NN0058

Research

on Marijuana
Research

on Marijuana

NN0058
ii

Introduction

The National Institute on Drug Abuse (NIDA) supports most of the world’s research on drug abuse and addiction.

NIDA-funded research enables scientists to apply the most advanced techniques available to the study of every aspect of

drug abuse, including:

• genetic and social determinants of vulnerability and response to drugs;

• short- and long-term effects of drugs on the brain, including addiction;

• other health and social impacts of drug abuse, including infectious diseases and economic costs;

• development and testing of medication and behavioral treatments for abuse and addiction; and

• development and evaluation of effective messages to deter young people, in particular, from abusing drugs.

Included in this document are selections of topic-specific articles reprinted from NIDA’s research newsletter, 

NIDA NOTES. Six times per year, NIDA NOTES reports on important highlights from NIDA-sponsored research, 

in a format that specialists and lay readers alike can read and put to use. Selections like the current one are intended 

to remind regular NIDA NOTES readers and inform other readers of important research discoveries during the periods

they cover.

We hope the information contained here answers your needs and interests. To subscribe to NIDA NOTES and for further

information on NIDA’s drug abuse and addiction research, please visit our Web site at www.drugabuse.gov.
iii

Table of Contents

Marijuana Smoking Is Associated With a Spectrum of

Respiratory Disorders (V21-1; October 2006) . . . . . . . 1

MTF Survey Finds Overall Decline in Teen Substance

Abuse (V20-5; April 2006) . . . . . . . . . . . . . . . . . . . . . . 3

Abuse Drops When High School Seniors View 

Marijuana as Dangerous (V20-5; April 2006) . . . . . . . 4

Twin Study Links Marijuana Abuse, Suicide, And

Depression (V20-2; August 2005) . . . . . . . . . . . . . . . . 5

NIDA Intensifies Focus on Marijuana Abuse 

(V20-1; August 2005) . . . . . . . . . . . . . . . . . . . . . . . . . 6

Marijuana-Related Disorders, But Not Prevalence 

Of Use, Rise Over Past Decade (V19-6; May 2005) . . 7

Teen Drug Abuse Continues Its Three-Year Decline 

(V19-6; May 2005) . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Marijuana Abuse: Age of Initiation, Pleasure of 

Response Foreshadow Young Adult Outcomes

(V19-5; January 2005) . . . . . . . . . . . . . . . . . . . . . . . . 10

Early Use of Drugs May Lead to Later Psychiatric

Disorders (V18-5; December 2003) . . . . . . . . . . . . . . 13

Cognitive Deficits in Marijuana Smokers Persist 

After Use Stops (V18-5; December 2003) . . . . . . . . . 15

Twins Study Links Early Marijuana Use to 

Increased Risk of Abuse or Dependence 

(V18-4; November 2003) . . . . . . . . . . . . . . . . . . . . . . 17

Gender and Ethnic Patterns in Drug Use Among 

High School Seniors (V18-2; August 2003) . . . . . . . . 19

Youths’ Opportunities to Experiment Influence Later 

Use of Illegal Drugs (V17-5; January 2003) . . . . . . . . 20

Teen Drug Use Declined in 2002, Report Shows

(V17-5; January 2003) . . . . . . . . . . . . . . . . . . . . . . . . 23

Study Demonstrates That Marijuana Smokers Experience

Significant Withdrawal (V17-3; October 2002) . . . . . 25

Cannabinoid Antagonist Reduces Marijuana’s Effects in

Humans (V17-3; October 2002) . . . . . . . . . . . . . . . . 27

Shortened Family Prevention Programs Yield 

Long-Lasting Reductions in Adolescent Drug Abuse 

(V17-2; May 2002) . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Chronic Marijuana Abuse May Increase Risk of Stroke

(V17-1; April 2002) . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Cognitive Deficits Associated With Heavy Marijuana 

Use Appear To Be Reversible (V17-1; April 2002) . . . 32

Adolescent Treatment Programs Reduce Drug Abuse,

Produce Other Improvements (V17-1; April 2002) . . 34

Television Public Service Announcements 

Decrease Marijuana Use in Targeted Teens 

(V16-4; October 2001) . . . . . . . . . . . . . . . . . . . . . . . 36

Adding Vouchers to Behavioral Therapies Improves

Marijuana Treatment Results (V16-3; August 2001) . . 37

Gender Differences in Prevalence of Drug Abuse Traced 

to Opportunities to Use (V15-4; September 2000) . . 38

Evidence Accumulates That Long-Term Marijuana Users

Experience Withdrawal (V15-1; March 2000) . . . . . . 40

Marijuana-Like Compound in Womb May Influence

Early Pregnancy (V15-1; March 2000) . . . . . . . . . . . . 42

Twin Studies Help Define the Role of Genes in

Vulnerability to Drug Abuse 

(V14-4; November 1999) . . . . . . . . . . . . . . . . . . . . . . 44

MERIT Award Research Helps Reveal Long-term and

Developmental Impact of Drug Abuse 

(V14-1; April 1999) . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Tracking Trends in Teen Drug Abuse Over the Years

(V14-1; April 1999) . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Institute Launches Science Education Campaign for

Middle Schoolers (V13-6; March 1999) . . . . . . . . . . . 50

New NIDA Drug Abuse Education Materials for Middle

School Students (V12-5; September/October 1997) . . 52

Smoking Any Substance Raises Risk of Lung Infections

(V12-1; January/February 1997) . . . . . . . . . . . . . . . . 53

Studies Show Cognitive Impairments Linger in Heavy

Marijuana Users (V11-3; May/June 1996) . . . . . . . . . 55

Marijuana Impairs Driving-Related Skills and Workplace

Performance (V11-1; January/February 1996) . . . . . . 57

Marijuana Antagonist Reveals Evidence of THC

Dependence in Rats (V10-6; November/

December 1995) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Marijuana Smoking Is Associated With a Spectrum of Respiratory

Disorders

Two NIDA-funded studies identify health risks that underscore the importance of curbing marijuana abuse.

By Patrick Zickler, NIDA NOTES Contributing Writer

Research Findings

Volume 21, Number 1 (October 2006)

A large new epidemiological study suggests that marijuana

smoke can cause the same types of respiratory damage 

as tobacco smoke. Significant associations between 

marijuana smoking and a variety of respiratory diseases

also have been confirmed by an extensive review of 

clinical literature.

Monitoring the Effects of Tobacco and Marijuana

Dr. Brent Moore and colleagues at Yale University, the

National Cancer Institute, and the University of Vermont

evaluated data from a nationally representative sample of

6,728 adults. Their analysis indicated that a history of

more than 100 lifetime episodes of smoking marijuana,

with at least one episode in the past month, increased an

individual’s risk of chronic bronchitis, coughing on most

days, wheezing, chest sounds without a cold, and

increased phlegm.

“The most significant difference between tobacco smoke

and marijuana smoke is their principal active ingredients—nicotine in tobacco and delta-9-tetrahydrocannabinol (THC) in marijuana. Beyond that, marijuana contains

at least as much tar and half again as many carcinogens as

smoke from conventional tobacco,” says Dr. Moore.

“Quitting marijuana smoking may benefit respiratory

health as much as quitting cigarettes, in addition to the

clear and considerable health, psychological, and social

benefits of no longer abusing an illicit drug.”

The information Dr. Moore and his colleagues analyzed

was gathered through the third National Health and

Nutrition Examination Survey (NHANES III), conducted

between 1988 and 1994. Participants included 4,789 nonsmokers of either tobacco or marijuana; 1,525 smokers of

tobacco but not marijuana; 320 smokers of both marijuana and tobacco; and 94 who smoked marijuana only. On

average, marijuana abusers had smoked the drug on 10 of

the preceding 30 days, with 16 percent reporting daily or

almost daily smoking. Tobacco smokers consumed roughly

the same number of cigarettes—averaging 19.2 per day—

whether or not they also smoked marijuana. Survey participants answered questions about their experiences of a

range of respiratory symptoms and were examined for

signs of respiratory abnormalities.

The researchers concluded that tobacco smokers who also

smoked marijuana had a higher prevalence of most respiratory symptoms than tobacco-only smokers. Compared

with tobacco-only smokers, however, those who also

smoked marijuana were less likely to have had pneumonia

during the previous year or to show spirometric evidence

of obstructive pulmonary disorder. Commenting on this

finding, Dr. Moore says that it is important to note that

the marijuana smokers in the sample were significantly

younger (average age 31.2 years) than the tobacco smokers

(average age 41.5 years). “The marijuana-related respiratory effects correspond to a relatively young population, and

NHANES III did not ask participants older than age 59

about drug use,” he adds. “It is likely that respiratory

effects will be higher in older marijuana smokers, and,

because of the high prevalence of tobacco use among marijuana smokers, there appears to be an increased risk for

illness due to cumulative effects of smoking both drugs.”

Marijuana’s Long-Term Pulmonary Effects 

Further evidence of marijuana’s respiratory toxicity

emerged from a study conducted by Dr. Donald Tashkin

at the University of California, Los Angeles. Dr. Tashkin

conducted an extensive review of clinical and epidemio1
logical research to determine the extent to which chronic

marijuana smoking might lead to long-term pulmonary

effects and diseases similar to those caused by tobacco.

Unlike the NHANES III data examined by Dr. Moore,

the studies evaluated by Dr. Tashkin made it possible to

assess a possible association between marijuana smoking

and respiratory cancers.

The results of animal and cell culture studies are mixed

with respect to the carcinogenic effects of THC, some

studies showing that THC promotes lung cancer growth

and others showing an anti-tumoral effect on a variety of

malignancies. Although the results of epidemiological

studies are also mixed, a large, recently completed casecontrol study has failed to find a direct link between marijuana use (including heavy use) and lung, throat, or other

head and neck cancers. “Nevertheless, there is evidence

that suggests precarcinogenic effects in respiratory tissue,”

Dr. Tashkin says. “Biopsies of bronchial tissue provide evidence that regular marijuana smoking injures airway

epithelial cells, leading to dysregulation of bronchial

epithelial cell growth and eventually to possible malignant

changes.” Moreover, he adds, because marijuana smokers

typically hold their breath four times as long as tobacco

smokers after inhaling, marijuana smoking deposits significantly more tar and known carcinogens within the tar,

such as polycyclic aromatic hydrocarbons, in the airways.

In addition to precancerous changes, Dr. Tashkin found

that marijuana smoking is associated with a range of damaging pulmonary effects, including inhibition of the

tumor-killing and bactericidal activity of alveolar

macrophages, the primary immune cells within the lung.

Taken together, Dr. Tashkin’s survey of clinical and epidemiological studies and Dr. Moore’s assessment of selfreported and clinically observed effects provide an extensive catalog of respiratory and pulmonary damage associated with marijuana smoking. Smokers are subject to:

• Coughing and phlegm production on most days;

• Wheezing and other chest sounds;

• Acute and chronic bronchitis;

• Injury to airway tissue, including edema (swelling),

increased vascularity, and increased mucus secretion;

and

• Impaired function of immune system components

(alveolar macrophages) in the lungs.

Sources

• Moore, B.A., et al. Respiratory effects of marijuana

and tobacco use in a U.S. sample. Journal of General

Internal Medicine 20(1):33-37, 2005.

• Tashkin, D.P. Smoked marijuana as a cause of lung

injury. Monaldi Archives for Chest Disease 63(2):93-

100, 2005.

• Hashibe, M., et al. Marijuana use and the risk of lung

and aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiology,

Biomarkers & Prevention 15(10):1829-1834, 2006.

2
MTF Survey Finds Overall Decline in Teen Substance Abuse

Research Findings

Volume 20, Number 5 (April 2006)

Substance abuse among teenagers in the United States

declined 19 percent over the past 4 years, with 15.8 percent reporting past-month abuse in 2005, compared with

19.4 percent in 2001, according to the latest Monitoring

the Future Survey. The nationwide survey of 8th-, 10th-,

and 12th-graders found that the overall decline was tempered by increases or unchanged rates of abuse of some

prescription drugs, inhalants, and other substances.

The 4-year decline has been driven largely by decreasing

rates of marijuana abuse. For example, since 2001, pastmonth abuse of marijuana fell by 28 percent among 8thgraders and by 23 percent among 10th-graders. Although

most year-to-year changes in the annual survey are not statistically significant, teen abuse of five substances—GHB,

LSD, MDMA/Ecstasy, methamphetamine, and steroids—

showed significant declines from 2004 to 2005.

The survey findings are encouraging because teenagers are

most vulnerable to the effects of drugs and youths who

abstain in their teen years are less likely to abuse drugs

later in life, NIDA Director Nora D. Volkow, M.D., says.

She notes, however, that teens’ abuse of prescription medications and inhalants has continued unabated in the past

few years. NIDA is particularly concerned about the nonprescribed use of opioid painkillers, such as OxyContin

and Vicodin. In 2005, 9.5 percent of 12th-graders reported abusing Vicodin in the past year, and 5.5 percent

reported OxyContin abuse, which has increased more

than one-third since 2002. “Using these drugs without a

prescription is dangerous. It’s imperative that teens get this

message,” Dr. Volkow stresses.

Abuse of inhalants, which are found in common household substances such as nail polish remover, glue, and

cleaning fluids and are very toxic, also has been rising in

recent years. Abuse among eighth-grade students has

increased significantly since 2002, Dr. Volkow says.

Smoking Decline May Be Tapering Off

Dr. Lloyd Johnston of the University of Michigan, the

principal investigator of the study, notes a worrisome signal that the decline in smoking may be tapering off: The

smoking rate among eighth-graders held steady in the latest survey, following a long-term decline over the past several years. Eighth-graders are considered an important

bellwether of drug-related trends among teenagers.

Moreover, smoking declines in the upper grades also

slowed in 2005. Survey data do not indicate long-term

declines in the abuse of marijuana and other illicit drugs

among 8th-graders, and declines among 10th- and 12thgrade students were very modest, Dr. Johnston notes.

On the positive side, cigarette smoking is at its lowest rate

in the 30-year history of the survey. Also, the proportion

of eighth-graders reporting that they have ever tried to

smoke cigarettes declined in the latest survey, which could

reflect shifts in behaviors and intentions that occurred several years earlier. 

The survey covered

about 50,000 students

in more than 400 public and private schools.

The University of

Michigan conducted

the survey under a

grant from NIDA, 

the National Institutes

of Health, and the

Department of Health

and Human Services.

Further details on 

the survey are 

available at 

www.drugabuse.gov/

DrugPages/MTF.html

and at monitoringthe

future.org.

3
Research Findings

Volume 20, Number 5 (April 2006)

4
Twin Study Links Marijuana Abuse, Suicide, And Depression 

By Patrick Zickler, NIDA NOTES Staff Writer

Research Findings

Volume 20, Number 2 (August 2005)

Men and women who smoked marijuana

before age 17 are 3.5 times as likely to

attempt suicide as those who started later.

Individuals who are dependent on marijuana have a higher risk than nondependent individuals of experiencing major

depressive disorder and suicidal thoughts

and behaviors. The researchers who discovered these relationships, in a recent

NIDA-funded large-scale epidemiological

study, say that although the causes are 

not clear, their findings demonstrate the

importance of considering associated

mental health issues in the treatment and

prevention of marijuana abuse.

Dr. Michael Lynskey and colleagues at the Washington

University School of Medicine in St. Louis, Missouri, gathered data from four groups of same-sex twin pairs (508 identical, 493 fraternal; 518 female, 483 male) enrolled in the

Australian Twin Registry. The groups and findings were:

• Among the 277 pairs who were discordant for marijuana

dependence (that is, one twin but not the other met the

criteria for a diagnosis of marijuana dependence), the

dependent twins were 2.9 times as likely as their nondependent co-twins to think about suicide without

attempting it, and 2.5 times as likely to make a suicide

attempt;

• Among the 311 pairs discordant for early marijuana initiation (just one twin in each pair smoked marijuana

before age 17), the early initiators were 3.5 times as likely as their twins to attempt suicide, but no more likely

to suffer a major depressive disorder (MDD);

• Among the 156 pairs discordant for diagnosis of MDD

before age 17, fraternal but not identical twins with

early diagnosis of MDD were 9.5 times as likely to

develop marijuana dependence; and

• Among the 257 pairs discordant for having suicidal

thoughts before age 17, fraternal but not identical twins

with early suicidal thoughts were 5.5 times as likely as

their twins to become dependent on marijuana.

“Overall, the associations between marijuana abuse and

depressive disorders suggest a relationship that is contributory but not necessarily causal. Depressive disorders in and of

themselves do not cause people to abuse marijuana, and

marijuana abuse and dependence do not of themselves cause

depression or suicidal behavior,” Dr. Lynskey says.

“Nevertheless, clinicians treating patients for one disorder

should take the other into account at initial assessment and

throughout treatment. In the context of treatment, both

need to be addressed, because it is not necessarily the case

that eliminating one disorder will get rid of the other.” The

fact that two of the relationships were observed in fraternal

but not identical twins suggests that the experiences related

in each—marijuana dependence and MDD, and marijuana

dependence and suicidal thoughts—may share a common

underlying genetic basis, notes Dr. Lynskey. 

The associations identified in this study are complex, but

point to a simple policy implication, observes Dr. Lynskey.

“It is important to see that prevention efforts aimed at one

disorder may well have the additional benefit of preventing

or reducing the other,” he says.

“Drug abuse and depression co-occur at rates much greater

than chance and constitute a serious public health concern,”

says Dr. Naimah Weinberg of NIDA’s Division of

Epidemiology, Services and Prevention Research.

“Understanding how each disorder may contribute to the

development and course of the other, and what factors may

underlie their co-occurrence, has important implications for

prevention and treatment of these disabling conditions.

Genetic epidemiologic approaches, such as those applied by

Dr. Lynskey and his colleagues, are very powerful tools to

help parse out the etiologic relationships between co-occurring disorders.”

Source

• Lynskey, M.T., et al. Major depressive disorder, suicidal

ideation, and suicide attempt in twins discordant for

cannabis dependence and early-onset cannabis use.

Archives of General Psychiatry 61(10):1026-1032,

2004. 

5

The study identified relationships between twins’ histories of marijuana abuse and mental health problems.
NIDA Intensifies Focus on Marijuana Abuse

By NIDA Director Nora D. Volkow, M.D.

Research Findings

Volume 20, Number 1 (August 2005)

More than 96 million Americans

have smoked marijuana at least once.

Marijuana abuse is particularly prevalent among adolescents: Of the more

than 2 million people who abuse the

drug for the first time every year,

two-thirds are between 12 and 17

years of age.

The damaging effects of marijuana

fall heavily on adolescents and young

adults. Half of all patients admitted

to treatment for marijuana abuse are

younger than 21. Cognitive impairments caused by marijuana linger a

month or more after an individual’s

last exposure, and the damage is dose

dependent—the more a person

smoked prior to abstinence, the more marked are the deleterious effects on visual perception, verbal and visual

memory, executive function, and manual dexterity, among

other mental capabilities (see “Cognitive Deficits in

Marijuana Smokers Persist After Use Stops,” NIDA

NOTES, Vol. 18, No. 5, p. 8). Loss of social and intellectual growth because of these impairments may have a lifelong impact on a person’s experience and achievement. As

well, compared with teens who never smoke marijuana, a

boy or girl who smokes marijuana before age 17 is more

than twice as likely to abuse opioids, three times as likely

to abuse cocaine or other stimulants, and nearly four

times as likely to abuse hallucinogens later in life (see

“Twins Study Links Early Marijuana Use to Increased Risk

of Abuseor Dependence,” NIDA NOTES, Vol. 18, No. 4,

p. 11). 

NIDA is intensifying efforts to fully understand the effects

of marijuana exposure from the earliest ages through adolescence and young adulthood. This research (see RFA

DA-04-016, “Consequencesof Marijuana Use on the

Developing Brain,” at http://grants2.nih.gov/grants/guide/

rfa-filesRFA-DA-04-016.html) will provide new insight

into the mechanisms by which marijuana affects brain

development, a continuum that begins before birth and

lasts into early adulthood. We are encouraging research

projects that focus on the effect of marijuana during all phases of neurological development, from the neurogenesis and cell differentiation that takes place in the womb to

the refinement of connections among cells

that continues past adolescence. Our

research initiative will produce a fuller

understanding of normative brain development. It also will illuminate the importance

of family and social contexts in adolescence

as well as the differing biological and environmental factors that precede marijuana

use or nonuse.

NIDA also is expanding support of research

to develop treatments for marijuana abuse

(see RFA DA-04-014, “Medications

Development for Cannabis-Related

Disorder,” at http://grants2.nih.gov/grants/guide/rfa-files/

RFA-DA-04-014.html). There is a clear public health need

for interventions to alleviate withdrawal symptoms and to

help chronic abusers deal with social and other factors that

make stopping marijuana abuse difficult. NIDA’s expanded research agenda will encourage development of medications to counter marijuana dependence through animal

studies as well as Phase I and Phase II clinical trials with

humans. Some medications will be aimed at marijuanaassociated disorders such as intoxication, delirium, psychosis, and anxiety. Other medications may address specific aspects of addiction recovery, such as withdrawal, craving, relapse, and complications such as cognitive impairment, sleep disorders, and depression and other mood disorders that often accompany marijuana abuse. 

Successful comprehensive treatment of marijuana-related

disorders will require a multidisciplinary approach.

Therefore, NIDA’s marijuana medications development

initiative will encourage investigation of treatments that

include behavioral intervention. This broad focus, building on the insights to be gained through increased understanding of marijuana’s developmental impact, will help

reduce the health costs and alleviate the damage inflicted

by widespread abuse of this dangerous drug. 

6
7

Marijuana-Related Disorders, But Not Prevalence of Use, 

Rise Over Past Decade

By Patrick Zickler, NIDA NOTES Staff Writer

Research Findings

Volume 19, Number 6 (May 2005)

More Americans suffer from marijuanarelated mental health disorders now than a

decade ago, even though the prevalence of

marijuana smoking has not increased. Survey

results from 2002, compared with data from a

decade earlier, showed that overall, rates of

marijuana consumption in adults 18 and

older held relatively steady at 4 percent of

respondents. However, rates of marijuanarelated disorders—discrete conditions defined

according to criteria established by the

American Psychiatric Association—increased

from 1.2 percent to 1.5 percent of respondents; this means that 37.5 percent of marijuana smokers were affected. The increase was

particularly sharp among young adult black

men and women aged 18-29, among whom

marijuana consumption rose only modestly

while the incidence of disorders tripled. Rates

of marijuana-related disorders among Hispanic men in the

same age span also increased sharply despite only a moderate increase in their rate of marijuana smoking.

“The rise in marijuana-related disorders means that there

were approximately 800,000 more adults in the United

States with marijuana abuse disorder or dependence in

2002 than a decade earlier,” says Dr. Wilson Compton of

NIDA’s Division of Epidemiology, Services and Prevention

Research. “In the 1992 survey, these problems were more

common among Whites than among minorities, but in

2002 the differences in rates among the different ethnic

groups had narrowed, in large part because of increases

that nearly tripled the rate among young African

American men and women and more than doubled the

rate among young Hispanic men.” 

Dr. Compton and colleagues at NIDA, and Dr. Bridget

Grant and colleagues at the National Institute on Alcohol

Abuse and Alcoholism (NIAAA), evaluated data from 

two large, national epidemiologic surveys— the National

Longitudinal Alcohol Epidemiologic Survey (NLAES),

conducted in 1991-1992, and the National

Epidemiological Survey on Alcohol and Related

Conditions (NESARC), conducted in 2001-2002. Both

studies define abuse and dependence using criteria that

match the diagnostic standards found in the Diagnostic

and Statistical Manual of Mental Disorders, 4th Edition

(DSM-IV); see “Defining Marijuana-Related Disorders.”

The study also reveals a shift in marijuana use and its

associated problems among older adults, Dr. Compton

says. “Marijuana smoking increased by 167 percent and

the prevalence of marijuana-related disorders quadrupled

among men and women aged 45 to 64,” he observes.

“Given this shift, the possibility that marijuana may contribute to health problems among the aging population

deserves research attention.” 

The surveys do not explain why disorders increased in

some groups and not in others. However, increased potency of marijuana in the last decade may be partly responsible for the overall upward trend of marijuana-related disorders, the researchers speculate. Regardless of the causes,

the sharp increases among minority groups merit further

investigation, Dr. Compton says. “We see what could be

described as a minor epidemic of marijuana-related disorders going on among young adult minorities. It probably

has been going on undetected for years, and points to the

need for specifically targeted prevention and intervention

efforts.”

Source

• Compton, W.M., et al. Increases in the prevalence of

marijuana use disorders in the United States 1991-

1992 and 2001-2002. JAMA 291(17):2114-2121,

2004. 

Older Americans, Young Blacks, and Hispanic Men Show

Largest Increases in Rates of Marijuana-Related Disorders

Survey data collected 1991-1992 and 2001-2002 show little increase over the

decade in rates of marijuana smoking, but overall prevalence of marijuana-related

disorders increased by 22 percent. Increases in a few demographic groups accounted

for most of this increase.
8

Research Findings

Volume 19, Number 6 (May 2005)

Teen Drug Abuse Continues Its Three-Year Decline

Illicit drug abuse among the Nation’s

youth declined by almost 7 percent

from 2003 to 2004, continuing an

encouraging trend that began in

2001. At the same time, the latest

report from the Monitoring the

Future (MTF) survey shows a recent

increase in the abuse of inhalants

among eighth graders and the

painkiller OxyContin among all

students surveyed. 

Overall, the trends in the past 3 years have been positive,

with a decline in past-month drug abuse among 8th,

10th, and 12th graders combined from 19.4 to 16.1 percent. This reduction translates into roughly 600,000 fewer

adolescent drug abusers than in 2001, advancing the goal

President George W. Bush set in February 2002 to reduce

drug use among youth by 25 percent in 5 years. The 2004

findings emerged from responses provided by nearly

50,000 students in 406 public and private schools across

the country. In addition to declines in past-month use,

students’ past-year use fell from 31.8 to 27.5 percent; their

lifetime use dropped from 41.0 to 36.4 percent between

2001 and 2004. 

“Drug use is preventable. The overall reduction in drug

abuse by America’s young people shows the power of partnership among all working to address the problem—from

scientists developing basic knowledge to people implementing services in the community to those making policy at all levels,” said NIDA Director Dr. Nora D. Volkow.

“Our concerted effort to provide students, teachers, and

families with accurate information about addiction and

drug abuse have had an impact, but we must sustain and

advance this work to realize further reductions in drug

abuse.”

The MTF survey, launched in 1975, measures drug,

alcohol, and cigarette abuse and attitudes about use

among 8th, 10th, and 12th graders nationwide. Funded

by NIDA, the survey has been conducted annually since

its inception by the University of Michigan’s Institute for

Social Research. Now in its 30th year, MTF questions

and analyses have changed with informational needs—for

example, expanding the list of drugs, analyzing data for 

all three grades combined, tracking students’ attitudes

toward drug abuse, and examining the impact of anti-drug

advertising. Although generally positive, this year’s MTF results for two

drugs raise concerns and bear close

monitoring. 

Lifetime abuse of inhalants among

eighth graders increased from 15.8

to 17.3 percent between 2003 and

2004. The survey showed that 8th

and 10th graders’ perceptions of

the risks associated with abusing

inhalants has declined in the past 3

years, suggesting a need to increase awareness of the

potentially dangerous consequences of abusing these often

inexpensive and easily obtainable intoxicants. The number

of high school students using the painkiller OxyContin

without medical supervision increased from 2002 to 2004.

Past-year abuse of this drug—an opioid with a high

potential for addiction—was disturbingly common at 1.7,

3.5, and 5.0 percent for grades 8, 10, and 12, respectively.

Key substance abuse patterns that emerged between 2001

and 2004 are:

• Cigarettes. Smoking among teenagers continues to

decline from peak levels in the mid-1990s, although

more slowly than in the past 8 years. Lifetime and

current abuse of cigarettes declined among 8th, 10th,

and 12th graders. Lifetime cigarette abuse dropped

19.5 percent, from 49.1 to 39.5 percent, and current

abuse fell 20.3 percent, from 20.3 to 16.1 percent.

• Marijuana. Abuse of marijuana declined significantly.

Current abuse declined 18.1 percent, from 16.6 to

13.6 percent; past-year abuse also declined 13.7 percent, from 27.5 to 23.7 percent; and lifetime abuse

declined 11.2 percent, from 35.3 to 31.3 percent. In

the past 2 years, students’ perceived risk of abusing

marijuana increased markedly; the proportion of teens

reporting that it would be easy for them to get the

drug also declined in recent years.

• Amphetamines. Abuse of this class of drug without

medical supervision has been widespread among

youth in the past, but has been gradually declining.

Lifetime abuse fell 19.6 percent—from 13.9 to 11.2

percent. Both past-year and current abuse fell as well,

from 9.6 to 7.6 percent and from 4.7 to 3.6 percent,

respectively.
9

• LSD and MDMA (Ecstasy). Students’ abuse of the

hallucinogens LSD and MDMA plummeted between

2001 and 2004. Lifetime abuse of LSD fell 55 percent, from 6.6 to 3.0 percent, and past-year and current abuse both dropped by approximately 60 percent. Lifetime use of MDMA dropped 40.7 percent,

with past-year and current abuse falling by more than

half, from 5.5 to 2.5 percent and 2.3 to 0.9 percent,

respectively. In the late 1990s and until 2001, the

sharp increase in the abuse of MDMA among teens

was a concern. Increases in students’ perceived risk of

abusing the drug preceded the decreases in abuse seen

since 2001. 
Marijuana Abuse: Age of Initiation, Pleasure of Response

Foreshadow Young Adult Outcomes

By Robin Eisner, NIDA NOTES Contributing Writer 

Research Findings

Volume 19, Number 5 (January 2005)

A boy or girl who is smoking marijuana at 13 is likely to

earn less money as a young adult than peers who aren’t

abusing the drug. An adolescent who smokes less marijuana than a friend but enjoys the experience more is likelier

to be addicted to the drug at 21. These are findings from

two recent studies that looked at adult outcomes associated with marijuana abuse in adolescence.

Dr. Phyllis L. Ellickson and colleagues at the RAND

Corporation in Santa Monica, California, surveyed 5,800

adolescents from 30 schools in California and Oregon

about their marijuana use between ages 13 and 23. A 

statistical analysis of the responses revealed four distinct

patterns related to marijuana abuse.

Approximately 45 percent did not smoke marijuana. The

researchers called these youths Abstainers. Of those who

did smoke marijuana:

• Some 5 percent were considered Early High Users—

teens who smoked marijuana from once a week to

monthly at age 13, decreased their abuse by age 18,

and as young adults smoked 3 to 10 times a year.

• About 17 percent were Stable Light Users—teens who

smoked infrequently at age 13 and never abused the

drug more than 10 times a year, on average. 

• Occasional Light Users made up 53 percent of the marijuana-abusing population. They were similar to

Stable Light Users but started after age 13 and abused

lower amounts than Stable Light Users throughout

the study period. 

• Steady Increasers, approximately 25 percent of the

abusers, started after age 13 and increased their usage

during the study period. 

The researchers found that the Early High Users lagged

behind all other groups in earnings and education when

resurveyed at age 29. Their average yearly earnings were

$20,940, compared with about $32,000 for the

Occasional Light Users and Abstainers and $28,140 for

the Steady Increasers. Both groups that initiated marijuana

abuse by age 13 reported less schooling than Abstainers

and those who first smoked after age 13: Early High Users

and Stable Light Users did not usually go to college, while

Steady Increasers completed on average one year of college, Occasional Light Users almost two years of college,

and Abstainers, almost three years of college.

“The bad news is that if you start marijuana use by age

13, even if you eventually decrease your usage, you are

likely to have a lower income and lower level of schooling

by age 29,” Dr. Ellickson says. “The good news is that 45

percent of the youths in our sample did not use marijuana

between adolescence and emerging adulthood. We need to

understand what helped those kids abstain over time.” Dr.

Ellickson says although her findings show an association

between marijuana abuse and reduced income and educational performance, they do not prove that marijuana contributes causally to those outcomes, which result from

multiple factors. The results also suggest that delaying initiation of marijuana abuse does not necessarily guarantee

better outcomes, especially if the late starters escalate

abuse. Youths who started after age 13, but steadily

increased their marijuana use during and after high

school, abused marijuana more than any other group as

young adults, smoking 3 to 10 times during the past

month on average. In young adulthood, the late starters

who intensified their use of marijuana also abused other

illegal drugs at rates similar to those of the early starters,

with 32 percent admitting to past-year abuse of illegal

drugs besides marijuana.

10

Relationship Between Number of Positive

Responses to Marijuana and Later Addiction

Positive Responses Marijuana-Addicted Subjects

0 5.2%

1 8.5%

2 13.3%

3 19.9%

4 28.7%

5 39.1%

Researchers examined whether teens’ positive responses to marijuana were related to later marijuana addiction. Positive responses

noted by participants included “got really high,” “felt happy,” “felt

relaxed,” “did silly things,” and “laughed a lot.” Almost 40 percent

of teens with five positive responses were addicted to marijuana

between ages 16 and 21 compared with 5.2 percent of those who

had no positive response.

Source: Fergusson, D.M.; Horwood, L.J.; Lynskey, M.T.; and Madden, P.A.F. (2003).
The patterns of abuse revealed by the study suggest that

interventions against marijuana abuse may be important

from primary school through to high school graduation,

says Dr. Kathleen Etz, of NIDA’s Division of

Epidemiology, Services and Prevention Research.

“At each stage, the goal will be to prevent children who

are at risk from initiating use, and to persuade any who

have already started to reduce or quit,” Dr. Etz says. “The

counseling ideally would educate children about the

potential problems of marijuana abuse and address 

the broad goal of self-awareness leading to healthy life

choices.”

Positive Initial Response Linked to Later Dependence

In the second study, led by Dr. David Fergusson of the

Christchurch School of Medicine and Health Sciences in

Christchurch, New Zealand, researchers found that positive emotional responses to initial marijuana abuse predicted later

addiction to

the drug better than did

the amount of

marijuana

smoked. The

researchers

worked with

data from the Christchurch Health and Development

study, a 21-year longitudinal project that followed a group

of children born in the city from birth through adolescence. Dr. Fergusson’s analysis included 1,011 of these

youths.

When the study participants were 15 or 16, they answered

a series of interview questions about their cannabis exposure in the preceding year. These included their frequency

of abuse as well as feelings about their most recent experience: Did they get “really high,”

feel happy, feel relaxed, do silly

things, laugh a lot, feel ill or

dizzy or frightened, or pass out?

In this first interview, 20 percent of those later included in

Dr. Fergusson’s study had

abused marijuana. Study participants were interviewed again at

ages 18 and 21. By then,

approximately 9 percent reported signs of being addicted to

marijuana; the prevalence

among those who started before

age 16 was 21.7 percent. Almost

half (46.7 percent) of those who

had reported five or more pleasurable responses to the drug in

the first interview reported

being addicted by age 21, compared with 3.9 percent of those

reporting no positive responses.

The results indicate that the

pleasure of early use, not how

much marijuana is used, determines the likelihood of later

addiction. “There are people

smoking a lot of marijuana who

aren’t addicted to it,” Dr.

Fergusson explains. “Others are

smoking less but are addicted or

headed for addiction.”

Dr. Fergusson says his findings

parallel those of studies on cigarette smoking and alcohol use

11

“At each stage, the goal

will be to prevent children

who are at risk from 

initiating use.”

Marijuana Abstainers Enter Adulthood Ahead

Note: Means/percentages are adjusted for sex, race/ethnicity, parental education, and nuclear family.

A result marked by a represents a significantly more favorable outcome such that a > b > c > d > e.

Same-letter superscripts in each row indicate no statistically significant differences between those entries. 1

Averages based on a scale of 1 to 5, with 1 indicating poor and 5, excellent. 2

Values ranged from 1 indicating 8th grade or less, to 11 indicating an advanced professional degree.

3

Based on a five-category index: 0 indicates no use; 1, < 3 times; 2, 3-10 times; 3, 11 times; and 4, 

> 11 times and 6 or more days in the past month.

Early High 

Users 

n=37

Steady

Increasers 

n=336

Stable Light

Users 

n=171

Occasional

Light Users 

n=753

Abstainers 

n=1,229

Overall Health1 3.53c 3.82b 3.86b 3.89b 4.03a

Mental Health1 3.64ab 3.67b 3.82ab 3.72b 3.84a

Life Satisfaction1 3.88b 3.99b 4.03b 4.10b 4.27a

Educational

Attainment2 5.56d 6.48c 5.99d 6.89b 7.43a

Yearly Earnings

($ in thousands)

20.94c 28.14b 27.71b 32.29a 31.93a

“Yes” to Past-Year

Other Drug Use

27.4%c 31.9%c 30.3%c 18.3%b 8.5%a

Frequency of PastMonth Marijuana Use3 .90c 2.17e 1.32d .53b .14a

Outcomes of Five Marijuana User Groups at Age 29

Source: Ellickson, P.L.; Martino, S.C.; and Collins, R.L. (2004).
among adolescents, which suggest that initial subjective

response to a drug might be a behavioral marker for biological addiction-vulnerability. This growing body of

research indicates that vulnerable individuals seem to

experience enhanced sensitivity to a drug’s positive effects,

diminished sensitivity to its negative effects, or a combination of the two responses.

Dr. Wilson Compton, director of the Division of

Epidemiology, Services and Prevention Research at the

National Institute on Drug Abuse, says that research in

animals has revealed genetic differences between those that

prefer alcohol and those that do not. Similar research

might identify the neurobiological factors underlying differences in the response to marijuana, perhaps eventually

leading to risk-reduction treatments, says Dr. Compton.

Sources

• Ellickson, P.L.; Martino, S.C.; and Collins, R.L.

Marijuana use from adolescence to young adulthood:

Multiple developmental trajectories and their associated outcomes. Health Psychology 23(3):299-307, 2004.

• Fergusson, D.M.; Horwood, L.J.; Lyndskey, M.T.;

and Madden, P.A.F. Early reactions to cannabis predict later dependence. Archives of General Psychiatry

60(10):1033-1039, 2003. 

12
Early Use of Drugs May Lead to Later Psychiatric Disorders

By Jill Schlabig Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 18, Number 5 (December 2003)

One of the challenges of research into comorbidity—the

co-occurrence of substance abuse and mental disorders—is

determining the order in which these disorders occur and

the factors that they share. Recent findings from a longitudinal study that followed more than 700 individuals from

early childhood into their late twenties now confirms one

sequence of events in the comorbidity conundrum.

Dr. Judith S. Brook and Dr. David W. Brook of New

York’s Mount Sinai School of Medicine and Dr. Patricia

Cohen of Columbia University, also in New York, provide

evidence that substance abuse significantly predicts the

later occurrence of psychiatric disorders, including major

depressive disorder (MDD), alcohol dependence, and substance use disorders (SUDs). Moreover, their findings suggest that there are common risk factors for both substance

abuse and MDD and that once abuse begins, it becomes

an additional risk factor for MDD.

“Most studies obtain data on psychiatric disorders and

drug abuse simultaneously, so it’s almost impossible to

determine which came first,” says Dr. Judith Brook. “This

longitudinal data set is unique because it follows one

group of people through their lives, collecting data roughly every 5 years on drug abuse patterns, psychiatric disorders, and other factors. This approach allows us to study

the progression of drug abuse, how it affects a person’s

functioning, and how it relates to subsequent psychiatric

disorders.”

Researchers from the City University of New York randomly selected 736 survey participants in 1975 as part of

an effort to identify the health needs of children in Albany

and Saratoga, New York. The ratio of boys to girls in the

study reflected that of the population of children in both

cities, as did the level of family intactness, family income,

and parents’ education level. The children were, on average, 6 years old when the study began.

Eight years later, Dr. Judith S. Brook and Dr. Cohen

acquired the original data set and study population with

support from NIDA and the National Institute of Mental

Health (NIMH). Subsequent interviews were completed

at approximately 5-year intervals. Participants were asked

about tobacco, alcohol, marijuana, and other illicit drug

abuse during each set of interviews, and psychiatric disorders were measured.

“Overall, alcohol and substance abuse during the early

years was significantly related to later psychiatric disorders,

even after we statistically controlled for age, sex, parents’

education level, family income, and episodes of prior psychiatric symptoms,” says Dr. Brook. “The cumulative frequency of substance abuse from childhood through early

adulthood is strongly associated with episodes of MDD,

alcohol dependence, and SUDs in the late twenties.”

Earlier marijuana and tobacco use were each more strongly related to participants’ development of MDD in their

late twenties than more recent use of these substances.

However, the opposite was true for alcohol use and other

illicit drug use—recent use was more strongly related to

development of MDD in the late twenties. The relationship between earlier use of all four substances—tobacco,

alcohol, marijuana, and other illicit drug use—was more

13

Early Substance Abuse Increases Likelihood of

Developing Psychiatric Disorders in Late Twenties

0

10

20

30

40

50

60

70

80%

SUDs

Alcohol

Dependence

MDD

Other Illicit

Drugs

Tobacco Alcohol Marijuana

Substances Abused in Childhood,Adolescence,

and/or Early Twenties

Increased Likelihood of Psychiatric

Disorders in Late Twenties

Longitudinal study participants who abused tobacco, alcohol, 

marijuana, and other illicit substances in earlier years were more

likely to have diagnoses of major depressive disorder (MDD), 

alcohol dependence, or substance use disorders (SUDs) in their late

twenties.
strongly related in every case to later alcohol dependence

or SUDs than to later episodes of MDD.

Dr. Brook cites results related to marijuana use as a particularly key finding. Earlier marijuana use showed substantial effects on later incidence of MDD, alcohol dependence, and SUDs—17, 23, and 40 percent more likely,

respectively. “Use of marijuana during childhood and adolescence should not be treated as benign, but rather may

signal the later development of MDD, alcohol dependence, and SUDs,” she says.

Treatment providers may benefit by considering the relationship between early substance abuse and later psychiatric disorders. “Well-coordinated interventions against

the earliest use of drugs may alleviate the physiological

and psychosocial problems that are related to adult psychiatric disorders,” says Dr. David W. Brook.

Dr. Leslie Cooper of NIDA’s Division of Epidemiology,

Services and Prevention Research agrees that the findings

in this study are significant. She cautions, however, that

results must be interpreted carefully because the study

sample is 92 percent white, with 93 percent of the participants having received at least a 12th-grade education.

Although the sample is not representative of the general

population, it was representative of the Northeast’s population when the data were originally collected, she notes.

“This longitudinal data set is extremely valuable because it

allows us to track the relationship between early drug

abuse and later psychiatric disorders,” Dr. Cooper says.

“But we can’t generalize these results to other populations.

We need to build on this study and gather information on

other populations.”

Dr. Brook will continue collecting data on this cohort

every 5 years. “We will be able to watch these individuals

as they move into their thirties and forties and see how

earlier substance use affects their functioning at that age.

We can also look at transmission across generations: How

will the children of participants fare?”

Source 

• Brook, D.W.; Brook, J.S.; et al. Drug use and the risk

of major depressive disorder, alcohol dependence, and

substance use disorders. Archives of General Psychiatry

59(11):1039-1044, 2002. 

14
Cognitive Deficits in Marijuana Smokers Persist After Use Stops

By Jill Schlabig Williams, NIDA NOTES Contributing Writer 

Research Findings

Volume 18, Number 5 (December 2003)

NIDA-funded scientists have found that cognitive impairments resulting from smoking marijuana can last up to at

least 28 days after an individual last smoked the drug. The

more a person had smoked prior to abstinence, the more

profound this impairment, with marijuana smokers with

lower IQs faring worse than their higher IQ peers, even if

the latter had routinely smoked more of the drug.

NIDA-funded researchers Dr. Karen Bolla from the Johns

Hopkins University School of Medicine in Baltimore and

Dr. Jean Lud Cadet from NIDA’s Intramural Research

Program (IRP) admitted marijuana smokers to IRP’s

Clinical Inpatient Research Unit on Hopkins’ Bayview

campus, tested them to ensure they abstained from marijuana use throughout their 4-week stay, and gave them a

battery of neurocognitive tests at the end of the study.

Twenty-two individuals participated. Their average age

was 22, 86 percent were male, and all reported consuming

fewer than 14 alcoholic drinks a week. The researchers

estimated that the group had been smoking marijuana for

an average of 4.8 years. Based on participants’ reports of

their current levels of marijuana use, the researchers

grouped them as light, medium, or heavy smokers.

“Determining an exposure index—how many joints participants smoked per week--and looking at the range of

use in the study population strengthened our ability to

make causal inferences,” says Dr. Bolla.

Very heavy abusers smoked an average of 94 joints a week

and scored worse than light abusers (average 11 joints per

week) on 24 of the 35 neurocognitive tests, even after 28

days of abstinence. The measures on which the heavy

abusers had comparative deficits included verbal and visual memory, executive functioning, visual perception, psychomotor speed, and manual dexterity. On some tests,

quantity of marijuana use accounted for more than half

the variance in test scores. “We found a dose-response

relationship,” says Dr. Bolla. “The more marijuana people

used, the worse they performed on the tests, especially

those for memory.”

“We know a lot about the acute effects of marijuana use,

but researchers are just now beginning to look at the longterm effects,” says Dr. Jag Khalsa of NIDA’s Center on

AIDS and Other Medical Consequences of Drug Abuse.

“This study demonstrates that marijuana smoking has

chronic, dose-related effects on cognitive impairments up

to 28 days after last use. But how long do these effects

persist beyond that point? That’s something we have to

examine.”

“We have shown that marijuana use is associated with 

persistent detrimental cognitive effects,” explains Dr.

Bolla. “These results are not attributable to use of other

drugs, because participants were excluded for current or

past history of significant use of other substances, including alcohol. Marijuana appears to be harmful when

smoked in very large quantities.”

The study results also suggested that some people are 

at higher cognitive risk from smoking marijuana than others. Cognitive performance in individuals with lower IQ

scores decreased as the number of joints smoked per week

increased, while those with higher IQ scores had fewer

decrements even as marijuana use increased. “This finding

demonstrates the concept of cognitive reserve,” says 

Dr. Bolla. “People with higher IQs do better than those

with lower IQs; the fewer cognitive reserves you have, 

the more impact you will see from a slight change in brain

function.”

The results of this study are consistent with study findings

obtained by Dr. Harrison Pope, Jr., at Harvard University

McLean Hospital in Belmont, Massachusetts (see “Studies

Show Cognitive Impairments Linger in Heavy Marijuana

Users,” NIDA NOTES, Vol. 11, No. 3). Dr. Pope and his

colleagues found that memory and learning problems

caused by heavy marijuana smoking lasted for at least a

week after use stopped, although the problems disappeared within a month. “Since marijuana has a half-life of

4 days, the neurocognitive effects seen in Dr. Pope’s study

after 7 days indicate that marijuana does have residual

effects,” says Dr. Khalsa. “Study differences in longer 

term effects could be explained by differences in the study

population.”

In the Harvard study,” Dr. Bolla notes, “participants were

older, ranging from age 30 to 55; had higher IQs; were

more affluent; and were more likely to be employed. Our

inpatient study was conducted in the inner city with a

younger, poorer population that used marijuana more

heavily. Plus, Dr. Pope measured lifetime episodes of

smoking marijuana, not the current number of joints

smoked per week.” In Dr. Bolla’s study, duration of use

was associated with a decrease in performance on just one

neurocognitive test, which measured participants’ ability

to copy a complex figure.

15
Source 

• Bolla, K.I., et al. Dose-related neurocognitive effects of

marijuana use. Neurology 59(9):1337-1343, 2002. 

16

Severity of Cognitive Deficits Varies by Level of Marijuana Use

Verbal Memory. In tests of logical memory, participants were read a paragraph and then asked questions

about it immediately and again after 30 minutes. The

Rey Auditory Verbal Learning Test (RAVLT) involved 

listening to 15 words and then repeating them either

immediately (Trial 1) or after 30 minutes. The response

patterns suggest difficulty with information recall, not

with the acquisition or retention of information, according to the researchers. 

Scores

0

10

20

30

40

50

Delayed

 Immediate

Light Medium Heavy

Logical Memory

Scores

0

5

10

15

Delayed

Trial 1

Light Medium Heavy

RAVLT

Level of Use Level of Use

Heavy marijuana users scored below light users on all measures of

verbal memory, although they had no problems recognizing previously learned material.

Visual Memory. In the Symbol-Digit Paired Associate

Learning test, seven flash cards featuring a symbol and 

a number were displayed; test subjects were then shown

only the symbol and asked to supply the number that 

originally accompanied that symbol. In the Rey Complex

Figure tests, participants were shown a complex figure and

asked to draw it from memory.

Scores

0

10

20

30

40

Light Medium Heavy

Rey Complex Figure

Scores 0

5

10

15

20

25

Light Medium Heavy

Symbol-Digit Paired 

Associate Learning

Level of Use Level of Use

Heavy marijuana use affected visual learning and memory.

Executive Cognitive

Functioning. In the

Wisconsin Card Sorting

Test (WCST), participants

are asked to sort cards by

three different concepts

that the tester changes. This

exercise tests the subject’s

ability to switch cognitive

sets based on feedback.

Poor performance indicates

difficulty incorporating

feedback to guide and

change incorrect response

selection. 

Scores

0

10

20

30

40

Errors

Categories completed

Light Medium Heavy

Executive Cognitive 

Functioning (WCST)

Level of Use

Greater marijuana use was 

associated with lesser executive

cognitive functioning. 

Heavy marijuana users showed

slower reaction times on a test of

simple reaction time.

Heavy marijuana use was associated with lower performance on

manual dexterity measures.

Psychomotor Speed.

Participants were given the

California Computerized

Assessment Package 

(CALCAP) to measure their

psychomotor speed. In this

test, they were asked to hit

a button when they saw a

light flash. Reaction time

measured the milliseconds

that elapsed between the

light flashing and the 

participant hitting the 

button.

Reaction Time Elapsed in msec

0

100

200

300

400

500

Light Medium Heavy

Psychomotor Speed

Level of Use

Manual Dexterity.

For this test, participants were asked to tap

a finger on their left

hand. Manual dexterity

was determined by the

number of taps made in

10 seconds. # of Finger Taps/10 s

0

10

20

30

40

50

Light Medium Heavy

Manual Dexterity

Level of Use
Twins Study Links Early Marijuana Use to Increased Risk of 

Abuse or Dependence

By Patrick Zickler, NIDA NOTES Staff Writer 

Research Findings

Volume 18, Number 4 (November 2003)

Many genetic, biological, and environmental factors can

influence whether and when an individual initiates drug

abuse or develops drug dependence or addiction. One tool

that helps scientists isolate and evaluate the effect of different factors is research on twins, who share many inherited biological traits and environmental influences. In a

study of more than 300 pairs of same-sex twins, NIDAsupported investigators found that smoking marijuana

before age 17 is linked to a greater likelihood of proceeding to serious problems with marijuana or other drugs. 

“This finding underlines the significance of early drug initiation,” says Dr. Wilson Compton, director of NIDA’s

Division of Epidemiology, Services and Prevention

Research. “Identical twins had the same inherited biological characteristics, and fraternal twins shared half their

genes. All the twins had common family influences and

social environments. Even though they had so much in

common, something influenced one twin to take drugs

earlier than the other, and that difference had a profound

impact on later experience with drugs.”

The same-sex twin pairs grew up in the same households

and attended the same schools. In each pair, one twin

smoked marijuana before his or her 17th birthday and the

other did not. “When we interviewed the twins as adults,

the early users were more than twice as likely to have

taken other illicit drugs. They also were from two to five

times more likely to move on to abuse or dependence on

alcohol, marijuana, stimulants, opioids, or sedatives,” says

Dr. Michael Lynskey, who conducted the study with colleagues at the Washington University School of Medicine

in St. Louis, Missouri; the Queensland Institute of

Medical Research in Brisbane, Australia; and the

University of Missouri in Columbia.

The researchers asked both members of 2,765 twin pairs

included in the Australian Twin Register if they had ever

smoked marijuana and, if so, how old they were when

they smoked it for the first time. The researchers identified 311 pairs of same-sex twins (average age 30) in which

one twin first smoked marijuana before age 17 and the

other twin had either never smoked the drug (77 pairs) or

did so for the first time at age 17 or older (234 pairs). Of

the 311 twin pairs, 136 (74 female, 62 male) were identical and 175 (84 female, 91 male) were fraternal. The

interviews were conducted by phone in Australia and the

data analyzed by scientists at Washington University and

the University of Missouri.

The investigators defined “use” as drug taking on one or

more occasions for a nonmedical reason. The researchers

defined “abuse” and “dependence” according to criteria

adapted from the Diagnostic and Statistical Manual of

Mental Disorders, Fourth Edition (DSM-IV). Abuse was

understood to involve taking the drug in physically hazardous situations or circumstances that interfered with

major obligations. According to the DSM-IV criteria,

twins described as drug- or alcohol-dependent had two or

17

Researchers investigated the drug use patterns of same sex twin pairs

in which one twin first smoked marijuana before age 17 and the

other either never smoked marijuana or first smoked the drug at

age 17 or older. As adults (average age 30), those who had smoked

before age 17 were more likely than their siblings to have used

other illicit drugs and to develop symptoms of abuse or dependence

on marijuana, cocaine or other stimulants, opioids, or sedatives.
more of the following symptoms: needing increasingly

larger amounts to achieve drug effect, using for longer

periods or more frequently than intended, and continuing

to use despite associated emotional problems or recurrent

desire to cut down use.

Overall, the researchers found, twins who smoked marijuana before age 17 were more than twice as likely as their

sibling to use opioids, three times as likely to use sedatives,

three times as likely to use cocaine or other stimulants,

and nearly four times as likely to use hallucinogens. Those

who smoked marijuana before age 17 also were from 1.6

to 6 times as likely to have reported abuse or dependence

on alcohol or an illicit drug. Nonetheless, Dr. Lynskey

points out, the majority (52 percent) of twins who

smoked marijuana before age 17 did not go on to develop

abuse or dependence. The increased odds of using other

drugs or for developing abuse or dependence were not

greater for identical than for fraternal twins, nor for males

or females.

“While these study findings indicate that early marijuana

use is associated with increased risk of progression to other

illicit drug use and possibly to drug abuse or dependence,

it is not possible to draw strong causal conclusions solely

on the basis of these associations,” Dr. Lynskey cautions.

Additional research in other cultures, using a range of

research designs, will be needed to determine the causes of

the association, he says.

“Given that early initiation of marijuana smoking appears

to be associated with increased risks,” says Dr. Lynskey,

“there is a need for greater physician awareness of those

risks. Focused interventions also are needed to prevent

escalation to use of other drugs among young people identified as being at risk.”

Source

Lynskey, M.T., et al. Escalation of drug use in early-onset

cannabis users vs. co-twin controls. Journal of the

American Medical Association 289(4):427-433, 2003. 

18
Gender and Ethnic Patterns in Drug Use Among High School

Seniors

Research Findings

Volume 18, Number 2 (August 2003)

Although rates of marijuana, alcohol,

and tobacco use by 12th-grade boys

and girls declined over the 25-year

period ending in 2000, the “gender

gap” in use of these drugs remained

largely unchanged. According to data

compiled by the annual Monitoring

the Future (MTF) survey, senior girls

were 77 percent as likely as boys (compared with 78 percent in 1976) to have

reported using marijuana in the past

month. Girls in the 12th-grade class of

2000 were 64 percent as likely (up

from 54 percent in 1976) to have had

five or more drinks in a row during the

past 2 weeks, and girls and boys were

equally likely to be daily smokers.

Ethnic differences in drug use—for

boys as well as girls—are much wider

than are gender differences. A recently

published review of MTF data reveals

that these ethnic differences are significant and have persisted since MTF

began collecting drug use data in

1976. Key substance use patterns

among ethnic groups and gender differences within those groups are presented below.

Smoking

Daily smoking declined among all ethnic groups between

1976 and 1990, then leveled off before beginning to

increase modestly between 1996 and 2000. Among ethnic

groups, Native Americans were most likely to smoke and

African Americans least likely. Within ethnic groups,

African-American girls were less likely than boys to be

daily smokers.

Alcohol

Girls were less likely than boys to report heavy alcohol use

(five or more drinks in a row within the past 2 weeks),

and the prevalence for girls and boys over the 25-year

period ending in 2000 generally decreased. Among ethnic

groups, Native Americans were most likely to report heavy

drinking; Asian-American and African-American 12thgraders reported the lowest prevalence. No significant 

gender differences in alcohol use emerged within ethnic

groups.

Marijuana

Overall, 12th-grade boys in all ethnic groups were somewhat more likely than girls to have used marijuana within

the past 30 days. Prevalence rates for girls and boys

declined between 1976 and 1990, held steady until 1995,

and increased between 1996 and 2000. Among ethnic

groups, Native Americans were most likely and Asian

Americans least likely to have used marijuana within the

past month.

Source

• Wallace, J.M., et al. Gender and ethnic differences in

smoking, drinking and illicit drug use among

American 8th, 10th and 12th grade students, 1976-

2000. Addiction 98(2):225-234, 2003. 

19

Substance Use Among High School Seniors, 1976-2000*

Daily Cigarette Smoking

White 28.8 23.6 22.6 22.2 27.2 24.4 18.6 19.2 22.3 26.3

Black 20.8 12.2 5.8 3.4 5.1 21.9 10.8 7.7 6.5 10.9

Mexican American 15.6 13.2 8.4 9.3 11.0 19.1 13.2 11.8 12.6 15.1

Puerto Rican/** 15.2 17.9 22.5 23.4

Other Latin American 10.8 9.8 8.9 15.3

Asian American 13.3 10.2 8.0 8.6 10.1 14.5 11.5 10.8 12.9 14.3

Native American 49.8 39.8 30.5 34.2 34.2 38.7 30.8 25.7 32.4 24.7

Heavy Alcohol Use Within Past 2 Weeks

White 32.1 34.1 30.8 24.6 28.0 53.4 52.9 46.8 39.7 42.4

Black 12.1 11.1 8.6 7.6 8.3 27.5 24.8 22.9 19.9 18.0

Mexican American 25.0 26.8 21.4 19.6 23.4 52.0 48.3 44.1 38.8 40.6

Puerto Rican/** 16.2 18.0 34.2 27.0

Other Latin American 15.5 19.4 26.7 32.6

Asian American 14.7 11.4 9.0 8.2 11.1 28.4 22.4 19.4 15.2 18.9

Native American 40.9 38.3 30.8 26.9 32.5 62.8 57.6 46.8 46.2 41.5

Marijuana Use Within Past 30 Days

White 30.8 24.6 17.9 15.0 20.8 40.4 31.6 22.5 19.7 26.0

Black 22.1 20.1 7.2 6.8 12.7 36.6 29.2 14.6 15.9 26.6

Mexican American 25.9 21.2 11.7 10.5 18.7 39.8 36.9 19.5 19.9 29.3

Puerto Rican/** 10.8 20.7 26.4 26.7

Other Latin American 11.0 12.9 13.7 19.6

Asian American 18.3 13.8 5.2 5.1 9.1 31.2 13.0 9.8 9.0 16.0

Native American 44.7 30.3 19.7 21.5 32.0 50.9 36.1 26.6 25.5 27.2

*Percentage prevalence shown as the mean for each 5-year span.

**Beginning in 1990, the data distinguish between Puerto Rican and Other Latin American.

12th-Grade Females 12th-Grade Males

‘76-'80 81-'85 '86-'90 '91-'95 '96-'00 '76-'80 '81-'85 '86-'90 '91-'95 '96-'00

18.0 15.0 12.4 18.7 13.7 12.4

21.9 18.5 13.0 36.6 34.6 30.3

19.5 14.4 8.7 34.7 22.7 17.2
20

Youths’ Opportunities To Experiment Influence Later Use of

Illegal Drugs

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

Research Findings

Volume 17, Number 5 (January 2003)

NIDA-supported researchers have reported new epidemiological evidence about the associations linking earlier alcohol or tobacco use with later use of marijuana, and the

link from earlier marijuana use to later use of other illegal

drugs such as cocaine and hallucinogens. This study builds

on the many prior NIDA-supported studies of the “gateway” theory of youthful drug involvement: Once use of

tobacco or alcohol begins, there is greater likelihood of

marijuana use, and once marijuana use begins, there is

greater likelihood of other illegal drug use.

“This research increases our understanding of the complex

relationship between the different stages of drug use and

raises concerns about factors that promote the transition

from opportunities to initiate drug use to patterned use,”

says Dr. Kathleen Etz of NIDA’s Division of

Epidemiology, Services and

Prevention Research. “We

know that earlier drug use is

associated with later, more

advanced use; however, this

research identifies a previously

overlooked aspect of this transition, opportunities to use.”

Using annual data from the

1991 through 1994 National

Household Survey on Drug

Abuse (NHSDA), the research

team, led by Dr. James C.

Anthony from Johns Hopkins

University Bloomberg School of Public Health in

Baltimore, analyzed the responses of 26,015 individuals

aged 12 to 18 who answered questions regarding marijuana use and the responses of 44,624 individuals aged 12

to 25 who answered questions regarding cocaine use.

The research focused on a concept called “drug exposure

opportunities.” This concept takes into account that some

young people actively seek out opportunities to try marijuana or cocaine, whereas others are more passive recipients of drug exposure opportunities.

The researchers found that alcohol and tobacco users were

more likely than nonusers to have an opportunity to try

marijuana and were also more likely to try the drug when

the opportunity arose. About 75 percent of alcohol or

tobacco users reported an opportunity to try marijuana by

age 18, and more than 85 percent of them made the transition to marijuana use. Only about 25 percent of nonsmokers and nondrinkers were given an opportunity to try

marijuana by the same age. Of these, fewer than 25 percent began smoking marijuana within 6 years after they

were first given the opportunity. Overall, alcohol or tobacco users were seven times more likely to start using marijuana than individuals who had used neither alcohol nor

tobacco. 

Prior marijuana use was closely associated with the opportunity to try cocaine and the likelihood of young people’s

starting to use cocaine once given the opportunity. Among

the young people who were given the chance to try cocaine,

those who were already using marijuana were 15 times

more likely to use cocaine than those who did not use marijuana. About 50 percent of marijuana users used cocaine within

2 years of their first opportunity

to do so. However, among

young people who never used

marijuana, fewer than 10 percent initiated cocaine use.

In a separate but related study,

the researchers analyzed data

from 41,271 young people

who participated in the 1991

through 1994 NHSDA, investigating the relationship between the use of marijuana and

use of hallucinogens. The results showed that marijuana

users are more likely than nonusers to be offered an

opportunity to use LSD, mescaline, mixed stimulant-hallucinogens, and PCP and more likely than nonusers to try

these hallucinogenic drugs when they’re offered. By age

21, nearly one-half of the teenagers who had smoked marijuana were presented with the opportunity to try hallucinogens, compared to only one-sixteenth of those who

had not used marijuana. Once given the opportunity to

use hallucinogens, marijuana smokers were about 12 times

more likely to use hallucinogens than those who did not

use marijuana.

“These studies are the first to support the idea of two separate mechanisms linking the use of alcohol, tobacco,

marijuana, cocaine, and hallucinogens—one mechanism

Prior marijuana use was

closely associated with the

opportunity to try cocaine and

the likelihood of young people’s

starting to use cocaine once

given the opportunity.
21

Drug Use Associated With More Opportunities To Use,

Higher Rates of Acceptance
involving increased drug exposure opportunity, and a separate mechanism involving increased likelihood to use

once the opportunity occurs,” says Dr. Anthony. “Even if

there is an underlying common vulnerability or predisposition that accounts for the observed sequencing of drug

exposure opportunities and actual drug use, these observations may have implications for the design and evaluation

of drug prevention activities. Drug users often are members of social circles where drug use and experimentation

are more common and friends are likely to share drugs.

In addition to trying to persuade young people not to use

drugs, it may be worthwhile for us to persuade users not

to share their drugs with friends.” Previous research has

also shown that although males are more likely than

females to have opportunities to use drugs, both are equally likely to make a transition into drug use once an opportunity to try a drug has occurred. Dr. Anthony and his

colleague, Dr. Fernando Wagner, also from Johns Hopkins

University Bloomberg School of Public Health, have made

similar observations in ongoing research studies.

Dr. Anthony believes that his research carries a strong

message for parents and pediatricians, who often neglect

the opportunity to ask children and adolescents about

whether they have had chances to try illegal drugs. As Dr.

Anthony notes, “Kids will talk to us about their chances

to try illegal drugs even when they are unwilling to talk

about actual drug use. Once the chance to try marijuana

or cocaine occurs, it is a red flag, and we need to be paying close attention to what happens next.”

“Future research in this area will be a great asset to the

development of effective drug prevention programs,” says

Dr. Etz. “It will assist us in understanding the process

through which the use of one drug is related to use of

another and help us to target prevention programs to individuals more likely to progress to advanced substance use.”

Sources

• Wagner, F.A., and Anthony, J.C. Into the world of

illegal drug use: Exposure opportunity and other

mechanisms linking the use of alcohol, tobacco, marijuana, and cocaine. American Journal of Epidemiology

155(10):918–925, 2001.

• Wilcox, H.C.; Wagner, F.A.; and Anthony, J.C.

Exposure opportunity as a mechanism linking youth

marijuana use to hallucinogen use. Drug and Alcohol

Dependence 66(2):127–135, 2002. 

22
23

Teen Drug Use Declined in 2002, Report Shows

By Patrick Zickler NIDA NOTES Staff Writer

Research Findings

Volume 17, No 5 (January 2003)

Drug use by American teenagers

declined in a broad range of

categories during 2002,

according to the latest

Monitoring the Future 

survey. Use of MDMA

(ecstasy) dropped for the

first time since it was

added to the annual survey in 1996, and marijuana use declined to its

lowest level in 8 years.

The numbers of 8th10th- and 12th-graders

who said they had smoked cigarettes in the month preceding the survey fell by 12 percent, 17 percent, and 10 percent, respectively. 

“Our science-based education and prevention efforts are

paying off,” said NIDA Acting Director Dr. Glen Hanson

at a press conference announcing the 2002 survey findings. “Teenagers are considering the information in the

messages before deciding whether or not to use drugs, and

they are making better decisions. In this survey we see that

teenagers are increasingly choosing not to use marijuana,

not to use ecstasy and other club drugs, not to begin

smoking or using alcohol. They should be

congratulated.”

The Monitoring the

Future survey (MTF) is

conducted annually by

the University of

Michigan’s Institute for

Social Research and has

been supported by NIDA throughout its 27-year history.

The survey tracks illicit drug use and attitudes toward

drugs among 8th-, 10th-, and 12th-grade students. The

2002 study surveyed a representative sample of more than

43,000 students in 394 schools across the Nation.

Students are asked about their attitudes toward drugs (Do

they perceive a risk associated with trying the drug? Do

they approve or disapprove of someone’s trying the drug?)

and about lifetime, past-year, and past-month drug use.

(“Lifetime” refers to use at least once during a respondent’s lifetime. “Past year” refers to an individual’s drug

use at least once during the year preceding their response

to the survey. “Past month” refers to an individual’s drug

use at least once during the month preceding their

response to the survey.)

Overall drug use—the proportion of students who reported using any illicit drug in the preceding year—declined

in grades 8 and 10. “This is the first time since

1998 that we have seen a significant

decline in overall illicit drug use among

10th-graders,” said Dr. Lloyd Johnston,

MTF principal investigator.

MTF results for 2002 show that teenagers’

attitudes about drugs are changing. Compared with

2001, this year more students in grades 10 and 12 said

they believed use of MDMA once or twice is harmful, and

the proportion of students who said they disapproved of

trying MDMA increased in all three grades. “We are gratified, but not satisfied. NIDA will continue to generate

and disseminate science-based information that leads to

increases in understanding of the harm that comes from

drug use,” said Dr. Hanson.

“These changes in perceived risk and disapproval are

encouraging indicators of future downturns in drug use,”

Dr. Johnston observed. “This has proven to be the case

with ecstasy. In 2000, only 38 percent of seniors said there

was great risk of harm associated with trying ecstasy. That

jumped to 48 percent in 2001 and increased again to 52

percent in 2002. These unusually rapid changes no doubt

reflect the effects of media coverage of adverse events as

well as NIDA’s efforts to document and disseminate information about the adverse consequences of using 

ecstasy.”

Similarly, the decreases in smoking reported for 2002 follow increases in the proportion of students who perceived

a negative image of smoking. Roughly half of students in

all three grades said they strongly agree with the statement

“I dislike being near people who are smoking.” Perhaps

more important to teens, Dr. Johnston noted, is the social

implication of changing attitudes toward smoking.

“Roughly three-quarters of boys and girls in all three

grades said they prefer to date nonsmokers. It now appears

that taking up smoking makes a youngster less attractive,

just the opposite of what cigarette advertising has been

promising.” 
Significant changes reported in the 2002 MTF survey

include the following:

• Marijuana—Among 10th-graders, marijuana use in

the past year and past month decreased, and daily use

in the past month was down. Past-year use decreased

from 32.7 percent to 30.3 percent; past-month use

went from 19.8 percent to 17.8 percent; and daily use

in the past month declined from 4.5 percent to 3.9

percent. 

• Cocaine—Crack use showed a significant increase in

past-year use among 10th-graders, returning to

around its 2000 level following a decline in 2001. For

2002, 2.3 percent of 10th-graders reported past-year

use of crack cocaine, compared with 1.8 percent in

2001 and 2.2 percent in 2000.

• Opiates—For the first time, MTF asked students

about nonmedical use of the prescription painkillers

OxyContin and Vicodin. Past-year use of OxyContin

without a doctor’s order was reported by 1.3 percent

of 8th-graders, 3.0 percent of 10th-graders, and 4.0

percent of 12th-graders. Nonmedical use of Vicodin

in the past year was reported by 2.5 percent of 8thgraders, 6.9 percent of 10th-graders, and 9.6 percent

of 12th-graders. 

• Inhalants—Lifetime, past-year, and past-month use

of inhalants decreased among 8th-graders, and lifetime use decreased among 10th-graders. Lifetime use

went from 17.1 percent in 2001 to 15.2 percent in

2002 among 8th-graders and from 15.2 percent to

13.5 percent among 10th-graders. 

• LSD—LSD showed major changes from 2001 to

2002. Rates of use decreased markedly in each grade

and reporting period. Past-year use, for example,

declined from 6.6 percent to 3.5 percent among 

12th-graders, from 4.1 percent to 2.6 percent among

10th-graders, and from 2.2 percent to 1.5 percent

among 8th-graders. These are the lowest rates of LSD

use in the history of the survey for each grade. 

• Club Drugs—Rates of MDMA (ecstasy) use

decreased significantly among 10th-graders. Their

past-year use declined from 6.2 percent to 4.9 percent, and past-month use went from 2.6 percent to

1.8 percent.

Findings from the 2002 MTF report are available through

NIDA’s Web site, www.drugabuse.gov, and at the MTF

Web site, http://monitoringthefuture.org. 

24

Monitoring the Future survey results show that

teen drug use declined in 2002. Tenth-grade students reported significant reductions in overall

drug use and in use of marijuana and cigarettes.

Use of MDMA (ecstasy) declined sharply among

all teenagers in 2002, reversing 3 years of

increased use. The decrease in use follows

increased perception among teens that MDMA

use has harmful consequences. 
25

Study Demonstrates That Marijuana Smokers Experience

Significant Withdrawal 

By Patrick Zickler, NIDA NOTES Staff Writer 

Animal research and controlled studies of marijuana

smokers during inpatient treatment suggest that marijuana

dependence, like dependence on other addictive drugs, is

associated with withdrawal symptoms—such as irritability,

anger, depressed mood, headaches, restlessness, lack of

appetite, and craving—that can make it difficult to stop

using the drug.

Now, NIDA-supported research conducted by Dr. Alan

Budney and colleagues at the University of Vermont in

Burlington has found that marijuana smokers who stop

using the drug while in their home environment suffer

withdrawal symptoms that appear as severe as those 

associated with tobacco-smoking.

“These findings represent a significant step toward general

acceptance of withdrawal as a key aspect of chronic 

marijuana use,” says Dr. Jag Khalsa of NIDA’s Center on

AIDS and Other Medical Consequences of Drug Abuse.

Treatment providers may not address the problem of 

Marijuana smokers living at home reported “clinically significant” withdrawal symptoms—such as sleep difficulty, marijuana

craving, aggression, and irritability—during periods of abstinence from the drug. The participants’ self-reports were confirmed,

in part, by observers who reported increased restlessness and irritability among the marijuana users when they were not smoking.

Volume 17, No. 3 (October 2002) 

Research Findings
26

marijuana withdrawal because the condition is not currently included in the Diagnostic and Statistical Manual of

Mental Disorders, Fourth Edition (DSM-IV), the standard

reference published by the American Psychiatric

Association. 

Dr. Budney and his colleagues evaluated withdrawal

symptoms in 12 adult marijuana smokers (7 male, 5

female, average age 30 years) over 3-day abstinence periods that followed 5-day periods when participants could

smoke marijuana at will. “We found consistent emotional

and behavioral symptoms that increased during abstinence

and dramatically decreased when marijuana smoking

resumed, suggesting that these types of symptoms are the

hallmark of acute marijuana withdrawal,” Dr. Budney

says. “The symptoms most closely resembled many of

those observed during nicotine withdrawal.”

During the study, participants lived at home and made

daily records rating the intensity of withdrawal symptoms

(on a scale from 0, “not at all,” to 3, “severe”) over the

preceding 24 hours. In addition, each participant designated an observer—a friend or family member who spent

at least 2 hours each day with the participant—to provide

an independent rating of the participant’s withdrawal

symptoms. The participants made daily laboratory 

visits during which their abstinence was confirmed by

urine tests.

During the abstinence periods, participants reported

increases in the severity of craving and sleep difficulty,

decreased appetite, and increased aggression, anger, and

irritability. In addition, participants reported an increase

in “strange dreams” during the second abstinence period.

Observers reported increased irritability and restlessness

among the participants during abstinence. 

“Marijuana withdrawal doesn’t include dramatic physical

symptoms such as the pain, nausea, heavy sweating, and

cramps associated with opiate withdrawal. Nevertheless,

the symptoms of marijuana withdrawal appear clinically

significant. It seems clear now that withdrawal from marijuana produces identifiable behavioral and emotional distress that may be as important as, if not more important

than, physical symptoms in the development of dependence and undermining attempts to quit using the drug,”

Dr. Budney says.

“Confirming withdrawal as part of marijuana dependence

will increase the likelihood that treatment providers 

will alert patients to its symptoms and will help them

cope with it through behavioral or pharmacological 

treatments,” says Dr. Khalsa.

Source

• Budney, A.J.; Hughes, J.R.; Moore, B.A.; Novy, P.L.

Marijuana abstinence effects in marijuana smokers

maintained in their home environment. Archives of

General Psychiatry 58(10):917-924, 2001. 
Cannabinoid Antagonist Reduces Marijuana’s Effects in Humans 

By Patrick Zickler, NIDA NOTES Staff Writer 

Marijuana smokers treated with an experimental compound reported reduced highs and had smaller heart rate

increases than untreated smokers in a recent study at

NIDA’s Intramural Research Program (IRP) in Baltimore.

The finding confirms the pivotal role played in marijuana

intoxication by certain structures—called cannabinoid

receptors—on brain cells. In addition, the study suggests

that the compound, called SR141716, may be useful as a

medication to help marijuana smokers quit. (See also,

“Study Opens Promising New Approach to Developing

Medications To Prevent Relapse to Cocaine Use,” in this

issue).

Marijuana, like other psychoactive drugs, achieves its

effects by attaching to nerve cells in the brain and altering

their function. The main psychoactive component of 

marijuana, tetrahydrocannabinol (THC), attaches to

cannabinoid receptors. Animal studies have led scientists

to believe that a particular type of cannabinoid receptor is

the site at which THC initiates the effects that produce

marijuana intoxication.

“Studies have shown in laboratory animals that the CB-1

cannabinoid receptors, which are found in high densities

in regions of the brain associated with attention, motor

control, and reasoning, play a major role in the effects of

marijuana. However, until our study, this had not been

confirmed in humans,” says Dr. Marilyn Huestis, an 

IRP researcher.

To evaluate the role of human CB-1 receptors, Dr. Huestis

and her colleagues studied the effects of SR141716 in 63

adult men with a history of smoking marijuana. The 

compound was developed by Sanofi-Synthelabo, Inc., of

Malvern, Pennsylvania, and clinical testing of the compound in marijuana users was conducted through a

Cooperative Research and Development Agreement with

NIDA. SR141716 has effectively blocked the effects of

marijuana at CB-1 receptors in studies involving rats,

pigeons, and monkeys. Participants in the NIDA research

received doses of 1, 3, 10, 30, or 90 mg SR141716 or

placebo. Two hours later, they smoked a marijuana cigarette containing THC or a marijuana cigarette without

THC. Immediately after smoking and up to 65 minutes

later, participants rated the strength of marijuana’s effects

on a scale ranging from 0 (no effect at all) to 100

(extremely strong effect).

“Participants who received the 90-mg dose of SR141716

reported 40 to 75 percent less drug effect than those who

didn’t receive the compound. Those who received lower

doses of the compound also reported less drug effect,” Dr.

Huestis says. “This demonstrates, first, that CB-1 receptors play a major role in THC’s effects in humans and,

second, that SR141716 can be used to at least partially

block the drug’s effects.” 

In addition to its psychological effects on humans, 

marijuana increases the heart rate. Heart rates of men who

smoked marijuana with THC but received no SR141716

increased by roughly 30 percent above baseline within 10

minutes of smoking marijuana and were 15 percent higher

at 1 hour after smoking. Increases in heart rate after marijuana with THC was smoked were diminished in a doserelated manner by SR141716.

Blood tests showed that men who smoked marijuana with

THC and who received 90 mg SR141716 had blood concentrations of THC similar to those of participants who

did not receive SR141716. This demonstrates that reduction of marijuana’s effects is attributable not to any effect

of SR141716 on THC concentration, but to blockade of

CB-1 receptors, Dr. Huestis says. 

Because SR141716 partially blocks THC’s intoxicating

effects, the compound may prove valuable in treating 

Participants received either placebo or active SR141716 before

smoking marijuana and were then asked to describe, on a scale

from 0 (not at all) to 100 (extremely), “How high do you feel

now?” “How stoned on marijuana are you now?” and “How strong

is the drug effect you feel now?” SR141716 (90 mg) reduced the

maximum mean rating of the drug effects. Participants who

received SR141716 also experienced smaller increases in heart rate

after smoking marijuana.

Research Findings

27

Volume 17, No. 3 (October 2002) 
marijuana addiction, the researchers say. If marijuana does

not provide its usual high, patients in treatment would be

less tempted to smoke it and less vulnerable to relapse. To

evaluate the compound’s role as a medication, NIDA

researchers currently are studying SR141716’s ability to

reduce the effects of THC when given in repeated doses

over 2 weeks. Other NIDA-supported research suggests

that a different formulation of the compound may be

effective in treatment of cocaine addiction (see this issue’s

“Study Opens Promising New Approach to Developing

Medications To Prevent Relapse to Cocaine Use”). 

In addition, Sanofi-Synthelabo is investigating the 

compound’s possible effects on other disorders related to

cannabinoid receptors, such as increased appetite and food

intake, and in smoking cessation treatment.

Source

• Huestis, M.A., et al. Blockade of effects of smoked

marijuana by the CB1-selective cannabinoid receptor

antagonist SR141716. Archives of General Psychiatry

58(4):322-328, 2001. 

28
Research Findings

29

Shortened Family Prevention Programs Yield Long-Lasting

Reductions in Adolescent Drug Abuse 

By Robert Mathias, NIDA NOTES Staff Writer 

Two brief family-focused drug abuse prevention 

programs have produced long-term reductions in

substance abuse among adolescents in rural Iowa

public schools who were assigned to the programs in

the sixth grade, a study funded by NIDA and the

National Institute of Mental Health has shown. 

The programs may offer communities a practical

approach to effective family-based drug abuse 

prevention.

The longer of the two programs reduced the proportion of students who used any marijuana, tobacco,

or alcohol in grades 6 through 10 as well as students’

current use of alcohol and tobacco. The shorter 

program decreased alcohol use among 10th-graders

significantly, along with reducing lifetime substance

use behaviors.

“The study demonstrates that brief family interventions can reduce drug use among young people during the high-risk years when they are making the

transition from childhood to adolescence,” says Dr.

Richard Spoth of Iowa State University in Ames,

who led the study. Reducing the number of children

who begin substance use during these years may have

important public health benefits because early initial use is

associated with higher rates of substance dependence in

later adolescence and young adulthood, he says.

A total of 667 families of sixth-graders from 33 public

schools in Iowa were recruited for the study. The children’s

schools were randomly assigned to either a five-session

program called Preparing for the Drug Free Years (PDFY),

a seven-session Iowa Strengthening Families Program

(ISFP), or a control group. The two programs were

designed for families with young adolescents. The ISFP

was adapted from a more extensive program that had previously been evaluated in a variety of settings and with

several racial and ethnic groups.

“The purpose of modifying longer programs and trying to

replicate their results in new settings is to make them

more practical for communities to implement and for

families to participate in them,” notes Dr. Elizabeth

Robertson of NIDA’s Division of Epidemiology, Services

and Prevention Research. “The fact that the adapted programs achieved very positive results indicates they can be

whittled down and still maintain their effectiveness,” 

she says.

Staff members from the Iowa Cooperative State Research,

Education, and Extension Service of the U.S. Department

of Agriculture worked with community facilitators to

implement either PDFY or ISFP in a total of 22 schools

with 459 families whose family, school, and community

characteristics had previously been assessed. Eleven schools

with 208 comparable families were assigned to a control

group that was mailed leaflets on adolescent development

and parent-child relationships. The programs were delivered in weekly evening sessions to participating families at

the schools. Parents in PDFY attended four sessions and

were joined by their children for a final joint session. In

the relatively more intensive ISFP, parents and children

attended both separate and joint sessions for 6 weeks and

a final joint session. The weekly PDFY and ISFP sessions

sought to improve how parents and children functioned

individually and as a family in a variety of situations. Both

programs taught skills such as effective parenting, appropriate management of family conflicts, and how to resist

peer pressure. The development of such skills has been

linked to delayed onset or reduction of substance abuse. 

Four years after 6th-grade students had received the programs, the researchers interviewed them and found that 

Lower percentages of ISFP and PDFY 10th-graders than control students

had initiated a number of substance abuse behaviors involving use of 

alcohol, cigarettes, and marijuana 4 years after they had received the 

programs in the 6th grade.

Volume 17, No. 2 (May 2002)
30

significantly lower percentages of ISFP than control 

10th-graders had ever initiated any of five substance abuse

behaviors. Specifically, lower percentages of ISFP students

than controls had begun to use alcohol, cigarettes, or 

marijuana; had ever used alcohol without parental permission; or had become drunk. The proportion of new 

marijuana users in the control group was 2.4 times greater

than it was among ISFP youths. Similarly, the proportion

of controls who had been drunk or smoked cigarettes were

1.7 and 1.5 times greater than they were among ISFP

youths. Participants in the PDFY program also showed

lower rates of initiation of all five substance use behaviors

than controls, but only the differences in lifetime drunkenness and marijuana use approached statistical significance. Nevertheless, the rates of new marijuana use and

ever getting drunk were 1.5 and 1.2 times greater for controls than they were for PDFY youths. Actual rates of substance use behaviors among 10th-graders in all three

groups are shown in the illustration on the preceeding

page.

Among those 10th-graders in the three groups who had

begun to use alcohol, tobacco, or marijuana, the study

found lower proportions of PDFY and ISFP students than

controls had used alcohol and tobacco in the preceding

month and marijuana during the preceding year. For

example, frequency of past-month alcohol use among

PDFY and ISFP students was

about two-thirds that of controls. Among ISFP students,

past-month cigarette use was

approximately half that of control group students.

“Developmental timing is an

important factor in the longterm effects of these interventions,” Dr. Spoth says.

“Intervening at this time, in

the sixth grade when kids are

experimenting with substances,

probably contributes greatly to

the positive effects,” he says.

The careful design of the interventions with their theorybased focus on parenting and

family interactions also is

important, he adds.

The critical element affected by

both programs is the parent component, says NIDA’s Dr.

Robertson. “When you provide parents with information

about what to expect of children at that age, what is typical and what is not, and how to deal with some of the

problems, you are shaping how parents relate to their children. Changing the family context can have a long-lasting

effect because you are positively influencing the day-today environment of the child over a long period of time,”

she says.

Whether the findings of this study would apply to more

diverse populations in other settings remains an open

question, Dr. Robertson says. However, the original programs from which the critical elements in these programs

were derived have been successfully tested in a variety of

settings, she notes. In addition, the ISFP has been adapted

for and is now being tested with urban and rural AfricanAmericans and Native American families. 

Source

• Spoth, R.L.; Redmond, C.; and Shin, C. Randomized

trial of brief family interventions for general populations: Adolescent substance use outcomes 4 years following baseline. Journal of Consulting and Clinical

Psychology 69(4):627-642, 2001. 

Initiation of marijuana use occurred at a slower rate among students who participated in the ISFP

and PDFY programs than among those in the control group.
Research Findings

31

Chronic Marijuana Abuse May Increase Risk of Stroke

Dr. Ronald I. Herning and Dr. Jean Lud Cadet, with 

colleagues at NIDA’s Intramural Research Program in

Baltimore, report preliminary evidence suggesting that

chronic abuse of marijuana can restrict blood flow to the

brain and increase the risk of stroke for young men aged

18 to 30. 

The investigators used transcranial Doppler sonography, a

noninvasive technology that uses sound waves to take measurements and create images, to calculate the pulsatility

index—a measure of resistance to blood flow—in cerebral

arteries of 35 male participants, 16 long-term marijuana

users and 19 nonusers of marijuana. Marijuana users had

higher resistance to blood flow to their brains than did

nonusers upon initial measurement, and the deficits persisted after the marijuana abusers remained abstinent for a

month, well past the time when acute withdrawal symptoms were reported. As a result, the deficits do not appear

to be related to a temporary withdrawal syndrome.

The findings suggest that, at least within the first 4 weeks

of marijuana abstinence, blood flow in the brain in young

marijuana abusers is comparable to that of 60-year-olds,

which may be of clinical importance because advancing

age increases the risk of stroke. 

The study was published in the June 2001 Annals of the

New York Academy of Science. 

Volume 17, No. 1 (April 2002)
Research Findings

32

Cognitive Deficits Associated With Heavy Marijuana Use Appear 

To Be Reversible

By Margi Grady, NIDA NOTES Contributing Writer

Memory and learning problems caused by

heavy marijuana smoking persist for at least a

week after cessation of use of the drug, but

they appear to resolve completely within a

month, a NIDA-supported study shows.

“Cognitive impairment from heavy marijuana use may linger for a week or longer,

but it does not appear to be permanent,” says

Dr. Harrison Pope, Jr., who led the study at

Harvard University’s McLean Hospital in

Belmont, Massachusetts. “Even if users

smoke a lot, these tests suggest they can

eventually recover,” he says. As a followup to

this research, Dr. Pope and his colleagues are

using functional magnetic resonance imaging

to determine whether the more sensitive

assessment tool reveals cognitive effects that

his pencil-and-paper tests could not detect.

“Even though our study suggests that heavy

users recover from cognitive deficits after 4

weeks of abstinence, it doesn’t follow that marijuana is a

benign substance,” says Dr. Pope. He notes that the study

revealed some startling demographic differences between

long-term heavy users and a control group. Data collected

on participants when they joined the study showed that

those who had used marijuana heavily for many years had

markedly lower income and education levels than the 

control group, regardless of whether they were still using

the drug.

Dr. Pope and his colleagues examined cognitive function

in 180 participants, including 63 current heavy marijuana

users, 45 former heavy users, and 72 control subjects.

Current heavy users had smoked marijuana a minimum of

5,000 times during their lives (the equivalent of at least

once a day for 13 years) and were smoking at least 7 times

a week at the beginning of the study. Former heavy users

had also smoked at least 5,000 times in their lives but no

more than 12 times during the previous 3 months. The

control subjects had smoked at least once but no more

than 50 times during their lives and no more than once in

the previous year. Participants ranged in age from 30 to

55. All three groups were carefully screened for unrelated

characteristics that might affect the study results.

All participants were required to remain abstinent from

marijuana and other drugs for the course of the 28-day

study and submit urine specimens that were used to 

confirm their abstinence. Their cognitive function was

evaluated through standardized neuropsychological tests 

at study entry and on the 1st, 7th, and 28th days of the

study. On study entry (day 0) and days 1 and 7, current

heavy marijuana users scored significantly lower than 

control subjects on tests of verbal learning and memory.

This finding confirms and extends the findings of previous studies by Dr. Pope’s group and others that have

shown impaired cognitive skills in heavy marijuana users

for up to 3 days after use is stopped. By day 28, the difference between the scores of the control group and those of 

current heavy marijuana users disappeared.

Two findings allowed the researchers to conclude that the

cognitive deficits were associated with recent heavy use

rather than total lifetime use. First, former heavy users

showed no significant difference from the control subjects

on any of the tests on any of the testing days. Also, the

researchers found a clear relationship between lower test

Information gathered on the Harvard study’s participants revealed that both 

current and former long-term heavy users of marijuana had markedly lower income

and less education than control subjects, even though the education and income 

of the two groups’ parents were similar, says Dr. Harrison Pope, Jr., the study’s 

lead investigator.

Income and education data suggest

consequences of heavy marijuana use.

Volume 17, No. 1 (April 2002) 
33

scores and higher levels of marijuana residues in urine at

the beginning of the study, but no relationship between

test scores and total lifetime marijuana use.

“This study is particularly significant for treatment,” 

says Dr. Steven Grant of NIDA’s Division of Treatment

Research and Development. “By stopping drug use, heavy

marijuana users are able to regain their memory and 

learning functions. Still, we cannot say there are no 

consequences to heavy marijuana use: The income and

education data suggest the opposite.”

Sources

• Fletcher, J.M., et al. Cognitive correlates of long-term

cannabis use in Costa Rican men. Archives of General

Psychiatry 53(11):1051-1057, 1996. 

• Pope, H.G., Jr., et al. Neuropsychological performance in long-term cannabis users. Archives of

General Psychiatry 58(10):909-915, 2001. 

• Pope, H.G., Jr., and Yurgelun-Todd, D. The residual

cognitive effects of heavy marijuana use in college students. Journal of the American Medical Association

275(7):521-527, 1996. 

• Solowij, N. Cannabis and Cognitive Functioning.

Cambridge, UK: Cambridge University Press, 

1998. 
Research Findings

34

Adolescent Treatment Programs Reduce Drug Abuse, 

Produce Other Improvements 

By Kimberly R. Martin, NIDA NOTES Contributing Writer 

In the first large-scale study designed to evaluate drug

abuse treatment outcomes among adolescents in agespecific treatment programs, NIDA-supported researchers

have found that longer stays in these treatment programs

can effectively decrease drug and alcohol use and criminal

activity as well as improve school performance and 

psychological adjustment.

The study, part of NIDA’s ongoing Drug Abuse Treatment

Outcome Studies for Adolescents (DATOS-A), analyzed

data from 23 community-based adolescent treatment 

programs that addressed peer relationships, educational

concerns, and family issues such as parent-child relationships and parental substance abuse. Successful elements of

adult treatment programs, such as participation in group 

therapy and participation in a 12-step program, were also

included in treatment plans.

“The results of this study are particularly impressive in

light of the fact that the adolescents had multiple problems,” says Dr. Christine Grella of the University of

California, Los Angeles (UCLA), Drug Abuse Research

Center, one of the study’s investigators. “Although this is

also typical of many adults in treatment, timely resolution

of these problems is even more critical for adolescents.

These young people are in the process of developing 

values, making lifestyle decisions, and preparing to assume

adult roles and responsibilities, such as family and work;

whereas when many adults enter treatment, they have

completed this process.”

Treatment Programs Varied

Dr. Yih-Ing Hser, also of UCLA, led the research team

that evaluated the treatment outcomes for 1,167 adolescents, age 11 to 18, who were admitted to one of the

treatment programs between 1993 and 1995. The 

treatment centers, located in Pittsburgh, Pennsylvania;

Minneapolis, Minnesota; Chicago, Illinois; and Portland,

Oregon, included eight residential programs, nine outpatient drug-free programs, and six short-term inpatient programs.

The 418 adolescents in the residential treatment programs

received education, individual and group counseling, and

interventions to develop social responsibility. The 292

adolescents in the outpatient drug-free programs received

education, skills training, and individual and group 

counseling. The 467 adolescents in short-term inpatient

programs received counseling and a 12-step program.

Family therapy was strongly emphasized, and adolescents

in these programs were referred to continued outpatient

treatment. The average length of treatment for adolescents

in the residential, outpatient drug-free, and short-term

inpatient programs was 5 months, 1.6 months, and 18

days, respectively.

The adolescents were interviewed when they began treatment and again 1 year after discharge by professional

interviewers who were not employed by the treatment

centers. Problem severity was determined at the initial

interview according to a number of criteria. Dependence

on drugs or alcohol was determined from standardized

diagnostic measures. To validate self-reports of drug use,

one-quarter of the participants were selected randomly to

submit urine samples during the posttreatment interview.

Before treatment, 25 percent of the participants used three

or more drugs, 36 percent were dependent on alcohol, 

An evaluation of more than 1,100 adolescents who received 

substance abuse treatment in residential, short-term inpatient, or

drug-free outpatient programs found improvement in rates of drug

use and social behavior. Some 53 percent of those treated met or

exceeded the minimum recommended stay in treatment.

Volume 17, No. 1 (April 2002)
35

64 percent were dependent on marijuana, and 10 percent

were dependent on cocaine. In addition to substance

abuse problems, 63 percent were diagnosed with a mental

disorder and 67 percent were criminally active.

Outcomes Overall

Research has indicated that in general the rate of drug and

alcohol use tends to increase during adolescence. In the

present study, however, improvements were observed in

many of the areas evaluated, although some of the 

participants did not complete their treatment program.

Comparing the year before treatment to the year after

treatment, the adolescents showed significant declines in

the use of marijuana and alcohol, which are considered to

be the major drugs of abuse for this age group. Weekly or

more frequent marijuana use dropped from 80 percent to

44 percent, and abstinence from any use of other illicit

drugs increased from 52 percent to 58 percent. Heavy

drinking decreased from 34 percent to 20 percent, and

criminal activity decreased from 76 percent to 53 percent.

Adolescents also reported fewer thoughts of suicide, lower

hostility, and higher self-esteem. In the year following

treatment, more adolescents attended school and reported

average or better-than-average grades. Some exceptions to

the general pattern of improvement were that overall,

cocaine and hallucinogen use did not improve during the

year after treatment.

Treatment Length and Outcomes

Previous research indicates that a minimum of 90 days of

treatment for residential and outpatient drug-free 

programs and 21 days for short-term inpatient programs is

predictive of positive outcomes for adults in treatment.

Better treatment outcomes were reported among adolescents who met or exceeded these minimum lengths of

treatment than for those who did not. Among the treatment participants, 58 percent of those in residential 

programs, 27 percent in outpatient drug-free programs,

and 64 percent in short-term inpatient programs met or

exceeded the minimum stay. In the year following treatment, those who met or exceeded the minimum treatment

were 1.52 times more likely to abstain from drug and

alcohol use and 1.2 times more likely to not be involved

in criminal activity. In addition, these adolescents were

1.34 times more likely to have average or better-thanaverage grades.

This study confirms that community-based drug treatment programs designed for adolescents can reduce substance abuse and have a positive impact on many other

aspects of their life, says Dr. Tom Hilton of NIDA’s

Division of Epidemiology, Services and Prevention

Research. These results justify new research to identify the

key elements common to effective treatment programs for

adolescents, he noted.

Source

• Hser, Y-I.; Grella, C.E.; Hubbard, R.L.; et al. An evaluation of drug treatment for adolescents in four U.S.

cities. Archives of General Psychiatry 58(7):689-695,

2001. 

In the year following treatment, 

more adolescents attended school

and reported average or 

better-than-average grades.
Research Findings

36

Television Public Service Announcements Decrease Marijuana Use

in Targeted Teens

By Kimberly R. Martin, NIDA NOTES Contributing Writer

NIDA-supported researchers have

helped clarify the necessary elements in

effective anti-drug public service

announcements (PSAs) directed at

high-sensation-seeking adolescents.

NIDA researchers have previously

shown that high-sensation-seekers—

individuals characterized by their need

for new, emotionally intense experiences and the willingness to take risks

to obtain these experiences—are at

greater risk for using marijuana and

other drugs and for using them at an

earlier age than other individuals.

Using a prevention approach developed

from previous NIDA-supported 

studies, the researchers produced five

anti-marijuana PSAs. The dramatic

and attention-getting PSAs were aired

during programs that appealed to 

high-sensation-seekers such as actionoriented television shows. The media

placement was supported by paid as

well as donated advertising to ensure

the most effective outreach to the target audience.

“To appeal to high-sensation-seekers, a PSA must be 

dramatic, intense, and highly original,” says Dr. Philip

Palmgreen, the research team leader at the University of

Kentucky in Lexington. “An effective PSA needs to show

the negative consequences that can occur as a direct result

of drug use. For example, high-sensation-seekers need to

see that they can end up in a wheelchair, lose their job, or

lose their girlfriend or boyfriend as a result of drug use.

We found that the threat of death is not a deterrent

because high-sensation-seekers do not believe that death is

a real possibility,” he says.

The PSAs were aired from January through April 1997 in

Fayette County, Kentucky, and from January through

April 1998 in Fayette County and Knox County,

Tennessee. One hundred students in 7th through 10th

grade were selected each month by random phone calls

and asked to participate in the

study. The students were interviewed to determine whether they

saw the PSAs and their attitudes

toward and whether they used

marijuana and other drugs.

Questions also were asked to determine their degree of sensationseeking. More than 70 percent of

the targeted age groups watched at

least three PSAs per week, the

researchers say.

Marijuana use declined substantially among teens during the campaigns in both counties and residual effects of the campaigns were

evident for several months.

According to Dr. Palmgreen, the

second campaign in Fayette

County had a “booster effect,”

resulting in further declines.

Overall, marijuana use decreased

by 38 percent in Fayette County.

In Knox County, marijuana use

declined among high-sensationseeking teens by 26.7 percent.

“We have shown that, for PSAs to be effective, they must

be designed for a specific audience and must air frequently

during programs watched by that audience,” says Dr.

Palmgreen. “PSAs typically are shown during donated airtime. However, the trend toward paid placements of PSAs,

as in various campaigns across the country, is a very 

positive approach.”

Source

• Palmgreen, P.; Donohew, L.; Lorch, E.P.; Hoyle, R.;

and Stephenson, M.T. Television campaigns and adolescent marijuana use: Tests of sensation seeking targeting. American Journal of Public Health 91(2):292-

296, 2001. 

Volume 16, Number 4 (October 2001)

Drs. Philip Palmgreen (left) and Lewis Donohew

review a public service announcement at the

University of Kentucky.
Research Findings

37

Adding Vouchers to Behavioral Therapies Improves Marijuana

Treatment Results

Enhancing behavioral treatments by adding the opportunity to earn vouchers for remaining drug-free has been

shown to improve abstinence rates among cocaine- and

opiate-addicted patients. Now, a NIDA-funded study has

shown that the combination of behavioral interventions

and voucher-based incentives also can improve treatment

results for heavy marijuana abusers.

Researchers at the University of Vermont in Burlington,

led by Dr. Alan J. Budney, recruited 60 heavy marijuana

users who wanted to quit. Most of the study participants

had long histories of marijuana abuse, smoked marijuana

almost daily, and smoked more than once a day. They

were randomly assigned to one of three treatments: 

motivational enhancement therapy, motivational enhancement plus behavioral coping skills therapy, or motivational

enhancement plus coping skills plus voucher-based incentives. Throughout the study, each participant gave urine

samples twice weekly to be tested for marijuana use. If

patients in the incentives group tested negative, they

earned vouchers that they could exchange for retail goods

or services, such as movie passes, sporting equipment, 

or vocational classes. Patients in the other two treatment

groups did not receive such tangible rewards for 

abstinence.

Over the 14-week study, 40 percent of patients in the

incentives group achieved at least 7 weeks of continuous

abstinence from marijuana, compared with 5 percent of

patients in each of the other groups. At the end of the

treatment period, 35 percent of the incentives group had

stopped using marijuana, compared to 10 percent of the

motivational enhancement plus coping skills group and 5

percent of the motivational enhancement group.

The study was published in the December 2000 issue of

the Journal of Consulting and Clinical Psychology. 

Adding voucher-based incentives to behavioral and motivational

treatments more than tripled the percentage of patients who

stopped using marijuana by the end of treatment.

Percentage of Participants

Marijuana Abstinence at End of Treatment

Motivational enhancement plus coping

skills plus voucher-based incentives

Motivational enhancement plus 

behavioral coping skills therapy

Motivational enhancement therapy

Volume 16, Number 3 (August 2001)
Research Findings

38

Gender Differences in Prevalence of Drug Abuse Traced to

Opportunities to Use

By Patrick Zickler, NIDA NOTES Staff Writer 

Males are more likely than females to abuse drugs.

According to the 1999 National Household Survey on

Drug Abuse (NHSDA)—an annual Substance Abuse and

Mental Health Services Administration survey of more

than 25,000 respondents—8.1 percent of males and 4.5

percent of females older than age 12 had used illicit drugs

within the past month, and this ratio has remained fairly

constant throughout the 29-year history of the survey.

Research by Dr. James Anthony, a NIDA-supported 

scientist at the Johns Hopkins University School of

Hygiene and Public Health in Baltimore, shows that these

gender differences in drug abuse are not related to gender

differences in susceptibility. Instead, they have their foundation in the very first stage of drug involvement—the

opportunity to use drugs. Once given the opportunity to

use, males and females are equally likely to use drugs.

Dr. Anthony and his colleagues analyzed NHSDA data for

1993 to look for information that might explain the gender difference in rates of drug abuse. “Males are more 

likely than females to have an opportunity to use drugs.

There is no male-female difference with respect to trying a

drug once an opportunity to do so has been experienced,”

Dr. Anthony says.

The findings are consistent for marijuana, cocaine, hallucinogens, and heroin, Dr. Anthony says. The proportion

of opportunities to use marijuana was 59 percent of males

compared with 43.9 percent of females; to use cocaine,

28.7 percent of males and 18.3 percent of females; to use

hallucinogens, 18.6 percent of males and 10 percent of

females; and to use heroin, 7.8 percent of males and 3.2

percent of females. 

Once presented with an opportunity to use drugs, 44.2

percent of males and 42 percent of females began using

marijuana within 1 year; 37.7 percent of males and 33.2

percent of females began using cocaine; 50.5 percent of

males and 50 percent of females began using hallucinogens; and 14.6 percent of males and 22.1 percent of

females began using heroin.

Dr. Anthony found that females were likely to get their

first opportunity to use cocaine at an earlier age than were

males (age 19 for females, age 20 for males) but that 

there were no differences among males and females in age

of first opportunity to use marijuana, heroin, or 

hallucinogens.

One benefit of improved understanding of the link

between opportunity and eventual use is that counselors

or physicians may be able to learn about young patients’

drug use by asking about their opportunities to use drugs.

“Young people may feel freer to answer a question about

the opportunity to use drugs rather than a question about

actual drug use, because the opportunity is less likely to 

be illegal or particularly sensitive,” Dr. Anthony says. 

According to the 1993 National Household Survey on Drug Abuse, boys are more likely to abuse drugs than girls. The graph

above shows the estimated percentage of boys and girls using each drug and the percentage having the opportunity to use each drug. 

59.0%

43.9%

28.7%

18.3% 18.6%

10.0%

7.8%

3.2%

39.2%

28.7%

14.5%

8.5%

11.8%

5.9%

Having Opportunity to Use Drugs Actual Drug Use 

Boys Girls

1.4% 0.8%

Marijuana Cocaine Hallucinogens Heroin Marijuana Cocaine Hallucinogens Heroin

Volume 15, Number 4 (September 2000)

Boys Girls
39

Understanding the differences in opportunities to use

drugs may also help shape prevention efforts, according to

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

Research Coordinator. “The prevalence of drug abuse is

greater for males than for females even though, given the

initial opportunity to use drugs, males and females are

equally likely to move on to drug use. It appears that the

opportunities themselves play a very important role in

drug abuse and need more investigation. Understanding

the sex differences in opportunities could make it possible

to develop prevention programs that reduce the opportunities and, therefore, the higher rate of drug abuse among

males. In fact, NIDA-supported research into sex differences in opportunities (see this issue’s “Boys and Girls

Encounter Different Drug Offers, Use Different Refusal

Strategies”) raises the possibility that gender-specific 

prevention interventions that focus on drug opportunities

could serve to reduce drug use by both males and

females,” Dr. Wetherington says.

Sources

• Van Etten, M.L., and Anthony, J.C. Comparative 

epidemiology of initial drug opportunities and 

transitions to first use: Marijuana, cocaine, 

hallucinogens and heroin. Drug and Alcohol

Dependence 54:117-125, 1999. 

• Van Etten, M.L.; Neumark, Y.D.; and Anthony, J.C.

Male-female differences in the earliest stages of drug

involvement. Addiction 94(9):1413-1419, 1999. 

44.2%

42.0%

37.7%

32.2%

50.5% 50.0%

14.6%

22.1%

66.8% 65.5%

50.6%

46.3%

66.1%

61.7%

17.7%

25.6%

Drug Use Within 1 Year of First Opportunity

Boys Girls

Marijuana Cocaine Hallucinogens Heroin Marijuana Cocaine Hallucinogens Heroin

This graph shows the percentage of drug use within 1 year of the first opportunity to use drugs and the percentage of boys and girls

to eventually use drugs, given the opportunity. 

Eventual Drug Use

Boys Girls
Research Findings

40

Evidence Accumulates That Long-Term Marijuana Users

Experience Withdrawal

By Patrick Zickler, NIDA NOTES Staff Writer 

Laboratory studies have shown that animals exhibit 

symptoms of drug withdrawal after cessation of prolonged

marijuana administration. Some human studies have also

demonstrated withdrawal symptoms such as irritability,

stomach pain, aggression, and anxiety after cessation of

oral administration of tetrahydrocannabinol (THC), 

marijuana’s principal psychoactive component. Now,

NIDA-supported researchers at McLean Hospital in

Belmont, Massachusetts, and Columbia University in

New York City have shown that individuals who regularly

smoke marijuana experience withdrawal symptoms after

they stop smoking the drug.

“These studies suggest that in real-world situations abstinence from daily marijuana smoking creates withdrawal

symptoms similar to those of other drugs of abuse,” says

Dr. Jag Khalsa of NIDA’s Center on AIDS and Other

Medical Consequences of Drug Abuse. “Marijuana 

smokers may continue to use the drug to prevent the 

irritability and discomfort they experience when they

stop.”

Aggression

Dr. Elena Kouri and her colleagues at the Biological

Psychiatry Laboratory at McLean Hospital found that

long-term heavy marijuana users became more aggressive

during abstinence from marijuana than did former or

infrequent users. Previous studies of withdrawal symptoms

have relied largely on patients’ subjective reports of a range

of symptoms, Dr. Kouri notes. “We studied measurable

changes in one specific symptom—aggression,” she says.

The researchers recruited two groups of male and female

volunteers: 17 current long-term users of marijuana and a

control group of 20 infrequent or former users. Current

long-term users were smoking marijuana daily at the time

of recruitment and had smoked marijuana at least 5,000

times—the equivalent of smoking once each day for more

than 13 years. The infrequent or former users had not

smoked more than 50 times in their life and had smoked

less than once per month in the past year, or had formerly

smoked at least daily but had not smoked more than once

per week for the past 3 months.

At the beginning of the study, all participants were

instructed to refrain from any marijuana use for 28 days.

Abstinence was monitored by analysis of daily observed

urine sampling. Cigarette smokers were allowed to 

continue their usual tobacco use.

Aggression was measured on the first day of the study and

after 1, 3, 7, and 28 days of abstinence. To measure

aggression, the researchers used a 20-minute computerized

test that participants were told would measure motor skills

and other physiological characteristics. Participants were

told that pressing one button in a certain pattern would

add points to their score and that pressing another button

would subtract points from the score of their opponent,

who could similarly add or subtract points.

“The results demonstrate that 

abstinence is associated 

with unpleasant behavioral 

symptoms that may contribute to 

continued drug use.”

Volume 15, Number 1 (March 2000)

During the first weeks of abstinence, long-term current marijuana

smokers made more aggressive responses on a computerized game than

did infrequent or former smokers. The graph shows the average number of aggressive responses in 17 long-term daily (Solid Square) and 

20 infrequent or former (Open Square) marijuana smokers. 

(Star = significantly different from former smokers.) 
41

In fact, Dr. Kouri says, there was no human opponent; the

computer was programed to subtract points randomly in

order to give the illusion of a human opponent. At the

end of each session, aggressive responses—those that 

subtracted from the supposed opponent’s points—were

compared with nonagressive responses—those that added

to the participant’s points. Dr. Kouri notes that studies

involving parolees with a history of violent behavior have

shown a close correlation between performance on this

game and actual aggression.

After 1, 3, and 7 days of abstinence, current marijuana

users registered significantly more aggressive responses—

more than twice as many on days 3 and 7—than the 

control group. By the 28th day, there was no significant

difference between groups. Aggressive behavior was limited to responses in the test situation, Dr. Kouri notes; participants did not display overt hostility. “At this point we

do not know exactly how these findings reflect changes in

aggressive behavior outside the laboratory,” Dr. Kouri says.

“But the results demonstrate that abstinence is associated

with unpleasant behavioral symptoms that may contribute

to continued drug use.” 

Other Withdrawal Symptoms

Studies at Columbia University in New York City have

demonstrated that, in addition to aggression, marijuana

smokers experience other withdrawal symptoms such as

anxiety, stomach pain, and increased irritability during

abstinence from the drug. “These results suggest that

dependence may be an important consequence of repeated

daily exposure to marijuana,” says NIDA-supported

researcher Dr. Margaret Haney.

Dr. Haney and her colleagues investigated the effects of

abstinence on 12 adult males with an average age of 28

years who, in the laboratory, smoked marijuana with

THC concentrations of 3.1 percent or 1.8 percent, or

marijuana cigarettes containing no active THC. All participants smoked inactive marijuana during the first 4 days

of the study followed by either the high concentration,

low concentration, or inactive marijuana on alternating 

4-day periods. Three times each day, the participants 

completed a 50-item checklist that rated physical conditions such as hunger, dizziness, and headache and aspects

of their mood, for example, anxiety, talkativeness, friendliness, or depression.

Abstinence from either high- or low-concentration marijuana resulted in reduced hunger, decreased ratings of

“friendly” and “content,” and increased ratings of “irritability,” “stomach pain,” and “anxiety.” Moreover, Dr.

Haney notes, participants receiving high-concentration

marijuana rated the drug’s effects higher (“good drug

effect,” “stimulated,” “high”) on the first day of exposure

than on the fourth day, indicating the development of 

tolerance to THC.

“It appears likely that the onset of the withdrawal 

symptoms we observed in this study may contribute to

maintaining chronic marijuana use,” Dr. Haney says.

“The withdrawal symptoms are not as dramatic as those

associated with withdrawal from opiates or alcohol, but

are still significant to the individual marijuana user. These

symptoms must be taken into account in order to develop

effective treatment programs for marijuana abuse.”

Sources

• Kouri, E.M.; Pope, H.G.; and Lukas, S.E. Changes in

aggressive behavior during withdrawal from long-term

marijuana use. Psychopharmacology, 143:302-308,

1999.

• Haney, M.; Ward, A.S.; Comer, S.D.; Foltin, R.W.;

and Fischman, M.W. Abstinence symptoms following

smoked marijuana in humans. Psychopharmacology,

141:395-404, 1999. 

“The withdrawal symptoms are not as

dramatic as those associated with

withdrawal from opiates or alcohol,

but are still significant.”
Research Findings

42

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 uterine tubes might retard embryo development until 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.

Volume 15, Number 1 (March 2000)
43

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

44

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

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. 

Volume 14, Number 4 (November 1999)
45

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 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-IV 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.

“The progression from the use 

of cocaine or marijuana to abuse 

or dependence was due largely 

to genetic factors.”
46

• 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. 
Research Findings

47

MERIT Award Research Helps Reveal Long-term and

Developmental Impact of Drug Abuse

By Patrick Zickler, NIDA NOTES Staff Writer 

Identifying the long-term impact of drugs is crucial to

understanding drug abuse and addiction. Chronic use of

drugs by adults may have effects that last long after drug

use has stopped. In children, exposure to drugs may

impair development or contribute to behavioral disorders.

But understanding these long-term effects requires welldesigned research projects that may last decades. Three

recent MERIT Award recipients are carrying out investigations that will provide answers to important questions

about the long-term impact of drug use. 

Studying the Long-term Consequences of Prenatal

Exposure to Marijuana and Cigarettes 

For more than 15 years, Dr. Peter A.

Fried, professor of psychology at

Carleton University in Ottawa,

Canada, has studied mother-child

pairs to determine whether prenatal

exposure to marijuana, cigarettes, or

both affects the development and

behavior of children and adolescents.

Dr. Fried’s MERIT Award will allow

him to continue to follow the 

mother-child pairs as the children

develop through their teenage years. 

“Dr. Fried’s research represents an immense opportunity

to obtain previously unattainable information on the longterm consequences of prenatal exposure to marijuana and

cigarettes,” says Dr. Vincent Smeriglio of NIDA’s Center

for AIDS and Other Medical Consequences of Drug

Abuse. “His research already has made a significant contribution not only to documenting infancy and childhood

consequences, but also to exploring possible mechanisms

for those consequences.”

Dr. Fried’s research involves more than 150 children born

in the Ottawa area who were exposed before birth to cigarettes, marijuana, or both. Dr. Fried and his colleagues

evaluated the children several hours after birth and at 

4 days, 7 days, 9 days, 30 days, 6 months, and 1 year. 

The researchers have evaluated the children annually since

their first year to look for developmental and behavioral

problems that might be related to prenatal exposure to

marijuana or cigarettes. The researchers’ findings suggest

that marijuana exposure is associated with impaired executive functioning—the ability to make decisions and plan

for the future—in the children at 9 to 12 years of age.

“The major finding in this study about regular marijuana

use during pregnancy is that marijuana can have an

impact that may prevent a child from achieving his or her

full potential,” Dr. Fried says. 

Children born to women who smoked cigarettes during

pregnancy showed, from infancy through early adolescence, a reduction in auditory-based abilities. From ages 9

to 12, children who were exposed prenatally to tobacco

smoke showed a reduction in language scores and poorer

performance in tests involving the auditory aspects of

reading compared with children born to nonsmokers, with

the most heavily exposed children performing worse than

those exposed to smaller amounts. “The continuity, over

approximately 12 years, of the relationship between auditory and language variables and prenatal exposure to 

cigarette smoke suggests that these important aspects of

behavior are directly affected by maternal smoking,” 

Dr. Fried says. 

The MERIT Award will simplify the continuation of this

research through a crucial period of the children’s development, Dr. Fried notes. “Testing the children at midadolescence is particularly critical. Subtle learning difficulties are

most likely to manifest themselves at this stage of development, which involves complex behaviors requiring focused

attention and cognitive skills,” he says. 

Investigating the Effects of Chronic Heavy 

Marijuana Use 

Research has shown that heavy and long-term marijuana

users suffer impaired cognitive 

function during and immediately 

following periods of marijuana use.

But does this impairment last, and

for how long, if marijuana use is 

discontinued? 

Answers to these questions may come

from NIDA-supported research

under way at the McLean Hospital

Biological Psychiatry Laboratory in

Belmont, Massachusetts. 

The research is part of the work being done by Dr.

Harrison Pope, Jr., who recently received a NIDA MERIT

Award to continue his investigations. 

Dr. Peter A. Fried

Dr. Harrison Pope, Jr.

Volume 14, Number 1 (April 1999)
48

Dr. Pope’s research focuses on 30- to 54-year-old 

individuals—including both men and women and 

representing a range of ethnic and socioeconomic

groups—who have smoked marijuana at least 5,000 times.

This rate of use is equivalent to having smoked marijuana

at least once daily for more than 13 years. The study participants will be given a series of neuropsychological tests

during a 28-day period of abstinence—monitored by

analysis of observed daily urine collections—from marijuana and other drugs. 

Using similar neuropsychological tests, Dr. Pope demonstrated that college-age heavy marijuana users performed

more poorly than light users on memory, learning, and

attention tests following a 24-hour period of supervised

abstinence. “Testing after a longer abstinence period in

our new study will allow us to distinguish between 

prolonged impairment that results from marijuana 

neurotoxicity and temporary impairment that might 

simply be the result of marijuana residues or withdrawal

effects,” Dr. Pope says.

“This unique research will allow us to get a much clearer

understanding of the residual effects of chronic heavy

marijuana use on brain function,” says Dr. Jag Khalsa of

NIDA’s Clinical Medicine Branch. “Equally important is

the MERIT Award’s potential for expanding the current

research using this rich database.”

Looking for Links Between Substance Dependence and

Adolescent Conduct Disorder

Many adolescents who suffer from

conduct disorder are also substance

dependent, and the two disorders

together represent a major health

problem for adolescents. Research

being conducted by MERIT Award

recipient Dr. Thomas Crowley will

help clarify the critical relationship

between conduct disorders and 

substance dependence. 

Dr. Crowley, at the University of

Colorado School of Medicine’s Addiction Research and

Treatment Service in Denver, has spent more than 20

years treating adolescents referred by criminal justice 

agencies. “Among the patients diagnosed with conduct

disorder, 80 percent are also dependent on marijuana, and

more than half are dependent on nicotine,” Dr. Crowley

says. He found that conduct disorders preceded substance

dependence in the majority of the adolescents referred to

his program with both conditions. Although many of the

patients began their substance use—usually with marijuana

or alcohol—as early as age 12, in 75 percent of the

patients conduct disorders began even earlier. 

“Conduct disorder is a major contributor to substance

dependence in these patients, and our work suggests that

conduct disorders will coexist with most substance dependence that begins early in adolescence,” Dr. Crowley says. 

Dr. Crowley says his MERIT-supported research will allow

him to investigate more fully the relationship between

conduct disorder, attention deficit/hyperactivity disorder,

and substance dependence. In addition, Dr. Crowley and

his colleagues will examine the possible role of genetic and

familial factors in patients suffering from both conditions. 

“Antisocial drug dependence—that is, substance dependence combined with conduct disorder or antisocial 

personality disorder—may be due in part to genetic influences and may need special treatment,” Dr. Crowley says.

He and other researchers will use behavioral studies and

brain imaging to investigate the action of tetrahydrocannabinol, the principal psychoactive component in 

marijuana, in the brains of adolescents with coexisting

conduct disorder and marijuana dependence. “We will

identify and quantify the characteristic of comorbidity in

these patients and use that information to investigate the

underlying behavioral genetics,” Dr. Crowley says. 

“Dr. Crowley and his research team are one of the very

few groups in the country who are addressing this clinical

population. Their MERIT-supported studies will be of

crucial importance in understanding the psychopathology

of conduct disorder, attention deficit/hyperactivity disorder, and antisocial behavior in young adolescents with

substance dependence disorder,” says NIDA’s Dr. Khalsa. 

Sources 

• Crowley, T.J., et al. Substance dependent, conductdisordered adolescent males: Severity of diagnosis predicts 2-year outcome. Drug and Alcohol Dependence

49:225-237, 1998. 

• Crowley, T.J.; Macdonald, M.J.; Whitmore, E.A.; and

Mikulich, S.K. Cannabis dependence, withdrawal,

and reinforcing among adolescents with conduct

symptoms and substance use disorder. Drug and

Alcohol Dependence 50:27-37, 1998. 

• Fried, P.A. Cigarette smoke exposure and hearing loss.

Journal of the American Medical Association

280(11):963, 1998. 

Dr. Thomas Crowley
Research Findings

49

Tracking Trends in Teen Drug Abuse Over the Years

In 1975, shortly after NIDA was established, NIDA’s first

Monitoring the Future study (MTF) began to collect data

on drug use among the Nation’s high school seniors. 

In 1991, 8th- and 10th-grade students were added to 

the annual study to examine drug use among younger

adolescents. 

Over the course of its 24-year history, MTF has charted

some significant changes in illicit

drug use among America’s schoolaged children. For example, some

trends in annual use—use in the

past year—include:

• Annual use of any illicit drug by

high school seniors peaked at

54.2 percent in 1979, declined

to a low of 27.1 percent in

1992, then climbed steadily to

42.4 percent in 1997. Seniors’

use of any illicit drug has been

stable since then. 

• Annual marijuana use among

high school seniors crested in

1979 at 50.8 percent, then

declined to 21.9 percent in

1992, before rising steadily to

38.5 in 1997. Marijuana use by

seniors has remained steady

since then. 

• Annual cocaine use more than doubled among high

school seniors from 5.6 percent in 1975 to 13.1 percent in 1985 then declined sharply to 4.9 percent in

1996. Seniors’ cocaine use has been stable since then. 

• Heroin use always has been relatively low among

school children. However, in recent years, the availability of cheap, high-purity heroin that enables users

to get high by snorting the drug rather than injecting

it has contributed to heroin use approximately doubling among high school seniors from 0.4 percent in

1991 to 1.0 percent in 1998. 

• Marijuana, cocaine, and heroin use bottomed out in

the early 1990s but has since risen among children 

at all grade levels. MTF figures for 1997 and 1998

suggest this trend toward increased illicit drug use is

leveling off and may be in the process of reversing.

The Monitoring the Future study is funded by NIDA and conducted by the University of

Michigan’s Institute for Social Research.

Trends in Past-year Use of Drugs by High School Seniors

P

ercenta

g

e

Who

Use

d

in P

ast Ye

ar

Volume 14, Number 1 (April 1999)
Research Findings

50

Institute Launches Science Education Campaign for 

Middle Schoolers

By Barbara Cire, NIDA NOTES Associate Editor 

NIDA has launched a new science education campaign to

provide middle school students with information about

how drugs work in the brain. “NIDA Goes to School,” a

compilation of resource materials, is being mailed to 

science teachers at 18,084 public and private middle

schools across the country and 256 Department of

Defense schools overseas. The

campaign, undertaken in partnership with the National Association

of Biology Teachers, was

announced in November at the

National Leadership Forum of the

Community Anti-Drug Coalitions

of America in Washington, D.C.

In December, at a national press

conference about teen drug use,

Health and Human Services

Secretary Dr. Donna E. Shalala

cited the campaign as an effective

tool for teaching young people

how drugs damage their minds

and bodies and helping them to

resist drugs. 

“Science-based education about drug abuse should be a

prominent part of the curriculum for all students,” says

NIDA Director Dr. Alan I. Leshner. “This new initiative

provides teachers easily usable, student-oriented materials

to help achieve this goal.”

The “NIDA Goes to School” kit contains a variety of

research-based materials for teachers and students about

drugs and how they affect the brain. (See “A Toolbox for

Teachers.”) In addition, a “NIDA Goes to School” Web

site has been established at NIDA’s home page on the

World Wide Web. Students and teachers can use this

interactive Web site to get additional information about

drugs of abuse. The site also will serve as a major source of

feedback from students, teachers, and parents. As new 

science education materials are developed, they will be

added to the site. 

“We are very excited about this project,” says Dr. Cathrine

Sasek, science education coordinator in NIDA’s Office of

Science Policy and Communications. “Science teachers

want information and resources that they can use in their

classes. “NIDA Goes to School” provides teachers with

tools they can use to explain the neurobiology of substance abuse. We also hope that teachers will use NIDA 

as a source for additional fact-based information 

about drugs.” 

Many of the materials are written

specifically for students in grades 5

through 9. Seven Mind Over

Matter magazines feature the

adventures of Sara Bellum, a girl

who explores the brain’s response

to particular drugs and introduces

key concepts in neuroscience. 

The series includes magazines on

marijuana, opiates, stimulants, hallucinogens, inhalants, steroids, and

nicotine. Each magazine unfolds

into a poster with a quote from a

noted scientist superimposed on a

vivid color image of a brain area or

neuron. For example, on the

reverse side of the magazine on

inhalants is a quote from Nobel

Prize winner Albert von Szent-GyÖrgyi (1893-1986):

“Discovery consists of seeing what everybody has seen and

thinking what nobody thought.” 

Also included in the materials is an interactive CD-ROM

that features information on drugs of abuse in a variety of

television show formats. Called ATOD-TV—ATOD

stands for alcohol, tobacco, and other drugs—the CDROM was developed by Dr. Danny Wedding of the

Missouri Institute of Mental Health with a NIDA Science

Education Drug Abuse Partnership Award. In each

ATOD-TV show, human and animated characters play

out scenarios that illustrate different aspects of drug abuse

and addiction. For example, “Neuronet” is a news program that provides information about the brain and how

it is affected by drugs. “The Torn and the Troubled” is a

soap opera that challenges myths about drugs and addiction. “Wheels of Misfortune” uses a game-show format to

supply statistical information about drug use by different

populations. An accompanying teacher’s guide suggests

student activities and provides a comprehensive list of

resources for further information. 

HHS Secretary Dr. Donna E. Shalala praised the

“NIDA Goes to School” campaign at a recent national

press conference on teen drug use. 

Volume 13, Number 6 (March 1999)
51

“Our goal for this campaign is to enhance science education, increase science literacy, and encourage young people

to pursue careers in the sciences,” says Dr. Sasek. “By

introducing students to the science of drug abuse, we

hope to stimulate their interest in neuroscience and 

substance abuse research.” 

To Receive This Resource 

All materials in the “NIDA Goes to School” kit, with the

exception of the ATOD-TV CD-ROM and teacher’s

guide, are available free from the National Clearinghouse

for Alcohol and Drug Information. The materials also can

be downloaded from NIDA’s home page on the World

Wide Web at http://www.nida.nih.gov/. The “NIDA 

Goes to School” Web site can be accessed from NIDA’s

home page. 

A Toolbox For Teachers

The “NIDA Goes to School” kit contains the following publications and materials: 

• Seven Mind Over Matter magazines and 40-page teacher’s guide; 

• “ATOD-TV” CD-ROM and 96-page teacher’s guide; 

• Marijuana: Facts for Teens, a 16-page brochure; 

• Marijuana: Facts Parents Need to Know, a 28-page brochure; 

• Preventing Drug Abuse in Children and Adolescents: A Research-Based Guide, a 38-page brochure; and 

• Twenty NIDA Infofax information sheets on topics of interest to teachers, such as youth drug abuse trends,

descriptions of more than 14 commonly abused drugs, and prevention and treatment methods.
Research Findings

52

New NIDA Drug Abuse Education Materials for Middle 

School Students

NIDA has released a new series of drug abuse education

materials called Mind Over Matter. Designed for students

in grades five through nine, the series consists of six fullcolor glossy magazines that unfold into posters. The 

package also includes a comprehensive teacher’s guide. In

each magazine, a girl named Sara Bellum—a play on

“cerebellum,” a section of the brain that helps control

coordination—explores the brain’s response to a particular

drug and introduces key concepts in neuroscience. 

The magazines teach students about the adverse effects of

marijuana, opiates, stimulants, hallucinogens, inhalants,

and steroids. A seventh in the series, which will discuss

nicotine, will be available early in 1998. The magazines

are designed to excite students about science in general

and neuroscience in particular. 

The series uses illustrations and cartoons to provide useful

information. Some illustrations show Sara Bellum scuba

diving in the depths of the brain, watching drug molecules alter nerve cell activity. The cartoons often depict a

nerve cell or body organ performing abnormally under the

influence of drugs. For example, a heart playing drums in

a rock band loses its rhythm due to cocaine

The posters on the reverse side of each magazine can be

seen after the magazine is unfolded. Each 18- by 38-inch

poster has a quote from a well-known scientist superimposed over a vivid color photograph of a brain image or

neuron. For example, on the back side of the opiates 

magazine and superimposed over a photograph of neurons

in the brain is a quote from Jacob Bronowski, the late

British mathematician, which reads, “The essence of 

science: Ask an impertinent question, and you are on the

way to a pertinent answer.” 

The teacher’s guide provides detailed information on 

the brain and how drugs of abuse affect it. It also lists

resources and suggests activities to help students remember

the principles discussed in the magazines. 

Mind Over Matter is a product of NIDA’s Science

Education Program, which funds programs to interest

children in pursuing careers in science and to increase

knowledge about drug abuse and addiction among the

general public. The six magazine-posters and the teacher’s

guide are available free. To order copies, contact the

National Clearinghouse for Alcohol and Drug

Information, P.O. Box 2345, Rockville, MD 20847-2345,

(800) 729-6686 or (240) 221-4019; TDD number: 

(800) 487-4889; fax: (240) 221-4292; e-mail:

info@health.org. 

Following are the six magazines and their subjects: 

• The Brain’s Response to Marijuana shows how marijuana affects emotions, memory,

judgment, balance, and coordination. 

• The Brain’s Response to Opiates discusses how opiates such as heroin act on many

places in the brain and spinal cord and how addiction and withdrawal affect neurons. 

• The Brain’s Response to Stimulants demonstrates how cocaine and amphetamines

change the way neurons in the brain communicate and disrupt the functioning of the

heart and blood vessels. 

• The Brain’s Response to Hallucinogens explains how hallucinogens such as LSD and

PCP affect the senses by disrupting the actions of chemical messengers in the brain. 

• The Brain’s Response to Inhalants illustrates how inhalants break down the electrical

insulation surrounding many of the body’s neurons, making it difficult for them to

transmit messages. 

• The Brain’s Response to Steroids describes how anabolic steroids can make people look

stronger on the outside and yet cause extensive damage on the inside. 

Volume 12, Number 5 (September/October 1997)
Research Findings

53

Smoking Any Substance Raises Risk of Lung Infections

By Michael D. Mueller, NIDA NOTES Staff Writer

Smoking any substance—tobacco, marijuana, or “crack,” 

a smokable form of cocaine—increases a smoker’s risk of

developing bacterial pneumonia and other infections of

the lungs, according to the findings of drug abuse, 

smoking and health, and AIDS researchers.

Although some drugs seem to have specific damaging

effects when smoked, smoking anything appears to damage or paralyze the cilia, the hair-like projections in the

lungs that sweep out microbes and other matter that can

cause disease, according to NIDA-funded studies.

Damaging the lung’s cilia, the respiratory system’s first line

of defense, can have severe consequences for people with

weak immune systems, the studies note.

A NIDA workshop held in

August 1995 examined current

research at that time on the 

cardio-pulmonary complications

of crack cocaine use. In a report

summarizing the major findings

presented at the workshop, 

Dr. Pushpa V. Thadani, a pharmacologist in NIDA’s Division

of Basic Research, notes that

smoking cocaine appears to 

weaken the crack smoker’s natural resistance to infection in the lungs.

“Pulmonary alveolar macrophages—cells that protect the

lungs from infectious agents—are exposed to the highest

concentrations of cocaine,” says Dr. Thadani. NIDAfunded studies show that alveolar macrophages from 

crack cocaine smokers are less active than are alveolar

macrophages from nonsmokers in destroying Staphylococcus aureus, a common cause of bacterial lung infection.

Preliminary findings also indicate that alveolar macrophages of cocaine smokers are more susceptible to HIVrelated infections than are alveolar macrophages of people

who do not smoke cocaine.

“Much remains unknown about the effects of crack 

smoking on the alveolar macrophages and other cells of

defense in the lungs,” says Dr. Thadani. “However, it

appears that there are profound effects, and this needs to

be further explored,” she says.

Dr. Donald P. Tashkin, a professor of medicine at the

University of California at Los Angeles School of

Medicine, and his colleagues recently examined the effects

that habitual smoking of tobacco, marijuana, and/or

cocaine has on the lining of the lung’s air passages. The

NIDA-funded study included 53 nonsmokers, 14 smokers

of crack cocaine only, 40 smokers of marijuana only, and

31 regular tobacco smokers. In addition, there were 16

smokers of both cocaine and marijuana, 12 smokers of

cocaine and tobacco, and 44 smokers of both 

marijuana and tobacco. Thirty-one patients smoked all

three substances.

The researchers found that smoking either marijuana or

tobacco produces significant damage to the cilia in the 

lining of the airways. Among smokers of both marijuana

and tobacco, it appears that the effects of marijuana add

to the effects of tobacco, and vice versa. “The damage to

the ciliated cells in the lining of the airways caused

by smoking tobacco,

and/or marijuana weakens

the ability of the lungs to

remove inhaled particles,

making the lungs more

vulnerable to infection,”

says Dr. Tashkin.

Cocaine smokers had fewer

significant abnormalities

than marijuana or tobacco smokers did—but more abnormalities than were detected among nonsmokers, Dr.

Tashkin says. Among people who smoke both tobacco and

cocaine, cocaine smoking appears to produce injury to the

mucosal lining of the airways beyond that caused by

smoking tobacco alone.

A NIDA-supported study by Dr. Waleska T. Caiaffa and

her colleagues at Johns Hopkins University in Baltimore

compared the medical records of 40 HIV-positive injecting drug users (IDUs) who had suffered from one bout of

bacterial pneumonia with those of 197 HIV-positive IDUs

with no history of bacterial pneumonia. The study found

that HIV-positive IDUs who smoked illicit drugs were

almost twice as likely to develop bacterial pneumonia as

were their counterparts who did not smoke illicit drugs.

This association was independent of age, degree to which

the natural immune system had been suppressed, and 

cigarette smoking. Among the 77 HIV-positive IDUs who

reported smoking drugs, 87.9 percent indicated that they

had smoked marijuana, 25.9 percent said that they had

used cocaine, and 9.1 percent admitted smoking crack.

Smoking anything appears to 

damage or paralyze the cilia, the 

hair-like projections in the lungs 

that sweep out microbes and other

matter that can cause disease.

Volume 12, Number 1 (January/February 1997)
54

Smoking is a serious issue among AIDS patients, 

according to several NIDA-supported studies. The health

effects of smoking illicit drugs are above and beyond those

caused by smoking cigarettes, the studies note. People

with AIDS often die of pneumonia and other lung 

problems, and smoking tobacco and/or illicit drugs

increases the risks for these diseases.

“The effect that smoking has on the lungs is more serious

than most people realize. Smoking anything is bad for

your health, especially if your immune system has been

weakened,” says Dr. Tashkin.

Sources 

• Caiaffa, W.T.; Vlahov, D.; Graham, N.M.;

Astemborski, J.; Solomon, L.; Nelson, K.E.; and

Munoz, A. Drug smoking, Pneumo-cystis carinii

pneumonia, and immunosuppression increase risk of

bacterial pneumonia in human immunodeficiency

virus-seropositive injection drug users. Am. J. of

Respiratory and Critical Care Medicine 150:1493-

1498, 1994.

• Fligiel, S.E.; Roth, M.D.; Kleerup, E.C.; Barsky, S.H.;

Simmons, M.S.; and Tashkin, D.P. Tracheobronchial

histopathology in habitual smokers of cocaine, marijuana, and/or tobacco. Chest 112(2):319-326, 1997.

• Thadani, P.V., et al. NIDA conference report on cardiopulmonary complications of “crack” cocaine use:

Clinical manifestations and pathophysiology. Chest

110:1072-1076, 1996. 
Research Findings

55

Studies Show Cognitive Impairments Linger in Heavy 

Marijuana Users

By Robert Mathias, NIDA NOTES Staff Writer 

Students who smoke marijuana heavily may be limiting

their ability to learn, according to a NIDA-funded study.

The study found that college students who used marijuana

regularly had impaired skills related to attention, memory,

and learning 24 hours after

they had last used the drug.

The finding supports the

results of previous NIDAfunded research that reported

that adults who were chronic

heavy marijuana users showed

residual impairment in 

cognitive abilities a day after

they had last used marijuana.

“Now we know that for 

students who smoke marijuana

heavily, the ability to learn is

affected not just while they are

high, but for at least a day

after,” says NIDA Director 

Dr. Alan I. Leshner. Together

with other NIDA-funded

research that has shown a

marked increase in daily marijuana use among young people in recent years, this finding underlines the importance

of the Marijuana Use Prevention Initiative launched by

Health and Human Services Secretary Dr. Donna Shalala

last year, Dr. Leshner says. NIDA is playing a leading role

in the initiative by providing science-based information to

educate the public about the consequences of marijuana

use. (For more information, “Marijuana Conference

Advances HHS Secretary’s Marijuana Initiative,” V10-6

November/December 1995, and “Facts About 

Marijuana and Marijuana Use,” V11-1, March/April

1996.)

Regular heavy marijuana use compromises the ability to

learn and remember information primarily by impairing

the ability to focus, sustain, and shift attention, says 

Dr. Harrison Pope, Jr., of McLean Hospital in Belmont,

Massachusetts, who directed the recent study. Noting that

the actual ability to recall information remains relatively

unaffected, Dr. Pope says, “If you could get heavy users to

learn an item, then they could remember it; the problem

was getting them to learn it in the first place.”

In the study conducted among college students, Dr. Pope

and Dr. Deborah Yurgelun-Todd, also of McLean

Hospital, tested the cognitive functioning of 65 heavy

cannabis users, most of whom had smoked marijuana at

least 27 out of the previous 

30 days. The researchers compared the heavy users’ cognitive functioning to that of a

comparison group of 64 light

users, most of whom had

smoked marijuana on no more

than 3 of the previous 30 days.

Heavy users ranged in age

from 18 to 24 years and light

users from 18 to 28 years. The

two groups were similar demographically and had comparable numbers of men and

women. Subjects in both

groups had smoked marijuana

for at least 2 years, and none

had smoked regularly for more

than a decade.

To ensure that the subjects did not smoke marijuana or

use other illicit drugs or alcohol during the study,

researchers monitored them for 19 to 24 hours. Then the

subjects performed a battery of standard tests designed to

assess their ability to pay attention, learn, and recall new

information. The tests indicated that heavy marijuana

users had more difficulty than light users in sustaining and

shifting attention and hence in registering, organizing, and

using information. Heavy users exhibited these cognitive

deficits by being less able than light users were to learn

word lists; by making a greater number of errors in sorting

cards by different characteristics, such as by color or

shape; and by making more errors when the rules for sorting the cards were changed without warning. Men in the

heavy users group showed somewhat greater impairment

than women in the same group.

While the residual cognitive impairments detected in the

study were not severe, they could be significant in the dayto-day life of chronic users, Dr. Pope says. The diminished

ability to pay attention and decreased mental flexibility

exhibited in these tests may cause chronic marijuana users

Using the Wisconsin Card Sorting Test, shown here, 

Dr. Harrison Pope, Jr. (left) found that 24 hours after they

stopped using the drug, heavy marijuana smokers made a

greater number of errors than light users made in sorting cards

into different categories.

Volume 11, Number 3 (May/June 1996)
56

important difficulties in adapting to intellectual and interpersonal tasks, he says.

“This is a fairly definitive study because it was methodologically sound and controlled for a wide number of factors, including the possible confounding effects of alcohol

and other drug use,” says Dr. Jagjitsing Khalsa of NIDA’s

Division of Clinical and Services Research.

Previous studies have produced mixed findings about 

the residual effects of heavy marijuana use on neuropsychological performance, notes Dr. Khalsa. Methodological 

problems such as ambiguous terminology, failing to take

into account cognitive differences in study participants

prior to initiation of marijuana use, and failing to note the

possible effect of alcohol and other drugs have raised 

questions about the results of many of these studies. 

(For more information about methodological issues, see

the Pope, Gruber, and Yurgelun-Todd article listed below.)

The study by Dr. Pope and Dr. Yurgelun-Todd joins a

growing body of well-controlled and well-designed studies

that indicate protracted cognitive impairment among

heavy marijuana users, says Dr. Khalsa. For example, in

1993, Dr. Robert Block of the University of Iowa College

of Medicine compared adult heavy marijuana users and

nonusers ranging in age from 18 to 42 years who had

been matched on the basis of their intellectual functioning

before the onset of drug use. Subjects who used marijuana

frequently—7 or more times weekly for at least 2 years—

showed deficits in mathematical skills and verbal expression and selective impairments in memory retrieval

processes, the study reported. Although the two studies

used different neuropsychological tests, “in general, both

studies showed some impairments in cognitive abilities

among heavy marijuana users,” Dr. Block says.

It remains unclear whether marijuana’s short-term residual

cognitive impairments are due either to a residue of the

drug that remains in the brain after marijuana’s acute

effects have dissipated, to a withdrawal effect from abrupt

discontinuation of the drug, or to a neurotoxic effect of

the drug on brain structure or function. Research has yet

to demonstrate conclusively that chronic heavy marijuana

use results in cognitive deficits that persist after a prolonged period of abstinence. However, NIDA-supported

animal studies do show structural damage to the hippocampus, a structure critical in learning and memory,

from the principal psychoactive ingredient in marijuana.

To help answer these and other questions about the longterm effects of marijuana, both Dr. Pope and Dr. Block

plan followup studies to examine the effects of chronic

heavy marijuana use on cognition and brain function after

longer periods of abstinence. Dr. Block proposes to use

neuroimaging techniques to look at heavy users’ brains

while they perform cognitive tasks to determine whether

brain function or structure is altered after abstinence from

marijuana for a minimum of 30 hours. Dr. Pope is planning a study to determine if cognitive impairments persist

in long-time heavy marijuana users for up to 28 days after

they have stopped using marijuana.

Sources

• Block, R.I., and Ghoneim, M.M. Effects of chronic

marijuana use on human cognition.

Psychopharmacology 110:219-228, 1993.

• Pope, H.G., Jr.; Gruber, A.J.; and Yurgelun-Todd, D.

The residual neuropsychological effects of cannabis:

The current status of research. Drug and Alcohol

Dependence 38:25-34, 1995.

• Pope, H.G., Jr., and Yurgelun-Todd, D. The residual

cognitive effects of heavy marijuana use in college 

students. JAMA 275(7):521-527, 1996. 

The study joins a growing body of

research that indicates protracted

cognitive impairment among heavy

marijuana users.
57

Research Findings

Marijuana Impairs Driving-Related Skills and 

Workplace Performance

By Robert Mathias, NIDA NOTES Staff Writer 

Marijuana use impairs driving-related functions and is

linked to a pattern of behaviors that leads to poor job 

performance, according to two NIDA-supported studies

on the effects of marijuana on human performance.

Findings from the studies were presented at NIDA’s first

National Conference on Marijuana Use.

“Driving and marijuana do not mix; that’s the bottom

line,” said Dr. Stephen J. Heishman, a research psychologist in the Clinical Pharmacology Branch of NIDA’s

Division of Intramural Research. Figures from previous

studies of automobile accident victims show that from 6

to 12 percent of nonfatally injured drivers and 4 to 16

percent of fatally injured drivers had tetrahydrocannabinol

(THC), the psychoactive ingredient in marijuana, in their

bloodstream, Dr. Heishman said. One study showed that

32 percent of drivers in a shock trauma unit in Baltimore

had marijuana in their bloodstream, he noted. However,

in most of these studies, the majority of subjects who 

tested positive for THC also tested positive for alcohol,

making it difficult to single out THC’s effect on driving.

In a laboratory study at NIDA’s Addiction Research

Center in Baltimore that controlled for alcohol’s confounding effect, Dr. Heishman tested marijuana’s effects

on the functional components of driving. Study subjects

smoked a marijuana cigarette, waited 10 minutes, then

smoked another cigarette. Both cigarettes contained either

0, 1.8, or 3.6 percent THC. Twenty minutes after smoking the cigarettes, the subjects were given a standard 

sobriety test similar to a roadside sobriety test. The test

showed that marijuana significantly impaired their ability

to stand on one leg for 30 seconds or touch their finger to

their nose. As the dose of THC increased, the subjects

swayed more, raised their arms, and had to put their feet

down in an attempt to maintain their balance. Subjects

also committed 2.5 times more errors when they attempted

to touch their nose with their finger.

The data from these laboratory studies show that marijuana

impairs balance and coordination—functional components

important to driving—in a dose-related way, said 

Dr. Heishman. These effects may be related to reported

marijuana-induced impairment of automobile driving, 

he stated.

Highway and urban driving studies conducted in the

Netherlands show less impact on actual driving. However,

these driving studies used very low doses of marijuana for

safety reasons, Dr. Heishman said. Future research using

appropriate safety measures should test the effect of higher

doses of marijuana on driving as well as the combined

effect of marijuana and alcohol on driving, he concluded.

In another study, Dr. Wayne Lehman of Texas Christian

University looked at how marijuana affects job performance. A series of surveys he conducted among 4,600

municipal employees in four cities in the Southwest indicated that 8 percent of employees had smoked marijuana

in the past year, and a large percentage of these users had

smoked marijuana in the past month, Dr. Lehman said.

“Employees who report marijuana use are different from

nonusers,” said Dr. Lehman. They are much more likely

than nonusers to have arrest histories, low self-esteem,

high rates of depression, and friends who are deviant.

Many marijuana smokers also have alcohol-related 

problems. One-third of marijuana users in the surveys

reported they drank frequently, one-half said they got

drunk, and 60 percent reported a problem with alcohol

use, according to Dr. Lehman.

This behavioral pattern in the personal backgrounds of

marijuana-smoking employees was associated with negative attitudes toward work and job performance, Dr.

Lehman said. The surveys found that marijuana users were

less likely than nonusers to commit to the organization,

had less faith in management, and experienced low job

satisfaction. These workers reported more absenteeism,

tardiness, accidents, workers’ compensation claims, and

job turnover than workers who had not used marijuana.

They were also more likely to report to work with a hangover, miss work because of a hangover, and be drunk or

use drugs at work.

These data indicate that marijuana use is strongly 

associated with problematic alcohol use and a pattern of

general deviance that leads to impaired behaviors and poor

workplace performance, Dr. Lehman concluded. 

At NIDA’s National Conference on Marijuana

Use, Dr. Stephen Heishman presented data from

laboratory studies showing that marijuana

impairs functions important to driving.

Volume 11, Number 1 (January/February 1996)
Research Findings

58

Marijuana Antagonist Reveals Evidence of 

THC Dependence in Rats

By Neil Swan, NIDA NOTES Contributing Writer 

For the first time, researchers have demonstrated that 

marijuana may cause drug dependency in animals. This

finding was made possible by the recent development of a

potent marijuana antagonist—an agent that blocks many

effects of the drug. The marijuana antagonist appears to

act like an on-off switch, allowing researchers to control

the effects of withdrawal from delta-9-tetrahydrocannabinol (THC), the principal psychoactive ingredient 

of marijuana.

Dr. Billy Martin, a NIDA-funded marijuana researcher at

Virginia Commonwealth University’s Medical College of

Virginia, who conducted one of two initial studies, presented his findings at NIDA’s National Conference on

Marijuana Use: Prevention, Treatment, and Research last

summer. During his research, rats were exposed to THC

for 4 days, then given a dose of the THC antagonist SR

141716A, which was developed by French scientists last

year. The rats immediately and “dramatically” exhibited

classic rodent behavioral withdrawal symptoms, indicating

that they were dependent on THC, Dr. Martin said.

Within 10 minutes after administration of the marijuana

antagonist, the rats exhibited behavior that included “wetdog shakes” and facial rubbing, which constitute “definite

evidence of withdrawal” from the effects of THC, said Dr.

Martin. This behavior mimics long-observed opiate withdrawal symptoms in rodents.

The shakes and rubbing were so striking and frequent that

they could be quantified by trained observers. Other, less

frequent withdrawal-like behaviors included head shakes,

biting, drooping eyelids, retropulsion (backing away), ear

twitching, chewing, licking, and arching the back, 

Dr. Martin said.

The wet-dog shakes were dose-dependent, meaning they

became more pronounced as dose levels of the antagonist

were increased in the THC-exposed animals.

Dr. Martin acknowledged that such behavior is not like

any marijuana withdrawal syndrome in humans.

“The fact that people do seek treatment for marijuana

dependence is evidence of marijuana withdrawal in

humans, but, even among those seeking treatment, we do

not see dramatic withdrawal symptoms,” said Dr. Martin.

“That’s because the withdrawal process in humans is so

long and drawn out, evidenced chiefly by mild distress or

anxiety. But with the rats, using SR 141716A as an 

effective antagonist, we compress and accentuate that

withdrawal process. The challenge for us now is to use

these animal data to design human studies-to determine

how small a dose of THC is needed to become dependent

on marijuana,” said Dr. Martin.

Dr. Martin, senior investigator Dr. Mario D. Aceto, and

colleagues at the Department of Pharmacology and

Toxicology of Virginia Commonwealth University have

published the results of their research.

“We have been searching for a marijuana antagonist for

many years,” said Dr. Martin, who has been a marijuana

researcher for 22 years.

Sources

• Aceto, M.D.; Scates, S.M.; Lowe, J.A.; and Martin,

B.R. Canna-binoid-precipitated withdrawal by a 

selective antagonist: SR 141716A. Eur. J. Pharmacol.

282(1-3):R1-R2, 1995.

• Rinaldi-Carmona, M., et al. SR 141716A, a potent

and selective antagonist of the brain cannabinoid

receptor. FEBS (Federation of European Biochemical

Societies) Letters 350(2-3):240-244, 1994.

• Tsou, K.; Patrick, S.; and Walker, M.J. Physical 

withdrawal in rats tolerant to delta-9-tetrahydrocannabinol precipitated by a cannabinoid 

receptor antagonist. Eur. J. Pharmacol. 

280:R13-R15, 1995. 

Dr. Billy Martin found that when rats 

that are adminstered the main psychoactive

ingredient in marijuana are then given doses 

of a compound that blocks the action of this 

ingredient, the rats “dramatically” exhibit 

classic rodent withdrawal symptoms.

Volume 10, Number 6 (November/December 1995)
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