Joint Treatment of PTSD and Cocaine Abuse May Reduce

Severity of Both Disorders (V18-1; June 2003) . . . . . . .1

New Animal Model Simulates Human Exposure,

Confirms Harm From Prenatal Cocaine

(V18-1; June 2003) . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

Substance-Abusing Adolescents Show Ethnic and Gender

Differences in Psychiatric Disorders 

(V18-1; June 2003) . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Animal Studies Show Sex Differences in Impact of Efforts

To Reduce Drug Seeking (V17-6; March 2003) . . . . . .8

Study Finds Significant Mental Deficits in Toddlers

Exposed to Cocaine Before Birth 

(V17-5; January 2003) . . . . . . . . . . . . . . . . . . . . . . . .10

Women and Smoking: Sensory Factors, Attitudes 

About Weight, Phase of Menstrual Cycle All Key To

Quitting (V17-4; November 2002) . . . . . . . . . . . . . . .12

Timing Quit Date May Help Women Smokers 

(V17-4; November 2002) . . . . . . . . . . . . . . . . . . . . . .14

Inhalant Abuse Among Young People

(V17-4; November 2002) . . . . . . . . . . . . . . . . . . . . . .15

Prenatal Exposure to Ecstasy May Impair Memory 

and Cognition (V17-3; October 2002) . . . . . . . . . . . .17

In Drug Abuse, Gender Matters 

(V17-2; May 2002) . . . . . . . . . . . . . . . . . . . . . . . . . . .19

Prenatal Exposure to Methamphetamine Increases

Vulnerability to the Drug’s Neurotoxic Effects in 

Adult Male Mice (V17-2; May 2002) . . . . . . . . . . . . .21

High-Risk Sex Is Main Factor in HIV Infection

for Men and Women Who Inject Drugs 

(V17-2; May 2002) . . . . . . . . . . . . . . . . . . . . . . . . . . .23

Cocaine’s Effects on Cerebral Blood Flow Differ 

Between Men and Women (V17-2; May 2002) . . . . .25

Childhood Sex Abuse Increases Risk for Drug

Dependence in Adult Women 

(V17-1; April 2002) . . . . . . . . . . . . . . . . . . . . . . . . . .27

Biochemical Brain Abnormality Found in 

School-Age Children Prenatally Exposed to Cocaine

(V16-4; October 2001) . . . . . . . . . . . . . . . . . . . . . . . 29

Similar Long-Term Effects Seen From Prenatal

Methamphetamine Exposure (V16-4; October 2001) . . 30

Pathological Obesity and Drug Addiction 

Share Common Brain Characteristics 

(V16-4; October 2001) . . . . . . . . . . . . . . . . . . . . . . . 31

NIDA Scientific Panel Reports on Prescription 

Drug Misuse and Abuse (V16-3; August 2001) . . . . . 33

Annual Survey Finds Increasing 

Teen Use of Ecstasy, Steroids (V16-2; May 2001) . . . 35

Adolescents, Women, and Whites More 

Vulnerable Than Others to Becoming Nicotine

Dependent (V16-2; May 2001) . . . . . . . . . . . . . . . . . 37

Maternal Smoking During Pregnancy 

Associated With Negative Toddler Behavior 

and Early Smoking Experimentation 

(V16-1; March 2001) . . . . . . . . . . . . . . . . . . . . . . . . . 38

Meeting the Challenge of Reducing 

Health Disparities (V16-1; March 2001) . . . . . . . . . . 40

Women and Smokeless Tobacco Use 

(V16-1; March 2001) . . . . . . . . . . . . . . . . . . . . . . . . . 41

Update on Nicotine Addiction And 

Tobacco Research (V15-5; October 2000) . . . . . . . . . 42

Drug Abuse and Conduct Disorder 

Linked to Maternal Smoking During 

Pregnancy (V15-5; October 2000) . . . . . . . . . . . . . . 43

Boys and Girls Encounter Different 

Drug Offers, Use Different Refusal 

Strategies (V15-4; September 2000) . . . . . . . . . . . . . . 44

Gender Differences in Drug Abuse 

Risks and Treatment (V15-4; September 2000) . . . . . 45

NIDA’s Epidemiological Compasses 

(V15-3; July 2000) . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

About Anabolic Steroid Abuse 

(V15-3; July 2000) . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

NIDA Initiative Targets Increasing 

Teen Use of Anabolic Steroids 

(V15-3; July 2000) . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Evidence Builds That Genes Influence 

Cigarette Smoking (V15-2; June 2000) . . . . . . . . . . . 51

Antibody May Treat PCP Overdose and Abuse, Also

Block Prenatal Harm (V15-2; June 2000) . . . . . . . . . 53

A Smithsonian Institution Seminar 

on Gender (V15-2; June 2000) . . . . . . . . . . . . . . . . . 55

Marijuana-Like Compound in Womb May 

Influence Early Pregnancy (V15-1; March 2000) . . . . 56

Facts About Drug Abuse and Hepatitis C 

(V15-1; March 2000) . . . . . . . . . . . . . . . . . . . . . . . . . 57

i

Table of Contents
UCLA Study Looks at Women in 

Treatment (V14-6; March 2000) . . . . . . . . . . . . . . . . 58

Female Rats Progress Quickly to 

Drug Abuse (V14-6; March 2000) . . . . . . . . . . . . . . . 59

NIDA Science Education Program 

Reaches Out to Young Rural Women 

(V14-5; December 1999) . . . . . . . . . . . . . . . . . . . . . . 60

High-Dose Methadone Improves Treatment 

Outcomes (V14-5; December 1999) . . . . . . . . . . . . . 61

The State of the Art in Drug Addiction 

Treatment (V14-5; December 1999) . . . . . . . . . . . . . 62

Support Group Improves Outcomes for 

Pregnant Drug Users (V14-4; November 1999) . . . . . 64

Twin Studies Help Define the Role of 

Genes in Vulnerability to Drug Abuse 

(V14-4; November 1999) . . . . . . . . . . . . . . . . . . . . . . 65

Drug Abuse and Mental Disorders: 

Comorbidity Is Reality (V14-4; November 1999) . . . 67

Gender Differences in Progression 

to AIDS (V14-3; September 1999) . . . . . . . . . . . . . . 69

Ethnic Identification and Cultural Ties May

Help Prevent Drug Use 

(V14-3; September 1999) . . . . . . . . . . . . . . . . . . . . . . 70

Drug Abuse Research Helps Curtail the 

Spread Of Deadly Infectious Diseases 

(V14-2; August 1999) . . . . . . . . . . . . . . . . . . . . . . . . 72

Infectious Diseases and Drug Abuse 

(V14-2; August 1999) . . . . . . . . . . . . . . . . . . . . . . . . 74

Drug Use Among America’s Teenagers 

Shows Slight Downward Trend 

(V14-1; April 1999) . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Study Shows How Genes Can Help Protect 

From Addiction (V13-6; March 1999) . . . . . . . . . . . . 77

NIDA Research Provides Data To Document 

and Improve the Effectiveness of Drug Abuse 

Health Services (V13-5; January 1999) . . . . . . . . . . . 78

New Publications Disseminate Research 

Findings on Nicotine (V13-5; January 1999) . . . . . . . 80

New NIDA Center Will Address Health 

Issues Associated With Drug Abuse 

(V13-5; January 1999) . . . . . . . . . . . . . . . . . . . . . . . . 81

Prenatal Cocaine Exposure Costs at 

Least $352 Million Per Year 

(V13-5; January 1999) . . . . . . . . . . . . . . . . . . . . . . . . 82

Men and Women in Drug Abuse Treatment 

Relapse at Different Rates and for Different 

Reasons (V13-4; November 1998) . . . . . . . . . . . . . . . 83

Researchers Find Gender Differences In 

How Drug Abusers Respond To HIV 

Prevention Strategies (V13-4; November 1998) . . . . . 85

Gender Matters in Drug Abuse 

Research (V13-4; November 1998) . . . . . . . . . . . . . . 86

Publications Focus On Women’s 

Health (V13-4; November 1998) . . . . . . . . . . . . . . . . 88

Facts About Nicotine and Tobacco 

Products (V13-3; July 1998) . . . . . . . . . . . . . . . . . . . 89

Exploring the Role of Child Abuse in 

Later Drug Abuse: Researchers Face Broad 

Gaps in Information (V13-2; June 1998) . . . . . . . . . . 90

Innovative Treatment Helps Traumatized 

Drug-Abusing Women (V13-2; June 1998) . . . . . . . . 93

NIDA Probes the Elusive Link Between 

Child Abuse and Later Drug Abuse 

(V13-2; June 1998) . . . . . . . . . . . . . . . . . . . . . . . . . . 95

NIDA’s “Report Card” (V13-1; June 1998) . . . . . . . . 97

Interagency Pacts and NIH Collaborations 

Extend NIDA’s Research Reach 

(V13-1; June 1998) . . . . . . . . . . . . . . . . . . . . . . . . . . 98

MERIT Awardee Examines Long-Term Effects 

Of Prenatal Cocaine Exposure in Rats 

(V13-1; June 1998) . . . . . . . . . . . . . . . . . . . . . . . . . 100

Contributions of Behavioral Research 

To AIDS Studies Recognized 

(V12-6; November/December 1997) . . . . . . . . . . . . 101

Study Sheds New Light on the State of 

Drug Abuse Treatment Nationwide 

(V12-5; September/October 1997) . . . . . . . . . . . . . 102

National Study Offers Strong Evidence of the

Effectiveness of Drug Abuse Treatment 

(V12-5; September/October 1997) . . . . . . . . . . . . . 107

Gender, Ethnicity, and Age Make a 

Difference In Drug Dependence 

(V12-5; September/October 1997) . . . . . . . . . . . . . 109

Steroid Prevention Program Scores With 

High School Athletes (V12-4; July/August 1997) . . . 110

Gender Affects Relationships Between 

Drug Abuse and Psychiatric Disorders 

(V12-4; July/August 1997) . . . . . . . . . . . . . . . . . . . . 113

ii
Women’s Dependence on Smoking Affected By 

Something in Addition to Nicotine 

(V12-3; May/June 1997) . . . . . . . . . . . . . . . . . . . . . 115

NIDA Responds to the Changing Dynamics 

of the AIDS Epidemic (V12-2; March/April 1997) . . 117

CDC Report Highlights Link Between 

Drug Abuse and Spread of HIV 

(V12-2; March/April 1997) . . . . . . . . . . . . . . . . . . . 119

Mental Health Problems of Addicted Mothers 

Linked to Infant Care and Development 

(V12-1; January/February 1997) . . . . . . . . . . . . . . . 121

National Survey of Drug Use During Pregnancy 

Available (V12-1; January/February 1997) . . . . . . . . . 123

Type A or B? Classification May Help in Treating 

Cocaine Abuse (V11-4; September/October 1996) . . 124

Drug Use During Pregnancy Associated With 

Increased Risk of Transmitting HIV to Infants 

(V11-4; September/October 1996) . . . . . . . . . . . . . . 127

Cocaine Affects Men and Women Differently, NIDA

Study Shows (V11-1; January/February 1996) . . . . . 128

Daughters of Mothers Who Smoked During 

Pregnancy are More Likely to Smoke, 

Study Says (V10-5; September/October 1995) . . . . . 130

31% of New York Murder Victims Had Cocaine in 

Their Bodies (V10-2; March/April 1995) . . . . . . . . . 132

NIDA Expands Its Research on Addiction and 

Women’s Health (V10-1; January/February 1995) . . 134

NIDA Survey Provides First National Data on 

Drug Use During Pregnancy 

(V10-1; January/February 1995) . . . . . . . . . . . . . . . . 136

Early Childhood Behavior and Temperament 

Predict Later Substance Use 

(V10-1; January/February 1995) . . . . . . . . . . . . . . . 138

Filling the Gender Gap in Drug Abuse 

Research (V10-1; January/February 1995) . . . . . . . . 142

About Women, Drug Abuse, 

and AIDS (V10-1; January/February 1995) . . . . . . . 144

Drug Use During Pregnancy 

(V10-1; January/February 1995) . . . . . . . . . . . . . . . . 145

iii

Joint Treatment of PTSD and Cocaine Abuse May Reduce Severity

of Both Disorders

By Robert Mathias, NIDA NOTES Staff Writer

Research Findings

Volume 18, Number 1 (June 2003)

Many individuals who abuse cocaine, alcohol, and other

substances also suffer from posttraumatic stress disorder

(PTSD) related to life-threatening or other traumatic

events they have experienced or witnessed. Individuals

with PTSD suffer recurring flashbacks, anxiety, and other

symptoms that can impede substance abuse treatment.

Similarly, substance abuse can make PTSD symptoms

worse. Thus, integrated treatment is recommended as the

way to treat patients with both disorders. Yet until recently, the most effective nonpharmacological treatment for

PTSD, known as exposure therapy, was considered too

risky to use with cocaine-dependent patients. The therapy

seeks to desensitize patients to the distressing emotional

effects of the trauma that triggered their PTSD by requiring them to repeatedly and graphically describe it.

“Researchers and clinicians have been reluctant to use

exposure therapy with cocaine-dependent patients,” says

Dr. Kathleen Brady of the Medical University of South

Carolina in Charleston. “Drug abuse patients were

thought to be likely to turn to alcohol and drugs to cope

with the emotional demands placed on them by recounting the fear-inducing experience.”

A preliminary study led by Dr. Brady suggests that the

belief that exposure therapy would do these patients more

harm than good may not be merited. In the study, instead

of triggering emotional distress and relapse to substance

abuse, treatment that combined exposure therapy for

PTSD with substance abuse counseling produced substantial improvement in both disorders.

Thirty-nine cocaine-dependent individuals with PTSD,

32 of them women, participated in the outpatient study.

The majority of participants had developed PTSD following such severe traumatic experiences as rape (74 percent),

aggravated assault (89 percent), and other physical assault

(95 percent). Individuals who feel intense fear and helplessness or horror during such terrifying events can later

develop distressing symptoms that can impair their ability

to live and work normally.

PTSD symptoms fall into three general categories: “intrusions,” such as flashbacks or nightmares in which the 

person reexperiences the traumatic event; “hyperarousal”

or anxiety, which can be marked by extreme vigilance and

jumpiness, difficulty sleeping or concentrating, and 

irritability; and “avoidance” of people, activities, and 

situations that might trigger memories of the incident.

When symptoms persist for more than 3 months, PTSD

is considered chronic. Chronic sufferers often have additional psychiatric disorders. An estimated 30 to 60 percent

of individuals with substance abuse disorders have PTSD,

according to studies cited by Dr. Brady.

The study used a psychotherapy developed by Dr. Brady

and her colleagues that combines counseling for drug

abuse with exposure therapy for PTSD. “We wanted to

evaluate whether cocaine-dependent PTSD patients could

1

Combination Psychotherapy Reduces Posttraumatic

Stress Disorder (PTSD) Symptoms and Cocaine Use

Fifteen cocaine-dependent patients with PTSD who completed

a psychotherapy that addressed both disorders significantly

reduced cocaine use and had fewer and less intense PTSD 

symptoms, as assessed by physicians.
safely tolerate the therapy and whether it would be effective in reducing the severity of their PTSD symptoms and

cocaine use,” Dr. Brady says. The combined therapy consists of 16 90-minute individual sessions. In the first 3

weeks, patients participate in two counseling sessions a

week that concentrate solely on their drug abuse problems

and developing relapse prevention skills. “The therapy in

those first sessions gives people a chance to experience

some sobriety and provides them the coping techniques

and strategies they will need to deal with high-risk situations and the urges to use drugs they may experience

when they get into the exposure therapy,” Dr. Brady says.

Once patients start to feel comfortable sharing their feelings with the therapist and are willing to engage in exposure therapy, a technique called imaginal exposure is used

to address their PTSD symptoms. In imaginal sessions,

patients describe in detail the circumstances and feelings

they experienced during the traumatic event that triggered

their disorder. They also develop a list of situations or

places they have been avoiding because they associate

them with the event. Between sessions, patients carry out

assignments in which they gradually expose themselves to

similar situations that are safe but fear-inducing. If, for

example, they were abducted from a parking lot and

assaulted, they may have become fearful of any parking lot

or areas with cars in them. Assignments could involve

going to such areas, first with a friend, then by themselves

in the middle of the day. 

“We are trying to get at the irrational fears and inappropriate avoidance of situations that are interfering with

their lives,” Dr. Brady says. “By talking about their experience over and over in the imaginal sessions, they are basically reliving it. The point of the exposure is to desensitize

them to the trauma, thereby reducing the fear, anxiety,

and emotion from the memory itself. By the end of successful therapy, patients are able to go through their entire

traumatic scenario and feel much less distressed because

they are able to separate irrational fears from simply thinking about the event.”

The goal of the therapy is that the intrusion, arousal, and

avoidance symptoms all recede. The exposure has done its

job when someone can go through his or her detailed

recalling of the event and score no higher than 5 on a 20-

point scale that measures how much distress they are feeling, says Dr. Brady. 

Fifteen of the 39 study participants completed the combined therapy, attending at least 10 of the 16 sessions,

including a minimum of 3 exposure therapy sessions.

Assessments by both patients and clinicians indicated that

those who completed treatment experienced significant

reductions in all three PTSD symptom categories and in

cocaine use from study entry to treatment completion.

Using a self-administered Impact of Events Scale, patients

reported a 53-percent reduction in “intrusion” symptoms

and a 27-percent reduction in inappropriate avoidance

behaviors. Over the same period, clinicians using a 30-

item structured clinical interview tallied a 66-percent

reduction in “intrusions,” a 70-percent reduction in

“avoidances,” and a 47-percent reduction in hyperarousal

symptoms. By the end of treatment, completers also had

reduced cocaine use by 60 percent and reported experiencing significantly fewer substance-related problems.

Followup assessments indicated that treatment completers

had maintained these improvements in both PTSD symptoms and cocaine use 6 months after treatment ended. In

contrast, no differences emerged in any PTSD or substance-abuse-related scores at treatment completion or 6

months later among noncompleters. 

“This study provides promising preliminary evidence that

exposure therapy can be used safely and effectively in

treating PTSD in some cocaine-dependent individuals

without increasing the risk of relapse,” says Dr. Brady. The

improvements in PTSD symptoms were comparable to

those reported by other studies that used exposure therapies to treat patients with no substance abuse disorder.

Dropout rates, though high, also were similar to those in

previous studies that used other psychotherapies to treat

cocaine-dependent patients.

Nevertheless, the small number of patients in the study

and the high dropout rates underscore the need for randomized controlled studies to replicate these results, Dr.

Brady cautions. Such studies also could provide information that would help to identify patients who are likely to

benefit from this treatment, as well as those who might

need different approaches.

Source

• Brady, K.T., et al. Exposure therapy in the treatment

of PTSD among cocaine-dependent individuals:

Preliminary findings. Journal of Substance Abuse

Treatment 21(1):47–54, 2001. 

2
New Animal Model Simulates Human Exposure, Confirms Harm

From Prenatal Cocaine

By Kimberly Martin, NIDA NOTES Contributing Writer 

Research Findings

Volume 18, Number 1 (June 2003)

Research has shown that some children exposed in the

womb to cocaine may have memory and attention deficits

that hinder their ability to learn. These children also may

have difficulties completing complex tasks or tests that

involve distractions, and they tend to perform poorly on

visual recognition memory and attention tasks.

Now, Dr. Bret Morrow and his colleagues at Yale

University have demonstrated in rats that prenatal exposure to cocaine may cause long-term changes in an area of

the brain responsible for short-term memory. Previous

animal studies have reported negative effects of cocaine on

cognitive performance, but doubts persisted about the

applicability of study results to humans. The new findings

help allay those doubts, which are based partly on differences in how people use cocaine and in how cocaine was

administered to rats in earlier experiments. By designing

an experiment that closely simulates the way humans use

cocaine, the Yale team has enhanced the applicability of

cognitive impairment in rats prenatally exposed to cocaine

to that observed in children.

“To more closely replicate the way human fetuses are

exposed to cocaine, we administered the drug to the pregnant rats intravenously. This enabled us to use dosages

similar to those taken by people. Also, the way cocaine is

absorbed and metabolized when it is administered intravenously is much closer to what we see in humans,” says

Dr. Morrow. “Additionally, tests commonly used in rat

studies to assess cognitive deficits—maze and swimming

tests—rely on artificial manipulation of the animal’s 

environment, such as food restriction, reward, or stress.

Our test, a two-object recognition task that relied on the

rat’s own motivation to complete the task, is comparable

to one used with human infants to assess short-term 

memory.”

Cocaine was administered to pregnant rats twice a day for

11 days before they gave birth. At ages equivalent to

human adolescence and adulthood, the male offspring

were placed in a cage with two identical objects, allowed

to explore the objects, then removed from the cage. After

delays of 20 minutes, 1 hour, and 24 hours, the rats were

returned to the cage with one of the former objects and a

new object. The time a rat spent actively exploring the

new and former objects was recorded. If he spent more

time exploring the new object, the rat was considered to

remember the former object. To count as “exploring”

time, the rat had to be actively exploring the object, with

his nose within about 2 cm of the object.

“The rats that were not exposed to cocaine spent more

time exploring the novel object than the familiar object

after 20-minute and 1-hour delays, but not after 24

hours,” says Dr. Morrow. "We interpreted this behavior as

memory of the familiar object from the previous exposure.

The rats that were prenatally exposed to cocaine did not

demonstrate a preference for the novel object over the

familiar object at any time. This behavior was interpreted

as their having no memory of the familiar object. These

findings indicate that in the rat model, prenatal exposure

to cocaine may result in long-lasting deficits in short-term

memory.”

In a separate study, the researchers found that adolescent

rats prenatally exposed to cocaine as described above had

long-term changes in the frontal cortex. They showed

excess activation of neurons in the prefrontal cortex, the

brain area governing short-term memory. Activation was

3

This rat is exploring an object during the two-object recognition

task. He was previously exposed to one object, whereas the other

is new. The rat was considered to remember the former object if

he spent more time exploring the new one. Rats exposed to

cocaine before birth did not demonstrate a preference for the

new object, indicating no memory of the familiar object.

Two-Object Recognition Test Mimics Test 

Used with Infants

Photo credit: Dorothy Cameron, the Johns Hopkins University BloombergSchool of Public Health.
measured by the concentration of Fos, a protein produced

by excited neurons. “Fos activation during development

can change the way a neuron responds in the future; in

other words, it undergoes a long-term adaptation,” says

Dr. Morrow. “In some cases, this may indicate important

adaptations that help the animal meet new challenges.

However, in cocaine-exposed animals, we believe that the

excessive Fos activation may lead to deficits in attention

and memory.”

“This type of animal model is valuable in guiding research

into the possible mechanisms and consequences of exposure to drugs of abuse during human development,” says

Dr. Laurence Stanford of NIDA’s Division of Treatment

Research and Development. “Animal models allow us to

reduce the number of variables and confounding factors

that are present when pregnant women abuse drugs.

Research with children strongly suggests a significant dose

effect, with the severity and presence of deficits linked to

the extent of exposure. Maternal health may also play a

role in the effects of prenatal drug exposure. For example,

the appetite-suppressing effects of cocaine and resulting

nutritional deficits can contribute to growth retardation in

the womb. For the purposes of reducing the number of

variables, and thus attempting to isolate the effects of 

prenatal cocaine exposure, this research is a valuable 

experiment.”

“This animal model may prove valuable not only for

probing neurological and cognitive deficits caused by 

prenatal cocaine exposure, but also for testing potential

therapies,” says Dr. Susan Volman of NIDA’s Division of

Neuroscience and Behavioral Research.

Sources

• Morrow, B.A., et al. Prenatal cocaine exposure disrupts nonspatial, short-term memory in adolescent

and adult male rats. Behavioral Brain Research 129

(1-2):217–223, 2002.

• Morrow, B.A., et al. Male rats exposed to cocaine in

utero demonstrate elevated expression of Fos in the

prefrontal cortex in response to environment.

Neuropsychopharmacology 26(3):275–285, 2002. 

4
Substance-Abusing Adolescents Show Ethnic and Gender

Differences in Psychiatric Disorders

By Kimberly Martin, NIDA NOTES Contributing Writer 

Research Findings

Volume 18, Number 1 (June 2003)

NIDA researchers have found that the patterns of cooccurring psychiatric disorders in adolescent substance

abusers differ between ethnic groups and between boys

and girls. This information may help clinicians be particularly alert to symptoms of the most common psychiatric

disorders when interviewing patients from each group.

Eventually, it may aid in the development of tailored

screening, assessment, and treatment interventions for 

different groups.

Ethnic Differences

Dr. Michael Robbins and colleagues from Florida’s

University of Miami found high rates of psychiatric disorders among Hispanic and African-American adolescent

substance abusers referred for outpatient therapy. Their

study distinguished externalizing disorders—characterized

by lack of self-control and acting-out behaviors, recurring

patterns of aggression, and behaviors that prevent the

development and maintenance of relationships—from

internalizing disorders, typified by sadness, withdrawal,

avoidance of interaction with others, and loss of interest 

in activities.

“Studies have consistently documented high rates of psychiatric disorders among adolescent substance abusers.

They also have found that certain co-occurring disorders

are associated with certain treatment outcomes. For example, depression or attention-deficit/hyperactivity disorder

(ADHD) may contribute to early dropout and poor treatment outcomes,” says Dr.

Robbins. “Therefore, treating

substance abuse alone may

not be enough. Treatment

providers need to address the

constellation of emotional

and behavioral problems presented by each individual.”

The researchers recruited 167

Hispanic and AfricanAmerican 12- to 17-year-olds

referred for outpatient treatment for substance abuse

between October 1997 and

March 2000. Participants’

substance use was assessed

before treatment with the

Adolescent Drug Abuse

Diagnosis, a standard assessment tool that provides information on the frequency of

use of alcohol, marijuana,

cocaine, and other drugs during the preceding month. The

youths also completed the

Diagnostic Interview Schedule for Children—Predictive

Scales, a questionnaire that screens for nine psychiatric

disorders, including social phobias, panic, anxiety, major

depression, ADHD, oppositional defiant disorder (ODD),

and conduct disorders (CD).

Dr. Robbins and colleagues found that Hispanic and

African-American youths were similar in the drugs they

used and their overall prevalence of co-occurring psychiatric disorders. More than 80 percent of the participants

reported using marijuana, and about 17 percent and 35

5

• Recurring patterns of aggression 

• Excessive arguing 

• Use of physical or verbal coercion 

• Noncompliance with reasonable

requests 

• Persistent pattern of tantrums 

• Persistent pattern of lying or stealing 

• Lack of self-control, acting-out

behavior 

• Behaviors that prevent development

or maintenance of relationships 

• Sad affect, depression, feelings of

worthlessness 

• Auditory or visual hallucinations 

• Constant repetition of certain

thoughts, ideas, or situations 

• Repetitive and useless actions 

• Frequent crying, atypical affect 

• Severe headaches or other somatic

problems 

• Talk of suicide 

• Decreased interest in activities 

• Restricted activity levels 

• Withdrawal, avoidance of interactions, lack of personal care

Externalizing Behaviors Internalizing Behaviors

Typical Behaviors in Adolescent Psychiatric Disorders
percent reported using cocaine and alcohol, respectively.

Overall, 87 percent of the youths reported symptoms of at

least one co-occurring psychiatric disorder. Of these,

about 19 percent reported symptoms for only one disorder, while more than 54 percent reported symptoms of

three or more disorders.

Hispanic youths had significantly more symptoms of

externalizing psychiatric disorders, such as ADHD and

ODD, than did African-American youths. More than 78

percent of Hispanics reported symptoms of at least one

externalizing disorder, compared with about 65 percent of

African-American youths. However, about twice as many

African-American adolescents reported symptoms for agoraphobia, an internalizing psychiatric disorder that finds

the sufferer severely anxious about going outside the

home. The researchers note, though, that the high rates of

symptoms associated with agoraphobia may instead reflect

legitimate fears about being in very dangerous public 

settings.

“Our findings suggest that substance abuse among

Hispanic youths may occur more often within a larger

context of problem behaviors,” says Dr. Robbins. “In

addition to enhancing Hispanic youths’ emotional and

behavioral functioning, interventions need to address

problems with their families, schools, peer group, and

other areas where co-occurring externalizing behaviors

often have severe and profound consequences.”

Dr. Robbins observes that his findings may be relevant

primarily to youths referred for outpatient treatment,

rather than all Hispanic and African-American substanceabusing youths. “We believe substance abuse among

African-American youths may be related to problem

behaviors as well. Our sample drew from community outpatient referrals. Further research is warranted to determine if there is a basic difference between ethnic groups in

the constellation of behavior problem symptoms or if our

numbers reflect a bias in the way youths are referred to

outpatient treatment. African-American youths may be

more likely to be referred to

other types of treatment

providers or sent to jail or

detention.”

Gender Differences

Dr. William Latimer and colleagues at the Johns Hopkins

University, Bloomberg School

of Public Health, in Baltimore,

and the University of

Minnesota, Twin Cities,

Minneapolis, examined gender

differences in rates of co-occurring psychiatric disorders in

substance-abusing adolescents.

They found that more male

teenage substance abusers also

had disruptive disorders, whereas females had higher rates of

depression.

“Gender may be useful in helping clinicians who assess youths

referred to drug treatment by

signaling the likely presence of

certain psychiatric disorders for

males and females. However,

clinicians should not rule out

the possibility of a disorder

based on the patient’s gender.”

says Dr. Latimer. “For example,

although co-occurring disruptive disorders are more common among males than

6

Co-Occurring Psychiatric Disorders Vary by Ethnicity and Gender in

Adolescent Substance Abusers (by Percent)

Psychiatric Disorder0

Attention-deficit/hyperactivity

disorder

Oppositional defiant disorder

Conduct disorder

Any disruptive behavior disorder

Agoraphobia

Major depressive disorder

Any mood disorder

African 

Americana

N=77

20.8%

41.6

53.6

NAc

40.3

26.0

NAc

Hispanica

N=90

41.4%

60.5

56.6

NAc

19.5

33.3

NAc

Femaleb

N=34

23.5%

26.5

47.1

76.5

NAc

44.1

50.0

Maleb

N=101

45.5%

18.8

72.3

94.1

NAc

16.8

36.6

Externalizing Behaviors

Internalizing Behaviors

a Robbins et al., Journal of the American Academy of Child and Adolescent Psychiatry, 2002.

Percentages indicate a probability estimate of the presence of psychiatric disorders.

b Latimer et al., Experimental and Clinical Psychopharmacology, 2002.

c Data not available.

Among substance-abusing youths referred for outpatient substance abuse treatment, Hispanics reported higher rates of externalizing disorders than did African Americans, while African Americans

reported higher rates of the internalizing disorder agoraphobia. In a separate study of adolescent substance abusers, boys were more likely to be diagnosed with externalizing disorders, while young

women were more likely to be diagnosed with depression, an internalizing disorder.
females, this shouldn’t obscure the equally important finding that high rates of these disorders are also present

among substance-abusing females.”

The researchers recruited 135 adolescents (ages 12 to 19)

who met the Diagnostic and Statistical Manual of Mental

Disorders criteria for one or more psychoactive substance

use disorders (PSUD), including alcohol abuse or dependence, marijuana abuse or dependence, and abuse or

dependence on drugs other than alcohol and marijuana.

Adolescents and their parents

completed the Diagnostic

Interview of Children and

Adolescents, which provided

information about PSUDs

and symptoms of ADHD,

ODD, CD, and mood disorders. Adolescents also completed the Personal

Experience Inventory, which

provided information about

3-month, 12-month, and lifetime alcohol and other drug

use frequencies and related

consequences. Adolescents’ reports of substance abuse

were verified by urine tests.

About 68 percent of the girls and 75 percent of the boys

were diagnosed with alcohol abuse or dependence, while

about 85 percent of the girls and 93 percent of the boys

were diagnosed with marijuana use disorders. More than

17 percent of the girls and 21 percent of the boys were

diagnosed with abuse or dependence on some other drug

or drugs. The patterns of single-substance versus polysubstance use also varied with gender. Girls were more likely

to be diagnosed with abuse or dependence on only one

drug, while boys were more likely to be diagnosed with

simultaneous abuse or dependence on more than 

one drug.

The researchers found that nearly twice the percentage of

teenage male substance abusers had co-occurring ADHD

or CD compared with female teen abusers, whereas

roughly three times the percentage of females had a 

co-occurring major depressive disorder. However, both

genders had similar rates of mild depression (dysthymia),

double depression (chronic depression with episodes of

major depression), and bipolar disorders.

“Drug abuse and psychiatric disorders co-occur at

extremely high rates in adolescents,” says Dr. Latimer.

“Therefore, drug treatment programs may be more 

effective if strategies that address multiple patterns of

simultaneously occurring disorders are included. Those

geared toward adolescent boys may benefit by incorporating strategies that address psychiatric problems related to

behavioral dysfunctions, while those intended for adolescent girls may need to include therapies that address major

depression.” Further examination of how simultaneously

occurring psychiatric and

substance abuse disorders

interact is needed, he notes.

“When a group of patients

shares a characteristic, such as

age or gender, it seems reasonable to expect that they

might require a treatment

sensitive to that characteristic,” says Dr. Melissa

Racioppo of NIDA’s

Behavioral Treatment

Development Branch. “But it is also possible that a characteristic may be irrelevant to treatment outcome. Drs.

Robbins’ and Latimer’s studies help identify characteristics

of groups of substance abusers, which lays the groundwork

for testing the relevance of these characteristics to treatment interventions. In the future, we may have effective

behavioral treatments that appropriately attend to gender

and racial/ethnic differences among adolescent substance

abusers.”

Sources

• Latimer, W.W., et al. Gender differences in psychiatric

comorbidity among adolescents with substance use disorders. Experimental and Clinical Psychopharmacology

10(3):310–315, 2002.

• Robbins, M.S., et al. Ethnic differences in comorbidity among substance-abusing adolescents referred to

outpatient therapy. Journal of the American Academy

of Child and Adolescent Psychiatry 41(4):394–401,

2002. 

7

Girls were more likely to be diagnosed

with abuse or dependence on only

one drug, while boys were more likely

to be diagnosed with simultaneous

abuse or dependence on more than

one drug. 
Animal Studies Show Sex Differences in Impact of Efforts To

Reduce Drug Seeking

By Jill Schlabig Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 6 (March 2003)

In recent studies, Dr. Marilyn Carroll and her colleagues

at the University of Minnesota looked at the impact of

two interventions on self-administration of heroin and

cocaine by rats and found that, in each case, the intervention produced a greater effect on the female rats studied

than on the male rats. These findings and the results of

other studies looking at sex differences suggest that the

most effective drug abuse treatments for men and women

may be quite different.

In one study, Dr. Carroll found that administering

baclofen, a muscle relaxer, suppressed the establishment of

cocaine use significantly more in female rats than in

males. The other study looked at the effect of offering

wheel-running as an alternative to drug-seeking behavior;

again, the result was that only female rats significantly

decreased their levels of drug self-administration—in this

case, cocaine.

“These studies highlight the importance of paying attention to sex differences in the development of pharmacotherapies and in other drug abuse research,” says Dr.

Cora Lee Wetherington, NIDA’s women and gender

research coordinator. “For example, some smoking cessation medications seem to work better for men; others

work better for women. As new medications are developed

for other forms of drug abuse, the story may be similar.

Treatment effects may not be the same in males and

females.” 

“We are increasingly finding that sex and hormonal status

are important determinants of drug abuse at all phases of

addiction—acquisition, maintenance, escalation/dysregulation, and reinstatement,” says Dr. Carroll, whose previous animal research has consistently found that females

tend to use more drugs, more quickly. Recent epidemiological data indicate that in humans, females also tend to

progress to dependence at a

faster rate than males. 

In the first study, Dr. Carroll and

her colleagues examined the

effects of baclofen on 44 rats

that had never been exposed to

cocaine. Previous animal studies

have demonstrated the promise

of baclofen, which modulates

several neurotransmitter systems,

as a potential treatment medication. Each rat participated in 30

daily sessions. During the first

six hours of each session, the rats

were given repeated, random

infusions of baclofen at a relatively low dose of 0.2 mg/kg. For

each infusion, a lever extended

into the cage where it stayed for

15 seconds, after which the

cocaine was administered and

the lever retracted. If the animal

touched the lever during the 15-

second latency period, cocaine

was administered immediately.

In this manner, the rats learned

within a few days to associate the

8

Pretreatment with baclofen has been shown to slow the establishment of cocaine use in rats.

Among rats pretreated with baclofen, only 15.4 percent of females self-administered an average of

100 cocaine infusions for 5 consecutive days during a 30-day trial, compared to 77.7 percent of

males. Under saline pretreatment, all of the animals tested reached this injection frequency and

consistency within 30 days.

Baclofen Slows Establishment of Cocaine Use in Females More Than Males
lever with drug infusions and to push the lever to selfadminister cocaine. A second 6-hour component each day

allowed the rats to freely self-administer cocaine; the lever

remained extended into the cage and a dose of cocaine

was delivered each time the lever was pressed.

To test the effects of baclofen on the rate of acquisition of

a habit of regular drug-taking, investigators divided the

rats into four groups. One male and one female group

were injected with baclofen prior to each session; another

male and another female group were pretreated with

saline. Researchers measured the number of infusions each

rat received during the self-administration session until it

reached the acquisition criterion or level at which it was

considered to have developed a habit of cocaine use,

defined as an average of 100 infusions per day for 5 days.

All of the female rats pretreated with saline reached the

acquisition criterion by day 14. All males pretreated with

saline met the criterion by day 19. In the group of female

rats pretreated with baclofen, only 15.4 percent met the

acquisition criterion within the 30-day limit. In contrast,

77.7 percent of males pretreated with baclofen met the

criterion within the 30-day limit. When baclofen treatment was discontinued, all of the females who initially did

not meet the acquisition criterion did so within 11 days.

“Pretreatment with baclofen slowed the rate at which the

rats reached the specified level of cocaine self-administration and reduced the percentage of rats reaching that level

to a greater extent in females than in males,” says Dr.

Carroll. “The propensity of the female rats to use cocaine

at the specified levels was no different than that of the

males, because they all acquired a habit of cocaine use

without baclofen. It was just that the baclofen had a different effect on the females.”

The next study looked at sex differences identified as a

result of a behavioral intervention to reducing drug use.

“Enriching the environment is a promising approach to

reducing the initiation, maintenance, and reinstatement 

of drug abuse,” says Dr. Carroll. (See also, “Social

Environment Appears Linked to Biological Changes in

Dopamine System, May Influence Vulnerabilility to

Cocaine Addiction,” NIDA NOTES Vol. 17, No. 5.) 

In this study, rats were offered access to a running 

wheel as an alternative to self-administering cocaine. 

Wheel-running is an activity rats enjoy, and research 

has shown that when given a choice between food and

running wheels, rats often chose running over eating. 

Seventeen rats were initially given access to a running

wheel alone until their average daily number of wheel

rotations stabilized. Next, rats were trained to self-administer cocaine (0.2 mg/kg) until they reached an average of

100 infusions a day for 5 consecutive days. The rats were

then given concurrent access to cocaine and the running

wheel. Researchers calculated the mean number of wheel

rotations and mean number of cocaine infusions during

the last five sessions of each phase.

Under cocaine-only conditions, both males and females

averaged 30 infusions per hour. Females saw a reduction

of 70.6 percent in infusions to fewer than 10 per hour

when there was concurrent access to the running wheel. In

males, while infusions decreased slightly (21.9 percent) to

an average of 25 infusions per hour, the reduction was not

statistically significant.

“Taken together, these studies suggest that females rats are

more responsive than males to treatments for drug abuse,”

says Dr. Carroll. Although few data exist on sex differences regarding treatment of drug abuse in humans,

research is beginning to point to hormones as one cause of

sex differences in drug abuse. “A growing body of research

indicates that ovarian hormones, such as estrogen, may

account for many of the sex differences in drug abuse,

increasing the subjective effects of drugs and their reinforcing potential.” More studies are needed, both in animals and humans, to better understand these sex differences and to use this knowledge to improve treatment

options.

Sources

• Campbell, U.C.; Morgan, A.D.; and Carroll, M.E.

Sex differences in the effects of baclofen on the acquisition of intravenous cocaine self-administration in

rats. Drug and Alcohol Dependence 66:61–69, 2002. 

• Cosgrove, K.P.; Hunter, R.G.; and Carroll, M.E.

Wheel-running attenuates intravenous cocaine selfadministration in rats: Sex differences. Pharmacology

Biochemistry and Behavior 73:663–671, 2002. 

9

Having access to a running wheel as an alternative to drug-seeking

behavior caused a 70-percent reduction in cocaine self-administration among females. The difference for males was not statistically

significant. In succession, the rats studied were given access to (1)

cocaine only; (2) cocaine and the wheel; and (3) cocaine only.
Study Finds Significant Mental Deficits in Toddlers Exposed to

Cocaine Before Birth

By Robert Mathias, NIDA NOTES Staff Writer 

Research Findings

Volume 17, Number 5 (January 2003)

Since the mid-1980s, up to 1 million children born in the

United States are estimated to have been exposed to

cocaine in the womb. Determining cocaine’s impact on

these children’s development has been difficult because

there often are other possible explanations for physical and

mental problems the children may have, such as the

mother’s use of other substances during pregnancy and

poor prenatal care. Now, a NIDA-supported study that

was able to separate the effects of cocaine from those of

many other such factors has found that children born to

poor, urban women who used cocaine throughout pregnancy were nearly twice as likely as children with similar

backgrounds but no prenatal cocaine exposure to have significant cognitive deficits during their first 2 years of life.

The study, led by Dr. Lynn Singer of Case Western

Reserve University in Cleveland, Ohio, is the first to show

a clear association between prenatal cocaine exposure and

cognitive impairment in 2-year-olds. “Since cognitive performance at this age is indicative of later performance,

these children may continue to have learning difficulties

that need to be addressed when they reach school age,”

Dr. Singer says. 

“The findings of this well-controlled study make an

important contribution to a growing body of knowledge

about the effects of prenatal cocaine exposure that may

help us to identify those exposed children who are at

increased risk of developmental harm,” says Dr. Vince

Smeriglio of NIDA’s Center on AIDS and Other Medical

Consequences of Drug Abuse. Previous findings from

other NIDA-supported studies that have been following

cocaine-exposed children from birth have produced conflicting results about cocaine’s impact on developmental

outcomes at this age, he notes. “Comparing and contrasting the circumstances in this study with those found in

other studies of cocaine-exposed children may enable us to

identify specific biological and environmental factors that

increase or reduce the developmental risk from cocaine

exposure,” Dr. Smeriglio says.

The study followed a group of 415 infants born at a large

urban teaching hospital from 1994 through 1996 to

mothers from low socioeconomic backgrounds who had

been identified by the hospital staff as being at high risk of

drug abuse. Women who participated in the study were

given urine tests for drug use immediately before or after

delivery and interviewed shortly after they gave birth to

produce estimates of the type, frequency, and amounts of

drugs they had used during pregnancy. Each baby’s first

stool, known as meconium, also was analyzed for the presence of cocaine and its metabolites to help establish the

level of drug exposure. Of the 415 babies in the study,

218 had been exposed to cocaine and 197 had not. Both

groups of infants also had been exposed to tobacco, alcohol, and marijuana during pregnancy.

10

Mental Development Scores For Prenatally CocaineExposed and Unexposed High-Risk Children

Tests of mental development at 6.5, 12, and 24 months showed

average scores of cocaine-exposed and unexposed children from

comparable backgrounds were below the normative score of 100

for children in the general population. At age 2, cocaine-exposed

children did significantly poorer in mental development than

children in the comparison group.
Researchers measured the children’s developmental

progress at 6.5, 12, and 24 months of age with the Bayley

Scales of Infant Mental and Motor Development. Motor

tests assessed the infants’ ability to control and coordinate

their movements. Mental tests assessed language, memory,

and ability to solve problems at 12 and 24 months. For

example, children were asked to describe objects in pictures, remember where an object had been hidden, and

put shaped objects into the correct spaces cut out on form

boards.

To isolate cocaine’s effect, researchers adjusted test results

for the effect of other risk factors, such as other drugs used

during pregnancy; characteristics of biological mothers

and alternative caregivers; the infants’ head size, weight,

length, and gestational age at birth; and the quality of

their postnatal home environments. The analysis showed

that while prenatal cocaine exposure had not affected the

infants’ motor development, it was clearly linked to significant deficits in their cognitive performance at age 2.

Cocaine-exposed children scored 6 points lower on the

Mental Development Index (MDI), averaging 82.7 percent compared to 88.7 percent for unexposed children

and an average general population score of 100. Other

findings include the following:

• From 6.5 to 24 months, MDI scores declined for

both groups, but cocaine-exposed children had a

greater decline—14 points compared to a 9-point

decline for unexposed children.

• Almost 14 percent (13.7 percent) of cocaine-exposed

children had scores in the mental retardation range,

below 70 on the MDI, nearly twice the 7.1-percent

rate found in the unexposed children and almost five

times the rate (about 2.8 percent) expected in the

general population.

• Nearly 38 percent (37.8 percent) of cocaine-exposed

children had developmental delays requiring remedial

intervention, nearly double the 20.9 percent rate for

unexposed children. 

The study found that other influences, including the

mother’s intelligence scores and educational level, exposure

to other substances, and the quality of the postnatal home

environment, also played significant roles in poor outcomes for cocaine-exposed children. “However, after controlling for these factors in our analysis, we found 

that cocaine still has a harmful effect on cognitive 

performance,” Dr. Singer says. Additional support for this

conclusion comes from mothers’ self-reports and biological data from mothers and infants that established a direct

link between cocaine dose and toddlers’ cognitive performance. These data showed that children of mothers

who used more cocaine and used it more frequently during pregnancy performed worse on the MDI than children

of mothers who used less of the drug.

“The only risk factor we couldn’t completely control for is

the effect of other drugs used during pregnancy,” Dr.

Singer says, “because it is nearly impossible to find children who have been exposed only to cocaine.” The study

partially adjusted for this influence by including children

who had been heavily exposed to alcohol, tobacco, and

marijuana in both groups. “Animal studies suggest there

are possible synergistic effects of these drugs in combination, and the study may not have been large enough to

control for these effects,” she notes. 

“We believe that cocaine exposure is a neurologic risk factor that may take a poor child who has a lower IQ potential because of maternal and other risk factors and push

him or her over the edge to mental retardation,” Dr.

Singer says. For example, average IQ scores for both

cocaine-exposed and unexposed toddlers in the study were

well below the average score for the general population.

“In effect, cocaine lowered the range of IQ scores and that

means more children may require early stimulation and

educational programs,” she says.

“While many children in this study may require special

educational services when they enter school, it is important not to assume that the findings from a single study,

with its unique characteristics, necessarily apply to all

cocaine-exposed children,” cautions NIDA’s Dr. Smeriglio.

Ultimately, NIDA’s extensive portfolio of research on

groups of cocaine-exposed children being raised in a variety of settings should provide detailed information about

mother, child, environment, and drug-use characteristics

that can be used to develop interventions that reduce risk

of harm and guide clinical care for cocaine-exposed children.

Source

• Singer, L.T., et al. Cognitive and motor outcomes of

cocaine-exposed infants. JAMA 287(15):1952–1960,

2002. 

11
NIDA-funded researchers are studying gender differences

in smoking behavior and working to develop treatment

plans that will help more women end their nicotine addiction. Three recent studies headed by Dr. Kenneth Perkins

of the University of Pittsburgh add to this knowledge and

test new treatment approaches for women.

In one set of studies, Dr.

Perkins has found that the

smell and taste of cigarettes

play a greater role in women’s

smoking behavior than in that

of men. Another study found

that cognitive-behavioral therapy aimed at changing attitudes

about weight promotes smoking cessation by women.

Additionally, Dr. Perkins found

that menstrual cycle phase has

an effect on both mood and

tobacco withdrawal symptoms

for women trying to quit

smoking—a finding that suggests that women could

improve their success rate 

simply by starting their quit 

attempt during certain days of

their cycle.

Sensory Factors in Smoking

Dr. Perkins and his colleagues

used a set of laboratory studies to examine the effects of

sensory cues—seeing a lit cigarette and smelling and tasting smoke—on smoking behavior of women versus men.

In one of the studies, researchers recruited 51 young

smokers (21 men, 30 women) from the nearby community for what subjects were told was a test of different kinds

of cigarettes. The smokers wore opaque goggles or swimmers’ noseclips while smoking to test the roles that visual

and olfactory cues—that is, cues related to seeing and

smelling—play in smoking pleasure and reinforcement.

Researchers measured smoking reinforcement—the number of puffs taken in different situations—and pleasure—

using subjective measures such as the Rose Sensory 

Questionnaire—to assess the extent that sensory cues reinforce smoking.

They found that blocking olfactory stimuli made a greater

difference to women than to men. While pleasure in

smoking was reduced for both women and men when

visual and olfactory cues were

blocked, women found 

significantly less pleasure in

smoking and also smoked less

than men under the blockade

conditions. This study shows

that sensory cues play a larger

role in smoking for women

than for men and further

demonstrates that the olfactory

cues, not the visual, were the

cause of the difference.

Dr. Perkins has recently tested

the effects of nicotine “dose”

in cigarettes on smoking

pleasure and reinforcement in

30 men and women smokers.

The smokers sampled, rated,

and then smoked their regular

brand of cigarette or an ultralow-nicotine cigarette, both of

which were presented with

brand markings concealed.

The nicotine dose of cigarettes

had less effect on self-reported

pleasure and reinforcement in

women compared to men, consistent with the notion that

nicotine may be a less important influence on smoking

behavior in women than in men. 

“Because women pay more attention to cues related to

smell than do men,” says Dr. Perkins, “they could benefit

from counseling to avoid those cues and could learn cognitive coping strategies to reduce the urge to smoke.” Such

behavioral counseling is not now used widely or effectively, he says. He suggests that future research could focus on

other conditioned reinforcers of smoking, such as brand

markings, “hand-mouth” activity, environmental contexts,

and consumption of other drugs (such as caffeine or 

alcohol), with the goal of finding ways to extinguish the

Women and Smoking: Sensory Factors, Attitudes About Weight,

Phase of Menstrual Cycle All Key To Quitting

By Jill S. Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 4 (November 2002)

12

Weight Control Methods Impact 

Smoking Abstinence

Women who participated in cognitive-behavioral therapy, 

learning to accept a modest weight gain while trying to quit

smoking, achieved greater abstinence levels than those in the

weight control group, who were given daily calorie goals, or the

social support group, who received counseling that did not focus

on weight issues.
reinforcing effects of these stimuli or finding sensory 

substitutes.

Dr. Cora Lee Wetherington, NIDA’s Women and Gender

Research Coordinator, points out that this study is consistent with other research showing that women may benefit

less from the nicotine patch or gum but more from the

nicotine inhaler than do men. “Women lose both the sensory cues and the nicotine when they quit smoking,” she

says. “Therefore, replacing those cues—something the

inhaler can do, but not the patch or gum—and learning

ways to avoid or cope with those cues may help more

women succeed in quitting.”

Attitudes About Weight Gain

Previous smoking cessation trials have found that more

than half of women smokers have a hard time quitting, at

least partly because of concerns about weight gain. The

average postquit weight gain of 10 pounds sabotages many

attempts to quit smoking early on and causes some

women to resist even trying to quit, to drop out of treatment, or to relapse after quitting. Research has found that

dieting to prevent this weight gain is ineffective and may

actually interfere with quit efforts. Now, a new study has

shown that cognitive-behavioral therapy (CBT) aimed at

reducing dietary restraint and changing attitudes about

weight proved more successful at both controlling weight

gain and promoting smoking cessation. 

Dr. Perkins and his colleagues studied 219 women

between the ages of 18 and 65 who wanted to quit smoking but were significantly concerned about gaining weight,

as determined by telephone interviews during subject

recruitment. The women, divided into three treatment

groups, all received standard smoking cessation counseling. Each group also received either behavioral weightcontrol counseling, CBT to reduce weight concerns, or

social support not focused on weight issues.

Members of the weight-control group were given daily

calorie goals and instructed to track food intake in a diary,

with the goal of reducing between-meal snacking (the primary source of excess calorie intake after quitting smoking). These women successfully prevented any weight gain

in the month after quitting, as expected.

The CBT group received therapy to help them accept a

modest weight gain in light of the benefits of quitting

smoking. In putting together a CBT approach for smokers, Dr. Perkins turned to his colleague Dr. Marsha

Marcus, who is an expert on eating disorders. “We wanted

to help women accept the likelihood that they may gain 5

to 10 pounds, and we used CBT to modify their attitude

toward that weight gain,” she says. “We identified unrealistic thoughts or beliefs about weight gain and smoking,

and we developed cognitive approaches to counteract

those thoughts. Our key message was, ‘adopt moderation

in eating, reduce stress levels, and exercise more during an

attempt to quit smoking.’”

At 1-year followup, 21 percent of the CBT group had successfully quit smoking, compared with 13 percent of the

weight-control group and 9 percent of the social support

group. Weight gain for those continuously abstinent at 1

year averaged 6 pounds for the CBT group, 12 pounds for

the weight-control group, and 17 pounds for the social

support group.

“Health care providers and smokers should be aware that

the CBT approach has more promise than the diet

approach,” says Dr. Perkins. He suggests that future

research can distill the key elements of the CBT 

intervention so it can be delivered concisely and test a

combination of CBT with medication to further improve

outcomes.

Today, researchers are paying more attention to the possibility of sex differences and analyzing those differences in

their own data. “Both women and health care providers

should recognize the obstacles women face and consider

how to approach them to maximize their chances of success at quitting smoking,” says Dr. Perkins.

Dr. Wetherington sees great value in this type of research:

“Because of the gender-based approach Dr. Perkins has

taken, we are beginning to see that what works best for

males may not work best for females, and vice versa. We

are beginning to develop better treatment strategies.”

Sources

• Perkins, K., et al. Sex differences in the subjective and

reinforcing effects of visual and olfactory cigarette

smoke stimuli. Nicotine & Tobacco Research

3(2):141–150, 2001.

• Perkins, K.A.; Jacobs, L.; Sanders, M.; and Caggiula,

A.R. Sex differences in the subjective and reinforcing

effects of cigarette nicotine dose. Psychopharmocology

163(2):194–201, 2002.

• Perkins, K.A., et al. Cognitive-behavioral therapy to

reduce weight concerns improves smoking cessation

outcome in weight-concerned women. Journal of

Consulting and Clinical Psychology 69(4):604–613,

2001. 

• Perkins, K.A.; Levine, M.; and Marcus, M. Tobacco

withdrawal in women and menstrual cycle phase.

Journal of Consulting and Clinical Psychology

68(1):176–180, 2000.

• Perkins, K.A. Smoking cessation in women: Special

considerations. CNS Drugs 15(5):391–411, 2001.

13
Timing Quit Date May Help Women Smokers

Research Findings

Volume 17, Number 4 (November 2002)

Women trying to quit smoking may be able to improve

their success rate by starting their quit attempt on certain

days of their cycle. In the course of the larger smoking cessation trial focused on weight issues, Dr. Perkins also

examined tobacco withdrawal and mood measures for 78

premenopausal women who maintained smoking abstinence for 1 week after quitting. Half of the women quit

during the follicular phase of their menstrual cycle (days 1

through 14) and half quit during the luteal phase (day 15

or later). He found that women quitting during the luteal

phase reported significantly more tobacco withdrawal

symptoms and depression than those who quit during the

follicular phase. 

“This research suggests a clear behavioral prescription for

increasing the odds of success in quitting,” says Dr.

Perkins. “Women should set a quit date early in the follicular phase. Withdrawal symptoms and depression may be

less intense. If withdrawal is blunted, quitting should be

easier. And this simple strategy for timing the quit day

costs nothing.” 

14

Tobacco Withdrawal Symptoms, Luteal Versus

Follicular Phase

Withdrawal symptoms for luteal-phase women 1 week after

quitting smoking were significantly higher than those of follicular-phase women. Symptoms of irritability, anxiety, difficulty

concentrating, restlessness, impatience, hunger, and depression

were rated by participants on a scale ranging from 0 (none) to

100 (extremely intense). The graph illustrates mean values for

all symptoms combined.
Inhalant Abuse Among Young People

Research Findings

Volume 17, Number 4 (November 2002)

Inhalant abuse is a public health problem that disproportionately affects young people. This page provides graphic

representation of recent trends in use, attitudes about

inhalants among U.S. schoolchildren, and current levels of

inhalant use in the United States, distributed by gender,

ethnicity, and age. The source of the data is NIDA’s annual Monitoring the Future survey of adolescents in grades

8, 10, and 12.

Current trends are positive in two respects. Increasingly,

young people surveyed see “great risk” in trying inhalants.

At the same time, the percentage reporting inhalant abuse

is declining.

Although the percentages of U.S. male and female students reporting past-year use of inhalants are virtually

identical among 8th- to 12th-graders, use by males is

more likely among older youths. Inhalant use is reported

by a greater percentage of Whites and Hispanics than by

Blacks. 

15

A consistent pattern shows higher rates of inhalant use in

earlier grades, with levels of use in all three grades peaking

in 1995 and declining from 1996 through 2001. The

decline in inhalant use that began in 1996 may be linked to

an increase in perception of inhalant risk, a trend that

began in 1995–1996.

From 1991 to 1993 roughly 40 percent of 8th- and 10thgraders perceived any experimentation with inhalants to be

very risky. Between 1995 and 2001, significant increases in

perceived risk were reported by both groups.

Percentage of Students Reporting Past-Year 

Use of Inhalants, by Grade

Percentage of 8th- and 10th-Graders Seeing 

“Great Risk” in Trying Inhalants Once or Twice
16

A slightly higher percentage of 8th-grade girls than boys

reported inhalant use. Among 12th-graders, a greater 

percentage of boys report past-year use of inhalants.

Higher rates of past-year inhalant use were found among

Whites and Hispanics, lower rates among Blacks.

U.S. Students Who Reported Past-Year Use 

of Inhalants, 2001, by Race/Ethnicity

U.S. Male and Female Students Who Reported 

Past-Year Use of Inhalants, 2001
Prenatal Exposure to Ecstasy May Impair Memory and Cognition

By Jill S. Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 3 (October 2002)

Dr. Harry Broening, Dr. Charles Vorhees, and colleagues

at the Cincinnati Children’s Research Foundation and the

University of Cincinnati have demonstrated that rats

exposed to MDMA—ecstasy—during the developmental

period corresponding to the third trimester of human

pregnancy suffer memory and learning deficiencies that

persist into adulthood.

Scientific studies have already established that ecstasy users

are at risk for dehydration, hypertension, hyperthermia,

and heart or kidney failure. The drug also has been shown

to damage nerves in the brain’s serotonin system and

appears to produce long-term deficits in memory and cognition. The new study suggests that unborn children of

ecstasy users may suffer deleterious effects that last into

adulthood. “The possibility that these findings in rats may

also apply to humans raises a concern because this drug,

which is incorrectly perceived as safe by many of its proponents, is sometimes being used by young women who

are pregnant,” says Dr. Jerry Frankenheim of NIDA’s

Division of Neuroscience and Behavioral Research.

Timing and Vulnerability

In designing the current study, the researchers drew on

previous studies by Dr. Vorhees on the effects of methamphetamine exposure on rodent brain development. These

studies identified specific periods late in rodent brain

development—days 11 to 20 after birth, which are analogous to late third-trimester human fetal brain development—in which the brain is quite vulnerable to methamphetamine-induced impairments of spatial learning and

memory. The question became, can related drugs, such as

MDMA and other synthetic stimulants, also cause such

impairments?

Dr. Vorhees and his colleagues decided to test the effects

of MDMA administered to rats at this same crucial 11 to

20 days postnatal developmental period and to a comparison group of rats on days 1 to 10 after birth (comparable

to early third trimester of human pregnancy). According

to Dr. Vorhees, the dosages given to rats in the study are

equivalent to a 110-lb woman taking 25 mg, a common

dose for MDMA users, up to 250 mg, an amount sometimes reached or exceeded by chronic abusers.

Testing for Learning, Memory

When the rats reached young adulthood, the researchers

put them through a series of maze and swimming trials to

assess the effects of MDMA exposure on learning and

memory. An initial test revealed no significant differences

between the MDMA-exposed rats and the controls in

terms of swimming performance or motivation to escape

from the water. Next, animals were evaluated in a test of

sequential learning called the multiple-T (Cincinnati)

water maze. The rats had to search through nine decision

points to find their way through the maze and out of the

water. The researchers found that the rats exposed to

MDMA on days 11 to 20 after birth made significantly

more errors and took significantly longer to escape the

maze than did either the MDMA-unexposed animals or

those exposed to MDMA on days 1 to 10 after birth.

17

Adult rats that had been exposed to MDMA doses of 10 or 20

mg/kg body weight (comparable to doses used by human MDMA

abusers) on days 11 to 20 after birth (a period comparable to late

in the third trimester of human pregnancy) took significantly

longer to escape the multiple-T water maze than did animals

exposed to saline solution. No statistically significant increase in

escape times was observed among rats exposed on days 1 to 10

after birth.

Animals Exposed to MDMA Take Longer To Escape

Multiple-T Water Maze
“The animals exposed to MDMA during the critical 11 to

20 days postnatal brain development period cannot seem

to eliminate errors the way normal animals do,” says Dr.

Vorhees. “The difference is the rate at which they learn.

All of the animals eventually learned how to navigate the

maze, but it took the MDMA-exposed animals significantly longer to do so.”

The Morris hidden platform maze was used to further

evaluate the animals’ spatial memory and cognitive abilities. A 6-foot diameter swimming pool was constructed

and a small clear acrylic platform was placed so that the

animals could escape if they found it. In increasingly difficult phases the rats had to find the platform when it was

above the water, below the water, moved to a new location,

or below the water and reduced in size. Memory trials

were also performed with the platform removed. Animals

exposed to MDMA on days 1 to 10 after birth performed

as well as unexposed animals on the trials. However, the

animals exposed to MDMA on days 11 to 20 after birth

showed significant impairment of memory and spatial

learning when the platform was submerged and on memory

trials when the platform was removed, but no differences

when the platform was above the water.

“These later trials test the animals’ ability to remember

something in space,” explains Dr. Vorhees. “We found

that as we made the task harder, MDMA-exposed animals

had a disproportionately harder time finding the platform.

The harder the task was, the more their learning disability

was revealed.”

Comparing Infant Versus Adult Exposure

Upon completion of the trials, the rats were sacrificed and

their brains were preserved for later analysis. The

researchers wanted to know if animals exposed to MDMA

during early brain development would show the same pattern of damage to neurotransmitters that has been shown

in adult animals exposed to MDMA. They did not. “This

was a surprise because we didn’t find the same damage to

neurotransmitters as was found in previous studies of animals exposed to MDMA as adults,” says Dr. Vorhees.

“Yet, the animals in the current study still show cognitive

impairment, as demonstrated by their performance on the

learning and memory trials.” He hypothesizes that a different mechanism is at work in animals exposed to

MDMA during brain development that later affects their

memory and learning ability. Future research will focus on

identifying this mechanism.

Dr. Frankenheim points out that this research is a warning

that what is happening in animals may also happen with

people. “The work of determining what drugs of abuse do

to fetuses when the mother takes them is very difficult. It

is not yet known whether human fetuses exposed to

MDMA will develop persistent memory and learning

problems. However, these findings in rats raise the concern that MDMA may pose a previously unrecognized risk

to the developing human brain,” he says.

Future research will involve determining whether there are

effects of MDMA exposure at earlier points in fetal development, such as during the period corresponding to the

first trimester in humans, when drug exposure is more

likely for women who may not yet be aware that they are

pregnant. The first trimester is also the developmental

period when humans are most sensitive to neurotoxins.

Source

• Broening, H.W.; Morford, L.L.; Inman-Wood, S.L.;

Fukumura, M.; and Vorhees, C.V. 3,4-methylenedioxymethamphetamine (ecstasy)-induced learning

and memory impairments depend on the age of exposure during early development. Journal of Neuroscience

21(9):3228–3235, 2001. 

18
In Drug Abuse, Gender Matters

By NIDA Acting Director Glen R. Hanson, Ph.D., D.D.S. 

Research Findings

Volume 17, Number 2 (May 2002)

Recent decades have seen a marked increase in awareness

of the importance of gender in medical treatment and

research. In the complex field of drug abuse research, scientists have helped us understand that there are genetic,

physiological, psychosocial, and environmental dimensions to drug abuse and addiction. Male

and female differences in any of these

dimensions can give rise to gender differences in the causes, effects, and consequences of drug abuse. Researchers and 

clinicians have developed a repertoire of

effective treatment and prevention principles that can now be enhanced through

their adaptation for the differing needs of

men and women and boys and girls.

NIDA’s National Drug Abuse Treatment

Clinical Trials Network adheres to the

overall National Institutes of Health

requirement for analysis of

data by gender and supports

gender-specific protocol

development. NIDA recently issued a Program

Announcement for support

of dissertation research in

five areas, one of which is

women and gender. A new

Program Announcement on

Women and Gender

Differences will be issued

soon to fund research specifically in the areas of epidemiology, prevention, and

treatment. These efforts will build on NIDA-sponsored

research that has established that important gender effects

exist in biological and behavioral responses to drugs, risk

for drug abuse, and treatment response.

Response to drugs: The neurobiological basis of drug

abuse and addiction is essentially the same, regardless of

the drug taken or the person taking it. Still, males and

females may differ in their biological and behavioral

responses to drugs. Laboratory studies have revealed sexrelated differences in the ways that male and female animals metabolize drugs, the amount of drug they will selfadminister, how soon after their first exposure they begin

to administer drugs, and their vulnerability to relapse after

abstinence. Preliminary results from studies of human

drug abusers appear to be consistent with the findings

from animal studies of gender differences in the patterns

and the biological impact of drug use. For example,

women typically progress from first use of cocaine, heroin,

or marijuana to dependence more quickly than

men. Additionally, cocaine-induced cognitive

impairments and risk for stroke have been

found to be more severe in men than in

women.

Risk for drug abuse: While risk factors related to drug abuse vulnerability in males and

females largely overlap, a variety of differences

exist. Depression is much more common

among women than men in the general public.

This gender difference is much less pronounced among drug abusers. Possible explanations are that depression is a more potent

risk factor for drug abuse among

men than among women, or that

drug abuse itself is more likely to

cause depression among men than

among women. Other risk factors

that appear to be stronger for one

gender than the other include conduct disorders, which correlate

more with drug abuse by adolescent females, and aggression, which

correlates with drug abuse by adolescent males.

Along with these differences, studies of gender and risk have revealed

an unexpected and important similarity between males and females. Most experts long

assumed that females were less attracted to or more wary

of drug abuse than were males. That seemed a straightforward conclusion based on the fact that the percentage of

women who abuse drugs is lower than the percentage of

men who abuse drugs. However, the conclusion turns out

to be not true. A recent study found that the lower rate of

drug abuse for females is largely a matter of opportunity.

(See “Gender Differences in Prevalence of Drug Abuse

Traced to Opportunities to Use.”) During the youthful

ages when most drug abuse initiation occurs, more boys

than girls receive offers of drugs. When drug offers are

made, both genders are equally likely to accept. Once 

19

Researchers and clinicians have

developed a repertoire of effective

treatment and prevention principles

that can now be enhanced through

their adaptation for the differing

needs of men and women 

and boys and girls. 
having accepted, males and females generally are equally

likely to become dependent. This underscores the importance of drug refusal skills in prevention efforts with both

genders.

Response to treatment: Success in drug treatment is

directly associated with the length of time spent in treatment: The more time in treatment, the better the outcome. Science-based drug treatments are equally effective

for men and women, but women often spend less time

than men in treatment. In part, this could reflect differences in social and economic circumstances. Women

entering treatment are more likely than men to be custodial parents and to have fewer economic resources; they

are less likely than men to have graduated from high

school, to be employed, or to have sufficient supportive

social networks. Studies also indicate that males and

females tend to relapse to drug use for different reasons.

For example, among men relapse is more likely to be associated with anxiety and positive feelings, while among

women depression and negative feelings appear to be more

common triggers. All these differences suggest that it may

be possible to enhance the effectiveness of treatment by

tailoring it for the patient’s gender.

The area of nicotine addiction is one in which our understanding of gender effects is relatively advanced, although

still far from complete. Research has shown that different

aspects of smoking more strongly influence addiction to

nicotine in men and women. For men, the compulsion to

smoke is driven more strongly by nicotine’s pharmacological effects on the brain, while women’s addiction owes

more to the visual, tactile, taste, and olfactory sensations

involved in smoking. Because of these differences, men

tend to get more relief overall from nicotine replacement

therapy, and women who use nicotine replacement do better with nicotine inhalers than the nicotine patch. Recent

NIDA research also suggests that women can increase

their chances for quitting by timing their attempt to coincide with the first half of their menstrual cycles, since

nicotine craving and withdrawal symptoms are generally

more severe during the second half of their cycles.

Although the focus on gender is relatively new in drug

abuse science, we already know that gender’s impact is far

reaching and complex. A comprehensive and detailed picture of gender-related effects can lead to improvements in

treatment and prevention efforts that bring us closer to

the goal of individualized interventions that best meet the

distinct needs of each patient. When it comes to reducing

the tremendous burden of drug abuse and addiction, gender most certainly matters. 

20

Although the focus on gender is relatively new in drug abuse science, we

already know that gender’s impact is

far reaching and complex. 
Prenatal Exposure to Methamphetamine Increases Vulnerability to

the Drug’s Neurotoxic Effects in Adult Male Mice

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 2 (May 2002)

A NIDA-funded study has shown that exposure to

methamphetamine before birth results in more severe neurotoxic effects in male mice given the drug as adults than

in females. These findings raise concerns regarding the

long-term health consequences of methamphetamine 

use, particularly for men who were exposed to the drug 

in utero.

Methamphetamine is known to be a neurotoxic agent that

damages the endings of brain cells containing dopamine, a

brain chemical that regulates movement, emotion, motivation, and feelings of pleasure. Previous research in animals

has indicated that methamphetamine causes damage to

cells in the striatal and cortical regions of the brain. In

humans, these regions are associated with memory, cognitive function, and movement.

“Many young people using club drugs such as methamphetamine are cavalier about its dangers. They mistakenly

believe that they can use these drugs with no consequences,” says Dr. Jerry Frankenheim of NIDA’s Division

of Neuroscience and Behavioral Research. “Although this

study was conducted in mice, these findings suggest that

the children, especially sons, of pregnant women who

abuse methamphetamine may suffer the consequences of

their mothers’ actions later in life.”

To investigate the effects of methamphetamine exposure

in utero, Drs. Alfred Heller and Lisa Won at the

University of Chicago injected pregnant female mice with

neurotoxic doses of methamphetamine or saline twice

daily from gestational days 7 through 18. At 11 weeks of

age (equivalent to young adulthood), the offspring

received two injections of either saline or methamphetamine in a range of doses. Rectal temperatures were measured hourly from just before the first injection to at least 4

hours after the second injection. Seven days later, the

mouse brains were analyzed for dopamine and its metabolites in the striatum, ventral and dorsal brainstem, cortex,

and cerebellum.

Fetal exposure to methamphetamine alone did not affect

dopamine or its metabolite levels, but after methamphetamine exposure of the adults, considerable differences were

observed between the adult male and female offspring.

Adult males had lower levels of dopamine and its metabolites in the striatum and cortex than did females. In addition, the prenatally methamphetamine-exposed males had

greater reductions than any other group. A 20 mg/kg dose

of the drug in an adult produced a 70-percent reduction

of striatal dopamine in prenatally methamphetamineexposed males, compared to a 55-percent reduction in

unexposed males. Females showed a 14- to 25-percent

reduction in striatal dopamine. In the brainstem, only the

prenatally methamphetamine-exposed males suffered a

reduction of dopamine from exposure to the drug as an

adult. Effects of methamphetamine on cortical dopamine

were not enhanced by prenatal exposure to the drug.

“The increased dopamine losses observed in prenatally

exposed males in response to adult exposure to the drug

occurred in the regions of the brain that are affected by

neurological disorders such as Parkinson’s disease,” says

Dr. Heller. “If similar neurological effects are occurring in

21

Adult mice were given two doses of methamphetamine 2 hours

apart. One week after the drug injections, their brains were analyzed for dopamine. Males that had been prenatally exposed to

methamphetamine had a greater reduction in striatal dopamine

levels compared with females and unexposed males. 

Effect of Prenatal Exposure to 

Methamphetamine on Striatal Dopamine

Levels of Male and Female Adult Mice
humans, males whose mothers used methamphetamine

during pregnancy may be at a greater risk for developing

these ailments.”

Previous research has indicated that the neurotoxic effects

of methamphetamine are associated, in part, with its ability to raise body temperature. Hyperthermia, however, did

not account for the increased susceptibility of prenatally

methamphetamine-exposed males compared to other

males. Adult males exhibited the same rise in body temperature whether or not they had been exposed to

methamphetamine in utero.

The hyperthermic effects of methamphetamine were a

contributing factor to the differences in neurotoxicity

observed between males and females. Adult females did

not exhibit a change in body temperature in response to

methamphetamine exposure, while adult males did exhibit

a rise in body temperature.

“The finding that the female mice in this study did not

experience the same degree of neurotoxicity or hyperthermic effects when given methamphetamine as adults does

not mean that female offspring are safe from harm,” cautioned Dr. Heller. “Other research indicates that the age of

adult exposure to methamphetamine may play a role in

susceptibility to the drug’s effects. This study was conducted in animals that were equivalent to young adults. The

same findings may not hold true for younger or more

mature female mice.”

Source

• Heller, A.; Bubula, N.; Lew, R.; Heller, B.; and Won,

L. Gender-dependent enhanced adult neurotoxic

response to methamphetamine following fetal exposure to the drug. Journal of Pharmacology and

Experimental Therapeutics 298:769–779, 2001. 

22
High-Risk Sex Is Main Factor in HIV Infection for Men and Women

Who Inject Drugs

By Robert Mathias, NIDA NOTES Staff Writer

Research Findings

Volume 17, Number 2 (May 2002)

A 10-year study has found that the biggest predictor of

HIV infection for both male and female injecting drug

users (IDUs) is high-risk sexual behavior, not sharing 

needles used to inject drugs. High-risk homosexual activity was the most important factor in HIV transmission for

men; high-risk heterosexual activity was most significant

for women. Risky drug-use behaviors also were strong 

predictors of HIV transmission for men but were less 

significant for women, the study found.

“In the past, we assumed that IDUs who were HIV-positive had been infected with the virus through needle-sharing,” says Dr. Steffanie Strathdee of the Johns Hopkins

University Bloomberg School of Public Health in

Baltimore, who conducted the NIDA-funded study. “Our

analysis indicates that sexual behaviors, which we thought

were less important among IDUs, really carry a heavy

weight in terms of risks for HIV seroconversion for both

men and women.” 

In the study, Dr. Strathdee led a team of researchers who

analyzed data collected every 6 months from 1,800 IDUs

in Baltimore from 1988 to 1998. Participants had to be at

least 18 years of age when they entered the study, have a

history of injection drug use within the previous 10 years,

and not have HIV infection or AIDS. More than 90 percent of the participants said they had injected drugs in the

6 months prior to enrolling in the study. In their semiannual interviews, study participants reported their recent

drug use and sexual behavior and submitted blood samples

to determine if they had become HIV-positive since their

last visit.

Researchers analyzed the role of homosexual activity in

HIV seroconversions among male IDUs in the study, after

taking into account other factors that increased their risk

of acquiring HIV, such as their drug injection practices.

This analysis revealed that the incidence of HIV infection

among male IDUs who had engaged in homosexual activity within the previous 6 months was 10.44 percent a year,

compared to 3.01 percent among men who did not report

having homosexual sex.

Visiting “shooting galleries,” where drug abusers gather to

obtain and inject drugs, sharing needles used to inject

drugs with multiple partners, and injecting drugs daily

also were independently linked to significantly higher rates

of HIV infection among men in the study. Men who said

they had used shooting galleries had an HIV incidence

rate of 6.28 percent per year, and men who shared needles

with more than one partner had a rate of 5.52 percent per

year. These infection rates were more than double those

found among men who had not engaged in these behaviors. Men who injected drugs at least once a day had HIV

infection rates of 4.68 percent, more than one and onehalf times the rate among men who had injected less than

once a day.

Sharing needles also increased risk of HIV infection

among women IDUs. However, high-risk heterosexual

activity was a much more important risk factor for these

women, the study found. In fact, other than being

younger than 30 years—which independently predicted

HIV infection for both sexes—high-risk heterosexual

activity was the main predictor of HIV seroconversion

among women. Women who reported having a recent sex23

High-risk sexual behavior played the biggest role in HIV 

infection for both male and female injection drug users (IDUs) in

this study of 1,800 IDUs. Significant risk factors for men were

high-risk homosexual activity, using shooting galleries, and sharing needles used to inject drugs with multiple partners. For

women, high-risk heterosexual activity, as indicated by reporting

a recent sexually transmitted disease (STD), was the most 

significant cause of HIV infection.

High-Risk Sexual Behavior Leading

Cause of HIV Infection Among Injection

Drug Users in 10-Year Study
ually transmitted disease (STD), an indicator of unprotected sex, had more than 2.5 times the rate of HIV infection of women who did not have an STD.

“Both homosexual men and heterosexual women IDUs

appear to be at dual risk for becoming infected with

HIV,” Dr. Strathdee says. “In previous studies by our

group, being a gay male IDU was closely linked to visiting

shooting galleries and sharing needles. Heterosexual

women IDUs tend to have more of an overlap in their

sexual partners and their drug use than men do. This puts

them at increased HIV risk because they are sharing 

needles and having unprotected sex with a partner who 

is more likely to be infected with the virus.

“HIV prevention programs have done a good job in

reducing needle-sharing and other drug-use behaviors that

spread the virus among IDUs,” Dr. Strathdee says.

“However, our study indicates that HIV prevention programs can achieve better results by also addressing sexual

risk behaviors among IDUs. A multifaceted approach is

needed that screens both men and women IDUs for STDs

at places where they go, such as needle-exchange programs

and methadone treatment programs, and provides comprehensive treatment at those sites. 

“HIV prevention efforts also should be gender-specific,

targeting the important differences we have found in sexual and drug-use behaviors among men and women that

increase their risk of acquiring and transmitting HIV,” Dr.

Strathdee says. “For example, women IDUs in stable relationships could be shown how to negotiate condom use

with their partners and offered couple counseling to educate both partners about HIV risks associated with their

drug use and sexual behaviors. We need more research to

identify and evaluate HIV prevention approaches for male

IDUs who have sex with men to determine what kinds of

interventions might work.”

Source

• Strathdee, S.A., et al. Sex differences in risk factors for

HIV seroconversion among injection drug users.

Archives of Internal Medicine 161:1281–1288, 2001.

24
Cocaine’s Effects on Cerebral Blood Flow Differ Between Men 

and Women

By Jill S. Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 2 (May 2002)

Researchers studying the effects of cocaine on the brain

have found that men and women with comparable drug

use histories do not exhibit comparable damage. One

study showed that women suffered less neuronal injury

than men; another, that cocaine-dependent women have

fewer abnormalities in blood flow to the brain than do

cocaine-dependent men. Now, a recent NIDA-funded

study has taken an important step toward explaining these

differences between the sexes.

Cocaine constricts blood vessels, temporarily narrowing

arteries and reducing blood flow to the brain, heart, and

other areas of the body. Repeated exposure to cocaine can

lead to blood-flow deficits in the brain that persist long

after cocaine use has ended, causing permanent damage.

Dr. Marc J. Kaufman and colleagues at McLean Hospital,

Harvard Medical School, in Belmont, Massachusetts,

found that cerebral blood flow during the follicular phase

of women’s menstrual cycles (days 1 through 14, prior to

ovulation) is not affected by exposure to cocaine. In

women during their luteal phase (after ovulation, typically

days 15 through 28) and in men, cocaine restricts cerebral

blood flow.

“We hypothesized that the differences in blood flow might

be caused by sex hormones,” says Dr. Kaufman. “We

decided to investigate whether women with high levels of

estrogen, which improves blood-vessel elasticity, are more

resistant to the vasoconstrictive effects of cocaine.”

Dr. Kaufman and his colleagues used dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) to

study cocaine-induced changes in cerebral blood volume

in 13 healthy young women (average age 28) with histories of occasional cocaine use. The women’s self-reported

lifetime cocaine use averaged 13 exposures (ranging from

1 to 40). 

Each woman was given a dose of cocaine and underwent a

DSC MRI scan of cerebral blood volume during both

phases of her menstrual cycle. During the first part of the

menstrual cycle, estrogen levels are high and progesterone

levels are low; during the second part, progesterone levels

rise. In each imaging session, two brain images were collected: one as a baseline measure of cerebral blood volume

and the second 10 minutes after cocaine administration.

The study found no significant changes in cerebral blood

volume after cocaine administration during the women’s

follicular phase. During the luteal phase, when progesterone levels are highest, the women’s cerebral blood flow

fell approximately 10 percent after cocaine administration.

These data compare to Dr. Kaufman’s findings in a 

similar 1998 study, that men experience, on average, a 

20-percent reduction in cerebral blood volume after

cocaine administration.

“We found what we were expecting,” says Dr. Kaufman.

“There was a minimal change in follicular cerebral blood

volume, attributable, we believe, to the protective effects

of estrogen. The greater vasoconstrictive effect of cocaine

25

Magnetic resonance (MR) image intensity was measured to compare the hemodynamic effects of cocaine during two phases of a

woman’s menstrual cycle. Following cocaine administration during

the follicular phase, image intensity was relatively high, reflecting

cerebral blood flow at 97 percent of its pre-cocaine baseline. When

the drug was given during the luteal phase, lower image intensity

reflected a fall in blood flow to 82 percent of baseline. The MR

technique is illustrated on the next page.

Cocaine’s Effect on Cerebral

Blood Volume Varies Throughout 

Menstrual Cycle
in luteal-phase women may be attributable to the progesterone, which has been shown to increase cocaine’s vascular toxicity.”

Dr. Kaufman’s next step will be to administer estrogen or

progesterone to men and luteal-phase women and measure

the effects on cerebral blood volume after cocaine administration. The ultimate goal will be to develop a hormonelike medication to counteract the vascular effects of

cocaine. 

“Beyond confirming that cocaine does have a damaging

effect on the brain and is not safe to use, this research

contributes to our understanding of the drug’s deleterious

effects,” says Dr. Steven Grant, of NIDA’s Division of

Treatment Research and Development. “Additionally, the

research points out that we’ve got to stop thinking of both

sexes as the same when it comes to the effects of drugs.

Dr. Kaufman has shown that cocaine affects men and

women differently.” 

Sources

• Kaufman, M., et al. Cocaine-induced cerebral vasoconstriction differs as a function of sex and menstrual

cycle phase. Biological Psychiatry 49(9):774–781,

2001. 

• Kaufman, M., et al. Cocaine decreases relative cerebral

blood volume in humans: A dynamic susceptibility

contrast magnetic resonance imaging study.

Psychopharmacology 138:76–81, 1998. 

26

A sequence of magnetic resonance images taken at 1-second intervals after a woman received an intravenous blood

marker progresses from light to dark to light as her cerebral blood flow carries the marker into her brain and washes it back out again. The total marker present in all the images, measured as their intensity (darkness), reflects total

cerebral blood volume. To study the hemodynamic effects of cocaine, investigators compared two such sequences,

obtained before and after administration of the drug, during each menstrual period.

Using Magnetic Resonance Imaging (MRI) To Track Cerebral Blood Volume

Seconds After Contrast Injection
Childhood Sex Abuse Increases Risk for Drug 

Dependence in Adult Women

By Patrick Zickler, NIDA NOTES Staff Writer 

Research Findings

Volume 17, Number 1 (April 2002)

Women who are sexually abused during childhood are at

increased risk for drug abuse as adults, according to

NIDA-supported research conducted at the Medical

College of Virginia Commonwealth University in

Richmond. Using data gathered from interviews of 1,411

adult twins, Dr. Kenneth Kendler and his colleagues

assessed the association between three levels of childhood

sex abuse (nongenital, genital, and intercourse) and six

adult disorders—major depression, generalized anxiety disorder, panic disorder, bulimia nervosa, alcohol dependence, and drug dependence. Women who experienced any

type of sexual abuse in childhood were roughly three times

more likely than unabused girls to report drug dependence

as adults.

“Overall, childhood sexual abuse was more strongly associated with drug or alcohol dependence than with any of

the psychiatric disorders,” Dr. Kendler says. “Only drug

and alcohol dependence were significantly associated with

all levels of abuse.”

In this study, 1,411 women born between 1934 and 1974

responded to written questionnaires that asked them if,

before they reached age 16, any adult or person older than

they had ever ("never,” “once,” or “more than once”):

• involved them in an incident that included an invitation or request to do something sexual; 

• kissed or hugged them in a sexual way; 

• subjected them to genital display or exposure; 

• touched or fondled them in a sexual way; 

• made them touch the older person or adult in a sexual

way; or 

• attempted intercourse. 

In addition, the researchers conducted written interviews

with 90 percent of the twins’ parents to assess family environment and parental psychopathology. The parental

interviews did not mention possible sexual abuse of the

children, but did provide data on family financial status;

parents’ disciplinary practices, including spanking, slapping, or hitting; church attendance; and measures of harmony, discord, authoritarianism, and protectiveness.

27

Among more than 1,400 adult females, childhood sexual abuse was associated with increased likelihood of drug dependence, alcohol dependence, and psychiatric disorders. The associations are expressed as odds ratios: for example, women who experienced nongenital sexual abuse in

childhood were 2.93 times more likely to suffer drug dependence as adults than were women who were not abused.

Association of Childhood Sex Abuse With Drug Dependence And Psychiatric Disorders in Adult Women
“Controlling for family factors and parental psychopathology produced a small change in some of the associations,

but the increased odds of reporting drug or alcohol

dependence in adulthood after suffering sexual abuse as a

child can’t be explained by these background factors,” 

Dr. Kendler says.

The women who participated in the research are part of

an ongoing research investigation of female twins included

in the Virginia Twin Registry, which represents a large

cross-section of the population and includes data on a

broad range of research topics, including psychiatric and

substance abuse disorders.

“This study has particular significance because it is based

on data from women in the general population,” says 

Dr. Cora Lee Wetherington of NIDA’s Division of

Neuroscience and Behavioral Research. “Numerous 

clinical studies have documented high rates of childhood

sexual abuse among women in treatment. This study, the

first to document it in a nonclinical population, is particularly important in addressing questions concerning the

relationship between sexual abuse and patterns of drug

abuse and addiction.”

Source

• Kendler, K.S., et al. Childhood sexual abuse and adult

psychiatric and substance use disorders in women: An

epidemiological and co-twin control analysis. Archives

of General Psychiatry 57(10):953–959, 2000. 

28
Biochemical Brain Abnormality Found in School-Age Children

Prenatally Exposed to Cocaine

By Robert Mathias, NIDA NOTES Staff Writer

Research Findings

Volume 16, Number 4 (October 2001)

Exposure to cocaine before birth may affect the way a

child’s brain functions many years later, according to a

recent NIDA-funded study. The brain-imaging study

found a chemical abnormality in the brains of 8-year-old

children that may reflect alterations in metabolic processes

that enable brain cells to use energy and function properly,

the researchers say.

“These children were exposed to cocaine only during gestation and their brains have had 8 years to recover from

that exposure,” says Dr. Joseph Frascella of NIDA’s

Division of Treatment Research and Development. “It is

surprising that they are still showing these deficits so many

years later.” The new finding suggests that early exposure

to drugs has more long-lasting effects on the brain than

previously thought, he notes.

The nature and extent of possible developmental damage

to infants and children from prenatal exposure to cocaine

has been the subject of much apprehension and scientific

study. In the 1980s, anecdotal reports of abnormalities

among cocaine-exposed children contributed to fears that

these children were irreparably damaged and would never

be able to function in society. Subsequent scientific

research has dispelled such exaggerated concerns for the

vast majority of prenatally exposed children.

NIDA-funded studies that have been tracking

the development of groups of cocaine-exposed

babies through adolescence now indicate that

most seem to function normally, but some

may have subtle impairments in their ability

to control emotions and focus attention that

could put them at risk of behavioral and

learning difficulties.

Previous brain-imaging studies of children

prenatally exposed to cocaine have yielded

conflicting information about the drug’s

effects on the developing central nervous system. Some studies have found abnormalities

in brain structure, while others have not.

Studies in abstinent adult cocaine abusers,

using an imaging technique called magnetic

resonance spectroscopy (MRS), have suggested that chronic cocaine use may cause persistent damage to neurons in the frontal lobes of

males and that brain metabolic abnormalities

also could exist despite a normal-appearing brain structure. Dr. Lynne Smith of the Harbor-UCLA Medical

Center in Torrance, California, and Dr. Linda Chang of

Brookhaven National Laboratory, in Upton, New York,

used this MRS technique to see if similar biochemical

abnormalities might be present in the brains of children

who had been prenatally exposed to cocaine, even if they

appeared to have no structural damage.

The researchers used magnetic resonance imaging (MRI)

to assess brain structure and MRS to examine brain 

biochemistry in 14 8-year-old children who had been

exposed to cocaine in the womb. They administered the

same brain scans to a control group of 12 age-matched,

nonexposed children. The MRS scans measured levels of

various chemicals in different brain regions. Increased or

reduced concentrations of these chemicals can indicate

either damage to nerve cells or alterations in brain cell

function in these regions. The researchers assessed a

frontal area of the brain, made up of “white matter,”

which consists mainly of nerve fibers and specialized support cells. They also looked at an area deep in the brain

called the basal ganglia, which contains clusters of nerve

cell bodies, or “gray matter.”

29

Creatine Level Alterations in Frontal White Matter of 

Cocaine-Exposed Children

MRS scans suggest cocaine-exposed children did not have significant nerve damage or

loss in the brain regions that were examined. However, cocaine-exposed children had

significantly higher levels of the brain metabolite creatine than nonexposed children

in a frontal area of the brain made up of “white matter,” which consists mainly of

nerve fibers and specialized support cells. The abnormality may reflect alterations in

metabolic processes that enable brain cells to use energy and function properly.
The study found no difference between the exposed and

nonexposed children in concentrations of N-acetyl-aspartate (NAA), a nerve cell metabolite, in either the frontal

area or the basal ganglia. Because NAA levels are markers

for the density and integrity of nerve cells, the normal

NAA found in children prenatally exposed to cocaine suggests they did not have significant nerve damage or loss in

the two brain regions that were examined. The MRI 

evaluations also showed no brain structure abnormalities in

children in either group. However, cocaine-exposed 

children had significantly higher levels of creatine in 

the white matter of the frontal lobes than nonexposed 

children. Elevated creatine levels indicate that the brain

cells of cocaine-exposed children use energy differently 

in this region.

“All brain cells require creatine for all functions,” says Dr.

Chang. “The altered creatine levels we found could affect

how both nerve cells and support cells are functioning in

the brain. We also have found the same abnormal creatine

levels in frontal white matter in adult cocaine abusers

more than a year after they have stopped using cocaine.

The drug seems to have a particularly long-lasting effect

on energy metabolism in this brain area that merits further investigation.”

“The frontal area of the brain is involved in our ability to

control impulses and sustain attention on a task,” notes

Dr. Frascella. Thus, it is possible that the altered brain

function found in this area could be a biological basis for

findings from other research that some cocaine-exposed

children are more impulsive and easily distracted than

their peers. However, additional research is needed to

make this determination, he says.

Sources

• Chang, L.; Ernst, T.; Strickland, T.; and Mehringer,

C.M. Gender effects on persistent cerebral metabolic

changes in the frontal lobes of abstinent cocaine users.

American Journal of Psychiatry 156(5):716–722, 1999.

• Chang, L., et al. Neurochemical alterations in asymptomatic abstinent cocaine users: A proton magnetic

resonance spectroscopy study. Biological Psychiatry

42(12):1105–1114, 1997.

• Smith, L.M.; Chang, L.; et al. Brain proton magnetic

resonance spectroscopy and imaging in children

exposed to cocaine in utero. Pediatrics

107(2):227–231, 2001.

30

Similar Long-Term Effects Seen From 

Prenatal Methamphetamine Exposure

Dr. Linda Chang of Brookhaven National Laboratory

in Upton, New York, and her colleagues at UCLAHarbor Medical Center in Torrance, California, have

followed up their brain-imaging study of cocaineexposed children with a preliminary study of schoolage children who were prenatally exposed to methamphetamine. The researchers assessed the same chemical

metabolites that they had assessed in the brains of

cocaine-exposed children.

“The findings in methamphetamine-exposed children

were very similar to what we saw with cocaine-exposed

children,” Dr. Chang says. “We found the same abnormalities in creatine levels in the frontal white matter,

which indicate altered energy metabolism. Unlike the 

cocaine-exposed children, methamphetamine-exposed

children also showed abnormalities of N-acetyl-aspartate (NAA), a marker of nerve cell integrity, similar to

those seen in adult methamphetamine and male

cocaine abusers,” she says. In the adult studies, the

researchers were able to conclude that such NAA levels

suggested methamphetamine abuse and cocaine abuse

by males could result in damaged or destroyed nerve

cells. In the prenatal methamphetamine study, too few

children were assessed for the researchers to determine

whether the differences in NAA levels between

methamphetamine-exposed and nonexposed children

were statistically significant.

Source

• Smith, L.M.; Chang, L.; Yonekura, M.L.; Grob,

C.; Osborn, D.; and Ernst, T. Brain proton magnetic resonance spectroscopy in children exposed

to methamphetamine in utero. Neurology

57(2):255–260, 2001.
Research Findings

Volume 16, Number 4 (October 2001)

31

Pathological Obesity and Drug Addiction Share Common 

Brain Characteristics

By Robert Mathias, NIDA NOTES Staff Writer

Reduced brain activity of dopamine, a naturally occurring

substance that modulates feelings of pleasure, may contribute to obesity as well as drug addiction, a NIDAfunded study suggests. The study found that the brains of

obese individuals have relatively few of the nerve cell components called D2 receptors through which dopamine acts

to stimulate pleasurable feelings from basic activities such

as eating and sex. Individuals with this deficiency may

need to overeat to get feelings of gratification from food,

the researchers say. Because a deficit of the same receptor

has been implicated in addiction to cocaine, heroin, and

other drugs of abuse, the researchers suggest that it may 

be linked to a range of compulsive behaviors.

“Although many complex factors may be involved in

excessive behaviors such as compulsive drug abuse,

overeating, and gambling, they are all similar in that the

brain is changed, reward circuits are disrupted, and the

behavior eventually becomes involuntary,” says Dr. Joseph

Frascella of NIDA’s Division of Treatment Research

and Development. “Finding low D2 receptors across 

various drugs of abuse and now obesity suggests a 

common brain mechanism that could contribute to 

such disorders,” he says.

In the study, Dr. Gene-Jack Wang and Dr. Nora

Volkow of Brookhaven National Laboratory in

Upton, New York, used positron emission tomography (PET) to assess metabolic activity and

dopamine D2 receptor levels in the brains of 10

severely obese and 10 nonobese subjects. The

obese group included five men and five women

and the control group had seven men and three

women. Obese subjects had an average body mass

index (BMI) of 51.2. Controls had an average

BMI of 24.7. BMI is a measure of weight in relation to height. An index of 25 or greater is considered overweight and an index of 30 or above is

considered obese.

The PET scans showed that, compared to controls, obese individuals had significantly fewer

dopamine D2 receptors in the striatum, an area

of the brain where dopamine receptors are particularly concentrated. Data analyses showed that

neither gender nor brain metabolism was related

to the differences in receptor availability

between the two groups. The best direct relationship to

receptor levels was BMI—the greater an individual’s BMI,

the fewer available dopamine D2 receptors.

The brain area the researchers imaged includes the nucleus

accumbens (NAc), the central structure in the brain’s

reward system. Eating increases extracellular levels of

dopamine in the NAc, producing feelings of satisfaction

and pleasure, the researchers explain. Previous research 

has shown that drugs that increase dopamine concentrations in this area decrease appetite. Conversely, drugs that

block dopamine receptors increase appetite and lead to

significant weight gain. “Thus, low D2 receptor levels in

obese individuals may contribute to continued overeating

to compensate for reduced stimulation of their brain

reward circuits,” Dr. Wang says.

“It is through activation of these circuits that we are 

motivated to do the things we perceive as pleasurable,”

Dr. Volkow says. “If you have a decrease in dopamine

receptors that transmit pleasurable feelings, you become

less responsive to the stimuli, such as food or sex, that

normally activate them,” she says. “When these activities

don’t reward you enough, your brain signals you to do

something that will stimulate the circuits sufficiently to

These composite brain scan images show that obese individuals have significantly

fewer dopamine receptors in the outlined area than control subjects. These receptors transmit pleasurable feelings from basic activities such as eating and sex. Low

levels of these receptors also have been found in people addicted to drugs of abuse.

The reduced reward experienced by people with this deficiency may make them

more likely to engage in addictive behaviors. 
create a sense of well-being. Thus, an individual who has

low sensitivity to normal stimuli learns behaviors, such as

abusing drugs or overeating, that will activate them.”

It remains unclear whether low D2 brain receptor levels

are a cause or a consequence of addictive behaviors—or

both. “This deficiency could be a double-edged sword that

cuts both ways,” says NIDA’s Dr. Frascella. First, the

reduced reward experienced by people with this deficiency

may make them more likely to engage in addictive behaviors. Then, the addictive behavior itself could make the

deficit worse as the brain further lowers D2 levels in

response to constant overstimulation of the reward 

pathway. “In the end, they could be much worse off 

biologically than when they started,” he says.

“This phenomenon has important implications for drug

abuse treatment,” Dr. Volkow says. “If the only behavior

that will activate reward centers is taking drugs, then people are going to take drugs. However, if treatment can

help drug abuse patients to develop alternative behaviors

that can activate these centers, they can start to replace

drug use with these behaviors.”

Source

• Wang, G-J.; Volkow, N.D.; et al. Brain dopamine and

obesity. Lancet 357(9253):354–357, 2001.

32
33

NIDA Scientific Panel Reports on Prescription Drug 

Misuse and Abuse

By Patrick Zickler, NIDA NOTES Staff Writer 

Research Findings

Volume 16, Number 3 (August 2001)

NIDA launched a new initiative on prescription drug

abuse, misuse, and addiction at a press conference in

Washington, DC, in April. NIDA developed the initiative

in response to reports of increased abuse of prescription

pain relievers and concern over abuse of other 

prescription drugs. A scientific program following the

press conference provided an overview of current research

into issues associated with prescription opioid drugs 

used in pain relief, central nervous system depressants 

prescribed for anxiety and sleep disorders, and stimulants

used to treat attention-deficit/hyperactivity disorder

(ADHD) and obesity. Dr. Alice Young, a NIDA-supported

researcher at Wayne State University in Detroit, presented

a discussion of the neurobiology of addiction. In subsequent presentations, researchers focused on investigations

into specific aspects of prescription drug abuse.

Dr. Howard Chilcoat of The Johns Hopkins University

School of Public Health and Hygiene in Baltimore discussed research into the epidemiology of prescription drug

abuse. Overall, he said, the number of people who abuse

prescription drugs each year roughly equals the number

who abuse cocaine—about 2 to 4 percent of the population. Whites are more likely than other racial or ethnic

groups to abuse prescription drugs, and many people who

abuse these drugs also have psychiatric disorders. Persons

age 18 to 25 are more likely than persons in other age

groups to begin abusing prescription drugs. Between the

ages of 12 and 17, girls are more likely than boys to begin

prescription drug abuse and are more likely to abuse stimulants and sedatives than other prescription drugs.

Dr. Kenneth Schmader of Duke University in Durham,

North Carolina, said that the elderly (persons age 65 or

older) represent about 13 percent of the U.S. population

but consume one-third of all prescription drugs. These

patients are generally less healthy than younger persons

and often suffer from multiple diseases for which they

take multiple drugs, Dr. Schmader said, and are therefore

more vulnerable than are younger patients to unintentionally misusing and becoming habituated to prescription

medications. In one study of more than 1,500 elderly

patients, 50 patients, roughly 3 percent, were abusing 

prescription drugs. In a study of consecutive admissions to

a treatment program, 70 of 100 elderly patients admitted

for prescription drug abuse were women. Eighty were

dependent (that is, they experienced withdrawl symptoms

if they tried to stop taking the drugs) on sedatives, 49 on

opioids, and 3 on stimulants. Thirty-six were dependent

on 2 drugs and 8 were dependent on 3.

Dr. Timothy Wilens of Massachusetts General Hospital 

in Boston discussed prospective studies designed to determine whether children treated for ADHD with the stimulant methylphenidate (Ritalin) are at risk for abuse of

As part of its initiative on prescription drug misuse and addiction,

NIDA is distributing 400,000 postcards with messages about the

dangers of prescription drugs. The cards are available in restaurants, book stores, clubs, record stores, coffee shops, gyms, and other

locations in several major cities.
34

other stimulant drugs. The research involved two groups

of patients diagnosed with ADHD of similar severity: one

group was treated with methylphenidate and the other

received treatment that did not include stimulants. Dr.

Wilens reported that those who were treated with

methylphenidate were less likely to abuse drugs, including

prescribed or unprescribed stimulants, during treatment

and throughout youth and adolescence.

Dr. Richard Brown of the University

of Wisconsin Medical School in

Madison said that physicians’ misunderstanding of the risks associated

with prescription drugs can lead to

inadequate treatment of some illnesses. Dr. Brown based his statement on

research in which he and his colleagues asked physicians how they

would treat a set of hypothetical

patients who suffered anxiety disorders, pain associated with cancer, or

back pain. The researchers gave the

clinicians detailed profiles of the

hypothetical patients that included a

treatment history and characteristics,

such as use of alcohol and history of

substance abuse, related to possible

misuse of prescription medication. The

researchers compared the physicians’

treatment plans with a plan developed by

a panel of experts. Compared to the experts, the 2,000

physicians who participated in the study were more reluctant to provide opioids and less cautious about prescribing

sedatives. For example, 5 percent of the respondents

would not prescribe opioids for severe cancer pain and

nearly 80 percent would avoid opioids for severe, chronic

back pain that had not responded to other treatments.

About 25 percent of the physicians would prescribe benzodiazepines (sedatives such as Valium or Xanax) for a

hypothetical patient with an adjustment disorder (anxiety

or sadness associated with a particular situation), even

though they showed several signs and symptoms of a current alcohol use disorder.

Dr. Steven Passik of Community Cancer Care, Inc., 

in Indianapolis, Indiana, discussed a study designed to

evaluate the risks of misuse or abuse of drugs prescribed

for management of chronic pain and to compare the risks

with the drugs' benefits. The research involved 264

patients being treated with opioids for chronic pain not

associated with cancer. On average, patients reported that

the drugs relieved nearly 60 percent of their pain, and

more than 90 percent said the pain relief made a significant improvement in their quality of life. Nearly 80 percent reported improvement in overall aspects of daily life

such as mood, physical functioning, relationships, and

sleep patterns. More than 60 percent of patients reported

some adverse side effects from their medication, but only

1.2 percent described the side effects as intolerable.

Overall, roughly 6 percent of patients (or their physicians)

reported abuse or misuse of prescribed drugs. Drug abuse

issues in pain management are complex, Dr. Passik said,

but his study results suggest that the risk of opioid abuse

is low compared with the benefits of the drugs in chronic

pain management.

In 1998 roughly 1.6 million people used prescription pain relievers nonmedically for the

first time—four times as many as in 1980.
Research Findings

35

Annual Survey Finds Increasing Teen Use of Ecstasy, Steroids

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 16, Number 2 (May 2001)

For the fourth year in a row, the percentages of 8th-,

10th-, and 12th-graders avoiding all use of illicit drugs

remained level or increased in 2000, according to the 26th

annual Monitoring the Future study. However, the nationwide survey of drug use among teenagers found that use

of MDMA (ecstasy) has increased in all age groups and

that use of steroids has risen among 10th-graders.

The findings marked the second consecutive year of

increased MDMA use among 10th- and 12th-graders and

the first increase among 8th-graders. In 2000, 8.3 percent

of 12th-graders reported that they had used MDMA at

least once in the past year, up from 5.6 percent in 1999

and 3.6 percent in 1998. Eighth-graders’ use of the drug

increased from 1.7 percent in 1999 to 3.1 percent in

2000. Among 10th-graders, past-year MDMA use

remained statistically unchanged, at 5.4 percent in 2000,

but use in the past month increased from 1.8 percent in

1999 to 2.6 percent last year, according to the study’s

principal investigator, Dr. Lloyd Johnston of the

University of Michigan in Ann Arbor.

Use of steroids during the year prior to the survey rose

from 1.7 percent in 1999 to 2.2 percent in 2000 among

10th-graders but remained stable at 1.7 percent among

8th- and 12th-graders. Among teenage males, where most

steroid use is concentrated, past-year 

use was reported by 2.2 percent of 

8th-graders, 3.6 percent of 10thgraders, and 2.5 percent of 12thgraders, Dr. Johnston said at a

December 2000 press conference

announcing the most recent findings.

The Monitoring the Future study,

conducted by the University of

Michigan’s Institute for Social

Research and funded by NIDA, has

tracked high school seniors’ illicit

drug use and attitudes toward drugs since 1975. Younger

teens, in grades 8 and 10, were added to the survey in

1991. Data for the 2000 survey represent responses of

more than 45,000 students in 435 schools across the

Nation to questions about lifetime use, use during the past

year, use during the past month, and daily use of various

illicit drugs, alcohol, cigarettes, and smokeless tobacco.

“This survey provides crucial information on the realworld experience of young people with drugs, and the

recent increases in MDMA use are a major concern,” said

NIDA Director Dr. Alan I. Leshner. “Ecstasy is not a ‘fun’

drug. It is neurotoxic—it severely damages

brain cells and has consequences that include

dehydration, hypertension, hyperthermia, and

heart or kidney failure.” 

The number of 8th-graders having used 

an illicit drug during the past year has declined

steadily from 22.1 percent in 1997 to 19.5 

percent in 2000. Among 10th-graders, use of

an illicit drug was reported by 38.5 percent in

1997 and 36.4 percent in 2000. For seniors,

past-year use of an illicit drug was reported by

42.4 percent in 1997 and by 40.9 percent 

in 2000.

Tenth-graders’ past-month use of cigarettes was 23.9 percent in 2000, roughly the same as in 1999; however, daily

cigarette smoking decreased significantly in this group,

from 15.9 percent to 14.0 percent. Daily smoking among

12th-graders declined from 23.1 percent in 1999 to 20.6

percent in 2000.

Past-month use of MDMA increased for all teenagers from 1999 

to 2000.

“This survey provides

crucial information

on the real-world

experience of young

people with drugs.” 
36

Reductions in other measures of smoking also occurred

among 8th-, 10th-, and 12th-graders. “For cigarettes, and

for smokeless tobacco as well, the overall declines from

peak levels of the mid-90s have been substantial,” Dr.

Johnston says. Alcohol use by teens remained largely

unchanged in 2000.

For More Information

• Additional information about the Monitoring the

Future study can be obtained from NIDA Infofax at

1-888-NIH-NIDA (644-6432) or from NIDA’s home

page at www.drugabuse.gov. Information is also available from the Monitoring the Future home page at

the Institute for Social Research at the University of

Michigan: www.monitoringthefuture.org. Information

about MDMA (ecstasy) is available at the NIDA club

drugs Web site, www.clubdrugs.org. Information

about steroids is available at NIDA’s steroids Web site,

www.steroidabuse.org.

Steroid use rose among 10th-grade boys and among girls in grades

8, 10, and 12.
Research Findings

37

Volume 16, Number 2 (May 2001)

Adolescents, Women, and Whites More Vulnerable Than Others to

Becoming Nicotine Dependent

By Patrick Zickler, NIDA NOTES Staff Writer 

Rates of drug dependence—the percentage of users who

experience symptoms that reinforce their drug use and

have trouble quitting—are higher for nicotine than for

marijuana, cocaine, or alcohol. Rates of dependence also

vary among different groups of smokers, according to

NIDA-supported research. A new study suggests that 

differences in sensitivity to nicotine make some smokers

more likely than others to develop nicotine dependence.

Age, sex, and race all appear to make a difference.

Dr. Denise Kandel and Dr. Kevin Chen of Columbia

University in New York City analyzed data collected

between 1991 and 1993 as part of the National Household

Survey of Drug Abuse, which surveys a representative

sample of the U.S. population 12 years and older. In

examining data from 22,292 respondents who had smoked

cigarettes during the preceding month, Dr. Kandel and 

her colleagues determined rates of nicotine dependence 

symptoms based on respondents’ reports of tolerance

(needing to smoke more to feel the effects), withdrawal

symptoms, smoking more than intended, failed efforts to

cut down, negative social and job-related consequences,

and persistent health problems.

The researchers found that among persons who smoke

one-half pack of cigarettes each day, nicotine dependence

rates are higher among females than males (31.6 percent

compared with 27.4 percent) and higher among whites

(31.3 percent) than among blacks (25 percent) and

Hispanics (27.6 percent). Adolescents smoke fewer 

cigarettes than adults but experience significantly higher

rates of dependence than adults at the same level of use.

Dependence rates are lowest among adults older than 50.

Overall, the researchers say, dependence rates increase

sharply as consumption moves up to 10 cigarettes per day.

The rates level off with higher consumption, although

dependent smokers need to smoke more to feel the 

physical effects of nicotine.

“Understanding the differences among groups in their 

vulnerability to developing nicotine dependence will be

valuable in developing targeted strategies for prevention,”

Dr. Kandel says. “The higher rates at which adolescent,

women, and white smokers develop symptoms of nicotine

dependence given the same quantity smoked daily seem 

to reflect differences in sensitivity to nicotine. Increased

sensitivity may also account for the fact that adolescents 

develop symptoms of dependence at lower doses of 

nicotine than adults.”

Adolescents appear to be particularly vulnerable to becoming

nicotine dependent, especially at low levels of cigarette

consumption and when they continue to smoke on a regular daily basis, according to the researchers. Adolescents’

nicotine dependence rates were associated with the length

of time that they had been daily smokers, in contrast with

adults, in whom dependence rates were associated with

the amount of tobacco smoked. “Once regular smoking

has been established, quantity smoked may become a

more important determinant of dependence than duration

of daily smoking,” Dr. Kandel says. “This possible 

connection suggests that with adolescents we should focus 

not only on preventing the uptake of smoking but on

shortening smoking careers as soon as possible.”

Source

• Kandel, D.B., and Chen, K. Extent of smoking and

nicotine dependence in the United States: 1991–1993.

Nicotine and Tobacco Research 2(3):263–274,

2000.

Data from the National Household Survey on Drug Abuse show

that the rate of nicotine dependence is higher in people younger

than 25 than in other age groups and that the dependence develops

with less exposure to nicotine.

Rates of Nicotine Dependence Are Greater 

for Young Smokers
Research Findings

38

Maternal Smoking During Pregnancy Associated With Negative

Toddler Behavior and Early Smoking Experimentation

By Josephine Thomas, NIDA NOTES Contributing Writer 

Volume 16, Number 1 (March 2001)

NIDA-funded researchers have added to the accumulating

scientific evidence that women’s smoking during pregnancy adversely affects their children’s health and development. Two new studies have linked prenatal tobacco 

exposure to negative behavior in toddlers and smoking

experimentation by pre-adolescents. 

In a study conducted by Dr. Judith Brook,

Dr. David Brook, and Dr. Martin

Whiteman of the Mount Sinai School of

Medicine in New York City, mothers who

smoked during pregnancy indicated that

their toddlers exhibited more negative

behaviors—impulsiveness, risk-taking, and

rebelliousness—than mothers who did not

smoke during pregnancy reported among

their children.

A study conducted by NIDA-funded

researchers Dr. Marie Cornelius and Dr.

Nancy Day demonstrates that, even more

than growing up in a home where the

mother smokes, prenatal exposure to

smoke may predispose children to early

smoking experimentation. Dr. Cornelius, 

Dr. Day, and their colleagues at the

University of Pittsburgh School of

Medicine found that not only does such

exposure to maternal smoking predict early

experimentation, it also appears linked to

child anxiety, depression, and behaviors such as hitting and

biting others.

Previous studies have supported a link between prenatal

smoking exposure and behavioral problems in later childhood and adolescence. Combined with earlier results, the

new studies suggest that prenatal smoking contributes to a

train of developmental difficulties and health risks that

begin at an early age.

Toddler Negativity

The Mount Sinai study included 99 mothers who smoked

and their 2-year-old children. The mothers are participants

in a large community study that Dr. Judith Brook has

been conducting with Dr. Patricia Cohen of Columbia

University in New York City for the past 25 years. In the

new study, the mothers answered a questionnaire that

elicited information about their children’s behaviors 

and their own smoking histories, alcohol and drug use,

personalities and attitudes, styles of child-rearing, and

socioeconomic characteristics.

Fifty-two of the women reported that they had smoked

while pregnant, and 47 said they

either stopped smoking during

pregnancy or did not begin to

smoke until after they had given

birth. The mothers who smoked

during pregnancy scored their

children higher on the questions

that measured toddler negativity. 

The mother’s disciplinary style

also was strongly linked to a toddler’s negative behavior. However,

when the researchers adjusted for

this factor in the analysis, they

determined that a mother’s smoking during pregnancy independently increased the estimated risk

of negativity at age 2 by fourfold.

“We found three major maternal

risk factors related to toddler negativity,” says Dr. Brook. “They are

maternal smoking during pregnancy, conflicts between the

mother and child, and the mother’s use of power-assertive discipline, such as hitting the

child. We can speculate that maternal smoking during

pregnancy causes disturbances in the neurophysiological

functioning of the fetus,” says Dr. Brook. “This, in turn,

could precipitate the toddler’s negative behavior.”

The potential implications of these findings reach beyond

early childhood. Previous studies have demonstrated that

toddlers who display negative behaviors are more likely to

use drugs, exhibit delinquent behaviors, and achieve less as

adolescents and to develop severe mental health problems

later in life.

Early Experimentation With Tobacco

Although the effects of maternal smoking on childhood

behaviors have been studied, few studies have investigated

the connection between maternal smoking and childhood
39

experimentation with tobacco. The connection is important because the earlier a person starts smoking, the more

likely he or she is to become a regular smoker, become

addicted, and suffer the long-term adverse health effects 

of smoking.

Dr. Cornelius and her colleagues interviewed 589 

10-year-olds. Six percent of the children said they had

tried cigarettes, smokeless tobacco, or both. Most of the

reported tobacco use was experimental; only a few children had used tobacco more than a few times.

In this prospective study, begun by Dr. Day in 1982, the

children’s mothers have been providing researchers with

information about themselves, and they reported on their

smoking at the time they were pregnant with the children

who are now 10. Putting data from the children together

with those reports, the researchers estimated that maternal

smoking of at least a half-pack of cigarettes per day during

pregnancy increased by fivefold the likelihood that a child

would have tried tobacco by age 10. The only factor that

produced a greater risk of early experimentation was 

exposure to smoking within the child’s peer group.

It is not yet clear exactly why these factors are related 

to early experimentation. “Perhaps the nervous system

damage caused by maternal smoking may later be

expressed as impulsivity, inattention, aggression, depression, and/or anxiety and may create a vulnerability in the

child that could contribute to poorer adjustment and an

increased likelihood of early initiation of tobacco use,” 

Dr. Cornelius says.

Dr. Cornelius notes that in her study, the 10-year-olds

who were exposed prenatally to tobacco were more likely

to have experimented than those whose mothers were 

current smokers. This finding reinforces the hypothesis

that a physiological effect of prenatal exposure to smoking, rather than a genetic vulnerability affecting both

mother and child, may be an important link between

mothers’ smoking during pregnancy and early childhood

experimentation.

Sources

• Brook, J.S.; Brook, D.W.; and Whiteman, M. The

influence of maternal smoking during pregnancy on

the toddler’s negativity. Archives of Pediatric and

Adolescent Medicine 154(4):381–385, 2000.

• Cornelius, M.D.; Leech, S.L.; Goldschmidt, L.; and

Day, N.L. Prenatal tobacco exposure: Is it a risk factor

for early tobacco experimentation? Nicotine & Tobacco

Research 2:45–52, 2000.
Research Findings

40

Volume 16, Number 1 (March 2001)

Meeting the Challenge of Reducing Health Disparities

NIDA Director Dr. Alan I. Leshner

Through more than 25 years of scientific research, NIDA has

dramatically advanced our understanding of the ways that

drugs act on cells, in the brain, and in the lives of individuals.

We have also learned how groups of individuals—populations distinguished by race, ethnicity, gender, or other characteristics—are affected by drug abuse. 

NIDA research shows that, contrary to a common stereotype, overall rates of drug abuse among racial and ethnic

minorities are similar to rates in the general population,

although some aspects of drug abuse may differ. For

example, the initiation and progression of drug use appear

to differ among populations. White youth begin using

drugs at a younger age than do minority youth, but evidence suggests young African Americans

who begin using drugs are more likely to

continue use than are whites. 

We also know that some populations suffer

disproportionately from consequences of

drug abuse. Since the AIDS epidemic

began, injection drug use has been directly

or indirectly responsible for more than a

third of all cases overall, but women with

HIV are twice as likely as men to have been

infected through injection drug use or through sexual activity

with an injecting drug user. Minority populations are disproportionately affected by the relationship between drug abuse

and HIV/AIDS. For example, between 1985 and 1999 more

than twice as many blacks (94,700) as whites (36,800) developed AIDS through injection drug abuse, even though there

are only one-fourth as many black injection drug users.

Roughly the same number of Hispanics (35,100) and whites

developed AIDS through injection drug abuse, even though

there are only one-eighth as many Hispanic injection drug

users. Of the drug-related AIDS cases in women reported

through June 2000, 56 percent were among AfricanAmerican women, 21 percent among Hispanic women, and

22 percent among white women. 

NIDA is committed to building scientific understanding of

the environmental, social, and biological factors that influence the different patterns and disproportionate consequences

of drug abuse among various populations. To coordinate and

accelerate research into the health disparities that complicate

efforts to prevent and treat drug abuse among populations,

NIDA has developed a Strategic Plan on Reducing Health

Disparities that will: 

• improve our understanding of the incidence and causes

of drug abuse and addiction in racial and ethnic populations, including Native Americans, Asians, and Pacific

Islanders; 

• strengthen and expand the community and institutional

infrastructure for conducting research within racial and

ethnic populations; 

• provide the scientific foundation for improved prevention and treatment for racial and ethnic groups at highest risk for addiction and medical consequences of drug

abuse and addiction; and 

• widely disseminate information that identifies the best

approaches to prevention and treatment of drug abuse

and the disease of addiction in racial and ethnic communities. 

To reach the goals established in the Strategic Plan, NIDA

has developed a Health Disparities Initiative, which is directed by the Institute’s Special Populations

Office and includes activities in each of

the Institute’s program divisions and

offices. The initiative will focus on four

major research areas: epidemiology,

prevention, treatment, and basic and

clinical research. In some cases, these

efforts will represent an expanded commitment to existing programs, but the

initiative also will include important

new activities. For example, NIDA will expand training

opportunities to increase the capacity of minority institutions—and the number of minority scientists—involved in

drug abuse research. The Center on AIDS and Other

Medical Consequences of Drug Abuse and the Division of

Epidemiology, Services and Prevention Research have jointly

issued a Request for Applications for research projects that

will encourage cross-disciplinary biomedical, epidemiological,

developmental, and social science research to develop more

effective interventions to reduce the impact of HIV/AIDS

and other disease consequences of drug abuse in minority

populations. NIDA also will convene a national conference

on health disparities and drug abuse, to be held in the fall,

that will bring together scientists, policymakers, and educators with expertise on minority populations. These experts

will explore the underlying reasons for health disparities related to drug abuse and develop insights about prevention and

treatment strategies that can be effective in specific minority

populations. 

These efforts are part of a concerted and comprehensive program of research that will help us fill significant gaps in

knowledge about the effects of drug abuse and addiction in

minority populations and will allow us to develop and verify

effective prevention and treatment services that reduce the

disproportionate suffering of these communities.

“Some populations 

suffer disproportionately

from consequences of

drug abuse.”
Research Findings

41

Volume 16, Number 1 (March 2001)

Women and Smokeless Tobacco Use

Although more than 90 percent of smokeless tobacco

users in the United States are male, a substantial number

of women also use smokeless tobacco products. In 1998,

0.5 percent of females over the age of 12, about 573,000,

were current users of smokeless tobacco products, according to the National Household Survey on Drug Abuse.

The comparatively small percentage of women who use

smokeless tobacco accounts in part for the lack of research

on the patterns of smokeless tobacco use among women,

says Dr. Dorothy Hatsukami of the University of

Minnesota School of Medicine. In addition, “women

rarely respond to our advertisements to participate in

smokeless tobacco treatment studies,” she says. For example, Dr. Hatsukami recently reported that 99.8 percent 

of 402 people who responded to advertisements for 

participation in a smokeless tobacco treatment study with

the nicotine patch were male. 

“Women may be embarrassed about admitting smokeless

tobacco use because the general perception is that smokeless

tobacco use is socially undesirable, and women don’t use

it,” Dr. Hatsukami speculates. Among the unattractive

features of smokeless tobacco use is the need to spit tobacco juice from time to time and dislodge particles of loose

tobacco that get trapped between the teeth. This disadvantage of smokeless tobacco use was the one most frequently

cited by women who participated in a study of female

smokeless tobacco users who weren’t seeking treatment,

conducted by Dr. Hatsukami and her colleagues.

In the study, 20 female smokeless tobacco users from the

upper Midwest completed a questionnaire and brief interview. The study revealed some similarities between

females’ smokeless tobacco use and what research has

shown about males’ smokeless tobacco use. For example,

on average, both sexes began using smokeless tobacco

between 16 and 18, and friends played a major role in

their initiating use. About 25 percent of men and women

also indicated they used smokeless tobacco to help them

stop smoking.

The study also revealed some differences in patterns of

smokeless tobacco use by females and the patterns of use

reported in a previous study that assessed features of

smokeless tobacco use among males who weren’t seeking

treatment. For example, on average, the women said they

used 3.6 dips of moist snuff daily, compared to the 6.3

dips reported by males, and women held the tobacco in

their mouths about 22.5 minutes, compared to 39.9 minutes for men. A tin of snuff lasted women anywhere from

2 days to 3 months with a median duration of 6 days per

tin. In contrast, men used approximately 2.8 tins per

week.

The women in this study may have used less smokeless

tobacco than men because they had used smokeless tobacco for less than 4 years, Dr. Hatsukami says. This contrasts with the men, who averaged more than 5 years of

smokeless tobacco use. Perceived social disapproval of

women using smokeless tobacco also may contribute to

lower patterns of use in women. In fact, 38 percent of the

women in Dr. Hatsukami’s study said they could not use

smokeless tobacco in the presence of certain people, and

another 25 percent cited social disapproval as a drawback

to smokeless tobacco use. These social concerns may

reduce opportunities for women to use smokeless tobacco

and lead to lower levels of use, Dr. Hatsukami says. In

spite of these drawbacks, a significant percentage of

women in the study said the relaxing and calming effects

and pleasure they associate with smokeless tobacco use are

advantages of using these products.

Identifying factors associated with smokeless tobacco use

by women and their current patterns of use could generate

ways to prevent and treat smokeless tobacco use among

women, Dr. Hatsukami says. “The data from this research

could help target some of the educational and prevention

messages that we should be giving to women,” she says.

“However, first we have to make women smokeless tobacco users aware that other women use smokeless tobacco

products and that they are not abnormal, so they are

willing to seek help,” she says.

Sources

• Boyle, R.G.; Gerend, M.A.; Peterson, C.B.; and

Hatsukami, D.K. Use of smokeless tobacco by young

adult females. Journal of Substance Abuse 10:19–25,

1998.

• Hatsukami, D.K.; Keenan, R.M.; and Anton, D.J.

Topographical features of smokeless tobacco use.

Psychopharmacology 96:428–429, 1988.
Research Findings

42

Update on Nicotine Addiction And Tobacco Research

Volume 15, Number 5 (October 2000)

What makes nicotine addictive? Why do some children

decide to smoke, while others never light up? What makes

quitting smoking so difficult, and how can we make it

easier? NIDA-funded researchers are seeking answers to

questions like these in nicotine- and tobacco-related 

studies. Following are highlights of recent gains in our

knowledge about nicotine and tobacco. 

Teen Smokers

The NIDA-funded Monitoring the Future survey of 

students in grades 8, 10, and 12 shows that the number 

of current teenage smokers has declined since 1997. Still,

nearly one in four high school seniors smokes every day,

and more than one in eight smokes a half-pack or more

each day.

Peer pressure, parental smoking, and family conflicts are

the most significant predictors of whether a child makes

the transition from occasional smoking to regular cigarette

use. In a study of 11- to 13-year-olds, researchers found

that 75 percent of the children who smoked had one or

two smoking parents. Researchers also found that the earlier teens start to smoke, the more severe their addiction

will be. Depression and delinquency also have been shown

to be powerful predictors of smoking urges and behavior.

Genetic Influences

Researchers have found that they can prevent nicotine

dependence in mice genetically altered so that they lack 

a portion of one of the brain receptors at which nicotine

binds to produce its rewarding effects. While normal mice

self-administered nicotine in laboratory tests, the altered

mice did not. Similarly, a natural genetic mutation has

been found in humans that inhibits nicotine metabolism.

Male smokers with this mutation are less likely to become

addicted to nicotine and more likely to find it easier to

quit smoking; however, the presence or absence of the

defective gene does not affect women’s smoking.

Gender Differences

In addition to the genetic difference described above, 

a number of other gender differences have been found

among smokers. For example, accumulating evidence

shows that, for women, nicotine intake may be less important in smoking behavior than it is for men. Studies have

shown that women take fewer and shorter puffs from cigarettes and are less sensitive to some of nicotine’s effects,

but they may be more sensitive to external stimuli, such as

the presence of a lit cigarette or the smell of smoke. 

Women also have been less successful than men with 

nicotine replacement therapy for smoking cessation.

Treatment Approaches

In addition to nicotine replacements in the form of gum,

skin patches, aerosol spray, and inhalers, medications to

aid smoking cessation include the non-nicotine compound bupropion (marketed as Zyban). Bupropion is a

prescription antidepressant that also blocks nicotine’s

pleasurable effects. Other medications used in the treatment of nicotine addiction include clonidine, mecamylamine, and buspirone.

To date, medication combined with behavioral treatment

has been the most effective approach to treating nicotine

addiction. Behavioral therapies such as relapse prevention/

skills training approaches, motivational enhancement, and

group or individual counseling are designed to support

both short-term and long-term abstinence from nicotine.

On the Horizon

NIDA has defined new areas of nicotine research to include

studies of regional brain metabolism, the role of multiple

nicotine receptors, genetic contributions to smoking initiation and persistence, and the phenomenon of craving.

NIDA’s Teen Tobacco Addiction Treatment Research

Clinic in Baltimore, a new outpatient research program

for treatment of nicotine-addicted adolescents, has 

implemented a 6-month controlled clinical trial addressing the safety, tolerability, and efficacy of two nicotine

replacement therapies—gum and patch—in combination

with either counseling or group support.

At Washington University in St. Louis, a large-scale gene

mapping study is under way to identify candidate genes

for risk of nicotine addiction. Researchers are examining

adult twins to learn more about the relative contributions

of genetic and environmental factors in both smoking 

initiation and continuing cigarette use.

New medications being studied for treating nicotine

addiction include methoxsalen, an approved treatment for

psoriasis, and NicVAX, a vaccine that can immunize

smokers against nicotine’s effects. Methoxsalen reduces the

action of an enzyme that metabolizes nicotine and so may

help smokers quit more easily. NicVAX has been successful in animal studies and soon will be tested in clinical 

trials. The vaccine, if successful with current smokers, also

might be effective in protecting children from the risk of

nicotine addiction.
Research Findings

43

Drug Abuse and Conduct Disorder Linked to Maternal Smoking

During Pregnancy

By Raymond Varisco, NIDA NOTES Contributing Writer 

Volume 15, Number 5 (October 2000)

Researchers at Columbia University in New York City

have found new evidence that children whose mothers

smoke during pregnancy are at much greater risk than

other children for drug abuse and conduct disorder. The

findings reinforce those of other studies spanning more

than 25 years that have shown similar problems associated

with prenatal exposure to smoke in children ranging from

toddlers through teens. The study also revealed marked

gender differences, with girls at significantly increased risk

for drug abuse and boys at significantly increased risk for

conduct disorder.

The investigators interviewed 147 mother-child pairs 3

times over 10 years, with the children ranging from ages 6

to 23 at the start of the study. Both mothers and children

were interviewed on entry into the study, again 2 years

after the initial interview, and, finally, about 10 years after

the initial interview. Because the researchers followed the

children through either adolescence or young adulthood—

something few studies have done before-they were able to

collect data about whether and when the children began

to abuse drugs, says Dr. Myrna Weissman, the study’s

principal investigator.

Data were gathered on psychiatric and substance abuse

disorders of parents; family environmental factors, such as

divorce and family discord; and maternal factors, such as

alcohol and coffee consumption and postnatal smoking, to

rule out other explanations for the presence of drug abuse

and conduct disorder.

The researchers found that maternal smoking during pregnancy has long-term effects on children’s behavior and

health that cannot be explained by any other factor

included in the study. Risk for adolescent drug abuse in

girls was more than 5-fold higher if their mothers smoked

more than 10 cigarettes a day during pregnancy. Among

boys whose mothers smoked more than 10 cigarettes a

day, risk for the onset of conduct disorder was greater than

4-fold that of boys whose mothers did not smoke, with

the increase appearing in boys younger than 13. The drug

most frequently abused by both boys and girls was marijuana, and the most frequent combination of drugs

abused was marijuana and cocaine. Of the females who

abused drugs, 70 percent abused more than one.

Why boys exposed to smoking before birth should be at

risk for conduct disorder and girls at risk for drug abuse

remains to be understood, Dr. Weissman says. She 

speculates that the differences may be related to sex 

differences in prenatal brain development.

Many of the findings of this study are consistent with

those of related studies, she notes. Researchers at the

University of Chicago also have found a link between

maternal smoking during pregnancy and conduct disorder

in boys, she says. Likewise, a 1994 study conducted by

Dr. Weissman’s coinvestigator Dr. Denise Kandel found

that maternal smoking during pregnancy increases risk for

adolescent-onset smoking in girls. Studies also have found

other behavioral problems in children exposed prenatally

to smoke. For example, scientists at Massachusetts General

Hospital found an association between prenatal exposure

to smoke and attention deficit hyperactivity disorder.

Similarly, a recent study by Dr. Judith Brook and her colleagues at Mount Sinai School of Medicine in New York

City has found negative behavior in 2-year-olds of mothers who smoked during pregnancy.

Sources

• Brook, J.S.; Brook, D.W.; and Whiteman, M. The

influence of maternal smoking during pregnancy on

the toddler’s negativity. Archives of Pediatrics and

Adolescent Medicine 154:381–385, 2000.

• Kandel, D.B.; Wu, P.; and Davies, M. Maternal

smoking during pregnancy and smoking by adolescent daughters. American Journal of Public Health

84:1407–1413, 1994.

• Wakschlag, L.S; Lahey, B.B.; Loeber, R.; Green, S.M.;

Gordon, R.A.; and Leventhal, B.L. Maternal smoking

during pregnancy and the risk of conduct disorder in

boys. Archives of General Psychiatry 54:670–676, 1997.

• Weissman, M.M.; Warner, V.; Wickramaratne, P.J.;

and Kandel, D.B. Maternal smoking during pregnancy

and psychopathology in offspring followed to adulthood. Journal of the American Academy of Child and

Adolescent Psychiatry 38:7, 1999.
Research Findings

44

Boys and Girls Encounter Different Drug Offers, Use Different

Refusal Strategies

Volume 15, Number 4 (September 2000)

NIDA-funded researchers at the Arizona State University

in Phoenix found that among 12-year-olds who have been

offered drugs, boys are most likely to have received those

offers from other males or their parents. Girls are most

likely to have been offered drugs by a female friend or

family member. Although the most common strategy for

rejecting these offers is a simple refusal, boys are more

likely than girls to explain their refusal.

Dr. Dreama Moon (now at California State University,

San Marcos) and Dr. Michael Hecht (now at Pennsylvania

State University) interviewed 2,622 7th-graders in the

metropolitan Phoenix area to determine patterns of 

exposure to and use of illicit drugs-alcohol, tobacco, 

marijuana, or “hard drugs” (described in the interviews as

hallucinogens, cocaine, or crack cocaine), and inhalants.

“Boys are more at risk than girls for offers at a younger

age, and more likely to be offered alcohol, marijuana, and

‘hard’ drugs by their parents or by other males—relatives,

acquaintances, and strangers,” Dr. Moon says. “On the

other hand, girls tend to be at risk for offers from other

girls-acquaintances or family members of roughly the

same age-or, to a lesser extent, from older boyfriends.”

The social settings and nature of drug offers also differ by

gender, the researchers say. Boys are more likely to receive

offers in a public setting, such as on the street or in a

park, and the offers to males typically emphasize the “benefits”—improved status or self-image—of drug use. Girls

are more likely to receive a straightforward “do you want

some?” offer or one that minimizes the risks of drug use.

For girls, these offers are usually made in a private setting

such as a friend’s home.

The strategies used to resist drug offers appear to have

gender-based influences, Dr. Moon notes. “Boys are often

socialized in a way that makes a simple ‘no’ unacceptable.

They are more likely to explain their refusal,” she says.

Girls, on the other hand, are less likely to use an “explain”

strategy because it leads to a counter explanation. “If this

continues through two or three cycles of explain-andcounter, girls may be susceptible to use,” according to Dr.

Moon. “Understanding the different ways in which boys

and girls experience and refuse offers of drugs is crucial to

the design of more effective intervention or prevention

programs,” she says.

Source

• Moon, D.G.; Hecht, M.L.; Jackson, K.M.; and

Spellers, R.E. Ethnic and gender differences and similarities in adolescent drug use and refusals of drug

offers. Substance Use & Misuse 34(8):1059–1083,

1999.
Research Findings

45

Volume 15, Number 4 (September 2000)

Gender Differences in Drug Abuse Risks and Treatment

Over the past few years NIDA has made a major research

commitment to identifying and understanding differences

in the ways that women and men—or girls and boys—

are first exposed to drugs, in their risks of abuse and

addiction, and in the effectiveness of drug treatment.

Understanding these differences, and incorporating that

understanding into drug abuse prevention and treatment,

can reduce the dangers and improve outcomes. NIDAsupported research has shown that gender differences play

a role from the very earliest opportunity to use drugs, that

women and men tend to abuse different drugs, that the

effects of drugs are different for women and men, and that

some approaches to treatment are more successful for

women than for men.

Are Women Less Likely Than Men to Abuse Drugs?

Men are more likely than women to have opportunities to

use drugs, but men and women given an opportunity to

use drugs for the first time are equally likely to do so and

to progress from initial use to addiction. However, women

and men appear to differ in their vulnerability to some

drugs. Both are equally likely to become addicted to or

dependent on cocaine, heroin, hallucinogens, tobacco, and

inhalants. Women are more likely than men to become

addicted to or dependent on sedatives and drugs designed

to treat anxiety or sleeplessness, and less likely than men

to abuse alcohol and marijuana. There are also differences

between men and women who seek treatment for drug

abuse. Women in treatment programs are less likely than

men to have graduated from high school and to be

employed and are more likely than men to have other

health problems, to have sought previous drug treatment,

to have attempted suicide, and to have suffered sexual

abuse or other physical abuse.

Are There Gender Differences In the Biological Effects

of Drugs?

Animal research and human studies have revealed that

males and females may differ in their biological responses

to drugs. In studies of animals given the opportunity to

self-administer intravenous doses of cocaine or heroin,

females began self-administration sooner than males and

administered larger amounts of the drugs. Women may be

more sensitive than men to the cardiovascular effects of

cocaine. In human studies, women and men given equal

doses of cocaine experienced the same cardiovascular

response despite the fact that blood concentrations of

cocaine did not rise as high in women as in men. In studies involving long-term cocaine users, women and men

showed similar impairment in tests of concentration,

memory, and academic achievement following sustained

abstinence, even though women in the study had substantially greater exposure to cocaine. Women cocaine users

also were less likely than men to exhibit abnormalities of

blood flow in the brain’s frontal lobes. These findings suggest a sex-related mechanism that may protect women

from some of the damage cocaine inflicts on the brain.

Does Gender Play a Role in Nicotine Addiction?

Women and men are equally likely to become addicted 

to nicotine, yet women typically smoke cigarettes with

lower nicotine content than those smoked by men, smoke

fewer cigarettes per day, and inhale less deeply than men.

Overall, however, women are less successful than men 

in quitting smoking and have higher relapse rates after

they do quit. Treatment involving nicotine replacement

therapy-nicotine gum or patch-works better for men 

than for women.

What Are Women’s Risks for HIV/AIDS?

Research suggests that there are sex-related differences in

some fundamental aspects of the HIV/AIDS disease

process. For example, an HIV-infected woman with half

the amount of virus circulating in the bloodstream as an

infected man will progress to a diagnosis of AIDS in about

the same time. And, according to the Centers for Disease

Control and Prevention, among cases that progress to a

diagnosis of AIDS, drug abuse accounts for a greater percentage of cases among women than among men. Nearly

half (47 percent) of all women diagnosed with AIDS are

injecting drug users (IDUs), whereas among men, IDUs

account for 32 percent of AIDS cases. An additional 19

percent of women, compared with 2 percent of men, with

AIDS report having sex with users who inject drugs. In

all, drug abuse is nearly twice as likely to be directly or

indirectly associated with AIDS in women (66 percent) as

in men (34 percent).

For More Information

• NIDA’s gender-related research is discussed in Drug

Addiction Research and the Health of Women, available on NIDA’s home page on the World Wide Web:

www.drugabuse.gov or from the National

Clearinghouse for Alcohol and Drug Information

(NCADI), P.O. Box 2345, Rockville, MD 20847-

2345, (800) 729–6686. 
Research Findings

46

NIDA’s Epidemiological Compasses

NIDA Director Dr. Alan I. Leshner 

Volume 15, Number 3 (July 2000)

Epidemiology is the science of identifying trends 

and patterns in the occurrence of health problems.

Epidemiological studies advance NIDA’s mission by gauging the scope and nature of the Nation’s drug problems

and providing information fundamental to improving

treatment and prevention.

NIDA sponsors two major epidemiological tracking 

programs. The Monitoring the Future study (MTF), now

in its 25th year, asks 50,000 students in a representative

sample of the Nation’s middle and high schools

to report on their use of drugs and attitudes

toward drug use. MTF provides a sensitive register of trends and patterns of drug use among

youth. The other program, NIDA’s Community

Epidemiology Work Group (CEWG), has

tracked drug abuse in 20 of the Nation’s largest

cities and the State of Texas for 24 years. CEWG

gathers information from State and local law

enforcement agencies, survey data, and a variety

of public health services. The researchers review

data on drug-related deaths and emergency

department visits, admissions to drug abuse

treatment programs, drug arrests,

and drug test results among

arrestees. CEWG investigators

also conduct focus groups and

interviews with community

members. CEWG is particularly

attuned to the harmful impacts

of drug abuse and has given early

warning of every emerging major

drug trend in recent decades.

NIDA uses MTF and CEWG to

document the size of the drug

abuse problem, spot trends, pinpoint the groups in the Nation’s

pop-ulation that are most in need

of prevention and treatment, and

assess the effectiveness of interventions. Epidemiological estimates of the number of people abusing a particular drug are also used to set NIDA’s

research agenda. These estimates may be weighed, along

with what is known or suspected about the health and

social consequences of abusing the drug and evaluations of

technical feasibility, in determining directions for research.

NIDA’s epidemiology programs also enable us to respond

rapidly to new trends in drug use. This is critical because,

when a new drug of abuse comes on the scene, young

people tend to hear first about its attractive properties.

They also need to hear—and hear quickly—about the

drug’s health and social consequences in order to quell the

trend at an early stage.

Within the past year alone, NIDA has twice mobilized

rapid responses to epidemiological evidence of new trends.

First, the latest MTF recorded a leveling

off of students’ overall drug use, but a

sharp rise in their use of anabolic-androgenic steroids from 1998 to 1999. The

results also showed a decrease in the percentage of 12th-graders reporting that

they believed these drugs are harmful.

NIDA immediately mobilized a campaign to alert parents and potential users

that steroids are anything but safe.

Steroid abusers are at risk for stunted

growth, increased aggression, and

(although this is rare) fatal liver disease.

Males may experience

testicular shrinkage and

breast enlargement, while

females may experience

masculinization and

menstrual irregularity. To

date, NIDA has spread

this message via a

Research Report, a

Community Drug Alert

Bulletin, a fact sheet and

press releases, two 

eye-catching postcards, 

and a special Web site,

www.steroidabuse.org. In

mid-April, NIDA and

influential partners from

the worlds of sports and medicine held a press conference

that drew media attention to the dangers of these drugs

and announced the first successful program to prevent

steroid abuse among high school athletes. One register of

the timeliness of this effort is the strong response from the

public. More than 1,000 individuals viewed the Web site

daily during the first days of its operation.

“NIDA uses two epidemiological 

tracking programs to document the

size of the drug abuse problem, spot

trends, pinpoint the groups in the

Nation’s population that are most in

need of prevention and treatment, 

and assess the effectiveness of 

interventions.”
47

In a second example of epidemiology findings galvanizing

a rapid NIDA response, last winter NIDA mounted a

similarly comprehensive public information campaign 

in response to a CEWG finding that use of MDMA

(ecstasy), Rohypnol, ketamine, and other so-called club

drugs was increasing. Clearly, drug dealers and the reports

of some users had convinced many young people that

these drugs offered low-risk pleasure. NIDA’s continuing

campaign emphasizes case reports of acute side effects

including heart attacks, strokes, coma, and death from 

respiratory depression, as well as research findings of longterm neurotoxicity and memory loss following exposure to

some of these drugs. (For more on NIDA’s research on

club drugs, see www.clubdrugs.org.)

Public information campaigns are among NIDA’s most

immediate responses to new trends revealed by MTF and

CEWG. For the longer term, epidemiological findings

highlight questions for research. Thus, NIDA has joined

with a number of institutional partners to earmark $54

million to investigate club drugs. As another recent striking example of epidemiological findings leading to a

research response, in the 1990s NIDA studies disclosed

that most new heroin use was occurring in suburbia rather

than—as previously—in urban centers. In addition, many

new users were inhaling rather than injecting the drug,

often lulled by beliefs that inhalation would not lead to

addiction or exposure to blood-borne diseases such as

HIV/AIDS and hepatitis C. To examine these beliefs,

NIDA sponsored a study of transition from heroin 

inhalation to injection. Not only did the results show that

transition was often rapid, they also documented very

high rates of hepatitis C infection among new injecting

drug users. NIDA is now disseminating this information

as a deterrent to the myth of safe heroin use.

Drug abuse in the Nation is never static. The availability

of new illicit drugs, changing circumstances in our communities, even generational shifts fuel new problems and

create new opportunities for interventions. By tracing the

complex patterns of drug abuse, MTF and CEWG help to

identify where prevention and treatment are most needed

and can be most effective. They also provide us the measure of our success in curbing the growth in drug abuse

that occurred in the 1990s, and of the challenge still

remaining.
Research Findings

48

Volume 15, Number 3 (July 2000)

About Anabolic Steroid Abuse

NIDA has issued an updated research report that summarizes the latest scientific information on anabolic steroids.

The eight-page Research Report, Anabolic Steroid Abuse, 

is part of a nationwide education initiative launched by

NIDA and several national organizations to counter a 

significant rise in anabolic steroid abuse among 

adolescents. Highlights from the report are: 

What are anabolic steroids?

Anabolic steroids are synthetic substances related to the

male sex hormones, called androgens. They have a number of physiological effects, most notably an anabolic

effect that promotes the growth of

skeletal muscle and androgenic

effects that foster the development of

male sexual characteristics. Although

the proper term for these compounds is an abolic-androgenic

steroids, they commonly are called

anabolic steroids.

Anabolic steroids are legally available

only by prescription in the United States. Doctors use these

drugs to treat delayed puberty, impotence, and body wasting

in patients with AIDS and other diseases. Abused steroids

most often are obtained from clandestine laboratories, smuggled, or illegally diverted.

What is the scope of steroid abuse?

Steroid abuse is higher among males than females but is

growing most rapidly among young women. An estimated

2.7 percent of 8th- and 10th- graders and 2.9 percent of

12th-graders have taken anabolic steroids at least once in

their lives, according to the 1999 Monitoring the Future

study, a NIDA-funded survey of drug abuse among adolescents. These figures represent increases since 1991 of

approximately 50 percent among 8th- and 10th-graders

and 38 percent among 12th-graders.

Why do people abuse anabolic steroids?

Abuse of anabolic steroids is motivated in most cases by a

desire to build muscles, reduce body fat, and improve

sports performance. Abuse is estimated to be very high

among competitive bodybuilders and may also be widespread among other athletes. Some men who abuse

steroids perceive their own bodies to be small and weak,

even if they are large and muscular. Some women who

abuse these drugs think they look obese or flabby, even

though they are actually lean and muscular. Other 

individuals abuse steroids because they are trying to

become bigger and stronger to protect themselves from

recurrence of physical or sexual assaults.

How are anabolic steroids used?

Anabolic steroids are taken orally as tablets or capsules, by

injection into muscles, or as gels or creams that are rubbed

into the skin. Doses taken by abusers can be up to 100 times

greater than doses used for treating medical conditions.

Anabolic steroids often are taken in combination in a

practice called “stacking,” in which the abuser mixes oral

and/or injectable types of anabolic

steroids. Steroid abusers often also

“pyramid” stacked compounds in

cycles of 6 to 12 weeks, meaning

that they gradually increase doses

then slowly decrease them to zero.

The belief that these practices produce bigger muscles and allow the

body to adjust to and recuperate

from high doses of steroids has

not been substantiated scientifically.

What are the potential health consequences of steroid

abuse?

Health consequences associated with anabolic steroid

abuse include:

• Hormonal system disruptions. Reduced sperm 

production, shrinking of the testicles, impotence, and

irreversible breast enlargement in boys and men.

Decreased body fat and breast size, deepening of the

voice, growth of excessive body hair, loss of scalp hair,

and clitoral enlargement in girls and women.

• Musculoskeletal system effects. Premature and 

permanent termination of growth among adolescents

of both sexes. 

• Cardiovascular diseases. Heart attacks and strokes. 

• Liver diseases. Potentially fatal cysts and cancer. 

• Skin diseases. Acne and cysts. 

• Infections. In injecting steroid abusers, HIV/AIDS, hepatitis B and C, and infective endocarditis, a potentially

fatal inflammation of the inner lining of the heart. 

• Behavioral effects. Increased aggressive behavior, 

particularly when high doses are taken. Depression,

mood swings, fatigue, restlessness, loss of appetite, and

reduced sex drive when steroid abuse is stopped. 

“Doses taken by abusers can

be up to 100 times greater

than doses used for treating

medical conditions.”
Research Findings

49

Volume 15, Number 3 (July 2000)

NIDA Initiative Targets Increasing Teen Use of Anabolic Steroids

By Patrick Zickler, NIDA NOTES Staff Writer

To reverse the rising use of anabolic steroids by high

school-age children, NIDA and seven national partners

have launched an initiative designed to alert the public

about the risks associated with anabolic steroid use.

“The most recent data from our Monitoring the Future

survey tell us that the trends in use of these drugs and in

teenagers’ attitudes about them are going in the wrong

direction,” said NIDA Director

Dr. Alan I. Leshner at a

Washington, DC, press conference to announce the 

initiative. “More than a half

million 8th- and 10th-grade

students are now using these

dangerous drugs, and increasing

numbers of high school seniors

say they don’t believe the drugs

are risky.”

Anabolic steroids are synthetic

compounds that mimic the

action of the male sex hormone

testosterone. The drugs have

some medical uses, but they

also are abused by some athletes

and sports enthusiasts who want

to increase muscle mass and improve performance. Some

teens use them because of concern about body image.

In adolescents, anabolic steroid abuse can halt bone

growth and has been associated with damage to the heart,

kidneys, and liver. In males, steroid abuse can lead to

impotence, shrunken testicles, and breast enlargement. 

In females, the drugs’ effects include menstrual irregularities, growth of body hair and loss of scalp hair, a deepened

voice, and reduction in breast size. Some of these biological

effects are irreversible. Use of anabolic steroids also has

been linked to increased and unpredictable levels of

aggression in human and animal studies.

NIDA’s initiative includes a new Web site—www.steroid

abuse.org—that provides science-based information about

the risks and prevention of steroid abuse. NIDA has also

released an updated Research Report on anabolic steroids

as part of the nationwide multimedia initiative. NIDA

and its partners will distribute 250,000 copies of a special

Community Drug Alert Bulletin on anabolic steroid abuse

and will place 500,000 “art cards”—colorful postcards

with messages about the harmful effects of steroid abuse—

in gyms, bookstores, restaurants, and clubs in Washington,

DC, Los Angeles, Miami, Baltimore, Seattle, and

Indianapolis.

The Institute’s partners in the initiative include the

National Collegiate Athletic Association, the American

Academy of Pediatrics, the American College of Sports

Medicine, the National Association

of School Nurses, the National

Federation of High Schools,

International Students in Action, and

Dr. Drew Pinsky, a physician who

hosts discussions about relationships

and sexual behavior on MTV’s

“Loveline” and the Web site

www.drDrew.com.

The press conference announcing the

initiative was followed by a scientific

session at which NIDA-supported 

scientists presented summaries of

research on anabolic steroids. Dr.

Charles Yesalis of Pennsylvania State

University discussed the history and

social context of steroid use and

abuse. Dr. Linn Goldberg and 

As part of NIDA’s anabolic steroids initiative, the Institute

has distributed more than 500,000 “art” cards—colorful

postcards with messages about the harmful effects of steroid

abuse—in gyms, restaurants, bookstores, and clubs. 

Dr. Linn Goldberg (left) of Oregon Health

Sciences University, explains the Adolescent

Training and Learning to Avoid Steroids

(ATLAS) program to reporters at a science session

following the NIDA press conference.
50

Dr. Diane Elliot of the Oregon Health Sciences University

in Portland described the Adolescent Training and

Learning to Avoid Steroids (ATLAS) program, a sciencebased prevention program that uses a team-centered

approach to educate young male athletes about the risk

and protective factors associated with steroid use. The

researchers are currently developing a similar program—

Athletes Targeting Healthy Exercise and Nutrition

Alternatives (ATHENA)—to prevent eating disorders and

abuse of steroids and other body-shaping drugs by young

women on school-sponsored athletic, dance and drill, and

rally teams. 

Dr. Harrison Pope of the McLean Hospital in Belmont,

Massachusetts, discussed results of a study designed to

examine the effects of steroids on mood and increased

aggression, a phenomenon referred to as “roid rage.” The

research, which involved 56 men who regularly work out

at gyms and health clubs, revealed increased aggressive

behavior in some participants who received testosterone in

dosages smaller than those typically used by athletes or

body-builders. Dr. Marilyn McGinnis of Mount Sinai

School of Medicine in New York City provided additional

evidence that steroid use can result in aggressive behavior.

She described recently-completed laboratory studies in

which rats with elevated levels of steroids exhibited 

unprovoked aggression toward passive, nonthreatening rats

as well as intensely aggressive responses to provocation.

For More Information

• The NIDA Research Report “Anabolic Steroid Abuse”

(NCADI publication #PHD561) can be obtained

from the National Clearinghouse for Alcohol and

Drug Information, P.O. Box 2345, Rockville, MD

20847; phone 800-729-6686; fax 301-294-5516; 

e-mail info@health.org. The report and other information about anabolic steroids can be found at the

special NIDA Web site: www.steroidabuse.org.

“Art” cards like this and the one on the previous page help spread

the word about the harmful effects of steroids.

“More than a half million 8thand 10th-grade students are now

using these dangerous drugs, and

increasing numbers of high school

seniors say they don’t believe 

the drugs are risky.” 
Research Findings

51

Evidence Builds That Genes Influence Cigarette Smoking

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 15, Number 2 (June 2000)

More than one in four Americans older than 17 regularly

smokes cigarettes despite increasing public awareness of

tobacco’s severe health risks. Some start younger than others and, among those who try to quit, some are more successful than others. NIDA-supported scientists are finding

increasing evidence that these differences may be due in

part to an inherited vulnerability to nicotine addiction.

At the St. Louis University Health Sciences Center, Dr.

William True and Dr. Hong Xian

interviewed male twin pairs to

assess genetic influences on smoking. In twin studies, researchers

compare patterns of tobacco use

in fraternal and identical twin

pairs, who typically are exposed

to common environmental influences. If genes play a role in

determining tobacco use, identical twins—who share the same

genes—will be more similar in

their use of tobacco than fraternal

twins, who share roughly half of

their genes. The St. Louis

University researchers found that

among the 3,356 twin pairs studied, genetic factors make a

stronger contribution to nicotine

dependence (61 percent) than do

environmental factors (39 percent) and also play a more prominent role (55 percent) than environmental factors (45 percent) in

alcohol dependence. In another

study, Dr. Kenneth Kendler and

his colleagues at the Medical

College of Virginia in Richmond

interviewed 949 female twin pairs and found that genetic

factors play a more important role (78 percent) than do

environmental factors (22 percent) in smoking initiation

and in nicotine dependence (72 percent vs. 28 percent).

“These studies emphasize the importance of understanding the role of genetic influences in smoking,” says Dr.

Jaylan Turkkan, chief of NIDA’s Behavioral Sciences

Research Branch. “The more we understand about 

vulnerabilities, risks, and possible protective factors, the

better able we will be to tailor treatments that help people

stop smoking.”

Other NIDA-supported scientists are studying genes that

are polymorphic—that is, in different individuals the same

gene has slight variations called alleles—and have found

that individuals with one type of allele are more likely to

begin smoking or to have greater success quitting than are

individuals with another type.

For example, researchers at the

University of Toronto have

found that different alleles in a

gene that helps regulate nicotine

metabolism may protect some

smokers from becoming 

dependent on nicotine. 

Dr. Caryn Lerman, principal

investigator of the NIDA-supported Transdisciplinary Tobacco

Use Research Center at

Georgetown University in

Washington, DC, and her 

colleagues studied two genes,

designated SLC6A3 and DRD2,

that may influence smoking

behavior by affecting the action

of the brain chemical dopamine.

In a study involving 289 smokers

and 233 nonsmokers (42 percent

male, 58 percent female, average

age 43), the researchers found

that smokers were less likely to

have an allele designated

SLC6A3-9 (46.7 percent) than

were nonsmokers (55.8 percent).

The likelihood of smoking was

even lower if the individual had both the SLC6A3-9 allele

and the DRD2-A2 allele. In addition, Dr. Lerman

observed that smokers with the SLC6A3-9 allele were

more likely to have started smoking later and to have had

longer periods of smoking cessation than those without

the allele. These findings imply that the allele may impart

a protective effect. Therefore, Dr. Lerman suggests, smokers without the SLC6A3-9 allele may be better able to

quit smoking if their treatment incorporates a medication

A Medical College of Virginia study involving 949

female twin pairs found genetic factors to be more

influential than environmental factors in smoking

initiation and nicotine dependence. Likewise, a 

St. Louis University study of 3,356 male twin pairs

found genetic factors to be more influential for

dependence on nicotine and alcohol. 
52

such as bupropion that acts on the brain’s dopamine pathway. This hypothesis is currently being tested in a 

randomized trial.

Dr. Lerman and her colleagues

also studied a polymorphism in a

gene, designated 5-HTTLPR, that

helps regulate the brain chemical

serotonin to determine the gene’s

possible role in smoking. The

polymorphism has two alleles,

one designated the short, or S,

allele, the other the long, or L

allele. In previous studies the S

allele has been linked to neuroticism—an anxiety-related

personality trait. Dr. Lerman and her colleagues studied

185 smokers (46 percent male, 54 percent female, and

average age 45) to investigate the possible relationship

between genetically influenced neuroticism and smoking

behavior. They found that neuroticism was associated with

increased nicotine dependence, smoking for stimulation,

and smoking to relieve negative mood in the group of

smokers who had the S allele. Among smokers with the L

allele, neuroticism was not associated with these smoking

patterns. “Anxious persons tend to smoke more and have

more difficulty quitting,” Dr. Lerman says. The new findings suggest that among smokers with neuroticism, determining the 5-HTTLPR genotype may help identify who

will be more responsive to a particular type of treatment.

“Once validated, these results may lead to targeted pharmacotherapy for smoking cessation,” says Dr. Lerman.

“This area of research represents our first small steps along

a very complicated path to understanding the role that

genes play in drug abuse,” notes

Dr. Harold Gordon of NIDA’s

Clinical Neurobiology Branch.

“Many genes interact with each

other and with other biological and

environmental factors. Defining

these interactions and understanding their influence on nicotine

addiction will be crucial to development of treatments for smoking

and for other addictions.”

Sources

• Kendler, K., et al. A population-based twin study in

women of smoking initiation and nicotine dependence.

Psychological Medicine 29(2):299–308, 1999. 

• Lerman, C., et al. Evidence suggesting the role of 

specific genetic factors in cigarette smoking. Health

Psychology 18(1):14–20, 1999. 

• Lerman, C., et al. Interacting effects of the serotonin

transporter gene and neuroticism in smoking practices

and nicotine dependence. Molecular Psychiatry

5(2):189–192, 2000.

• True, W.R., et al. Common genetic vulnerability for

nicotine and alcohol dependence in men. Archives of

General Psychiatry 56(7):655–661, 1999.

“The more we understand

about vulnerabilities, risks, and

protective factors, the better

able we will be to help people

stop smoking.”
Research Findings

53

Volume 15, Number 2 (June 2000)

Antibody May Treat PCP Overdose and Abuse, 

Also Block Prenatal Harm

By Robert Mathias, NIDA NOTES Staff Writer 

A monoclonal antibody being developed by NIDAsupported scientists may treat PCP (phencyclidine) overdose and abuse and also may block or reduce the fetal

brain damage that can result from prenatal exposure to

PCP. The antibody, which like other monoclonal antibodies is derived from a single cell and then produced in large

quantities, reduces PCP’s psychoactive and toxic effects by

attaching itself to PCP in the bloodstream and blocking or

reversing its chemical actions in the brain.

Researchers led by Dr. Michael Owens, who directs the

Center for Alcohol and Drug Abuse Studies at the

University of Arkansas Medical Center in Little Rock,

have been testing the PCP antibody in an extensive series

of studies aimed at increasing understanding of how such

antibodies work in the body to counter the harmful effects

of abused drugs. These studies have shown that a fragment

of the PCP antibody, called “Fab,” can rapidly remove

PCP from the brains of rats. The full antibody,

immunoglobulin G (IgG), can provide significant longterm reductions in PCP brain concentrations and reduce

PCP’s behavioral effects in rats given repeated doses 

of the drug.

Treating PCP Overdose

Every year, many PCP abusers are treated in hospital

emergency rooms for psychotic symptoms, such as 

delusions and paranoia, or for overdose of the drug. 

PCP alone or in combination with other drugs prompted

2,287 visits to hospital emergency departments across the

United States in the first 6 months of 1997, according to

Drug Abuse Warning Network data compiled by the 

Substance Abuse and Mental Health Services Administration.

People under the influence of PCP often become violent

or suicidal. Thus, a treatment that could quickly detoxify

PCP abusers with a single injection would be valuable in

reducing the harm that PCP abusers can cause to themselves or others. It could also shorten hospital stays and

reduce the long-term costs associated with their recovery.

In their studies, the researchers showed that a single large

dose of “Fab” completely removed PCP within 15 minutes

from the brains of living rats whose bodies had been saturated with PCP. The body processes “Fab” more quickly

than it does the whole antibody and can eliminate it rapidly through the kidneys along with the PCP that is

bound to it, Dr. Owens explains. “Fab’s fast-in/fast-out

action makes it perfect for treating the acute toxic effects

of drug overdose in hospital emergency rooms,” he says.

With NIDA’s support, Dr. Owens plans to complete the

necessary preclinical research and apply for approval from

the Federal Food and Drug Administration (FDA) to

begin clinical trials of “Fab” in humans.

Long-Term Treatment for PCP Abuse

The researchers found that, in contrast to the short-term

effects of “Fab,” a single, large dose of IgG, given 24 hours

after they started infusing rats with PCP, significantly

reduced PCP brain concentrations during 27 days of continuous high-dose PCP infusion. In other studies, a single

injection of IgG greatly reduced such PCP-induced effects

as hyperactivity and distance traveled by rats given escalating doses of PCP every 90 minutes, on every third day,

over 2 weeks. Measurements of these behavioral effects

Measurements of rats’ movement showed that administering the PCP antibody, “Fab,” dramatically reduced the distance PCP-treated rats

traveled during the experiment. The antibody reduced PCP’s behavioral effects almost immediately to levels of rats that were not given PCP.
54

during the experiment showed that IgG-treated rats had

significant decreases in PCP-induced responses for the

entire 2-week period compared to rats that had been treated with an inactive saline solution.

Although many details must be worked out before IgG

and similar antibodies can be used in long-term treatment

of drug abuse, the results from these animal studies are

encouraging, Dr. Owens says. If, as these studies suggest, 

a single injection of IgG can significantly reduce PCP

brain concentrations and behavioral effects in rats for

extended periods, antibody-based medications might be

able to block or significantly blunt the rewarding effects of

the drug for a month or more in humans, he says. Thus, 

if someone in treatment relapsed to drug use, the PCP

antibody would diminish the drug’s pleasurable effects and

reduce the incentive to use it again. “Therefore, this might

make a good medication to combine with behavioral

approaches in a comprehensive treatment plan to give

people a better chance of recovery,” Dr. Owens says.

Prenatal Protection From PCP Exposure

Because the PCP antibody would remove the drug from

the bloodstream of a pregnant woman, theoretically it

would be possible to use it to block the fetal brain damage

that prenatal PCP exposure has been shown to cause in

rats, Dr. Owens says. “We have no reason to believe that 

if the antibody were used properly it wouldn’t work to

pull PCP out of the placenta in the same way it pulls it

out of other organs that we have tested, such as the brain

and testes,” he says.

Pregnant women with deficient immune responses have

been given massive doses of antibodies to supplement

their immune systems with no ill effects, Dr. Owens

points out. “Therefore, it may be possible to give pregnant

women the large doses we use in our animal studies,” he

says. Furthermore, “if the antibody does not harm the

mother, it is unlikely that it will harm the fetus.” The key

is to use forms of the antibody that do not trigger an allergic reaction in the mother or fetus, he says.

“The potential for the PCP antibody to block harmful

prenatal effects certainly would be worth examining,” 

says Dr. Jamie Biswas of NIDA’s Division of Treatment

Research and Development. However, considerable

research would be needed to establish the risks to both 

the mother and fetus of using the antibody versus the

potential benefits of blocking PCP’s possible fetal brain

damage, she says.

Sources

• Hardin, J.S.; Proksch, J.W.; Wessinger, W.D.; and

Owens, S.M. Pharmacodynamics of a monoclonal

anti-phencyclidine Fab with broad specificity for

phencyclidine-like drugs. Journal of Pharmacology and

Experimental Therapeutics 285(3):1113–1122, 1998.

• Hardin, J.S.; Wenger, G.R.; Wessinger, W.D.; and

Owens, S.M. Monoclonal antibodies as long-term

antagonist of phencyclidine (PCP). Clinical

Pharmacology and Therapeutics 65(2):153, 1999.

• Proksch, J.W.; Gentry, W.B.; and Owens, S.M. Antiphencyclidine monoclonal antibodies provide longterm reductions in brain phencyclidine concentrations

during chronic phencyclidine administration in rats.

Journal of Pharmacology and Experimental

Therapeutics, 292(3):831–837, 2000.
Research Findings

55

Volume 15, Number 2 (June 2000)

A Smithsonian Institution Seminar on Gender

By Raymond Varisco, NIDA NOTES Contributing Writer 

Dr. Leshner delivered the opening remarks

and NIDA-supported investigators discussed

specific areas of research during an all-day

seminar, “Gender Differences in Addiction

and Recovery,” at the Smithsonian

Institution in Washington, DC “This forum

gives us an excellent chance to help disseminate some of the important information our

research has revealed about the biological,

psychological, and social differences between

the patterns of drug use and the effects 

that drugs have on women and men,” 

Dr. Leshner said.

The event, cosponsored by NIDA and the

Society for Women’s Health Research

(SWHR) was held January 29. Nearly 200

attendees heard Dr. Mary McCaul of The

Johns Hopkins University in Baltimore 

provide an overview of gender differences in drug abuse

and alcoholism; Dr. Kathleen Brady of the Medical

University of South Carolina in Charleston discuss issues

associated with comorbidity in women being treated for

substance abuse; Dr. David Vlahov of the New York

Academy of Medicine in New York City describe health

consequences of drug abuse; Dr. Dace Svikis of The Johns

Hopkins University discuss treatment issues for pregnant

or HIV-positive women; and Dr. Brenda Miller of the

University of Buffalo, New York, discuss drug-abusing

women’s increased risks for violence and victimization. In

addition to these NIDA-supported scientists, Dr. Florence

Haseltine, founder of the SWHR, and Dr. Neil Grunberg

of the Uniformed Services University of Health Sciences,

Bethesda, Maryland, made presentations on aspects of

gender differences in drug abuse, treatment, and

recovery.

At the Smithsonian Institution’s seminar, 

Dr. Mary McCaul discusses gender differences 

in drug abuse and alcoholism. 

Left: NIDA Director Dr. Alan I. Leshner delivers opening remarks at the

Smithsonian Institution seminar. Right: Dr. Neil Grunberg presents information 

on gender differences in tobacco use and cessation at the Smithsonian seminar.
Research Findings

56

Volume 15, Number 1 (March 2000)

Marijuana-Like Compound in Womb May Influence Early Pregnancy

By Steven Stocker, NIDA NOTES Contributing Writer 

Ever since scientists began discovering in the early 1990s

that marijuana-like compounds are normally produced in

various parts of the body, they have been investigating the

function of these compounds. Research has suggested that

in the brain, the compounds, called endocannabinoids,

inhibit pain perception and help to regulate movement. In

the spleen and blood, endocannabinoids seem to be partly

involved in suppressing inflammation and other responses

of the immune system. Now NIDA-funded researchers

have discovered that in the female mouse reproductive

tract, one of these endocannabinoids, called anandamide,

appears to help regulate the early stages of pregnancy.

Dr. Sudhansu K. Dey and his colleagues at the University

of Kansas Medical Center in Kansas City, Kansas, have

found that the mouse uterus contains the highest anandamide levels yet discovered in any mammalian tissue. At

times, parts of the uterus contain anandamide levels that

are more than 100 times higher than those in the brain.

The researchers have also found that mouse embryos contain cannabinoid receptors—proteins on the cell surfaces

that latch on to endocannabinoids in the vicinity—again,

at levels that exceed those of the brain.

To find out why the uterus contains anandamide and the

embryo contains cannabinoid receptors, the scientists first

examined the effects of anandamide on embryo development. When they placed embryos from mice in cell culture, about 90 percent proceeded to the next stage of

embryonic development, the blastocyst, which normally

implants into the wall of the uterus and eventually

becomes a fetus. With the addition of anandamide, only

36 percent proceeded to the blastocyst stage. However, if

these embryos were then placed in cell culture without

anandamide, most started developing again.

In addition to inhibiting the growth of embryos prior to

implantation, anandamide probably also inhibits implantation itself, the researchers found. They determined that

administering compounds similar to anandamide prevented

blastocysts from implanting in the uterine wall.

Functions of Anandamide

Anandamide may be serving at least three functions before

and during implantation, suggests Dr. Dey. First, the compound may be involved in synchronizing the development

of the embryo with the preparation of the uterus for receiving it. For example, anandamide secreted into the fluid of

the uterus is ready to receive the implanting blastocyst and

to sustain it once it has implanted.

Second, anandamide may be involved in embryo selection.

“In the mouse, about 15 percent of embryos never

implant, and in humans, as many as 60 percent either

don’t implant or don’t survive after implantation,” says 

Dr. Dey. “Perhaps these rejected embryos are inferior in

some way, and high anandamide levels in the uterine wall

may prevent them from implanting or surviving after

implantation.” 

Finally, Dr. Dey suggests, anandamide may prevent a 

second blastocyst from implanting nearby one that has

already implanted. After the first one implants, the anandamide level in the surrounding area increases again, which 

prevents other blastocysts from implanting at the same site.

Understanding how anandamide acts in the female 

reproductive tract may lead to an explanation for some

cases of infertility in women, if anandamide is found to

exist in the human uterus, suggests Dr. Dey. In these infertile women, excessive uterine levels of anandamide may 

be disrupting embryo development and implantation, 

says Dr. Dey.

This research may also lead to the development of new

contraceptives that can inhibit embryo development and

implantation in the same manner as anandamide.

Conversely, it could also lead to the development of 

fertility agents that act in ways opposite to those of 

anandamide.

Sources

• Paria, B.C.; Das, S.K.; and Dey, S.K. The preimplantation mouse embryo is a target for cannabinoid 

ligand-receptor signaling. Proceedings of the National

Academy of Sciences 92:9460–9464, 1995.

• Paria, B.C.; et al. Fatty-acid amide hydrolase is

expressed in the mouse uterus and embryo during the

periimplantation period. Biology of Reproduction

60:1151–1157, 1999.

• Schmid, P.C.; et al. Changes in anandamide levels in

mouse uterus are associated with uterine receptivity for

embryo implantation. Proceedings of the National

Academy of Sciences 94:4188–4192, 1997. 

• Yang, Z-M; Paria, B.C.; and Dey, S.K. Activation of

brain-type cannabinoid receptors interferes with

preimplantation mouse embryo development. Biology

of Reproduction 55:756–761, 1996.
Research Findings

57

Volume 15, Number 1 (March 2000)

Facts About Drug Abuse and Hepatitis C

What is Hepatitis C?

Hepatitis C, a viral disease that destroys liver cells, is the

most common blood-borne infection in the United States.

Approximately 36,000 new cases of acute hepatitis C infection occur each year in the United States, according to the

Centers for Disease Control and Prevention (CDC) in

Atlanta. People with acute HCV infection may exhibit such

symptoms as jaundice, abdominal pain, loss of appetite, nausea, and diarrhea. However, most infected people exhibit

mild or no symptoms.

About 85 percent of people with acute hepatitis C develop a

chronic infection. Chronic hepatitis is an insidious disease

whose barely discernible symptoms can mask progressive

injury to liver cells over 2 to 4 decades. An estimated 4 million Americans are infected with chronic hepatitis C, according to CDC.

Chronic hepatitis C often leads to cirrhosis of the liver and

liver cancer and causes between 8,000 and 10,000 deaths a

year in the United States. It is now the leading cause of liver

cancer in this country and results in more liver transplants

than any other disease.

How Is HCV Transmitted?

People become infected with the hepatitis C virus (HCV)

through direct contact with an infected person’s blood.

Although this contact can occur in a number of ways, injection drug use now accounts for at least 60 percent of HCV

transmission in the United States, according to CDC. This

estimate may be conservative because about 10 percent of

people newly diagnosed with HCV do not report an identifiable risk factor. Some of these cases may represent people

who are reluctant to identify injection drug use as a risk factor. Because HCV is highly transmissible through the blood,

anyone who has ever injected drugs is at risk for liver disease

and should be tested for the virus.

Injecting drug users (IDUs) contract hepatitis C by sharing

contaminated needles and other drug injection paraphernalia. One recent study found that 64.7 percent of IDUs 

who had been injecting for 1 year or less were already infected with the virus. Overall prevalence of HCV was 76.5 

percent among IDUs who had been injecting drugs for 6

years or less.

Additional research indicates that rates of hepatitis C among

past or current IDUs are extremely high in a number of

cities in the United States. For example, last year a NIDAand CDC-funded study detected HCV infection in approximately 85 percent of 3,000 IDUs in Seattle. Researchers in

Texas reported similar percentages in several Texas cities and

noted that many recovering IDUs who tested positive for

HCV reportedly had not injected for 5 to 15 years.

Hepatitis C, HIV/AIDS, and hepatitis B share common risk

factors for infection. IDUs have a high prevalence of coinfection with the viruses that cause these diseases. It is

important to test IDUs for all three viruses.

Prior to the development of sophisticated HCV blood

screening tests in the early 1990s, blood transfusions

accounted for a substantial proportion of HCV infections.

Now, there is only 1 chance in 100,000 that someone will

get HCV from transfused blood or blood products.

However, people who received blood transfusions prior to

July 1992 should be tested for HCV.

The risk of perinatal transmission of hepatitis C is relatively

low. About 5 of every 100 infants born to HCV-infected

women become infected. However, about 17 out of every

100 infants born to HCV-infected women who are also

infected with HIV become infected with HCV. HCV infection among women with HIV also is associated with

increased maternal-infant transmission of HIV.

Can HCV Infection Be Prevented?

Although there are vaccines for other forms of hepatitis,

none exists to protect against HCV. However, prevention

of illegal drug injection would eliminate the greatest risk

factor for HCV infection in the United States, according

to CDC. Therefore, drug addiction treatment can play a

major role in reducing HCV transmission. Research shows

that drug users who enter and remain in treatment reduce

high-risk activities, such as sharing needles and other drug

injection paraphernalia, that are responsible for spreading

HCV. AIDS outreach and HIV prevention programs for

out-of-treatment drug users that reduce HIV risk also

reduce the risk of HCV transmission.

How Can HCV Infection Be Treated?

Available antiviral drugs to eliminate the virus and reduce

liver injury are not highly effective for patients with chronic

hepatitis C. Side effects can be severe and the treatment is

costly, lengthy, and effective for only 30 to 40 percent of

those with the disease.

For More Information

• Patients and health care providers can obtain information on hepatitis C from the Centers for Disease

Control and Prevention, Hepatitis Branch: Mailstop

G-37, 1600 Clifton Road, NE, Atlanta, GA 30333,

1-888-443-7232. CDC’s hepatitis Web site at www.cdc.

gov/ncidod/diseases/hepatitis contains a variety of educational materials on HCV and links to additional sources

of information.
Research Findings

58

Volume 14, Number 6 (March 2000)

UCLA Study Looks at Women in Treatment

Women in women-only drug abuse treatment programs

were more than twice as likely to complete treatment as

women in mixed-gender programs, according to a NIDAfunded study conducted by Dr. Christine E. Grella of the

University of California, Los Angeles. The study also

found that, on average, pregnant women had used their

primary drug for less time than nonpregnant women; and

pregnant women in women-only drug abuse treatment

programs averaged more days in treatment than did those

in mixed-gender programs, 87.4 days vs. 74 days. Overall,

pregnant women spent about 15 percent less time in treatment than nonpregnant women.

Dr. Grella’s study compared the characteristics of 4,117

women through data reported from 1987 to 1994 by all

publicly funded drug abuse treatment programs in Los

Angeles County. The statistical analyses of the treatment

program data by pregnancy status and gender composition

support the premise that women in drug abuse treatment

programs have different needs than men in treatment, and

a successful program for women often depends on meeting those different needs, Dr. Grella says.
Research Findings

59

Volume 14, Number 6 (March 2000)

Female Rats Progress Quickly to Drug Abuse

In a study conducted by Dr. Wendy Lynch and Dr.

Marilyn Carroll of the University of Minnesota in

Minneapolis, female rats gave themselves more cocaine

and heroin sooner than male rats, a finding consistent

with human studies suggesting that women progress faster

than men to drug addiction.

The experiment consisted of a series of 6-hour sessions in

which rats could administer the drugs to themselves freely

by pushing a lever. Seventy percent of the females, but only

30 percent of the males, progressed to a predetermined level

of cocaine use. For heroin, 90 percent of the females and

91.7 percent of the males reached that level.

The female rats reached the predetermined level of cocaine

use in a mean of 7.57 sessions compared to 16.67 sessions

for males. They reached the level for heroin use in a mean

of 8.7 sessions compared to 13 sessions for males. Among

the rats that reached that level of use, both cocaine and

heroin use were higher in females than in males, and

cocaine use was significantly higher.
Research Findings

60

Volume 14, Number 5 (December 1999)

NIDA Science Education Program Reaches Out to 

Young Rural Women 

By Patrick Zickler, NIDA NOTES Staff Writer 

A program developed by NIDA-supported researchers at

the University of Kentucky in Lexington has begun introducing young women from rural Appalachia to the 

excitement of hands-on 

science—and to the possibility of pursuing a career

in drug abuse research. The

program—Young Women

in Science—brings high

school students to the university for intensive 3-week

sessions each summer and

five weekend sessions during the school year.

During the first summer

session, completed last

August, a group of 26

ninth-grade girls worked

with researchers to learn

basic concepts of physiology and biology and to

understand the methods of

scientific research. 

A second group of at 

least 26 young women 

will begin the program 

next summer.

“Very few opportunities

exist for young women

from rural areas to learn about scientific research. This

program offers them a chance to work with university

professors during a summer session and to stay involved

by working with women mentors back in their communities,” says Dr. Carl Leukefeld, Director of the Center for

Drug and Alcohol Research at the University of Kentucky

College of Medicine. “Our hope is that it will attract more

women to the field of drug abuse research, but an equally

important goal is to get more young women exposed to

and involved in male-dominated scientific fields.”

During their second year in the program, the young women

will concentrate on behavioral aspects of drug abuse and

traditional treatment interventions. The third year will

involve research that

matches the young women

with successful women 

scientists. Dr. Leukefeld

developed the program 

curriculum in cooperation

with colleagues at the

University of Kentucky

Center for Science and

Health Careers.

The program includes a

stipend for each summer

session, and will provide a

$1,000 college scholarship

to each young woman 

who completes the 3-year

program, whether they

choose to major in science

or some other subject.

“One of NIDA’s goals has

always been to attract

young students, and 

in particular young women,

to careers in drug abuse

research,” says Dr. Cathrine

Sasek of NIDA’s Office of

Science Policy and Communications. “This program reaches out to rural areas of Appalachia to encourage young

women to become involved in science and nurtures their

interests by linking them with local community leaders,

educators, or researchers who can serve as mentors.”

The young women in the program were selected based 

on academic achievement in math and science, 

involvement in school and community volunteer 

activities, personal references, and their interest in 

pursuing a career in science.

Above: Learning about drug abuse research begins with lessons in 

anatomy and physiology for students selected for the Young Women in

Science program at the University of Kentucky. Here the teenagers

study structure and function of the lungs and heart. From left, Carter

Florence, Amanda Melvin, Christina Davis, Samantha Prater, and

Megan Howard. Photo by Jahi Chikwendiu, Lexington Herald-Leader.
Research Findings

61

Volume 14, Number 5 (December 1999)

High-Dose Methadone Improves Treatment Outcomes

By Patrick Zickler, NIDA NOTES Staff Writer 

Methadone has been used effectively for more than 30

years as a treatment for heroin addiction. The medication

blocks heroin’s narcotic effects without creating a drug

“high,” eliminates withdrawal symptoms, and relieves the

craving associated with addiction. Methadone is administered orally in licensed clinics and its effects typically last

24 to 36 hours. 

Although methadone has been used for decades, no clinical

consensus has been reached about the most effective daily

dose. Many clinics do not adjust dosages according to the

needs of individual patients. Instead, they administer fixed

doses. One clinic might use doses of 25 milligrams (mgs) per

day for all patients; others may administer daily doses of 60

mg. “Federal regulations require that a clinic receive a special

exemption in order to provide patients with doses greater

than 100 mg per day, but no contemporary studies have

examined the effectiveness of daily doses greater than 80

mg,” says Dr. Eric Strain, a NIDA-supported researcher at

The Johns Hopkins University Medical Center in Baltimore. 

Dr. Strain and his colleagues investigated the effectiveness of

high-dose—80 to 100 mg per day—methadone treatment

and found this dosage to be more effective in reducing

heroin use than treatment with a moderate dose of 40 to 50

mg per day. The study involved 192 patients. Sixty-five percent of participants were male; pregnant women were

excluded from the study group. 

During the first week of treatment all patients received 

30 mg daily methadone doses. Daily doses were increased

until, by the 8th week, half the patients were receiving a

moderate dose of 40 to 50 mg per day and the other half

were receiving a high dose of 80-to-100 mg per day. These

doses were maintained through the study’s 30th week.

Dosages were then decreased by 10 percent each week 

during the final 10 weeks of the program. Patients were

encouraged to enroll in long-term community-based treatment programs following completion of the 40-week study. 

Dr. Strain and his colleagues evaluated the effectiveness of

treatment through analysis of twice-weekly observed urine

testing, weekly patient reports of heroin use, and the length

of time patients remained in treatment. “The high-dose

group used opiates significantly less during treatment than

did the moderate-dose group on average,” Dr. Strain says.

“Patients in the high-dose group reported using opiates no

more than once a week. The moderate-dose group reported

using drugs two to three times per week on average.”

Among patients who completed the 30-week active phase,

33 percent of high-dose patients remained in treatment

throughout a 10-week methadone phase-out, compared

with 20 percent of moderate-dose patients. There were no

gender-related differences in outcome for high- or moderate-dose groups, and no difference was reported between

the high- and moderate-dose patients for side effects such as

grogginess or constipation. 

In an earlier study, the researchers found that moderate-dose

treatment of 50 mg per day was more effective than low-dose

treatment of 20 mg per day. “The current study provides

strong evidence that we can achieve much better outcomes at

dose rates much higher than 50 mg per day,” Dr. Strain says.

Dosages exceeding the currently regulated ceiling of 100 mg

per day may provide the best result for some patients, Dr.

Strain says, but he notes that clinical trials would be needed

to support changing this regulation. “The most important

aspect of our research from a therapeutic and public health

perspective is that methadone treatment over a broad range

of doses results in significant clinical improvement for 

opioid-addicted patients,” he says. 

Sources

• Strain, E.C.; Bigelow, G.E.; Liebson, I.A.; and Stitzer,

M.L. Moderate- vs high-dose methadone in the treatment of opioid dependence: A randomized trial.

Journal of the American Medical Association

281(11):1000–1005, 1999. 

• Strain, E.C.; Stitzer, M.L.; Liebson, I.A.; and Bigelow,

G.E. Dose-response effects of methadone in the treatment of opioid dependence. Annals of Internal

Medicine 119:23–27, 1993. 

Following a 1-week orientation period, patients receiving high-dose

(80-100 mg) methadone treatment had less self-reported heroin use

and lower rates of drug-positive urine samples than patients on

moderate-dose (40-50 mg) treatment. Urine results are shown as 

3-week averages of twice-weekly samples.
Research Findings

62

Volume 14, Number 5 (December 1999)

The State of the Art in Drug Addiction Treatment

NIDA Director Dr. Alan I. Leshner 

NIDA’s recent publication, Principles of Drug Addiction

Treatment: A Research-Based Guide, distills the lessons of

25 years of scientific investigation. Principles is written for

health care providers, to stimulate their awareness of the

variety of effective approaches to drug treatment. It is also

for patients and potential patients and their families, to

help them understand the nature of addiction and to tell

them about scientifically based treatments and what to

expect if they enter treatment. And it serves

planners and policymakers as well, enabling

them to make informed decisions concerning treatment programs.

In short, this book is for you. That is why

NIDA mailed a copy in October to every

NIDA NOTES reader in the United States.

If you have not yet read yours, I urge you

to do so. If you did not receive a copy or

want additional copies to pass on to friends

or colleagues, the Tearoff on page 15 of this

issue of NIDA NOTES gives ordering

information.

Based on a yearlong review of treatment

research, Principles describes where we

stand today in our quest for the most

effective, replicable treatments for drug

abuse. The book contains many important

messages, but one is central.

Treatment is effective. Scientifically based

drug addiction treatments typically reduce

drug abuse by 40 percent to 60 percent.

These rates are not ideal, of course, but

they are comparable to compliance rates

seen with treatments for other chronic diseases such as asthma, hypertension, and

diabetes. Moreover, treatment markedly

reduces undesirable consequences of drug

abuse and addiction—such as unemployment, criminal activity, and HIV/AIDS

and other infectious diseases—whether or

not patients achieve complete abstinence. Research has

shown that every $1 invested in treatment saves $4 to $7

in costs related to drug abuse.

That treatment is effective will not be news to treatment

providers or to the tens of thousands of individuals and

families who have benefited from treatment. Unfortunately, many members of the public still mistakenly doubt

that treatment can help someone overcome addiction, 

perhaps because—as Principles explains—recovery from

addiction can be a long-term process and frequently

requires multiple episodes of treatment. To these people,

the message of Principles is: We have the tools, let’s do 

the job.

By describing the current state of the art, Principles also

clarifies the many challenging research pathways that

remain to be traversed on the way to our

goal of fully effective treatment for every

patient. To cite just a few of the more

pressing objectives, we need to:

• Understand the complete behavioral and

biological mechanisms of addiction;

• Obtain a full picture of the transition

from drug use to drug addiction and the

stages of recovery in order to fashion

optimal treatments for patients at every

point along that trajectory; 

• Understand better how gender affects 

vulnerability to drug addiction and the

response to treatment in order to more

appropriately tailor treatments for men

and women; 

• Develop additional medications for 

treating opiate addiction and effective

medications for addiction to stimulants

such as cocaine and methamphetamine; 

• Continue to test the effectiveness of 

treatments in real-life community-based

settings. 

NIDA is adjusting its organizational structure and has instituted key procedures to

expedite the next stage of our treatment

research journey. As I write, the Institute is

completing the creation of a new Division

of Treatment Research and Development

(DTRD). The new Division will facilitate

research on combined medication and behavioral treatments, which appears to be an essential strategy for

improving many patients’ chances of successful treatment

outcomes. 

With the support of its Medications Development

Division, one of DTRD’s predecessors, NIDA has developed cooperative links with the pharmaceutical industry

that enable NIDA-supported researchers to obtain 

“Based on a yearlong review of 

treatment research,

Principles describes

where we stand

today in our quest for

the most effective, 

replicable treatments

for drug abuse.”
63

proprietary chemical compounds for testing as possible

medications for drug abuse. As a first fruit of these partnerships, a new cocaine “vaccine” is currently being tested

in a large-scale clinical trial. Based on NIDA-supported

basic studies, this new medication appears to reduce the

desire to use cocaine by blocking the drug’s euphoric

effects. NIDA also is exploring ways for new medications

to reach more of those in need. The demonstrated effectiveness of buprenorphine and naloxone in treating opiate

addiction, for example, suggests that these drugs may be

safely dispensed by physicians in controlled settings. 

With respect to behavioral therapies, NIDA has established a three-stage process for developing, evaluating, and

introducing new approaches into mainstream clinical use.

The potential of each proposed new behavioral treatment

is first explored in a small pilot study. If the preliminary

data are promising, the treatment is tested in a full-scale

clinical trial. If the trial demonstrates efficacy, clinicians

take the treatment out of the research setting and adapt it

as necessary for mainstream use. This new model establishes the first clear benchmarks for testing, comparing,

and implementing behavioral treatments. To date, two

new treatments have passed the preliminary stage of testing and moved on to the clinical trials stage. 

As regular readers of NIDA NOTES are aware, the largest

initiative in NIDA’s history is focused on treatment. This

is the National Drug Abuse Treatment Clinical Trials

Network (CTN), in which research centers ally with nearby community treatment programs to set research goals

and participate in large-scale multisite clinical trials.

NIDA recently announced the establishment of the first

five CTN locations. Ultimately, the CTN will provide a

nationwide coordinating infrastructure with sufficient

patient numbers and diversity to enable scientists to 

optimize treatment effectiveness by matching treatments

with appropriate patient groups. 

There is a pattern in scientific research in which knowledge and techniques are slowly, painstakingly developed

until they reach a critical mass that makes possible a more

rapid and direct approach to problem solving. This first

edition of Principles reflects the power of this pattern of

progress to produce epochal advances in public health and

welfare. With well-defined questions and powerful new

technologies and research techniques coming on line every

year, we do not expect to wait very long before publishing

the second edition of Principles.
Research Findings

64

Support Group Improves Outcomes for Pregnant Drug Users

Volume 14, Number 4 (November 1999)

Participation in a support group while pregnant can

improve maternal and infant outcomes among drugdependent women, according to a NIDA-supported study.

Researchers from The Johns Hopkins University School of

Medicine in Baltimore, the University of Maryland in

Baltimore, Emory University in Atlanta, and the

University of Kansas in Lawrence found that women who

participated in a drug abuse support group had more 

prenatal care visits than drug-abusing women who did not

attend the support group, and their infants had higher

birthweights. The study also found that support group

participation resulted in lower medical care costs for

mothers and their infants.

The researchers studied 121 drug-dependent pregnant

women registered for prenatal care during a 16-month

period at a high-risk obstetric clinic in a poor urban

neighborhood. A total of 54 women attended the weekly

support group meetings held at the clinic, and 67 did not

attend. The groups were led by a drug abuse counselor

and discussed how drugs affect the developing fetus, how

to avoid drug-related situations, and the benefits of staying

in touch with each other outside of the weekly meetings.

Average maternal medical care costs were almost $1,000

less for support group attenders than nonattenders. Costs

were derived from review of Medicaid claims data and calculated from 1 week before delivery through 3 weeks after.

For infants of support group attenders, average medical

costs were about $1,500 less in their first 3 weeks than for

those whose mothers did not attend.

The researchers believe that locating the support group at

the prenatal clinic provides a cost-effective way to deliver

drug abuse treatment. They conclude that this type of

“low-intensity intervention” may be an effective way for

some women to reduce or eliminate their drug use during

pregnancy. For other women, the support group may 

lead to more intensive drug abuse treatment, the

researchers suggest. 
Research Findings

65

Volume 14, Number 4 (November 1999)

Twin Studies Help Define the Role of Genes in 

Vulnerability to Drug Abuse 

By Patrick Zickler, NIDA NOTES Staff Writer 

Some individuals who use drugs become drug abusers—

they continue taking drugs even though doing so causes

serious problems in their lives. Others avoid abuse or

addiction. By studying patterns of drug use in pairs of

twins, NIDA-supported researchers are beginning to 

clarify the role that genes play in predisposing individuals

to drug abuse.

“Twin studies explore the roles and interrelationship of

genetic and environmental risk factors in the development

of drug use, abuse, and dependence,” says Dr. Naimah

Weinberg of NIDA’s Division of Epidemiology, Services,

and Prevention Research.

In twin studies, researchers interview both members of

identical (monozygotic) and fraternal (dizygotic) twin

pairs, who typically are exposed to common environmental influences. If genes influence their risk for drug abuse,

identical twin pairs, who share the same genes, will tend

to be concordant-that is, both will abuse drugs or not

abuse drugs. Fraternal twin pairs, on the other hand, are

no more similar genetically than non-twin siblings, and so

will be less concordant—there will be more pairs in which

one twin abuses drugs and the other does not. By comparing the degree of concordance in

identical and fraternal twins,

researchers can estimate the extent

to which genes influence vulnerability to drug abuse.

Marijuana and Cocaine Abuse

Among Female Twins

NIDA-supported researchers Dr.

Kenneth Kendler and Dr. Carol

Prescott at the Medical College of

Virginia in Richmond have examined the patterns of marijuana and

cocaine use by female twins and

found that genetic factors play a

major role in the progression from

drug use to abuse and dependence.

The researchers interviewed 1,934

twins, ranging in age from 22 to

62, recruited from the Virginia

Twin Registry, a database compiled

from Commonwealth birth

records.

In the study, drug “use” involved at least one nonprescribed use of a drug; “abuse” was based on the definition

provided in the Diagnostic and Statistical Manual of

Mental Disorders, Fourth Edition (DSM-IV), which

includes symptoms such as recurrent use in situations

where it presents a physical danger, failure to meet obligations at work or school, or recurrent social or interpersonal problems caused by effects of the drug; and “dependence” was based on the DSM-IV

definition and included characteristics such as physical symptoms of

tolerance or withdrawal, taking

larger amounts of the drug or

using it over a longer period than

intended, or spending large

amounts of time seeking, obtaining, and recovering from the

effects of the drug.

“Our research supports other studies that indicate family and social

environmental factors are influential in determining whether an

individual begins using these

drugs,” Dr. Kendler says. “But our

findings suggest that the progression from the use of cocaine or

marijuana to abuse or dependence

was due largely to genetic factors.”

In addition, Dr. Kendler says, the

study found that concordance 

If genes influence the risk for drug abuse, identical twin pairs,

who share the same genes, will tend to be concordant—that

is, both will abuse drugs or both will not abuse drugs. 

Percentages of pairs in which both twins used, abused,

or were dependent on marijuana or cocaine were 

higher in identical twins than in fraternal twins. 

Illustration © 1998 by Richard Lillash
66

rates—both twins using, abusing, or being dependent on

drugs—were higher for identical than fraternal twins (see

chart). For cocaine use, concordance was 54 percent in

identical twins and 42 percent in fraternal twins; for abuse,

47 percent in identical twins and 8

percent in fraternal twins; and for

dependence, 35 percent in identical

twins and zero for fraternal twins.

“Abuse and dependence are highly

heritable,” Dr. Kendler says. “For

both cocaine and marijuana, genetic

factors are responsible for roughly 60

to 80 percent of the differences in

abuse and dependence between 

fraternal and identical twin pairs.”

Genetic Risk Factors Differ Among Drugs and

Between Males and Females

Dr. Ming Tsuang, a NIDA-supported researcher at

Harvard University in Cambridge, Massachusetts, has

found that, in males, genetic influences are stronger for

abuse of some drugs than for others. Dr. Tsuang and his

colleagues studied drug use in 1,874 identical male twin

pairs and 1,498 fraternal male twin pairs recruited from

the Vietnam Era Twin Registry, a database compiled from

Department of Defense records. The average age of participants was 45.

The researchers found evidence to suggest that genetic

influences contribute to a common vulnerability for abusing marijuana, sedatives, stimulants, heroin or opiates, and

psychedelics. “There is some characteristic of the individual that imparts vulnerability to the abuse of all categories

of drugs. Abusing any category of drugs was associated

with a marked increase in the probability of abusing every

other category of drugs,” Dr. Tsuang says. In addition to

this shared vulnerability, the researchers found different

vulnerabilities for different drugs. “Each category of drugs

we looked at, except psychedelics, had unique genetic

influences,” Dr. Tsuang says. “The genetic influence for

abuse was greater for heroin than for any other drug.”

NIDA-supported studies involving male and female twins

suggest that genetic factors for drug abuse are stronger in

males than in females. Dr. Marianne van den Bree and Dr.

Roy Pickens of NIDA’s Intramural Research Program and

their colleagues studied 188 twin pairs in which at least 1

twin was recruited through a drug treatment program.

The sample included 56 identical male pairs, 66 fraternal

male pairs, 38 identical female pairs, and 28 fraternal

female pairs. Participants were interviewed to determine

drug use (five times or more) and clinical diagnosis

(according to DSM criteria) of drug abuse, dependence,

or both for sedatives, stimulants, opiates, marijuana, or

cocaine. For most drugs, clinical diagnosis of abuse,

dependence, or both was more strongly influenced by

genetic factors than was drug use.

In addition, for most drugs,

genetic influences for abuse or

dependence were greater for

males than for females.

“For females, genetic influences

accounted for 47 percent of the

differences between identical and

fraternal twins in abuse, dependence, or both for any drug, compared with 79 percent for males,” Dr. van den Bree says.

The impact of genetic factors also seems to differ for specific drugs, she notes. The researchers found no evidence

for genetic influence for opiate or sedative abuse, dependence, or both in females, but in males genetic influences

were generally larger than environmental influences.

“The results we see from these twin studies are making

important advances in our understanding of the role of

genetic influences in drug abuse,” observes NIDA’s Dr.

Weinberg. “Although the studies can’t tell us anything

about the risk for a particular individual, they are of 

enormous value in helping define the variations in drug

abuse vulnerability in the population.”

Sources

• American Psychiatric Association, Diagnostic and

Statistical Manual of Mental Disorders (4th Edition)

Washington, DC: American Psychiatric Association,

1994.

• Kendler, K., and Prescott, C. Cannabis use, abuse,

and dependence in a population-based sample of

female twins. American Journal of Psychiatry

155(8):1016–1022, 1998.

• Kendler, K., and Prescott, C. Cocaine use, abuse, and

dependence in a population-based sample of female

twins. British Journal of Psychiatry 173:345–350,

1998.

• Tsuang, M., et al. Co-occurrence of abuse of different

drugs in men. Archives of General Psychiatry

55:967–972, 1998.

• Van den Bree, M.; Johnson, E.; Neale, M.; and

Pickens, R. Genetic and environmental influences on

drug use and abuse/dependence in male and female

twins. Drug and Alcohol Dependence 52(3):231–241,

1998.

“The progression from the use

of cocaine or marijuana to

abuse or dependence was due

largely to genetic factors.”
Research Findings

67

Volume 14, Number 4 (November 1999)

Drug Abuse and Mental Disorders: Comorbidity Is Reality

NIDA Director Dr. Alan I. Leshner 

A quarter century of basic and clinical research has provided

us with a substantial number of scientifically developed and

tested pharmacological and behavioral techniques for treating drug abuse and addiction. A main thrust of NIDA’s current

research is to discover which combinations

of treatments and services work best for

individual patients with particular constellations of problems. The goal is to customize

treatment for every patient, including those

with coexisting problems such as multiple

drug abuse, drug abuse-related infectious

diseases, histories of sexual abuse, or homelessness.

Drug abusers who have concurrent, or comorbid, mental

health problems are at the top

of the list of those who will

benefit from this research, for

two reasons. First, they are

numerous. Recent epidemiologic studies have shown that

between 30 percent and 60 percent of drug abusers have concurrent mental health diagnoses

including personality disorders,

major depression, schizophrenia, and bipolar disorder.

Second, drug abusers with mental illness comorbidity are more

likely to engage in behaviors

that increase risk for HIV/AIDS. For example, two studies

of injecting drug abusers have found that antisocial personality disorder (APD) is associated with a higher frequency of needle sharing.

In order to direct treatment and services research to where it

is most needed, NIDA supports epidemiologic studies of

mental health comorbidities. The results to date suggest

that the most common are personality disorders including

APD and borderline personality disorder; anxiety disorders

including post-traumatic stress disorder (PTSD); and

depression. Some evidence suggests that men who use drugs

are more likely to have APD, while women and minorities

are more likely to have depression or PTSD. While people

with schizophrenia do not constitute a large portion of the

drug-abusing population, an extraordinarily high percentage

of people with this disease abuse drugs.

A concurrent mental disorder can complicate drug abuse

treatment in a multitude of ways. For example, research

suggests that clinically depressed individuals have an

exceptionally hard time resisting environmental cues

to relapse—that is, urges to resume drug taking that

commonly occur when abstinent addicts encounter

people, places, or things associated with their previous

drug use. In some cases, treatment for mental disorders must be adjusted because of concurrent drug

abuse. For example, opiate users with anxiety disorders are considered poor candidates for standard 

therapy with anti-anxiety drugs of the benzodiazepine

class because these drugs can cause a second addiction.

NIDA-supported researchers have identified effective ways to tailor treatment

for some patients with dual diagnoses.

In one study, opiate addicts with APD

responded better when standard contingency management therapy was modified. In the standard type of this therapy, patients receive small rewards for

abstinence that become progressively

greater the longer abstinence is maintained. In the modified version, treatment professionals gave more frequent

rewards for desirable behaviors, such as

attending scheduled counseling sessions

and testing clean for drugs. NIDA

NOTES Vol. 11, No. 4, p.10. In another

study, drug craving was reduced among

teenage cocaine abusers with bipolar disorder who receive lithium, and in depressed heroin abusers

who were treated with imipramine. In this issue of NIDA

NOTES, we report on promising results with methylphenidate

and antidepressants in children with attention-deficit/hyperactivity disorder (ADHD) and with methylphenidate in

adult cocaine abusers with ADHD.

Just as the co-occurrence of drug abuse and mental health

problems presents special problems for treatment, so does it

also for research. The problems arise in part because drug

abuse and other mental health disorders can intertwine in

several ways. For example, successful treatment of cocaine

addiction often also dispels concurrent depression, while

nicotine addicts’ depression commonly persists after 

successful smoking cessation treatment. Such variations

make it difficult to generalize treatment research findings

across large patient groups. As a result, progress has been

made in relatively small increments. 

“Recent epidemiologic 

studies have shown that

between 30 percent and 

60 percent of drug abusers

have concurrent mental 

health diagnoses including

personality disorders, major

depression, schizophrenia, 

and bipolar disorder.” 
68

Another problem facing researchers is that a study population that is ostensibly uniform because all individuals have

the same drug abuse and mental health disorders may actually be nonuniform. The reason is that the relationship

between the two disorders may vary in different patients.

For example, some people with a mental disorder may initiate drug use as an inappropriate form of self-medication,

some people who take drugs may develop mental disorders

as a consequence of their drug use, and a third group may

simply have the two disorders at the

same time. If an intervention is evaluated in a study population where

some patients have drug abuse as a

primary disorder and others as a secondary disorder, the treatment may

appear to be ineffective even though

it works well for one of these subgroups.

A structural difficulty that complicates research on drug abuse and

mental illness comorbidity is that few drug abuse treatment

programs treat enough patients with a particular mental

health disorder to easily generate the preliminary data necessary to justify a full-scale study of a treatment 

for the disorder. To overcome this difficulty and accelerate

the pace of discovery, NIDA’s Behavioral Therapy

Development Program places special emphasis on pilot

studies in drug abuse and mental illness comorbidity. The

program represents a kind of research “venture capital,”

making possible the rapid initial testing of many ideas, the

best of which will then proceed rapidly to further, more

definitive testing. Starting next year, NIDA’s Clinical Trials

Network will accelerate this wider testing by facilitating the

recruitment of large numbers of patients with the drug

abuse and comorbidity characteristics that treatments are

designed to address. 

Drug abuse and mental health professionals both confront

the difficulty of providing effective

care to patients whose problems

overlap two health care specialties

that share much, but are also in

many ways very distinct. In

response to this situation, NIDA

and the National Institute of

Mental Health have been actively

collaborating on epidemiologic

and treatment research on comorbidity. For example, the two

Institutes are examining the problem of treating the relatively small population of patients

who abuse drugs and also have severe mental disorders,

such as schizophrenia or bipolar disorder. These patients

require integrated specialty treatments.

In drug abuse as in other areas of health care, isolated 

disorders are simplest to study and treat, but comorbidity 

is reality for many individuals. NIDA research has laid 

the foundation for successful investigations of these complex

realities.

“Drug abusers who have 

concurrent, or comorbid, 

mental health problems are at

the top of the list of those who

will benefit from this research.” 
Research Findings

69

Volume 14, Number 3 (September 1999)

Gender Differences in Progression to AIDS

NIDA-funded research on injecting drug users (IDUs)

conducted by Dr. Homayoon Farzadegan and his colleagues at The Johns Hopkins University School of

Hygiene and Public Health in Baltimore has shown that

the course of HIV infection differs in women and men, so

that gender-specific treatment may be needed. This study

of 2,960 adult IDUs, begun in 1988 with followup in

1992 and 1997, revealed that although women progressed

to AIDS as rapidly as men, they had approximately half

the viral load in their bloodstreams when they developed

AIDS. Initiation of AIDS treatment is based on HIV viral

load, and current treatment guidelines are derived mainly

from studies with men. 

The researchers speculate that physiological factors such as

hormones may account, in part, for their findings. Dr.

Farzadegan and the research team believe that these gender

differences must be explored further, and the possibility

that women are being under-treated based on current

guidelines warrants considering a change in when women

start therapy. The study was published in Lancet in

1998.
Research Findings

70

Ethnic Identification and Cultural Ties May Help Prevent Drug Use 

By Patrick Zickler, NIDA NOTES Staff Writer 

Among Puerto Ricans, African Americans, and Asians,

cultural influences and ethnic identification may significantly influence drug use. Studies conducted by NIDA

researchers in New York City suggest that Puerto Rican

and African-American adolescents who strongly identify

with their communities and cultures are less vulnerable to

risk factors for drug use and benefit more from protective

factors than do adolescents without this identification. In

San Francisco, NIDA-supported research demonstrated

different patterns of drug use among different subgroups

of the Asian community.

These findings suggest that

incorporating ethnic and

cultural components into

drug abuse prevention programs can make these 

programs more effective. 

In one study, Dr. Judith

Brook at the Mount Sinai

School of Medicine in New

York City examined the extent to which ethnic and cultural factors influenced drug-related behavior in Puerto

Rican adolescents. She and her colleagues interviewed 275

males and 280 females aged 16 to 24. The researchers

asked the participants to describe the importance in their

lives of cultural and ethnic factors such as observation of

Hispanic holidays and customs, preference for speaking

Spanish or English, feelings of attachment to their ethnic

group, ethnic affiliation of their friends, and the value

placed on the family. The participants also answered questions designed to assess their personal risk for drug use;

these risk factors included the use of drugs by parents or

siblings, peer use or tolerance of drug use, perception of

the riskiness of drug use, and the availability of illegal

drugs in their environment. The participants were categorized into stages of drug use: no reported drug use, used

alcohol or tobacco only, used marijuana but no other 

illicit drug, or used illicit drugs other than or in addition

to marijuana.

“Other studies have looked at ethnic identification in 

isolation, not as an interactive part of a young person’s

cultural and social context,” Dr. Brook says. “We wanted

to determine the extent to which ethnic and cultural 

factors might mitigate risk factors or enhance protective

factors and lead to lower stages of drug use. We found

that strong ethnic identification acts to offset some risks,

resulting in less drug use.

“For example, strong identification with Puerto Rican cultural factors offsets drug risks such as a father’s drug use,

peer tolerance of drugs, and the availability of drugs.

Identification with Puerto Rican friends offsets risks 

associated with family tolerance for drug use and drug

availability,” Dr. Brook notes. 

Ethnic identification also serves to amplify the effect of

protective factors, Dr. Brook says. For example, among

participants whose siblings were not drug users, those with

a strong Puerto Rican affiliation were significantly more

likely to be in a lower stage of

drug use than those whose affiliation was weaker.

In a related study that focused on

late-adolescent African Americans

in New York City, Dr. Brook and

her colleagues found a similar

interaction between ethnic and

cultural identification and drug

use. The study involved 627 participants-259 male and 368 female-aged 16 to 25 years. 

The researchers found that components of ethnic identity—

such as awareness of African-American history and tradition, identification with African-American friends, or participation in African-American cultural activities such as

Kwanzaa—interacted with other factors to reduce risk or

to enhance protection. 

“In isolation, few specific components of ethnic identity

play a role as main effects on drug use. Instead, they act in

combination with family, personality, or peer influences to

blunt the negative impact of risk factors and magnify the

positive value of protective factors,” Dr. Brook says.

“Together, the research with Puerto Rican and AfricanAmerican populations points out the importance of incorporating ethnic identity into drug programs,” Dr. Brook

concludes. “It can be a valuable part of drug prevention

programs in communities and can also be applied to individual treatment programs.”

Cultural Differences Lead to Different Patterns of

Drug Use

In another NIDA-supported study, Dr. Tooru Nemoto

and his colleagues at the University of California, San

Francisco, have identified patterns of drug use among

Asian drug users that are unique to ethnicity, gender, age

group, and immigrant status. 

“Adolescents who strongly identify

with their communities and cultures

are less vulnerable to risk factors 

for drug use.”

Volume 14, Number 3 (September 1999)
71

“Large multiracial studies have not distinguished between

Asian ethnic groups,” Dr. Nemoto says. “The purpose of

our study was to describe the patterns of drug use in

Chinese, Filipino, and Vietnamese groups and to assess

the relationship between cultural factors and drug use

among the groups.”

The San Francisco study was based on qualitative interviews with 35 Chinese, 31 Filipino, and 26 Vietnamese

drug users who were not enrolled in treatment programs.

All participants were 18 years or older, with an average age

of 32.5, and had used illicit drugs more than three times

per week during the preceding 6 months. Overall, 

immigrants and women represented 66 percent and 

36 percent, respectively. However, all Vietnamese 

were immigrants. 

Overall, participants born in the U.S. began using drugs

at an earlier age—15 years-than did immigrant Asians—

19 years—and were more likely than immigrants to use

more than one drug. In general, women started drug use

at about the same age as men—about 17.5 years—but

ethnic groups showed a varied pattern. Chinese women

began earlier—at 15.2 years-than Chinese men—at 18.5

years. Filipino women began using drugs later—at 15.5

years—than Filipino men-at 13.1 years. Vietnamese

women in the study started drug use much later—at 27.8

years-than did Vietnamese men—at 19.9 years.

Dr. Nemoto and his colleagues identified differences in

drug use among the ethnic groups. Filipino drug users

were most likely to have begun drug use with marijuana,

while Vietnamese drug users in the study most often started

with crack or powder cocaine. Chinese and Vietnamese

were twice as likely as Filipinos to be using crack as their

current primary drug. Filipinos were four times more likely

to be using heroin than were Chinese or Vietnamese.

Filipino study participants were more likely than Chinese

or Vietnamese to be injecting and less likely to be smoking

drugs. There were also significant differences in the characteristics of drug user networks among the ethnic groups.

For example, Filipinos were more than twice as likely as

Chinese or Vietnamese participants to use drugs in groups

that included members of other races or ethnic groups.

“These differences among ethnic groups have important

implications for the way we design programs aimed at

Asian drug users,” Dr. Nemoto says. “Prevention programs

should address the common factors among Asian drug

users, such as stigma associated with injection drug use,

but we should also be careful to incorporate factors that

are unique to each target group.” 

Sources

• Brook, J.S., et al. Drug use among African Americans:

Ethnic identity as a protective factor. Psychological

Reports 83:1427–1446, 1998.

• Brook, J.S.; Whiteman, M.; Balka, E.B.; Win, P.T.;

and Gursen, M.D. Drug use among Puerto Ricans:

Ethnic identity as a protective factor. Hispanic Journal

of Behavioral Sciences 20(2):241–254, 1998.

• Nemoto, T., et al. Drug use behaviors among Asian

drug users in San Francisco. Addictive Behavior

24(6):823–838, 1999. 
Research Findings

72

Drug Abuse Research Helps Curtail the Spread Of Deadly

Infectious Diseases

NIDA Director Dr. Alan I. Leshner 

Volume 14, Number 2 (August 1999)

Drug abuse plays a central role in the spread of infectious

diseases that threaten our Nation’s health. Injection drug

use now accounts for about one-third of all new cases of

AIDS reported in the U.S. each year, according to figures

from the Centers for Disease Control and Prevention.

Other statistics show that drug abuse is strongly linked to

the spread of hepatitis, tuberculosis (TB), and

syphilis and other sexually transmitted diseases. 

To address this major public health challenge,

NIDA has long supported a broad program of

research on drug abuse and infectious diseases. 

Over the last decade, NIDA-funded researchers

have developed and evaluated a range of interventions to reduce the spread of HIV among

drug abusers, their sexual partners, and their

children. Drug abuse treatment and communitybased outreach and education programs have

consistently demonstrated that drug abusers will

reduce the drug-use and sexual behaviors that

put them at risk for HIV and other blood-borne

infectious diseases and that these

changes in behavior lead to declines in

new HIV infections. For example, one

study of heroin addicts conducted by

NIDA-supported researchers at the

University of Pennsylvania in

Philadelphia found that injecting drug

users (IDUs) in a methadone treatment program contracted HIV at onesixth the rate of addicts who were not

in treatment. 

NIDA-supported researchers also have

contributed to meeting the serious

public health challenge posed by the re-emergence of TB

in the last decade. HIV became prevalent among IDUs in

the mid-1980s and transformed the latent TB infection

that has always been widespread in this population into

the contagious form of the disease. NIDA-supported epidemiologic, community, and treatment research among

drug users at high risk for HIV and TB played an important role in a coordinated Federal and State initiative that

led to the implementation of effective strategies to prevent

and treat TB. As a result, from a peak of 26,673 cases in

1992, new TB cases fell to an all-time low of 19,851 in

1997. 

NIDA’s TB and HIV research has demonstrated that 

providing medical care to IDUs in conjunction with drug

abuse treatment can curb the spread of infectious diseases.

NIDA now is promoting further research to identify factors that support or hinder linkages between drug abuse

treatment and primary medical care among a variety of

populations, particularly women and

racial and ethnic minorities. 

NIDA-supported research also has

developed approaches that can check the

spread of infectious diseases among the

approximately 85 percent of IDUs who

are not in treatment. For example, one

long-term study in Baltimore providing

directly observed preventive therapy and

a variety of health care services in one

convenient setting virtually eliminated

new TB cases among out-of-treatment

IDUs. We now are developing additional

research initiatives to add drug abuse

treatment to vans that 

provide comprehensive medical services in neighborhoods

with large populations of outof-treatment heroin addicts.

We believe these coordinated

mobile clinics may lead to further reductions in drug abuse

and infectious diseases in this

population. 

Noninjection drug use also

fosters the spread of infectious

diseases. For example, smokers

of crack cocaine, particularly women who exchange sex for

drugs, are at high risk for infection with HIV, hepatitis,

TB, and sexually transmitted diseases. In addition, it

appears that many heroin users who begin by snorting

that drug sooner or later progress to injection drug use

with its attendant risks. Early data from a NIDA-supported study by scientists at National Development and

Research Institutes, Inc., in New York City indicate that a

substantial portion of heroin snorters become injectors,

engage in a high level of risky drug-use and sexual behaviors, and begin to contract hepatitis C soon after they start

injecting drugs. By also shedding light on the complex

Research has consistently

demonstrated that drug abusers

will reduce the drug-use and

sexual behaviors that put them

at risk for HIV and other bloodborne infectious diseases. 
73

individual and social factors that contribute to transition

from noninjection to injection drug use, this study will

help us develop new approaches to forestall the progression to injection drug use and infectious disease. 

While we have made much progress in preventing and

treating infectious diseases among drug abusers, the continued high prevalence of diseases such as HIV/AIDS and

hepatitis in this population indicates that much remains

to be done. Therefore, NIDA recently established the

Center on AIDS and Other Medical Consequences of

Drug Abuse. Headed by Dr. Henry Francis, the Center is

coordinating a multidisciplinary program of research on

the full spectrum of critical health issues associated with

drug abuse. Components of the program include tracking

the extent and progression of infectious diseases among

drug users, assessing the effect of illicit drugs on the

immune system, linking drug abuse treatment and medical care, and developing new educational and behavioral

strategies for drug abusers who are not in treatment.

Ultimately, the program will generate new strategies for

reducing the spread of infectious diseases. 

Because drug abuse and infectious disease have implications for many areas of biomedical research, the Center

also is fostering collaborative research efforts with other

institutes of the National Institutes of Health (NIH), government agencies, and private sector groups. Currently,

NIDA supports more than 10 interagency and interinstitute studies involving drug abuse and infectious disease.

For example, the Women and Infants Transmission Study

being conducted by NIDA, the National Institute of

Allergy and Infectious Diseases, and the National Institute

of Child Health and Human Development is investigating

mother-to-infant transmission of HIV. NIDA also is participating in a new, congressionally mandated NIH

research initiative that is responding to the health problems associated with hepatitis C. Approximately 4 million

Americans are infected with this virus, which can cause

chronic liver disease that results, in many cases, in death

due to cirrhosis and liver cancer. NIDA-supported

research will be critical to the success of the NIH initiative

because of the major role injection drug use plays in the

transmission of this insidious infection. 

In the years ahead, drug abuse and infectious disease will

continue to pose challenges to the Nation’s health. NIDA’s

broad program of research on the medical consequences of

drug abuse will continue to provide the scientific knowledge needed to overcome those challenges with multifaceted public health responses. 

“Early data from a NIDA-supported

study by scientists at National

Development and Research Institutes,

Inc., in New York City indicate 

that a substantial portion of heroin

snorters become injectors, engage in

a high level of risky drug-use and 

sexual behaviors, and begin to 

contract hepatitis C soon after they

start injecting drugs.”
Research Findings

74

Volume 14, Number 2 (August 1999)

Drug abuse involves health

risks that often are as dangerous as the physiological

effects of the drugs themselves. Injecting drug users

(IDUs) are at high risk for

direct exposure to a variety of

blood-borne bacterial and

viral infections. As a result,

drug users are more likely

than nonusers to contract a

variety of infectious diseases

and, when infected, to

progress to serious illness and

death. 

HIV/AIDS

Injection drug use has been

responsible for more than one-third of all adult and adolescent AIDS cases reported in the U.S. since the beginning of the AIDS epidemic, according to the Centers for

Disease Control and Prevention (CDC) in Atlanta. More

than one-half of all preadolescent AIDS cases in the U.S.

have resulted from a transmission chain whereby a woman

contracts HIV as a result of injection drug use and passes

the disease to her child during pregnancy or birth. Of

adult and adolescent AIDS cases, approximately 32 percent were among IDUs, and another 4 percent involved

heterosexual sex with an IDU. During 1998, approximately one-third of all new AIDS cases in the U.S. were related

directly or indirectly to injection drug use (See chart for a

breakdown of the injection drug use-related cases).

Noninjection drug use can also contribute to HIV transmission. Studies have shown that inner-city youths who

smoke crack cocaine are up to three times more likely to

be infected with HIV than are inner-city youths who do

not. Noninjecting drug users who trade sex for drugs or

who engage in unprotected sex while under the influence

of drugs increase their risk of infection.

Hepatitis

Hepatitis B (HBV) and hepatitis C (HCV) are viral diseases that destroy liver cells and can lead to cirrhosis and

liver cancer. People can become infected with HBV

through sexual intercourse with an infected person or

through exposure to an infected person’s blood, as may

happen when IDUs share needles. Blood transfusion and

needle sharing are the most common routes of infection

with HCV. NIDA-supported

research has shown that the

risk of infection by HBV and

HCV is extremely high in

the first year after beginning

injection drug use. One

study found overall HCV

and HBV prevalences of 76.9

percent and 65.7 percent,

respectively, in a group who

had been injecting drugs for

6 years or less.

Tuberculosis

Tuberculosis (TB) is transmitted from person to person

by airborne bacteria. This

disease is most prevalent in

crowded low-income areas with substandard health conditions. Drug users are from two to six times more likely to

contract TB than nonusers. CDC estimates that in 1996

at least 11 percent of new TB cases were in drug users

with noninjecting drug users twice as likely as IDUs to

contract the disease. Compared to others with TB, IDUs

are more likely to develop the disease in multiple organs

and sites, rather than only in the lungs.

Other Infectious Diseases

Drug users have a high incidence not only of HIV/AIDS

but also of other sexually transmitted diseases including

syphilis, chlamydia, trichomoniasis, gonorrhea, and genital

herpes. The geographic distribution of syphilis and gonorrhea infections across the U.S. reflect the geographical distribution of the use of crack cocaine and its associated

high-risk behaviors, such as unprotected sex and the

exchange of sex for drugs.

Among IDUs, the most common cause for medical treatment is skin infection at the site of injection. Complications from these infections range from skin ulcers and

localized abscesses to stroke, botulism, tetanus, destruction

of lung tissue, and infection of the heart valves.

Bacterial and viral infections associated with injection

drug use can progress to systemic infections and damage

any body system. Directly observed medication therapy, in

which the patient takes medic-ations in the presence of a

health care provider, is generally recommended for

addicts, many of whom may have difficulty following

treatment regimens.

Infectious Diseases and Drug Abuse

1998 AIDS Cases Related to Injection Drug Use
Research Findings

75

Drug Use Among America’s Teenagers Shows Slight 

Downward Trend

By Patrick Zickler, NIDA NOTES Staff Writer 

Volume 14, Number 1 (April 1999)

The prevalence of illicit drug use among America’s

teenagers dropped slightly in 1998. The decrease follows a

leveling off in 1997, and suggests that the increasing use

of drugs by teenagers that marked most of the 1990s may

have begun to turn around. 

Data compiled by the NIDA-supported Monitoring the

Future study show that, overall, teenagers were less likely

to use marijuana, hallucinogens, or inhalants last year than

they had been the year before. Heroin use leveled off in

1998, following several years of slight increases. Among all

illicit drugs included in the survey, only crack and tranquilizers were used by a significantly higher percentage of

teenagers in any grade in 1998 than in 1997, according to

the study. 

The Monitoring the Future study, funded by NIDA and

conducted annually by the Institute for Social Research at

the University of Michigan in Ann Arbor, surveyed nearly

50,000 students—including equal numbers of males and

females—in 8th, 10th, and 12th grades at more than 420

public and private schools across the country. Data from the

most recent survey, conducted in the spring of 1998, were

released by Secretary of Health and Human Services Dr.

Donna E. Shalala at a press conference in December 1998. 

“These new findings are encouraging, since they represent

a leveling off in teens’ use of illicit drugs,” Secretary

Shalala said. “It’s not easy to convince our young people

that drug use is illegal, dangerous, and wrong, but it is

absolutely critical to their future.” 

The survey also asked students about the risks associated

with drug use. The percentage of students who said there

is a “great risk” associated with drug use rose or remained

unchanged for most illicit drugs. 

“We seem to be in the middle of a turnaround in young

people’s use of most kinds of illicit drugs following an 

earlier period of sustained increases,” Dr. Lloyd Johnston,

principal investigator for the study, said. “These behaviors

sometimes change very slowly, and often only after there

has been some reassessment by young people of how 

dangerous these various drugs are. Such reassessment now

appears to be occurring for many drugs, but very gradually.” 

Teenagers now are responding to increased knowledge of

the facts about illicit drug use, NIDA Director Dr. Alan I. 

Leshner said. “The more that scientific research helps us

understand what addiction is and how illicit drugs change

the brain and behavior, the better able students and others

will be to make informed decisions. The findings from

this year’s report suggest that many of our educational

efforts are beginning to pay off,” Dr. Leshner said. 

Highlights of the 1998 Monitoring the Future Study

• Marijuana. Use declined among all three grades, and

this accounted for most of the overall decline in 1998

drug use. Eighth-grade use declined for the second

successive year. Nonetheless, marijuana use is still

prevalent: 22 percent of 8th-graders and nearly half of

12th-graders surveyed reported that they have tried

marijuana. However, the perceived risk of marijuana

use has increased among 8th-graders. 

• Heroin. Although use did not decline, it remained

unchanged among all students in 1998: 1.3 percent of

8th-graders, 1.4 percent of 10th-graders, and 1.0 

percent of 12th-graders reported using heroin at least

once during the previous 12 months. This leveling 

in heroin use follows a rise in perceived risk over the

previous 2 years. 

• Stimulants. Use decreased for the second consecutive

year to 7.2 percent among 8th-graders, showed a 

1-year drop to 10.7 percent among 10th-graders, and

leveled off at 10.1 percent among 12th-graders. 

• Hallucinogens. Overall use decreased slightly at all

grade levels—to 3.4 percent among 8th-graders, 

6.9 percent among 10th-graders, and 9.0 percent

among 12th-graders. Decreases in use of MDMA, or

ecstasy, were recorded for the second year in a row for

10th- and 12th-grade students. 

• Crack Cocaine. Among 8th-graders, use of crack

cocaine increased to its highest level, 2.1 percent,

since 1991, when the drug was first included in the

8th grade survey. Slight increases—also to their highest levels in recent years—were reported for crack use

by 10th-graders, to 2.5 percent, and 12th-graders, to

2.5 percent. 

• Inhalants. Use declined among all students for the

third consecutive year. In 1998, 11.1 percent of 8thgraders, 8.0 percent of 10th-graders, and 6.2 percent
76

of 12th-graders reported using inhalants at least once

in the past year. This decrease follows an upward shift

in 1996 in the proportion of students associating

great risk with inhalant use. 

• Gender. Overall, higher percentages of males than

females reported using illicit drugs at least once 

during the previous year. As has been the case 

since 1991—the first year for which data are 

available—younger girls are more likely than boys to

use illicit drugs other than marijuana, primarily due

to their greater use of stimulants and tranquilizers;

12.1 percent of 8th-grade girls and 9.6 percent of

boys reported using drugs other than marijuana. In

10th grade, 17.5 percent of girls and 15.6 percent of

boys reported using drugs other than marijuana at

least once during the previous year. Among 12thgraders, 21.7 percent of boys and 18.0 percent of 

girls reported using drugs other than marijuana. 

For More Information

• Additional information about the Monitoring the

Future study can be obtained by calling NIDA

Infofax at 1-888-NIH-NIDA (644-6432) or by

accessing NIDA’s home page on the World Wide Web

at http://www.nida.nih.gov/ and clicking on

Information on Drugs of Abuse. Information is also

available from the Monitoring the Future home page

at the Institute for Social Research at the University of

Michigan: http://www.isr.umich.edu/src/mtf. 
Research Findings

77

Study Shows How Genes Can Help Protect From Addiction

By Robert Mathias, NIDA NOTES Staff Writer 

Volume 13, Number 6 (March 1999)

A recent NIDA-funded study illustrates how genetic differences can contribute to or help protect individuals from

drug addiction. The study shows that people with a gene

variant in a particular enzyme metabolize or break down

nicotine in the body more slowly and are significantly less

likely to become addicted to nicotine than people without

the variant. In addition, people with the genetic variant who

do become tobacco-dependent smoke fewer cigarettes than

individuals without the variant, the study indicates. 

“This study shows the importance of looking at the role of

genetics in drug addiction and treatment,” says Dr. Jonathan

Pollock of NIDA’s Division of Basic Research. Ultimately,

increased knowledge about underlying genetic vulnerability

might lead to more effective treatments for nicotine 

addiction that are tailored to particular types of smokers, 

Dr. Pollock says. 

In the study, Dr. Edward Sellers and coinvestigator Dr. Rachel

Tyndale of the University of Toronto examined the role that a

gene for an enzyme called CYP2A6 plays in nicotine dependence and smoking behavior. CYP2A6 metabolizes nicotine,

the addictive substance in tobacco products. Three different

gene types, or alleles, for CYP2A6 have been identified by 

previous research—one fully functional allele and two inactive

or defective alleles. Each person has a paternal and maternal

copy of the gene. Therefore, a person can have two active

forms of the gene and normal nicotine metabolism; one active

and one inactive copy and impaired nicotine metabolism; or

two inactive copies, which would further impair nicotine

metabolism. 

The study found that people in a group who had tried smoking but had never become addicted to tobacco were much

more likely than tobacco-dependent individuals in the study

to carry one or two defective copies of the gene and have

impaired nicotine metabolism. The researchers theorize that

the unpleasant effects experienced by people learning to

smoke, such as nausea and dizziness, last longer in people

whose bodies break down nicotine more slowly. These longer

lasting aversive effects would make it more difficult for new

smokers to persist in smoking, thus protecting them from

becoming addicted to nicotine. 

“We have proven that the risk of becoming a smoker significantly decreases if you have one of the inactive alleles for this

enzyme,” Dr. Sellers says. Individuals who have two defective

copies of the gene would have an even lower risk of becoming

a smoker, he predicts. Although only 1 to 2 percent of the

general population may carry two defective alleles, individuals

with at least one defective allele constitute about 16 to 25 

percent of the general population, Dr. Sellers says. “We’ve 

calculated that the frequency of defective alleles that we’ve

found would be protecting about 7 million North Americans

from becoming smokers,” he says. 

The study also found that individuals with impaired nicotine

metabolism who do go on to become addicted to nicotine are

afforded a measure of protection from the harmful effects of

nicotine addiction. The study shows that smokers with at least

one inactive allele smoked significantly fewer cigarettes daily

and weekly than smokers with two active copies of the allele.

Generally, smokers with slower nicotine metabolism do not

need to smoke as many cigarettes to maintain constant blood

and brain concentrations of nicotine, the researchers explain.

However, this slower nicotine metabolism had a greater

impact on reducing smoking among men than women in 

the study. This is probably because women’s smoking is 

controlled less by nicotine dependence than is men’s, the

researchers suggest. 

In addition to illustrating the role genetics can play in vulnerability to addiction, identification of the effect of the defective

gene on smoking has prevention and treatment implications,

Dr. Sellers says. “If you could find a chemical or some other

way of causing the same effect, such as blocking the enzyme,

you might be able to prevent people from becoming smokers,” he says. “If you did the same kind of thing in people who

were already smokers, they would be likely to smoke less,

which could lead to smoking cessation,” Dr. Sellers concludes. 

Source 

• Pianezza, M.L.; Sellers, E.M.; and Tyndale, R.F.

Nicotine metabolism defect reduces smoking. Nature

393(6687):750, 1998.

Nonsmokers in a study at the University of Toronto were more likely than smokers to carry a copy of the CYP2A6 gene variant, which

slows nicotine metabolism. 

Percentages of Smokers and Nonsmokers With 

Gene Variant That Slows Nicotine Metabolism 
Research Findings

78

NIDA Research Provides Data To Document and Improve the

Effectiveness of Drug Abuse Health Services

NIDA Director Dr. Alan I. Leshner 

Volume 13, Number 5 (January 1999)

As part of its mission to treat and prevent drug abuse and

addiction, NIDA has supported the development of

numerous research-based drug abuse treatment protocols

and drug abuse prevention models. In keeping with standard scientific methodology, these programs have been

tested in tightly controlled practice settings with carefully

selected populations. 

Once these programs are tested the critical question

becomes: Will the promising treatment outcomes 

produced in a controlled research environment hold in

widely varying real-life treatment settings and for a wide

range of patients? Likewise, will the prevention model that

worked on a small scale continue to work in communities

that may vary in any number of factors from size and 

ethnic composition to geography and the nature of their

school systems? 

To answer these questions, NIDA supports an extensive

and growing portfolio of health services research. That

portfolio is designed to give drug abuse treatment and 

prevention service providers the scientific data and

research-based methodologies they need to gauge and

enhance how well their programs will work for real-life

patients in real-life settings. NIDA’s health services

research also encompasses economic analyses that provide

answers to questions such as: Does this drug abuse 

program provide effective services that are accessible to

patients at a reasonable cost? How does this program compare to similar programs in terms of its cost-effectiveness

and accessibility? Does this program not only reduce drug

abuse and addiction, but also reduce costs to society from

drug-related crimes and health expenditures? 

While much remains to be done, NIDA-funded scientists

have built a solid foundation of science-based information

that can be used to document and improve the effectiveness of drug abuse health services. Much of the Institute’s

research in this area is conducted at its health services

research centers, which investigate the Nation’s pressing

drug abuse health services issues. 

For example, investigators at the Center for Managed Care

and Drug Abuse at Brandeis University in Waltham,

Massachusetts, and Harvard University in Cambridge,

Massachusetts, are assessing the impact of managed care

on drug abuse treatment availability, content, duration,

and utilization. They also are studying how managed care

affects the organization and financing of drug abuse treatment facilities. At the Community-Based Health Services

Research Center on Chronic Drug Users at the University

of Miami in Florida, researchers are using the Dade

County, Florida, health services system as a case study to

find ways to improve drug abuse patients’ access to both

primary medical care and drug abuse treatment. The

investigators are exploring how the Dade County system

identifies, assesses, and serves chronic drug users, and, in

particular, whether health care access and effectiveness

vary by ethnicity or gender. 

The Institute has supported three nationwide studies to

assess the effectiveness of drug abuse treatment using

numerous measures of treatment outcomes. All three studies have shown that drug abuse treatment patients in the

four most common types of treatment programs—outpatient methadone, outpatient nonmethadone, long-term

residential, and short-term inpatient—dramatically reduce

their drug use following treatment, reduce drug-related

criminal activities, and improve their physical and mental

health. (For results of the most recent study—the Drug

Abuse Treatment Outcome Study—see NIDA NOTES,

September/October 1997.) 

These studies and other NIDA-funded research highlight

the value of providing patients with services in addition to

drug abuse treatment. A recent study at the Treatment

Research Institute in Philadelphia has found that providing drug abuse patients with services based on their needs

in three areas—employment, family relations, and psychiatric problems—can boost the effectiveness of treatment.

NIDA-funded studies on the economics of treatment and

prevention services are comparing the costs of drug abuse

services with measures that can be quantified in dollar

amounts, such as reduced costs of crime and avoided costs

for medical consequences of drug use. Other such studies

compare the costs of drug abuse services with measures

that cannot be quantified in dollar amounts, such as how

long a patient remains abstinent or a patient’s degree of

social functioning. These studies consistently show that

resources spent on drug abuse services result in substantial

savings to society. For example, results from the

Midwestern Prevention Project—a comprehensive, NIDAfunded prevention study that was conducted in Kansas

City, Kansas; Kansas City, Missouri; and Indianapolis,

Indiana—indicated that every dollar spent on prevention
79

programs saved $68 per affected family in health and

social costs. 

To help treatment providers improve treatment outcomes

and reduce costs, NIDA is developing a manual to guide

them in conducting economic analyses on their own programs. The new manual—titled Measuring and Improving

Cost, Cost-Effectiveness, and Cost-Benefit for Substance

Abuse Treatment Programs—will provide managers with

step-by-step procedures for analyzing the costs of their

services and for producing economic analyses. These

analyses will provide valuable insights into how providers

can serve their patients more efficiently. In the future, the

economic data generated by treatment providers throughout the country may be pooled by researchers to produce

further large-scale economic studies of drug abuse treatment, which, in turn, will give policymakers and insurance companies more science-based information to help

them make decisions related to financing drug abuse treatment. In the coming months, the manual will be available

both in print and on NIDA’s home page on the World

Wide Web. The Web site will also enable treatment

providers to communicate with each other about the 

manual and their findings. 

To keep pace with rapid advances in health services

research, NIDA regularly evaluates its health services

research agenda by drawing on resources both in the drug

abuse field and in the health services research field at

large. In December 1997 the Institute began hosting a

series of meetings intended to help define an agenda for

health services research. These meetings culminated in a

research symposium at the annual conference of the

Association for Health Services Research in June. We will

use the information and ideas gleaned from these meetings

in the coming months as we develop plans for advancing

our research to improve health services for drug abusers. 

We must press forward in our search to find ways to 

provide quality treatment to all drug abuse patients at 

reasonable costs. Likewise, we must continue to work to

insure that promising drug abuse prevention research 

findings translate to real reductions in drug use among

our Nation’s children. 

An economic analysis of the

Midwestern Prevention Project

indicated that every dollar spent 

on prevention programs saved $68

per affected family in health 

and social costs.
Research Findings

80

Volume 13, Number 5 (January 1999)

Two new publications that provide research-based information on nicotine addiction were released at NIDA’s

Addicted to Nicotine Conference in July. 

“Nicotine Addiction,” an eightpage report, provides the latest

information about nicotine and its

addictive properties, including: 

• how nicotine in tobacco

smoke and chewing tobacco

affects the body; 

• how nicotine tolerance develops over time; 

• the medical consequences of

nicotine use; 

• gender differences in nicotine sensitivity; and 

• the risks of smoking during pregnancy. 

Current treatments for nicotine addiction, including nicotine replacements,

behavioral therapies, and a new nonnicotine prescription drug, also are discussed. A glossary and list of resources

for further information are included.

“Nicotine Addiction” is part of the

NIDA Research Report series. 

“The Brain’s Response to Nicotine” is

a new addition to NIDA’s award-winning Mind Over Matter magazine

series. The series is designed to teach

students in grades 5 through 9 how

specific drugs affect the brain. The full-color minimagazine on nicotine describes how tobacco smoke delivers nicotine to the brain, how nicotine disrupts brain

function, and why it is so difficult for people to stop

smoking. The magazine unfolds into an 11-by-23-inch

poster displaying an image of the nerve cells involved in

pain and touch. 

Both publications can be downloaded from NIDA’s home

page on the World Wide Web at www.nida.nih.gov.

Copies are available from the National Clearinghouse on

Alcohol and Drug Information, P.O. Box 2345, Rockville,

MD 20847-2345, (800) 729-6686 or (301) 468-2600,

TDD number: (800) 487-4889, fax: (301) 468-6433, 

e-mail: info@health.org.

NIDA Director Dr. Alan I. Leshner presents the new NIDA publication, “Nicotine Addiction,” to conference participants. 

New Publications Disseminate Research Findings on Nicotine
Research Findings

81

Volume 13, Number 5 (January 1999)

New NIDA Center Will Address Health Issues Associated 

With Drug Abuse

By Barbara Cire, NIDA NOTES Associate Editor 

NIDA has established a new center to coordinate research,

collaborate with other of the National Institutes of Health

(NIH) institutes and related organizations, and provide

leadership to NIDA offices and divisions on issues about

HIV/AIDS and other medical consequences of drug

abuse. The Center for AIDS and Other Medical

Consequences of Drug Abuse, headed by Dr. Henry

Francis (right), was established through a merger of

NIDA’s Office on AIDS and

Clinical Medical Branch, but

its mission and responsibilities go beyond those of these

two components. 

“The new Center represents

an important initiative to

increase NIDA’s multidisciplinary drug abuse research,”

says NIDA Director Dr.

Alan I. Leshner. “The Center

will allow us to address the

full spectrum of health issues

associated with drug abuse,

including HIV/AIDS.” 

The Center will develop multidisciplinary national and

international programs on HIV/AIDS; the medical,

health, and developmental consequences of drug abuse;

and the effects of drug use on other diseases. Program

areas include the origins, treatment, and prevention of

hepatitis C; HIV disease progression; the links between

drug abuse treatment and medical care; tuberculosis in

drug users; clinical research on human development and

drug abuse; and prescription drug abuse. 

“The connection between HIV/AIDS and injection drug

use is well-known,” says Dr. Francis. “Now is the time to

step up our examination of that connection as well as the

connections between drug abuse and other diseases related

to drug abuse, including hepatitis, tuberculosis, hypertension, and sexually transmitted diseases in addition to

AIDS. A number of mental health conditions also are

associated with drug abuse, including severe depression,

schizophrenia, personality disorders, and manic-depressive

disorder. Sometimes mental health problems precede drug

abuse, but in other cases they co-occur with drug abuse. 

It is important to address the impact of these disorders 

on drug abuse and the impact of drug abuse on these 

disorders.” 

The Center is currently supporting several collaborative

studies with other NIH Institutes and government agencies, as well as nongovernment groups. For example,

NIDA is participating in the Women’s Interagency HIV

Study/HIV Epidemiology Research Study with the

National Institute of Allergy and Infectious Diseases

(NIAID), the National Cancer Institute, the National

Institute of Child Health and Human Development

(NICHD), the National Institute of Dental and

Craniofacial Research, and the Centers for Disease

Control and Prevention. This study is examining the 

medical and psychosocial impact of HIV on women.

NIDA is also collaborating with NIAID and NICHD on

the Women and Infants Transmission Study, which is

investigating mother-to-infant transmission of HIV. 

“Drug addiction is a cross-over disease that permeates virtually all of the research areas addressed by NIH,” says Dr.

Francis. “Thus, a multidisciplinary approach is best suited

to exploring the health aspects of drug abuse.” 

Prior to this appointment, Dr. Francis served for 2 years as

chief of the Clinical Medicine Branch in the Division of

Clinical and Services Research at NIDA. He was the

director of the U.S. Public Health Service and Belgium

Projet SIDA (Project AIDS) Research Laboratories in

Kinshasa, Zaire, from 1984 to 1988. Dr. Francis received

his medical degree from Howard University College of

Medicine and performed his clinical training in internal

medicine at the Long Beach Veterans’ Administration

Department of Medicine at the University of California at

Irvine. He was a fellow, and later assistant professor, in the

Division of Infectious Diseases at The Johns Hopkins

Medical School. He is widely published and has written

articles on HIV/AIDS that have appeared in the Journal of

the American Medical Association, Lancet, the New England

Journal of Medicine, the Journal of Immunology, and the

Journal of Infectious Diseases, among others.

Dr. Henry L. Francis
Research Findings

82

Volume 13, Number 5 (January 1999)

Prenatal Cocaine Exposure Costs at Least $352 Million Per Year 

Prevention of cocaine or crack use during pregnancy could

save $352 million per year, according to a study by

researchers at Brown University in Providence, Rhode

Island. The research, which analyzed data from eight 

longitudinal studies of school-age children prenatally

exposed to cocaine, was reported in the October 23 issue

of Science. 

The study, funded by the Robert Wood Johnson

Foundation, found that up to 80,550 children will have

subtle deficits in IQ and language development as a result

of prenatal exposure to cocaine. Special education to keep

them from failing in school will cost at least $352 million

per year nationwide, researchers estimate. 

“These figures are underestimates,” notes Dr. Barry Lester,

NIDA grantee and lead member of the research team.

“These are costs attributable only to new cases each year,

and do not include the accumulating costs and burdens

associated with annual additions.” 

“Every dollar of prevention saves five times that amount

in treatment and other costs to society,” says NIDA

Director Dr. Alan I. Leshner. “This study emphasizes the

need for more drug abuse prevention efforts, particularly

those directed at women of child-bearing age. The findings also argue for early identification and intervention 

for children most at risk for developing these problems.”
83

Research Findings

Men and Women in Drug Abuse Treatment Relapse at Different

Rates and for Different Reasons

By Steven Stocker, NIDA NOTES Contributing Writer 

Volume 13, Number 4 (November 1998) 

Recent NIDA-funded studies have found that women in

drug abuse treatment relapse less frequently than men do,

at least partly because women are more likely to engage in

group counseling. Other NIDA-supported researchers

have found that cocaine-addicted women and men differ

in the factors that cause them to relapse, indicating that

males and females might benefit from different relapse

prevention strategies. 

Likelihood of Relapse 

In a study conducted at the University of California, Los

Angeles, Dr. Robert Fiorentine and his colleagues have

found that women drug abusers are less likely than men

drug abusers to relapse after entering treatment because

women participate more frequently in group counseling

and that this more intensive level of treatment engagement

helps them to remain drug-free. 

The researchers followed 182 women and 148 men in 26

public outpatient drug abuse treatment programs in Los

Angeles County. The programs provided group, individual, and family counseling; educational activities; and

referrals to other health and social services. The treatment

lasted 6 months. 

About half the patients regularly used just one drug—

primarily crack cocaine, marijuana, or powder cocaine,

and about half used more than one drug. Regular use 

was defined as three or more times per week. The patients

were interviewed while in treatment and approximately 

6 months after the first interview. 

The scientists found that the women in their sample were

less likely than the men to relapse: only 22 percent of the

women compared to 32 percent of the men relapsed 

to drug use in the 6 months between interviews. The

researchers considered several theories to account for 

this finding. 

One possibility was that the women used drugs less than

the men, so abstaining from drug use was easier for them.

However, the study findings showed otherwise. In the year

preceding treatment, more women had used crack cocaine

than men, and about the same percentages of women and

men had used powder cocaine, marijuana, and other

drugs. In addition, women used all drugs as frequently as

men, except for crack and heroin, which women used

more frequently. Finally, about the same percentage of

women and men used two or more drugs. 

Another possibility the researchers considered was that the

women received more social support than the men from a

variety of sources, such as families, friends, and coworkers.

The investigators found that, although the women were

more likely than the men to maintain a social network,

they were no more likely than men to receive emotional

support for their problems and encouragement to stop

using drugs. 

What did appear to explain the difference in relapse was

the fact that the women were more likely to engage in

treatment, particularly group counseling, says Dr.

Fiorentine. In his study, the women engaged in an average

of 10.9 sessions of group counseling per month compared

to 7.9 sessions a month for the men. Research has shown

that more intense participation in treatment is associated

with lower rates of relapse. 

The women did not seem to be attending group counseling sessions more often than men because the sessions

were somehow oriented more toward women. The sessions

dealt with the problems of both genders more or less

equally and were usually attended by both men and

women, Dr. Fiorentine says. 

The reason that women attended group counseling sessions more than men may stem from women’s greater willingness to seek professional help for their health problems,

speculates Dr. Fiorentine. “Women appear to be more

willing to seek help for their problems, including their

substance abuse problems,” he says. “Men, on the other

hand, are more likely to say, I’m OK. I don’t need help. I

can take care of this. It’s just a little problem.’” He recommends that treatment providers discuss with male drug

abusers the possibility that their reluctance to seek help

may be hampering their recovery. 

Even though the women attended more group counseling

sessions than men, they did not attend more individual

counseling or family counseling sessions than men did. 

If women are more likely to use services in general, why

did they not engage more often in these other types of

therapies? The explanation seems to be that these other

therapies are not offered as frequently as group counseling

in Los Angeles County, primarily because of the county’s

budget constraints, Dr. Fiorentine suggests. “Individual

counseling, for example, is expensive and there are only so

many counselors to go around, so treatment programs

ration individual counseling,” he says. 
84

“Both women and men already may be attending the

maximum number of individual counseling sessions they

can attend. If patients could attend as many of these sessions as they desired, you might see more women than

men in these sessions, just as you see more women than

men in group counseling sessions.” 

In a related study, Dr. Roger Weiss and his colleagues at

McLean Hospital in Belmont, Massachusetts, also found

less likelihood of relapse for women than for men among

patients who were hospitalized for cocaine addiction.

When 74 patients were interviewed 6 months after the

hospitalization, 51 percent of the women had remained

abstinent compared to 25 percent of the men. 

Like Dr. Fiorentine, Dr. Weiss theorizes that the women

in his sample were more motivated for therapy than the

men were. “Studies have identified barriers to entering

drug abuse treatment programs that exist for women but

not for men,” says Dr. Weiss. “These include childcare

difficulties and the predominance of male patients and

staff. There is also more social stigma for women in being

labeled an addict. Women who come to these treatment

facilities must be willing to overcome these barriers, which

could lead to a higher percentage of women who are motivated to change.” 

Reasons for Relapse 

In addition to identifying gender differences in the likelihood that drug abusers relapse, scientists also have identified gender differences in drug abusers’ experiences before

and during relapse. Dr. James McKay and his colleagues at

the University of Pennsylvania in Philadelphia found that

women in treatment for cocaine addiction were more likely

than men to report negative emotions and interpersonal

problems before they relapsed. The men, on the other

hand, were more likely to report positive experiences 

prior to relapsing and were more likely to engage in 

self-justification and rationalizing afterward. They reported, for example, that they felt entitled to use cocaine or

that they believed they could control their cocaine use.

The women also were much more likely to be impulsive

in their return to cocaine use. Fifty-six percent of the

women, compared with only 17 percent of the men,

reported that they relapsed immediately after the thought

of using cocaine occurred to them. 

These gender differences in relapse factors suggest that different relapse prevention strategies might be emphasized

for women and men, says Dr. McKay. For example,

women might benefit more from techniques that enable

them to deal more effectively with unpleasant emotions

and interpersonal problems. “One strategy is to take

action quickly as your mood starts to deteriorate rather

than waiting until you are in a really bad mood and then

trying to do something about it,” he says. “If it’s a small

problem, planning an enjoyable activity might be all that

is needed. If, however, it’s a serious depression, medication

or psychotherapy might be necessary.” 

In contrast, men might benefit more from strategies that

counter their tendency to let down their guard when feeling good, Dr. McKay says. “These strategies are derived

from concepts taught in 12-step programs, such as not

getting too cocky or confident when your mood

improves,” he says. “Patients are told to be on the lookout

for warning signs that might be present when they’re feeling good, such as thinking to themselves, ‘I’m feeling great

today. I don’t need to go to that meeting. I can go hang

out with this friend of mine. I know he uses, but I’m feeling

good today, and I’m not vulnerable to using.’” 

More Research 

Gender differences in drug abuse are of intense interest to

NIDA, says Carol Cowell of NIDA’s Division of Clinical

and Services Research. “Researchers are finding gender differences across the broad spectrum of drug abuse research

—from basic research to studies such as these on treatment and services—and we would like to encourage more

study of these differences,” she says. She occasionally suggests that NIDA-funded researchers analyze their data in

terms of gender differences. “This sometimes results in a

study that increases our knowledge of the role of gender in

treatment outcomes,” she says. 

“Performing gender analyses is simply a matter of doing

good science,” says Dr. Cora Lee Wetherington, NIDA’s

women’s health coordinator. When gender differences exist

but investigators fail to test for them, flawed conclusions

may be drawn, either for males or females or both, she says. 

Sources 

• Fiorentine, R.; Anglin, M.D.; Gil-Rivas, V.; and

Taylor, E. Drug treatment: Explaining the gender paradox. Substance Use and Misuse 32(6):653–678, 1997. 

• Fiorentine, R.; Nakashima, J.; and Anglin, M.D.

Client engagement in drug treatment. Journal of

Substance Abuse Treatment 17(3):199–206, 1999. 

• McKay, J.R.; Rutherford, M.J.; Cacciola, J.S.;

Kabasakalian-McKay, R.; and Alterman, A.I. Gender

differences in the relapse experiences of cocaine

patients. The Journal of Nervous and Mental Disease

184(10):616–622, 1996. 

• Weiss, R.D.; Martinez-Raga, J.; Griffin, M.L.;

Greenfield, S.F.; and Hufford, C. Gender differences

in cocaine dependent patients: A 6 month follow-up

study. Drug and Alcohol Dependence 44(1):35–40,

1997.
Research Findings

85

Volume 13, Number 4 (November 1998) 

Men who abuse drugs are more likely to reduce their sexual risks of HIV infection if they are given risk-reduction

information on the street, while women drug abusers

respond better if they are given

this information in an office

with counseling. This is one of

the findings of a NIDA-funded

study on the effectiveness of

HIV risk-reduction programs

tested in two towns in Arizona. 

Dr. Robert Trotter and his colleagues at Northern Arizona

University in Flagstaff developed

two enhanced programs for

reducing drug-related and sexual

risks for HIV transmission and

added the programs to a standard program developed by the

Centers for Disease Control and

Prevention and modified by

NIDA. The standard program

recruits drug abusers on the

street and then provides HIV

risk-reduction information at the project office. In the

office, counselors provide information on proper condom

use and bleach disinfection of drug injection equipment.

Drug abusers also are offered testing for HIV infection. 

One of the enhanced programs developed by the

researchers, called the active outreach intervention, 

provides the HIV risk-reduction information on the street

rather than in the office. Later, the entire network of people who use drugs together and share drug use equipment

is invited into the office for a group discussion of HIV

transmission risks. 

The other enhanced intervention, called the office-based

intervention, involves the same recruitment procedure as

the standard intervention, but additional counseling techniques are used when the drug abuser visits the office. In

the office, the person is first asked to identify at least one

HIV risk in his or her life. The person is then asked how

this risk might be reduced and is encouraged to do so.

Like the active outreach intervention, the office-based

intervention also involves a subsequent group session with

the network of drug abusers. 

All three interventions, both the

standard and the two enhanced,

reduced HIV risk behaviors; however, for reducing sexual risks, the

researchers found that the active

outreach intervention worked better for men, and the office-based

intervention worked better for

women. The men seemed to

respond well to being taught about

HIV risk-reduction on the street

because that was the environment

in which HIV risks often

occurred, Dr. Trotter speculates.

“Some pretty solid social science

theory states that, for certain

kinds of behavior, providing the

behavior reduction intervention in

the context in which the behavior

occurs is more effective,” he says. 

However, this theory did not apply to the women in the

study. The women told the researchers that they felt safe

discussing sensitive matters in the office, where they were

not under pressure from family and other drug abusers. “If

we had conducted the interventions with these women on

the street or in their homes, people would be around who

might hear what they were saying, and the women were

afraid of the repercussions. In the office, the women felt

emotionally and physically protected,” Dr. Trotter says. 

Source 

• Trotter, R.T.; Bowen, A.M.; Baldwin, J.A.; and Price,

L.J. The efficacy of network-based HIV/AIDS riskreduction programs in midsized towns in the United

States. Journal of Drug Issues 26(3):591–605, 1996.

Researchers Find Gender Differences In How Drug Abusers

Respond To HIV Prevention Strategies

By Steven Stocker, NIDA NOTES Contributing Writer 

Dr. Robert Trotter of Northern Arizona University discusses with his staff possible strategies for reducing HIV

transmission risks among drug abusers who use drugs

together and share drug injection equipment.
Research Findings

86

Volume 13, Number 4 (November 1998)

Gender Matters in Drug Abuse Research

NIDA Director Dr. Alan I. Leshner 

Accumulating evidence indicates that drug abuse may

begin and progress differently, have different consequences, and require different prevention and treatment

approaches for women and men. Therefore, NIDA has

strongly supported research to identify gender differences

and gender-specific aspects of drug abuse and addiction

and to apply these findings toward more effective drug

abuse prevention, treatment, and services for

both women and men. 

Historically, NIDA has supported a broad program of research on the effect of women’s drug

use on pregnancy, maternal health, and childhood development. A little more than 5 years

ago, NIDA broadened the scope of its genderrelated research by issuing program announcements calling for research to examine the causes

and consequences of drug abuse among women

of all ages, regardless of their parental status. In

the fall of 1994, NIDA sponsored a landmark

national conference on addiction and women’s

health. This meeting launched our expansion of

research on the role of gender in all

aspects of drug abuse and addiction.

Since then, our Women and Gender

Research Group, which is made up of

representatives from every NIDA

Division and Office, has been working

to further develop NIDA’s research on

women’s health and gender 

differences and to disseminate the

findings to professionals in the field

and the general public. 

Today, gender-related research is integrated throughout NIDA’s entire portfolio. This research extends from basic molecular and cellular studies to clinical and epidemiologic studies and is

grouped into four major areas: etiology, consequences,

prevention, and treatment and services. Through this

research, we are learning more and more about differences

between women and men in the origins of drug abuse, the

consequences of drug abuse and addiction, and the factors

that influence drug abuse relapse and recovery. 

Our research on the origins of drug abuse has found gender differences in factors affecting initiation, progression,

and maintenance of drug use. For example, basic 

behavioral and neurochemical research has suggested that

women may be more sensitive than men to the rewarding

effects of drugs, perhaps due to differences in brain chemistry. Animal studies also have shown that females respond

more than males to the stimulating and reinforcing properties of abused drugs. Other studies indicate that the

intensity of a drug’s effects on women varies during different phases of the menstrual cycle. These

physiological differences may help

account for data indicating that women

may proceed to drug abuse and addiction

more rapidly than men do after initial

drug use. 

Evidence also indicates that psychosocial

factors, such as childhood physical and

sexual abuse, depression and posttraumatic stress disorder, relationships with a significant other, and partner violence play a

more important role for women than for

men in beginning and continuing drug

use. For example, one research study suggests that women’s tobacco use is

controlled more by social and

sensory factors and less by

dependence on nicotine itself,

compared to men’s tobacco use. 

NIDA-supported research also is

finding gender differences in the

consequences of drug abuse. For

example, both animal and

human studies indicate that

men may be at greater risk than

women for strokes and for mental deficits from chronic cocaine

abuse. Other research suggests that the female hormone

estrogen may play a role in reducing cocaine toxicity in

women. 

One of the most devastating health consequences of illicit

drug use for both women and men is AIDS, with half of

all new HIV infections now linked to injection drug use.

Approximately two-thirds of AIDS cases in women and

more than half of pediatric AIDS cases in the United

States are related to injection drug use by women or their

sexual contact with an injecting drug user. 

“In the last 5 years, NIDA has

greatly increased scientific

knowledge about genderrelated differencs in almost

every aspect of drug abuse

and addiction.”
87

NIDA’s comprehensive AIDS initiative is uncovering significant gender-related differences in factors that contribute to and protect from HIV risk. For example, one

study of female injecting drug

users has found that the family

plays a more important role for

women than for men in resistance to needle-sharing behaviors. 

Other studies in our AIDS

research portfolio are identifying gender-specific strategies to

decrease injection drug use and

high-risk sexual behaviors among

women and men. For example,

researchers at Northern Arizona

University in Flagstaff have

found that male drug abusers are

more likely to reduce their highrisk sexual behaviors if given

HIV risk-reduction information

on the street, while female drug abusers respond better if

this information is given along with counseling in the

more protective environment of an office. 

The ultimate goal of our research is to apply our increased

understanding of gender-specific drug abuse factors to the

development of prevention and treatment interventions

that better meet the unique needs of both women and

men. For example, a recent NIDA-supported study indicates that treatment interventions need to address differences in psychosocial factors that influence women’s and

men’s relapse to drug use following treatment. In the

study, researchers at the University of Pennsylvania found

that negative emotions and interpersonal relations are

linked to relapse among cocaine-dependent women while

men are more likely to experience positive emotions prior

to relapse. 

In the last 5 years, NIDA has greatly increased scientific

knowledge about gender-related differences in almost

every aspect of drug abuse and addiction. However, we

still have tremendous gaps to fill in that knowledge. We

need to learn more about how gender relates to the impact

of violence and victimization, devise better gender-specific

treatment for comorbid mental disorders, and learn how

to adequately address gender-related cultural factors in

prevention and treatment, to name

just a few. 

To fill those gaps and build on our 

current knowledge, we are encouraging

research that addresses gender-specific

issues and gender differences in such

diverse drug abuse areas as origins

and pathways, biomedical factors,

comorbid mental disorders, epidemiology, medical and health consequences, health services, special populations, HIV/AIDS, prevention, and

treatment. 

Evidence from NIDA’s gender-related

research indicates that prevention and

treatment strategies that address gender differences can be more effective than one-size-fits-all

approaches in preventing drug abuse and relapse following

treatment. Through our continued strong emphasis on the

role of gender throughout our research portfolio, NIDA is

working to speed the day when gender differences are successfully addressed in all areas of drug abuse prevention and

treatment. 

For More Information

• An overview of NIDA’s research program on women’s

health and gender differences, details of research

advances and opportunities, program announcements,

publications, and research reports can be found under

“Women’s Health and Gender Differences,” on

NIDA’s home page on the World Wide Web at

www.nida.nih.gov. Information about women and

drug abuse also is available from Infofax, NIDA’s

automated information retrieval system, at 1-888-

644-6432. In addition, the “Bulletin Board” includes

a description and ordering information for a recently

released NIDA publication, Drug Addiction Research

and the Health of Women. 

“Through this research, we are

learning more and more about

differences between women

and men in the origins of drug

abuse, the consequences of

drug abuse and addiction, and

the factors that influence drug

abuse relapse and recovery.” 
Research Findings

88

Volume 13, Number 4 (November 1998)

Publications Focus On Women’s Health 

NIDA has released two companion publications on

research related to drug addiction and women’s health.

Drug Addiction Research and the Health of Women grew out

of presentations at a national conference of the same name

held by NIDA in 1994. In the 581-page volume, indepth

reviews of current research provide extensive data on the

differences between men and women in the causes and

effects of drug abuse and addiction. 

The companion volume, the 142-page Drug Addiction

Research and the Health of Women: Executive Summary,

contains condensed versions of conference presentations

and discussions. 

Both publications can be obtained through the National

Clearinghouse for Alcohol and Drug Information

(NCADI), P.O. Box 2345, Rockville, MD 20847-2345, at

1-800-729-6686. Request NCADI publication #BKB258

for the research volume and #BKB259 for the executive

summary. The publications also can be downloaded from

NIDA’s home page on the World Wide Web by accessing

the list of NIDA publications on women’s health and gender differences located at http://www.nida.nih.gov/

WHGD/WHGDPub.html.
Research Findings

89

Facts About Nicotine and Tobacco Products

Volume 13, Number 3 (July 1998)

About 62 million people in the United States ages 12 and

older, or 29 percent of the population, are current cigarette smokers, according to the 1996 National Household

Survey on Drug Abuse. This makes nicotine, the addictive

component of tobacco, one of the most heavily used

addictive drugs in the United States.

Effects of Nicotine

When a person inhales cigarette smoke, the nicotine in

the smoke is rapidly absorbed into the blood and starts

affecting the brain within 7 seconds. In the brain, nicotine

activates the same reward system as do other drugs of

abuse such as cocaine or amphetamine, although to a lesser degree. Nicotine’s action on this reward system is

believed to be responsible for drug-induced feelings of

pleasure and, over time, addiction. Nicotine also has the

effect of increasing alertness and enhancing mental performance. In the cardiovascular system, nicotine increases

heart rate and blood pressure and restricts blood flow to

the heart muscle. The drug stimulates the release of the

hormone epinephrine, which further stimulates the nervous system and is responsible for part of the “kick” from

nicotine. It also promotes the release of the hormone 

beta-endorphin, which inhibits pain.

People addicted to nicotine experience withdrawal when

they stop smoking. This withdrawal involves symptoms

such as anger, anxiety, depressed mood, difficulty concentrating, increased appetite, and craving for nicotine. Most

of these symptoms subside within 3 to 4 weeks, except for

the craving and hunger, which may persist for months.

Health Effects of Tobacco Products

Besides nicotine, cigarette smoke contains more than

4,000 substances, many of which may cause cancer or

damage the lungs. Cigarette smoking is associated with

coronary heart disease, stroke, ulcers, and an increased

incidence of respiratory infections. Smoking is the major

cause of lung cancer and is also associated with cancers of

the larynx, esophagus, bladder, kidney, pancreas, stomach,

and uterine cervix. Smoking is also the major cause of

chronic bronchitis and emphysema.

Women who smoke cigarettes have earlier menopause.

Pregnant women who smoke run an increased risk of 

having stillborn or premature infants or infants with low

birthweight. Children of women who smoked while 

pregnant have an increased risk for developing conduct

disorders.

Cigar and pipe smokers and users of chewing tobacco and

snuff can also become addicted to nicotine. Although

cigar and pipe smokers have lower death rates than cigarette smokers do, they are still susceptible to cancers of the

oral cavity, larynx, and esophagus. Users of chewing tobacco and snuff have an elevated risk for oral cancer.

Treatment

Like addiction to heroin or cocaine, addiction to nicotine

is a chronic, relapsing disorder. A cigarette smoker may

require several attempts over many years before that 

person is able to permanently give up smoking. Less than

10 percent of unaided quit attempts lead to successful

long-term abstinence. However, studies have shown 

significantly greater cessation rates for smokers receiving

interventions compared to control groups who do not

receive the interventions. Interventions that involve both

medications and behavioral treatments appear to show 

the most promise.

The primary medication therapy currently used to treat

nicotine addiction is nicotine replacement therapy, which

supplies enough nicotine to the body to prevent withdrawal symptoms but not enough to provide the quick

jolt caused by inhaling a cigarette. Four types of nicotine

replacement products are currently available. Nicotine

gum and nicotine skin patches are available over the

counter. Nicotine nasal spray and nicotine inhalers are

available by prescription. On average, all types of nicotine

replacement products are about equally effective, roughly

doubling the chances of successfully quitting.

Another medication recently approved by the Food and

Drug Administration as an aid for quitting smoking is the

antidepressant bupropion, or Zyban®. The association

between nicotine addiction and depression is not yet

understood, but nicotine appears to have an antidepressant effect in some smokers. Paradoxically, though, buproprion is more effective for treating nicotine addiction in

nondepressed smokers than in smokers who are depressed.

For More Information

• More information about nicotine addiction and

tobacco can be found at the NIDA Web site at

http://www.nida.nih.gov, or by calling Infofax,

NIDA’s automated information retrieval system, at 1-

888-NIH-NIDA. Information is also available from

the National Clearinghouse for Alcohol and Drug

Information (NCADI), P.O. Box 2345, Rockville,

MD 20847-2345, (800) 729-6686. The NCADI Web

site is http://www.health.org.
Research Findings

90

Exploring the Role of Child Abuse in Later Drug Abuse:

Researchers Face Broad Gaps in Information 

By Neil Swan, NIDA NOTES Staff Writer 

Volume 13, Number 2 (June1998)

As many as two-thirds of all people in treatment for drug

abuse report that they were physically, sexually, or emotionally abused during childhood, research shows.

However, the role of child abuse—physical trauma, rape

and sexual abuse, neglect, emotional abuse, and witnessing

or being threatened with violence or other abuse—in the

pathway to drug abuse needs closer examination.

Although studies probing the effects of child abuse have

increased in recent years, researchers still are confronted

with broad gaps in information. 

“The sheer weight of the many

reports over the years certainly implicates child abuse as a possible factor

in drug abuse for many 

people,” says Dr. Cora Lee

Wetherington, NIDA’s Women’s

Health Coordinator. “But we lack

hard data that clearly establish and

describe the role of child abuse 

in the subsequent development 

of drug abuse. Is child abuse 

indeed a cause of drug abuse, or 

is child abuse a marker for other

unidentified factors?” 

Many critical questions remain unanswered, NIDA

researchers agree. How can child abuse victims be identified and studied to track the variables that may contribute

to subsequent drug abuse? What factors lessen or strengthen the risk that child abuse will progress to drug abuse?

What, in fact, constitutes child abuse? 

Answers to questions such as these will help develop creative new drug abuse therapies and prevention strategies.

With new knowledge, special interventions could target

victims of child abuse to prevent progression to drug

abuse. A better understanding of the consequences of

child abuse would enable researchers to develop ways to

tailor drug abuse treatment to adults who are victims of

child abuse. Awareness of this potential has prompted

interest among NIDA researchers in further studies into

the relationship between child abuse and progression to

drug abuse. 

However, important obstacles hamper these investigations,

which involve not only the researchers and the victims and

their families, but also doctors, hospitals, psychologists,

child welfare agents, police, and the justice system. The

involvement of so many professional disciplines and divergent interests makes identifying victims of child abuse and

gathering information from them and their families

extremely difficult. Some critical information is not 

publicly available due to both the need for confidentiality

laws designed to protect minors and the secrecy spawned

by feelings of guilt or shame by victims, abusers, and 

family members. 

These barriers severely limit data

gathering during the period when

child abuse is occurring. Most

data are gathered years later, in

what are called retrospective

assessments, from victims’ 

memories and self-reports. Thus,

much assessment occurs only 

after victims have grown up 

or at least reached adolescence,

entered treatment programs 

for drug abuse, and often 

are also experiencing other 

psychological disorders. 

Nevertheless, researchers are

making inroads. Most information about the role of child

abuse has come indirectly—from studies of drug abuse

that bring to light information about childhood trauma.

Some of these studies trace stress-related disorders in adult

drug abusers back to childhood traumas. One example is a

NIDA-funded review by Dr. Lisa M. Najavits and her colleagues at Harvard Medical School in Boston that examined 49 studies involving drug-abusing women with posttraumatic stress disorder (PTSD). Victims of PTSD reexperience trauma and terror through unexpected flashbacks or nightmares. Child abuse is one trauma that is frequently reported by PTSD patients who are drug abusers. 

While drug abusers overall show high rates of coexisting

PTSD diagnoses, female drug abusers show much higher

rates of this dual diagnosis than do males who abuse

drugs. Various studies reviewed by Dr. Najavits report that

from 30 percent to 59 percent of women in drug abuse

treatment also have PTSD—two to three times higher

than the rate among men in treatment, according to 

Dr. Najavits’ review. 

The involvement of so many

professional disciplines and

divergent interests makes 

identifying victims of child abuse

and gathering information from

them and their families

extremely difficult. 
91

A history of trauma independent of PTSD is even more

common among women in drug abuse treatment. The

reviewed studies show that from 55 percent to 99 percent

of these women reported a history of physical or sexual

trauma. Most of the trauma occurred before age 18 and

was commonly related to repetitive childhood physical or

sexual assault. When the women are victims of both types

of abuse, they are twice as likely to abuse drugs as are

those who experienced only one type of abuse. 

In another study, Dr. Najavits and her colleagues reviewed

data from NIDA’s Collaborative Cocaine Treatment Study,

which collected treatment and outcome data from patients

at five drug abuse treatment sites in eastern cities. Dr.

Najavits examined lifetime traumatic events and current

PTSD symptoms of 122 adult cocaine-dependent men

and women outpatients. She found a high rate of lifetime

exposure to traumatic events—an average of 5.7—and a

20.5 percent rate of currently diagnosed PTSD. The

patients with PTSD showed significantly more impairments and different circumstances related to their trauma.

For example, they reported that their first trauma occurred

at an average age of 8.4 years, significantly younger than

patients without a current PTSD diagnosis, whose first

reported trauma was at the average age of 13.1.

Another NIDA-funded study, which documents that

women rape victims are dramatically more likely to abuse

drugs than are women who are not victims, also directly

implicates child abuse. Dr. Dean G. Kilpatrick at the

Medical University of South Carolina found that more

than 61 percent of rapes of the 4,008 women in his study

occurred by age 17. About half of those occurred by age

11; these obviously were cases of child abuse. The rape

victims, compared to others who were not raped, were: 

• more than three times as likely to have used 

marijuana; 

• six times more likely to have used cocaine; and 

• more than 10 times as likely to have used drugs other

than cocaine, including heroin and amphetamines.

One recent study illustrates both progress in studying the

relationship of child abuse to subsequent drug abuse and

the difficulty in gathering data that specifically address

that relationship. The 1997 NIDA-funded study examined data from previous ethnographic studies of drugabusing adults in New York City. The study found a significant statistical association between inhalant abuse and

the abusers’ reports that they were abused as children.

However, the data do not demonstrate a causal relationship between the two, says Dr. Michael Fendrich of the

University of Illinois at Chicago, the study’s principal

author. Evidence of a causal role for child abuse would

require more data to substantiate that the onset of child

abuse occurred before the onset of inhalant abuse, 

he points out. 

The fact that most data marking a trail from child abuse

to drug abuse are collected retrospectively poses a variety

of problems for researchers. Investigators recognize that

memory is subjective. Also, drug abusers may choose 

consciously to emphasize the role of parents or others in

their retrospective accounts of events leading to their 

drug abuse. Thus, researchers, may seek additional data

from other sources, such as juvenile court records of child

abuse cases. 

But NIDA-funded researchers are seeking innovative

approaches to address these information-gathering problems to understand the connections between child abuse

and later drug abuse. Dr. Cathy Spatz Widom of the State

University of New York at Albany is comparing rates of

drug abuse between a group of adults who had courtsubstantiated cases of child abuse and neglect and a control group of their childhood peers who did not have such

records. Her initial findings show little difference in rates

of drug abuse between the two groups. She recognizes that

other factors are, of course, involved. For example, since

many cases of child abuse never wind up in court, some in

the control group with no court records may have been

abused as well. Also, court-ordered interventions and therapies may have reduced the prevalence of drug abuse

among court-documented child abuse victims. Even so,

the preliminary results cause Dr. Widom to express concerns. “Child abuse is a factor in subsequent drug abuse,

but it may be much less a factor than we now believe,” she

says. “Child abuse may be an important factor primarily

for certain subgroups—some groups of women, for example—more than for the population in general.” Other factors, such as poverty or family substance abuse problems,

play a role, too, she says. 

Difficulties such as these have hindered development of

drug abuse treatment and prevention approaches that

specifically address the needs of child abuse victims.

However, some progress has been made in enhancing

treatment for specific groups, such as drug-abusing

women with PTSD, that include high percentages of 

child abuse victims.

A better understanding of the 

consequences of child abuse would

enable researchers to develop ways 

to tailor drug abuse treatment to 

the needs of drug abusers who 

say that they are victims of 

child abuse.
92

Recognizing the need for broad new research agendas,

NIDA continues to encourage studies into child abuse

and its relationship to drug abuse during adolescence and

young adulthood. Examining the role of child abuse is a

major goal of the Interagency Consortium on Violence

Against Women and Violence Within the Family that

NIDA has joined with a number of other Federal 

agencies. Also under discussion is a NIDA-sponsored 

scientific meeting in 1998 on drug abuse and the 

childhood environment. 

Sources 

• Fendrich, M.; Mackesy-Amiti, M.E.; Wislar, J.S.; and

Goldstein, P.J. Childhood abuse and the use of

inhalants: Differences by degree of use. American

Journal of Public Health 87(5):765–769, 1997. 

• Kilpatrick, D.G.; Edmunds, C.N.; and Seymour, A.K.

Rape in America: A Report to the Nation. Crime

Victims’ Research and Treatment Center, Charleston,

SC, 1992. 

• Najavits, L.M., et al. Cocaine dependence with and

without PTSD among subjects in the National

Institute on Drug Abuse Collaborative Cocaine

Treatment Study. American Journal of Psychiatry

155:214–219, 1998. 

• Najavits, L.M.; Weiss, R.D.; and Shaw, S.R. The link

between substance abuse and posttraumatic stress disorder in women: A research review. American Journal

on Addictions 6(4):273–283, 1997.
Research Findings

93

Volume 13, Number 2 (June 1998)

A NIDA-funded

researcher has 

developed an 

innovative treatment

program to meet the

special needs of drugabusing women who

also are diagnosed with

posttraumatic stress 

disorder (PTSD), a 

disorder often associated

with physical, sexual,

or other abuse during

childhood. PTSD 

victims re-experience

their trauma, sometimes

years later, through

unexpected and recurring flashbacks or 

nightmares. The trauma that sparks PTSD may range

from battlefield shock or childhood sexual molestation to

violence related to drug dealing. 

PTSD symptoms include “avoidance” behavior, which

may be marked by loss of interest in favorite activities,

avoidance or suppression of thoughts or emotions, feelings

of detachment, or difficulty thinking about the distant

future. PTSD victims may suffer increased arousal or anxiety, as shown in extra vigilance against perceived dangers,

trouble concentrating, exaggerated responses to being startled, and outbursts of anger. 

PTSD combined with drug abuse can be devastating for

women struggling to survive in the street drug culture.

One study, which evaluated women crack cocaine abusers

with PTSD in New York City’s Harlem, found that they

are forced into vicious cycles in which they use crack to

counteract the distress of trauma, suffer more drug-related

trauma, and then turn to crack again. 

Development of new treatment strategies for drug abusers

with coexisting PTSD, especially women, should be a

high priority, says Dr. Lisa M. Najavits of Harvard

Medical School, who conducted a NIDA-funded review

of research focusing on women with these problems.

Treatments developed either for PTSD or substance abuse

alone may not be sufficient, she says. Further, existing

treatments for men with PTSD and drug abuse may not

be directly applicable to women, she adds. 

Dr. Najavits developed an innovative treatment program

called “Seeking Safety” that consists of 24 sessions that

teach women new coping skills to manage both disorders

at once. Patients learn how to ask for help, set boundaries

in relationships, nurture themselves, and fight cues and

urges to relapse to drug use. 

The safety theme is emphasized as the key to recovery

from both PTSD and drug abuse. 

“Safety” in this situation means abstaining from drugs and

alcohol, reducing self-destructive behavior, establishing a

network of supportive people, and guarding against the

dangers associated with both disorders, such as HIV and

domestic violence. 

Of 27 women enrolled in the “Seeking Safety” program,

17 completed treatment. After treatment, these women

showed significant reductions in drug use, trauma-related

symptoms, suicide risk, and suicidal thoughts. They

showed improvements in social adjustment, family functioning, problem solving, depression, and thoughts about

substance abuse, according to Dr. Najavits. “While this 

is a small sample, an uncontrolled pilot study, the data

indicate that, when provided with treatment tailored to

their needs, these difficult-to-treat women appear highly

responsive and show improvements in both of their 

diagnoses,” she says. 

Her treatment design is now undergoing further evaluation

in three demonstrations where it is being compared to

usual treatment regimens. 

Sources 

• Fullilove, M.T.; Fullilove, R.E.; Smith, M.; et al.

Violence, trauma, and post-traumatic stress disorder

among women drug users. Journal of Traumatic Stress

6(4):533–543, 1993. 

• Najavits, L.M.; Weiss, R.D.; and Liese, B.S. Group

cognitive-behavior therapy for women with PTSD

and substance use disorder. Journal of Substance Abuse

Treatment 13:13–22, 1996. 

Innovative Treatment Helps Traumatized Drug-Abusing Women

By Neil Swan, NIDA NOTES Staff Writer 

Dr. Lisa Najavits of Harvard

Medical School has developed an

innovative treatment program for

drug-abusing women with posttraumatic stress disorder resulting

from traumas such as child abuse. 
94

• Najavits, L.M.; Weiss, R.D.; and Shaw, S.R. The link

between substance abuse and posttraumatic stress disorder in women: A research review. American Journal

on Addictions 6(4):273–283, 1997. 

• Najavits, L.M.; Weiss, R.D.; Shaw, S.R.; and Muenz, 

L.R. Seeking Safety: Outcome of a new cognitive 

psychotherapy for women with posttraumatic stress 

disorder and substance dependence. Journal of

Traumatic Stress 11(3):437–456, 1998. 
Research Findings

95

Volume 13, Number 2 (June 1998)

NIDA Probes the Elusive Link Between Child Abuse and 

Later Drug Abuse

NIDA Director Dr. Alan I. Leshner 

Substantial evidence points to childhood victimization as a

major risk factor for later drug abuse. At least two-thirds

of patients in drug abuse treatment centers say they were

physically or sexually abused as children. However, we

know relatively little about the details of

that apparent link between child abuse

and later drug use. NIDA-supported

researchers are working intensively on

this critically important public health

question. 

Determining the exact relationship

between child abuse and drug abuse is

exceedingly difficult given the role that

variables such as poverty, family dysfunction, the level of social support for

victims, or the child’s gender and age

play. Further, not all child abuse victims

later become drug abusers.

What factors protect a child

abuse victim from becoming a

drug abuser? What factors

make an abused child more

vulnerable to drug abuse? In

addition, child abuse victims

may suffer severe emotional

damage—even years later as

adults. How can investigators

conduct research without risk

of exacerbating that damage? 

NIDA has built a solid foundation of information and

methodologies that researchers

can use in seeking answers to these questions. For example, an expert panel convened by the Institute in 1996

reviewed the research on the role of childhood trauma in

later drug abuse. Among the panel’s conclusions was that

the characteristics of the trauma, the child, and the child’s

environment interact to either buffer or aggravate the

impact, which subsequently can produce a wide range of

dysfunctional behaviors that can include drug abuse.

NIDA researchers have extensively examined and evaluated

risk and protective factors for drug abuse. Researchers

have developed drug abuse prevention protocols that 

maximize protective factors and target risk factors. These

findings can serve as a starting point for developing prevention approaches that specifically target abused children.

In addition, research to better treat the emotional scars of

drug abusers who are child abuse victims can

draw on NIDA research on treating drug abusers

with coexisting mental and emotional problems. 

However, many challenges for research in this

area are unique to child abuse. Because society

must act decisively to deter child abuse and at

the same time protect its victims, legal questions

relating to privacy, confidentiality, and informed

consent—and the legal rights of accused

abusers—limit researchers’ access to information

about child abuse. 

These challenges pose a different set of questions

for researchers. How can abused 

children be appropriately identified and

their experiences accurately classified?

How can reports and statements about

abusive incidents be gathered and 

evaluated? Researchers usually have

approached their investigations retrospectively, looking back over time and

examining the psychological histories of

adult patients being treated for drug

abuse. That is where studies have found

the strong correlations between childhood abuse and the subsequent development of drug abuse in adolescence

and adulthood. 

However, these studies rely primarily on memories of

adult drug abusers. Scientists have long wrestled with the

subjectivity of memory. With this in mind, NIDAfunded scientists are evaluating and refining methods 

for gathering, assessing, and verifying retrospective recall

and looking for other sources of information, including

court records. 

NIDA is well situated to help these researchers and others

bridge bureaucratic and disciplinary gaps among the many

governmental and social service entities—health and child

welfare agencies, drug abuse treatment and prevention

Research to better treat the

emotional scars of drug

abusers who are child abuse

victims can draw on NIDA

research on treating drug

abusers with coexisting mental

and emotional problems. 
96

service providers, doctors and hospitals, and the justice

system—that are seeking to expand their knowledge of,

and response to, child abuse and drug abuse. NIDA can

also bring past experience to bear to enhance integration

of diverse scientific disciplines, pooling of resources, and

rapid dissemination of research findings and viable prevention and treatment strategies. NIDA’s current leadership role in the Interagency Consortium for Research on

Violence Against Women and Violence Within the

Family, which has child abuse as an important focus, is a

prime example of how the Institute can respond to this

need for coordination and cooperation. 

In addition, NIDA continues to recruit, encourage, and

support researchers who will seek further answers to questions surrounding the links between child abuse and 

drug abuse. For example, could early identification of

child abuse victims coupled with intervention prevent

subsequent drug abuse? Do child abuse victims respond

differently to different drug abuse treatment approaches?

Does a history of child abuse affect treatment, retention,

and relapse outcomes? The Institute also is planning a

major scientific conference on drug abuse and the childhood environment that will address these and other issues

related to children and drug abuse. 

On the broad scale, NIDA’s public health mission and

experience will be of great value here, combining the

expertise of its grantees and staff in many disciplines to

shed more light on the elusive link between child abuse

and drug abuse. And as our stockpile of science-based

knowledge in this area grows, we can speed our pursuit of

two goals: preventing abused children from becoming

drug abusers and designing better treatments for that

majority of drug abusers who report that they are also the

victims of child abuse.
Research Findings

97

NIDA’s “Report Card”

Volume 13, Number 1 (June 1998)

NIDA constituent groups have a lot to say about NIDA’s

activities, and the Institute is taking note. 

Each year at NIDA’s constituent conference, members of

national groups in the field of drug abuse take on the role

of advisors, providing invaluable advice and feedback to

the Institute, noted NIDA Director Dr. Alan I. Leshner at

this year’s gathering. In what has become an important

part of the 2-day meeting, constituents split up into work

groups to focus on specific drug abuse issues. Out of their

discussions come recommendations to NIDA program

staff about research and other activities they think the

Institute should undertake or strengthen to advance its

public health mission. 

After the conference, NIDA carefully sifts through these

recommendations, folding them into the many research

and program initiatives it implements every year. At the

next constituent conference, NIDA reports on the actions

it has taken in direct response to the input it received at

previous conferences. NIDA calls this detailed list of 

activities its “Report Card.” 

This year’s Report Card lists 109 NIDA activities that

address constituents’ recommendations. Below is a sampling of these activities. 

• Established a Memorandum of Understanding with

the Substance Abuse and Mental Health Services

Administration to collaborate in information

exchange and dissemination, planning NIDA’s health

services research program, collaborative research and

services projects, and facilitating linkages between

researchers and service providers. 

• Teamed with Howard University Research Center in

Washington, DC, to sponsor a meeting with faculty

and staff from historically black colleges and universities who are forming a consortium to research 

substance abuse and other health issues among

women on black college campuses. 

• Is expanding its home page on the World Wide Web,

at http://www.nida.nih.gov, and its links to constituency group Web sites and will continue to add

more education materials to its Web site. 

• Launched a new Children and Adolescents Initiative

with two major components: preventing drug use and

preventing individuals, their offspring, and society

from suffering the health consequences of drug abuse. 

• Launched a major Treatment Initiative to increase

dramatically the quality and extent of drug treatment

and to foster the interchange of useful information on

drug addiction treatment. 

• Published the first ever science-based guide to drug

abuse prevention, Preventing Drug Use among

Children and Adolescents. 

• Is funding a Resource Center that will enhance

NIDA’s resources and strengthen its ability to identify

and answer key research questions about the financing, organization, costs, and outcomes of drug abuse

treatment and prevention services. 

• Coordinated the development of abstracts on key

research related to drug abuse and HIV/AIDS for the

1998 World AIDS Conference in Geneva to highlight

and present U.S. research findings in this area.
Research Findings

98

Volume 13, Number 1 (June 1998)

Interagency Pacts and NIH Collaborations Extend NIDA’s 

Research Reach 

By Neil Swan, NIDA NOTES Staff Writer 

Teamwork with sister Institutes of the National Institutes

of Health (NIH) and other Federal agencies is increasing

the cost-effectiveness and extending the reach of 

NIDA’s research. 

In one current research collaboration, NIDA is a key 

participant in a broad new effort extending across several

Federal agencies to examine the links among violence,

crime, and drug abuse. Research focuses on a host of

criminal, medical, and social problems that are often related to drug abuse. These problems include sexual and

physical abuse of children, violence against women,

teenage crime and violence, trends in public attitudes

toward violence, and violence-related demands on the

Nation’s courts, prisons, and delivery of health services. 

Called the Violence Initiative, the cooperative research

enterprise involves more than 20 Federal agencies collaborating under an Interagency Agreement. Two departments

spearhead the Initiative: the Department of Health and

Human Services (HHS), with NIDA taking a lead role;

and the Department of Justice, represented by its research

agency, the National Institute of Justice (NIJ). NIJ 

conducts research to fight crime, improve criminal justice,

and evaluate criminal justice programs. 

The 3-year Interagency Agreement for violence-related

research also involves the Department of Housing and

Urban Development, which has an interest in crime and

social issues in public-supported housing. Also participating are the Department of Education, the Centers for

Disease Control and Prevention (CDC), and other NIH

Institutes in addition to NIDA—agencies with diverse

objectives but a common interest in violence, its causes,

and its consequences. 

The Initiative is formally named the Interagency

Consortium for Research on Violence Against Women

and Violence Within the Family. It allows NIDA and the

other agencies to bridge the gap between two bodies of

research—studies relating to drug abuse, drug addiction,

and mental health and studies relating to social and criminal justice questions. The Initiative spans academic 

disciplines to make the benefits of NIDA’s biological and

behavioral drug abuse research—ranging from basic neuroscience studies to investigations of the cost-effectiveness

of drug abuse treatment innovations—applicable to 

those agencies interested in the many drug-related aspects

of violence. 

The research interests of NIDA and NIJ frequently overlap. For example, NIJ is vitally interested in causes of

recidivism—the return to jail of inmates who have 

committed new crimes since their release—says Dr.

Donald Vereen, NIDA’s representative to the founding

interdepartmental group. Recidivism and other disruptive

or criminal behaviors may relate to what research has

shown are drug-induced changes in the brains of drug

abusers, which may be associated with drug craving,

explains Dr. Vereen, who is NIDA’s special assistant to the

Director for medical affairs. Thus, drug abuse research can

help in designing inmate drug abuse education and treatment programs, he says. NIDA-funded research already

has provided much of the impetus toward innovative

“drug courts” that seek to address both criminal justice

and addiction problems by striving to keep offenders

enrolled in drug abuse treatment programs, he says. 

The initial research findings under the Initiative have not

yet been reported, but previous cooperation between NIJ

and NIDA has already proved productive, says Sally

Hillsman, NIJ deputy director. “For example, we have

benefited greatly from the work of NIDA’s Community

Epidemiology Work Group [which monitors trends in

drug use patterns in selected U.S. cities].” 

After the agreement was signed in late 1995, the 

participating agencies called for research proposals relating

to various aspects of violence. Ten projects have now been

funded, all of them studying drug or alcohol abuse-related

violence issues, according to Dr. Coryl Jones of NIDA’s

Epidemiology Research Branch, who is monitoring the

projects. Sometimes the substance abuse factor in the violence studies becomes much more apparent as the project

continues, she says. For example, one Initiative project is

studying violence toward female care providers—wives

and daughters—over age 55. As the project continues,

researchers are finding strong evidence that drug and alcohol abuse by the women’s mates or parents is an important

factor in their victimization by violence, she says. 

Planning for the $1.8 million Violence Initiative evolved

from policymakers’ interest in the Violence Against

Women Amendment to the Violent Crime Control and

Law Enforcement Act of 1994. “Early on, NIDA Director

Dr. Alan Leshner got involved. He pushed us to get 

people from agencies outside of NIDA to participate,”

says Dr. Vereen. 
99

The agencies are able to collaborate thanks to the

Interagency Agreement, a formal contract that spells out

terms and financial commitments for participant agencies.

“The Interagency Agreement is tailor-made for broad

cooperative efforts like the Violence Initiative,” says Dr.

Vereen. “It’s good for research as an enterprise, and it’s

good for science. It takes advantage of an existing infrastructure. All the participating agencies get something out

of it.”

The Interagency Agreement is a good tool for funding in

situations when there is no handy

grant mechanism,” says Carol

Cornwell, a budget analyst in NIDA’s

Program and Financial Management

Branch, who manages the Initiative’s

funds since NIDA was designated

“banker” for the collaborative operation. “Several of the Violence

Initiative’s participating agencies do

not have a grant-issuing mechanism.

But they can participate in the

Interagency Agreement, making funding contributions, and have a say in

the type of research that is funded.”

NIDA is also involved in other Interagency Agreements,

including collaborating with the State Department to

improve drug abuse research in South America (see

“NIDA Advances Drug Abuse Research in Andean

Countries,” NIDA NOTES, September/October 1997).

The Institute is also working with other NIH Institutes,

the Department of Energy, and the Department of

Veterans Affairs to develop improved “informed consent”

policies to ensure that people participating in research are

adequately informed of related ethical issues and risks to

their health. 

Interagency Agreements are only one way that NIDA

teams up with fellow Federal agencies. There are also 

collaborations in which NIDA joins with other NIH

Institutes to conduct mutually beneficial research. These

collaborations have proven to be productive and beneficial, says Dr. Vincent Smeriglio of NIDA’s Clinical

Medicine Branch. 

NIDA currently is involved in four major collaborations

with other NIH Institutes and public health agencies. In

the Maternal Lifestyles Study, NIDA collaborates with the

National Institute of Child Health and Human

Development (NICHD), the HHS Administration on

Children, Youth, and Families, and the Center for

Substance Abuse Treatment. The agencies are studying the

health and development of infants and children who are

exposed to illicit drugs during their mothers’ pregnancies.

More than 11,000 mothers were interviewed about their

pregnancies and drug use, and some 1,400 infants are

enrolled in followup studies. The continuing project is

building valuable information for developing enhanced

interventions to better address prenatal drug exposure and

its possible consequences. 

The Women and Infants Transmission Study (WITS) is a

six-site collaborative project studying mother-to-infant

transmission of HIV. NIDA is collaborating with the

National Institute of Allergy and Infectious Diseases

(NIAID), the lead NIH Institute involved in HIV and

AIDS research, and NICHD. More than 1,200 HIVinfected women and 800 of their children have been

enrolled. Approximately half of the WITS participants 

are current or former drug abusers.

NIDA joined the collaboration to

support and promote focused

research regarding the impact of

drug use on the transmission and

course of HIV disease. 

Reaching for Excellence in

Adolescent Care and Health

(REACH) is an NICHD-initiated

project with NIDA as a key collaborator. REACH seeks to learn

more about HIV disease progression and its relationship to other

health factors, such as drug use among adolescents aged

12 to 19. NIDA support emphasizes research on both the

impact of drug use on the course of HIV disease as well as

the impact of HIV on drug use. Also participating in the

REACH collaboration are NIAID and the Health

Resources and Services Administration. 

The Women’s Interagency HIV Study (WIHS) and the

companion HIV Epidemiology Research Study (HERS)

investigate the medical and psychosocial impact of HIV

on women. Most of the women being studied have a history of current or past drug use. The studies have enrolled

2,500 HIV-positive women and 775 HIV-free women.

NIDA collaborates in these studies with NIAID,

NICHD, the National Cancer Institute, the National

Institute of Dental Research, and the CDC. NIDA funding supports research on how drug use and addiction may

influence women’s vulnerability or resistance to HIV

infection, the consequences of coinfection with HIV and

other diseases associated with drug abuse, the effectiveness

of HIV medical treatment, and biomedical factors related

to the development of HIV disease. 

“Each of these collaborations ensures that NIDA’s knowledge and expertise in drug abuse and related conditions

are pooled with the knowledge of our colleagues in other

Institutes and agencies conducting vital HIV research,”

says Dr. Smeriglio. “It’s a highly cost-effective way to bolster NIDA’s clinical research and to expand interest in

drug abuse issues among a larger pool of investigators.”

Together with the Interagency Agreements, these 

collaborations broaden the consequences of NIDA

research and extend NIDA’s science-based findings into

new realms.

“The Interagency Agreement

is tailor-made for broad

cooperative efforts like the

Violence Initiative. It’s good

for research as an enterprise,

and it’s good for science.” 
Research Findings

100

Volume 13, Number 1 (June 1998)

NIDA MERIT (Method to Extend Research In Time)

Award winner Dr. Sheldon Sparber, at the University of

Minnesota Medical School in Minneapolis, studies the

effects of prenatal drug exposure on the fetus

and newborn and the effects that may continue

into adulthood. His animal studies on opiates

and opiate withdrawal have greatly influenced

the treatment of opiate-addicted pregnant

women in methadone maintenance programs

and their newborns, and his current research on

cocaine could prove to be just as important.

In the 1980s, Dr. Sparber’s animal studies 

provided a new perspective on whether opiateaddicted women should be treated with

methadone. Earlier research findings had suggested that methadone is dangerous to the fetus

and probably should not be given to pregnant

heroin addicts. However, Dr. Sparber’s group

showed that the toxic effects on the offspring demonstrated

in the earlier studies were due to excessively high doses of

methadone and the stress of sudden withdrawal from

methadone. “Unlike with adults, severe sudden withdrawal

can be deadly for fetuses and infants,” explains Dr.

Sparber. “This is true for both animals and humans. But 

if you maintain human pregnant mothers on low but adequate doses of methadone and provide the newborns with

medications, if necessary, to allow them to go through

slow, mild withdrawal, their prognosis can be quite good.”

In his current research, Dr. Sparber is investigating the

effects of prenatal cocaine exposure in chickens and rats.

He has found that cocaine injected into chicken eggs

interferes with the hatching of the chicks, probably by

restricting blood flow to the embryos. He also has discovered that this effect could be blocked with a medication

called ritanserin, which, according to Dr. Sparber, opens

up the possibility of a treatment to prevent the adverse

effects of prenatal cocaine exposure.

In his studies with rats, Dr. Sparber is finding that prenatal cocaine exposure causes only minimal effects on brain

chemistry and behavior—until the rats reach middle age.

When tested at age 10 months to a year, rats that were

exposed to cocaine during the last trimester of pregnancy

start to show serious learning and memory deficits. “If the

data from our animal studies are real and can be generalized to humans exposed to cocaine in utero, it would 

mean that those people might start showing learning and

memory deficits at about age 30 to 40 or perhaps later,”

says Dr. Sparber.

As part of the research funded by the MERIT

Award, Dr. Sparber will be investigating

whether cocaine’s long-term effects can be 

prevented by altering the rearing environment

of the infant rats or by treating the pregnant

mothers with medications such as ritanserin.

According to Dr. Sparber, the MERIT Award

with its longer period of funding will allow

him to take risks in his research that he might

not be willing to take with a conventional

grant. “The MERIT Award gives you the

opportunity to do innovative work that you

wouldn’t normally doif you had a 3-year

grant,” says Dr. Sparber. He adds that many

important discoveries in biomedicine are made

through serendipity. “If you have your eyes open and don’t

have any preconceived notions about what you’re going 

to see, you might come up with some very exciting 

observations.”

Dr. Sparber has been funded continuously by NIDA 

since 1972. Dr. Jerry Frankenheim of NIDA’s Division of

Basic Research describes Dr. Sparber as being “at the cutting

edge of his field.” He salutes Dr. Sparber’s “willingness to

tackle the truly relevant questions in psychopharmacology,

no matter how tough.”

Dr. Sparber is a professor of pharmacology, psychiatry, and

psychology at the university. He has published more than

150 scientific papers and has edited two books. 

Sources 

• Sparber, S.B.; Lichtblau, L.; and Kuwahara, M.D.

Experimental separation of direct and indirect effects

of drugs upon neurobehavioral development. In: N.A.

Krasnegor, et al. (eds.), Advances in Behavioral

Pharmacology. Volume V: Developmental Behavioral

Pharmacology, Lawrence Erlbaum Associates, Inc.,

Hillsdale, N.J., pp. 225–263, 1986. 

• Zhang, X.; Schrott, L.M.; and Sparber, S.B. Evidence

for a serotonin-mediated effect of cocaine causing

vasoconstriction and herniated umbilici in chicken

embryos. Pharmacology, Biochemistry, and Behavior

59(3): 585–593, 1998.

MERIT Awardee Examines Long-Term Effects Of Prenatal Cocaine

Exposure in Rats

By Steven Stocker, NIDA NOTES Contributing Writer 

Dr. Sheldon Sparber
Research Findings

101

Volume 12, Number 6 (November/December 1997)

Behavioral and social sciences research is playing an increasingly critical role in the Nation’s public health response to

the spread of AIDS, according to experts at a National

Institutes of Health (NIH) symposium last summer. 

Dr. James Curran, an AIDS epidemiologist and professor at

Emory University in Atlanta, said that science has made significant advances in recognizing the “previously marginal”

role for behavioral studies related to AIDS. He spoke at the

half-day symposium, Substance Abuse and AIDS: Research

from the Behavioral and Social Sciences. The meeting at 

the NIH campus in Bethesda, Maryland, was cosponsored

by NIDA.

AIDS is still a young epidemic, said

Dr. Curran, formerly head of the

Division of HIV/AIDS Prevention

at the Centers for Disease Control

and Prevention (CDC) in Atlanta.

Early public responses tended to

“ghettoize” those with AIDS, downplaying its spread into the general

population through heterosexual

contacts, he said. As a result, the

public mistakenly has failed to recognize the importance of

heterosexual contacts in the spread of HIV. Among women,

particularly among poor and minority women, heterosexual

sex is key to the currently increasing rate of HIV infections,

he said. Statistics from the CDC support this view. In

September, the CDC reported that the number of AIDS

cases is increasing faster among women than among men

and that sex with infected men has overtaken drug abuse as

the leading cause of HIV infection among women. From

1991 through 1995, the number of men diagnosed with

AIDS increased by 12.8 percent, versus an increase of 63

percent for women. However, many of the sex partners of

these HIV-infected women are men whose own infections

are drug abuse related. 

Behavioral factors play an important part in these gender

differences, say experts. Studies show that homosexual men,

who now account for approximately 48 percent of all AIDS

patients, are often well educated, aggressive about their 

treatment options, and responsive to prevention efforts. But

many women with HIV are poor, are not well educated, and

may have limited access to health care. As a result, these

women may not respond as well as some men do to 

prevention or treatment efforts.

Behavioral studies are vital to learning more about the

spread of the HIV infection, agreed Dr. William Paul, 

former director of NIH’s Office on AIDS Research. After

reviewing NIH-supported AIDS research, outside experts

recommended strengthening the social sciences and behavioral components of the research portfolio, advice now being

heeded in NIH’s AIDS research agenda, said Dr. Paul.

NIDA ranks third among NIH Institutes in the level of

funding it receives for AIDS studies, and much of the

NIDA-supported research is already devoted to behavioral

and social sciences investigations into the link between drug

abuse and AIDS.

“AIDS and drug abuse are two epidemics that are totally

intertwined,” NIDA Director Dr. Alan I. Leshner reminded

those attending the session. “It’s

impossible to speak about one and

not the other. Behavioral and social

science research is critical to gaining

insights into the epidemiology of

AIDS, and it helps the broader scientific community get a handle on

this intersection of drug abuse and

AIDS.” 

Studies of social and personal networks are vital to understanding HIV transmission and 

prevention, said Dr. Carl Latkin, a NIDA-supported

researcher at Johns Hopkins University in Baltimore. “We

need to look not so much at individual behavior but more at

social-network aspects of behavior,” he said. “We need to

learn more about support networks that provide protection

against HIV transmission and risk networks that actually 

promote high-risk behaviors.”

Numerous studies have documented that significantly lower

rates of HIV risk behaviors are practiced by drug abusers who

are enrolled in treatment programs, said Dr. David Metzger,

another NIDA-funded researcher at the University of

Pennsylvania. “The consistency of these findings suggests that

increasing the access to drug abuse treatment is a legitimate

and absolutely necessary HIV prevention activity,” he said.

“Although the data [supporting the effectiveness of drug abuse

treatment in preventing HIV transmission] are strongest for

methadone treatment of opiate dependence, there also is

growing awareness of the important role that noninjection

drug use has played in the sexual transmission of HIV.” 

He noted that the protective effects of drug abuse treatment

are not immediate and not universal. This underscores the

need to investigate all modalities of treatment to document

the effectiveness of each in changing behaviors to prevent

HIV transmission. 

Contributions of Behavioral Research To AIDS Studies Recognized

By Neil Swan, NIDA NOTES Staff Writer 

“Increasing access to drug

abuse treatment is a legitimate

and absolutely necessary HIV

prevention activity.” 
Research Findings

102

Study Sheds New Light on the State of Drug Abuse 

Treatment Nationwide

By Michael D. Mueller and June R. Wyman, NIDA NOTES Staff Writers 

Volume 12, Number 5 (September/October 1997)

The four most common forms of drug abuse treatment

are all effective in reducing drug use. That is the major

finding from a NIDA-sponsored nationwide study of

drug abuse treatment outcomes. The Drug Abuse

Treatment Outcome Study (DATOS) tracked 10,010

drug abusers in nearly 100 treatment programs in 11

cities who entered treatment between 1991 and 1993. 

“DATOS is the largest study of drug abuse treatment

outcomes since the early 1980s and the most important

in the last 10 years in terms of telling us how treatment

programs are doing,” says Dr. Bennett Fletcher, chief of

NIDA’s Services Research Branch. 

DATOS investigators measured treatment outcomes

using a random sample of approximately 3,000 patients.

The researchers compared patients weekly and daily

drug use for the 12 months before they entered treatment with their weekly and daily drug use 12 months

after they stopped treatment. Patients in outpatient

methadone treatment who were still in treatment were

interviewed approximately 24 months after admission.

Other outcomes that the researchers measured included: 

• whether patients reported fewer illegal acts, including assault, robbery, burglary, larceny, forgery, and

fencing stolen property; 

• whether patients were working full time, defined as at

least 35 hours per week; and 

• whether patients reported fewer

attempts or thoughts of suicide,

which was used as a marker for

depression. The researchers

chose that marker because several previous studies had established its validity as an indicator

of depression. 

The four types of programs with the

number of programs that DATOS

studied in parentheses were outpatient methadone (29),

outpatient drug-free (32), long-term residential (21), and

short-term inpatient (14). Three of the four types were

also studied in DATOS’s two predecessors: the Drug

Abuse Reporting Program (DARP), which included

admissions to treatment from 1969 to 1973, and the

Treatment Outcome Prospective Study (TOPS), which

covered admissions from 1979 to 1981. The short-term

inpatient treatment programs, originally developed to treat

alcohol abuse but admitting increasing numbers of

cocaine abusers during the

1990s, were studied in

DATOS but not in the two

earlier projects. 

Highlights From the Study 

For the four treatment

types, DATOS investigators

found reductions almost

without exception in the use

of all drugs including

cocaine, heroin, and marijuana after treatment. Likewise,

after treatment a smaller percentage of patients reported

committing illegal acts, working less than full time, and

thinking about or attempting suicide. The data also

revealed that: 

• Except in outpatient methadone programs, cocaine

was the primary drug of abuse, with alcohol running

a close second. Cocaine abuse was common even in

Percentage of Patients Reporting Weekly or More

Frequent Cocaine Use Before and After Treatment 

In all four types of treatment programs that the Drug Abuse Treatment

Outcome Study examined, the percentage of patients reporting frequent

use of cocaine dropped dramatically after treatment. 

“The Drug Abuse Treatment

Outcome Study found reductions

in the use of all drugs—

including cocaine, heroin, and

marijuana—after treatment.”

* Outpatient methadone patients still in treatment were 

interviewed approximately 24 months after admission. 
103

outpatient methadone treatment programs for heroin

addicts. About 42 percent of patients who entered

methadone treatment programs also abused cocaine. 

• Heroin use had decreased since the 1979-to-1981

period that TOPS studied. Large declines in the abuse

of depressants such as barbiturates and tranquilizers

had also occurred since TOPS. 

• Short-term inpatient treatment programs yielded 

significant declines in drug use, even though patients

stayed in these programs no more than 30 days. “This

is one of our most surprising findings,” Dr. Fletcher

says. “This treatment mode had a high percentage of

patients reporting daily or weekly use of cocaine in

the year before treatment and a sharp decline in weekly

and daily use after treatment.” The percentage of

patients reporting illegal acts and thoughts of suicide

also declined significantly after treatment in these 

programs. The researchers are exploring whether

continuing involvement in outpatient services and

mutual help groups may have contributed to these

positive outcomes. 

• In every city studied in DATOS, support services

such as medical, legal, financial, psychological,

employment, and family services had declined dramatically since TOPS, while the need for those services

had increased. 

• Patients surveyed by DATOS reported that it took them about 7 years

after they first used their primary

drug to enter treatment.

New Demographics 

Demographic characteristics of patients

studied in DATOS had changed since

the earlier study. For example, DATOS

patients were older and had more years of

schooling than TOPS patients, and a

greater percentage of them were women. 

In DATOS, 39 percent of patients

admitted to outpatient methadone 

programs were women compared to

approximately 31 percent in TOPS.

Women made up approximately 33 

percent of the patients admitted to longterm residential programs, as opposed 

to 22 percent for TOPS. Outpatient

drug-free programs saw little change

from TOPS to DATOS, with women

accounting for approximately 33 percent

of patients in these programs in both

studies. In DATOS, about 37 percent of

patients admitted to short-term inpatient

programs, which were not included in TOPS, were

women. The researchers are conducting additional analyses to further explore the characteristics and outcomes for

women in DATOS. 

Substance Abuse and Psychological Disorders 

DATOS researchers looked at co-occurring psychological

disorders and dependencies in 7,402 patients in the

DATOS programs who were diagnosed as substance

dependent. They found that 32.1 percent of those patients

were dependent on cocaine alone. Of that 32.1 percent,

59.1 percent were male. Another 26.3 percent of the

patients were dependent on both cocaine and alcohol,

and, of those, 69.8 percent were male. In addition, 10.6

percent of the patients were dependent on heroin alone,

and 64.2 percent of those were male. 

The prevalence of co-occurring psychological disorders

among the group was high, especially for antisocial 

personality disorder (APD) and major depression. APD

was characterized as a pattern of disregard for the rights 

of others, irresponsibility, and lack of remorse. Major

depression was characterized as either a depressed mood 

or a loss of interest or pleasure for 2 weeks or more. 

The prevalence of those two disorders differed widely

among men and women. Approximately 40 percent of the

group was diagnosed with APD, and males were twice as

Four Common Types of Drug Abuse Treatment

Investigators with the Drug Abuse Treatment Outcome Study (DATOS)

studied patients in the four most common kinds of treatment programs: 

• Outpatient methadone programs administer the medication

methadone to reduce cravings for heroin and block its effects.

Counseling, vocational skills development, and case management 

to help patients access support services are used to gradually stabilize

the patients functioning. Some patients stay on methadone for long

periods, while others move from methadone to abstinence. 

• Long-term residential programs offer around-the-clock, drug-free

treatment in a residential community of counselors and fellow recovering addicts. Patients generally stay in these programs several months or

up to a year or more. Some of these programs are referred to as therapeutic communities. 

• Outpatient drug-free programs use a wide range of approaches 

including problem-solving groups, specialized therapies such as

insight-oriented psychotherapy, cognitive-behavioral therapy, and 

12-step programs. As with long-term residential treatment programs,

patients may stay in these programs for months or longer. 

• Short-term inpatient programs keep patients up to 30 days. Most of

these programs focus on medical stabilization, abstinence, and lifestyle

changes. Staff members are primarily medical professionals and trained

counselors. Once primarily for alcohol abuse treatment, these programs expanded into drug abuse treatment in the 1980s. 
104

likely as females to be diagnosed

with the disorder. While 12 percent

of the group had experienced a

major depression, female patients

were twice as likely as male patients

to have done so. 

Keeping Patients in Treatment 

When the researchers looked at

retention rates, they found big 

differences within each of the four

treatment types and among individual programs. “We found a lot of

diversity in how well they’re doing 

at keeping patients in treatment, and

we wanted to know why,” says Dr.

Dwayne Simpson of Texas Christian

University in Fort Worth. 

The investigators found that programs with low retention rates tended

to have patients with the most problems, particularly antisocial personality disorder, cocaine addiction, or

alcohol dependence. In addition,

heroin abusers who also abused crack

cocaine but not powder cocaine 

had significantly lower retention

rates than other heroin abusers did.

“These programs are dealing with

some tough people. Programs with

the highest concentration of these

problem patients naturally tend to

have low retention,” Dr. Simpson

says. 

When the researchers

looked at retention

rates, they found big 

differences within 

each of the four 

treatment types 

and among 

individual programs.
What makes patients stay in treatment? The researchers found that

the major predictors were: • high motivation; 

• legal pressure to stay in

treatment; 

• no prior trouble with the law; • getting psychological counseling

while in treatment; and 

• lack of other psychological

problems, especially antisocial

personality disorder. 

Lessons From DATOS 

What were the overall conclusions?

“Clearly there were significant

changes from before to after treatment

in each of the four modalities,” says

Dr. Fletcher. That finding raises

some interesting questions, he adds.

“For example, retention has been

our most powerful and consistent

predictor of treatment outcomes—

yet even people in short-term 

inpatient treatment for 30 days or

less improved significantly.”

Although DATOS replicated the

finding from DARP and TOPS that

time in treatment is important, the relationship to retention of other

factors such as motivation, psychiatric

comorbidity, and treatment process

needs to be studied more, he says. One would also expect worse outcomes from DATOS compared to TOPS because of the steady decline

in availability of support services,

says Dr. Fletcher. A possible explanation for the better DATOS outcomes is that although support 

services have decreased, core treatment

services have improved. “Core 

services—basic treatment techniques

such as drug abuse counseling,

mutual-help groups, and patient

participation in devising treatment

plans—may have improved over the

past 10 years. What we’re seeing may

be a result of this improvement,

even though availability and use of

noncore support services have

declined,” Dr. Fletcher says. 

105
The study’s encouraging results verify the effectiveness of

drug abuse treatment no matter what its form, says NIDA

Director Dr. Alan I. Leshner. “The service system has

changed dramatically over the last two decades. This study

gives us a unique opportunity to understand the effect of

those changes and to have an impact on the way 

treatment is delivered,” Dr. Leshner says. 

Sources 

• Etheridge, R.M.; Hubbard, R.L.; Anderson, J.;

Craddock, S.G.; and Flynn, P.M. Treatment structure

and program services in DATOS. Psychology of

Addictive Behavior 11(4):244–260.

• Flynn P.M.; Craddock, S.G.; Luckey, J.W.; Hubbard,

R.L.; and Dunteman, G.H. Comorbidity of antisocial

personality and mood disorders among psychoactive

substance-dependent treatment clients. Journal of

Personality Disorders 10(1):56–67, 1996. 

• Hubbard, R.L.; Craddock, S.G.; Flynn, P.M.;

Anderson, J.; and Etheridge, R.M. Overview of oneyear follow-up outcomes in DATOS. Psychology of

Addictive Behavior 11(4):261–278. 

• Simpson, D.D.; Joe, G.W.; Broome, K.M.; Hiller,

M.L.; Knight, K.; and Rowan-Szal, G.A. Program

diversity and treatment retention rates in DATOS.

Psychology of Addictive Behavior 11(4):279–293. 

106
Research Findings

107

Volume 12, Number 5 (September/October 1997)

National Study Offers Strong Evidence of the Effectiveness of Drug

Abuse Treatment

NIDA Director Dr. Alan I. Leshner 

A newly released nationwide study shows impressive

reductions in drug use for patients in the four common

types of drug abuse treatment. This

good news comes from the NIDA-supported Drug Abuse Treatment

Outcome Study (DATOS)—a major

research effort that tracked more than

10,000 patients in almost 100 programs in 11 cities around the Nation

over 3 years. Building on two earlier

nationwide studies of treatment outcomes, DATOS investigators have

amassed a wealth of information on

drug abuse treatment outcomes, psychological disorders, retention rates,

and treatment histories of drug abusers.

The study also provides new

information on changes in

availability of drug abuse

treatment services—ranging

from basic drug abuse counseling to medical, legal,

employment, and financial

help—over the last two

decades. 

DATOS overwhelmingly confirms the effectiveness of drug

abuse treatment. Although the two earlier studies and

many smaller-scale studies have documented this effectiveness, DATOS proves it with nationwide findings for the

1990s. Among the patients that DATOS studied, drug use

dropped significantly from the 12 months before treatment to 12 months after treatment began. This was true

for all four types of treatment studied: outpatient

methadone, outpatient drug-free, long-term residential,

and short-term inpatient. Treatment also led to significant

improvements in other aspects of patients’ lives such as

reduced involvement in illegal acts. 

DATOS is one of the few national longitudinal studies to

collect data on psychological disorders among drug

abusers in treatment. The study also provides invaluable

insight into critical differences between men and women

entering drug abuse treatment. Knowing the genderspecific problems of addicts entering treatment can help

providers tailor treatment to patients’ specific needs. 

DATOS also provides a wealth of information on

the demographic characteristics and treatment

histories of addicts in treatment. As more data are

analyzed, researchers will be able to link patients’

treatment outcomes to their backgrounds, gender,

treatment histories, psychological disorders, and

the specific services they have or have not

received. This knowledge will enable us to refine

and strengthen treatment by helping service

providers determine what treatments work best

for what kinds of patients. 

Although much of the news from DATOS is

good, there is also cause for concern. The study

identified an alarming drop over time in

the provision of services such as medical, legal, employment, and financial

help. This decline is of special concern,

since drug abusers often need help in

one or more of these areas to get into

and stay in treatment. Since NIDA’s last

national study of treatment outcomes,

conducted from 1979 to 1981, the provision of these services has declined

strikingly while the need for them has

increased. From 1991 to 1993, during

the time DATOS researchers were collecting data, the typical length of stay in short-term inpatient treatment

dropped from 28 days to 14 or fewer days as insurers

reduced coverage for addiction treatment. These changes

did not go unnoticed by patients. More than half of

DATOS participants in the four kinds of treatment programs surveyed did not report receiving support services

that they said they needed. And, nearly 75 percent of

patients in short-term inpatient programs reported not

getting the psychological help they needed. 

The reality is that we now have a treatment system that

faces major resource constraints. As drug abuse treatment

comes increasingly under managed care and resources are

more tightly controlled, we must stay focused on the 

scientific facts about addiction and how to treat it adequately. Managed care providers must make tough 

The Drug Abuse Treatment

Outcome Study overwhelmingly

confirms the effectiveness of

drug abuse treatment with new

nationwide findings. 
108

decisions in allocating their resources, and DATOS 

can provide the hard scientific data they need to guide

those decisions.

Given the wealth of findings coming from this study, our

challenge is to communicate this information to health

care organizations, managed care companies, and public

policymakers. We have a new mechanism in place to do

that. Disseminating research findings is a primary goal of

NIDA’s new Treatment Initiative, as described in the last

issue of NIDA NOTES. (See “NIDA Initiative Will

Stimulate Improvements in Drug Abuse Treatment,” and

“NIDA Launches Drug Abuse Treatment Initiative,” in

NIDA NOTES, July/August 1997.) The DATOS results

together with the Treatment Initiative can help us bridge

the gap between public perceptions of drug addiction and

what science has again shown—that drug abuse and

addiction can be treated successfully with science-based

methods, adequate treatment, and vigilant followup.
Research Findings

109

Volume 12, Number 5 (September/October 1997)

Gender, Ethnicity, and Age Make a Difference In Drug Dependence 

A new analysis of data from the

National Household Survey on

Drug Abuse offers information

about gender differences in drug

dependence. 

NIDA grantee Dr. Denise Kandel

at Columbia University in New

York City and her colleagues

looked at survey data from the

years 1991, 1992, and 1993 and

found, for example, that: 

• Among adolescents, rates of

dependence on alcohol and marijuana are higher in

females than in males, but only rates of cocaine

dependence are significantly higher in females. 

• Adolescent females are significantly more at risk for

becoming dependent on alcohol and marijuana than

are women in any other age group. 

• Among adults, rates of dependence on alcohol and

marijuana are higher among males than among

females, but rates of dependence on nicotine are lower

among males. 

• Among people who used drugs

in the last year, whites are more

likely than other ethnic groups

to be dependent on nicotine.

African Americans are more

likely to be dependent on

cocaine.

The findings were reported in the

June 10, 1997 issue of Drug and

Alcohol Dependence.
Research Findings

110

Steroid Prevention Program Scores With High School Athletes

By Robert Mathias, NIDA NOTES Staff Writer

Volume 12, Number 4 (July/August 1997)

A NIDA-funded drug abuse prevention program is showing high school football players that they do not need to

take anabolic steroids to build powerful muscles and

improve athletic performance. By educating student 

athletes about the harmful effects of anabolic steroids 

and providing nutrition and weight-training alternatives

to steroid use, the program has increased football 

players’ healthy behaviors and reduced their intentions 

to use steroids.

Until now, anabolic steroids, drugs derived from the male

hormone testosterone, have rarely been the focus of drug

abuse prevention studies, says Dr. Ro Nemeth-Coslett of

NIDA’s Division of Epidemiology and Prevention

Research. This may be because steroids are not widely

abused. Only about 2 percent of 8th, 10th, and 12th

grade students have ever used

steroids, according to the NIDAsupported Monitoring the Future

study for 1996. However, steroid

abuse occurs more often among

young people who are involved in 

physical training because anabolic

steroids can increase muscle mass,

strength, and stamina, Dr.

Nemeth-Coslett points out.

Although adolescent boys, 

particularly those involved in athletics such as football or body

building, make up the majority of

high school steroid users, national

surveys show that adolescent girls

also are vulnerable to the lure of

steroid use. However, that lure 

contains a hook—anabolic steroid

use can have severe physical and

emotional consequences for both

males and females. Physical effects

can include stunted growth, high

blood pressure, and liver tumors.

Psychological effects can include

wide mood swings that range

from episodes of uncontrolled

anger and aggressiveness to clinical depression when steroid use is

stopped. 

“The Adolescents Training and Learning to Avoid Steroids

(ATLAS) program uses a team-oriented educational

approach that motivates and empowers student athletes to

make the right choices about steroid use,” says Dr. Linn

Goldberg of Oregon Health Sciences University in

Portland, who led the research team that developed and

tested the program. The program consists of classroom,

weight-training, and parent information components.

Together, they give student athletes the knowledge and

skills to resist steroid use and achieve their athletic goals in

more effective, healthier ways, he says.

In ATLAS’s classroom component, football coaches and

student leaders conduct seven highly interactive sessions

that explore the effects of steroids, the elements of sports

nutrition, and strength-training alternatives to steroid use.

These classes also hone the athletes’ decisionmaking and

drug-refusal skills. In a typical session, the football team is

split into squads of six or seven students, with student

squad leaders conducting the sessions and teaching most

of the intervention, according to Dr. Goldberg. “It’s kids

talking to kids; that’s an important

ingredient in our program,” he says.

Coaches, who have a substantial 

influence on these student athletes,

also play an important role on the

steroid prevention team, Dr.

Goldberg says. Coaches introduce

topics and wrap up each session, he

explains.

“The ATLAS program is voluntary, and

students get no credit for it, so it better be

entertaining,” he says. As a result, ATLAS

classroom sessions are designed to combine fun and games and learning.

Coaches move from squad to squad and

introduce a topic, such as the effects of

anabolic steroids. Then squad leaders take

over and initiate an action game that incorporates the topic. For example, players may

toss a football to each other as they answer

questions about problems that stem from

steroid use. “Although they are playing a

game, each one is paying attention and listening because someone is flipping the ball

to them,” says Dr. Goldberg. “No one is Students in the ATLAS program learn that

stunted growth and many other harmful

effects can result from steroid use.
saying to them, ‘Watch out, steroids cause liver disease,

acne, and so forth,’” he notes. “But while they are laughing

and having a good time, they are actually watching and

learning at every step of the way.”

“Football players are athletes; they like to compete,” Dr.

Goldberg notes. Therefore, several games pit squads

against each other to try and earn the most points for correct answers about weight training, nutrition, and steroids.

In addition to games, “students do mock public service

announcements, they do ‘rap,’ they do songs, and they do

newspaper articles in the classroom sessions,” he says.

In ATLAS's weight-training component, research staff

members conduct seven hands-on sessions that teach the

students proper weight training techniques. These sessions

are designed to help student athletes build the muscular

strength and agility needed to achieve their athletic goals

without using steroids.

In the parent information component, parents participate

in an information and discussion session about the program with the ATLAS staff. The staff gives the parents a

family sports nutrition guide and encourages them to support and reinforce the antisteroid and nutritional goals of

the program at home. Students in the program say their

parents are more opposed to steroid use after the intervention and often provide healthier meals at home, according

to Dr. Goldberg.

Late last year, Dr. Goldberg reported results of an ongoing

study of ATLAS’s effectiveness in preventing steroid use

among more than 1,500 football players from 31 high

schools in the Portland area. Some 702 football players at

randomly selected schools received the 7-week program

during football season. Another 804 football players at

matched schools served as a control group and received

only a standard informational brochure on the dangers of

steroid use.

Assessments conducted immediately after the intervention

and 1 year later show that, compared with control students, student athletes who participated in the ATLAS

program knew more about exercise, nutrition, and the

harmful effects of anabolic steroids. ATLAS participants

also had an increased sense of personal vulnerability to

negative effects of steroids, more unfavorable attitudes

toward their own and others’ use of steroids, and reduced

intent to use steroids. ATLAS students also showed greater

improvement in their nutritional habits than did control

students. For example, they were more likely to eat highprotein low-fat meals at school, home, and fast-food

restaurants. In addition, ATLAS students were more likely

than students who did not participate in the program to

use established weight-lifting and strength-conditioning

techniques.

“The program’s positive effects flow from changing the

student athletes’ attitudes and perceptions about steroids

and then changing their nutrition and exercise behaviors,”

Dr. Goldberg says. These changes in behavior are reinforced by conducting periodic tests of the athletes' body

composition, strength, and power. “If they are training

properly, they are a heck of a lot stronger. So, it's real positive reinforcement to them,” he says.

“Student athletes who participate in the ATLAS program

achieve,” Dr. Goldberg says. The year before they entered

the program, the football teams that were randomly

assigned to receive the intervention had much worse wonlost records in football than the teams in the control

group had, he says. At the end of the first year, the two

groups’ records were about the same, but teams in the

ATLAS program did slightly better. At the end of the 

111

Adolescent Girls Abuse Steroids, Too

What do anabolic steroids have in common with

amphetamines, tobacco, diet pills, laxatives, and

anorectics? They all are drugs used by adolescent 

girls seeking to stay thin, says Dr. Linn Goldberg of

Oregon Health Sciences University. The use of these

drugs, which often goes hand in hand with eating

disorders, is particularly prominent among adolescent

girls engaged in athletic activities ranging from track

and field, soccer, basketball, and volleyball to school

dance and drill teams, Dr. Goldberg says. 

Dr. Goldberg and his colleague Dr. Dianne Elliot

have been conducting preliminary research, funded

by NIDA, to identify risk factors that influence 

adolescent girls’ use of harmful drugs. Among 

other things, the researchers have found that many

adolescent girls use drugs to maintain thinness, 

Dr. Goldberg says. National surveys indicate that

girls account for about one-third of the high school

students who abuse steroids, Dr. Goldberg says. 

“The primary reason that these girls use steroids 

is to lose fat and gain lean muscle,” he says.

Dr. Elliot and Dr. Goldberg have already developed

an effective steroid prevention program for male high

school athletes described beginning on the previous

page. Now, they are developing a similar drug abuse

prevention program for adolescent girls. In their

future research, the researchers hope to test the effectiveness of the intervention in reducing drug use and

eating disorders among female athletes in Oregon’s

public middle and high schools.
second year, the won-lost records of the ATLAS teams

were substantially better than those of the control teams,

with some of the ATLAS teams making the playoffs at the

end of the season. “I don’t know whether these teams’

improved performance is due to the ATLAS program,”

Dr. Goldberg says. “I do know some of those schools 

hadn't been to the playoffs in 25 years. The data showing

improvements in program participants’ body composition

and muscle mass are consistent with these teams’ success,”

he says.

For More Information 

• ATLAS, Oregon Health Sciences University, 3181

S.W. Sam Jackson Park Rd., CB 615, Portland, OR

97201-3098, (503) 494-7900.

Source

• Goldberg, L.; Elliot, D.; Clarke, G.N.; MacKinnon,

D.P.; Moe, E.; Zoref, L.; Green, C.; Wolf, S.L.;

Greffrath, E.; Miller, D.J.; and Lapin, A. Effects of a

multidimensional anabolic steroid prevention intervention: The adolescents training and learning to

avoid steroids (ATLAS) program. JAMA

276(19):1555-1562, 1996. 

112

The prevention program gives student

athletes the knowledge and skills to

resist steroid use and achieve their

athletic goals in more effective,

healthier ways.
Research Findings

113

Volume 12, Number 4 (July/August 1997)

Gender Affects Relationships Between Drug Abuse and 

Psychiatric Disorders

By Neil Swan, NIDA NOTES Staff Writer

In the general population, women are more than twice as

likely as men to suffer depression. But among cocaine and

alcohol abusers, men are as likely to be diagnosed with

depression as women, a NIDA-funded study indicates. 

Why? Is cocaine more likely to trigger depression among

men than among women? Perhaps. 

Researchers have long been aware that many drug abusers

also have serious mental disorders, a status referred to as

dual diagnosis or comorbidity. Does the psychiatric disorder precede and perhaps contribute to the onset of drug

abuse? Or, conversely, do drug abuse and addiction develop first, perhaps contributing to the development of the

mental disorder? 

A study conducted by Dr. Kathleen T. Brady and her 

colleagues at the Medical University of South Carolina

provides insights into these questions. The researchers

examined gender differences in psychiatric disorders 

among 100 treatment-seeking cocaine and alcohol abusers.

Among these substance abusers, comorbidity with mental

disorders was substantive. Some 48 percent of the men

and 70 percent of the women had a comorbid affective or

anxiety disorder. In addition, a substantial number were

also dually diagnosed with other mental disorders including

passive-aggressive, obsessive-compulsive, and antisocial

personality disorders. Some 56 percent of the men and 68

percent of the women abusers had one or more of these

additional disorders, either alone or with an affective or

anxiety disorder. 

The study’s preliminary findings suggest that both onset

scenarios—drug abuse first or mental disorder first—

sometimes may occur. It is possible that the sex of the

drug abuser may be a factor in determining which comes

first, depending on the comorbid psychiatric disorder

involved. 

In the case of depressive episodes, Dr. Brady’s study suggests that for women, depression comes first more often;

for men, drug abuse appears to come first more often.

Because cocaine has such powerful effects on the brain, it

may be that in many people cocaine use activates depressive

episodes that linger after the period of euphoria and withdrawal, she says. “Perhaps men are at greater risk for this

response to cocaine, which would help explain the lack of

gender differences in depression rates among cocaine

abusers we studied compared to rates in the general population,” explains Dr. Brady. Also, men typically consume

more alcohol and use more cocaine, which would increase

the damaging effects of these substances, which, in turn,

might lead to depression, she adds. 

The study shows that women more

often than men were diagnosed with

not just depression but with other 

psychiatric disorders as well before

they began using drugs (see table on

following page). For example, as with

depression, women are significantly

more likely than are men to have a

diagnosis of panic disorder before the

onset of drug abuse, says Dr. Brady, 

a psychiatrist. Panic disorder is manifested in sudden attacks of acute 

anxiety or terror that may be uncontrollable.

The most dramatic gender difference

in prevalence rates found by the

South Carolina researchers was in the

diagnosis of posttraumatic stress 

disorder (PTSD)—emotional shock

ignited by the threat of death or actual

or threatened injury resulting in

Percentage of 100 Cocaine and Alcohol Abusers 

Who Were Ever Diagnosed With Comorbid Psychiatric Disorders 

Individuals may have been diagnosed with more than one psychiatric disorder

during their lifetimes.

Men (50) Women (50)

Any affective or anxiety disorder 48% 70%

Major depressive episode 36% 40%

Bipolar disorder (severe mood swings) 6% 4%

Panic disorder 10% 18%

Social phobia 14% 10%

Posttraumatic stress disorder (PTSD) 24% 46%
114

severe fear, feelings of helplessness or horror, and recurrent

memories. Of the 50 men and 50 women whom Dr.

Brady studied, some 46 percent of women were diagnosed

with lifetime PTSD, compared to only 24 percent of the

men (see table on previous page). 

Social phobia—extreme shyness and fear of embarrassment and humiliation or performance anxiety such 

as stage fright—was found in 12 percent of the study

group compared to only 2.8 percent of the population at

large, which other studies have shown. The onset of social

phobia predated drug abuse in 100 percent of both

women and men diagnosed with the disorder in this

study. This suggests that patients may use drugs to selfmedicate their social phobia, says Dr. Brady. 

Other epidemiologic studies have shown that social 

phobia is 1.5 times more common in women than men.

“But we found little gender difference in the prevalence of

social phobia in the group of substance abusers,” she says.

“This means that while social phobia is a risk factor for

substance abuse in both sexes, it appears that it may be a

greater risk factor for men. Perhaps cultural expectations

for men to be more socially aggressive prompt men more

to use drugs or alcohol to overcome shyness and other

aspects of social phobia.” 

The study found no gender differences in the study group

in prevalence of other psychiatric disorders such as antisocial personality disorder, paranoid or schizoid personality

disorders, or obsessive-compulsive disorder. In general, the

study demonstrates important gender differences in some

psychiatric disorders, but not in others, among the substance abusers and compared to the population at large. 

Dr. Brady’s data on these disorders show similar rates of

prevalence for these diagnoses in men and women.

Particularly for antisocial personality disorder, these similar rates are in contrast to several earlier studies, she notes.

In the general population, as well as in alcoholics and opiate abusers, a higher prevalence of antisocial personality

disorder in men than in women has been reported. But in

one earlier study of psychopathology in cocaine abusers,

no significant gender differences in antisocial personality 

disorder rates were noted. The majority of the women in

her study were cocaine-dependent, which may partially

explain the discrepancy between her data and some of the

other studies, Dr. Brady says. 

Her study results imply that different psychiatric factors

may have differing roles prior to—or in response to—

drug abuse in women compared to men, says Dr. Brady.

These preliminary findings are important indicators for

designing research to develop and implement improved

gender-specific drug abuse treatment strategies, says Dr.

Cora Lee Wetherington, NIDA’s Women’s Health

Coordinator. 

In another study, Dr. Brady examined cocaine-abusing

men and women who also were diagnosed with PTSD,

dividing them by order of onset of diagnosis—cocaine

first or PTSD first. In the cocaine-first group, the PTSDcausing trauma was generally related to the dangers

involved in procuring and using cocaine and was more

common among men. In the PTSD-first group, the trauma was generally childhood abuse and was more common

among women, the study found. For women, PTSD preceded cocaine dependence in 77 percent of the cases; for

men, this figure was 38 percent. 

“Because much of the PTSD in substance-abusing women

appears to be closely related to the sexual and physical victimization of women, my colleagues and I are now investigating this relationship in hopes of finding new treatments

for PTSD and drug abuse that would address important

gender differences,” Dr. Brady says. 

Sources 

• Brady, K.T.; Dansky, B.; Saladin, M.; and Sonne, S.

PTSD and cocaine dependence: The effect of order of

onset. Presentation at annual meeting of the College

on Problems of Drug Dependency. San Juan, P.R.,

1996. 

• Brady, K.T.; Grice, D.E.; Dustan, L.; and Randall, C.

Gender differences in substance use disorders.

American Journal of Psychiatry 150(11):1707–11,

1993.

Men (50) Women (50)

Total with No. with Total with No. with

Disorder Disorder First Disorder Disorder First

Major depressive episode 18 4 20 10

Bipolar disorder (severe mood swings) 3 1 5 2

Panic disorder 5 1 9 8

Social phobia 7 7 5 5

Posttraumatic stress disorder (PTSD) 11 8 23 18

Cocaine and Alcohol Abusers Who Had Psychiatric Disorders Before the Onset of Substance Dependence
A number of studies have

shown that women find it

more difficult than do men to

quit smoking cigarettes. This is

especially evident in studies of

nicotine replacement therapies

that use nicotine patches or

nicotine gum. Now two separate NIDA-funded studies

examining gender differences

related to smoking suggest

that something in addition to

nicotine is involved in

women’s dependence on

smoking tobacco.

“It appears that, compared to

men, women may smoke less

for nicotine and more for nonnicotine effects of smoking,”

says Dr. Kenneth A. Perkins, a

psychologist at the University

of Pittsburgh Medical Center.

These nonnicotine influences

might include nondruginduced sensory effects like

seeing and smelling tobacco

smoke, conditioned responses

to these smoke stimuli, or

social pleasures involved in

smoking rituals, he suggests.

For example, one observer

has noted that smokers may exhibit gender differences in

the way they gather outside buildings to smoke, Dr.

Perkins says. Male smokers tend to be loners; females tend

to gather in social groups. These behaviors may indicate

critical gender-based differences relating to tobacco smoking that may have little to do with nicotine, observers theorize. Dr. Perkins calls these nonnicotine influences “external stimuli.”

If further research supports this view of gender differences

in external and behavioral influences related to smoking,

says Dr. Perkins, it will be important to revise smoking

cessation treatments for women trying to quit. This would

mean tailoring therapy for women to increase behavioral

support and rely less on nicotine replacement.

Dr. Perkins reviewed scores of

studies of smoking and its

addictive properties and

smoking cessation programs.

He found that these epidemiological and clinical studies

consistently show that while

smoking is declining among

Americans, it is not decreasing as rapidly among women

as among men. If present

trends continue, women

smokers will outnumber men

by the next decade, says Dr.

Perkins. The research suggests

that this is at least partly

because of the greater difficulty women have in quitting.

Women in the studies tend to

be less successful in smoking

cessation trials, especially those

using nicotine replacement

therapy.

Lower cessation rates for

women could be expected 

if women smoked more cigarettes or inhaled more nicotine than did men. Both are

indicative of nicotine dependence, and smokers who are

more strongly nicotinedependent often have greater

difficulty quitting. But just the opposite appears to be the

case, says Dr. Perkins. Women tend to smoke fewer cigarettes per day, to smoke brands with lower nicotine yields,

and to be less likely to inhale deeply, compared to men,

according to his research review. Thus, evidence indicates

women smokers are less, not more, nicotine-dependent

than are men.

Further support for the notion of additional, nonnicotine

addiction factors comes from a study of gender differences

in the effects of different doses of nicotine gum on tobacco withdrawal symptoms. Dr. Dorothy Hatsukami, a psychiatry professor at the University of Minnesota, found

that nicotine gum did not work as well to ease withdrawal

Research Findings

115

Women’s Dependence on Smoking Affected By Something in

Addition to Nicotine

By Neil Swan, NIDA NOTES Staff Writer

Volume 12, Number 3 (May/June 1997)

Women using nicotine gum therapy to quit smoking reported

greater withdrawal symptoms than men did. The withdrawal

Symptom Score was calculated from self reports of the degree to

which study participants experienced symptoms such as craving

for a cigarette, irritability, anxiety and tenseness, and excessive

hunger. A high score represented greater symptoms. Source: D.

Hatsukami in Experimental and Clinical Psychopharmacology,

1995, American Psychological Association. Reprinted by 

permission of the author.

Withdrawal Is Different for Women—Appetite,

Craving Greater Than Men’s
116

symptoms for women trying to quit smoking as it did for

men trying to quit. As in Dr. Perkins’ review, her results

seemed contrary to expectations. If women are more 

sensitive to or dependent on the effects of nicotine than are

men, as their lower smoking cessation rates would suggest,

then women should be more responsive than are men to

nicotine replacement, she reasoned. But this was not shown

in her data, which paralleled Dr. Perkins’ findings. Women

were less sensitive to the effects of nicotine, she says.

The lower cessation success with

nicotine replacements in women

compared to men may in part be

attributed to this reduced effectiveness of the replacement therapy in

relieving nicotine withdrawal

symptoms. It also may indicate that

something else is involved besides

nicotine dependence, says Dr.

Hatsukami. Like Dr. Perkins, she

concluded that women may be more affected by other

aspects of smoking.

What is the “something else?” In his review, Dr. Perkins

examines alternative possibilities such as gender variations

related to body weight or physiological effects of the 4,000

compounds found in cigarettes in addition to nicotine. He

finds no strong evidence to support these or other alternative

explanations for gender differences in responses to smoking

or attempts to quit smoking, leading to his speculation on

the role of nondrug, or external, factors.

One answer might lie in psychophysiology studies that

compare men’s and women’s abilities to detect changes

within their bodies, such as heart-beat rate fluctuations,

explains Dr. Perkins. Women are consistently less able

than are men to detect changes in heart rate when no

external clues are provided, according to a research review

published in 1995 by Southern Methodist University 

scientists. But this gender difference narrows significantly

when subjects are provided with an external context, 

or clue, for the internal changes, such as viewing a 

horror film.

Thus, external stimuli appear to be more important to

women than to men. It can be theorized, then, that

women may be less responsive to internal stimuli such as

nicotine and more responsive to external stimuli such as

the sight and smell of tobacco and its smoke, he says.

Dr. Perkins emphasizes that it is wrong to conclude that

nicotine is not important in reinforcing tobacco smoking

among women. Women clearly experience nicotine withdrawal symptoms, he says. “The point is that there may be

relatively subtle—but very important—differences in the

sources of reinforcement [reward]

that tobacco smoking provides to

women relative to men,” he says.

Some observers have speculated on

the role of external influences in

gender differences related to the

use of other abused drugs.

Research with users of cocaine,

heroin, and other drugs points up

the significance of external drugcraving “cues” such as persons,

activities, or locations associated with prior drug use. Are

there critical gender differences in responses to these powerful craving cues?

More research is essential, says Dr. Perkins. For tobacco,

more study is called for because studies of nonnicotine

reinforcement may help develop more effective smoking

cessation therapies for women, he says.

Sources

• Hatsukami, D.; Skoog, K.; Allen, S.; and Bliss, R.

Gender and the effects of different doses of nicotine

gum on tobacco withdrawal symptoms. Experimental

and Clinical Psychopharmacology 3(2):163–173, 1995.

• Perkins, K.A. Sex differences in nicotine versus 

nonnicotine reinforcement as determinants of tobacco

smoking. Experimental and Clinical Psychopharmacology

4(2):166–177, 1996.

• Pennebaker, J.W., and Roberts, T.A. Toward a his and

hers theory of emotion: Gender differences in visceral

perception. Journal of Social and Clinical Psychology

11:199–212, 1992.

Compared to men, women

may smoke less for nicotine

and more for nonnicotine

effects of smoking.
Research Findings

117

NIDA Responds to the Changing Dynamics of the AIDS Epidemic

NIDA Director Dr. Alan I. Leshner

Volume 12, Number 2 (March/April 1997)

Drug abuse and the spread of HIV/AIDS, as well as other

infectious diseases such as hepatitis and tuberculosis, are

inextricably linked public health problems that require

many and multifaceted solutions.

A majority of new HIV infections in this Nation are related to drug abuse—through sharing of contaminated drug

injection paraphernalia, through sexual contact with an

injection drug user, or through the transmission of HIV

perinatally. NIDA has expanded its research efforts in this

area to meet this challenge. The Institute has also set 

policies to ensure that all participants in NIDA-supported

AIDS research are offered HIV testing and counseling.

NIDA-funded research has found that, through drug

abuse treatment, prevention, and community-based outreach programs, drug abusers can change their behaviors.

They can reduce or eliminate drug

use, drug-related HIV risk behaviors

such as needle sharing, unsafe sex

practices, and, in turn, the risk of

HIV/AIDS. NIDA research also is

working to reduce HIV and other

AIDS-related illnesses and improve

overall survival rates for HIV-infected drug abusers by increasing their

access and adherence to medical

treatment. With a comprehensive

research portfolio that is responsive

to the changing dynamics of the AIDS epidemic, NIDA is

improving the quality of life for many, as well as saving

both lives and enormous costs to society.

NIDA-funded research has clearly shown that drug abuse

treatment is highly effective in preventing the spread of

HIV. Numerous studies have shown that individuals who

enter drug abuse treatment programs reduce their drug

use, which, in turn, leads to fewer instances of HIV 

high-risk behaviors.

NIDA’s research into this field began early in the AIDS

epidemic. One of the Institute’s first investigations of 

drug use patterns among injection drug users (IDUs)—

conducted in methadone treatment programs in New York

City, Philadelphia, and Baltimore—found that not only

did participants report reduced sharing of needles, but

also, 70 percent reported that they no longer injected

drugs daily.

In addition to reducing injection drug use, individuals in

drug abuse treatment programs have been found to have

significantly lower HIV infection rates than drug abusers

not in treatment. Researchers in Philadelphia compared

HIV infection rates among drug abusers enrolled in

methadone treatment programs to rates among those not

in treatment. During the first 18 months of the study,

those who remained out of treatment were nearly seven

times more likely to have become infected with the AIDS

virus than those in treatment. The investigators also found

that the longer drug abusers remained in treatment, the

less likely they were to become infected.

In aggregate, studies that look at abuse of drugs other than

heroin and other injection drugs also are showing that

drug abuse treatment lowers rates of HIV risk behaviors

and infection. The bottom line is that providing access 

to effective drug abuse treatment

programs is a proven way to 

prevent the spread of HIV/AIDS.

This is encouraging news. The discouraging news, of course, is that

only a small percentage of those

who need drug abuse treatment

receive it. In fact, about 85 

percent of chronic drug abusers

are not in drug abuse treatment at

any given time.

To reach that 85 percent, NIDA launched research to

develop community-based outreach interventions to

reduce the spread of HIV. The National AIDS

Demonstration Research (NADR) Program was the first

multisite research program to deliver and evaluate HIV

risk reduction outreach programs to drug abusers not in

treatment. As part of the interventions, outreach staff

indigenous to the selected communities met with IDUs in

their natural settings to distribute HIV risk reduction

information and offer additional counseling and HIV testing. The outreach workers acted as credible messengers,

provided risk reduction materials and education, and

arranged for IDUs to receive free, private HIV testing and

counseling. The ongoing Cooperative Agreement for

AIDS Community-Based Outreach/Intervention Research

Program uses similar behavioral interventions to reduce

HIV risk taking and increase protective behaviors.

“Drug abuse treatment, 

prevention, and communitybased outreach programs can

change behaviors to decrease

the risk of HIV/AIDS.”
118

These programs and other NIDA-funded research have

helped identify intervention models that enable IDUs to

reduce their drug use, needle-sharing practices, unsafe sex

behaviors, and, importantly, their HIV infection rates.

For example, a 4-year study at one of the first NADR

projects in Chicago used ex-addicts to deliver HIV 

prevention services such as HIV testing and counseling.

IDUs who were exposed to the intervention showed a significant decrease in the rate of new HIV infections. This is

just one illustration of how outreach can help IDUs not in

treatment change their HIV risk behaviors.

While we continue to fund research on interventions that

change behaviors and prevent HIV transmission, we are

also studying how to link HIV-infected drug abusers to

the medical care they need for their HIV and related 

illnesses. Other NIDA-funded research is examining ways

to increase drug abusers’ compliance with medical treatment. Long-term studies are examining the influence of

drug use on the progression of HIV and on the effectiveness of medical treatment.

We are also funding research that is examining the special

needs of HIV-infected women who are drug abusers.

Unfortunately, with AIDS now being the fourth leading

cause of death among women 15 to 44, the need is greater

than ever to address the multitude of issues concerning

this population. Among other things, NIDA-funded

research is investigating the impact of drug use on maternal-infant HIV transmission, the course of the disease in

drug-abusing women and their infants, and treatment

with HIV medications to reduce transmission.

Given the public health implications of HIV/AIDS and

drug abuse, NIDA must work to disseminate its research

findings to the public health community at large. NIDA 

is teaming with the Centers for Disease Control and

Prevention to reach their network of public health professionals in order to inform them what NIDA’s research is

showing about the inextricable link between these two 

diseases. 

Despite substantial progress in HIV/AIDS prevention

with drug abusers, unacceptably high numbers of new

HIV infections are occurring in drug abusers, their sex

partners, and their children. Many drug abusers still are

engaging in high risk practices. To curtail or reverse this

trend, NIDA will continue to build a comprehensive

research portfolio that will respond to the changing

dynamics of the AIDS epidemic. Equipped with the

knowledge that drug abuse treatment, prevention, and

community-based outreach programs can change behaviors to decrease the risk of HIV/AIDS, NIDA is in a 

position to develop the most innovative and effective 

programs possible through its research.
Research Findings

119

Volume 12, Number 2 (March/April 1997)

CDC Report Highlights Link Between Drug Abuse and 

Spread of HIV

By Neil Swan, NIDA NOTES Staff Writer

An extensive review of existing research data confirms that

behavior associated with drug abuse is the single largest

factor in the spread of HIV/AIDS in this country. Half of

all new infections with HIV, the virus that causes AIDS,

now occur among injecting drug users (IDUs), according

to the data review, which was conducted at the Centers for

Disease Control and Prevention (CDC) in Atlanta.

The study focused on three groups recognized as being at

highest risk for transmission of HIV: IDUs, men who

have sex with men, and heterosexual men and women

who are at risk because they have sex with IDUs and/or

bisexual or gay men. The review used data gathered from

America’s 96 largest cities, where HIV infection rates are

the highest in the Nation. The trends in HIV infection

rates found in these cities also apply to the Nation’s 

population in general, says the CDC reviewer 

Dr. Scott D. Holmberg.

Most newly HIV-infected IDUs live in northeastern cities

from Boston to Washington, DC, as well as in Miami and

San Juan, Puerto Rico, reports the CDC reviewer. In these

cities, where injection drug use rates are also the highest

among the 96 cities surveyed, an average of 27 percent of

all IDUs are HIV-infected.

“These data confirm and underscore the connection

between injection drug use and the continuing spread of

HIV and AIDS,” says NIDA Director Dr. Alan I. Leshner.

“Drug abuse and HIV are truly interlinked epidemics.”

“The information further demonstrates that NIDA has a

critical role indeed in addressing the drug abuse-HIV connection and in focusing scientific research to understand

and deal with the further spread of this devastating 

disease,” he says.

The data confirm earlier figures from periodic CDC

reports on the number of newly diagnosed cases of AIDS

and HIV infection, which suggested that the proportion

of new HIV cases linked to drug abuse was close to 

one-half. (See “NIDA Plays Key Role in Studying Links

Between AIDS and Drug Abuse,” NIDA NOTES, 

May/June 1995, p. 1.)

Dr. Holmberg set out to estimate the size and direction of

the HIV epidemic in major U.S. cities with populations

greater than 500,000. He compiled a large computer

model for tracking disease trends by reviewing more than

350 documents, several large research data sets, and information from 220 public health authorities. Some of the

reports date back 10 or more years.

The 96 metropolitan areas Dr. Holmberg looked at have

an estimated 1.5 million IDUs, 1.7 million gay and bisexual men, and 2.1 million at-risk heterosexuals. Among

these three risk groups there are currently an estimated

565,000 HIV infections, with 38,000 new infections

occurring each year. Using these data to make nationwide

projections, the review concludes that there are about

700,000 current HIV infections, with 41,000 new HIV

infections occurring each year in the U.S. population.

Estimated New HIV

Estimated Number Estimated Percent Infections Each Year Per 

Risk Group in Risk Group HIV Positive 100 Group Members

Injecting Drug Users 1.5 million 14.0% 1.5

Men Who Have Sex 

With Men 1.7 million 18.3% 0.7

At-Risk Heterosexuals* 2.1 million 2.3% 0.5

* Men and women who are at risk because they have sex with injecting drug users and/or bisexual or gay men. 

Chart shows percentages of at-risk groups in major cities who tested positive for HIV. Estimates were compiled in 1996.

HIV Infections Among At-Risk Populations In America’s 96 Largest Cities
120

An estimated 19,000 IDUs are infected each year in these

96 metropolitan areas, indicating an HIV incidence rate

of about 1.5 infections per 100 IDUs per year, Dr.

Holmberg reports. Infection rates are lower for the other

two high-risk groups. Although gay and bisexual men still

represent the group with the greatest number of current

HIV infections, the rate of infection—except in young

and ethnic/minority gay men—is much lower now than it

was a decade ago, Dr. Holmberg reports. For gay and

bisexual men, the HIV infection rate per 100 persons per

year is 0.7; for at-risk heterosexuals—those who have sex

with IDUs or gay and bisexual men—the rate is 0.5 infections per 100 persons per year. At-risk heterosexual

women outnumber at-risk heterosexual men about 4 to 1.

In the research review, HIV incidence rates for metropolitan areas were broken down by estimated numbers

of HIV-infected people in each of the three at-risk groups.

An estimated HIV infection rate for each group in each

city was also provided. “This is highly valuable epidemiological information for better targeting prevention 

strategies,” says Dr. Leshner.

“The HIV epidemic is now clearly driven by infections

occurring among injecting drug users, their sex partners,

and their offspring,” concludes Dr. Holmberg in his

review. However, NIDA-funded efforts to educate IDUs

to modify their risky drug use behaviors have proven

effective, he says. Evidence shows that HIV infection rates

in injecting drug users have declined over the past several

years in the largest drug-using communities, he reports.

In cities in New York and northern New Jersey, the 

epicenter of the AIDS epidemic among injecting drug

users, many IDUs are switching to practices that may

lessen their risk of contracting HIV, such as using sterile,

never-used needles and syringes; cleaning needles and

paraphernalia; sniffing rather than injecting heroin and

cocaine; or abstaining from drug use altogether. This

shows that drug abuse and AIDS prevention programs 

targeting IDUs are working, Dr. Holmberg says.

His review further illuminates the link between the AIDS

epidemic and drug abuse as primarily a public health

issue. Within this public health perspective, the CDC 

scientist’s review also provides important insights for policymakers, clinicians, and administrators who are planning

and implementing drug abuse and HIV prevention and

treatment programs. Targeting HIV treatment and prevention programs to IDUs also holds potential for reducing

the spread of other blood-borne infections, including 

hepatitis B and C viruses.

Source

• Holmberg, S.D. The estimated prevalence and incidence of HIV in 96 large U.S. metropolitan areas.

American Journal of Public Health 86(5):642–654,

1996.
Research Findings

121

Mental Health Problems of Addicted Mothers Linked to Infant Care

and Development

By Robert Mathias, NIDA NOTES Staff Writer

Volume 12, Number 1 (January/February 1997)

Women who abuse cocaine while they are pregnant often

share many characteristics, such as addiction, poverty, and

low literacy levels. However, they differ in the quality of

care they give their children, a NIDA-funded study says.

In fact, how well cocaine-addicted mothers care for their

infants appears to be strongly influenced by the type and

severity of psychological problems these women suffer

from, according to the study. The quality of care these

mothers provide is important because it affects the 

cognitive development of their cocaine-exposed infants,

the study notes.

“Self-reported symptoms of psychological problems

among addicted women really did affect maternal 

caregiving,” says Dr. Judy Howard of the University of

California at Los Angeles (UCLA), who directed the

study. This finding indicates that drug abuse treatment

programs should work on other issues, such as mental

health problems, in addition to helping addicted mothers

become abstinent, Dr. Howard says.

The UCLA study of cocaine-addicted women and their

infants was one of NIDA’s Perinatal-20 treatment research

demonstration projects. The 5-year program, which ended

last year, evaluated the effectiveness of providing comprehensive therapeutic programs that include drug abuse

treatment plus a range of additional social and health services for drug-abusing women of child-bearing age and

their children. The projects in the program have yielded

new information about the characteristics and treatment

needs of pregnant and parenting women who abuse drugs.

(See “NIDA’s Perinatal-20 Projects,” NIDA NOTES,

November/December 1994, p. 6.)

The cocaine-abusing women in the study, which was conducted by Dr. Howard and Dr. Leila Beckwith, also of

UCLA, were similar demographically to the women in

many of the other Perinatal-20 projects. On average, they

were about 29 years old, had less than a high school 

education, were single, had a history of being physically 

or sexually abused, and belonged to minority groups. 

The women had a long history of cocaine and other 

drug abuse.

Despite their similarities, including heavy drug use, “these

women are not a homogeneous group,” stresses 

Dr. Howard. The women in this study exhibited a wide

range of psychological symptoms and maternal caregiving

abilities that affected the development of their infants, 

she says. Specifically, mothers who reported more symptoms of a narcissistic, paranoid, histrionic, or borderline

personality disorder were the least sensitive caregivers. In

turn, many of these mothers’ babies showed signs of

delayed cognitive development at 6 months of age, 

Dr. Howard notes.

Recently, Dr. Howard and her colleagues conducted a 

further analysis of the data collected about the women’s

drug use and parenting behaviors 6 months after they 

gave birth. That analysis indicates that although the

women who exhibited the most severe psychological

symptoms reduced their drug use, they were still the least

sensitive caregivers.

“These findings suggest a clinically significant relationship

between a mother’s psychopathology and her ability to

care for her newborn, which, in turn, might negatively

affect her child’s development,” says Dr. Elizabeth

Rahdert, a research psychologist with NIDA’s Division of

Clinical and Services Research, who has been involved

with the Perinatal-20 program since its inception. In addition, the finding that many of these women have severe

mental health problems suggests that treatment programs

should include a psychiatric component to assess and

address women’s mental health problems on an individual

basis, Dr. Rahdert says. Social service programs that do

not have mental health professionals on their staff can

make sure women receive the therapy they need by establishing strong links to the mental health care system within their communities, says Dr. Rahdert.

Mental health professionals should play a key role in drug

treatment for drug-abusing mothers, agrees Dr. Howard,

but they need to be trained in addiction-related problems,

she says. In the final analysis, the study’s findings argue for

comprehensive treatment programs and coordination of

addiction treatment, mental health, and pediatric 

services to adequately meet the needs of these women and

their children, concludes Dr. Howard.
122

Sources 

• Howard, J.; Beckwith, L.; Espinosa, M.; and Tyler, R.

Development of infants born to cocaine-abusing

women: Biologic/Maternal influences. Neurotoxicology

and Teratology 17(4):403–411, 1995.

• Howard, J.; Espinosa, M.; and Beckwith, L.

Psychological status and parenting behaviors in

cocaine-using mothers. Abstract presented at the 58th

Annual Scientific Meeting of the College on Problems

of Drug Dependence, San Juan, Puerto Rico,

1996.
Research Findings

123

Volume 12, Number 1 (January/February 1997)

National Survey of Drug Use During Pregnancy Available

Copies of NIDA’s National Pregnancy and Health Survey—

a national assessment of the extent of drug use by women

during pregnancy—are available free from the National

Clearinghouse for Alcohol and Drug Information

(NCADI).

The survey findings show that an estimated 5.5 percent of

the 4 million women who gave birth in the United States

in 1992 used illegal drugs while they were pregnant. The

survey results provide vital information for physicians and

other health practitioners, public health policymakers,

lawmakers, and drug abuse prevention and treatment

practitioners.

The survey, which was published in 1996, notes that the

data may actually underestimate true rates of drug use but

adds that the findings clearly indicate that “a substantial

number of newborns were exposed to harmful substances

in utero.” (The survey results are summarized in “NIDA

Survey Provides First National Data on Drug Use During

Pregnancy,” NIDA NOTES, January/February 1995, p. 6.)

The 460-page publication contains estimates on the number of women who used drugs during pregnancy, their

demographic characteristics, and their patterns of drug

use. For example, the survey report provides drug use estimates by race and ethnicity, age, marital status, employment condition, and method of hospital payment.

The survey gathered information from self-report questionnaires filled out by a national sample of 2,613 women

who delivered live babies in 52 urban and rural hospitals

during 1992. The data indicate that an estimated 221,000

women who gave birth that year had used illicit drugs

while they were pregnant. The two illicit drugs most frequently used during pregnancy were marijuana, by 2.9

percent of all women who gave birth, and cocaine, 

by 1.1 percent.

The survey found that 20.4 percent of women delivering

live babies smoked cigarettes and 18.8 percent drank 

alcohol during pregnancy. Significantly, the survey also

revealed a strong link between the use of cigarettes 

and alcohol and the use of illicit drugs. This finding

emphasizes the need for doctors and other practitioners to

closely monitor the use of both licit drugs—cigarettes and

alcohol-and illicit drugs during pregnancy, say public

health authorities.

The survey report provides detailed information on the

results of urine testing and on the design and execution of

the survey. It also makes recommendations for improving

the design of similar surveys.

The publication, National Pregnancy and Health Survey—

Drug Use Among Women Delivering Livebirths: 1992, is

available from NCADI, P.O. Box 2345, Rockville, MD

20847-2345, (800) 729-6686, TDD: (800) 487-4889.

Ask for NCADI publication No. BKD192.
Research Findings

124

Type A or B? Classification May Help in Treating Cocaine Abuse

By Neil Swan, NIDA NOTES Staff Writer 

Volume 11, Number 4 (September/October 1996)

For a number of years, researchers have been

testing the concept of classifying, or subtyping,

alcoholics as Type A or Type B. Now they are

finding the concept useful in studying cocaine

abusers, too.

Subtyping is a system for classifying and studying

individuals who share one or more common

characteristics. Subtyping alcoholics provides a

greater understanding of the complex interactions

between genetic, personality, and environmental

risk factors in the development of alcoholism, as

well as resiliency against succumbing to these

risk factors.

This typing process for alcoholics assesses multiple characteristics of each client, such as factors

leading to abuse, severity of symptoms, and consequences of heavy drinking. By typing alcoholics

as A or B using defining characteristics, researchers

can better sort out the factors associated with

their abuse problems and devise appropriate

treatment strategies.

Alcohol abuse is more severe among Type B alcoholics

than among those who are Type A. Type B alcoholism

appears to be more related to hereditary factors than Type

A and to be more likely to occur among men than

women. Type Bs are more impulsive and tend to have a

stronger family history of alcohol abuse; they have more

childhood conduct problems and more severe alcohol

dependence, polydrug abuse, and psychiatric disorders,

especially antisocial personality.

Inspired by advances in subtyping alcoholics, Dr. Samuel

A. Ball of Yale University School of Medicine and his 

colleagues conducted a NIDA-funded study examining

whether subtyping is valid for cocaine abusers as well.

They found strong evidence that it is.

“Our research may prove useful in explaining different causes of abuse in different types of cocaine abusers,” says Dr.

Ball. “We found that certain vulnerability factors, such as

family history, sensation-seeking behavior, and childhood

conduct problems, seem to predispose cocaine users to a

more virulent form of cocaine dependence—Type B,” he

explains. “Other cocaine abusers who don’t have these characteristics [Type As] may develop their cocaine dependence

more from social or environmental influences relative to

inherited, temperamental, or psychiatric influences.”

The researchers studied abuse characteristics in 399

cocaine abusers, 69 percent of whom were male. Of these,

298 had sought treatment, 149 in an outpatient treatment

program and another 149 in an inpatient, hospital-based

program. The remaining 101 were cocaine abusers not 

in treatment. The study participants had a median age 

of 28 and were, generally, single, high school graduates,

and had a low socioeconomic status. Fifty percent were

white, 48 percent were African American, and 2 percent

were Hispanic.

As part of a larger diagnostic study of cocaine abusers, for

which Yale University’s Dr. Bruce J. Rounsaville was 

principal investigator, participants were given a battery of

standard assessment tests that included the Sensation

Seeking Scale, the Addiction Severity Index, the Schedule

for Affective Disorders and Schizophrenia, and Family

History Research Diagnostic Criteria tests. Subsequently,

Dr. Ball and his colleagues sorted these measures into

three variables, similar to the factors generally used to 

categorize alcoholics:

• predisease risk factors, such as family history of substance abuse, childhood conduct disorder and attention-deficit disorder, sensation-seeking traits, and age

when drug abuse began; 

After years of studies, researchers are able to identify factors that classify alcoholics

as Type A or Type B. Recent NIDA-funded studies show that, in general, the same

multiple criteria are valid in classifying cocaine abusers. Results may prove useful

in explaining different causes of abuse and in designing specific prevention and

treatment interventions.

TYPE A TYPE B

Cause of Abuse Problem More Environmental More Genetic

Gender Equal Male/Female More Male

Personality Low Impulsivity High Impulsivity,

and Sensation Seeking, Sensation Seeking

High Harm Avoidance

Childhood Factors Few Early Risk Factors Conduct Disorder

Age of Onset Later Earlier

Substance Abuse Severity Less Severe, More Chronic and

More Episodic Severe; Polydrug

Psychopathology Lower Severity, Higher Severity,

More Affective More Antisocial

Classifying Cocaine Abusers
125

• substance abuse variables, including frequency of

cocaine use, years of heavy cocaine use, cocaine

dependence symptoms, alcohol dependence symptoms, polydrug use, and medical and social consequences; and 

• psychiatric problems, such as symptoms of depression

and antisocial personality disorder, and the severity of

these psychiatric problems. 

Based on placement within the variables identified by the

assessment tests, the researchers classified the cocaineabusing study participants as either Type A or Type B 

and then examined differences in behavioral and other

characteristics between the two groups.

Researchers found that cocaine abusers classified as Type B

scored higher than Type As in assessments of sensation

seeking, aggression, criminality, violence, and impairment

of social adjustment. Type Bs also used greater amounts of

cocaine more frequently and for longer durations than

Type A cocaine abusers. Type Bs also suffered more

adverse effects from their drug use, such as unconsciousness, chest pain, and violence, and they reported a greater

degree of additional drug abuse to relieve withdrawal distress. Type B abusers became involved with cocaine at

younger ages for: first use, first binge, first regular use,

first daily use, and first symptoms of addiction.

No differences were found between the two subtypes in

regard to the length of time between first use of cocaine

and first symptoms of dependence; route of use, such as

snorting, smoking, or injection; number of strategies used

in attempting to control use; and previous periods of

abstinence from illicit drugs or alcohol.

Overall, more than half of the participants were classified

as Type As, but among those in inpatient treatment, there

were nearly equal numbers of Type As and Bs. Among the

outpatient and not-in-treatment participants, 75 percent

were Type A. This suggests that studies assessing only

cocaine abusers who are enrolled in inpatient treatment

may not provide valid estimates of the relative proportion

of Type A and B abusers who are in outpatient treatment

or not in treatment, Dr. Ball warns.

With few exceptions, the classification model assessment

results seemed consistent across gender and race. Although

women and African Americans were Type As more often

than men and whites were, a significant number of

women and African Americans showed the kind of Type B

abuse risk factors, severity, impairment, and antisocial

behavior that some researchers had previously thought

were related to alcoholism among men and among whites. 

“If Type A substance abuse is in fact more influenced by

social relationships and environment, relative to genetic

and personality factors, then we might speculate that

women and African Americans might be more susceptible

to developing alcohol or cocaine addictions for more

socially, environmentally, or culturally determined reasons,” says Dr. Ball. But future research is needed on this

topic to determine if this typology holds in other ethnic

groups such as Latinos/Hispanics, Asians, and Native

Americans, as well as in other cultures and countries, 

he adds.

Dr. Rounsaville, who coauthored the study, notes that

while there has been some experimental work using 

typology-based treatment and prognostic findings, the

practice of assessing and classifying substance abusers as

Type A or B is not now widely practiced in drug abuse

treatment programs. For one thing, classification procedures must be validated and made suitable for simple, 

routine use in treatment programs. But typology research

continues with hope that advances can lead to new

insights for evaluating causes of substance abuse and 

for preventing and treating it in the treatment program

setting, he adds.

Sources

• Babor, T.F., and Dolinsky, Z.S. Alcoholic typologies:

Historical evolution and empirical evaluation of some

common classification schemes. In: Rose, R.M., and

Barrett, J., eds. Alcoholism: Origins and Outcome. 

New York: Raven Press, 1988, pp. 245–266.

A classification of cocaine abusers by Dr. Samuel A. Ball shows

results similar to these found in many studies of alcoholics.

Although women and African Americans are more often Type As

compared to men and whites, a significant number of women and

African Americans nevertheless show the kind of Type B abuse risk

factors, severity, impairment, and antisocial behavior thought by

some earlier researchers to be related to alcoholism among men and

among whites.

Percentages of Type A and Type B Cocaine Abusers

TYPE A TYPE B

Males 61% 39%

Females 79% 21%

African American Males 68% 32%

African American Females 86% 14%

White Males 57% 43%

White Females 78% 22%
126

• Babor, T.F.; Hofmann, M.; DelBoca, F.K.; Hessborck,

V.; Meyer, R.E.; Dolinsky, Z.S.; and Rounsaville, B.

Types of alcoholics, I: Evidence for an empirically

derived typology based on indicators of vulnerability

and severity. Archives of General Psychiatry

49:599–608, 1992.

• Ball, S.A.; Carroll, K.M.; Babor, T.F.; and

Rounsaville, B.J. Subtypes of cocaine abusers: Support

for a type A-type B distinction. Journal of Consulting

and Clinical Psychology 63:115–124, 1995.
Research Findings

127

Volume 11, Number 4 (September/October 1996)

Drug Use During Pregnancy Associated With Increased Risk of

Transmitting HIV to Infants

By Robert Mathias, NIDA NOTES Staff Writer 

A national, multicenter study has found that HIV-infected

women who used illicit drugs during pregnancy had a

higher risk of transmitting HIV to their infants than 

did HIV-infected women who did not use drugs 

while pregnant. 

The study, known as the Women and Infants

Transmission Study (WITS), was launched in 1989 by 

the National Institute of Allergy and Infectious Diseases

(NIAID) to track the natural history of HIV in infected

women and their infants. The study currently is funded 

by NIAID, NIDA, and the National Institute of Child

Health and Human Development. 

In the study, researchers analyzed data on 530 HIV-infected pregnant women and their infants who were treated in

obstetric and pediatric clinics in five cities across the

United States. The analysis showed that the HIV perinatal

transmission rate for women who used drugs during pregnancy was 27 percent compared with a 16 percent transmission rate among HIV-infected women who did not 

use drugs. Forty-two percent of the women in the study

used illicit drugs during pregnancy; 44 percent of those

women used multiple drugs. The most commonly used

drug was cocaine, used either alone or in combination

with other drugs. 

The study’s findings emphasize the critical role of drug

abuse treatment in prenatal health care for HIV-infected

pregnant women who use drugs, according to Dr. Evelyn

M. Rodriguez of the Health Resources Services

Administration and her colleagues in the WITS. The

WITS findings also underscore the importance of ensuring

that all HIV-infected women receive information on how

AZT (zidovudine) treatment during pregnancy can significantly reduce perinatal transmission of HIV, the

researchers conclude. 

Large multisite studies such as the WITS enable

researchers to investigate both the behavioral and basic

biological factors that may contribute to maternal-infant

transmission of HIV, according to Dr. Vincent Smeriglio

and Katherine Davenny of NIDA’s Division of Clinical

and Services Research, who are members of the WITS

research staff. Further research is planned to verify the

association between maternal drug use and infant HIV

infection and to clarify the possible mechanisms of this

association, they indicate. 

Source 

• Rodriguez, E.M.; Mofenson, L.M.; Chang, B.H.;

Rich, K.C.; Fowler, M.G.; Smeriglio, V.; Landesman,

S.; Fox, H.E.; Diaz, C.; Green, K.; and Hanson, I.C.

Association of maternal drug use during pregnancy

with maternal HIV culture positivity and perinatal

HIV transmission. AIDS 10(3):273–282, 1996.
Research Findings

128

Cocaine Affects Men and Women Differently, NIDA Study Shows

By John A. Bowersox, NIDA NOTES Contributing Writer 

Volume 11, Number 1 (January/February 1996)

A recent NIDA-funded study suggests that gender differences will become an increasingly important consideration

in drug abuse treatment strategies. The study by

researchers affiliated with Harvard Medical School found

that cocaine affects men and women differently and that

hormonal fluctuations play an important role in women’s

responses to the drug.

In the study, Dr. Scott E. Lukas and his colleagues at the

Alcohol and Drug Abuse Research Center in Belmont,

Massachusetts, measured a variety of responses to cocaine

in six male and six female volunteers. On separate days,

the volunteers snorted single doses of cocaine and placebo

powder in equal amounts relative to their body weights.

The men were tested once, but the women were tested at

two different times during their menstrual cycle: once

during their follicular phase and again during their luteal

phase. The follicular and luteal phases, respectively, correspond to the times before and after ovulation. The

researchers calculated the phases of each woman’s cycle

from the onset of menstruation:

• Dose 1 (midfollicular phase) was given 5 to 9 days

after the onset of menstruation; 

• Dose 2 (midluteal phase) was given 18 to 22 days

after onset of menstruation. 

The researchers found that at both points in the menstrual

cycle the women were much less sensitive to the drug than

the men were. The men in the study had significantly more

episodes of euphoria, or good feelings, and dysphoria, or

bad feelings. When asked to rate the severity of their 

dysphoria, the men judged the bad feelings to be more

unpleasant than the women did. The men also experienced greater heart rate and blood pressure increases and

detected cocaine’s effects sooner than the women did.

Although the men and women received equivalent doses

of cocaine, women had lower levels of the drug in their

blood than the men; their cocaine blood levels were even

lower when they took the drug during the luteal phase of

their menstrual cycle.

Dr. Lukas says that differences in the speed with which

cocaine is metabolized may account for the drug’s different effects in men and women. In the body, cocaine is

broken down into inactive metabolites by enzymes known

as cholinesterases. Although men have higher levels of

these enzymes in their blood plasma, women have higher

levels of a type of cholinesterase enzyme found in red

blood cells, Dr. Lukas explains. The red blood cell enzyme

metabolizes cocaine much more actively than the plasma

enzyme does.

Physical changes that occur during the menstrual cycle

also may contribute to women’s decreased sensitivity to

intranasal cocaine, says Dr. Lukas. The increase in certain

hormone levels during the luteal phase causes women’s

mucous membranes, including those that line the nasal

passages, to secrete more mucus. Dr. Lukas says that the

increased mucus may act as a barrier to the absorption of

cocaine when women snort the drug during the luteal

phase of their menstrual cycle.

“We believe that the gender differences in cocaine’s effects

that we observed are due to a combination of metabolic

differences and the greater physical barrier to cocaine

absorption created by the increase in mucosity,” says Dr.

Lukas. He adds that other as yet unknown factors could

also help produce cocaine’s differing effects.

Dr. Lukas says the findings, which he presented at the

1994 meeting of the College on Problems of Drug

Dependence, might help explain, at least from a physiological perspective, why the prevalence of cocaine use

among women has traditionally been much lower than it

has been among men. According to the National

Household Survey on Drug Abuse, approximately 3.1 

million men and 1.4 million women used cocaine at least

once during 1993. Women also appear to take cocaine less

frequently than men do. The 1993 survey, which was 

conducted by the Substance Abuse and Mental Health

Services Administration, estimates that about 365,000

men compared with 111,000 women used cocaine at least

once a week.

Many women have reported that they did not get high

when they first tried cocaine, says Dr. Lukas, adding that

women’s low sensitivity to the drug combined with its

high price create a strong disincentive to its continued use.

On the other hand, he says, some women may become

heavy users because they need to take more cocaine to get

the same effect as men.
129

If further studies substantiate Dr. Lukas’ findings, they

could have important implications for the treatment of

cocaine abusers, says Dr. Elizabeth Rahdert, a research

psychologist in NIDA’s Division of Clinical and Services

Research.

“Therapists would have to realize that for women, the

response to cocaine will be different at different times 

of the month and not a steady state as it is for men,” 

she says.

Presumably, she adds, patterns of craving and response to

withdrawal could also fluctuate with a woman’s menstrual

cycle, and treatment professionals would have to recognize

that women could be more vulnerable to relapse at different points in their cycle. Furthermore, treatment strategies

designed to address male usage patterns would have to be

modified in accordance with women’s usage patterns.

Dr. Lukas’ work reflects NIDA’s increased interest in

examining the gender-specific effects of drug abuse. Basic

research findings such as the discovery that sex hormones

can interact with neurotransmitters during normal brain

functioning have fueled this interest.

“Previously, drug abuse research on women focused mainly on issues related to pregnancy and the effects of drug

abuse on the developing fetus,” says Dr. Cora Lee

Wetherington, a psychologist in NIDA’s Division of Basic

Research.

“More recently, we’ve seen a shift with the realization that

the treatment needs of women may be different from

those of men. Although issues related to childbearing and

child-rearing are still important areas of drug abuse

research, researchers are questioning whether treatment

strategies that were developed through research conducted

largely on male subjects are appropriate for women,” says

Dr. Wetherington.

Source

• Lukas, S.E.; Sholar, M.B.; Lundahl, L.H.; et al. Sex

differences in plasma cocaine levels and subjective

effects after acute cocaine administration in human

volunteers. Psychopharmacology 125(4):346–354,

1996.
Research Findings

Volume 10, Number 5 (September/October 1995)

130

Daughters of Mothers Who Smoked During Pregnancy are More

Likely to Smoke, Study Says

By Robert Mathias, NIDA NOTES Staff Writer 

Researchers have long wondered about the impact of 

prenatal exposure to drugs on a child’s vulnerability to

drug abuse. Now, NIDA-funded studies have documented

a relationship between prenatal exposure to nicotine and

adolescents’ use of tobacco. Dr. Denise Kandel of

Columbia University found that daughters of women who

smoked cigarettes while they were pregnant are four times

more likely to begin smoking during adolescence and to

continue smoking than daughters of women who did not

smoke during pregnancy. 

“The clearest message from the study is that mothers

should not smoke during

pregnancy,” says Dr. Kandel.

The study suggests that nicotine, which crosses the placental barrier, may affect the

female fetus during an

important period of development so as to predispose the

brain to the addictive influence of nicotine more than a

decade later, she says. 

Prenatal smoking by these

mothers did not have a

strong effect on their sons’

smoking, but it is not clear

why, says Dr. Kandel. Male

hormones or structural differences of male and female

brains may protect the developing male fetus from the

nicotine entering the brain,

she says, but notes, “That is

all very speculative.”

Prenatal exposure to smoking

has previously been linked

with impairments in memory, learning, cognition, and

perception in the growing child, says Dr. Jagjitsing Khalsa

of NIDA’s Division of Clinical and Services Research. The

results of Dr. Kandel’s study suggest that smoking during

pregnancy may create a risk of early and continued smoking among these women’s children, he says. Noting that

other NIDA researchers are looking at the possible intergenerational transmission of a tendency to use marijuana

through prenatal exposure, Dr. Khalsa says, “We need to

let women know that if they take drugs during pregnancy

they may put their offspring at risk for future drug use.” 

In previous research, Dr. Kandel had examined the intergenerational effects of drug use by following a cohort of

New York State adolescents who were periodically reinterviewed over the course of 19 years. That research indicated

that a mother’s cigarette smoking had a greater effect than

a father’s on smoking among both sons and daughters.

When analyses of different social influences could not

identify the reason for this maternal effect, Dr. Kandel

focused on one factor that

differentiated mothers from

fathers—a mother’s smoking 

during pregnancy. 

In her most recent study, 

Dr. Kandel analyzed followup interview data on 192

mothers and their first-born

adolescents from the New

York State study. The children’s mean age was 12 1/2.

The analysis revealed that

26.4 percent of girls whose

mothers smoked while pregnant had smoked in the last

year. By comparison, only

4.3 percent of girls who were

not prenatally exposed to

nicotine had smoked in the

last year. While more prenatally exposed boys had also

smoked in the last year 

compared with boys whose

mothers had not smoked

during pregnancy, the difference was not statistically 

significant. 

Subsequently, Dr. Kandel replicated her New York State

analysis with pre- and postnatal smoking data on 797

mothers and their children drawn from the National

Longitudinal Survey of the Work Experience of Youth

Cohort, a Bureau of Labor Statistics survey that has been

conducted annually since 1979. The second analysis confirmed the findings from the New York State survey, says

Source: NIDA’s Monitoring the Future Studies, 1991-94 

According to NIDA’s Monitoring the Future Study, the percent

of adolescent girls who smoke cigarettes has increased in the

last 4 years. Although smoking among adolescent girls has been

linked to many different factors, Dr. Kandel’s study is the first

to document a possible link between prenatal exposure to 

nicotine and an adolescent girl’s tendency to smoke cigarettes.

Trends in Adolescent Girls’ Current Use of Cigarettes
131

Dr. Kandel. The combined data from both surveys indicated a fourfold greater risk of smoking for girls whose

mothers smoked during pregnancy. 

To ensure that it was a mother’s prenatal smoking and not

her postnatal smoking that affected her daughter’s smoking, the researchers analyzed the impact of those mothers’

smoking both during and after pregnancy. They found

that, regardless of the amount or duration of current or

past maternal smoking, the strongest correlation between

maternal smoking and a daughter’s smoking occurred

when the mother smoked during pregnancy. 

Smoking activates several brain neurotransmitter systems

including the dopamine system, which is involved in the

reinforcing effects of addictive drugs in general, points out

Dr. Kandel. Since this study raises the possibility that

nicotine may modify the developing fetus’s dopamine system,

making it more susceptible to the effects of nicotine at a

later time in life, “The children whose mothers smoked

during pregnancy are not only going to be more likely to

smoke, but also may be more likely to use and become

dependent on other drugs,” she predicts. Dr. Kandel hopes

to research this issue by following the adolescents in her

study for another 6 years. 

Source

• Kandel, D.B.; Wu, P.; and Davies, M. Maternal

smoking during pregnancy and smoking by adolescent daughters. American Journal of Public Health

84(9):1407–1413, 1994.
Research Findings

132

31% of New York Murder Victims Had Cocaine in Their Bodies

By Neil Swan, NIDA NOTES Contributing Writer

Volume 10, Number 2 (March/April 1995)

Nearly 3 out of every 10 homicide victims in New York

City in the early 1990s had evidence of cocaine in their

bodies when they died. Overall, murder victims in the city

are 10 to 50 times more likely than members of the general population to be cocaine users, depending on age, race,

and gender, according to NIDA-funded research using

data from the New York City medical examiner. 

Dr. Kenneth Tardiff of

Cornell University Medical

College in New York City

headed a team of researchers

that studied the 4,298 homicides that occurred in New

York City during 1990 and

1991. Cocaine was found in

the bodies of 31 percent of

the victims. About threefourths of all the murders

involved firearms. 

“Homicide victims may have

provoked violence through

irritability, paranoid thinking, or verbal or physical

aggression, which are known

to be pharmacologic effects of cocaine,” the researchers

hypothesized. Drug dealers’ efforts to protect their sales

territories from invading competitors also promote 

violence and homicide, they suggested. 

Young African-American and Latino men were more likely

to be victims of homicide than were members of all other

demographic groups, the study

found. Two-thirds of the victims

were between the ages of 15 and

34, 86 percent were male, and

87 percent were African

American or Latino. The rate of

homicide was highest for

African-American males ages 15

to 24, followed by AfricanAmerican males ages 25 to 34.

The next highest homicide rates

were among young Latino men

ages 25 to 34 and 15 to 24,

respectively. 

African-American women and

Latino women had much lower

rates of death by homicide than

their male counterparts.

Cocaine was found in 31 percent of the 4,298 people 

murdered in New York City in 1990 and 1991.

Percentage of New York City Homicide Victims in 1990 and 1991 

Positive for Cocaine Metabolites in Each Age Group by Gender and Race*

White African American Latino Asian/Other

Age in Male Female Male Female Male Female Male Female Total

Years (n=272) (n=74) (n=1,583) (n=276) (n=1,344) (n=184) (n=138) (n=19) (n=3,890)

14 or under 0 25.0 2.4 0 3.7 0 0 0 4.1

15-24 18.4 16.7 18.9 35.6 23.7 28.1 8.6 0 21.5

25-34 37.5 59.1 44.4 71.8 43.4 36.1 4.9 0 43.9

35-44 34.0 26.7 49.3 40.8 42.0 31.0 12.1 0 40.9

45-54 12.2 0 27.8 20.0 26.4 14.3 0 0 20.7

55 or over 2.3 0 14.0 0 16.3 0 0 0 7.2

Total 22.4 25.7 31.6 39.5 39.9 27.7 6.5 0 31.0

* Denominators include only cases in which there were toxicologic analyses for benzoylecgonine, a cocaine metabolite, and in which the interval between injury

and death was 48 hours or less. 

This table was adapted from an article that appeared in The Journal of the American Medical Association, Vol. 272, No. 1, July 6, 1994, pp. 43–46. Copyright

1994, American Medical Association. 
However, their rates were slightly higher than those of

white males, particularly in the 15- to 34-year-old age

group. White females had the lowest homicide rates of any

demographic group. 

Among some of the young demographic groups of victims, cocaine use surprisingly was higher among females

than among males. For example, 59 percent of white

women and 72 percent of African-American women ages

25 to 34 had been using cocaine before they died compared with 38 percent of white men and 44 percent of

African-American men in that age group. This “high 

proportion” of cocaine users among white and AfricanAmerican female homicide victims is contrary to surveys

showing that women in general are less likely to be drug

users and shows that drug use is a key risk factor for

homicide victimization among women, the study authors

said. “It is possible that female users of cocaine are more

likely than nonusers to be victims of violence from spouses, boyfriends, or, in the case of prostitutes, their clients,”

said the researchers. 

The investigators attributed the high homicide rate they

found among African Americans and Latinos to the

increased availability and abuse of crack cocaine and the

increased availability and lethal firepower of guns. 

“There is no clear answer as to how we can decrease the

heavy use of cocaine, particularly in our cities,” the

researchers said. “There is a major need for public treatment programs, but these will be very expensive, and

treatment for cocaine addiction has no methadone analog

yet. Prevention programs aimed at schools require 

adequate evaluation.” 

Source

• Tardiff, K.; Marzuk, P.M.; Leon, A.C.; Hirsch, C.S.;

Stajic, M.; Portera, L.; and Hartwell, N. Homicide in

New York City: Cocaine use and firearms. JAMA

272:43–46, 1994.

133

Characteristics of Homicide Victims Killed in 1990

and 1991 in New York City (Residents Only) 

Characteristics # of % of All

Cases Homicides

AGE IN YEARS

Less than 1 46 1.1

1-14 93 2.2

15-24 1,442 33.7

25-34 1,457 34.0

35-44 693 16.2

45-54 289 6.8

55-64 126 2.9

65 and older 132 3.1

Total 4,278* 100.0

GENDER

Male 3,682 85.7

Female 614 14.3

Total 4,296* 100.0

RACE

White 402 9.4

African American 2,069 48.2

Latino 1,648 38.4

Asian/other 171 4.0

Total 4,290* 100.0

CAUSE OF DEATH

Firearms 3,131 72.8

All other methods 1,167 27.2

Total 4,298 100.0

* Numbers are less than 4,298 because of unknowns for age, gender, and race. 

This table was adapted from an article that appeared in The Journal of the

American Medical Association, Vol. 272, No. 1, July 6, 1994, pp. 43–46.

Copyright 1994, American Medical Association. 
Research Findings

Volume 10, Number 1 (January/February 1995)

134

NIDA Expands Its Research on Addiction and Women’s Health

By Robert Mathias, NIDA NOTES Staff Writer

Women’s health, long neglected in medical research,

stepped into the spotlight at a NIDA-sponsored 

conference held last September to assess the current state

of scientific knowledge about addiction and women’s

health. In addition to showcasing what is known about

women and drug abuse, NIDA hosted the conference to

identify the many gender-related issues that the field of

drug abuse research needs to address to meet the health

needs of women. 

“NIDA wants to

hear from you,”

Dr. Loretta P.

Finnegan, NIDA’s

former senior

advisor on

women’s issues,

told the nearly

200 scientists,

health care 

professionals,

treatment practitioners, representatives of women’s

groups, and policy

and program staff

from NIDA and

other Federal

agencies who

attended the

landmark conference on Drug

Addiction

Research and the

Health of Women. “We want to know what we have

missed. We want to know what we can do to improve our

research priorities with regard to women. And, most of all,

we want to improve the situation for those women who

are suffering from drug addiction,” said Dr. Finnegan,

who now directs the Women’s Health Initiative at the

National Institutes of Health. 

NIDA Director Dr. Alan I. Leshner told conference participants that NIDA is placing a high priority on research on

drug addiction among women, noting that “historically,

drug abuse research has focused primarily on men, as has

most health research. Drug abuse may present significantly

different challenges to women’s health, may progress 

differently in women than in men, and may require different

treatment approaches. And that, of course, is why we’re

here,” Dr. Leshner said. 

“Not only does this conference mark the demise of 

male-only research, it also signals a new era in NIDA’s

approach to research on women,” said Richard A.

Millstein, NIDA’s deputy director. “While we can say with

some accuracy that NIDA has had a long history of studying women and gender differences, the fact is that most of

those studies have been among pregnant women and their

offspring,” Millstein said. “We need to expand beyond

that to look at women independently, not just in relation

to their status as mothers of children,” he said. 

Conference participants from a wide range of disciplines

heeded the call from NIDA policymakers to raise the 

critical questions that the Institute needs to address as it

expands its research agenda on women, drug abuse, and

addiction. For 2 1/2 days, scientists and practitioners presented gender-related findings from epidemiologic, basic,

clinical, and health services research studies and discussed

the implications of these findings for the prevention and

treatment of drug abuse, addiction, and related diseases

such as HIV/AIDS among women. The fact that nearly

70 percent of AIDS cases among women are drug related

coupled with the rapid rise of AIDS among women makes

it imperative that we address drug abuse problems in

women, said Dr. Mary Jeanne Kreek, a NIDA-funded

researcher at Rockefeller University, in her keynote address

to the conference. 

Conference presentations covered such topics as: 

• the nature and extent of drug abuse among women.

Speakers pointed to a lack of reliable epidemiological

data on drug abuse among different groups of minority

women and among women of different sexual 

orientation; 

“Drug abuse may present significantly

different challenges to women’s

health, may progress differently in

women than in men, and may require

different treatment approaches.”

NIDA is expanding its research on women

to gain a better understanding of drug

abuse and addiction and their impact on

women’s health.

Some photos taken from NIDA 

videotape “Door to Recovery.”
135

• the many factors thought to be involved in the etiology of drug use among women, including childhood

and adolescent sexual victimization, partner violence,

and anxiety disorders and depression, which are much

more prevalent among women than men; 

• a history of inadequate and inappropriate treatment

of women’s anxiety and affective disorders, resulting

in overprescription and abuse of psychotherapeutic

medications; 

• biological and behavioral mechanisms that may

underlie women’s patterns of drug use and differences

in how drugs affect men and women. For example,

animal and human studies indicate a possible link

between the menstrual cycle of women addicts and

drug seeking; 

• the medical and health consequences of drug abuse,

which include disruption of women’s menstrual

cycles, reproductive function, and immune function

and a high risk of contracting HIV/AIDS; 

• the psychiatric consequences of drug abuse, which

include phobic, depressive, and antisocial personality

disorders; 

• the social and behavioral consequences of drug abuse,

such as homelessness and high-risk sexual behaviors; 

• the legal consequences of drug abuse, such as the

criminalization and prosecution of drug-abusing

mothers, particularly those from minority groups; 

• the impact of negative social, economic, and legal circumstances on drug abuse and addiction among

African-American, Native-American, Hispanic,

Asian/Pacific Islander, and lesbian women. 

Taken together, conference presentations underscored that

the causes, correlates, pharmacokinetics, mechanisms, and

consequences of drug abuse and addiction vary considerably in men and women. Yet, as a number of speakers

pointed out, most drug abuse prevention and treatment

interventions have been shaped by men’s characteristics

and needs. 

Drug abuse prevention and treatment interventions for

girls and women need to respond to specific gender-based

risk factors, such as childhood sexual abuse, partner 

violence, and the prevalence of anxiety and depressive disorders, a number of researchers said. For example, the

high incidence of anxiety and depression among women

suggests that psychosocial and behavioral treatments

might be particularly effective for women, said Dr. Karla

Moras of the University of Pennsylvania. 

Researchers and practitioners alike also need to acknowledge that women who abuse drugs are not a homogeneous

group, noted several conference participants. Adolescents,

pregnant women, housewives, older women, women from

different ethnic groups, and lesbians may all experience

significant variations in the factors that lead to drug abuse

and addiction. For example, the effects of racism and

community violence may contribute to making AfricanAmerican women more vulnerable to depression and 

substance abuse. In like manner, a disproportionately large

percentage of lesbians appear to suffer from drug and 

alcohol disorders that may be related to their having to

deal with negative societal responses to their sexual orientation, said Marj Plumb of the National Center for

Lesbian Rights. 

Overall, NIDA’s conference on addiction and women’s

health indicated that “despite some promising findings,

the basic take-home message is that there are more gaps in

knowledge about women in all areas of drug abuse

research than there are findings,” said Millstein. NIDA

plans to start filling those gaps by incorporating into its

agenda recommendations from conference participants

that the Institute support more research on the impact 

of women’s biology, environment, relationships, and 

experiences on health behaviors, Millstein said. 

“As we all strive to move the concerns of women to a

higher level in our overall priorities, we can be proud that

we’ve done so much. But, we have a great deal more to

accomplish,” summed up Dr. Finnegan, who headed the

NIDA Women’s Advisory Committee, which organized

the conference. 
Research Findings

136

Volume 10, Number 1 (January/February 1995)

NIDA Survey Provides First National Data on Drug Use 

During Pregnancy

By Robert Mathias, NIDA NOTES Staff Writer

More than 5 percent of the 4 million women who gave

birth in the United States in 1992 used illegal drugs while

they were pregnant, according to the first nationally 

representative survey of drug use among pregnant women.

The NIDA-sponsored survey, which was released last fall,

provides the best estimates to date of the number of

women who use drugs during pregnancy, their demographic characteristics, and their patterns of drug use. 

“Information from NIDA’s National Pregnancy and

Health Survey can help to guide public health policymakers who have to make decisions about prevention and

treatment programs aimed at reducing the problem of

drug abuse during pregnancy,” said NIDA Director 

Dr. Alan I. Leshner. Dr. Leshner reported the survey’s

findings at a press briefing held during NIDA’s conference

on Drug Addiction Research and the Health of Women

last September. 

The survey gathered self-report data from a national 

sample of 2,613 women who delivered babies in 52 urban

and rural hospitals during 1992. Based on these data, an

estimated 221,000 women who gave birth in 1992 used

illicit drugs while they were pregnant. Marijuana and

cocaine were the most frequently used illicit drugs—2.9

percent, or 119,000 women, used marijuana and another

1.1 percent, or 45,000 women, used cocaine at some time

during their pregnancy. 

The survey found a high incidence of cigarette and alcohol use among pregnant women. At some point during

their pregnancy, 20.4 percent, or 820,000, pregnant

women smoked cigarettes and 18.8 percent, or 757,000,

drank alcohol. 

“We know for certain that these [legal] substances affect

the health of the fetus and a woman during and after

pregnancy,” said Dr. Loretta D. Finnegan, NIDA’s former

senior advisor on women’s issues. Health care practitioners

should ask women about their use of cigarettes and 

alcohol during prenatal checkups and educate them about

the health risks of licit drugs, said Dr. Finnegan, who now

directs the Women’s Health Initiative at the National

Institutes of Health. 

The survey also uncovered a strong link between cigarette

smoking and alcohol use and the use of illicit drugs in this

population. Among those women who used both cigarettes and alcohol, 20.4 percent also used marijuana and

9.5 percent took cocaine. Conversely, of those women

who said they had not used cigarettes or alcohol, only 0.2

percent smoked marijuana and 0.1 percent used cocaine.

“This finding reinforces the need for health practitioners

to monitor the status of both licit and illicit drug use during pregnancy,” said Dr. Leshner. 

The survey found that an estimated

113,000 white women, 75,000 

African-American women, 

and 28,000 Hispanic women 

used illicit drugs during pregnancy. 
137

Besides providing the first national estimates of drug use

during pregnancy, the survey also examined differences in

the amount and types of drugs used by several racial and

ethnic groups of women. Overall, 11.3 percent of AfricanAmerican women, 4.4 percent of white women, and 4.5

percent of Hispanic women used illicit drugs while pregnant. While African Americans had higher rates of drug

use, in terms of actual numbers of users, most women

who took drugs while they were pregnant were white. 

The survey found that an estimated 113,000 white

women, 75,000 African-American women, and 28,000

Hispanic women used illicit drugs during pregnancy. 

The survey also described different patterns of licit and

illicit drug use among white women and ethnic minorities. African-American women had the highest rates of

cocaine use, mainly “crack,” during pregnancy. About 4.5

percent of African-American women used cocaine compared with 0.4 percent of white women and 0.7 percent 

of Hispanic women who did so. 

White women had the highest rates of alcohol and cigarette use. Nearly 23 percent of white women drank alcohol and 24.4 percent smoked cigarettes. By comparison,

15.8 percent of African-American women and 8.7 percent

of Hispanic women drank alcohol and 19.8 percent of

African-American women and 5.8 percent of Hispanic

women smoked cigarettes. “These findings point to the

importance of attending to cultural issues in drug abuse

prevention and treatment efforts,” said Dr. Finnegan. 

Although women who used drugs during pregnancy generally decreased their rates of drug use throughout their

pregnancy, they did not discontinue drug use, Dr. Leshner

noted. “This finding indicates how gripping an illness

drug addiction can be, even in the face of what may 

seem to be the ultimate incentive to stay drug free,” 

Dr. Leshner said. Nevertheless, “it is a disease that can 

be treated and managed with appropriate interventions,”

he stressed. 

“With the information the survey provides about the patterns of drug use by women during pregnancy, we will be

better able to identify priorities we must address,” said Dr.

Finnegan. This will enable researchers to develop and test

more effective approaches to the differential drug abuse

treatment and prevention needs of women of childbearing

age, she concluded.
Research Findings

138

Volume 10, Number 1 (January/February 1995)

Early Childhood Behavior and Temperament Predict Later

Substance Use

By Neil Swan, NIDA NOTES Contributing Writer

By the first grade, or earlier, children show temperament

and behavior traits that are powerful indicators of their

inclination to use and abuse drugs in their teenage and

adult years. Researchers have identified not only common

childhood risk factors and behaviors

that predict drug abuse potential but

also protective factors that shield some

children from influences to use drugs. 

A number of long-range NIDA-funded

studies have traced at-risk children into

adulthood and parenthood, trying to

determine why some children are able to

resist persistent influences to use substances of abuse. Studies have zeroed in

on several important factors in predicting a first-grader’s subsequent use of

substances: shyness, aggressiveness,

rebelliousness, and gender. External risk

factors include substance use among

peers, drug use by parents, and troubles

with the police. Protective factors include achievement in

school or after-school activities and close family ties. The

researchers are now designing drug abuse prevention and

intervention strategies based on these findings made over

20 or more years.

Some of the earliest studies, by Dr. Margaret E.

Ensminger and Dr. Sheppard G. Kellam and colleagues 

of The Johns Hopkins University, started in the 1960s

with first-graders and their families in Woodlawn, a poor,

urban African-American community on the South Side 

of Chicago.

Today the researchers are following about 1,000 of the

1,242 original first-graders to continue to identify and

monitor early childhood factors affecting later drug use

and symptoms of psychiatric problems. These first-graders

are now 32 or 33 years old.

Interviews in 1993 show that key risk factors such as

aggressive behavior and shy-aggressive behavior identified

26 years ago continue to hold and are valid predictors of

the subjects’ current levels of cocaine use as adults.

During their studies, Dr. Ensminger and her colleagues

rated each first-grader’s mental health using two criteria:

social adaptation and psychological health. To measure

pupils’ social adaptation to school, researchers used teachers’ ratings of children’s classroom social performance and

intelligence as well as the results of standardized tests.

Psychological health was determined by a number of 

criteria, including psychological symptoms, abnormal

behavior, and level of self-esteem.

Two important risk factors identified as

predictors of later drug use are shy

behavior—described by the teachers as

sitting alone, having few friends, and

not speaking up in class—and aggression—described as fighting with others

or breaking rules. Shyness and aggression are types of poor social adaptation

distinct from symptoms of anxiety or

depression, which are internal feelings,

noted the researchers.

While shyness and aggressiveness are 

key predictors of drug use, a complex

relationship exists between the two 

factors. Among boys, aggressive behavior 

in the first grade leads to increased teenage substance

abuse, while first-grade shyness alone without aggressiveness

leads to lower levels of substance abuse as teenagers.

However, the combination of shyness and aggressiveness

leads to even higher levels of adolescent substance use

among boys than aggressiveness without shyness does, the

studies found.

Boys whose teachers said they had problems concentrating

in class had higher levels of later substance abuse because

concentration problems appear to be closely related to

aggressiveness, the studies reported. By contrast, neither

aggressiveness, nor shyness, nor concentration problems in

the first grade were associated with later substance use

among girls.

Understanding Gender Differences

Shyness and aggressiveness may be less important 

predictors of substance use among females than among

males because girls’ peer groups are smaller and less

important to them, she adds. These gender-based considerations are now being studied in drug abuse prevention

programs, says Dr. Ensminger, who was among the first

researchers to urge colleagues to stop dismissing gender 

as a possible key consideration in predicting children’s

subsequent drug use.

For both sexes, higher

scores on first-grade IQ

and readiness-forschool tests were associated with higher levels

of beer or wine, hard

liquor, and marijuana

use 10 years later. 
139

When the first-graders reached

age 16 or 17, girls used smaller

amounts of beer, wine, liquor,

and marijuana and other illicit

drugs but not cigarettes than

boys did. For both sexes, higher

scores on first-grade IQ and

readiness-for-school tests were

associated with higher levels of

beer or wine, hard liquor, and

marijuana use 10 years later, the

researchers found. “This tells us

that the children who are most

ready for school are also those

most ready to experiment with

drugs,” says Dr. Ensminger.

Psychological well-being and

family relationships in the first

grade seemed more important to girls than to boys in

terms of influencing psychiatric symptoms 10 years later.

Mothers had an important effect on the psychological status of their daughters but not of their sons. Mothers’

expectations of how far daughters would go in school and

mothers’ own psychological health were positive factors in

their daughters’ psychological well-being 10 years later, the

study found. Girls with strong family bonds tend to use

drugs less than other girls do, but the same family influence is not so apparent with boys, said Dr. Ensminger.

Results from the Woodlawn study served as the basis for

prevention programs started in Baltimore in the 1980s by

Dr. Kellam and colleagues. That prevention effort focused

on aggressive behavior because of its relationship to 

later drug use and on underachievement because of its

relationship to depressed feelings.

Recent data gathered on the Woodlawn study subjects

show that early childhood aggression is still a valid predictor of drug abuse when measured against the now-adult

subjects’ levels of use of cocaine, Dr. Ensminger reports.

Those data are now being prepared for publication.

Examining Protective Factors

Another long-term study of drug-use predictors focuses on

children in Northeastern States. For 20 years, Dr. Judith

S. Brook of Mt. Sinai School of Medicine has studied risk

factors identified in early childhood and in adolescence

that are related to drug use during adolescence. She is

conducting a study of 1,000 children and their mothers

that began in 1975 in two communities representative of

the population of the Northeastern United States. In the

continuing research, Dr. Brook is examining not only risk

factors but also protective factors that help shield children

and adolescents from these risk factors.

Dr. Brook and her colleagues

have identified a number of

risk factors for subsequent drug

use such as childhood aggression, which includes anger,

aggression toward siblings,

noncompliance, temper, and

nonconforming behavior.

Other risk factors are unconventionality—an attitude of

deviance, rebelliousness, and

evasion of responsibility—the

extent of drug use among

peers, and parental sociopathy,

that is, parents’ problems with

drinking, drugs, or the police.

Dr. Brook’s group examined 

the risk factors and their implications during childhood, ages 5 to 10; middle adolescence, ages 13 to 18; and late adolescence, ages 15 to 20.

They found that childhood aggression and parental

sociopathy predicted increased levels of drug use in late

adolescence. They also determined that unconventionality

during the early years of adolescence had an “important

and pervasive impact on all aspects of middle and late

adolescent functioning,” including increased drug use.

The research team is now observing the original subjects’

children, beginning at age 2, and interviewing both parents of these children to collect data on the new generation. “So we’re now studying the third generation—the

grandchildren of the mothers [of the original subjects] 

initially studied in 1975,” says Dr. Brook. “And we’re

finding a great deal of consistency down through the 

generations in regards to personality and family characteristics,” including traits that are drug-use risk factors.

The researchers also have studied interactions among risk

factors and their implications for subsequent drug use as

the children grow older. In addition to childhood aggression, they found three additional factors that influence

late-adolescent drug use—unconventionality and drug use

in middle adolescence and parental sociopathy during

childhood. They found that little or no drug use in middle adolescence when combined with conventionality 

during the same age span resulted in the least amount of

subsequent drug use.

As expected, parental sociopathy is related to late-teen

drug use. Parents who drink or use drugs or both may be

the most strict with their children, telling them, “Do as I

say, not as I do,” according to Dr. Brook’s study. These

admonitions might be effective in middle adolescence,

when children are more likely to be influenced by parental

demands, but not in later adolescence, when the family

A number of long range NIDA-funded studies have traced atrisk children into adolescence and beyond trying to determine

why some of them are able to resist influences to use substances

of abuse.
140

has less control and the parents’ own display of negative

behaviors becomes a drug-use risk factor, she says.

Dr. Brook agrees with other researchers that there are

childhood protective factors that can be very powerful

shields to safeguard children and adolescents from the 

recognized risk factors. These protective factors include

achievement, religious commitment, strong family bonds,

and a solid attachment to and emulation of a wholesome

role model, she says.

“Some of these children are remarkably resilient,” says Dr.

Brook. Among those who become successful, she found

evidence of protective factors such as church attendance,

childhood achievement in school or in extracurricular

activities, or close ties to brothers and sisters.

“Many of these kids go on to lead successful, productive

lives, yet we tend to focus on the ones that don’t,” says Dr.

Brook. “I want to learn more about what makes those that

do well do so.”

Family Relationships Critical

Still another continuing study of predictive factors for

drug use focuses on a different population segment—atrisk children of white families living in small and medium-sized communities in Oregon. The study by Dr.

Hyman Hops and colleagues of the Oregon Research

Institute examines family and peer-group influences on

adolescent substance use and is now in its 10th year.

About 500 subjects were ages 11 through 15 at their first

assessment in 1984 and will be 21 through 25 at their last

assessment this year.

Among those studied, 90 percent of subjects who progressed from one substance of abuse to another did so in

the following sequence—abstinence, alcohol, cigarettes,

marijuana, and hard drugs. The most dramatic increase in

drug use occurred between the ages of 13 and 14, when

adolescents are going from middle to high school.

Parents’ use of substances, including cigarettes, is an

important predictive factor influencing their children’s

drug use. Within two-parent families, Dr. Hops found

that fathers’ drinking appears to have a greater impact

than mothers’ drinking on both girls and boys, while

mothers’ drinking has an effect only on adolescents under

14, before they enter high school. Parents who use 

cigarettes and alcohol may influence not only their 

children’s use of the same substances but illicit substances

as well, he says.

Family conflict and strife are strongly associated with

increased substance abuse, based on the researchers’ direct

observations of problem-solving scenarios between parents

and adolescents. Their findings suggest that families with

substance-abusing children typically are unable to easily

resolve problems and that the resulting confrontations

negatively affect drug use.

In examining peer influences, the Oregon researchers balanced each study subject’s self-reports of levels of substance use against reports of his or her substance use level

from the child’s best friend. The scientists reported that

the amount of both family cohesion and peer encouragement to use drugs was predictive of initial levels of

substance abuse. A good family relationship may play a

powerful role as a protective factor in middle and late 

adolescence, they say. On the other hand, peer encouragement to use substances plays a stronger role across the

age range and also suggests that early peer influences may

encourage higher levels of drug use at later ages.

“These findings underscore the importance of family

influences on substance abuse throughout adolescence and

suggest greater attention to the family, as well as the peer

group, in designing prevention strategies,” says Dr. Hops.

“You’ve got to have a healthy family relationship to counter the very powerful peer influences that kids face today.”

Sources

• Andrews, J.A.; Hops, H.; Ary, D.; Tildesley, E.; and

Harris, J. Parental influence on early adolescent substance use: Specific and nonspecific effects. Journal of

Early Adolescence 13:285–310, 1993. 

• Brook, J.S.; Whiteman, M.; Cohen, P.; and Tanaka,

J.S. Childhood precursors of adolescent drug use: A

longitudinal analysis. Genetic, Social, and General

Psychology Monographs 118(2):195–213, 1991. 

• Brook, J.S.; Whiteman, M.; Gordon, A.S.; and

Brook, D.W. The psychosocial etiology of adolescent

drug use: A family interactional approach. Genetic,

Social, and General Psychology Monographs

116(2):113–267, 1990. 

• Brook, J.S.; Whiteman, M.; Hamburg, B.A.; and

Balka, E.B. African-American and Puerto Rican drug

use: Personality, familial, and other environmental risk

factors. Genetic, Social, and General Psychology

Monographs 118(4):417–438, 1992. 

• Ensminger, M.E. Sexual activity and problem behaviors among black, urban adolescents. Child

Development 61:2032–2046, 1990. 

• Ensminger, M.E.; Brown, C.H.; and Kellam, S.G. Sex

differences in antecedents of substance use among

adolescents. Journal of Social Issues 38(2):25–42,

1982. 
141

• Hops, H.; Tildesley, E.; Lichtenstein, E.; Ary, D.; and

Sherman, L. Parent-adolescent problem-solving interactions and drug use. American Journal of Drug and

Alcohol Abuse 16:239–258, 1990. 

• Kellam, S.G.; Brown, C.H.; Rubin, B.R.; and

Ensminger, M.E. Paths leading to teenage psychiatric

symptoms and substance use: Developmental epidemiological studies in Woodlawn. In: Guze, S.B.;

Earls, F.J.; and Barrett, J.E., eds. Childhood

Psychopathology and Development. New York: Raven,

pp. 17–51, 1983. 
Research Findings

142

Volume 10, Number 1 (January/February 1995)

Drug abuse and addiction among women are major public

health problems. More than 4.4 million women currently

use illicit drugs, and women make up more than 37 percent of the illicit-drug-using population. Yet, as with 

the other major diseases of our time, most research 

on addiction has been conducted with men. 

In recent years, the National

Institutes of Health has implemented a new initiative to promote research on women’s health.

To ensure that the field of drug

abuse is in the vanguard of this

exciting new era of women’s health

research, NIDA is expanding its

agenda to increase our understanding of drug abuse and addiction

and their impact on women’s health. Our expanded

research on addiction and women’s health will look at 

differences between men and women who abuse drugs.

Across our entire research portfolio, from basic science to

clinical applications, we will be supporting studies that

examine gender differences in vulnerability and resilience

to drug dependence; in metabolism and the effects of

drugs; in the medical, behavioral, and social consequences

of drug abuse; and in the prevention and treatment of

drug abuse. 

Most of what we already know about women and addiction has come from years of NIDA-supported research on

drug abuse during pregnancy and the impact of a woman’s

drug use on her offspring. This research has been both

needed and appropriate because drug abuse during pregnancy affects the health of more than 5 percent of all

pregnant women and their children, according to NIDA’s

recently released National Pregnancy and Health Survey. 

While continuing NIDA’s research on prenatal drug

abuse, we have been working to broaden the scope of this

research to reflect the fact that drug abuse affects women

regardless of their maternal role. In 1993, NIDA issued

program announcements to stimulate research on the

causes and consequences of drug abuse among women 

of all ages, to assess gender differences in the behavioral

effects of abused drugs, and to promote studies of drug

abuse treatment for women of childbearing age. NIDA’s

AIDS program announcements have addressed partner

notification of HIV-infected drug users and strategies 

to reduce sexual practices that put women at risk of 

contracting HIV. We have held technical reviews at which

researchers discussed methodological issues in the study of

drug abuse among women and the impact of drug abuse

and HIV infection on women and children. And NIDA’s

Medications Development Division has worked to ensure

that the percentages of women in our clinical trial of

potential drug abuse treatment medications reflect the gender makeup of

the drug-abusing population. 

Last September, NIDA’s Women’s

Advisory Committee organized a

landmark conference on drug addiction and women’s health. At the conference, researchers and practitioners

discussed what we know, what we

don’t know, and what we should be

doing to fill the gaps in our knowledge about women and

drug abuse.

In response to recommendations from participants at our

women’s conference, we will be working to conduct more

research on biological and behavioral mechanisms of 

drug abuse among women. And we will be considering

the effects of race, ethnicity, sexual orientation, and

psychological and socioeconomic circumstances on the use

and abuse of drugs by women. 

We also will be expanding our research on how addiction

affects women’s health, including how addiction affects

the progression of AIDS in women. Nearly 70 percent of

AIDS cases among women are related to their use of

injecting drugs or to their having sex with an injecting

drug user. NIDA’s national AIDS community outreach

programs have educated drug-dependent women about

AIDS risk factors and strategies to change their high-risk

behaviors. We are now emphasizing the need to explore

the links between drug abuse and AIDS among women in

all areas of our research agenda. 

We already know that there are differences between men’s

and women’s vulnerability to HIV infection and risk

behaviors. Furthermore, AIDS appears to progress differently in men and women. We need to know why these

differences exist to design more targeted interventions. 

From the time they are diagnosed with HIV infection,

women die of AIDS much more rapidly than men do.

Research findings presented at NIDA’s women’s 

conference suggest this apparent accelerated course of

Filling the Gender Gap in Drug Abuse Research

By Dr. Alan I. Leshner, NIDA Director

We will be expanding our

research on how addiction

affects the progression of

AIDS in women.
143

HIV infection may occur because HIV-positive women

enter treatment at much later stages of infection than men

do. We need more research to find out why women infected with HIV wait so long before presenting themselves for

treatment. Among the possible avenues for gender-based

exploration are the role of social and cultural stigmas and

the availability, accessibility, and appropriateness of AIDS

treatment for drug-dependent HIV-positive women. 

The expanded women’s research program that we have

launched reflects NIDA’s commitment to filling the gender gap that exists in drug abuse research, prevention, and

treatment. To carry out that commitment, we have established a women’s health issues group at NIDA to coordinate and monitor our women’s research efforts. With the

assistance and guidance of scientists, public health and

drug abuse prevention and treatment practitioners, and

the members of NIDA’s national advisory bodies, we will

be working to ensure that research on addiction and

women’s health ultimately reveals the biological and

behavioral factors we need to address to improve drug

abuse prevention and treatment for women. 
Research Findings

144

Volume 10, Number 1 (January/February 1995)

• Almost half of all women in their childbearing years,

ages 15 to 44, have used illicit drugs at least once in

their lives. 

• 10.3 million women age 12 and older have used at

least one illegal drug in the past year. 

• More than 4.4 million women age 12 and older currently use illegal drugs. 

• 4 million women have taken prescription drugs nonmedically during the past year. 

• An estimated 221,000 women who gave birth in the

United States in 1992 used illicit drugs while they

were pregnant. 

• AIDS is now the fourth leading cause of death among

women ages 25 to 44 in the United States. 

• More than 34,000—about 67 percent—of the AIDS

cases among women are drug related. 

Sources

• 1993 National Household Survey on Drug Abuse 

• NIDA National Pregnancy and Health Survey 

• Centers for Disease Control and Prevention

HIV/AIDS Surveillance Report, June 1994. 

About Women, Drug Abuse, and AIDS
Research Findings

145

Volume 10, Number 1 (January/February 1995)

NIDA’s National Pregnancy and Health Survey, conducted

during 1992, is the first national survey of drug use among

pregnant women in the United States. The survey collected

data from a representative sample of the 4 million women

who delivered babies during 1992. Data from the survey,

presented in the chart below, provide the best estimates to

date of the number of American women who use drugs

during pregnancy and their patterns of drug use. 

Drug Use During Pregnancy 

Substance Used Percentage of Pregnant Women Number of Pregnant Women

Any illicit drug1 5.5 220,900

Marijuana 2.9 118,700

Cocaine 1.1 45,100

Crack 0.9 34,800

Other cocaine 0.3 12,700

Methamphetamine 0.1 4,500

Heroin 0.1 3,600

Methadone 0.1 3,400

Inhalants 0.3 12,100

Hallucinogens 0.2 8,700

Nonmedical use of any

psychotherapeutics2 1.5 61,200

Amphetamines 0.0 1,200

Sedatives 0.3 10,300

Tranquilizers 0.0 1,900

Analgesics 1.2 48,700

Alcohol 18.8 756,900

Cigarettes 20.4 819,700

Medical use of any

psychotherapeutics3 10.2 412,300

Amphetamines 0.3 13,400

Sedatives 3.6 144,100

Tranquilizers 1.4 55,400

Analgesics 7.6 305,200

1 Use of marijuana, cocaine (all forms), methamphetamine, heroin, methadone, inhalants, hallucinogens, or nonmedical

use of psychotherapeutics during pregnancy.

2 Nonmedical use of any prescription amphetamines, sedatives, tranquilizers, or analgesics during pregnancy.

3 Medical use of any prescription amphetamines, sedatives, tranquilizers, or analgesics during pregnancy.