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Director's Report to the National Advisory Council on Drug Abuse - September, 2002

Research Findings - Research on AIDS and Other Medical Consequences of Drug Abuse

Methamphetamine Increases Lentivirus' Ability to Replicate in Brain Tissue

A study led by Dr. Michael Podell, Ohio State University, found that exposing astrocytes infected with feline immunodeficiency virus (FIV) - a surrogate for HIV - to methamphetamine in tissue culture for two weeks increases those brain cells' ability to replicate the virus as much as 15-fold. It is known that astrocytes serve as a reservoir of chronic brain lentivirus infection. The concentration of methamphetamine the astrocytes were exposed to was equal to an average level of methamphetamine in an adult abuser's bloodstream. The paper also reports that before an astrocyte can become infected with the virus, it must be associated with a specific type of lymphocyte, or immune cell, known as a peripheral blood mononuclear cell (PBMC). Lastly, the researchers discovered that, once the virus infects the astrocytes, it mutates into a form (containing 4 amino acid substitutions in the envelope polyprotein) that no longer needs this PBMC association to reproduce. Thus, lentiviral infection of the brain in the presence of methamphetamine may result in enhanced astrocyte viral replication, producing a more rapid and increased brain viral load. Gavrilin, M.A., Mathes, L.E., and Podell, M. Methamphetamine Enhances Cell-associated Feline Immunodeficiency Virus Replication in Astrocytes. J. Neurovirol., 8(3), pp. 240-249, 2002.

Risk Networks and Racial/Ethnic Differences in HIV Among Injection Drug Users

A number of studies have found higher prevalence of HIV between African American and Puerto Rican IDUs than among White IDUs. Researchers examined how risk networks might contribute to racial/ethnic variations in HIV prevalence. They sought to determine whether African American and Puerto Rican IDUs engage in greater levels of risk behaviors than their White counterparts; the extent that racial/ethnic selectivity of risk networks explain variations in HIV prevalence; whether White IDUs who have network contacts with minority IDUs are at higher risk of HIV than their counterparts who do not have such contact; and whether racial/ethnic differences in HIV persist after adjusting for risk behaviors and network characteristics. They recruited 662 IDUs on the street in Bushwick, New York City, interviewed these individuals, and tested them for HIV. Risk behaviors and networks were analyzed to explain racial/ethnic variations in HIV. The study found that 40% of IDUs were HIV positive and that HIV prevalence was greater among Puerto Ricans (45%) and African Americans (44%) than Whites (32%). The personal sexual and drug risk networks of IDUs were predominantly racially and ethnically homogeneous. After multivariate adjustments for risk behaviors and risk networks, African American-White differences in HIV prevalence were no longer significant. Although differences between Puerto Ricans and Whites persisted, post hoc analyses suggested that network partner characteristics might explain these. Although the study was not able to fully explain the sustained high prevalence of HIV among Puerto Rican IDUs, it appears that network patterns within and between racial/ethnic groups may continue to be a key factor in the future of the epidemic. Moreover, in Bushwick, racially/ethnically discordant risk partnerships involving African American IDUs may function as potential bridges of transmission between groups. Kottiri, B.J., Friedman, S.R., Neaigus, A., Curtis, R., and Des Jarlais, D.C. Risk Networks and Racal/Ethnic Differences in the Prevalence of HIV Infection Among Injection Drug Uses. J Acquired Immune Deficiency Syndromes, 30, pp. 95-104, 2002.

Decreases in Self-Reported Risks and Increases in New STDs among HIV+ Adults

Researchers examined high-risk sexual behavior among HIV-positive individuals as a factor contributing to the spread of the HIV epidemic. They conducted a retrospective chart review to compare self-reported STD risk behaviors and clinic diagnoses of 191 known HIV-positive clients attending Miami-Dade STD clinics with those of 191 uninfected controls. The analysis included 130 men (68.1%) and 61 (31.9%) women. HIV-positive clients were significantly more likely than controls to be African American, to report a history of injection drug use, to be no more likely than controls to have had sex with an IDU, to be more likely to report no sexual activity in the last 2 months, or if active, to report condom use at last sexual intercourse. Two themes are discussed as emerging from this study: First, although HIV-positive STD clinic patients were more likely than controls to report fewer sexual risk behaviors, they were more likely to be diagnosed with infectious syphilis and/or gonorrhea and to have sex partners with documented gonorrhea, chlamydia, or syphilis. Second, there appears to be a subset of HIV-positive adults who represent core transmitters: they have known about their HIV positive serostatus for a long time, are more likely to have had 4 or more sex partners in the past year, are more likely to have used crack cocaine, and are more likely to be symptomatic for an STD and in need of treatment for exposure to infectious syphilis, gonorrhea or chlamydia. This subset of HIV-positive clients continues to engage in high-risk sexual behavior after their diagnosis of HIV. This group of individuals seems to be playing a key role as core transmitters of HIV and bacterial STDs in the African American community in Miami and is in need of targeted intervention. Brewer, T.H., Metsch, L.R., and Zenilman, J.M. Use of a Public STD Clinic by Known HIV-Positive Adults: Decreased Self-Reported Risk Behavior and Increased Disease Incidence. J Acquired Immune Deficiency Syndromes, 29, pp. 289-294, 2002.

Peer-Driven Intervention to Improve Drug Users' Adherence to HIV Treatment

Active drug users with HIV often have low utilization of and adherence to primary care. Combining drug treatment and primary care on-site can help to reduce these problems by creating a social support structure wherein treatment staff can monitor patient adherence while also providing encouragement and social support. Researchers conducted a 6-month feasibility study to assess an alternative support structure, called a peer-driven intervention, that serves as a functional equivalent to drug treatment for increasing drug users' adherence to HIV therapeutics. The study included 14 adult drug users receiving medical care for HIV. As a health advocate, each subject was assigned and asked to meet with another subject weekly at the project storefront to provide peer support and counseling. As a peer, each subject was assigned and asked to meet with another health advocate weekly to receive support in keeping up his/her medical care. No two subjects played both roles for one another, and advocates earned nominal monetary rewards for eliciting positive responses from their peers in keeping appointments, responding to physician referrals, picking up prescriptions on time and attending weekly meetings with the advocate. Although this study was small, it suggested that it is possible to harness peer pressure of drug users to promote positive behavioral changes. In particular, the results indicate that an alternative social support structure to drug treatment is feasible for increasing active drug users' adherence to medical care. Broadhead, B., Heckathorn, D., Altice, F., van Hulst, Y., Carbone, M., Friedland, G., O'Connor, P., and Selwyn, P. Increasing Drug Users' Adherence to HIV Treatment: Results of a Peer-Driven Intervention Feasibility Study. Social Sci and Medicine, 55, pp. 235-246, 2002.

Selection Effect of Needle Exchange in Anchorage, Alaska

Researchers examined participation bias (selection bias) as a potential threat to validity in studies that attempt to evaluate the effects of needle exchange programs (NEPs). They focused on IDUs who were randomly assigned to a needle exchange condition in a 2-arm randomized clinical trial of needle exchange. Time to follow-up between the experimental NEP condition (n=296; median = 261 days) and pharmacy sales conditions (n=304; median=256 days) was not significantly different. Within the NEP condition, a similar analysis comparing time to follow-up between IDUs who used the NEP (n=65, median=199 days) and those who refrained from using the NEP (n=231, median=286 days) was highly significant. Moreover, within the NEP condition, follow-up rates differed between those who used the NEP and those who did not. Of drug users randomly assigned to an NEP, the ones who actually used the NEP had higher levels of drug use. Predictors of who used the NEP were consistent with other studies reporting bias in a nonrandomized study of IDUs who use a voluntary NEP. This study found that there is an inherent selection bias among IDUs who use NEPs; that is, IDUs who use NEPs engage in higher frequency drug use and higher levels of other risk behaviors compared to IDUs who do not use NEPs, Moreover, IDUs who used both the NEP and the pharmacy to obtain sterile syringes injected significantly more often than other IDUs. This indicates that it is need, rather than compliance, that leads to the use of multiple sources of syringes. Fisher, D.G., Reynolds, G.L., and Harbke, C.R. Selection Effect of Needle Exchange in Anchorage, Alaska, 79(1), pp. 128- 135, 2002.

Localized vs Citywide Trends in the AIDS Epidemic Among IDUs in New York City

Researchers examined trends over phases of the AIDS epidemic among injection drug users in New York City, which accounts for almost 25% of the AIDS cases among IDUs in the U.S. They sought to determine whether recent declining trends in AIDS among IDUs were localized within boroughs of the city or generalized across the boroughs. Two methods were used: (1) the compilation and analysis of existing data on historical AIDS case rates, recent HIV sero- prevalence, and HIV prevention service levels by borough and (2) a qualitative study (key informant interviews and focus groups) in two communities (Staten Island and Rockaway, Queens) an hour from Manhattan where services are less accessible. Findings indicated that (1) epidemiological differences in risk behaviors and in services existed from early in the epidemic (i.e., before 1984), (2) HIV prevention services have been and continue to be concentrated in Manhattan; and (3) the long-term concentration of prevention programs in Manhattan appears to be related to the greater number of new infections associated with IDU and female heterosexual transmission in the Bronx and Brooklyn compared to Manhattan since 1984. This study suggests that the AIDS epidemic in New York City among IDUs and their sexual partners may have been shaped by the long-term, unequal geographic distribution of HIV prevention and outreach services in the City's boroughs. It also suggests that enhancing access to services for IDUs in the boroughs outside Manhattan will be needed to sustain declining trends in AIDS cases among IDUs throughout the boroughs of the City. Rockwell, R., Deren, S., Goldstein, M.F., Friedman, S.R., and Des Jarlais, D.C. Trends in the AIDS Epidemic Among New York City's Injection Drug Users: Localized or Citywide? J Urban Health, 79(1), pp. 136-146, 2002.

The First Decade of High Prevalence of HIV Among Injecting Drug Users in Bangkok

In order to examine the long-term structure of the HIV epidemic among IDUs in Bangkok, researchers conducted annual surveys on HIV seroprevalence at drug use treatment clinics of the Bangkok Metropolitan Administration (BMA) from 1987 onward, as well as risk behavior surveys with IDUs in 1989, 1993, and 1997. They also conducted a large cohort study to measure HIV incidence among clients of the BMA clinics from 1995 to 1998. Findings indicate that HIV prevalence rose rapidly in 1988 and then remained stable at 30-40%. By the fall of 1989, more than 90% of IDUs reported reducing their injection risk behaviors (stopping or reducing injecting, not sharing injection equipment). Reduction in injecting risks was not risk elimination, however: moderate percentages of IDUs continued to report injecting with a syringe that had been used by someone else. Sexual risk behavior (i.e., without a condom) occurred most often within primary relationships. The estimated HIV incidence was moderate to high at 5.8/100 person-years at risk from 1995 to 1998. Incarceration and injecting while incarcerated were strongly associated with incident HIV infections. The researchers conclude that the HIV epidemic among IDUs in Bangkok appears to have reached a rough equilibrium. Deaths among HIV positive IDUs and the continuing entry of new injectors (most of whom are HIV negative) into the population serve to decrease HIV prevalence. The stability of the epidemic has not yet brought it under control, however: the incidence rate remains too high (5.8/100 person-years at risk). The authors describe four key lessons learned from Bangkok's experience: one is that HIV can spread very rapidly among IDUs and therefore, prevention programs should be implemented as early as possible; the second is that even after rapid HIV transmission has occurred, IDUs will change their HIV risk behaviors (both injection and sexual risks); the third is that risk reduction is not risk elimination because residual risk behavior is likely to remain even after a majority of IDUs are aware of AIDS and have taken steps to reduce their risk behaviors; and finally, a long-term perspective is needed on controlling HIV epidemics among IDUs, especially since there seems to be a continuing entry of new injectors. Vanichseni, S., Choopanya, K., Des Jarlais, D.C., Sakuntanaga, P., Kityaporn, D., Sujarita, S., Raktham, S., Hiranrus, K., Wasi, C., Mock, P.A., and Mastro, T.D. HIV Among Injecting Drug Users in Bangkok: The First Decade. International J Drug Policy, 3, pp. 39-44, 2002.

Increased Substance Use among Residents of Manhattan, N.Y. after September 11th

Investigators examined the effects of the September 11th attacks on substance use behaviors among 988 adults in Manhattan, New York City. They conducted a random digit dial telephone survey of households and achieved an overall response rate of 64.3%. Interviews inquired about cigarette smoking, alcohol drinking, and marijuana use pre- and post- September 11th as well as demographic characteristics, other types of traumatic events that may have occurred before 9/11, and mental health status (PTSD, depression). They found that 28.8% of respondents reported increased use of any one of the 3 substances (cigarettes, alcohol, marijuana); 9.7% reported an increase in smoking; 24.6% reported an increase in alcohol consumption; and 3.2% reported an increase in marijuana use. Persons who reported an increase in cigarette use and marijuana use were significantly more likely to experience PTSD than those who did not (24.2% vs 5.6% PTSD for cigarettes; 36.0% vs 6.6% for marijuana). Depression was more common among those who increased than for those who did not increase cigarette smoking (22.1 vs 8.2%), alcohol consumption (15.5% vs 8.3%), and marijuana smoking (22.3% vs 9.4%). These results suggest a substantial increase in substance use among Manhattan residents in the acute post-disaster period after September 11th. Increased substance use may be a significant problem in the immediate aftermath of a disaster and may frequently co-occur with PTSD and depression. Vlahov, D., Galea, S., Resnick, H., Ahern, J., Boscarino, J.A., Bucuvalas, M., Gold, J., and Kilpatrick, D. Increased Use of Cigarettes, Alcohol, and Marijuana among Manhattan, New York, Residents after the September 11th Terrorist Attacks. Amer J Epidemiol., 155(110), pp. 988-996, 2002.

Needle Exchange-Based Health Services Help to Reduce Emergency Department Use

Researchers in New Haven, Connecticut examined the impact of the New Haven Community Health Care Van, a mobile needle exchange-based health care delivery system, in reducing emergency department (ED) use among out-of-treatment IDUs over the 2-year period of January 1996 to December 1998. A pre-post comparison of ED utilization was performed using linked medical records from New Haven's only two EDs. Among 373 IDUs, 117 (31%) were clients of the mobile NEP clinic and 256 had not used its services. At baseline, the mobile NEP clinic users were more frequent users of ED services (p<.001). After full-scale implementation of the mobile NEP clinic, mean ED utilization declined among its clients by more than 20% and increased within the non-client group. Use of the mobile NEP clinic was significantly associated with reductions in ED use; these reductions were striking because the mobile clinic was not specifically designed or intended to achieve this result. Reduced ED use appears to have resulted indirectly from other efforts of the mobile NEP clinic to improve the health status of clients and to use case management and outreach to provide continuity of care. The study's findings suggest that NEP-based health care services can reduce ED utilization among high-risk IDUs and have an important role within communities with high rates of drug use and HIV/AIDS. Pollack, H.A., Khoshnood, K., Blankenship, K.M., and Altice. F.L. The Impact of Needle Exchange-Based Health Services Emergency Department Use. J Gen Intern Med, 17, pp. 341-348, 2002.

Risk Behaviors Associated with Transition to Injection Drug Use in Young Drug Users

Researchers in Baltimore, MD sought to identify discrete high-risk circumstances occurring early on in a young drug user's life (such as age at first sexual experience, trading sex, rape or assault, high school dropout, juvenile detention) that would help determine whether such factors known to be associated with adolescent substance use and HIV were, in fact, also associated with being a recent onset IDU. An age-matched case-control analysis was performed from a cohort study in Baltimore (1997-1999) of street-recruited non-injection and injection drug users aged 15-30. Cases were IDUs injecting less than 2 years and controls were age-matched persons who used non-injection heroin, cocaine, or crack. At baseline, all were interviewed about prior year-by-year behaviors; data analysis was based on information for the year prior to injection onset for the case and the same calendar time for the controls as well as recent behaviors for both groups. Of 270 participants, most were African American (78%), female (61%), and HIV seroprevalence was 7% at baseline. IDUs were significantly more likely than controls to be non-African American and report high school dropout, early sex trading, and recent violence victimization. Given that new injectors are at high risk for HIV and hepatitis yet difficult to reach for prevention efforts, these data suggest some categories to use to target non-injectors who are likely to transition into injection drug use. Fuller, C.M., Vlahov, D., Ompad, D.C., Shah, N., Arria, A., and Strathdee, S.A. High-risk Behaviors Associated with Transition from Illicit Non-Injection to Injection Drug Use among Adolescent and Young Adult Drug Users: A Case-Control Study. Drug and Alcohol Dependence, 66, pp. 189-198, 2001.

Cognitive and Motor Outcomes of Cocaine-Exposed Infants

Dr. Lynn Singer and colleagues at Case Western Reserve University have reported that tests of infant cognitive development at 2 years of age (Bayley Scales of Infant Development, Mental Development Index, or MDI)) showed a significant association with prenatal exposure to cocaine, after taking account of potentially confounding factors (e.g., maternal age, parity, prenatal care, maternal and current caregiver non-verbal intelligence, education, home environment quality, and maternal use of tobacco, alcohol, marijuana, and other drug use). The average difference in the developmental quotient was 6 points (82.7 for the exposed and 88.7 for the non-exposed). The average MDI score for the general population is 100. When children were grouped by developmental scores in the range of mental retardation (<70 MDI) at 2 years of age, cocaine-exposed children were almost twice as likely to be so classified - specifically 13.7% of the cocaine-exposed children relative to 7.1% of the non-cocaine-exposed children. The percentage in the exposed group is 4.89 times higher than expected in the general population. Mild delays (<80 MDI) were present in 37.6% of exposed and 20.9% of non-exposed children. No associations were found between prenatal cocaine exposure and motor development at 2 years of age (Bayley Scales of Infant Development, Psychomotor Development Index, or PDI). As noted in an accompanying editorial to this publication, this "is the only 1 of 10 peer-reviewed, adequately-controlled, large scale, prospective longitudinal studies to show an unequivocal association between toddlers' developmental scores and prenatal exposure to cocaine." These findings illustrate the importance of multiple studies on the topic, allowing for comparison across studies and potential explanations for differences in findings, which in turn may guide appropriate interventions and clinical care. Singer, L.T., Arendt, R., Minnes, S., Farkas, K., Salvator, A., Kirchner, H.L., and Kliegman, R. Cognitive and Motor Outcomes of Cocaine-Exposed Infants. Journal of the American Medical Association, 287(15), pp. 1952-1960, 2002; Zuckerman, B., Frank, D.A., and Mayes, L. Cocaine-Exposed Infants and Developmental Outcomes: "Crack Kids" Revisited. Journal of the American Medical Association, 287(15), pp. 1990-1991, 2002.

Prenatal Alcohol, Marijuana, and Tobacco Exposure: Neuropsychological Outcomes at 10 Years of Age

In a longitudinal study at the University of Pittsburgh, neuropsychological outcomes at 10 years of age have recently been reported for a sample of 593 children, who had been assessed at multiple times since birth. The mothers had been recruited into the study during pregnancy. Half of the women were African-American, and half were Caucasian. They were generally from lower socioeconomic status families, and light to moderate level users. At the 10-year follow-up, prenatal alcohol use was found to be significantly and negatively associated with performance on a test of memory and learning skills. Prenatal marijuana exposure also was negatively associated with learning and memory performance, as well as with a measure of impulsivity. These associations persisted when other predictors of learning and memory were controlled (e.g., child's intelligence level, gender, and anxiety; parents' socioeconomic level and intellectual ability). An earlier publication (2001) on this sample focused on prenatal tobacco exposure, and documented, after statistically controlling for such factors as other prenatal substance use, current tobacco use, and multiple socioeconomic covariates, an association of prenatal tobacco exposure with various outcomes at 10 years of age (i.e., deficits in verbal learning and design memory, slowed responding on a test of eye-hand coordination, reduced ability for flexible problem solving, and more impulsivity). The investigators are continuing to follow this sample into the adolescent years. Richardson, G.A., Ryan, C., Willford, J., Day, N.L., and Goldschmidt, L. Prenatal Alcohol and Marijuana Exposure: Effects of Neuropsychological Outcomes at 10 Years. Neurotoxicology and Teratology, 24, pp. 309-320, 2002; Cornelius, M.D., Ryan, C.M., Day, N.L., Goldschmidt, L., and Willford, J.A. Prenatal Tobacco Effects on Neuropsychological Outcomes among Preadolescents. Developmental and Behavioral Pediatrics, 22(4), pp. 217-225, 2001.

Head Growth and Neurodevelopment of Infants Born to HIV-Infected Drug-Using Women

Researchers from the Women and Infants Transmission Study (WITS) continue to examine health and development outcomes of children born to HIV-positive mothers, with attention to drug use as a variable of importance. The WITS is a multi-site study of mother-infant HIV transmission and outcomes in the mothers and their children, and is collaboratively supported by three NIH Institutes (NIAID, NICHD, NIDA). Enrollment began in 1990 and has continued since that time. Macmillan et al. report on neurodevelopment and head growth during the first 30 months of life among HIV-positive and HIV-negative infants with and without in utero exposure to opiates and cocaine. Of the 1,094 infants in the analysis, 147 were HIV-positive and 383 were exposed in utero to opiates or cocaine (maternal self-report or positive urine screen). There were differences in developmental test scores and head circumference among the groups at 4 months of age (HIV+/drug negative, and HIV-/drug positive showing the lowest scores and head circumference); by 24 months of age, only HIV infection was found to be associated with decreased neurodevelopment test performance and smaller head circumference. The authors note that as the children enter their school-age years, a more detailed examination of specific developmental domains will be possible (i.e., language, attention, memory , and behavior). Macmillan, C., Magder, L.S., Brouwers, P., et al. Head Growth and Neurodevelopment of Infants Born to HIV-1-Infected Drug-Using Women. Neurology, 57, pp. 1402-1411, 2001.

Development of Thrombocytosis in HIV+ Drug Users: Impact of Antiretroviral Therapy

Miguez-Burbano et al. report for the first time thrombocytosis in 9% of the HIV+ patients receiving highly active antiretroviral therapy (HAART) being followed in a nutritional clinical trial. Patients were evaluated every 6 months during a 2-year period (1998-2000) and blood drawn for biochemical, hematological and immunological parameters. Natural killer (NK) cells were negatively correlated with platelet counts in the total cohort (p=0.018) and persistently elevated with antiretroviral therapy. Chronic thrombocytosis was associated with significantly lower NK percentages (p=0.005). Twenty-five percent of the patients with thrombocytosis developed a cardiovascular disease. Together, these results support the proposal that HAART may increase the risk of hematological dysfunction and impact the risk of cardiovascular disease. Miguez, M.J., Burbano, X., Rodriguez, A., Lecusay, R., Rodriguez, N., and Shor-Posner, G. Platelets, 12(8), pp. 456-461, 2002.

Effect of Cocaine Use on Coronary Calcium Among Black Adults in Baltimore, Maryland

Lai et al. report for the first time significantly high levels of calcium deposits in coronary arteries of African-Americans who abuse cocaine, a finding that suggests cocaine use might promote subclinical atherosclerosis. A total of 187 African-American subjects (average age of 38; 67% men; recruited from the ALIVE cohort) were enrolled in a longitudinal study to examine if subclinical atherosclerosis was related to HIV infection and cocaine use. Data showed that of the 139 participants, about 33% had detectable coronary calcium suggesting that cocaine use was independently associated with a higher coronary calcium after controlling for age and gender. The findings suggest that cocaine use may have an important effect on the natural history of subclinical atherosclerosis and that strategies to reduce drug abuse may be critical in early prevention of cardiovascular disease in the US. Lai, S., Lai, H., Meng, Q., Tong, W., Vlahov, D., Celentano, D., Strathdee, S., Nelson, K., Fishman, E.K., and Lima, J.A.C. Am J. Cardiology, 90, pp. 326-328, 2002.

Use of HIV Protease Inhibitors Is Associated with Left Ventricular Morphologic Changes and Diastolic Dysfunction

Lai and his colleagues report for the first time that treatment of HIV/AIDS with protease inhibitors is associated with serious adverse effects such as left ventricular hypertrophy and that should be taken into consideration in the analysis of cardiac structure and function in patients with HIV infection. The investigators assessed the effects of PIs (e.g., nelfinavir, indinavir, ritonavir, saquinavir) on cardiac function and structure in 98 African-American adults aged 25-45 years with HIV infection and who were being treated with antiretroviral therapy. Substance use prevalence was quite high. Echocardiographic examinations, blood pressure and other cardiac function examinations showed that left ventricular posterior wall (LVPW) and interventricular septum (IVS) thickness were increased along with decreased LV diastolic function in HIV-infected participants on PI therapy compared with those not on PI therapy suggesting that PI therapy is associated with ventricular structural changes and thus dysfunction. Further, cardiac diastolic dysfunction was present in the absence of systolic dysfunction. Although substance use was quite common, no significant changes in cardiac effects could be attributed to any one specific drug. Meng, Q., Lima, J.A.C., Lai, H., Vlahov, D., Celentano, D., Strathdee, S., Nelson, K., Tong, W., and Lai, S. JAIDS, 30, pp. 306-310, 2002.

Mechanism of Cocaine-induced Hyperthermia in Humans

Ron Victor and his colleagues report that in humans cocaine use increases body temperature by impairing heat dissipation mechanisms. Cocaine abuse is a major cause of life-threatening cardiovascular emergencies, inlcuding hypertensive crisis, acute myocardial infarction, and ventricular arrythmias. Furthermore, lethal effects of cocaine are also related to cocaine's propensity to cause hyperthermia, the mechanism of which is unknown. Investigators conducted a randomized double-blind, placebo-controlled crossover trial to test the effects of cocaine on body temperature regulation in seven (7) healthy, 23-37 year old, men and women. The body temperature (esophageal), skin blood flow, forearm sweat rate, heart rate, EKG, mean arterial blood pressure, cutaneous vascular conductance were all measured on the participants after receiving intranasal cocaine hydrochloride (2 mg/kg bw, 10% solution) or lidocaine (2 mg/kg bw, 10% solution, as a control). See the paper for detailed methodology. Results showed: (1) that cocaine significantly augmented the progressive increase in esophageal temperature during heat stress, but it also attenuated the increase in thermal discomfort; and (2) cocaine significantly attenuated the progressive increase in cutaneous vascular conductance and sweating during heat stress. This experiment shows that cocaine impairs the perception of heat stress further confirming that cocaine acts centrally to alter thermoregulatory responses. Participants experienced less thermal discomfort with low non-euphoric doses of cocaine even though core temperature was higher than with lidocaine. Larger doses of cocaine produce intoxication, agitation, and increased locomotor activity and heat production leading to impaired heat dissipation and toxic/fatal hyperthermia, particularly in warm environments of nightclubs or at "rave parties". Craig, G., Vongpatanasin, W., and Victor, R. Ann Intern Med., 136, pp. 785-791, 2002.

Marijuana Use and Cessation of Tobacco Smoking in Adults from a Community Sample

Ford and his colleagues from Johns Hopkins University report that those adults who smoke tobacco and marijuana find it harder to give up tobacco smoking. This analysis is based on interview data from 431 adults less than 45 years of age who reported recent tobacco smoking in the 1981 baseline interview in the house-hold based Baltimore Epidemiologic Catchment Area study and were re-interviewed 13 years later. At baseline 41% of the tobacco smokers reported marijuana ever use, 27% reported monthly use, and 9% reported daily use for 2 weeks or more in the last 30 days. At follow-up 13 years later, 79% of the original 431 smokers were still smoking tobacco. The monthly users were more likley to use tobacco than non-users. Data indicate that tobacco smokers who also smoke marijuana are less likely to have stopped tobacco smoking over a period of 13 years of follow-up. Recent use of marijuana at baseline, and especially sustained daily use, was more associated with continued tobacco smoking than past use of marijuana. Authors state that difficulty in tobacco cessation might be considered one of the most important adverse effects of marijuana use. They suggest that clinicians working with patients who are trying to stop tobacco smoking may be aided by routinely assessing history of marijuana use, particularly with the recent increase in co-smoking of marijuana and tobacco. Ford, D.E., Vu, H.T., and Anthony, J.C. Drug Alc Dep, 67, pp. 243-248, 2002.


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