The ramifications of drug abuse extend far beyond the individual drug abuser, because the health and social consequences of drug abuse HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome), violence, tuberculosis, fetal effects, crime, and disruptions in family, workplace, and educational environments (Box 7.1)-have devastating impacts on society and exact a cost of billions of dollars annually.1 Drug abuse is often the result of a constellation of factors including socioeconomic status, educational achievement, co-occurring psychiatric disorders, access to health care, employment status, and numerous other factors present in the lives of drug-abusing individuals (see Chapter 5). Regardless of the factors at work, it is the ultimate goal of the nation's investment in drug abuse research to take more effective measures to prevent drug abuse and to reduce its associated costs and consequences.
A comprehensive assessment of knowledge and research opportunities on the multiple consequences of drug abuse would have far exceeded the committee's allowable time frame and expertise. Consequently, it chose to focus on three areas that involve pronounced social consequences, where the need for strategic interventions are greatest: (1) the transmission and course of HIV infection; (2) fetal and child development; and (3) violent behavior.
BOX 7.1 Consequences of Drug Abuse
It now appears that injection drug use is the leading risk factor for new human immunodeficiency virus (HIV) infections in the U.S. (Holmberg, 1996). Drug and alcohol abuse heightens the risk for unsafe sexual behavior and is a factor in perinatal transmission of HIV.
Tuberculosis (TB) rates have increased significantly among drug-using populations, especially drug-resistant TB in HIV-infected drug users.
Other diseases and illnesses
Injection drug users (IDUs) are more likely to develop serious infections and illnesses (e.g., viral hepatitis, endocarditis, pneumonia, other bacterial infections) than the non-IDU population due to the harmful effects of drug injection and their infrequent use of primary medical care services. Additionally, some forms of psychiatric disorders may result in part from drug abuse (e.g., depression, PCP-precipitated psychosis).
Fetal and child development
Drug abuse can impact the health of the developing fetus and child. Consequences include retardation of fetal growth, fetal alcohol syndrome, neonatal withdrawal syndrome, and neonatal neurobehavioral affects.
Violence and crime
Violence and crime are linked to illicit drug abuse through the often violent nature of drug sales and distribution. Additionally, some drug addicts resort to theft to support their drug habits. Pharmacological effects of drug abuse associated with violent actions may occur de novo or with predating co-occurring psychiatric disorders.
Violence and crime are linked to illicit drug abuse through the often violent nature of drug sales and distribution. Additionally, some drug addicts resort to theft to support their drug habits. Pharmacological effects of drug abuse associated with violent actions may occur de novo or with predating co-occurring psychiatric disorders.
Drug abuse plays a role in numerous transportation or other accidents. For example, the National Highway Traffic Safety Administration estimates that 40.8 percent of traffic fatalities were alcohol related (NHTSA, 1995).
Loss of human capital
Drug abuse can have devastating impacts on an individual's potential (e.g., school delinquency, dropping out of school, involvement in illicit drug selling), thus reducing future educational and job opportunities.
Employee drug use, particularly heavy use or abuse, has been found to be associated with increased absenteeism, accidents, job turnover, counterproductive behavior, and job dissatisfaction (NRC, 1994). However, drug abuse does not occur in isolation, and other related life-style behaviors are strongly correlated with employment difficulties.
Drug abuse leads to reallocation of economic support away from the family; lack of participation in family activities, including caregiving; lack of emotional commitment and support for parents and children; and the inability to provide a reliable and adequate role model for other family members, especially children. This impact on the family affects children's development, leaming, and social relations whether or not actual child abuse and neglect occur.
Drug-abusing students may develop cognitive and behavioral difficulties; disrupt classes; have increased psychosocial problems; or be delinquent in attending school or drop out of school (Kandel and Davies, 1996). Additionally, violence increases as buying and selling of drugs occurs at the school site.
Today more than 17 million people worldwide, including an estimated 1 million Americans, are infected with the human immunodeficiency virus (HIV) which causes AIDS. In the United States, according to the Centers for Disease Control and Prevention (CDC), AIDS is now the leading cause of death among 25- to 44-year-olds (Swan, 1995).
It now appears that injection drug use is the leading risk factor for new HIV infection in the United States (Holmberg, 1996). More than onethird of AIDS cases reported through December 1995 were related to injection of illicit drugs through three mechanisms: the sharing of contaminated injection equipment, heterosexual contact with an injection drug user (IDU), or through maternal injection of illicit drugs (Table 7.1) (CDC, 1995a). In women, the percentages of AIDS cases involving injection of illicit drugs are alarmingly high. Of the 71,818 female AIDS cases reported to CDC through December 1995, almost half (33,452 cases) were related to injection of illicit drugs and another 18 percent (13,046 cases) to sex with infected IDU partners (CDC, 1995a).
HIV can be transmitted through direct needle sharing when contaminated blood remains in the syringe and may be released into the next user or through certain injection drug practices during which blood is drawn into the syringe and mixed with the drug. Transmission of the virus can also occur indirectly by the sharing of drug injection equipment such as cotton balls or rinse water (NRC, 1995), and increased frequency of injection and the use of shared equipment increase the risk for seropositivity. HIV risk is also associated with the locations in which drug use occurs.
TABLE 7.1 AIDS Cases Related to Injection of Illicit Drugs (percentage of total cases)
Cases Reported in 1995
Cumulative Total Reported Through December 1995
Injection drug use
Heterosexual contact with an injection drug user
Men who have sex with men and inject drugs
Pediatric cases (<13 years old)
Mother who is an injection drug user
Mother who has sex with an injection drug user
Total cases related to injection drug use
Total cases reported
SOURCE: CDC (1995a).
Injection drug use frequently occurs in ''shooting galleries" where users can rent a syringe and needle that is supplied from a common container. The injection equipment may or may not be rinsed, and if rinsed, may be rinsed with infected water.2
All drug users, injecting and noninjecting, place themselves at great risk for HIV transmission when engaging in unsafe sexual behavior while under the influence of drugs, such as alcohol and cocaine, or exchanging sex for money or drugs (Edlin et al., 1994; O'Connor et al., 1994). One study found that as many as 80 percent of male IDUs were in a primary
relationship with women who did not use drugs themselves (Des Jarlais et al., 1984). Since the beginning of the crack cocaine epidemic, that drug has been seen as a sexual stimulant, as well as the cause of high-risk sexual behavior in many users. The disinhibiting effect is stronger than that of depressants such as alcohol or heroin due to the rapid onset of the drug's "high" with a related rapid release of inhibitions (Fullilove and Fullilove, 1989; Chaisson et al., 1991; Edlin et al., 1994). Sex-for-drug exchanges and prostitution—associated with the need to acquire crack cocaine or the money to buy the drug—have resulted in the transmission of HIV to the non-drug-using populations (IOM, 1994).
Maternal-infant transmission of HIV is often an indirect health consequence of injection drug use. Of the 6,948 cases of AIDS in children under 13 years of age reported to CDC through December 1995, 90 percent are attributable to perinatal HIV transmission. Most (54 percent) of the pediatric AIDS cases are associated with injection of illicit drugs—37 percent with maternal injection of drugs and 17 percent with maternal sexual contact with an IDU (CDC, 1995a). Of all infants born to HIV-infected mothers who do not receive antiretroviral therapy (e.g., AZT), an estimated 15-35 percent of those infants become infected (Hardy, 1991; CDC, 1994, 1995b).
As the AIDS epidemic continues to spread, the financial burden of the disease on those affected, the health care system, and society in general will continue to grow. Because data on the use of and expenditures for medical services of persons with AIDS are scarce, the Agency for Health Care Policy and Research (AHCPR) established the AIDS Cost and Service Utilization Survey (ACSUS) in 1989. Estimates in 1992 forecast that the cumulative (national) costs of treating all HIV-infected individuals would surpass $15.2 billion in 1995 (see Table 7.2). That figure, which represents a 48 percent increase from the cost of $10.3 billion in 1992, reflects an increase in the average amount of services used by those infected with HIV as well as the availability of better data on the utilization of medical services (Hellinger, 1992; Oncology, 1993).
TABLE 7.2 Estimated Costs of AIDS
Cost of treating all HIV-infected persons in the United States
SOURCES: Adapted from Scitovsky and Rice (1987), Hellinger (1992), Oncology (1993).
The United States funds 85 percent of the world's public sector investment in AIDS research, primarily through the National Institutes of Health (NIH) whose AIDS and AIDS-related research portfolio is currently a $1.4 billion effort (OAR, 1996). Research is aimed at all phases of the etiology, prevention, and treatment of the disease. The research accomplishments to date are numerous. This section highlights future research directions related to IDUs and AIDS research. Chapter 8 discusses further research opportunities in the treatment of HIV-infected drug abusers.
Measuring HIV prevalence (the number of infections at a point in time) and incidence (the number of new infections over time) is crucial to monitoring the course of the epidemic. Statistics on the incidence and prevalence of HIV infection provide a more complete assessment of the magnitude of the epidemic than end-stage statistics of AIDS cases. Efforts to determine HIV prevalence in the drug-abusing population have been based on a range of seroprevalence studies primarily of IDUs. The number of IDUs in the United States has been estimated to range from 1.1 million to 1.8 million (NRC, 1989; OTA, 1990). Estimates of HIV seroprevalence in the IDU population range from 0 to 50 percent depending largely on geographic location. In New York City, HIV seroprevalence was found to be slightly more than 50 percent in a study of injection drug users (Des Jarlais et al., 1994). The Centers for Disease Control and Prevention's HIV/AIDS Surveillance Report provides data on new HIV cases in IDUs. However, these data are not representative of all persons with HIV infection because some states also offer anonymous HIV testing, and the collection of demographic and risk information varies greatly among states (CDC, 1995a).
Because of the difficulties in locating and gaining access to the populations initiating or relapsing into injecting drugs, most of the epidemiological studies to date have focused on long-term, chronic IDUs (IOM, 1994). As a result, little is known about younger, new IDUs who may actually be at increased risk for HIV transmission due to engaging in higher levels of risk behaviors, including needle sharing and use of shooting galleries (Battjes et al., 1992). Additionally, little is known about the extent of HIV transmission that is due to sex-for-drug activities or drug-related prostitution.
Studies are needed to determine the prevalence of HIV infection among vulnerable populations of drug users. Information from such stud-
ies may help establish a basis for possible intervention programs directed at preventing further HIV transmission. More extensive epidemiological data regarding HIV incidence in the drug-using population are needed in order for AIDS treatment programs to accurately and adequately meet the needs of those infected.
Prevention and Risk Reduction Strategies
AIDS prevention intervention research is focused mainly on identifying and modifying behaviors known to be associated with HIV transmission; it targets individuals at high risk because of drug use and sexual contact. Education on hygienic injection practices and HIV transmission routes, condom distribution programs, and enrollment in drug abuse treatment are currently the major risk reduction interventions aimed at drug users in the United States. Additionally, there are other programs to prevent HIV infection that have incorporated social interventions to effect change in risky behaviors (Friedman et al., 1992).
Drug abuse treatment has demonstrated varying degrees of success in the reduction of risk factors for HIV among populations of IDUs, primarily through prevention education (Watkins et al., 1992). Studies have shown that drug abuse treatment is associated with reductions in HIV risk behaviors, including reductions in drug use, in risky injection practices, and in the number of sex partners (Ball et al., 1988; Watkins et al., 1992; Longshore et al., 1994; Serpelloni et al., 1994). In general, it has proven to be more difficult to change sexual risk behaviors than to change drug injection behaviors (Des Jarlais, 1992; Battjes et al., 1995).
Recent evidence has shown a decrease in the use of contaminated drug paraphernalia when needle exchange is available (Des Jarlais et al., 1994). For example, the use of contaminated needles declined from 51 percent of injections in 1984 to 7 percent in 1992 in a study of New York City IDUs (Des Jarlais et al., 1994). That work confirms other studies that found HIV risk reduction behaviors among IDUs (Vlahov et al., 1991; Schottenfeld et al., 1993). As noted in a recent National Research Council (NRC, 1995) report, research has also shown that needle exchange programs do not affect the level of drug use among participants and do not appear to recruit new users to injection drugs. Additionally, needle exchange programs can also provide strategic and important sites for the deployment of primary care services and referral for persons with or at risk of HIV infection. Whereas needle exchange programs have been adopted in some European countries and have been associated with a reduction in the incidence of HIV infection (Hart et al., 1989; Hartgers et al., 1989; Ljungberg et al., 1991) and no increase in illicit drug use, such
programs have been resisted in the United States.3 Continued research is needed on the impact of needle exchange programs and on ways to improve their effectiveness along the lines recommended in the NRC report (see also Chapter 10).
Although risk reduction strategies have primarily targeted current injection drug users, it is important for research to focus also on preventing initiation into intravenous drug use. A study by Battjes and colleagues (1992) found that early age of first injection is associated with higher levels of injection and sexual risk behaviors (including needle sharing, frequency of injection, use of shooting galleries, multiple sex partners, and prostitution).
The committee recommends continued and expanded research efforts regarding noninjecting and injecting drug use and HIV transmission. Specifically, epidemiological studies of the prevalence and correlates of HIV infection in vulnerable populations of drug users and IDUs; and studies of effective risk reduction strategies for changing sexual risk behaviors and drug injection behaviors are needed.
IMPACTS ON FETAL, INFANT, AND CHILD DEVELOPMENT
Drug abuse can have a significant impact on the health of children who either are exposed to nicotine, alcohol, or illicit drugs prenatally through maternal drug abuse or grow up in a drug-abusing household. Although it is difficult to estimate the number of children in drug-abusing households, the National Pregnancy and Health Survey, sponsored by the National Institute of Drug Abuse (NIDA), provides nationwide estimates of the use of nicotine, alcohol, and illicit drugs by pregnant women. The survey estimated that in 1992, 20.4 percent of the women (an estimated 820,000 women) smoked cigarettes and 18.8 percent (757,000) used alcohol during pregnancy (NIDA, 1996). The survey also found that 5.5 percent of the women who gave birth (approximately 221,000 women out of 4 million nationally) used one or more illicit drugs during pregnancy; an estimated 119,000 women (2.9 percent) used marijuana, 45,000 (1.1 percent) used cocaine (34,800 of whom used crack cocaine), and 3,600 used heroin during pregnancy (NIDA, 1996).4
The economic costs of maternal drug use during pregnancy were estimated to exceed $500 million in 1990 for cocaine-exposed infants and $652 million annually for maternal cigarette smoking (Manning et al., 1989a,b; Phibbs et al., 1991; Frank et al., 1993). Prenatal exposure to these drugs may result in prematurity and low birth weight, which is one of the primary causes of extended hospital stays for drug-exposed infants. For example, a premature cocaine-exposed infant's hospital stay costs an average of $5,200 more than the cost of an unexposed infant (Phibbs et al., 1991). It is more difficult to estimate the cost of other health effects due to prenatal exposure (e.g., HIV infection5) or the collateral effects (e.g., homelessness, child abuse, neglect, and malnutrition) of growing up in a drug-abusing household.
The next section provides an overview of the known effects of nicotine, alcohol, heroin, marijuana, and cocaine on fetal development and on later behavior and developmental outcomes. It is followed by a discussion of opportunities for future research on prenatal exposure and on the effects of growing up in a drug-abusing household. Discussion is limited to nicotine, alcohol, heroin, marijuana, and cocaine because those drugs appear to be the most widely used during pregnancy, with the possible exception of caffeine. Before describing the accomplishments, however, the methodological difficulties associated with conducting research on prenatal exposure are discussed.
Nicotine, alcohol, heroin, marijuana, and cocaine readily cross the placenta and the blood-brain barrier, creating a potentially increased risk of adverse biological consequences to overall fetal development and specifically to fetal brain development. In most instances, however, demonstrating links between prenatal exposure and immediate or later outcomes is complicated by issues such as interactions with associated conditions
(e.g., poor nutrition, parental stress and psychiatric illness, sexually transmitted diseases) that may also impact on development (Frank et al., 1993; Finnegan, 1994). Further, the majority of women who use heroin, marijuana, or crack cocaine also use varying amounts of alcohol and/or nicotine and may use one or more illicit drugs in combination. Thus, rarely is it possible to speak, for example, of a "pure" crack cocaine effect.
Additionally, longitudinal studies of the developmental outcome of prenatal drug exposure in human infants face four methodological issues that cut across the specific agent of abuse and exposure (reviews by Jacobson and Jacobson, 1995; Neuspiel, 1995; Olson et al., 1995). First, there are difficulties in ascertaining the amount, frequency, and duration of drug abuse during pregnancy due to inaccuracies of maternal selfreport and limitations of current biological markers of exposure (Coles, 1992; Kidwell, 1992). Second, the high rate of attrition is a problem in studies of drug-abusing populations (Mayes and Cicchetti, 1995). Third, there are difficulties in choosing the appropriate comparison group (e.g., determining whether the comparison group is drug free or free only of the primary drug of interest, choosing appropriate demographic comparison cohorts). Fourth, determining the appropriate time (developmentally) and length of time to assess infants is another crucial issue. Traditional models of behavioral teratology presume effects that are present at least early in infancy but may or may not persist through childhood. Less frequently discussed are drug-related effects that are not apparent until later in development, when central nervous system processing of information or social skills are required, or during periods of major central nervous system reorganization (e.g, between age 4 and 5 years or during puberty) (see Weiss, 1995).
Animal models provide some basis for comparison because the amount of exposure and environmental conditions may be controlled. Animal models have been particularly useful for studies of the effects of prenatal exposures and for modeling drug-related effects on brain development at the structural, cellular, and functional levels. Neurobehavioral data from animal models should be viewed carefully, however, when extrapolating results from animal models to the complex developmental capacities found in higher primates and humans (e.g., language, complex problem-solving tasks, and neuropsychological functions such as certain domains of memory) (see Stanton and Spear, 1990).
Prenatal Nicotine Exposure
Nicotine acts as a vasoconstrictor, reducing placental blood flow and
the amount of oxygen and nutrients available to the fetus through several mechanisms. Additionally, smoking reduces the mother's appetite, and carbon monoxide from cigarette smoke crosses the placenta, increasing fetal carboxyhemoglobin levels (Werler et al., 1985). Those mechanisms are associated with retarding intrauterine growth in an apparent doseresponse relationship; the more cigarettes smoked, the lower is the birth weight (Zuckerman, 1991).6 Maternal cigarette smoking is also linked to higher rates of negative outcomes, including spontaneous abortions (Risch et al., 1988), stillbirths and perinatal death (Cnattingius et al., 1988; Malloy et al., 1988), and sudden infant death syndrome (SIDS) (Werler et al., 1985; Kandall and Gaines, 1991; Fried, 1992). Additionally, other toxins in cigarettes, including cadmium, lead, and thiocyanate, may also have adverse effects on the developing fetus (Kuhnert, 1991).
Nicotine may affect fetal brain development both indirectly (through nicotine-associated hypoxia) and directly (through specific nicotinic receptors) (Slotkin, 1992). In animal models, it appears that there is a lower dose threshold for adverse effects of fetal nicotine exposure on neuronal development than on overall growth (Slotkin, 1992). The literature regarding later neuro-behavioral outcomes in nicotine-exposed infants and children is not as extensive or as conclusive as those studies regarding pregnancy and birth outcomes (Fried, 1992). One study has found that maternal smoking during pregnancy, when postnatal smoking was controlled, selectively increased the probability that female children would smoke as adolescents and would continue to smoke (Kandel et al., 1994). There is suggestive evidence of a relationship between maternal smoking and later adverse developmental outcomes, including effects on attention and auditory responsiveness (Fried and Watkinson, 1988, 1990). However, those effects, if any, have a small attributable risk.
Prenatal Alcohol Exposure
Alcohol in high doses is a potentially potent teratogen associated with a range of consequences, including congenital anomalies and neurodevelopmental impairments (reviewed in IOM, 1995). In high doses, alcohol acts as a direct neuroteratogen, affecting all aspects of fetal growth (including brain growth, structure, and function) through mechanisms
that have not yet been elucidated (Schenker et al., 1990; Goodlett and West, 1992).
Studies of gestational ethanol exposure in nonhuman primates have explored dose-response relationships (e.g., Clarren et al., 1988, 1992). Fetal alcohol syndrome (FAS) is caused by prenatal exposure to high levels of alcohol and is characterized by intrauterine growth retardation with concomitant poor growth in fetal weight and/or height; a pattern of specific minor physical anomalies that include a characteristic facial appearance; and central nervous system deficits including microcephaly, delayed development, hyperactivity, attention deficits, intellectual delays, and learning disabilities (Clarren and Smith, 1978; Smith, 1982). Even in the absence of signs of FAS, infants born to alcoholic mothers show an increased incidence of intellectual impairment, congenital anomalies, and decreased birth weight (Sokol et al., 1980; Day, 1992; Aronson et al., 1985). Some children exposed prenatally to alcohol may show delayed development in their first two to three years (e.g., Jacobson et al., 1993; Day and Richardson, 1994) while others do not exhibit this tendency (Greene et al., 1990; Boyd et al., 1991).
Prenatal Opiate Exposure
Newborns who have been exposed prenatally to opiates (heroin or methadone), taken by the mother chronically during the pregnancy, are born passively dependent on the drug and may exhibit withdrawal symptoms in the first days to weeks after delivery (Desmond and Wilson, 1975). The withdrawal symptoms are characterized by hyperirritability, tremors, diarrhea, vomiting, and tachypnea (Finnegan, 1986). Prenatal opioid exposure increases the risk of reduced birth weight and head circumference (e.g., Zagon and McLaughlin, 1984; Doberczak et al., 1987) and of SIDS (e.g., Finnegan, 1979; Kandall et al., 1993). Similar findings in animal models that control for exposure to other drugs, such as alcohol and tobacco, and for poor maternal health support these findings on the effect of opiates on fetal growth (Zagon and McLaughlin, 1984).
Neurobehavioral assessments in the newborn period find that opiateexposed infants are more easily aroused, are more irritable, and have poor motor control (Strauss et al., 1976; Marcus and Hans, 1982; Jeremy and Hans, 1985). Such neurobehavioral abnormalities generally diminish over the first month of life (Jeremy and Hans, 1985) and thus are assumed to reflect the transitory symptoms of narcotic withdrawal rather than evidence of permanent neurological dysfunction (Hans, 1992).
Follow-up studies of opiate-exposed and non-opiate-exposed children have continued to report few to no differences in developmental and cognitive performance in comparison to social class-matched controls,
although there is some indication of problems with motor coordination (Strauss et al., 1976). There are fewer studies of the long-term effects in school-age children of prenatal opiate exposure, and those available usually lack a nonexposed control group or are not based on a longitudinal design (Hans, 1992).
Prenatal Marijuana Exposure
Tetrahydrocannabinol (THC), a psychoactive compound in marijuana, readily crosses the placenta and, in heavy users, it is also concentrated in breast milk (Blackard and Tennes, 1984; Levy and Koren, 1992). Marijuana has an indirect effect on fetal oxygenation through the high level of carbon monoxide found in marijuana smoke, which in turn results in fetal hypoxia. THC during pregnancy has adverse effects (in animals and humans) on pituitary and ovarian function, prolactin secretion, and uterine contractility (Harclerode, 1980). However, studies on the relationship between marijuana use and length of gestation or birth weight have conflicting results (Fried et al., 1983; Zuckerman et al., 1989b).
Studies on marijuana's neurobehavioral affects are inconclusive; some studies have reported that human neonates exposed to maternal marijuana use exhibit increased tremors, higher-pitched cries, and disturbances in sleep patterns (Fried, 1980, 1982; Fried and Makin, 1987; Scher et al., 1988). The paucity of long-term follow-up studies makes it difficult to conclude whether or not prenatal marijuana exposure has a direct effect on later developmental functions such as memory, attention, or impulse control, and/or whether such effects cannot be identified until later in development.
Prenatal Cocaine Exposure
The effect of cocaine on fetal growth may be due to the norepinephrineand serotonin-related effects of cocaine on vascular tone, which decreases uteroplacental blood flow and contributes to uteroplacental insufficiency (acute and chronic), maternal hypertension, and fetal vasoconstriction (Moore et al., 1986; Woods et al., 1987), in turn resulting in a relative state of fetal hypoxia. Reduced placental blood flow probably contributes to the relation between cocaine and poor fetal growth (low birth weight and microcephaly) (Oro and Dixon, 1987; Chouteau et al., 1988; Zuckerman et al., 1989b; Handler et al., 1991). Other cocaine-associated perinatal effects in pregnant women include premature birth, placenta previa, abruptio placentae, and neonatal cerebrovascular hemorrhage; however, the results to date are inconsistent (Zuckerman and Bresnahan, 1991; Frank et al., 1993; Holzman and Paneth, 1994). Addition-
ally, cocaine has effects on overall adult nutrition, maternal appetite, and compliance with prenatal care, as well as associations with polydrug use such as alcohol, tobacco, and opiate use (Frank et al., 1988; Amaro et al., 1989).
Further, there is some evidence that cocaine may alter the neurotransmitter systems, thus possibly modifying a number of critical processes in brain development. Human infants exposed to cocaine prenatally have exhibited increased norepinephrine and dopamine metabolite levels in cerebrospinal fluid and blood in early infancy (Mirochnick et al., 1991; Needlman et al., 1993). In animal models of prenatal cocaine exposure, significant changes in monoaminergic activity are noted compared to controls (Dow-Edwards et al., 1988; Dow-Edwards, 1989; Seidler and Slotkin, 1992).
Findings on neurobehavioral effects in the newborn period are inconsistent (Anday et al., 1989; Spear et al., 1989a,b; Magnano et al., 1992; Alessandri et al., 1993; Mayes et al., 1993). On general measures of developmental competency, such as the Bayley Scales of Infant Development, few differences are apparent between cocaine-exposed and nonexposed infants (Chasnoff et al., 1992). However, such measures may not be sensitive to subtle effects resulting from prenatal cocaine exposure. Preliminary evidence is beginning to accumulate about impairment of specific functions, such as neonatal habituation, attention or arousal regulation, reactivity to novelty, and conditioned learning. Longer-term follow-up of cocaine-exposed children into school age is necessary in order to explore the potential implications of prenatal exposure for later learning and development.
Research to date has begun to elucidate many of the biological mechanisms and health consequences of maternal drug abuse on the fetus and neonate. Additionally, the impact on the child's development of growing up in a drug-abusing household is a growing area of research. However, many unanswered questions still need to be addressed.
Windows of Biological Vulnerability
Critical stages exist throughout gestational development during which the fetus is particularly vulnerable to chemical exposure; consequently, the impact of maternal drug abuse on the fetus will vary depending on the stage of fetal development. The brain develops during the entire course of pregnancy and on into infancy, making it especially vul-
nerable to developmental toxins.7 Important data regarding dose-response curves and the relation of developmental outcomes to the severity of exposure in humans are essentially unavailable and, realistically, may be most adequately addressed through animal models. Research is needed to clarify how different drug-using patterns (amount, frequency, duration, method of drug taking) and the timing of drug exposure affect fetal development in order to refine models of teratogenesis for specific drugs of abuse.
Effects of Multiple Drug Use
As already noted, most illicit drug abusers also abuse nicotine and alcohol and frequently abuse more than one illicit drug. These drugs interact in the body, potentially causing additive, synergistic, or antagonistic effects. For example, studies have shown that the presence of cocaine and ethanol in the liver produces cocaethylene, a compound that is more cardiotoxic than cocaine and has a longer half-life (Hearn et al., 1991a,b). Additionally, the effects of opiate-cocaine interactions have not been studied beyond the newborn period. Studies of the consequences of maternal polydrug use on the developing fetus are needed to clarify areas and extent of drug interactions.
Self-Reports and Biological Markers of Exposure
Objective quantification of dose exposure is problematic, particularly for drug exposure during the first trimester when pregnancy may not be recognized. Maternal self-reports of drug use can be inaccurate in the report both of actual use and of amount and frequency. One study found that 12 percent of marijuana use and 35 percent of cocaine use during pregnancy were not reported (Zuckerman et al., 1989c). One contributing factor to underreporting is fear of the legal consequences of disclosure (see Chapter 10). Continued efforts are required to develop drug abuse interviews that are appropriate for pregnant women.
Development of biological markers of exposure will assist in verification of self-reports of drug use. Advances in drug testing, of both fetal hair and meconium, can improve the detection of the presence or absence of drug exposure and may provide an approximation of cumulative dose
(see Ostrea, 1995). There is currently no biological marker for quantifying a peak dose (a binge equivalent), however, that may be physiologically critical. Biological markers are needed to develop dose-response analyses to determine if there is a linear correlation between amount of exposure and severity of effect or if a threshold level exists.
Effects of Paternal Drug Use
Drug use and abuse are higher in men than in women, but there has been little research on the biological consequences to the fetus of paternal drug use or on the developmental effects of drug-abusing fathers as caregivers or as partners of drug-abusing mothers. Cocaine binds to human sperm in vitro, and studies have shown that extended use of cocaine increases the risk of lower sperm motility, lower sperm concentration, and higher proportion of morphologically abnormal sperm (Bracken et al., 1990; Yazigi et al., 1991). Thus, research is needed on the biological consequences, developmental outcomes, and psychological effects associated with parenting by a drug-abusing father.
Ongoing longitudinal research across geographic and sociodemographic ranges should be promoted to identify the health and developmental problems and delays caused by prenatal drug exposure or a drugabusing environment. As suggested earlier, the possibility of drug-related effects appearing either later in development or under stressful conditions later in life requires carefully maintained longitudinal cohorts. Studies to date have focused primarily on drug-abusing mothers in poor urban areas; the focus must be expanded to cover a wider geographic and socioeconomic range. Longitudinal studies also provide some modeling of the contribution of environmental disruption to the developmental course of apparent drug effects.
Studies of responsive caregiving in a stimulating social environment have shown the plasticity of neurobehavioral development and the potential that premature neonates have to catch up developmentally with full-term children (Beckwith and Parmalee, 1986; Kronstadt, 1991). Research is needed to study whether this plasticity is applicable to drugexposed infants because it will have important implications for preventive interventions and treatment efforts.
A major issue in neurotoxicology in general, as well as drug abuse research in particular, is how to measure noncognitive neurobehavioral outcomes (e.g., attention, affect regulation, social cognition) across the life span. Studies begun in the 1980s, during the height of crack cocaine use,
are just beginning to yield longitudinal data. This type of long-term research is critical for providing public and private programs with necessary data on the needs for treatment and prevention services.
Effects of Parental Drug Abuse
When an infant is born, parental abuse of illicit drugs or alcohol may continue, often resulting in a chaotic life-style and an environment with increased incidence of child neglect, child abuse, and a lack of social interaction or responsive caregiving (Mayes, 1995). Children without prenatal exposure may also suffer collateral health effects due to growing up in a drug-abusing household.8 There is strong correlation between parental drug abuse and child abuse and neglect (Kelleher et al., 1994; Dore et al., 1995). Additionally, children may be exposed to drugs and nicotine by accidental ingestion, breast-feeding, or passive inhalation. Children's exposure to environmental tobacco smoke increases the risk of respiratory infections (e.g., bronchitis, pneumonia), increases the severity of asthma symptoms, and is a risk factor for new cases of asthma in children (U.S. DHHS, 1993). As with research on prenatal exposure, many variables can be identified that affect the child's development (e.g., poor nutrition, lead exposure), making it difficult to isolate the effects due to drug abuse.
Numerous correlative findings suggest that drug abuse impairs parenting capacities (Mayes, 1995). These include the association of parental drug abuse with (1) other psychiatric disorders, including depression and antisocial personality; (2) multigenerational transmission of both drug abuse patterns and psychiatric disorders; (3) a high incidence of violence, both between adults and toward children; (4) an increased risk of abandonment and neglect; and (5) a generally poor sense of competence as a parent and a poor understanding of the needs of children. How those factors combine to influence an adult's interactive capacities with a child, and how child characteristics influence these patterns of adult interactiveness, are questions that are only now being studied systematically. It is likely that impairments in parenting (the withdrawn or excessively intrusive behaviors seen in observational studies of drug-abusing adults) are not related solely to drug abuse per se but are a cumulative reflection of the many psychological risk factors that accompany drug abuse. Many drug abusers also suffer from co-occurring psychiatric disorders such as depression, which adds to the potential for dysfunctional parenting (Burns et al., 1985; Zuckerman et al., 1989a).
The committee recommends continued research on the magnitude and extent of the effects of maternal drug abuse on the prenatally exposed infant and child over time and the effects on children of growing up in a drug-abusing household.
DRUG ABUSE AND VIOLENCE
Violence is a leading public concern in American society and is recognized as a major public health problem (Rosenberg and Fenley, 1991). The public health model—emphasizing prevention, research, and education— is being brought to bear on this devastating issue, and the CDC has made the prevention of violence one of its highest priorities (Rosenberg et al., 1992).
The complex and intertwined relationship between drug abuse and violence involves three primary links—systemic, economic, and pharmacological (Goldstein, 1985). It is noteworthy that different forms of violence are linked to different types of abused drugs. The systemic link, the most prevalent form of cocaine- and heroin-related violence, is the result of the violent nature of illicit drug selling and distribution (Goldstein, 1985; see Chapter 10). Illicit drug traffickers use violent acts or the threat of violence to protect and expand markets and to deal with competitors, buyers, or sellers suspected of cheating or with witnesses (BJS, 1992). A recent study of gun use found that it is predominantly sellers of illicit drugs, not users, who employ guns in their activities (Butterfield, 1995). Drug sales and crime are more strongly related than drug use and crime (Chaiken and Chaiken, 1990).
It is difficult to estimate the extent of systemic violence in the illicit drug trade. Police departments have reported that noticeable increases in violent crimes are associated with the sale and distribution of cocaine (Fagan and Chin, 1989). A 1987 study found that cocaine was involved in one-fifth of homicides in San Diego County (Bailey and Shaw, 1989). A 1993 National Research Council study estimated that crimes related to illicit drugs accounted for 10 percent of all homicides nationwide, more than 30 percent of homicides in certain cities, and more than 70 percent of homicides in high-risk areas of certain cities (NRC, 1993).
Income-generating crime is the indirect economic link between illicit drugs and violence. Drug-dependent individuals, particularly those dependent on heroin or cocaine, need substantial amounts of cash to support their drug habits, and some resort to robbery, motor vehicle theft, or other means of illegal and sometimes violently obtained income. In a 1991 survey of state prison inmates, 27 percent of those incarcerated for robbery reported committing the crime to obtain money to buy drugs
(BJS, 1993). However, the majority of crimes committed by drug users are of a nonviolent nature (e.g., shoplifting, prostitution) (Goldstein, 1985).
Pharmacological Effects of Drugs and Violence
One of the most complex and controversial links between drug abuse and violence has been the potential relationship between the pharmacological effects of alcohol or illicit drugs and violence. Individuals initially use alcohol or illicit drugs because they produce some noticeable change in mood or emotional state; the extent and nature of that change varies depending on the specific drug or drug combination and the individual. However, it is difficult to determine a simple cause-effect relationship between the pharmacological actions of alcohol or illicit drugs and an individual's violent behavior because of the many interacting physiological, psychological, and social variables, each of which can have an impact on the drug-violence connection (NRC, 1993). At the biological level, differences between individuals include the amount and chronicity of drug use as well as individual variations in endocrine mechanisms (e.g., modulation of aggression by androgens), neurotransmitter activity, and genetic interactions (Miczek et al., 1994a). At the psychosocial level, risk factors correlated with an increase in aggressive or violent behavior associated with alcohol and illicit drug use include gender (which may involve biological, expectational, and social factors) childhood aggression (associated with alcohol and violent behavior) and co-occurring psychiatric disorders (discussed in more detail below) (NRC, 1993). Macrosocial factors also play a determining role in the link between violence and drug abuse. There are striking cultural and subcultural differences associated particularly with alcohol use and violence (Miczek et al., 1994b). The drug user's expectations and the situation or environment in which drug use takes place are additional macrosocial factors. Research on the link between drug abuse and violence is also complicated by the difficulties inherent in replicating realistic conditions or precursors of violence in laboratory studies on animals or humans (see Chapter 2).
The following sections present an overview of current knowledge on the pharmacological links between drug abuse and violence, followed by a discussion on directions for future research. This overview draws heavily from recent comprehensive reviews of the literature (NRC, 1993; Miczek et al., 1994b).
Alcohol is the drug most studied and most closely associated with violence, although a simple cause-effect relationship has not been estab-
lished (see Gottheil, 1983; Brain, 1986; NRC, 1993). Studies have shown that chronic or problem drinkers have more frequent histories of violence and more previous arrests for violent crimes than comparable samples (Fagan, 1993; NRC, 1993). Alcohol use is a significant risk factor in domestic violence and sexual assault; studies have reported that 25-68 percent of batterers use alcohol and that the severity of abuse is correlated positively with alcohol use by the assailant (Rosenberg et al., 1992; Fagan and Browne, 1994). It is important to note, however, that most drinking events do not result in interpersonal violence.
Although there are wide individual differences, studies have shown arousing and aggression-heightening effects in the early phases of acute alcohol use in both animal and human studies (Miczek et al., 1994b). Chronic alcohol use and alcoholism also have symptoms associated with aggression, including depression, despair, insomnia, anxiety, and irritability. The neurobiological mechanism for alcohol's aggressive effects is currently being studied; proposed mechanisms have focused on brain serotonin metabolism and the GABAA receptor complex in the brain (Miczek et al., 1994b). Research has shown that alcoholism has a genetic component (see Chapter 5), although the nature of any genetic influence on alcohol-related violence has not been studied. Additionally, other psychiatric disorders may impact on the aggressive actions of alcohol abusers (Miczek et al., 1994b). Individuals with diagnosed antisocial personality disorder who abuse alcohol have increased prevalence of violent actions (Linnoila et al., 1983; NRC, 1993).
Opiates have a high abuse liability because they initially produce analgesia and a sense of tranquility or well-being. However, chronic use of opiates can lead to hostility, suspicion, and confusion. Withdrawal is characterized by depression and by heightened aggressive or defensive actions (Meyer and Mirin, 1979). The primary link between opiates and violence, however, has been reported in association with the need to support an expensive drug habit. Criminal activity significantly increases during times of narcotic dependence; although, crimes by heroin abusers are largely nonviolent property crimes (McGlothin, 1979; Miczek et al., 1994b).
Cocaine has a stimulant effect on the central nervous system, and users initially experience an increased sense of energy and sensory awareness. However, the crash that follows can result in irritability, fatigue,
depression, and/or anxiety (Gawin et al., 1994). Use of smokable crack cocaine produces a rapid and intense onset of euphoria (inhaled cocaine reaches the brain about eight seconds after smoking) (U.S. DHHS, 1991). Animal studies have shown that acute use of cocaine increased defensive reactions to stress but disrupted aggressive behavior and that chronic cocaine intake did not result in aggressive behavior (Moore and Thompson, 1978; Emley and Hutchinson, 1983). Chronic cocaine use in humans has been associated in a small number of cases with triggering a paranoid or psychotic state leading to aggressive or violent behavior (APA, 1994). As mentioned above, the cocaine drug trade is reported to be the most violent of all illicit drug trafficking.
Most studies of the pharmacological effects of lysergic acid diethylamide (LSD) and its relationship to violence were conducted in the 1960s and 1970s during the height of LSD use in the United States. Studies in humans show that LSD use is infrequently correlated with violence, but in cases where psychopathology predates LSD use, violent outbursts can be exacerbated (Miczek et al., 1994b).
Phencyclidine (PCP) use has been reported in some cases to be associated with violent behavior. However, it has been found that such individuals generally use PCP in conjunction with alcohol and other drugs (Miczek et al., 1994b). Animal studies have shown acute intake of PCP to be associated with inappropriate social signals, provocative actions, and hyperactivity which could be precursors of aggression (Tyler and Miczek, 1982; Schlemmer and Davis, 1983).
Marijuana users have been reported to have decreased aggression compared with nonusers (Cherek and Steinberg, 1987; Miczek et al., 1994b). Animal studies show that acute doses of THC, the psychoactive ingredient in marijuana, can inhibit attack or threat behavior (Miczek et al., 1994b). Large-scale studies of incarcerated adolescents found that marijuana was the drug least likely to be associated with sexual or assaultive crimes (Tinklenberg et al., 1976).
As noted, it is difficult to isolate the independent effect of the drug's pharmacology on an individual's violent behavior. Drugs may act as a cause, response, moderator, and/or mediator of violence (Fagan, 1993). Research is needed to determine the relationship between violence and the pharmacological effects of alcohol and illicit drugs in order to develop effective preventive interventions and treatment strategies, including research on patterns of alcohol and drug abuse involved in violent behavior and events in the early life history that are associated with violent behavior related to alcohol or drug abuse.
Although laboratory models should be developed to distinguish between the many confounding variables influencing the relationship between drug abuse and violence (Chapter 2), the difficulties inherent in replicating realistic conditions or precursory violence in the laboratory make this a formidable endeavor.
Violence, Drug Abuse, and Co-Occurring Psychiatric Disorders
There is evidence of a complex linkage among violence, drug abuse, and co-occurring psychiatric disorders. As discussed in Chapter 4, illicit drug and alcohol abuse are significantly more prevalent among persons who suffer from psychiatric disorders (e.g., schizophrenia, bipolar disorder, and depression) than among persons without psychiatric disorders and are particularly common among those with personality disorders9 (Regier et al., 1990). Those individuals with co-occurring psychiatric disorders and drug abuse who are also at risk for violent behavior tend to manifest poor outcomes in standard treatment programs and often receive no treatment at all. Thus, they pose a special challenge to the treatment system, as well as to the criminal justice system (Drake and Wallach, 1989; Bartels et al., 1993; Drake et al., 1993; Narrow et al., 1993; Regier et al., 1993). It also has been found that personality disorders often precede the onset of drug abuse and other psychopathologies in persons who become violent criminals (Robins et al., 1991; Hien and Levin, 1994; Kessler and Magee, 1994; North et al., 1994; Widiger and Trull, 1994). Contextual factors-including race, gender, age, discrimination, poverty, homelessness, stressful life events, the characteristics of social networks, and the quality of living environments-are all likely to exert significant moderating effects on the relationships among victimization, co-occurring psychiatric disorders, and violent behavior (Pianta and Egeland, 1994; Hiday, 1995).
Studies have shown that the co-occurrence of psychiatric disorders with alcohol or drug abuse is associated with significantly increased risk for violent behavior in adults (Lindqvist and Allebeck, 1989; Swanson et al., 1990; Swanson, 1993; Mulvey, 1994). Although persons with co-occurring psychiatric disorders and drug abuse comprise only about 3.3 percent of the population (Regier et al., 1993), a recent study found that 7 percent of those diagnosed for depression (without a drug abuse diagnosis) had a history of violence, compared with 21 percent if comorbid for
drug abuse and depression (Monahan, 1995). Of those with bipolar disorder (without drug abuse), 5 percent had a history of violence, compared to more than 12 percent of those comorbid for drug abuse and bipolar disorder.
Some of the most important findings regarding the co-occurrence of psychiatric illness, drug abuse, and violence in the general population come from the Epidemiologic Catchment Area (ECA) surveys. This study of more than 20,000 community and institutional residents in five metropolitan areas found lifetime rates of drug abuse or dependence disorders to be as high as 47 percent among respondents with schizophrenia, 32 percent for those with major depressive illness, 56 percent for persons with bipolar affective disorder, and 87 percent for those with antisocial personality disorder (Regier et al., 1990). In data pooled from three ECA sites, about 2 percent of respondents with no disorder reported some violent behavior occurring within a one-year period. By comparison, the violence rates were 7 percent among those with a major psychiatric disorder only (schizophrenia or affective disorder) and 22 percent among those with co-occurring psychiatric and drug abuse disorders.
In multivariable models that controlled for age, sex, race, socioeconomic status, and marital status, the co-occurrence of psychiatric and drug abuse disorders emerged as one of the strongest predictors of violence toward others. Certain demographic covariates also increased the risk of violence among respondents with co-occurring disorders; among younger adult males of lower socioeconomic status, who reported a history of arrest and hospitalization, the predicted probability of violent acts within one year was 64 percent (Swanson, 1994).
Four mechanisms have been proposed to explain the underlying relationship between co-occurring drug abuse and psychiatric disorders and violence (Smith and Hucker, 1994). The first hypothesis is that violence in this group is linked primarily to the chemical effects of psychoactive drugs (e.g., cocaine may stimulate impulsive and aggressive behavior; alcohol may have a disinhibiting effect, possibly reducing tolerance for frustrating situations). Such effects may occur at lower doses for people with underlying psychiatric disorders (Drake et al., 1990). Antisocial personality traits often underlie both drug abuse and violence, and those antisocial traits may co-occur with psychotic disorders or other major psychiatric disorders as well. A third proposed mechanism is that drug use may exacerbate psychiatric symptoms, such as paranoid delusional beliefs, which can lead to violent actions in response to perceived threats. Finally, it has been proposed that social and economic factors—such as poverty and crime in the surrounding environment—largely account for the increased risk of violence among persons with co-occurring psychiatric and drug abuse disorders (Hiday, 1995). Limited evidence exists for each of
those hypotheses individually; however, no studies to date have adequately assessed all of those factors together in an effort to examine their relative and interacting effects over time on interpersonal violence.
Although a sizable body of research has accumulated on selected aspects of violence, drug abuse, and co-occurring psychiatric disorders, key questions remain. They include the underlying mechanisms, developmental framework, and social context, as well as the long-term effectiveness of interventions that may be appropriate for this population. Thus, the committee urges a more comprehensive understanding of the risk factors associated with co-occurring psychiatric disorders and drug abuse and violence. Additionally, a more complete understanding of the types of interventions that may prove successful is needed.
The committee recommends research on violence, drug abuse, and co-occurring psychiatric disorders. Particular emphasis should be placed on the mechanisms underlying comorbidity and violent behavior and on developing effective prevention and treatment interventions.
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