was a greater risk factor for violent victimization in the United States than in Newfoundland and Scandinavia. There are relatively few studies of illicit drug toxicology reports from homicide victims that allow for cross-cultural comparisons. This study provides a basis for comparing future local toxicology test results to estimates from existing research.

Lester BM; Padbury JF. Third pathophysiology of prenatal cocaine exposure. (review). Developmental Neuroscience 31(2): 23-25, 2009. (237 refs.)

The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects, we suggest a 'third pathophysiology' in which altered fetal programming affects the acute and long-term adverse effects of in utero cocaine exposure. We describe how cocaine as a stressor alters the expression of key candidate genes, increasing exposure to catecholamines and fetal cortisol-altering neuroendocrine (hypothalamic-pituitary-adrenal axis) activity, leading to infant behavioral dysregulation, poor behavioral control and emotion regulation during childhood and phenotypes that confer vulnerability to substance use in adolescence. This model is discussed in relation to follow-up studies of the effects of in utero cocaine exposure and maturational changes in brain development.

Lindsay JA; Stotts AL; Green CE; Herin DV; Schmitz JM. Cocaine dependence and concurrent marijuana use: A comparison of clinical characteristics. American Journal of Drug and Alcohol Abuse 35(3): 193-198, 2009. (39 refs.)

Background/Objectives: Marijuana is the most commonly used illicit substance, yet among the least studied in medication development research. Cocaine-dependent individuals frequently also use marijuana; however, little is known about the effect of this combined use on treatment presentation. Methods: Marijuana use was assessed in 1183 individuals seeking outpatient treatment for cocaine dependence. Based on past 30 days of use, the sample was divided into three groups: (1) patients reporting no recent marijuana use (n = 634); (2) occasional use (n = 403); (3) and frequent concurrent marijuana use (n = 146). Differences on baseline measures of substance use, addiction severity (ASI), psychopathology, and sociodemographic characteristics were examined as a function of level of marijuana use. Results: Frequent marijuana users were more likely to be female, Caucasian, and younger than other groups. Cocaine-dependent patients with frequent marijuana use also used more cocaine and alcohol, and reported more medical, legal, and psychiatric problems, including antisocial personality disorder. Conclusion and Scientific Significance: Cocaine-dependent patients with frequent marijuana use present for treatment with more severe impairment. Accounting for this heterogeneity among participants may improve treatment outcome.

Lloyd-Smith E; Wood E; Li K; Montaner JSG; Kerr T. Incidence and determinants of initiation into cocaine injection and correlates of frequent cocaine injectors. Drug and Alcohol Dependence 99(1-3): 176-182, 2009. (37 refs.)

Purpose: To investigate the incidence and correlates of cocaine injection initiation and the impacts of daily cocaine injection among a cohort of injection drug users. Methods: Among 1603 participants, from May 1996 to December 2005, risk factors for initiation of cocaine injection among baseline heroin users were determined by Cox proportional hazards regression and correlates of daily cocaine injection by generalized estimating equations. Findings: Of the 238 individuals who had never injected cocaine, 200 (84%) had at least one follow-up visit and 121 (61%) consequently initiated into cocaine injection, yielding an incidence density of initiation into cocaine injection of 21.9% (95% confidence interval (121): 17.9-25.8) per 100 person-years. In a multivariate model, Downtown Eastside (DTES) residence (adjusted hazard ratio (AHR)=2.46, 95% Cl:1.68-3.60) incarceration (AHR = 1,507 95% Cl: 1.01-2.24), requiring help injecting (AHR = 1.57, 95% CI: 0.99-2.49), and binge drug use (AHR = 1.82, 95% Cl: 1.22-2.73) remained associated with initiation into cocaine injection. DTES residence (adjusted odds ratio (AOR) = 1.99, 95% Cl: 1.62-2.46), unstable housing (AOR = 1.28, 95% Cl: 1.04-1.53), incarceration (AOR = 1.29, 95% CI: 1.04-1.60), sex trade involvement (AOR = 1.46, 95% Cl: 1.15-1.85), requiring help injecting (AOR = 2.11, 95% Cl: 1.73-2.58)), borrowing syringes (AOR = 1.81, 95% Cl: 1.35-2.43) and binge drug use (AOR = 2.16, 95% Cl: 1.81-2.58) were independently associated with daily cocaine injection. Conclusions: The baseline prevalence and subsequent incidence of initiation into cocaine injection was high. Daily cocaine injection was independently associated with a number of health and social harms, including elevated HIV risk behavior.

Madea B; Musshoff F. Knock-out drugs: Their prevalence, modes of action, and means of detection. (review). Deutsches Arzteblatt International 106(20): 341-U12, 2009. (25 refs.)

Background: Knock-out drugs are used to facilitate the commission of a crime, generally either robbery or sexual assault. Although media reports on the use of knock-out drugs have become more frequent, there are no robust epidemiological data on the incidence of drug-facilitated robbery or sexual assault, presumably because many crimes of these types do not enter into official statistics. Methods: The authors describe the modes of action and toxicological means of detection of the substances most frequently used as knock-out drugs on the basis of a selective literature research on the terms "drug-facilitated sexual assaults" (DFSA) and "drug-facilitated crimes" (DFC). Results: The most frequently used drug in cases of sexual assault is still alcohol (ca. 40% to 60%), followed by illegal drugs (cannabis, cocaine). The presence of involuntarily consumed medications and drugs of abuse is demonstrated by routine toxicological analysis only in relatively few cases (ca. 2%). The substances most commonly found are benzodiazepines, followed by other hypnotics. In Europe, the illegal substance gamma-hydroxybutyric acid (GHB, "Liquid Ecstasy"), often mentioned as a "date-rape drug," is only rarely detected with sufficient medicolegal certainty. This may be due to its rapid elimination (it is detectable in blood for up to 8 hours, in urine for up to 12 hours) as well as its physiological occurrence in the body. If the toxicological analysis of blood and urine is negative in a case of suspected DFSA, then the analysis of a hair sample about four weeks after the assault can detect the presence of drugs consumed at that time. If the victim has long hair, it may be possible to detect knock-out drugs taken more than four weeks earlier. In Europe, convictions for drug-facilitated crimes are comparatively rare, mainly because of the difficulty of demonstrating conclusive evidence. Conclusions: A careful medical history and physical examination and the careful taking of biological samples for toxicological analysis form the basis for the detection of drug-facilitated crimes.

Makaryus JN; Volfson A; Azer V; Bogachuk E; Lee A. Acute stent thrombosis in the setting of cocaine abuse following percutaneous coronary intervention. Journal of Interventional Cardiology 22(1): 77-82, 2009. (40 refs.)

The treatment of acute coronary syndrome (ACS) in patients with documented cocaine abuse has always presented significant challenges. Issues related to medication compliance, the potential risks of beta adrenergic blockade, and possible continued cocaine abuse postmyocardial infarction necessitate a unique, individualized approach to these patients. Recent data in the era of extensive percutaneous coronary interventions (PCI) and intracoronary stent (ICS) implantation have raised questions regarding the safety of ICS in patients who may revert to cocaine abuse postacute coronary syndrome as a result of the potentially higher risk of stent thrombosis in these patients. While the precise reason as to why cocaine use may increase the risk of stent thrombosis is not fully understood, it is likely the result of a confluence of factors, including coronary vessel vasoconstriction, impaired vascular compliance, as well as the platelet-activating effect of cocaine. We present the case a 46-year-old male with a history of cocaine abuse who presented with an acute stent thrombosis 2 days post-PCI likely as a result of cocaine abuse on the day of discharge following initial stent implantation for a non-ST-elevation myocardial infarction (NSTEMI). We also review the literature regarding the safety of PCI in cocaine abusers.

Malek A; Obrist C; Wenzinger S; von Mandach U. The impact of cocaine and heroin on the placental transfer of methadone. Reproductive Biology and Endocrinology 7(article 61), 2009. (40 refs.)

Background: Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods: Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results: Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/-SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by = 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion: The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast.

Mari F; Politi L; Biggeri A; Accetta G; Trignano C; Di Padua M et al. Cocaine and heroin in waste water plants: A 1-year study in the city of Florence, Italy. Forensic Science International 189(1-3): 88-92, 2009. (25 refs.)

The diffusion and trends in use of each substance is a basic information in policy planning of strategies aiming at deterrence of drug abuse or in the organization of the fight against drug trafficking. The actual diffusion of illicit drugs in a population is hardly measurable, but, among the various measures available, the analysis of waste water plants represents one of the most reliable source of data. We analyzed waste water in order to monitor illicit drug use by local population. We investigated the use of cocaine and heroin in the city of Florence, Italy, over a I-year (July 2006-June 2007) period using state-of-the-art measuring techniques from waste water samples. Cocaine, benzoylecgonine, and morphine were determined in water samples by gas chromatography-mass spectrometer, and the amount of illicit substance was estimated. Data indicate for cocaine a bimodal distribution (December and March), while heroin showed a main peak in April. The heroin-to-cocaine use ratio in terms of estimated doses per month ranged from 0.11 to 0.76, representing new evidence of wider distribution of cocaine than heroin in Florence. Waste water analysis can become a valuable tool in monitoring use of illicit drugs over time. In particular, it can highlight changes in the magnitude and relative use of illicit drug at a population level thereby becoming useful to develop strategies against drug trafficking and abuse. If routinely performed, it can be part of Epidemiologic Surveillance Programmes on drug abuse.

Martinez D; Slifstein M; Narendran R; Foltin RW; Broft A; Hwang DR et al. Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine. Neuropsychopharmacology 34(7): 1774-1782, 2009. (54 refs.)

The goal of this study was to determine D-1 receptor availability in human cocaine-dependent (CD) subjects and matched healthy controls (HCs). In addition, the CD subjects performed cocaine self-administration sessions in order to explore the association between D-1 receptor availability and cocaine-seeking behavior. Twenty-five CD subjects (40 +/- 4 years, 19M/6 F) and 23 matched HCs (38 +/- 4 years, 19M/4F) were scanned with PET and the radiotracer [C-11]NNC 112. During the cocaine self-administration sessions, CD volunteers were given the choice to self-administer cocaine (0, 6, and 12 mg) or to receive a monetary voucher worth $5. D-1 receptor availability was measured in the limbic, associative, and sensori-motor striatum in addition to cortical brain regions. No difference in D-1 receptor availability was seen between the two groups. A negative association was seen between D-1 receptor BPND in the limbic striatum and the choice for the 6 mg dose of cocaine (r = -0.47, p = 0.02, corrected for age). These results do not support the hypothesis that cocaine dependence is associated with a reduction in D-1 receptor availability in the striatum. However, within the CD subjects, low D-1 receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D-1 receptor availability may be associated with an increased risk of relapse in cocaine dependence.

McCrystal P; Percy A. A profile of adolescent cocaine use in Northern Ireland. International Journal of Drug Policy 20(4): 357-364, 2009. (60 refs.)

Background: The image of cocaine as a 'party' drug used by more affluent members of society has begun to change as the levels of use of the drug rise amongst school aged young people. Methods: Cocaine use patterns amongst young people aged 13-16 years who were participating in the Belfast Youth Development Study, a longitudinal study of adolescent drug use was explored. Data was collected through an annual datasweep in participating schools. This paper includes data collected in years 3, 4 and 5 of the study. Results: The results show higher levels of cocaine use amongst this age group than reported in much of the existing harm reduction literature. Lifetime use was 3.8% at age 13-14 years, rising to 7.5% at 15-16 years. The profile indicated that adolescent cocaine users were more likely to be female, live in disrupted families and experience social deprivation which is similar to existing adolescent drug use profiles. There was also some evidence of experimental cocaine use amongst the sample. Conclusions: These findings provide further evidence for the development of age appropriate school focused harm reduction initiatives and continued monitoring of contemporary trends of use of cocaine amongst school aged young people.

McCutcheon VV; Heath AC; Edenberg HJ; Grucza RA; Hesselbrock VM; Kramer JR et al. Alcohol criteria endorsement and psychiatric and drug use disorders among DUI offenders: Greater severity among women and multiple offenders. Addictive Behaviors 34(5): 432-439, 2009. (41 refs.)

Purpose: Data from the Collaborative Study on the Genetics of Alcoholism (COGA), a high-risk family study of alcohol dependence. were used to examine differences in alcohol diagnostic criteria endorsement and psychiatric and drug use disorders by gender and by number of DUI offenses. Results: Individuals with two or more DUls exhibited greater severity of alcohol dependence than those with none or one DUI This severity was characterized in three ways: (1) higher endorsement of alcohol diagnostic criterion items. with evidence of greater severity among women, (2) higher prevalence of co-occurring lifetime psychiatric disorders, and (3) higher rates of drug use and of dependence on cocaine, stimulants, and, for women only, marijuana and opiates. Conclusions: By examining gradations of disorder within a combination of two high-risk indicators. DUI and family vulnerability, this study provides useful information for clinical research about individuals with chronic and severe alcohol problems. In addition, the observed gender differences in this high-risk sample will contribute to the literature on alcohol dependence among women at the more severe end of the dependence spectrum.

McGrath KK; Jenkins AJ. Detection of drugs of forensic importance in postmortem bone. American Journal of Forensic Medicine and Pathology 30(1): 40-44, 2009. (11 refs.)

There is a paucity of literature detailing the disposition of drugs in bone and bone marrow. Infrequently, in deaths involving skeletonized remains, fragmentation, decomposition, and exsanguination, traditional specimens may be unavailable for toxicological testing. This study examined the utility of bone for the detection of benzodiazepines, opiates, cocaine and metabolites, and basic drugs in 39 cases. Cases were identified on the basis of a positive blood result. After specimen preparation, samples were assayed by liquid-liquid or solid phase extraction with gas chromatographic and gas chromatographic mass spectrometric detection. The majority of decedents were white males with 28% of individuals between the ages of 41 to 50 years. The cause of death was drug intoxication in 22 cases. The most prevalent drugs detected in the blood males and females were opiates and bases. Morphine, codeine, and oxycodone were detected in bone, whereas 6-acetylmorphine and hydrocodone were absent. For alkaline extractable drugs, in only 57% of blood positive specimens, the corresponding bone was also positive. These included antidepressants and antihistamines. Diazepam and nordiazepam were detected in the bone of all blood positive cases. Bone concentrations were higher than blood levels. Benzoylecgonine was the most common cocaine analyte detected in bone. These data demonstrated that drugs may be detected in bone using current technologies and that in general concentrations were higher than those observed in corresponding blood specimens. A negative result in bone, however, should be interpreted with caution because multiple factors determine the deposition of a drug in this matrix.

McMahon RC; Enders C. Personality disorder factors predict recovery of employment functioning among treated cocaine abusers. American Journal of Drug and Alcohol Abuse 35(3): 138-144, 2009. (36 refs.)

Background: Identifying treatments that produce specific benefits in nondrug psychosocial functioning areas such as employment functioning has been illusive. Examination of dimensions of clinical status that moderate such effects may be useful in planning more effective interventions. Objectives: The purpose of this study is to determine if life stress and four dimensions of personality and psychopathology previously found to predict early post-treatment relapse in diverse groups of substance abusers, predict less recovery in employment functioning among 240 cocaine dependent males after completion of residential treatment. Methods: Latent growth curve analysis was used to determine if antisocial, avoidant, dependent, paranoid-delusional personality dimensions, and life event stress predict employment problem severity evident at drug treatment discharge and change in employment problems over three 3-month follow-up intervals. Results: Individuals with higher employment severity at intake and those who spent less time in treatment tended to have greater employment problems at the predischarge. Two covariates were significant predictors of the linear growth component, and the set of covariates explained approximately 18% of the variation in the linear growth rates. Individuals with higher paranoid/delusional scores and lower educational attainment experienced less improvement in their employment status over follow-up. Conclusions: Current findings appear consistent with those of McLellan and colleagues who found that greater psychiatric severity predicts poor response to treatment across multiple psychosocial outcomes including employment status. Clinical Significance: More intensive and long-term psychiatric treatment and vocational-educational rehabilitative services may be required for improvement in employment functioning among those with relatively severe psychopathology.

Meghani SH; Wiedemer NL; Becker WC; Gracely EJ; Gallagher RM. Predictors of resolution of aberrant drug behavior in chronic pain patients treated in a structured opioid risk management program. Pain Medicine 10(5): 858-865, 2009. (25 refs.)

Objective. To identify demographic and clinical predictors of the resolution of aberrant drug-related behaviors (ADRBs) in a group of patients referred to the Opioid Renewal Clinic (ORC) by their primary care providers (PCPs). ORC is a program supporting PCPs' use of opioids for chronic pain in patients perceived as at risk for opioid abuse or those with demonstrated ADRBs. Methods. A retrospective chart review was conducted for 195 consecutive subjects referred to the ORC from January 17, 2002 to August 27, 2004, for ADRBs. Binary logistic regression was employed to identify independent predictors of aberrant behavior outcome at 1 year. Results. Of the 195 referred, 45.6% (N = 89) resolved their ADRB at 1 year. Other outcomes, classified as nonresolution of ADRB, self-discharged or discharged by the ORC for inability to adhere to the opioid treatment agreement (N = 86, 44.1%) and acceptance of referral for addiction treatment (N = 20, 10.2%). A history of cocaine abuse increased the odds of failing the program by five times (odds ratio [OR] = 4.97, P = 0.001). Each additional pain diagnosis reduced the odds of failure by 16% (OR = 0.837, P = 0.008). When compared with singles, married individuals were 62% less likely to fail the ORC program (OR = 0.38, P = 0.028). Conclusions. Nearly half of the patients resolved their aberrant behavior within the ORC. Patients with cocaine abuse were at higher risk for failure, suggesting a need for further research into safe and effective ways to manage pain in this complex subset of patients. Aberrant behaviors tended to resolve in patients with multiple pain locations, possibly because of their desire for relief.

Mizuno Y; Purcell DW; Zhang J; Knowlton AR; De Varona M; Arnsten JH et al. Predictors of current housing status among HIV-seropositive injection drug users (IDUs): Results from a 1-Year Study. AIDS and Behavior 13(1): 165-172, 2009. (45 refs.)

Using longitudinal data collected from 821 HIV-seropositive injection drug users (IDUs) who participated in a multi-site behavioral intervention study, we identified predictors of current housing status at baseline and 12-month follow-up time points. The study was conducted in Baltimore, Miami, New York, and San Francisco from 2001 to 2005. Logistic regression, incorporating the general estimating equations (GEE) method was performed. Multivariate analysis found that Miami participants (OR = 0.56) were less likely to report having current housing (P < 0.05). Among the potential barriers to housing, lower income (OR = 0.68), injection cocaine/crack use (OR = 0.66) and recent incarceration (OR = 0.10) were statistically significant (P < 0.05). Among the potential facilitators of housing, case management (OR = 1.38), outpatient drug treatment attendance (OR = 1.74), and social support (OR = 1.39) were significant. The association between social support and housing was stronger among those who had been recently incarcerated. Additional research is needed to identify types of support and resources beyond what is currently provided in order to better serve housing needs of HIV-seropositive IDUs.

Moeller SJ; Maloney T; Parvaz MA; Dunning JP; Alia-Klein N; Woicik PA et al. Enhanced choice for viewing cocaine pictures in cocaine addiction. Biological Psychiatry 66(2): 169-176, 2009. (56 refs.)

Background: Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. in two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Methods: Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures -- nder explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards) -- was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Results: Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects' choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Conclusions: Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

Mooney ME; Herin DV; Schmitz JM; Moukaddam N; Green CE; Grabowski J. Effects of oral methamphetamine on cocaine use: A randomized, double-blind, placebo-controlled trial. Drug and Alcohol Dependence 101(1-2): 34-41, 2009. (54 refs.)

Background: No medication is currently approved for the treatment of cocaine dependence, but several preclinical and clinical reports suggest agonist-like medications, e.g., amphetamine analogues, may be a productive strategy for medication development. Objective: This current proof-of-concept study sought to evaluate the safety, tolerability, and effectiveness of methamphetamine as a candidate treatment for cocaine dependence. Methods: A randomized, double-blind, placebo-controlled study served to evaluate three treatment conditions in 82 cocaine-dependent individuals: (1) placebo (0 mg, 6x/day; n = 27),(2) immediate release (IR) methamphetamine (5 mg, 6x/day; n = 30),(3) sustained release (SR) methamphetamine (30 mg first pill, 1x/day; 0 mg 5x/day; n = 25). The study employed a sequential, two-phase design (i.e., 4 weeks of medication and counseling followed by 4 weeks of medication/counseling plus a contingency management procedure). Results: Both preparation forms of methamphetamine were well-tolerated, with similar retention to placebo (0 mg, 33%; 30 mg IR, 30%, 30 mg SR, 32%). Methamphetamine SR was associated with decreased sleep and increased weight loss. Medication adherence rates were high for the first dose of the day (95%), while adherence for subsequent capsules was lower. Those in the SR condition exhibited consistently lower rates of cocaine-positive urine samples (0 mg, 60%; 30 mg IR, 66%; 30 mg SR, 29%), p < 0.0001, and reported the greatest reduction in craving for cocaine, p < 0.05. Conclusions: SR methamphetamine significantly reduced cocaine use and craving. Additional research is warranted to develop and evaluate agonist-like medications that may effectively treat cocaine dependence.

Morgan PT; Paliwal P; Malison RT; Sinha R. Sex differences in sleep and sleep-dependent learning in abstinent cocaine users. Pharmacology, Biochemistry and Behavior 93(1): 54-58, 2009. (36 refs.)

Sleep and sleep-dependent learning are impaired in male cocaine users during abstinence, but for female users little is known. Cocaine dependent men (n = 12) and women (n = 14), and control participants (n = 19) participated in this study of sleep and sleep-dependent learning. Cocaine users were assessed at 3, 10 and 20 days of abstinence and controls were studied over one night. Total sleep time, sleep efficiency and overnight motor learning were the main outcome measures. Cocaine dependent men compared to women exhibited deteriorations in sleep time, sleep efficiency, and overnight learning as abstinence progressed from 3 to 20 days. At abstinence day 3, cocaine dependent men and women were no different than control participants in the main outcomes. However, there were significant differences between cocaine men at abstinence day 20 and controls in sleep time and sleep-dependent learning, but no differences between controls and cocaine dependent women. There is growing evidence that sleep disturbances are associated with cocaine abuse and abstinence and have functional consequences that may be relevant to the development of effective treatments. The absence of sleep disturbances in women suggests a need to understand the mechanisms underlying these differences. as such knowledge could lead to novel therapies in cocaine dependence.

Ober A; Shoptaw S; Wang PC; Gorbach P; Weiss RE. Factors associated with event-level stimulant use during sex in a sample of older, low-income men who have sex with men in Los Angeles. Drug and Alcohol Dependence 102(1/3): 123-129, 2009. (28 refs.)

Prior research shows that stimulant use is consistently associated with high-risk sexual behavior in samples of men who have sex with men (MSM), but few studies have explored factors associated With use of crack or methamphetamine during sex during specific sexual events among older, very low-income MSM. This study examined stimulant use during the most recent sexual episodes in a sample of primarily older, very low-income MSM (n = 779). Although crack use was more prevalent than methamphetamine use (33% vs. 22%), findings suggest that methamphetamine users may be at greater risk for HIV transmission. HIV prevalence was higher among methamphetamine users (49%) than among Crack users (24%). Having unprotected sex (OR 2.77, 95% CI 1.46-5.26), having sex in a public sex venue (OR 3.63, 95% CI 1.52-8.64). having sex with an HIV positive rather than with in HIV negative partner (OR 6.15, 95% CI 2.14-17.62), having exchanged sex for money or drugs (OR 4.16, 95% CI 1.78-9.72), and having a higher number of sexual partners (OR 1.67, 95% CI 1.17-2.38) all were associated with increased odds of methamphetamine use during sex. Fewer high-risk behaviors were associated with increased odds of using crack during sex. Having unprotected sex was associated with increased odds of crack use during sex only when sex partners were perceived to be HIV negative rather than to be HIV positive or of unknown status. Findings provide observations on associations between stimulant use during sex and risk behaviors that may be important to HIV prevention and drug treatment approaches for urban, older, very poor MSM.

Oleson EB; Roberts DCS. Behavioral economic assessment of price and cocaine consumption following self-administration histories that produce escalation of either final ratios or intake. Neuropsychopharmacology 34(3): 796-804, 2009. (45 refs.)

Various self-administration procedures are being developed to model specific aspects of the addiction process. For example, 'increased cocaine intake over time' has been modeled by providing long access (LgA) to cocaine during daily self-administration sessions under a fixed-ratio (FR1) reinforcement schedule. In addition, 'increased time and energy devoted to acquire cocaine' has been modeled by providing access to cocaine during daily self-administration sessions under a progressive-ratio ( PR) schedule. To investigate the distinctiveness of these models, the behavioral economics variables of consumption and price were applied to cocaine self-administration data. To assess changes in consumption and price, cocaine self-administration was tested across a descending series of doses (0.237-0.001 mg per injection) under an FR1 reinforcement schedule to measure drug intake in the high dose range and thresholds in the low range. Cocaine consumption remained relatively stable across doses until a threshold was reached, at which maximal responding was observed. It was found that a history of LgA training produced an increase in cocaine consumption; whereas a history of PR training produced an increase in the maximal price (P-max) expended for cocaine. Importantly, the concepts of consumption and price were found to be dissociable. That is, LgA training produced an increase in consumption but a decrease in P-max, whereas PR training produced an increase in P-max without increasing consumption. These results suggest that distinct aspects of the addiction process can be parsed using self-administration models, thereby facilitating the investigation of specific neurobiological adaptations that occur through the addiction process.

Oleson EB; Talluri S; Childers SR; Smith JE; Roberts DCS; Bonin KD et al. Dopamine uptake changes associated with cocaine self-administration. Neuropsychopharmacology 34(5): 1174-1184, 2009. (54 refs.)

The present study was designed to reveal the relationship between cocaine-induced dopamine uptake changes and patterns of cocaine self-administration observed under a fixed-ratio schedule. Cocaine was intravenously infused into anesthetized rats, according to inter-infusion intervals obtained from self-administering animals, and dopamine uptake changes (apparent K-m) were assessed in the nucleus accumbens using voltammetry. The data demonstrate that cocaine-induced dopamine transporter (DAT) inhibition accounts for the accumbal dopamine fluctuations, which are associated with the cyclic regularity of cocaine intake observed during self-administration. Specifically, the inter-infusion intervals that are maintained during cocaine self-administration correlate with the maintenance of a rapidly changing level of dopamine uptake inhibition, which appears to be tightly regulated. Furthermore, this maintained level of dopamine uptake inhibition was found to shift upward using intervals from animals that had shown an escalation in the rate of cocaine self-administration. Although no significant change in the apparent K-m was revealed in animals that exhibited an escalation in the rate of cocaine intake, an increased dopamine uptake rate was found suggesting an upregulation of DAT number in response to a history of high cocaine intake. This is the first demonstration of the tight correlation that exists between the level of dopamine uptake inhibition and rates of cocaine self-administration. Moreover, a new mathematical model was created that quantitatively describes the changes in cocaine-induced dopamine uptake and correctly predicts the level of dopamine uptake inhibition. This model permits a computational interpretation of cocaine-induced dopamine uptake changes during cocaine self-administration.

Olmstead TA; Petry NM. The cost-effectiveness of prize-based and voucher-based contingency management in a population of cocaine- or opioid-dependent outpatients. Drug and Alcohol Dependence 102(1/3): 108-115, 2009. (33 refs.)

Objective: To evaluate the cost-effectiveness of using prize-based and Voucher-based contingency management (CM) as additions to standard treatment for cocaine- or heroin-dependent outpatients in community treatment centers. Methods: This cost-effectiveness analysis is based on a randomized clinical trial conducted at three community-based outpatient psychosocial substance abuse treatment clinics. A total of 142 cocaine- or heroin-dependent outpatients were randomly assigned to one of three treatment conditions: standard treatment (ST), ST with prizes (prize CM), or ST with vouchers (voucher CM) for 12 weeks. The primary patient outcome was the longest duration of confirmed abstinence (LDA) from cocaine, opioids and alcohol during treatment. Unit costs were collected from the three participating clinics. Resource utilizations and patient outcomes were obtained from the clinical trial. Incremental cost-effectiveness ratios (ICERs) and acceptability Curves were used to evaluate the relative cost-effectiveness of the interventions. Results: Based on the ICERs and acceptability curves, ST is likely to be the most cost-effective intervention when the threshold Value to decision makers of lengthening the LDA during treatment by I week is less than approximately $166, and prize CM is likely to be the most cost-effective intervention when the threshold value is greater than approximately $166. Conclusions: Prize CM was found likely to be the most cost-effective intervention over a comparatively wide range of threshold Values for lengthening the LDA during treatment by I week. However, additional studies with alternative incentive parameters are required to determine the generalizability of our results.

Orson FM; Kinsey BM; Singh RAK; Wu Y; Kosten TR. Vaccines for cocaine abuse. (review). Human Vaccines 5(4): 194-199, 2009. (56 refs.)

Treatments for cocaine abuse have been disappointingly ineffective, especially in comparison with those for some other abused substances. A new approach, using vaccination to elicit specific antibodies to block the access of cocaine to the brain, has shown considerable promise in animal models, and more recently in human trials. The mechanism of action for the antibody effect on cocaine is very likely to be the straightforward and intuitive result of the binding of the drug in circulation by antibodies, thereby reducing its entry into the central nervous system and thus its pharmacological effects. The effectiveness of such antibodies on drug pharmacodynamics is a function of both the quantitative and the qualitative properties of the antibodies, and this combination will determine the success of the clinical applications of anti-cocaine vaccines in helping addicts discontinue cocaine abuse. This review will discuss these issues and present the current developmental status of cocaine conjugate vaccines.

Oudejans SCC; Schippers GM; Merkx MJM; Schramade MH; Koeter MWJ; van den Brink W. Feasibility and validity of low-budget telephonic follow-up interviews in routine outcome monitoring of substance abuse treatment. Addiction 104(7): 1138-1146, 2009. (31 refs.)

Routine outcome monitoring (ROM) is receiving growing attention. However, follow-up interviews are time-consuming and costly. This study examines the feasibility and validity of low-budget telephonic follow-up interviews for ROM in a substance abuse treatment centre (SATC). Observational study using data collected for routine outcome monitoring. The study was performed in a SATC in an urban area in the Netherlands. Feasibility and validity were assessed on data of 2325 patients. Data on pre-treatment socio-demographic and clinical characteristics were collected using electronic patient records (EPRs) and the European version of the Addiction Severity Index (EuropASI). Data on intensity of treatment were also collected through the EPRs. Telephonic follow-up interviews were conducted between 9 and 10 months after intake. A 53% follow-up rate was achieved; 35% of the patients could not be contacted, 3% explicitly refused and in 8% other reasons accounted for non-participation. About 50% of the interviews took place in the intended time-frame. Costs were 40 ($57) per completed interview. There were indications of selection bias, because patients with cocaine as their primary problem and patients with polysubstance abuse were under-represented in the follow-up sample; the presence of these disorders is associated with negative treatment outcome. Implementing telephonic low-budget follow-up interviews for ROM is feasible, but selection bias threatens internal validity of data, limiting generalization to the total treatment population. Increased efforts to track patients for follow-up may improve generalization.

Pakula B; MacDonald S; Stockwell T. Settings and functions related to simultaneous use of alcohol with marijuana or cocaine among clients in treatment for substance abuse. Substance Use & Misuse 44(2): 212-226, 2009. (20 refs.)

Objectives: The paper identifies the central theoretical components for developing a typology of alcohol use with other substances. The settings and functions related to the simultaneous use of alcohol with marijuana or cocaine are examined using a dataset from a study of treatment clients in Ontario, Canada (data collected between the years 2003 and 2005). Methods: A cross-sectional design was used where patients 18 years or older completed a self-administered questionnaire upon admission to various treatment programs. Clients who reported using marijuana (n = 499) or cocaine (n = 375) in the past year were asked how often they use these substances in combination with alcohol. Findings: Simultaneous use is very common among treatment clients, with differences in the settings and functions associated with alcohol used in combination with cocaine or marijuana, and by various sociodemographic characteristics. The study's limitations are noted.

Pallonen UE; Timpson SC; Williams ML; Ross MW. Stages of consistent condom use, partner intimacy, condom use attitude, and self-efficacy in African-American crack cocaine users. Archives of Sexual Behavior 38(1): 149-158, 2009. (49 refs.)

This study examined how condom use attitude, self-efficacy, and partner intimacy related to five stages of consistent condom use. Interview data were collected from sexually active, heterosexual, African-American crack cocaine smokers (N = 366). Dependent measures assessed both the participants' own responses and their perceptions about their last sex partner's own personal condom use attitude and participants' condom use self-efficacy expectations. Partner intimacy was assessed both as a continuous attitudinal and as a discrete relationship measure. Less than 10% were classified as consistent condom users. Two thirds of inconsistent users were in the Precontemplation (PC) stage. The contemplation (C) and preparation (P) stages were equal among the remainder of the inconsistent condom users. Higher partner intimacy reduced modestly readiness for consistent condom use. The stage but not the intimacy group was related to the condom use attitudes and self-efficacy measures. Last partners' perceived own negative attitudes were significantly related to the stages of consistent condom use and was especially low in the action (A) and maintenance (M) stages. Participants' own negative attitudes were unrelated to the stages. Of the self-efficacy measures, both participants' performance and situational condom use self-efficacies increased significantly after the PC stage and were highest in the P, A, and M stages. However, situational self-efficacy accounted for most of performance self-efficacy variance. In sum, consistent condom use was rare. A partner's attitudes and the participants' own situational self-efficacy expectations, rather than intimacy, determined the readiness to adopt consistent condom use.

Parsons JT; Grov C; Kelly BC. Club drug use and dependence among young adults recruited through time-space sampling. Public Health Reports 124(2): 246-254, 2009. (46 refs.)

Objectives. Ketamine, methylenedioxymethamphetamine (MDMA/ecstasy), cocaine, gamma-hydroxybutyrate (GHB), methamphetamine, and cl-lysergic acid diethylamide (LSD/acid) have been identified as "club drugs" because of their link to club culture among young adults. Yet little is known about users' demographic differences in the prevalence of club drugs. This study sought to provide a comprehensive profile of users' demographic differences in prevalence of club drug use and dependence. Methods. Using time-space sampling, a stratified sample of 400 18- to 29-year-old club-going young adults was recruited into the Club Drugs and Health Project. Results. Though participants reported using an array of club drugs, almost all participants (90.0%) were cocaine users. Although there were several sexual orientation and gender differences in recent drug exposure, patterns of use (measured in days) were fairly similar across gender, sexual orientation, and age. Finally, a majority of individuals (58.5%) met or exceeded criteria for club drug dependence, with most (61.7%) indicating cocaine was the one drug causing them significant problems. Conclusions. Cocaine is a major drug in club culture. It is essential to develop culturally appropriate drug education and prevention initiatives for young adults using club drugs.

Patra J; Fischer B; Maksimowska S; Rehm J. Profiling poly-substance use typologies in a multi-site cohort of illicit opioid and other drug users in Canada-a latent class analysis. Addiction Research & Theory 17(2): 168-185, 2009. (85 refs.)

'Poly-substance use' is increasingly prevalent among street drug user populations. The objective was to employ latent class analysis (LCA) to empirically categorize and extract potential typologies of poly-substance users within a multi-site cohort of illicit opioid and other drug users (OPICAN) in Canada, and examine potential associations with social and health indicators. Drug use patterns of 582 participants from the most recent follow-up (2005) of the cohort study-focusing on drug use prevalence indicators in the past 30 days-were empirically analyzed via LCA. These classes were further examined for associations with social and health variables using chi-square, ANOVA. Binomial logistic regression models were used to predict class membership. LCA analysis resulted in eight distinct user typologies, characterized both by the distinct relative prevalence of different substances (e.g., including: heroin, prescription opioids, benzodiazepines, cocaine, crack, alcohol, cannabis, and others) used and administration routes (e.g., injection or noninjection), the majority of which were described by the predominant use of two or more distinct substance groups (e.g., opioids and stimulants). At least two of the active poly-substance user classes were described by predominant noninjection as the primary route of administration. 'Poor or fair' health status was reported at the highest prevalence level by the class of intensive poly-substance injectors, while HCV-positive status was disproportionately low in the classes of current noninjectors. Analytical examination of poly-substance use patterns is a distinct challenge for meaningful drug use monitoring, also providing important evidence for targeted prevention and treatment interventions.

Peake STC; Das S; Greene S; Dubrey SW. Cocaine 'body packers' and the clinical management of packet rupture. British Journal of Hospital Medicine 70(2): 110-111, 2009. (7 refs.)

This is a case report of the management of the rupture of packets ingested by "body packers." The first case report of transport of illicit drugs was in 1973, when a condom containing hashish led to bowel obstruction. Of note, Heathrow Airport (England) reports indentifying on 5-8 individuals per week who have smuggled drugs by this method. Nigeria is the most common point of origin. In cases of packet rupture, death is likely to occur prior to reaching a hospital. Typically people carry up to 1 kg of cocaine, divided into 50-100 packets. A single packet contains a lethal dose. The case report required surgical intervention. There is also discussion of drug therapies to deal with the acute effects of the illicit drugs, such as agitation, hypertension, and myocardial ischemia.

Peirce JM; Petry NM; Roll JM; Kolodner K; Krasnansky J; Stabile PQ et al. Correlates of stimulant treatment outcome across treatment modalities. American Journal of Drug and Alcohol Abuse 35(1): 48-53, 2009. (25 refs.)

Objective: This study evaluated variables associated with stimulant use outcomes in stimulant users (N = 800) receiving care in community outpatient psychosocial or methadone maintenance treatment clinics as part of a national multi-site clinical trial. Methods: Results from the full sample were examined first, and then predictors were examined separately in the two treatment modalities. Results: A cocaine-positive urine sample at study intake was the most robust and consistent correlate of stimulant use outcome in all analyses. Psychiatric distress, social environment and employment had differential effects on outcome across modalities. Conclusions/Significance: This study confirms that intake assessments have considerable value in identifying problems to be addressed in treatment.

Phillips K; Luk A; Soor GS; Abraham JR; Leong S; Butany J. Cocaine cardiotoxicity: A review of the pathophysiology, pathology, and treatment options. (review). American Journal of Cardiovascular Drugs 9(3): 177-196, 2009. (189 refs.)

Cocaine is a powerful stimulant that gives users a temporary sense of euphoria, mental alertness, talkativeness, and a decreased need for food and sleep. Cocaine intoxication is the most frequent cause of drug-related death reported by medical examiners in the US, and these events are most often related to the cardiovascular manifestations of the drug. Once playing a vital role in medicine as a local anesthetic, decades of research have established that cocaine has the ability to cause irreversible structural damage to the heart, greatly accelerate cardiovascular disease, and initiate sudden cardiac death. Although pathologic findings are often reported in the literature, few images are available to support these findings, and reviews of cocaine cardiopathology are rare. We describe the major pathologic findings linked to cocaine abuse in earlier research, their underlying mechanisms, and the treatment approaches currently being used in this patient population. A MEDLINE search was conducted to identify all English language articles from January 2000 to June 2008 with the subject headings and key words 'cocaine', 'heart', 'toxicity', and 'cardiotoxicity'. Epidemiologic, laboratory, and clinical studies on the pathology, pathophysiology, and pharmacology of the effects of cocaine on the heart were reviewed, along with relevant treatment options. Reference lists were used to identify earlier studies on these topics, and related articles from Google Scholar were also included. There is an established connection between cocaine use and myocardial infarction (MI), arrhythmia, heart failure, and sudden cardiac death. Numerous mechanisms have been postulated to explain how cocaine contributes to these conditions. Among these, cocaine may lead to MI by causing coronary artery vasoconstriction and accelerated atherosclerosis, and by initiating thrombus formation. Cocaine has also been shown to block K+ channels, increase L-type Ca2+ channel current, and inhibit Na+ influx during depolarization, all possible causes for arrhythmia. Additionally, cocaine use has been associated with left ventricular hypertrophy, myocarditis, and dilated cardiomyopathy, which can lead to heart failure if drug use is continued. Certain diagnostic tools, including ECG and serial cardiac markers, are not as accurate in identifying MI in cocaine users experiencing chest pain. As a result, clinicians should be suspicious of cocaine use in their differential diagnosis of chest pain, especially in the younger male population, and proceed more cautiously when use is suspected. Treatment for cocaine-related cardiovascular disease is in many ways similar to treatment for traditional cardiovascular disease. However use of beta-receptor antagonists and class Ia and III anti-arrhythmics is strongly discouraged if the patient is likely to continue cocaine use, because of documented adverse effects. The medical community is in urgent need of a pharmacologic adjunct to cocaine-dependence treatment that can deter relapse and reduce the risks associated with cardiovascular disease in these patients.

Popa DS; Vlase L; Leucuta SE; Loghin F. Determination of cocaine and benzoylecgonine in human plasma by LC-MS/MS. Farmacia 57(3): 301-308, 2009. (0 refs.)

A high-throughput Liquid chromatography/ Mass spectrometry/ Mass spectrometry (LC/MS/MS) method for simultaneous quantification of cocaine (COC) and benzoylecgonine (BZE) in human plasma was elaborated. After the protein precipitation with methanol in the plasma samples, the analytes were separated on a Zorbax SB-C18 column under isocratic conditions using a 32:68 (v/v) mixture of methanol and 0.1% formic acid in water at 45 degrees C, with a flow rate of 1 mL/min. The detection was in multiple reaction monitoring (MRM) mode (m/z 290 -> m/z 168 for BZE and m/z 304 -> m/z 182 for COC, respectively). Calibration curves were generated over the range of 20-2000 ng/mL for both BZE and COC (r > 0.992). In the laboratories that are not equipped with a LC/MS/MS system, the LC analysis of COC and BZE requires a previous isolation step. Therefore, the elaborated LC/MS/MS method was applied for the study of optimum experimental conditions for the isolation of COC and BZE from human plasma. Several solvent mixtures and solid-phase extraction (SPE) cartridges were tested at different pH values. The best results for both analytes were obtained by SPE on Oasis HLB cartridges (mean recovery of 71 % for COC and 92.4 % for BZE, n = 3). Both the elaborated LC/MS/MS method and the best extraction conditions can successfully be applied in clinical and forensic toxicology for the rapid quantification of COC and BZE in human plasma.

Ramful P; Zhao XY. Participation in marijuana, cocaine and heroin consumption in Australia: a multivariate probit approach. Applied Economics 41(4): 481-496, 2009. (32 refs.)

This article investigates factors affecting the participation in marijuana, cocaine and heroin using micro-unit data from an Australian national survey on recreational drugs. Accounting for cross-drug correlation potentially induced by unobserved personal characteristics such as individual tastes and addictive personalities, we estimate a trivariate probit model, where the participation decisions are jointly modelled as a system with correlated error terms. The estimated correlation coefficients are significant across all three drugs. The study provides valuable empirical information on conditional and joint probabilities of drug participation. The multivariate approach is shown to provide better analysis relative to a univariate approach that does not address the endogeneity of all drug participation variables.

Reed SC; Haney M; Evans SM; Vadhan NP; Rubin E; Foltin RW. Cardiovascular and subjective effects of repeated smoked cocaine administration in experienced cocaine users. Drug and Alcohol Dependence 102(1/3): 102-107, 2009. (30 refs.)

Studies using rodents have shown that behavioral responses to a stimulant are enhanced when the stimulant is given within the same context as previous stimulant administrations; this increase in effect related to context is often referred to as sensitization. We examined the role of environmental stimuli in modulating the subjective and cardiovascular effects of cocaine in humans (1) within a daily "binge" and (2) after cocaine abstinence. Ten non-treatment seeking users of smoked cocaine were admitted to the hospital for 17 consecutive clays. Participants smoked cocaine (25 mg/dose) under two counterbalanced conditions: paired stimuli (same stimuli presented each session) and unpaired stimuli (varied stimuli presented each session). Under each stimulus condition, participants had cocaine test sessions for three consecutive days, no sessions for the next 3 days, then another cocaine test session on the following day, for a total of eight test days. Stimulus condition had no effect on cardiovascular or subjective effects so data were analyzed as a function of repeated cocaine administration over 2 weeks. Maximal ratings on "good drug" and "drug rating" subjective effects clusters decreased over days of repeated cocaine exposure. In contrast, baseline and peak heart rate and systolic pressure increased over days of repeated cocaine administration. Thus, repeated administration of smoked cocaine to experienced cocaine users resulted in increases in baseline blood pressure and heart rate and modest decreases in positive subjective effects. These data indicate modest tolerance rather than sensitization to the positive subjective effects of cocaine with repeated exposure.

Reid MS; Thakkar V. Valproate treatment and cocaine cue reactivity in cocaine dependent individuals. Drug and Alcohol Dependence 102(1/3): 144-150, 2009. (67 refs.)

Based on prior clinical trials indicating that gamma-aminobutyric acid (GABA)-based anticonvulsant medications reduce drug craving in cocaine dependent Study participants, we tested the effects of valproate treatment on cue-induced cocaine craving. Crack cocaine dependent individuals (N=20) were tested in a randomized, placebo-controlled, within-subjects, crossover study design. Valproate treatment was titrated up to 1500 mg/day by Day 6 of treatment. Cue testing was completed on Day 8 of treatment, and all study participants underwent a washout period of 5 days between active and placebo medication treatment periods. Testing included both cocaine and neutral cue exposure sessions, presented in a random and counterbalanced order. Main effects of cue exposure were found for subjective ratings of "desire to use cocaine now", the cocaine craving index, cocaine-like high, and cocaine withdrawal. Treatment interaction effects were found with "desire to use cocaine now", which underwent a greater increase following cocaine cue exposure in the valproate condition. Main effects of medication treatment were found, in which lower blood pressure and heart rate, and higher plasma cortisol levels, were associated with valproate treatment. Valproate treatment was also associated, at a trend level, with higher pre-test cocaine craving levels. The results demonstrate that cocaine cue reactivity is a robust phenomena across two assessment sessions, but fail to support the use of valproate as a means of reducing spontaneous and cue-induced cocaine craving. The use of valproate as a treatment for cocaine dependence is not supported.

Risser JMH; Padgett P; Wolverton M; Risser WL. Relationship between heterosexual anal sex, injection drug use and HIV infection among black men and women. International Journal of STD & AIDS 20(5): 310-314, 2009. (33 refs.)

US blacks carry a disproportionate risk of heterosexually transmitted HIV. This study aimed to evaluate the association between self-reported heterosexual anal intercourse and HIV. Using respondent-driven sampling (RDS), we recruited and interviewed 909 blacks from areas of high poverty and HIV prevalence in Houston, Texas, and who reported heterosexual sex in the last year. All individuals were tested for HIV. Weighted prevalence values were calculated to account for non-random recruitment associated with RDS. The weighted population prevalence of HIV infection was 2.4% and 2.5% among men and women, respectively. Education, employment status, income and crack cocaine use were not associated with HIV infection. Lifetime injection drug use (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.33%) and heterosexual anal intercourse (OR 2.41, 95% Cl 1.02-5.73%) were, associated with HIV infection. Individuals who reported both injection drug use and heterosexual anal intercourse had 6.21 increased odds of HIV (95% Cl 2.47-15.61%). Our results suggest that heterosexual anal sex may be a vector for HIV transmission, especially in the context of injection drug use. Prevention strategies directed at curbing the HIV epidemic among black heterosexuals require that we correctly identify the risks so that appropriate interventions can be developed.

Roberts JR; Price C; Mazzeo T. Intravenous epiepherine: A minimally invasive treatment for priapism in the emergency department. Journal of Emergency Medicine 36(3): 285-289, 2009. (11 refs.)

Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.

Rose-Jacobs R; Waber D; Beeghly M; Cabral H; Appugleise D; Heeren T et al. Intrauterine cocaine exposure and executive functioning in middle childhood. Neurotoxicology and Teratology 31(3): 159-168, 2009. (89 refs.)

This longitudinal study evaluated whether the level of intrauterine cocaine exposure (IUCE) or the interaction between IUCE and contextual variables was related during middle childhood to executive functioning, as assessed with the Stroop Color-Word and Rey Osterrieth Complex Figure tests. The Stroop Interference score measures verbal inhibitory control while the Rey Osterrieth Organizational score evaluates skills such as planning, Organization and perception. Masked examiners assessed 143 children at 9.5 and I I years of age (74 with IUCE and 69 demographically similar children without IUCE). Level of IUCE (Unexposed; Lighter. and Heavier) was documented by positive postpartum maternal reports and infant meconium assays. In covariate-controlled regressions, level of IUCE was not significantly associated with Stroop Interference or Rey Osterrieth Organization scores. However, in covariate controlled post-hoc tests comparing the Heavier exposed group to the combined Lighter/Unexposed group, children in the Heavier group had significantly Poorer Stroop Interference scores, but there was no significant group difference for Rey Osterrieth Organizational scores. Children's average Organization scores in Unexposed, Lighter, and Heavier exposed groups were well below the test norm means. Results of this study indicate that heavier IUCE may be associated with mild compromise on school-aged children's ability to inhibit prepotent verbal responses.

Rush CR; Stoops WW; Hays LR. Cocaine effects during D-amphetamine maintenance: A human laboratory analysis of safety, tolerability and efficacy. Drug and Alcohol Dependence 99(1-3): 261-271, 2009. (44 refs.)

Agonist replacement therapies are effective for managing substance abuse disorders including nicotine and opioid dependence. The results of preclinical laboratory studies and clinical trials indicate that agonist replacements like D-amphetamine may be a viable option for managing cocaine dependence. This experiment determined the physiological and behavioral effects of cocaine during D-amphetamine maintenance in seven cocaine-dependent participants. We predicted cocaine would be well tolerated during D-amphetamine maintenance. We also predicted D-amphetamine would attenuate the behavioral effects or cocaine. After 3-5 days of D-amphetamine maintenance (0, 15, and 30 mg/day), volunteers were administered ascending closes of cocaine (4, 30, 60 mg, IN) within a single session. Cocaine doses were separated by 90 min. Cocaine produced prototypical physiological (e.g., increased heart rate, blood pressure, and body temperature) and subject-rated (e.g., increased ratings of Good Effects) effects. During maintenance on the highest D-amphetamine dose, the heart rate increasing effects of cocaine were larger than observed during placebo maintenance, These effects were not clinically significant and no unexpected or serious adverse events were observed. D-Amphetamine attenuated some of the subject-rated effects of cocaine. These results are concordant with those of previous preclinical studies, human laboratory experiments and clinical trials, further suggesting that agonist replacement therapy may be a viable strategy for managing cocaine abuse. Additional research in humans is needed to determine whether D-amphetamine attenuates the effects of cocaine Under different experimental conditions (e.g., higher cocaine doses) and behavioral arrangements (e.g., drug self-administration or discrimination).

Santamarina-Rubio E; Perez K; Ricart I; Rodriguez-Sanz M; Rodriguez-Martos A; Brugal MT et al. Substance use among road traffic casualties admitted to emergency departments. Injury Prevention 15(2): 87-94, 2009. (45 refs.)

Objective: To describe the prevalence of recent psychoactive substance use and associated factors among road traffic casualties admitted to emergency departments. Methods: A cross-sectional study was carried out, including adults injured in road traffic crashes admitted to the emergency department (ED) of eight hospitals in Catalonia (Spain), during three cross-sections, each of 4 days duration (2005-2006). Information sources were an interview, an oral fluid specimen and the patient's clinical record. Dependent variables were presence of alcohol, cannabis, cocaine, ecstasy, opiates or benzodiazepines. Independent variables were socioeconomic characteristics and circumstances of the injuries and admission. Prevalence and exact 95% confidence intervals were estimated for men and women. Bivariate analyses and multivariate binomial regression modelling were carried out to study factors associated with substance use in male drivers and pedestrians. Results: The prevalence of substance use was higher in men (n = 226) than in women (n = 161) for any substance (34.4% and 16.2%), any illegal substance (19.3% and 7.6%), alcohol (18.5% and 9.2%) and cannabis (17.0% and 3.8%), respectively. In male drivers and pedestrians, alcohol use was associated with being in the 25-30-year age group, being injured at night and the weekend, and arriving at the ED by ambulance; cannabis use was only associated with being in the 18-30-year age group. Conclusions: A high prevalence of recent psychoactive substance use, especially alcohol, cannabis and cocaine, was observed in all age groups. The results indicate the need to screen for substance use and to give simple advice to casualties at EDs.

Schmitz JM; Mooney ME; Green CE; Lane SD; Steinberg JL; Swann AC et al. Baseline neurocognitive profiles differentiate abstainers and non-abstainers in a cocaine clinical trial. Journal of Addictive Diseases 28(3): 250-257, 2009. (44 refs.)

Previous studies have shown that cocaine users have higher levels of impulsivity and impaired decision making; however, few have examined these factors as predictors of treatment success. We obtained baseline neurocognitive measures from 75 cocaine-dependent individuals participating in a 12-week clinical trial targeting impulsivity with behavioral therapies and pharmacotherapy. Participants treated with citalopram had higher cocaine abstinence rates compared to placebo-treated participants. The aim of this secondary analysis study was to determine whether profiles of performance on neurocognitive measures administered at baseline discriminated among patients who achieved abstinence and those who did not. Participants completed the Immediate and Delayed Memory Task, Barratt Impulsiveness Scale-11, and Iowa Gambling Task. Profile analysis results showed different patterns of performance on these baseline measures as a function of outcome. Compared with non-abstinent participants, abstinent participants had higher scores on the Barratt Impulsiveness Scale-11 Non-Planning subscale and better performance on the Iowa Gambling Task. Profile differences for the two outcome groups did not vary as a function of treatment condition. Results suggest that cocaine-dependent patients entering treatment with higher impulsivity and less impaired decision-making abilities may respond favorably to targeted behavioral interventions. Neurocognitive profiles may be useful in understanding population heterogeneity and predicting differential outcomes in subgroups of cocaine abusers.

Schnell T; Koethe D; Daumann J; Gouzoulis-Mayfrank E. The role of cannabis in cognitive functioning of patients with schizophrenia. Psychopharmacology 205(1): 45-52, 2009. (50 refs.)

Cognitive deficits are commonly found both in patients with schizophrenia (SCH) and in people with cannabis use disorders (CUD). Surprisingly, some small recent studies reported better cognitive performance in SCH patients with comorbid cannabis use disorders (SCH + CUD) compared to other SCH patients. The aim of the present study was to investigate the residual impact of CUD and specific patterns of consumption on cognition in a larger sample of SCH + CUD patients. We administered a cognitive test battery to 34 SCH and 35 currently abstinent SCH + CUD patients. We explored the association between patterns of cannabis consumption and cognitive performance. Potential confounds with influence on cognitive ability were assessed and controlled for. SCH + CUD patients had poorer academic achievements and lower vocabulary scores, but they performed better in tests of verbal and working memory, visuomotor speed and executive function (p < .05). More frequent cannabis use was associated with better performance in attention and working memory tasks. Although our findings might be interpreted as beneficial effect of cannabis use on cognition in patients with schizophrenia, we favorise an alternative interpretation: in our view, the better cognitive functioning of SCH + CUD patients may rather reflect a relatively lower vulnerability to psychosis compared to the SCH group. Lower vulnerability may correspond to a higher level of functioning such as cognitive ability. This conclusion is consistent with the view of cannabis playing a critical role in the manifestation of psychosis in at least some of the SCH + CUD patients.

Shakleya DM; Huestis MA. Simultaneous quantification of nicotine, opioids, cocaine, and metabolites in human fetal postmortem brain by liquid chromatography tandem mass spectrometry. Analytical and Bioanalytical Chemistry 393(8): 1957-1965, 2009. (42 refs.)

A validated method for simultaneous LCMSMS quantification of nicotine, cocaine, 6-acetylmorphine (6AM), codeine, and metabolites in 100 mg fetal human brain was developed and validated. After homogenization and solid-phase extraction, analytes were resolved on a Hydro-RP analytical column with gradient elution. Empirically determined linearity was from 5-5,000 pg/mg for cocaine and benzoylecgonine (BE), 25-5,000 pg/mg for cotinine, ecgonine methyl ester (EME) and 6AM, 50-5000 pg/mg for trans-3-hydroxycotinine (OH-cotinine) and codeine, and 250-5,000 pg/mg for nicotine. Potential endogenous and exogenous interferences were resolved. Intra- and inter-assay analytical recoveries were a parts per thousand yen92%, intra- and inter-day and total assay imprecision were a parts per thousand currency sign14% RSD and extraction efficiencies were a parts per thousand yen67.2% with a parts per thousand currency sign83% matrix effect. Method applicability was demonstrated with a postmortem fetal brain containing 40 pg/mg cotinine, 65 pg/mg OH-cotinine, 13 pg/mg cocaine, 34 pg/mg EME, and 525 pg/mg BE. This validated method is useful for determination of nicotine, opioid, and cocaine biomarkers in brain.

Shannon LM; Havens JR; Mateyoke-Scrivner A; Walker R. Contextual differences in substance use for rural Appalachian treatment-seeking women. American Journal of Drug and Alcohol Abuse 35(2): 59-62, 2009. (20 refs.)

Objective: To examine differences in substance use among a sample of women entering treatment from rural Appalachian and non-Appalachian areas. Participants: A total of 2,786 women participating in state-funded substance abuse treatment programs statewide. Measures: Substance use measures were based on the SAMHSA CSAT Government Performance and Results Act (GPRA) gathering information on lifetime and past 12-month use of alcohol, marijuana, opiates, sedatives/tranquilizers, cocaine, and stimulants. Results: Women entering treatment in rural Appalachia had disproportionately high rates of opiate and sedative/tranquilizer use while methamphetamine, cocaine, marijuana, and alcohol were more prevalent for women in non-Appalachian areas. Conclusions: Women entering treatment in rural Appalachia were significantly more likely to report opiate and sedative/tranquilizer use compared to non-Appalachian women. In order to begin to understand the elevated rates of prescription drug abuse in rural Appalachian Kentucky, substance use must be considered within the context of demographic, geographic, social, and economic conditions of the region.

Sheinkopf SJ; Lester BM; Sanes JN; Eliassen JC; Hutchison ER; Seifer R et al. Functional MRI and response inhibition in children exposed to cocaine in utero. Psychiatric Services 31(1/2): 159-166, 2009. (43 refs.)

This study investigated the potential long-term effects of cocaine exposure on brain functioning using fMRI in school-aged children. The sample included 12 children with prenatal cocaine exposure and 12 non-exposed children (8-9 years old). Groups did not differ on IQ, socioeconomic status, or perinatal risk factors. A response inhibition task was administered during an fMRI scan using a 1.5-T MRI system. Task performance did not differentiate groups, but groups were differentiated by patterns of task-related brain activity. Cocaine-exposed children showed greater activation in the right inferior frontal cortex and caudate during response inhibition, whereas non-exposed children showed greater activations in temporal and occipital regions. These preliminary findings suggest that prenatal cocaine may affect the development of brain systems involved in the regulation of attention and response inhibition.

Simmons LA; Havens JR; Whiting JB; Holz JL; Bada H. Illicit drug use among women with children in the United States: 2002-2003. Annals of Epidemiology 19(3): 187-193, 2009. (40 refs.)

PURPOSE: Given research that shows youth exposed to maternal addict ion have increased rates of cognitive, socioemotional, and behavioral problems, we examined the prevalence and correlates of past year illicit drug abuse or dependence among women with children younger than 18 years of age in the home to identify maternal risk factors. METHODS: Data were from the 2002 and 2003 National Survey on Drug Use and Health, a nationally representative sample of the U.S. civilian population. The current analysis utilized a subsample of women (N = 19,300) who reported having children Younger than 18 years in the home. Past year abuse or dependence on cocaine, heroin, marijuana, stimulants, and hallucinogens as well as nonmedical use of prescription medications were assessed. RESULTS: The prevalence of illicit drug abuse or dependence was 1.9%. Mothers reporting drug abuse or dependence had increased odds of being unmarried, controlling for other demographics. They also were more likely to report stress, poorer health status, and meet the criteria for serious mental illness (SMI). CONCLUSIONS; Prevention and intervention strategies should focus on developing and tooting methods to screen for both risk factors associated with maternal drug abuse and actual substance abuse in primary and emergency care settings to reduce youth exposure and improve child developmental outcomes.

Sivapalan H. Khantzian's 'self-medication hypothesis' of drug addiction and films by Martin Scorsese. International Review of Psychiatry 21(3, Special Issue): 285-288, 2009. (23 refs.)

The portrayal of self-medication and drug use was studied in three films by Martin Scorsese: Raging Bull (1980), Goodfellas (1990) and The Departed (2006). Self-medication using nicotine in Raging Bull, cocaine in Goodfellas and sedatives in The Departed, exhibit mixed portrayals of the self-medication hypothesis. The temporal aspects of the hypothesis and credibility of character psychopathology show variation between the films. Across all films, the selection of particular drugs of choice for certain symptom clusters is consonant with that detailed in the self-medication hypothesis put forward by Khantzian.

Smith MJ; Thirthalli J; Ben Abdallah A; Murray RM; Cottler LB. Prevalence of psychotic symptoms in substance users: A comparison across substances. Comprehesive Psychiatry 50(3): 245-250, 2009. (45 refs.)

Background: psychotic symptoms (delusions and hallucinations) are reported to be increased among persons using illicit substances, but little is known about the comparative frequency with which the symptoms occur with abuse of different substances. To establish this, we interviewed individuals who had wide experience of commonly used drugs. Methods: Four hundred seventy-six intravenous drug users, crack-cocaine users, and heroin snorters recruited via street outreach were interviewed using the Composite International Diagnostic Interview-Substance Abuse Model to assess dependence on a number of substances including amphetamines, cannabis, cocaine, and opioids. As a part of this assessment, we assessed a history of delusions and hallucinations in the context of use of, or withdrawal from, these specific substances. Results: From 27.8% to 79.6%, users of amphetamine, cannabis, cocaine, and opiates met Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, dependence for that specific substance. The prevalence of psychotic symptoms associated with each specific substance ranged from users with no diagnosis to users with severe dependence as follows: amphetamines (5.2%-100%), cannabis (12.4%-80.0%), cocaine (6.7%-80.7%), and opiates (6.7%-58.2%). The risk of psychotic symptoms increased for respondents who abused (odds ratio [OR], 12.2) or had mild (OR, 17.1), moderate (OR, 47.0), or severe dependence (OR, 114.0) on cocaine when compared to those who were users with no diagnosis. A similar pattern was evident in cannabis, opiate, and amphetamine users. Conclusions: Most users dependent on illicit substances experience psychotic symptoms in the context of use of, or withdrawal from, these substances. Psychotic symptoms increased with the severity of the substance use disorders for all 4 Substances. These findings emphasize the importance of developing services to target this population as they are at a heightened risk for developing psychotic symptoms.

Sofuoglu M; Sewell RA. Norepinephrine and stimulant addiction. (review). Addiction Biology 14(2): 119-129, 2009. (122 refs.)

No pharmacotherapies are approved for stimulant use disorders, which are an important public health problem. Stimulants increase synaptic levels of the monoamines dopamine (DA), serotonin and norepinephrine (NE). Stimulant reward is attributable mostly to increased DA in the reward circuitry, although DA stimulation alone cannot explain the rewarding effects of stimulants. The noradrenergic system, which uses NE as the main chemical messenger, serves multiple brain functions including arousal, attention, mood, learning, memory and stress response. In pre-clinical models of addiction, NE is critically involved in mediating stimulant effects including sensitization, drug discrimination and reinstatement of drug seeking. In clinical studies, adrenergic blockers have shown promise as treatments for cocaine abuse and dependence, especially in patients experiencing severe withdrawal symptoms. Disulfiram, which blocks NE synthesis, increased the number of cocaine-negative urines in five randomized clinical trials. Lofexidine, an alpha(2)-adrenergic agonist, reduces the craving induced by stress and drug cues in drug users. In addition, the NE transporter (NET) inhibitor atomoxetine attenuates some of d-amphetamine's subjective and physiological effects in humans. These findings warrant further studies evaluating noradrenergic medications as treatments for stimulant addiction.

Solinas M; Thiriet N; El Rawas R; Lardeux V; Jaber M. Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine. Neuropsychopharmacology 34(5): 1102-1111, 2009. (55 refs.)

It is known that negative environmental conditions increase vulnerability to drugs, whereas little is known on whether positive environmental conditions such as enriched environments (EE) have protective effects against addiction. We have previously found that EE consisting of bigger cages containing several toys that were changed once per week reduce cocaine-induced increases in locomotor activity. Here, we also show that the rewarding effects of cocaine are blunted in mice reared from weaning to adulthood in EE compared to mice reared in standard environments (SE). In addition, although both EE and SE mice develop behavioral sensitization to cocaine, EE mice show less activation in response to repeated administration of cocaine injections and reduced responses to cocaine challenges. In vivo microdialysis experiments demonstrate that the protective effects of EE do not depend on reduced cocaine-induced increases in the dopamine levels in the ventral or dorsal striatum. On the other hand, they were associated with reduced cocaine-induced expression of the immediate early gene zif-268 in the nucleus accumbens (shell and core) of EE mice. Finally, basal levels of Delta-Fos B, a transcription factor known to be increased by sustained activation of striatal neurons, are higher in the striatum of EE compared to SE mice and repeated administration of cocaine increases Delta-Fos B levels in SE mice but decreases them in EE mice. Altogether our results demonstrate that exposure to complex environments during early stages of life produce dramatic changes in the striatum that result in reduced reactivity to drugs of abuse.

Stalnaker TA; Takahashi Y; Roesch MR; Schoenbaum G. Neural substrates of cognitive inflexibility after chronic cocaine exposure. (review). Neuropharmacology 56(Supplement 1): 63-72, 2009. (107 refs.)

Cognitive changes in addicts and animals exposed to addictive drugs have been extensively investigated over the past decades. One advantage of studying addiction using cognitive paradigms is that neural processing in addicts or drug-exposed animals can be compared to that in normal subjects. Tests of cognitive flexibility that measure the ability to change responding to a previously rewarded or punished stimulus are of potential interest in the study of addiction, because addiction can itself be viewed as an inability to change responding to stimuli previously associated with drug reward. One such test is reversal learning, which is impaired in cocaine addicts and animals that have chronically self-administered or been exposed to cocaine. A circuit including orbitofrontal cortex, basolateral amygdala and striatum subserves reversal learning. In rats that have been previously exposed to cocaine, neurons in these regions show selective and distinct changes in how they encode information during reversal learning. These changes suggest that in these rats, orbitofrontal cortex loses the ability to signal expected outcomes, and basolateral amygdala becomes inflexible in its encoding of cue significance. These changes could explain cocaine-induced impairments to cognitive flexibility and may have theoretical importance in addiction.

Stein MD; Herman DS; Anderson BJ. A motivational intervention trial to reduce cocaine use. Journal of Substance Abuse Treatment 36(1): 118-125, 2009. (34 refs.)

The aim of this study was to test if a motivational intervention would reduce cocaine use. We performed a randomized trial with 6-month follow-up for 198 persons who used cocaine at least weekly. Participants were randomly assigned to a four-session motivational intervention or an assessment control group. We performed an intent-to-treat analysis of past 30-day self-reported cocaine use at 6 months, with those lost to follow-up assumed to use cocaine at their baseline level. Participants were 62% male, 40% Caucasian, and used cocaine an average of 13.8 days over the past month. In the full cohort, there were no significant intervention effects on mean change in cocaine use days (P = .21), past 30-day abstinence (33% vs. 26%, p = .26), or >50% reduction in cocaine use days from baseline (55.7% vs. 46.5%, p = .20). However, among those using cocaine on 15 or more of the 30 days prior to baseline, motivational interviewing participants had a significantly larger mean reduction in cocaine use days (p = .023). There were also no significant group differences in days of employment, quality of life, or substance abuse treatment entry. We conclude that this motivational intervention was more effective than assessment alone at reducing cocaine days among the heaviest community-based users. Both study conditions induced positive effects on cocaine use.

Storti CC; De Grauwe P. Globalization and the price decline of illicit drugs. International Journal of Drug Policy 20(1): 48-61, 2009. (25 refs.)

Background: This study aims at understanding the mechanisms underlying the dramatic decline of the retail prices of major drugs like cocaine and heroin during the past two decades. It also aims at analysing the implications of this decline for drug policies. Methods: We use a theoretical model to identify the possible causes of this price decline. This allows us to formulate the hypothesis that the major driving force behind the price decline is a reduction of the intermediation margin (the difference between the retail and producer prices). We also develop the hypothesis that globalization has been an important factor behind the decline of the intermediation margin. We then analyse the statistical information to test these hypotheses. Results: We find that the decline in the retail prices of drugs is related to the strong decline in the intermediation margin in the drug business, and that globalization is the main driving force behind this phenomenon. Globalization has done so by increasing the efficiency of the distribution of drugs, by reducing the risk premium involved in dealing with drugs, and by increasing the degree of competition ill the drug markets. Conclusion: We conclude that the cocaine and heroin price declines were due to a sharp fall in the intermediation margin, which was probably influenced by globalization. This phenomenon might have a strong impact on the effectiveness of drug policies, increasing the relative effectiveness of policies aiming at reducing the demand of drugs.

Tonioni F; Martinotti G; Barra A; Martinelli D; Autullo G; Rinaldi C et al. Cocaine use disorders and serum magnesium profile. Neuropsychobiology 59(3): 159-164, 2009. (45 refs.)

Introduction: Magnesium influences the nervous system via its actions on the release and metabolism of neurotransmitters, and abnormal magnesium metabolism has been implicated in several neuropsychiatric disorders with prominent mood symptoms. The aim of this study was to compare the serum levels of magnesium of cocaine addicts to those of heroin addicts and normal controls. We also attempted to clarify the relationship between the pathophysiology of cocaine abuse and magnesium levels by investigating their association with various clinical dimensions. Methods: Eighty-five consecutive subjects with a history of cocaine or opiate use disorders were recruited, evaluated and compared with 100 controls. The cocaine and heroin abusers were assessed with a 10-cm Visual Analogue Scale, the Symptom Check List-90 Revised, the Brown-Goodwin Scale, and the Barrat Impulsiveness Scale. Results: Magnesium levels were higher in the cocaine group compared to the opiate group and control. Male subjects had lower magnesium levels than the females of all three groups. Scores of impulsiveness, aggressiveness, craving and psychiatric symptomatology were not significantly different between the opiate and cocaine addicts. Discussion: This is the first study evaluating the magnesium level in cocaine addicts. Cocaine addicts showed higher total plasma magnesium levels than opiate addicts and normal controls, even though they remained in the normal range. The roles of the psychiatric comorbidity, of a pharmacokinetic association and of a pharmacodynamic interaction are discussed. Further prospective studies comparing serum levels of cocaine at different times are needed.

Vadhan NP; Hart CL; Haney M; van Gorp WG; Foltin RW. Decision-making in long-term cocaine users: Effects of a cash monetary contingency on gambling task performance. Drug and Alcohol Dependence 102(1/3): 95-101, 2009. (40 refs.)

Background: The Iowa Gambling task, which typically incorporates hypothetical monetary earnings and losses for performance, has been widely used to measure decision-making in substance abusers. We examined the effects of a cash monetary contingency on gambling task performance in cocaine abusers and control participants. Methods: Twenty-two long-term cocaine sniffers who met DSM-IV criteria for cocaine dependence and 24 non-cocaine-using Control participants completed this study. Both groups were similar in terms of age, executive function, and self-reported alcohol and marijuana Use. All participants performed the gambling task under two counterbalanced conditions: under one condition, earnings and losses were hypothetical, and under the other condition, earnings and losses were in cash. Results: Condition x group interactions on card selection and task completion time were noted (p < 0.05). Under the hypothetical payment condition, cocaine abusers selected a greater proportion of cards from disadvantageous decks than advantageous decks (p < 0.05), but took a similar amount of time to complete the task, relative to control participants. However, under the cash payment condition, no group differences were seen for card selection and cocaine abusers took more time than controls to complete the task (p < 0.05). Conclusions: The application of tangible consequences improved the decision-making and effort of cocaine abusers on the gambling task, relative to control participants. These findings underscore the importance of considering population-specific factors (e.g., sensitivity to instructional vs. consequential control) when conducting neuropsychological research in substance abusers.

van der Poel A; Rodenburg G; Dijkstra M; Stoele M; van de Mheen D. Trends, motivations and settings of recreational cocaine use by adolescents and young adults in the Netherlands. International Journal of Drug Policy 20(2): 143-151, 2009. (35 refs.)

Background: In recent years the use of powder cocaine among socially integrated adolescents and young adults has normalised. It is no longer an extraordinary drug to use in trendy/innovative as well as mainstreams clubs. Not much research has been done on motivations for and settings in which this cocaine use takes place. Methods: To gain insight in normalisation and trends in cocaine use, we used quantitative data from the National Prevalence Study on Substance Use (NPS) 1997, 2001 and 2005. To gain insight in social settings and motivations (initiation and continuation), and in the combined use of cocaine with alcohol and/or other drugs, we analysed mostly qualitative data from in-depth interviews with 55 adolescents and young adults who used cocaine in the past year. Results: The NPS studies show a rising trend in lifetime cocaine use, a fall in incidence, and a fall in continuation rates. From the interviews we learn that cocaine has further normalised. Cocaine is - and stays - attractive because of the ritual of snorting (the route of administration). Initiation is often planned. Effects play a role in the continuation of use, not in initiation. Motivations for use are divided into three categories: physical, mental and social. Cocaine is used in nightlife and home settings, together with friends, and it is often combined with alcohol (on the same occasion), because of feeling mentally clear and being able to drink more. Conclusion: About 5% of adolescents have used cocaine at least once in their lives. They feel it can be used in every setting, since it leaves a user in control. While acknowledging the negative side effect,;, young users, try to regulate their cocaine use in order to regulate these effects. Although high frequent use is an exception in our sample, we cannot foretell how many might develop a pattern of problematic use.

van Gelder MMHJ; Reefhuis J; Caton AR; Werler MM; Druschel CM; Roeleveld N. Maternal periconceptional iIlicit drug use and the risk of congenital malformations. Epidemiology 20(1): 60-66, 2009. (35 refs.)

Background: In 2004, the Survey on Drug Use and Health showed that 5% of American women reported use of an illicit drug during pregnancy. The results of studies determining the association between periconceptional illicit drug use and birth defects have been inconsistent. Methods: We analyzed data from the National Birth Defects Prevention Study, a case-control study of major birth defects, and assessed all birth defects categories in which there were at least 250 interviewed case mothers. We included 10,241 infants with major congenital malformations (case infants) and 4,967 infants without major congenital malformations (control infants) born between 1997 and 2003 for whom there was a completed maternal interview with detailed information on prenatal illicit drug use and potential confounders. We used multivariable logistic regression to estimate the associations between cannabis, cocaine, and stimulant use in the month before pregnancy or during the first trimester (periconceptional period) and the occurrence of selected birth defects. Results: In the periconceptional period, 5% of the 15,208 mothers reported any use of illicit drugs. We did not find associations between illicit drug use and most of the 20 eligible categories of congenital malformations. Periconceptional cannabis use seemed to be associated with an increased risk of anencephaly (adjusted odds ratio = 1.7; 95% confidence interval = 0.9-3.4), whereas cocaine use in the periconceptional period was associated with the risk of cleft palate (2.5; 1.1-5.4). Conclusions: There were very few suggestions of positive associations between periconceptional illicit drug use and the 20 birth defects categories.

Vocci FJ; Montoya ID. Psychological treatments for stimulant misuse, comparing and contrasting those for amphetamine dependence and those for cocaine dependence. Current Opinion in Psychiatry 22(3): 263-268, 2009. (33 refs.)

Purpose of review: The aim is to compare and contrast psychological treatments for amphetamine and cocaine dependence. Recent findings: Stimulant dependence, in the form of cocaine or amphetamine/methamphetamine dependence, is prevalent worldwide, and their ratio may vary across different countries and regions of countries. The treatment of stimulant disorders has greatly advanced in recent years, and scientific evaluation of behavioral therapies, using randomized clinical trials designs and a stage-wise approach, have demonstrated the safety and efficacy of interventions. Psychological interventions such as cognitive behavioral therapy and contingency management for cocaine and methamphetamines use disorders are well tolerated and moderately effective in achieving drug abstinence. There is evidence that contingency management interventions can help to improve retention in treatment and, in turn, other treatment outcomes. Although there are important differences in the neuropsychiatric and medical consequences of cocaine and amphetamine use disorders, there is currently no evidence for a differential treatment effect of any psychosocial treatment in the management of these disorders. Summary: As there are no Food and Drug Administration-approved medications for the treatment of these disorders, psychological interventions form the basis of their treatment. More research is needed to address the specific psychosocial needs of cocaine and amphetamine-dependent individuals in order to improve their treatment outcomes.

Vroegop MP; Franssen EJ; van der Voort PHJ; van den Berg TNA; Langeweg RJ; Kramers C. The emergency care of cocaine intoxications. (review). Netherlands Journal of Medicine 67(4): 122-126, 2009. (30 refs.)

Cocaine is frequently used, especially among adolescents and by men between the age of 25 and 44. Many of them are able to use cocaine in normal day-to-day life, without any problems. Reduced prices of cocaine and other recreational drugs such as MDMA (ecstasy) and gamma hydroxybutyrate (GHB) has led to an increased incidence of intoxications with these drugs.' Since the production of cocaine is illegal, it may be impure and mixtures with other drugs such as atropine may occur. The treatment of patients with an acute cocaine intoxication can be complicated. Combination of cocaine with other drugs results in clinical pictures which are difficult to discriminate and that may have important consequences for treatment.

Vuchinich R; Wallace D; Milby JB; Schumacher JE; Mennemeyer S; Kertesz S. Relations between in-treatment and follow-up abstinence among cocaine-dependent homeless persons in three clinical trials. Experimental and Clinical Psychopharmacology 17(3): 165-172, 2009. (20 refs.)

Clinical trials with cocaine-dependent outpatients have found a strong relation between in-treatment and follow-up abstinence, and the strength of this relation is constant across treatment conditions with variable efficacy in generating abstinence. The authors conducted secondary analyses of data from 3 clinical trials to determine whether this relation generalizes to cocaine-dependent homeless persons. The 3 trials (total N = 543) were conducted in a community health care facility for homeless people. The 7 treatment arms across the 3 trials were combinations of day treatment, abstinence-contingent housing, and vocational training. Drug use was measured with urine toxicology testing. Consecutive weeks of abstinence during treatment were strongly related to abstinence at the 12-month follow-up, whether or not missing 12-month data were included in the analysis. The treatment arms differed in their efficacy in generating abstinence, but the relation between in-treatment and follow-up abstinence did not differ across treatment arms. These results replicate earlier reports of these relations and extend them to a population of homeless people. The lack of differences between treatment arms in the in-treatment-follow-up abstinence relation implies that that relation is independent of the treatment-specific intervention components that generate group differences in abstinence.

Walsh SL; Stoops WW; Moody DE; Lin SN; Bigelow GE. Repeated dosing with oral cocaine in humans: Assessment of direct effects, withdrawal, and pharmacokinetics. Experimental and Clinical Psychopharmacology 17(4): 205-216, 2009. (49 refs.)

Cocaine withdrawal symptoms are thought to play a role in relapse; Studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1-4 & Days 9-12, cocaine 175 nigh p.o.; 5 hourly closest 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5-8). After these 12 days, an additional period of 28 days of placebo maintenance Followed (Days 13-40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The closing regimen produced cocaine plasma concentrations (C-max of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were Sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high closes of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours.

Walton MA; Cunningham R; Chermack ST; Tripathi S; Weber J; Maio RF et al. Predictors of violence following Emergency Department visit for cocaine-related chest pain. Drug and Alcohol Dependence 99(1-3): 79-88, 2009. (76 refs.)

This study examined 1-year violence outcomes among non-injured patients treated in the Emergency Department (ED) for cocaine-related chest pain. All urban Level I ED required patients with chest pain (age 60 and Younger) provide it Urine sample for cocaine testing. Cocaine-positive consenting patients (n=219) were interviewed in the ED; 80% completed follow-tip interviews over 12-months (n = 174; 59% males 79% African-American, mean age = 38.8, standard deviation 9.06; range = 19-60). Baseline rates of past year violent victimization and perpetration history were: 38% and 30%, respectively. During the 12-month follow-up, rates of victimization and perpetration outcomes were 35% and 30%, respectively. Predictors of violence outcomes (either victimization or perpetration) in the year post-ED visit based on characteristics were measured at baseline or during the follow-up period (i.e., gender, age, psychological distress, binge drinking days, cocaine use days, marijuana use days, substance abuse/dependence diagnosis, victimization/perpetration history). Victimization during the Follow-up was related to younger age, more frequent binge drinking and marijuana use at baseline, and victimization history, and to substance abuse/dependence, more frequent binge drinking, and psychiatric distress at follow-up. Specifically. participants who reported victimization at baseline were approximately 3 times, more likely to report victimization at 12-month follow-up. Perpetration during the follow-up was related to younger age and more frequent binge drinking at baseline, and to substance abuse/dependence, more frequent binge drinking, and psychiatric distress at follow-up. Overall, no significant gender differences were observed in violence; however, women were more likely than men to report injury during the most severe partner violence incident. Violence is a common problem among patients presenting to all inner-city ED for cocaine-related chest pain, with younger age and frequency of binge drinking being it consistent marker of continued violence involvement. Intervention approaches to link these not-in-treatment cocaine users to services and reduce cocaine use must take into account concomitant alcohol Mmsuse and violence.

Weeks MR; Convey M; Dickson-Gomez J; Li JH; Radda K; Martinez M et al. Changing drug users' risk environments: Peer health advocates as multi-level community change agents. American Journal of Community Psychology 43(3/4): 330-344, 2009. (59 refs.)

Peer delivered, social oriented HIV prevention intervention designs are increasingly popular for addressing broader contexts of health risk beyond a focus on individual factors. Such interventions have the potential to affect multiple social levels of risk and change, including at the individual, network, and community levels, and reflect social ecological principles of interaction across social levels over time. The iterative and feedback dynamic generated by this multi-level effect increases the likelihood for sustained health improvement initiated by those trained to deliver the peer intervention. The Risk Avoidance Partnership (RAP), conducted with heroin and cocaine/crack users in Hartford, Connecticut, exemplified this intervention design and illustrated the multi-level effect on drug users' risk and harm reduction at the individual level, the social network level, and the larger community level. Implications of the RAP program for designing effective prevention programs and for analyzing long-term change to reduce HIV transmission among high-risk groups are discussed from this ecological and multi-level intervention perspective.

Weeks MR; Li J; Dickson-Gomez J; Convey M; Martinez M; Radda K et al. Outcomes of a peer HIV prevention program with injection drug and crack users: The risk avoidance partnership. Substance Use & Misuse 44(2): 253-281, 2009. (30 refs.)

The Risk Avoidance Partnership (RAP) Project conducted in Hartford, Connecticut, tested a program to train active drug injectors and crack cocaine users as Peer Health Advocates (PHAs) to deliver a modular HIV, hepatitis, and STI prevention intervention to hard-to-reach drug users in their networks and others in the city. The intervention was designed to diffuse health promotion and risk-reduction interventions by supporting PHAs to model prevention practices and deliver risk- and harm-reduction materials and information. We compared change in behaviors and attitudes between baseline and 6-month follow-up of 112 primarily African-American and Latino PHAs, 223 of their drug-user network contact referrals, and 118 other study recruits (total n = 523). Results indicated significant HIV risk reduction among all study participants, associated with significant health advocacy action conducted by PHAs, and a relationship between exposure to the RAP peer-delivered intervention and risk reduction among all study groups. Findings suggest that active drug users' engagement in peer health advocacy can set in motion a feedback and diffusion process that supports both the continued work of the PHAs and the adoption of harm reduction and mimicking of health advocacy by their peers.

Wells JE; Mcgee MA; Baxter J; Agnew F; Kokaua J. Onset and lifetime use of drugs in New Zealand: Results from Te Rau Hinengaro: The New Zealand Mental Health Survey 2003-2004. Drug and Alcohol Review 28(2): 166-174, 2009. (31 refs.)

Introduction and Aims. Onset and lifetime use of drugs have not previously been reported for all adult ages in New Zealand. This paper reports such results and, for people born in New Zealand, compares age of onset across ethnic groups. Design and Methods. A nationally representative cross-sectional survey was carried out in 2003-2004, with oversampling of Maori and Pacific people. Participants were aged 16 years or more, living in permanent private dwellings. In the Composite International Diagnostic Interview (CIDI 3.0), participants were asked if they had ever used drugs (alcohol, tobacco and five groups of other drugs) and the age of first use (except for tobacco). Estimates are weighted. Results. The response rate of 73.3% yielded 12 992 interviews. The percentage of participants who had ever used drugs was: 94.6% for alcohol, 50.8% for tobacco and 42.6% for any extramedical drug, including 41.6% for cannabis, 4.2% for cocaine and 2.9% for opioids. Use was much more common in recent cohorts for extramedical drugs. The median age of onset in each age cohort was always lowest for alcohol, then cannabis, then opioids, then cocaine. Among those born in New Zealand, Maori were more at risk of use than 'Others' with the lowest risk for Pacific people. Discussion and Conclusions. Interventions to prevent or to delay the onset of drug use need to occur before and during adolescence. The major cohort differences and the widespread experience of cannabis use help to explain the diversity of opinion in New Zealand about how to deal with this drug.

Wells K. Substance abuse and child maltreatment. Pediatric Clinics of North America 56(2): 345+, 2009. (70 refs.)

Pediatricians and other medical providers caring for children need to be aware of the dynamics in the significant relationship between substance abuse and child maltreatment. A caregiver's use and abuse of alcohol, marijuana, heroin, cocaine, methamphetamine, and other drugs place the child at risk in multiple ways. Members of the medical community need to understand these risks because the medical community plays a unique and important role in identifying and caring for these children. Substance abuse includes the abuse of legal drugs as well as the use of illegal drugs. The abuse of legal substances may be just as detrimental to parental functioning as abuse of illicit substances. Many substance abusers are also polysubstance users and the compounded effect of the abuse of multiple substances may be difficult to measure. Often other interrelated social features, such as untreated mental illness, trauma history, and domestic violence, affect these families.

Weston BW; Krishnaswami S; Gray MT; Coly G; Kotchen JM; Grim CE et al. Cocaine use in inner city African American research volunteers. Journal of Addiction Medicine 3(2): 83-88, 2009. (24 refs.)

Objectives: To determine the prevalence of cocaine use and associated risk factors in African Americans volunteering as research subjects for a hypertension study. Methods: African Americans recruited from Milwaukee's inner city received $25 for completing a blood pressure screening protocol with the potential to participate in an additional protocol for $200, contingent on a negative drug test for cocaine. This study is based on the characteristics of the participants who completed the drug screen for cocaine. The significance of differences in the frequencies of categorical variables between users and nonusers was determined by X-2 analysis or Fisher exact test. Results: Of 389 drug-tested participants, 35% tested positive for cocaine. Cocaine Positive volunteers were slightly older (P = 0.02), had a lower body mass index (P = 0.001), a smaller waist circumference (P = 0.005), and lower serum cholesterol levels (P = 0.04). Those testing positive were more likely to be tobacco smokers (P < 0.0001), unemployed (P 0.001), and alcohol users (P < 0.0001), but less likely to use prescription medications (P = 0.01). Income and education did not differ between cocaine positive and negative subjects. Individuals employed full-time were less likely to test positive than the unemployed, whereas part-time employees were intermediate (P = 0.0003). Although those testing positive were slightly less likely to have a living mother (P = 0.07), there was no association with living fathers. Cigarette smokers were almost five times more likely to test positive for cocaine than nonsmokers (OR 4.88, 95% CI 2.73-8.71). Additional predictors of positive tests were alcohol consumption (OR 1.90, 95% CI 1.18-3.19), a reported history of substance abuse (OR 1.83, 95% CI 1.05-3.19), and a family history that included one or more deceased siblings (OR 1.82, 95% CI 1.03-3.21). Conclusions: A high prevalence of substance use was detected among inner city African Americans offered financial incentives for participating in a general medical research protocol. This information may be relevant for designing future clinical trials and drug use intervention programs.

Wheeler RA; Carelli RM. Dissecting motivational circuitry to understand substance abuse. (review). Neuropharmacology 56(Supplement 1): 149-159, 2009. (105 refs.)

An important goal of cocaine addiction research is to understand the neurobiological mechanisms underlying this disease state. Here, we review studies from our laboratory that examined nucleus accumbens (NAc) cell firing and rapid dopamine signaling using electrophysiological and electrochemical recordings in behaving rodents. A major advantage of these techniques is that they allow for the characterization of NAc activity and rapid dopamine release during specific phases of motivated behavior. Moreover, each approach enables an examination of the dynamic nature of NAc signaling as a function of factors such as hedonics and associative learning. We show that NAc neurons differentially respond to rewarding and aversive stimuli and their predictors in a bivalent manner. This differential responding is modifiable and can be altered by the presentation of other natural rewards or cocaine. Likewise, the dynamic nature of NAc cell firing is also reflected in the differential activation of distinct populations of NAc neurons during goal-directed behaviors for natural versus drug rewards, and the heightened activation of some NAc neurons following cocaine abstinence. Our electrochemical data also show that rapid dopamine signaling in the NAc reflects primary rewards and their predictors and appears to modulate specific NAc neuronal responses. In some cases, these influences are observed in a regionally specific manner that matches previous Pharmacological manipulations. Collectively, these findings provide critical insight into the functional organization of the NAc that can be used to guide additional Studies aimed at dissecting the neural code underlying Compulsive drug-seeking behavior.

Wilkinson JL; Li C; Bevins RA. Pavlovian drug discrimination with bupropion as a feature positive occasion setter: substitution by methamphetamine and nicotine, but not cocaine. Addiction Biology 14(2): 165-173, 2009. (62 refs.)

Bupropion can serve as a discriminative stimulus (S-D) in an operant drug discrimination task, and a variety of stimulants substitute for the bupropion S-D. There are no reports, however, of bupropion functioning as a Pavlovian occasion setter (i.e. feature positive modulator). The present experiment seeks to fill this gap in the literature by training bupropion in rats as a feature positive modulator that disambiguates when a light will be paired with sucrose. Specifically, on bupropion (10 mg/kg intraperitoneal) sessions, offset of 15-second cue lights were followed by brief delivery of liquid sucrose; saline sessions were similar except no sucrose was available. Rats readily acquired the discrimination with more conditioned responding to the light on bupropion sessions. Bupropion is approved for use as a smoking cessation aid, and more recently has drawn attention as a potential pharmacotherapy for cocaine and methamphetamine abuse. Accordingly, after discrimination training, we tested the ability of cocaine (1-10 mg/kg), methamphetamine (0.1 to 1 mg/kg) and nicotine (0.00625 to 0.2 mg/kg) to substitute for the bupropion feature. Nicotine (0.05 mg/kg) and methamphetamine (0.3 mg/kg) substituted fully for bupropion; cocaine did not substitute. These results extend previous research on shared stimulus properties between bupropion and other stimulants to a Pavlovian occasion setting function. Further, this is the first report of nicotine and methamphetamine substitution for bupropion. The overlap in stimulus properties might explain the effectiveness of bupropion as a smoking cessation aid and highlight the possible utility of bupropion for treatment of stimulant use disorder.

Wille SMR; Raes E; Lillsunde P; Gunnar T; Laloup M; Samyn N et al. Relationship between oral fluid and blood concentrations of drugs of abuse in drivers suspected of driving under the influence of drugs. Therapeutic Drug Monitoring 31(4): 511-519, 2009. (66 refs.)

In recent years, the interest in the use of oral fluid as a biological matrix has increased significantly, particularly for detecting driving under the influence of drugs (DUID). In this study, the relationship between the oral fluid and the blood concentrations of drugs of abuse in drivers suspected of DUID is discussed. Blood and oral fluid samples were collected from drivers Suspected of DUID or stopped during random controls by the police in Belgium, Germany, Finland, and Norway for the ROSITA-2 project. The blood samples were analyzed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), sometimes preceded by immunoassay screening of blood or urine samples. The oral fluid samples were analyzed by GC-MS or LC-MS(/MS). Scatter plots and trend lines of the blood and oral fluid concentrations and the median, mean, range, and SD of the oral fluid to blood (OF:B) ratios were calculated for amphetamines, benzodiazepines, cocaine, opiates, and Delta(9)-2 tetrahydrocannabinol. The ratios found in this study were comparable with those that were published previously, but the range was wider. The ORB ratios of basic drugs such as amphetamines, cocaine, and opiates were > 1 [amphetamine: median (range) 13 (0.5-182), methylenedioxyamphetamine: 4 (1-15), methylenedioxymethamphetamine: 6 (0.9-88), methamphetamine: 5 (2-23), cocaine: 22 (4-119), benzoylecgonine: 1 (0.2-11), morphine: 2 (0.8-6), and codeine: 10 (0.8-39)]. The ratios for benzodiazepines were very low, as could be expected as they are highly protein bound and weakly acidic, leading to low oral fluid concentrations [diazepam: 0.02 (0.01-0.15), nordiazepam: 0.04 (0.01-0.23), oxazepam: 0.05 (0.03-0.14), and temazepam: 0.1 (0.06-0.54)]. For tetrahydrocannabinol, an OF:B ratio of 15 was found (range 0.01-569). In this study, the time of last administration, the dose, and the route of administration were unknown. Nevertheless, the data reflect the variability of the OF:B ratios in drivers thought to be under the influence of drugs. The wide range of the ratios, however, does not allow reliable calculation of the blood concentrations from oral fluid concentrations.

Woicik PA; Moeller SJ; Alia-Klein N; Maloney T; Lukasik TM; Yeliosof O et al. The neuropsychology of cocaine addiction: Recent cocaine use masks impairment. Neuropsychopharmacology 34(5): 1112-1122, 2009. (95 refs.)

Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine.

Woratanarat P; Ingsathit A; Suriyawongpaisal P; Rattanasiri S; Chatchaipun P; Wattayakorn K et al. Alcohol, illicit and non-illicit psychoactive drug use and road traffic injury in Thailand: A case-control study. Accident Analysis and Prevention 41(3): 651-657, 2009. (34 refs.)

The objective of this study was to determine the relationship between alcohol use, psychoactive drug use and road traffic injury (RTI). A case-control study was conducted among drivers in Bangkok, Thailand. Two hundred cases and 849 controls were enrolled between February and November 2006. Cases who sustained a RTI were matched with four controls recruited from petrol stations within a 1-km radius of the reported crash site of the case. A positive alcohol breath test (>= 50mg/dl), and positive tests for the presence of illicit (amphetamine, cocaine, marijuana) and non-illicit psychoactive drugs (antihistamine, benzodiazepine, antidepressants), using gas chromatography/mass spectrometry (GC/MS) were documented as primary measures. There were significantly higher odds of an alcohol breath test >= 50mg/dl (adjusted odds ratio (OR) 63.6 (95% CI: 25.5-158.9)), illicit psychoactive drugs (adjusted OR 3.4 (95% CI: 1.7-6.6)) and non-illicit psychoactive drug (adjusted OR 3.1 (95% CI: 1.5-6.3)) among cases than controls. Even though driving under the influence of psychoactive drugs has been significantly linked to RTI, its contribution to road safety is much lower than driving under the influence of alcohol. With limited resources, the priority for RTI prevention should be given to control of driving under the influence of alcohol.

Wu LT; Blazer DG; Patkar AA; Stitzer ML; Wakim PG; Brooner RK. Heterogeneity of stimulant dependence: A national drug abuse treatment Clinical Trials Network Study. American Journal on Addictions 18(3): 206-218, 2009. (38 refs.)

We investigated the presence of DSM-IV subtyping for dependence on cocaine and amphetamines (with versus without physical dependence) among outpatient stimulant users enrolled in a multisite study of the Clinical Trials Network (CTN). Three mutually exclusive groups were identified: primary cocaine users (n = 287), primary amphetamine users (n = 99), and dual users (cocaine and amphetamines; n = 29). Distinct subtypes were examined with latent class and logistic regression procedures. Cocaine users were distinct from amphetamine users in age and race/ethnicity. There were four distinct classes of primary cocaine users: non-dependence (15%), compulsive use (14%), tolerance and compulsive use (15%), and physiological dependence (tolerance, withdrawal, and compulsive use; 56%). Three distinct classes of primary amphetamine users were identified: non-dependence (11%), intermediate physiological dependence (31%), and physiological dependence (58%). Regardless of stimulants used, most female users were in the most severe or the physiological dependence group. These results lend support for subtyping dependence in the emerging DSM-V.

Wu LT; Pan JJ; Blazer DG; Tai B; Brooner RK; Stitzer ML et al. The construct and measurement equivalence of cocaine and opioid dependences: A National Drug Abuse Treatment Clinical Trials Network (CTN) study. Drug and Alcohol Dependence 103(3): 114-123, 2009. (50 refs.)

Introduction: Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each Criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups. Methods: Item response theory (IRT) and multiple indicators-multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N = 383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. Providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist. Results: IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. "Withdrawal" identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence. Conclusions: Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.

Wu LT; Parrott AC; Ringwalt CL; Patkar AA; Mannelli P; Blazer DG. The high prevalence of substance use disorders among recent MDMA users compared with other drug users: Implications for intervention. Addictive Behaviors 34(8): 654-661, 2009. (55 refs.)

Aim: In light of the resurgence in MDMA use and its association with polysubstance use, we investigated the 12-month prevalence of substance use disorders (SUDs) among adult MDMA users to determine whether they are at risk of other drug-related problems that would call for targeted interventions. Methods: Data were drawn from the 2006 National Survey on Drug Use and Health. Past-year adult drug users were grouped into three mutually exclusive categories: 1) recent MDMA users, who had used the drug within the past year; 2) former MDMA users, who had a history of using this drug but had not done so within the past year; and 3) other drug users, who had never used MDMA. Logistic regression procedures were used to estimate the association between respondents' SUDs and MDMA use while adjusting for their socioeconomic status, mental health, age of first use, and history of polydrug use. Results: Approximately 14% of adults reported drug use in the past year, and 24% of those past-year drug users reported a history of MDMA use. Recent MDMA users exhibited the highest prevalence of disorders related to alcohol (41%), marijuana (30%). cocaine (10%), pain reliever/opioid (8%), and tranquilizer (3%) use. Adjusted logistic regression analyses revealed that, relative to other drug users, those who had recently used MDMA were twice as likely to meet criteria for marijuana and pain reliever/opioid use disorders. They were also about twice as likely as former MDMA users to meet criteria for marijuana, cocaine, and tranquilizer use disorders. Conclusions: Seven out of ten recent MDMA users report experiencing an SUD in the past year. Adults who have recently used MDMA should be screened for possible SUDs to ensure early detection and treatment.

Zuo L; Kranzler HR; Luo X; Yang BZ; Weiss R; Brady K et al. Interaction between Two Independent CNR1 Variants Increases Risk for Cocaine dependence in European Americans: A replication study in family-based sample and population-based sample. Neuropsychopharmacology 34(6): 1504-1513, 2009. (65 refs.)

We recently reported that, in a European-American (EA) sample, the interaction between two cannabinoid receptor 1 gene (CNR1) variants significantly increased risk for drug dependence (DD), including cocaine dependence (CD). This study aimed to investigate directly the association between CNR1 and CD in four independent samples. Eight markers across the 45 kb CNR1 region and four large samples, ie, family-based European-American (EA) sample (n = 734), case-control EA sample (n 862), family-based African-American (AA) sample (n = 834) and case-control AA sample (n = 619) were examined in the present study. We investigated the association of these markers with CD and cocaine-induced paranoia (CIP) in the EA family sample first, and then replicated positive results in the other three samples. The interaction between two independent CNR1 variants, ie, the G allele-containing genotypes of rs6454674 (SNP3 boolean AND G(+)), and the T/T genotype of rs806368 (SNP8 boolean AND T/T), significantly increased risk for CD in the EA family (P-GEE = 0.015) and EA case-control (P-regression = 0.003) samples. EA subjects with SNP3 boolean AND G(+) and SNP8 boolean AND T/T had higher risk to develop CD than those EA subjects with the other genotypes for these two SNPs (LR+ 1.4). The SNP3 boolean AND G-SNP8 boolean AND T haplotype also showed significant association (P = 0.018) with CD in the EA case-control sample. SNP8-containing haplotypes showed significant association with both CD (P-global = 0.007) and CIP (P-global = 0.003) in the EA family sample. In the AA family sample, SNP8 boolean AND T/T significantly conferred higher risk for CD (P = 0.019). We conclude that two independent CNR1 variants have significant interaction effects on risk for CD in EAs; they may also have effects on risk for CD in AAs.