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1.  A Mechanism for the Inhibition of Neural Progenitor Cell Proliferation by Cocaine 
PLoS Medicine  2008;5(6):e117.
Background
Prenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation.
Methods and Findings
Microarray analysis followed by quantitative real-time reverse transcription PCR was used to screen cocaine-responsive and cell cycle-related genes in a neural progenitor cell line where cocaine exposure caused a robust anti-proliferative effect by interfering with the G1-to-S transition. Cyclin A2, among genes related to the G1-to-S cell cycle transition, was most strongly down-regulated by cocaine. Down-regulation of cyclin A was also found in cocaine-treated human primary neural and A2B5+ progenitor cells, as well as in rat fetal brains exposed to cocaine in utero. Reversing cyclin A down-regulation by gene transfer counteracted the proliferation inhibition caused by cocaine. Further, we found that cocaine-induced accumulation of reactive oxygen species, which involves N-oxidation of cocaine via cytochrome P450, promotes cyclin A down-regulation by causing an endoplasmic reticulum (ER) stress response, as indicated by increased phosphorylation of eIF2α and expression of ATF4. In the developing rat brain, the P450 inhibitor cimetidine counteracted cocaine-induced inhibition of neural progenitor cell proliferation as well as down-regulation of cyclin A.
Conclusions
Our results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of cocaine N-oxidative metabolism by P450 inhibitors may provide a preventive strategy for counteracting the adverse effects of cocaine on fetal brain development.
Investigating the mechanism of cocaine's effect on fetal brain development, Chun-Ting Lee and colleagues find that down-regulation of cyclin A by a cocaine metabolite inhibits neural proliferation.
Editors' Summary
Background.
Every year, cocaine abuse by mothers during pregnancy exposes thousands of unborn infants (fetuses) to this powerful and addictive stimulant. Maternal cocaine abuse during early pregnancy increases the risk of miscarriage; its use during late pregnancy slows the baby's growth and can trigger premature labor. Babies exposed to cocaine shortly before birth are often irritable and have disturbed sleep patterns. They can also be very sensitive to sound and touch and consequently hard to comfort. These problems usually resolve spontaneously within the first few weeks of life but some permanent birth defects are also associated with frequent cocaine abuse during pregnancy. In particular, babies exposed to cocaine before birth sometimes have small heads—an abnormality that generally indicates a small brain—and, although they usually have normal intelligence, the development of their thinking skills and language is often delayed, and they can have behavioral problems.
Why Was This Study Done?
Exposure to cocaine before birth clearly interferes with some aspects of brain development. More specifically, it reduces the number and position of neurons (the cells that transmit information in the form of electrical impulses around the body) within the brain. All neurons develop from neural progenitor cells, and previous research suggests that cocaine exposure before birth inhibits the proliferation of these cells in the developing brain. It would be useful to understand exactly how cocaine affects neural progenitor cells, because it might then be possible to prevent the drug's adverse effects on brain development. In this study, therefore, the researchers investigate the molecular mechanism that underlies cocaine's effect on neural progenitor cells.
What Did the Researchers Do and Find?
When the researchers investigated the effects of cocaine on AF5 cells (rat neural progenitor cells that grow indefinitely in the laboratory), they found that concentrations of cocaine similar to those measured in fetal brains after maternal drug exposure inhibited the proliferation of AF5 cells by blocking the “G1-to-S transition.” This is a stage that cells have to pass through between each round of cell division (the production of two daughter cells from one parent cell). Next, the researchers showed that cocaine-treated AF5 cells made much less cyclin A2, a protein that controls the G1-to-S transition, than untreated cells. Cocaine also decreased cyclin A2 levels in neural progenitor cells freshly isolated from human fetal brains and in fetal rat brains exposed to the drug while in their mother's womb. Treatment of AF5 cells with a cyclin A2 expression vector (a piece of DNA that directs the production of cyclin A2) counteracted the down-regulation of cyclin A2 and restored AF5 proliferation in the presence of cocaine. Other experiments indicate that the reduction of cyclin A2 by cocaine in AF5 cells involves the accumulation of “reactive oxygen species,” by-products of the breakdown of cocaine by a protein that is a member of a family of proteins called cytochrome P450. Finally, treatment of pregnant rats with cimetidine (which inhibits the action of cytochrome P450) counteracted both the inhibition of neural progenitor cell proliferation and the cyclin A2 down-regulation that cocaine exposure induced in the brains of their unborn pups.
What Do These Findings Mean?
These findings show that the cocaine-induced inhibition of neural progenitor cell proliferation involves, at least in part, interfering with the production (that is, causing down-regulation) of cyclin A2. They also show that this down-regulation is induced by the breakdown of cocaine by cytochrome P450, and that in both a rat cell line and in fetal rats, the cytochrome P450 inhibitor cimetidine (a drug that is already used clinically for stomach problems) can block the adverse effects of cocaine on the proliferation of neural progenitor cells. These findings need to be confirmed in animals more closely related to people than rats, and the long-term effects of cimetidine need to be investigated, in particular its effects on cocaine toxicity. Nevertheless these results raise the possibility that giving cimetidine or other drugs with similar effects to pregnant women who are addicted to cocaine might prevent some of the harm that their drug habit does to their unborn children, although it is not clear whether there is a dosage of cimetidine that might be both safe and adequate for this purpose.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050117.
A PLoS Medicine Perspective article by Steven Hyman further discusses this study
The US National Institute on Drug Abuse provides a fact sheet on cocaine (in English and Spanish)
The UK charity Release provides information and advice to the public and professionals about the law and drugs, including information about cocaine
MedlinePlus also provides a list of links to information about cocaine (in English and Spanish)
The March of Dimes Foundation, a US nonprofit organization for the improvement of child health, provides information about illicit drug use during pregnancy (in English and Spanish)
The Organization of Teratology Information Specialists also provides a fact sheet on cocaine and pregnancy (in English, Spanish, and French)
doi:10.1371/journal.pmed.0050117
PMCID: PMC2504032  PMID: 18593214
2.  Acute effects of cocaine on the neurobiology of cognitive control 
Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control.
doi:10.1098/rstb.2008.0106
PMCID: PMC2607334  PMID: 18640911
cocaine; impulsivity; functional magnetic resonance imaging; addiction
3.  Cocaine treatment admissions at three sentinel sites in South Africa (1997–2006): findings and implications for policy, practice and research 
Background
Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa.
Methods
Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria) and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU). A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment.
Results
Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs.
Conclusion
These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that treatment practitioners are adequately trained to address stimulant problems, poly drug use, and HIV and other risk behaviour related to crack cocaine use. Possible gaps in access to treatment by certain sectors of the population should be addessed as a matter of urgency.
doi:10.1186/1747-597X-2-37
PMCID: PMC2266915  PMID: 18163901
4.  Reactivity and Regulation in Children Prenatally Exposed to Cocaine 
Developmental psychology  2006;42(4):688-697.
Children prenatally exposed to cocaine may be at elevated risk for adjustment problems in early development because of greater reactivity and reduced regulation during challenging tasks. Few studies have examined whether cocaine-exposed children show such difficulties during the preschool years, a period marked by increased social and cognitive demands and by rapid changes in reactivity and regulation. The authors addressed this question by examining frustration reactivity and regulation of behavior during a problem-solving task in cocaine-exposed and -unexposed preschoolers. Participants were 174 4.5-year-olds (M age = 4.55 years, SD = 0.09). Frustration reactivity was measured as latency to show frustration and number of disruptive behaviors, whereas regulation was measured as latency to approach and attempt the problem-solving task and number of problem-solving behaviors. Results indicated that cocaine-exposed children took longer to attempt the problem-solving task but that cocaine-exposed boys showed the most difficulties: They were quicker to express frustration and were more disruptive. Effect sizes were relatively small, suggesting both resilience and vulnerabilities.
doi:10.1037/0012-1649.42.4.688
PMCID: PMC1861810  PMID: 16802901
reactivity; regulation; prenatal cocaine exposure
5.  Genome-Environmental Risk Assessment of Cocaine Dependence 
Cocaine-associated biomedical and psychosocial problems are substantial twenty-first century global burdens of disease. This burden is largely driven by a cocaine dependence process that becomes engaged with increasing occasions of cocaine product use. For this reason, the development of a risk-prediction model for cocaine dependence may be of special value. Ultimately, success in building such a risk-prediction model may help promote personalized cocaine dependence prediction, prevention, and treatment approaches not presently available. As an initial step toward this goal, we conducted a genome-environmental risk-prediction study for cocaine dependence, simultaneously considering 948,658 single nucleotide polymorphisms (SNPs), six potentially cocaine-related facets of environment, and three personal characteristics. In this study, a novel statistical approach was applied to 1045 case-control samples from the Family Study of Cocaine Dependence. The results identify 330 low- to medium-effect size SNPs (i.e., those with a single-locus p-value of less than 10−4) that made a substantial contribution to cocaine dependence risk prediction (AUC = 0.718). Inclusion of six facets of environment and three personal characteristics yielded greater accuracy (AUC = 0.809). Of special importance was the joint effect of childhood abuse (CA) among trauma experiences and the GBE1 gene in cocaine dependence risk prediction. Genome-environmental risk-prediction models may become more promising in future risk-prediction research, once a more substantial array of environmental facets are taken into account, sometimes with model improvement when gene-by-environment product terms are included as part of these risk predication models.
doi:10.3389/fgene.2012.00083
PMCID: PMC3355331  PMID: 22629285
cocaine dependence; genome-environmental risk prediction; childhood abuse; GBE1 gene; tree-assembling ROC
6.  Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs 
Background
Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection.
Methods
We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996–Nov. 30, 1999 (period 1), Dec. 1, 1999–Nov. 30, 2002 (period 2), and Dec. 1, 2002–Dec. 30, 2005 (period 3).
Results
Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57–1.85; period 2: HR 1.68, 95% CI 1.01–2.80; and period 3: HR 2.74, 95% CI 1.06–7.11).
Interpretation
Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.
doi:10.1503/cmaj.082054
PMCID: PMC2764753  PMID: 19841052
7.  The Effects of Prenatal Cocaine-Exposure on Problem Behavior in Children 4-10 Years 
Neurotoxicology and teratology  2010;32(4):443-451.
Background
Children prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions.
Objective
To assess behavioral outcomes of cocaine (CE) and non-cocaine exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors.
Methods
Low socioeconomic status (SES), primarily African-American children (n = 381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10 years of age, controlling for confounders.
Results
Prenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR=1.93, CI: 1.09-3.42, p<.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR=3.57, CI: 1.67-7.60, p<.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4, 9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions.
Conclusion
Prenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.
doi:10.1016/j.ntt.2010.03.005
PMCID: PMC3586186  PMID: 20227491
behavior; delinquency; prenatal cocaine-exposure; lead exposure; longitudinal
8.  Social context and perceived effects of drugs on sexual behavior among individuals who use both heroin and cocaine 
Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be due to the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine versus heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants’ perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g. with friends, family or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug.
doi:10.1037/a0019635
PMCID: PMC3198869  PMID: 20545385
sexual behavior; cocaine; social context
9.  Long-Term Cocaine Use and Antiretroviral Therapy Are Associated with Silent Coronary Artery Disease in African Americans with HIV Infection Who Have No Cardiovascular Symptoms 
Background
Long-term use of cocaine (⩾15 years) and antiretroviral therapy (ART) have been implicated in cardiovascular complications. Nevertheless, the individual and combined effects of ART and cocaine use on silent coronary artery disease have not been fully investigated.
Methods
Computed tomography coronary angiography was performed for 165 human immunodeficiency virus (HIV)–infected African American study participants aged 25–54 years in Baltimore, Maryland, with contrast-enhanced 64-slice multidetector computed tomography imaging.
Results
Significant (⩾50%) coronary stenosis was detected in 24 (15%) of 165 participants. The prevalence of significant stenosis among those who had used cocaine for ⩾15 years and had received ART for ⩾6 months was 42%. Exact logistic regression analysis revealed that long-term cocaine use (adjusted odds ratio, 7.75; 95% confidence interval, 2.26–31.2) and exposure to ART for ⩾6 months (adjusted odds ratio, 4.35; 95% confidence interval, 1.30–16.4) were independently associated with the presence of significant coronary stenosis. In addition, after controlling for confounding factors, both stavudine use for ⩾6 months or combivir use for ⩾6 months were independently associated with the presence of significant coronary stenosis.
Conclusions
Long-term exposure to ART may be associated with silent coronary artery disease; however, the magnitude of increased risk associated with ART was much lower than the risk associated with cocaine use or traditional risk factors. Cardiovascular monitoring and aggressive modification of cardiovascular risk factors are essential for reducing the risk of coronary artery disease in HIV-infected individuals. Extensive efforts should also be made to develop effective cocaine use cessation programs for HIV-infected cocaine users.
doi:10.1086/526782
PMCID: PMC2716694  PMID: 19641630
10.  Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in rhesus monkeys 
Biological psychiatry  2012;72(10):856-863.
Background
Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized.
Methods
Adult male rhesus monkeys with an extensive cocaine self-administration history (~ 5 years) and age-matched controls (n=4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography (PET) and [18F]-fluorodeoxyglucose (FDG) was employed to assess cerebral metabolic rates of glucose utilization (MRglu) during cognitive testing.
Results
Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multi-dimensional discriminations, compared to controls. Cocaine-naive but not cocaine-experienced monkeys showed greater MRglu during a multi-dimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, regions associated with attention, error-detection, memory, and reward. Using a delayed match-to-sample (DMS) task, there were no differences in baseline working memory performance between groups. High dose cocaine self-administration disrupted DMS performance, but tolerance developed. Acute abstinence from cocaine did not affect performance but by day 30 of abstinence, accuracy increased significantly while performance of cocaine-naive monkeys was unchanged.
Conclusions
These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment-seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies.
doi:10.1016/j.biopsych.2012.05.001
PMCID: PMC3440537  PMID: 22672928
[18F]-fluorodeoxyglucose (FDG); CANTAB; delayed match-to-sample; PET imaging; set shifting; cerebral metabolic rates of glucose utilization
11.  The Relationship between Cocaine Use and Human Papillomavirus Infections in HIV-Seropositive and HIV-Seronegative Women 
Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV. Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types. Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97). Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.
doi:10.1155/2008/587082
PMCID: PMC2324195  PMID: 18437233
12.  Prenatal cocaine exposure: Effects on mother- and teacher-rated behavior problems and growth in school-age children 
Neurotoxicology and teratology  2010;33(1):69-77.
In this longitudinal study of prenatal cocaine exposure (PCE), school-age physical and cognitive development and behavioral characteristics were examined, while controlling for other factors that affect child development. At this follow-up phase, children were on average 7.2 years old, and their caregivers were 33.7 years old, had 12.5 years of education, and 48% were African American. During the first trimester, 20% of the women were frequent cocaine users (≥ 1 line/day). First trimester cocaine exposure predicted decreased weight and height at 7 years. There was no significant relationship between PCE and the cognitive and neuropsychological measures. Third trimester cocaine use predicted more total and externalizing behavior problems on the Child Behavior Checklist [3] and the Teacher Report Form [4], and increased activity, inattention, and impulsivity on the Routh Activity [67] and SNAP scales [55]. Children who were exposed to cocaine throughout pregnancy had more mother- and teacher-rated behavior problems compared to children of women who stopped using early in pregnancy or who never used cocaine prenatally. These detrimental effects of PCE on behavior are consistent with other reports in the literature and with the hypothesis that PCE affects development through changes in neurotransmitter systems. These school-age behaviors may be precursors of later adolescent behavior problems.
doi:10.1016/j.ntt.2010.06.003
PMCID: PMC3026056  PMID: 20600846
prenatal cocaine exposure; school age; growth; cognitive development; behavior problems
13.  Increased incidence of intraventricular hemorrhage and developmental delay in cocaine-exposed, very low birth weight infants 
The Journal of pediatrics  1994;124(5 0 1):765-771.
This study sought to determine whether very low birth weight (VLBW) infants (<1500 gm) with fetal cocaine exposure differed from non-cocaine-exposed VLBW infants in incidence of neonatal medical complications and in later developmental outcome. Forty-one cocaine-exposed, VLBW infants, followed in a longitudinal study, were compared with 41 non-cocaine-exposed, VLBW infants of comparable race, social class, age, and incidence of bronchopulmonary dysplasia. Cocaine-exposed infants were identified on the basis of combined findings of maternal and/or infant urine immunoassay and on the basis of maternal self-report. At birth, groups did not differ on medical risk factors except that cocaine-exposed infants had a higher incidence of mild (grades I to II) intraventricular hemorrhage. Cocaine-using women were also more likely to use other drugs, especially alcohol, marijuana, and tobacco. At follow-up, at mean corrected ages of 16.5 ± 8 months for 30 cocaine-exposed infants and 18.5 ± 7 months for 37 non-cocaine-exposed infants, standardized assessments of cognitive (Mental Development Index) and motor (Psychomotor Development Index) development were administered. Cocaine-exposed infants had lower mean cognitive (83 ± 27 vs 91 ± 19), and motor (85 ± 25 vs 96 ± 18) scores; the incidence of developmental delay was significantly higher even after control for the effects of intraventricular hemorrhage and chronologic age. Cocaine-exposed VLBW infants were also more likely to be living with relatives or in foster homes. We conclude that these VLBW, cocaine-exposed infants were at increased risk of intraventricular hemorrhage, were more likely to be placed outside maternal care, and had higher incidences of cognitive and motor delays at follow-up.
PMCID: PMC4181569  PMID: 7513757
14.  HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance dependent and independent populations 
Journal of neurovirology  2013;19(5):10.1007/s13365-013-0204-8.
It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptor 1 and 2. (DRD1, DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P<0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P<0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain and again, the direction of the correlation differed between substance dependent and independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.
doi:10.1007/s13365-013-0204-8
PMCID: PMC3856629  PMID: 24078558
HAND; cocaine; opiate; SNP
15.  A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence 
Drug and alcohol dependence  2013;133(1):94-99.
BACKGROUND
Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs.
METHODS
The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings.
RESULTS
Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate.
DISCUSSION
Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence.
doi:10.1016/j.drugalcdep.2013.05.026
PMCID: PMC3786029  PMID: 23810644
topiramate; cocaine; alcohol; clinical trial; placebo
16.  An Intervention to Reduce HIV Risk Behavior of Substance-Using Men Who Have Sex with Men: A Two-Group Randomized Trial with a Nonrandomized Third Group 
PLoS Medicine  2010;7(8):e1000329.
In a randomized trial of a behavioral intervention among substance-using men who have sex with men, aimed at reducing sexual risk behavior, Mansergh and colleagues fail to find evidence of a reduction in risk from the intervention.
Background
Substance use during sex is associated with sexual risk behavior among men who have sex with men (MSM), and MSM continue to be the group at highest risk for incident HIV in the United States. The objective of this study is to test the efficacy of a group-based, cognitive-behavioral intervention to reduce risk behavior of substance-using MSM, compared to a randomized attention-control group and a nonrandomized standard HIV-testing group.
Methods and Findings
Participants (n = 1,686) were enrolled in Chicago, Los Angeles, New York City, and San Francisco and randomized to a cognitive-behavioral intervention or attention-control comparison. The nonrandomized group received standard HIV counseling and testing. Intervention group participants received six 2-h group sessions focused on reducing substance use and sexual risk behavior. Attention-control group participants received six 2-h group sessions of videos and discussion of MSM community issues unrelated to substance use, sexual risk, and HIV/AIDS. All three groups received HIV counseling and testing at baseline. The sample reported high-risk behavior during the past 3 mo prior to their baseline visit: 67% reported unprotected anal sex, and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. The three groups significantly (p<0.05) reduced risk behavior (e.g., unprotected anal sex reduced by 32% at 12-mo follow-up), but were not different (p>0.05) from each other at 3-, 6-, and 12-mo follow-up. Outcomes for the 2-arm comparisons were not significantly different at 12-mo follow-up (e.g., unprotected anal sex, odds ratio = 1.14, confidence interval = 0.86–1.51), nor at earlier time points. Similar results were found for each outcome variable in both 2- and 3-arm comparisons.
Conclusions
These results for reducing sexual risk behavior of substance-using MSM are consistent with results of intervention trials for other populations, which collectively suggest critical challenges for the field of HIV behavioral interventions. Several mechanisms may contribute to statistically indistinguishable reductions in risk outcomes by trial group. More explicit debate is needed in the behavioral intervention field about appropriate scientific designs and methods. As HIV prevention increasingly competes for behavior-change attention alongside other “chronic” diseases and mental health issues, new approaches may better resonate with at-risk groups.
Trial Registration
ClinicalTrials.gov NCT00153361
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS first emerged in the early 1980s among gay men living in the US. As the disease spread around the world, it became clear that AIDS also affects heterosexual men and women. Now, three decades on, more than 30 million people are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and, globally, most sexual transmission of HIV now occurs during heterosexual sex. However, 5%–10% of all new HIV infections still occur in men who have sex with men (MSM, a term that encompasses gay, bisexual, transgendered, and heterosexual men who sometimes have sex with men) and, in several high-income countries, male-to-male sexual contact remains the most important HIV transmission route. In the US, for example, more than half of the approximately 50,000 people who become infected with HIV every year do so through male-to-male sexual contact.
Why Was This Study Done?
In countries where MSM are the group at highest risk of HIV infection, any intervention that reduces HIV transmission in MSM should have a major effect on the overall HIV infection rate. Among MSM, sexual behaviors that increase the risk of HIV infection (for example, not using a condom, having anal sex, having sex with a partner of unknown HIV status, and having sex with many partners) are associated with the use of alcohol and noninjection drugs (for example, inhaled amyl nitrite or poppers) during or shortly before sexual encounters. In this study (Project MIX), the researchers investigate whether a group-based behavioral intervention reduces sexual risk behavior in substance-using MSM.
What Did the Researchers Do and Find?
The researchers recruited substance-using MSM from four US cities who had had risky sex at least once in the past 6 months. Participants were randomized to a cognitive-behavioral intervention or to an attention-control group; a third, nonrandomized group of MSM formed a standard HIV counseling and testing only group. All the groups had HIV counseling and testing at the start of the study and completed a questionnaire about their substance use and sexual risk behavior during their most recent anal sex encounter. The cognitive-behavior group then received six weekly 2-hour group sessions focused on reducing substance use and sexual risk behavior by helping the men change their thinking (cognition) and behavior regarding sexual risk taking. The attention-control group received six group sessions about general MSM issues such as relationships, excluding discussion of substance use, and sexual risk behavior. The participants in both of these groups completed the questionnaire about their substance use and sexual risk behavior again at 3, 6, and 12 months after the group sessions; the participants in the standard HIV counseling and testing group completed the questionnaire again about 5 months after completing the first questionnaire (to control for the time taken by the other two groups to complete the intervention). At baseline, about 67% of the participants reported unprotected anal sex and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. At the 3-month follow-up, the incidence of sexual risk behavior had fallen to about 43% in all three groups; the incidence of substance use during sex had fallen to about 50%. Risk taking and substance use remained at these levels in the intervention and attention-control groups at the later follow-up time points.
What Do These Findings Mean?
These findings suggest that this cognitive-behavioral intervention is no better at reducing sexual risk taking among substance-using MSM than is an unrelated video-discussion group or standard HIV counseling and testing. One explanation for this negative result might be that brief counseling is especially effective with people who are ready for a change such as MSM willing to enroll in an intervention trial of this type. Alternatively, just being in the trial might have encouraged all the participants to self-report reduced risk behavior. Thus, alternative scientific designs and methods might be needed to find behavioral interventions that can effectively reduce HIV transmission among substance-using MSM and other people at high risk of HIV infection. Importantly, however, these findings raise the question of whether more extensive, multilevel interventions or broader lifestyle and positive health approaches (rather than single-level or single-subject behavioral interventions) might be needed to reduce sexual risk behavior among substance-using MSM.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000329.
Information is available from the US Department of Health and Human Services on HIV prevention programs, research, and policy
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including information on HIV transmission and transmission in gay men and other MSM, on substance abuse and HIV/AIDS, and on safer sex
Information is available from Avert, an international AIDS nonprofit, on all aspects of HIV/AIDS, including information on HIV, AIDS, and men who have sex with men and on drink, drugs, and sex (in English and Spanish)
The US Centers for Disease Control and Prevention also have information for the public and for professionals about HIV/AIDS among men who have sex with men (in English and Spanish)
The US National Institute on Drug Abuse has information on HIV/AIDS and drug abuse, including a resource aimed at educating teenagers about the link between drug abuse and the spread of HIV in the US (in English and Spanish)
doi:10.1371/journal.pmed.1000329
PMCID: PMC2927550  PMID: 20811491
17.  Prenatal cocaine exposure and infant cognition 
Infant behavior & development  2005;28(4):431-444.
The present study examined the relationship of prenatal cocaine exposure to infant information processing in the first year of life.
In a prospective, longitudinal study of 177 cocaine-exposed and 175 non-exposed infants, the Fagan Test of Infant Intelligence (FTII) was used to measure attention, visual recognition memory and information processing speed at 6.5 and 12 months of age. Groups were compared over time using mixed linear model analyses.
Prenatal cocaine exposure predicted poorer visual recognition memory at 12 months, with exposed infants obtaining lower mean scores and a higher percentage of scores in the risk range. Across exposure groups, information processing speed increased with age, demonstrating a developmental effect. Tobacco and marijuana exposures were related to faster looking times, which did not relate to visual recognition memory.
Cognitive deficits and attentional problems noted in prior studies of cocaine-exposed children at later ages may be detectable in infancy.
doi:10.1016/j.infbeh.2005.03.002
PMCID: PMC2601650  PMID: 19079636
Cocaine; Infants; Visual recognition; Memory; Fagan Test of Infant Intelligence
18.  Prenatal Cocaine Exposures and Dose-Related Cocaine Effects on Infant Tone and Behavior 
Neurotoxicology and teratology  2006;29(3):323-330.
Background
In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development. In humans, numerous studies have sought clinical correlates, but few have focused on dose-related effects, especially as regards neurologic function beyond the neonatal period.
Objective
To assess whether prenatal cocaine exposure has adverse effects on infant neurologic, developmental and behavioral outcomes and whether any effects are dose-dependent.
Design/Methods
Infants (398) were enrolled at birth from an urban hospital. Drug exposure was ascertained with biomarkers in hair (n=395), urine (n=170) and meconium (n=109). Children were followed prospectively and 286 (72%) were evaluated blind to drug exposure at 6 months of age with the Bayley scales, Fagan Scale of Infant Intelligence and a standardized neurological examination.
Results
Certain neurological findings increased significantly by the amount of cocaine detected in maternal hair, e.g. abnormality of tone, as indicated by extensor posture was detected among 28% of cocaine-unexposed infants, 43% of infants exposed to lower and 48% exposed to higher cocaine levels in maternal hair (p<0.009). Persistent fisting increased in a similar dose-dependent manner. These associations persisted in adjusted analyses. Prenatal cocaine exposure was not associated with developmental scores (mental, motor or novelty preference) but was associated with lower orientation scores in adjusted analyses.
Conclusions
At 6 months of age, prenatal cocaine exposure was associated with abnormalities of tone and posture and with lower orientation scores. Perturbations in monoaminergic systems by cocaine exposure during fetal development may explain the observed neurological and behavioral symptoms. Whether such findings in infancy increase the risk of later neurobehavioral problems requires further study.
doi:10.1016/j.ntt.2006.12.002
PMCID: PMC4307783  PMID: 17234383
perinatal; cocaine exposure; drug use; hypertonia; child development
19.  Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design 
Background
Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators.
In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children.
In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age18.
Results
Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances.
In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05.
Conclusion
Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.
doi:10.1186/1747-597X-1-4
PMCID: PMC1435999  PMID: 16722564
20.  Web-Based Cognitive Behavioral Self-Help Intervention to Reduce Cocaine Consumption in Problematic Cocaine Users: Randomized Controlled Trial 
Background
Web-based self-help programs that reduce problematic substance use are able to reach hidden consumer groups in the general population. These programs are characterized by their low treatment threshold and nonrestrictive intervention settings. They are also cost effective, making them of interest to both low-income and high-income industrialized countries with ever-increasing health costs.
Objective
To test the feasibility and effectiveness of an anonymous, fully automated, Web-based self-help intervention as an alternative to outpatient treatment services for cocaine users.
Methods
A total of 196 cocaine-using participants were recruited through various online and offline media for a randomized controlled trial. Participants in the intervention group received interactive cognitive behavioral modules and a consumption diary to reduce cocaine use, whereas participants in the control group received online psychoeducative information modules. Web-based follow-up assessments were conducted after 4 weeks, 6 weeks, and 6 months. Treatment retention was examined and compared between the intervention and control groups. Severity of cocaine dependence was the main outcome measure. Secondary outcomes were cocaine craving, depression symptoms, and alcohol and other substance use.
Results
This Web-based intervention attracted older and more educated participants than existing outpatient treatment programs for which cocaine is the primary substance of abuse. Participants in the intervention group showed greater treatment retention compared with the control group (P = .04). Low response rates at the follow-up assessments restricted the explanatory power of the analyses. At the follow-up assessments, the severity of cocaine dependence did not differ between the intervention and control groups (P = .75). Furthermore, there were no differences in cocaine craving, depression, or alcohol and other substance use. Using the consumption diaries, the average number of cocaine-free days per week did not change significantly, whereas the weekly quantity of cocaine used decreased equally in both groups (P = .009).
Conclusions
For cocaine users with low dependence severity, a fully automated Web-based cognitive behavioral self-help intervention is a feasible alternative with limited effectiveness in outpatient treatment services. However, this type of intervention may attract specific user groups that are rarely reached by existing outpatient treatment and may help them to control their cocaine consumption anonymously.
Trial Registration
ISRCTN93702927; http://www.controlled-trials.com/ISRCTN93702927 (Archived by WebCite at http://www.webcitation.org/6CTMM10MR)
doi:10.2196/jmir.2244
PMCID: PMC3510710  PMID: 23192752
Cocaine; Cognitive Behavioral Therapy; Internet; Randomized Controlled Trial
21.  Chronic Cocaine Exposure in the SCID mouse model of HIV Encephalitis 
Brain research  2006;1134(1):214-219.
Clinical and preclinical evidence suggests that cocaine exposure hastens progression of the HIV disease process. An established active, euphoric dose of cocaine (20 mg/kg) was administered to SCID mice according to a regimen consistent with exposure to the drug by cocaine-abusing HIV-infected patients to determine the effects of cocaine on four previously established pathological characteristics of HIV encephalitis: cognitive deficits, fatigue, astrogliosis, and microgliosis. Mice were intracranially inoculated with either HIV-infected, or uninfected macrophages and then injected with either cocaine or saline in a 2(Infection) × 2(Cocaine) factorial design. Cognition was assessed by acquisition and retention of a spatially cued learning task. Fatigue was assessed by monitoring motor activity following a 2 minute forced swim. Mice were then sacrificed to determine the extent of astrogliosis and microgliosis in the four groups. Results indicated that in comparison to uninfected controls, HIV positive mice had increased astrogliosis and microgliosis, cognitive deficits, and recovered more slowly from fatigue. However, despite evidence that the cocaine exposure regimen activated the central nervous system and had long-term CNS effects, the drug did not alter the behavioral or the neuropathological deficits noted in HIV-infected SCID mice.
doi:10.1016/j.brainres.2006.11.059
PMCID: PMC1839831  PMID: 17189621
AIDS; Dementia; HIV -associated Dementia; Animal models; Drug Abuse
22.  Cocaine use and the likelihood of cardiovascular and all-cause mortality: data from the Third National Health and Nutrition Examination Survey Mortality Follow-up Study 
Background:
Numerous case series have implicated cocaine use as a cause of both myocardial infarction (MI) and stroke on the basis of the temporal relationship between drug use and event onset. The relatively high prevalence of cocaine use in the US population, especially in younger individuals, mandates a more extensive investigation of this relationship.
Methods:
We determined the relationship between cocaine use and cardiovascular and all-cause mortality in a nationally representative sample of 9013 US adults aged 18 to 45 years who participated in the Third National Health and Nutrition Examination Survey Mortality Follow-up Study using Cox proportional hazards analyses. We categorized the participants as nonusers if they responded to the lifetime cocaine use question as never used, as infrequent users if they responded as using <10 times, and as frequent or regular users if they reported using 10–99 times or >100 times, respectively. Potential confounding factors in the association between cocaine use and death (cardiovascular and all cause) included age, sex, race/ethnicity, cigarette smoking, hypertension, diabetes mellitus, hyperlipidemia, educational attainment, body mass index, and insurance status. To estimate the impact of cocaine use on MI or stroke, we calculated the population attributable risk (PAR) percent for cocaine use with cardiovascular and all-cause mortality. We also estimated the years of life lost and total annual financial cost due to premature deaths in persons who reported regular use of cocaine.
Results:
A total of 60 cardiovascular deaths and 384 all causes deaths were reported during a mean follow-up period of 14.7 ± 2.6 years. After adjusting for differences in potential confounders, persons who reported regular lifetime cocaine use had a significantly higher likelihood of all-cause mortality (relative risk [RR], 1.9; 95% confidence interval [CI], 1.2–3.0 for ≥100 times in lifetime) but not cardiovascular mortality (RR, 0.6; 95% CI, 0.1–4.7 for ≥100 times in lifetime). The PAR of regular cocaine use for all cause mortality among was 1.79%. The years of life lost due to regular cocaine use was 10.3 years for an adult aged 31 years. The overall yearly cost incurred due to premature deaths related to regular cocaine use was $1.1 billion.
Conclusion:
Regular cocaine use was associated with an increased risk of all cause mortality but this effect was not mediated through cardiovascular events. Behavior modification by public awareness and education may reduce the mortality and financial burden associated with cocaine use.
PMCID: PMC4051909  PMID: 24920992
cocaine; cardiovascular mortality; all-cause mortality; years of life lost; national survey
23.  Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence 
Brain research  2007;1171:83-92.
Cocaine abstinence is associated with impaired performance in cognitive functions including attention, vigilance and executive function. Here we test the hypothesis that cognitive dysfunction during cocaine abstinence reflects in part impairment of cortical and subcortical regions modulated by dopamine. We used functional magnetic resonance imaging (fMRI) to study brain activation to a verbal working memory task in cocaine abusers (n = 16) and healthy controls (n = 16). Compared to controls, cocaine abusers showed: (1) hypoactivation in the mesencephalon, where dopamine neurons are located, as well as the thalamus, a brain region involved in arousal; (2) larger deactivation in dopamine projection regions (putamen, anterior cingulate, parahippocampal gyrus, and amygdala); and (3) hyperactivation in cortical regions involved with attention (prefrontal and parietal cortices), which probably reflects increased attention and control processes as compensatory mechanisms. Furthermore, the working memory load activation was lower in the prefrontal and parietal cortices in cocaine abusers when compared with controls, which might reflect limited network capacity. These abnormalities were accentuated in the cocaine abusers with positive urines for cocaine at time of study (as compared to cocaine abusers with negative urines) suggesting that the deficits may reflect in part early cocaine abstinence. These findings provide evidence of impaired function of regions involved with executive control, attention and vigilance in cocaine abusers. This widespread neurofunctional disruption is likely to underlie the cognitive deficits during early cocaine abstinence, and to reflect involvement of dopamine as well as other neurotransmitters.
doi:10.1016/j.brainres.2007.06.102
PMCID: PMC2048813  PMID: 17765877
24.  HIV infection and drugs of abuse: role of acute phase proteins 
Background
HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated.
Methods
Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured.
Results
Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects.
Conclusions
These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression.
doi:10.1186/1742-2094-10-113
PMCID: PMC3848479  PMID: 24044608
Drugs of abuse; HIV; Plasma; C-reactive protein; Serum amyloid A
25.  Crack Cocaine Use and its Relationship with Violence and Hiv 
Clinics (Sao Paulo, Brazil)  2009;64(9):857-866.
OBJECTIVES
To evaluate crack cocaine use practices, risk behaviors associated with HIV infection among drug users, and their involvement with violence.
INTRODUCTION
HIV infections are frequent among drug users due to risky sexual behavior. It is generally accepted that crack cocaine use is related to increased levels of violence. Several reports point to an increase in violence from those involved in drug trafficking. Although HIV infections and risky sexual behavior among drug users have been quite well studied, there are few studies that evaluate violence as it relates to drugs, particularly crack.
METHODS
A total of 350 drug users attending drug abuse treatment clinics in São Paulo, Brazil were interviewed about their risky behaviors. Each patient had a serological HIV test done.
RESULTS
HIV prevalence was 6.6% (4.0 to 10.2). Violence was reported by 97% (94.7 to 99.1) of the subjects (including cases without personal involvement). Acts of violence such as verbal arguments, physical fights, threats, death threats, theft, and drug trafficking were significantly higher among crack users. A decrease in frequency of sexual intercourse was observed among users of injected drugs, though prostitution was observed as a means of obtaining drugs. A high number of crack cocaine users had a history of previous imprisonment, many for drug-related infractions.
DISCUSSION
The data presented are in accordance with other reports in the literature, and they show a correlation between drug use, imprisonment, violence, and drug trafficking.
CONCLUSION
A high HIV prevalence and associated risky sexual behaviors were observed among crack cocaine users. The society and the authorities that deal with violence related to crack users and drug trafficking should be aware of these problems.
doi:10.1590/S1807-59322009000900006
PMCID: PMC2745146  PMID: 19759879
HIV; Drug use; Crack cocaine; Risk behavior; Violence

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