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DOCUMENT RESUME
ED 478 366 CG 032 474
TITLE A Collection of NIDA Notes: Articles That Address Research onMarijuana.
INSTITUTION National Inst. on Drug Abuse (DHHS/PHS), Bethesda, MD.REPORT NO NN0058
PUB DATE 2003-07-00
NOTE 64p.
AVAILABLE FROM For full text: http://165.112.78.61/NIDA_Notes/ NN0058.html.PUB TYPE Collected Works General (020)
EDRS PRICE EDRS Price MF01/PC03 Plus Postage.DESCRIPTORS Drug Abuse; Drug Rehabilitation; Illegal Drug Use;
*Marijuana; Prevention; *Research
ABSTRACT
Included in this document are selections of topic-specificarticles on marijuana research reprinted from the National Institute on DrugAbuse's (NIDA) research newsletter, NIDA Notes. The collection featuresarticles originally published from 1995 through 2002. Topics include long-term cognitive impairments in heavy marijuana users, evidence that chronicmarijuana users experience withdrawal upon quitting, the influence of genesand the environment on drug abuse vulnerability, the body's natural THC-likecompounds, epidemiology, prevention, and treatment. (GCP)
Reproductions supplied by EDRS are the best that can be madefrom the original document.
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Articles That Address
RESEARCHON MARIJUANA
U.S. DEPARTMENT OF EDUCATIONOffice of Educational Research and Improvement
EDUCATIONAL RESOURCES INFORMATIONCENTER (ERIC)
o This document has been reproduced asreceived from the person or organizationoriginating it.
0 Minor changes have been made toimprove reproduction quality.
Points of view or opinions stated in thisdocument do not necessarily representofficial OERI position or policy.
U.S. Department of Health and Human ServicesNational Institutes of Health
National Institute on Drug Abuse
BEST (707,7' /\7ARLABLE
NN0058
A Collection of
Articles That Address
RESEARCHON MARIJUANA
U.S. Department of Health and Human ServicesNational Institutes of Health
National Institute on Drug Abuse
3BEST COPY AVAILABLE
NN0058
Introduction
The National Institute on Drug Abuse (NIDA) supports more than 85 percent of the world's research on drug abuse andaddiction. 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 andeconomic 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 periodsthey cover.
We hope the information contained here answers your needs and interests. To subscribe to NIDA NOTES and for furtherinformation on NIDA's drug abuse and addiction research, please visit our Web site at www.drugabuse.gov.
4
Table of Contents
Teen Drug Use Declined in 2002, Report Shows(V17-5; January 2003) 1
Study Demonstrates That Marijuana Smokers ExperienceSignificant Withdrawal (V17-3; October 2002) 3
Cannabinoid Antagonist Reduces Marijuana's Effects inHumans (V17-3; October 2002) 5
New Research Report Presents Marijuana Facts(V17-3; October 2002) 7
Shortened Family Prevention Programs YieldLong-Lasting Reductions in Adolescent Drug Abuse(V17-2; May 2002) 8
Chronic Marijuana Abuse May Increase Risk of Stroke(V17-1; April 2002) 10
Cognitive Deficits Associated With Heavy MarijuanaUse Appear To Be Reversible (V17-1; April 2002) . . .11
Adolescent Treatment Programs Reduce Drug Abuse,Produce Other Improvements (V17-1; April 2002) .
Television Public Service AnnouncementsDecrease Marijuana Use in Targeted Teens(V16-4; October 2001) 15
MERIT Award Research Helps Reveal Long-term andDevelopmental Impact of Drug Abuse(V14-1; April 1999) 31
Tracking Trends in Teen Drug Abuse Over the Years(V14-1; April 1999) 33
Institute Launches Science Education Campaign forMiddle Schoolers (V13-6; March 1999) 34
Research Must Determine Medical Potential ofMarijuana, NIH Expert Panel Concludes(V12-6; November/December 1997) 36
New NIDA Drug Abuse Education Materials for MiddleSchool Students (V12-5; September/October 1997) 38
Promising Advances Toward Understanding the GeneticRoots of Addiction (V12-4; July/August 1997) 39
Smoking Any Substance Raises Risk of Lung Infections(V12-1; January/February 1997) 42
.13 Studies Show Cognitive Impairments Linger in HeavyMarijuana Users (V11-3; May/June 1996) 44
Marijuana Impairs Driving-Related Skills and WorkplacePerformance (V11-1; January/February 1996) 46
NIDA Conference Advances HHS Secretary's Marijuana.16 Initiative (V10-6; November/December 1995) 47
Adding Vouchers to Behavioral Therapies ImprovesMarijuana Treatment Results (V16-3; August 2001) .
Gender Differences in Prevalence of Drug Abuse Tracedto Opportunities to Use (V15-4; September 2000) . . .17
Cocaine, Marijuana, and Heroin Abuse Up, Methamphet-amine Abuse Down (V15-3; August 2000) 19
Evidence Accumulates That Long-Term Marijuana UsersExperience Withdrawal (V15-1; March 2000) 21
Marijuana-Like Compound in Womb May InfluenceEarly Pregnancy (V15-1; March 2000) 23
Twin Studies Help Define the Role of Genes inVulnerability to Drug Abuse(V14-4; November 1999) 25
Student Use of Marijuana Linked to Perceptions of Risk(V14-4; November 1999) 28
Ethnic Identification and Cultural Ties May HelpPrevent Drug Use (V14-3; September 1999) 29
5
Marijuana Antagonist Reveals Evidence of THCDependence in Rats (V10-6; November/December 1995) 49
NIDA Takes a Lead Role in National MarijuanaInitiative (V10-4; July/August 1995) 50
Marijuana Initiative Features Scientifically Accurate,Credible Messages (V10-4; July/August 1995) 51
NIDA Survey Provides First National Data on Drug UseDuring Pregnancy (V10-1; January/February 1995) . . 53
Early Childhood Behavior and TemperamentPredict Later Substance Use (V10-1; January/February 1995) 55
NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVol 17, No 5 (January 2003)
Teen Drug Use Declined in 2002, Report ShowsBy Patrick Zickler NIDA NOTES Staff Writer
Drug use by American teenagersdeclined in a broad range ofcategories during 2002,according to the latestMonitor-ing the Futuresurvey. Use of MDMA(ecstasy) dropped for thefirst time since it wasadded to the annual sur-vey in 1996, and mari-juana use declined to itslowest level in 8 years.The numbers of 8th-10th- and 12th-graderswho said they had smoked cigarettes in the month preced-ing the survey fell by 12 percent, 17 percent, and 10 per-cent, respectively.
"Our science-based education and prevention efforts arepaying off," said NIDA Acting Director Dr. Glen Hansonat a press conference announcing the 2002 survey find-ings. "Teenagers are considering the information in themessages before deciding whether or not to use drugs, andthey are making better decisions. In this survey we see thatteenagers are increasingly choosing not to use marijuana,not to use ecstasy and other club drugs, not to begin
smoking or using alco-
CVM the hol. They should becongratulated."
Te, The Monitoring the
(S.) Ala Future survey (MTF) is
Ticonducted annually bythe University of
a continuing study of American youth Michigan's Institute forSocial Research and has
been supported by NIDA throughout its 27-year history.The survey tracks illicit drug use and attitudes towarddrugs among 8th-, 10th-, and 12th-grade students. The2002 study surveyed a representative sample of more than43,000 students in 394 schools across the Nation.Students are asked about their attitudes toward drugs (Dothey perceive a risk associated with trying the drug? Dothey 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 respon-dent's lifetime. "Past year" refers to an individual's drug
cuse at least once during the year preceding their responseto the survey. "Past month" refers to an individual's druguse at least once during the month preceding theirresponse to the survey.)
Overall drug usethe proportion of students who report-ed using any illicit drug in the preceding yeardeclined
in grades 8 and 10. "This is the first time since1998 that we have seen a significantdecline in overall illicit drug use among10th-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 saidthey believed use of MDMA once or twice is harmful, andthe proportion of students who said they disapproved oftrying MDMA increased in all three grades. "We are grati-fied, but not satisfied. NIDA will continue to generateand disseminate science-based information that leads toincreases in understanding of the harm that comes fromdrug use," said Dr. Hanson.
"These changes in perceived risk and disapproval areencouraging indicators of future downturns in drug use,"Dr. Johnston observed. "This has proven to be the casewith ecstasy. In 2000, only 38 percent of seniors said therewas great risk of harm associated with trying ecstasy. Thatjumped to 48 percent in 2001 and increased again to 52percent in 2002. These unusually rapid changes no doubtreflect the effects of media coverage of adverse events aswell as NIDA's efforts to document and disseminate infor-mation about the adverse consequences of usingecstasy."
Similarly, the decreases in smoking reported for 2002 fol-low increases in the proportion of students who perceiveda negative image of smoking. Roughly half of students inall three grades said they strongly agree with the statement"I dislike being near people who are smoking." Perhapsmore important to teens, Dr. Johnston noted, is the socialimplication of changing attitudes toward smoking."Roughly three-quarters of boys and girls in all threegrades said they prefer to date nonsmokers. It now appearsthat taking up smoking makes a youngster less attractive,just the opposite of what cigarette advertising has beenpromising."
6BEST COPY AVAILABI F
Significant changes reported in the 2002 MTF surveyinclude the following:
Marijuana-Among 10th-graders, marijuana use inthe past year and past month decreased, and daily usein the past month was down. Past-year use decreasedfrom 32.7 percent to 30.3 percent; past-month usewent from 19.8 percent to 17.8 percent; and daily usein the past month declined from 4.5 percent to 3.9percent.
Cocaine-Crack use showed a significant increase inpast-year use among 10th-graders, returning toaround its 2000 level following a decline in 2001. For2002, 2.3 percent of 10th-graders reported past-yearuse of crack cocaine, compared with 1.8 percent in2001 and 2.2 percent in 2000.
Opiates-For the first time, MTF asked studentsabout nonmedical use of the prescription painkillersOxyContin and Vicodin. Past-year use of OxyContinwithout a doctor's order was reported by 1.3 percentof 8th-graders, 3.0 percent of 10th-graders, and 4.0percent of 12th-graders. Nonmedical use of Vicodinin the past year was reported by 2.5 percent of 8th-graders, 6.9 percent of 10th-graders, and 9.6 percentof 12th-graders.
Inhalants-Lifetime, past-year, and past-month useof inhalants decreased among 8th-graders, and life-time use decreased among 10th-graders. Lifetime usewent from 17.1 percent in 2001 to 15.2 percent in2002 among 8th-graders and from 15.2 percent to13.5 percent among 10th-graders.
LSD-LSD showed major changes from 2001 to2002. Rates of use decreased markedly in each gradeand reporting period. Past-year use, for example,declined from 6.6 percent to 3.5 percent among12th-graders, from 4.1 percent to 2.6 percent among10th-graders, and from 2.2 percent to 1.5 percentamong 8th-graders. These are the lowest rates of LSDuse in the history of the survey for each grade.
Club Drugs-Rates of MDMA (ecstasy) usedecreased significantly among 10th-graders. Theirpast-year use declined from 6.2 percent to 4.9 per-cent, and past-month use went from 2.6 percent to1.8 percent.
Findings from the 2002 MTF report are available throughNIDA's Web site, www.drugabuse.gov, and at the MTFWeb site, http://monitoringthefuture.org.
Past-Month Drug Use by10th-Graders Declines
Monitoring the Future survey results show thatteen drug use declined in 2002. Tenth-grade stu-dents reported significant reductions in overalldrug use and in use of marijuana and cigarettes.
MDMA Use Down,Perceived Risk Up
10%
8
6
2
0
60%
so
40
Past-Year Use of MDMA (Ecstasy)
12th-Graders
1997 1998 1999 2000 2001 2002
Percentage of Students Who Said Using MDMAOnce or Twice Is Harmful
30
o1997 1998 1999
12th-Graders
10th- Graders
0*"..8th - Graders
2000
Source: Monitoring the Future.2002.
2001 2002
Use of MDMA (ecstasy) declined sharply amongall teenagers in 2002, reversing 3 years ofincreased use. The decrease in use followsincreased perception among teens that MDMAuse has harmful consequences.
2 7
Study Demonstrates That Marijuana Smokers ExperienceSignificant WithdrawalBy Patrick Zickler, NIDA NOTES Staff Writer
Animal research and controlled studies of marijuanasmokers during inpatient treatment suggest that marijuanadependence, like dependence on other addictive drugs, isassociated with withdrawal symptomssuch as irritability,anger, depressed mood, headaches, restlessness, lack ofappetite, and cravingthat can make it difficult to stopusing the drug.
Now, NIDA-supported research conducted by Dr. AlanBudney and colleagues at the University of Vermont in
Burlington has found that marijuana smokers who stopusing the drug while in their home environment sufferwithdrawal symptoms that appear as severe as thoseassociated with tobacco-smoking.
"These findings represent a significant step toward generalacceptance of withdrawal as a key aspect of chronicmarijuana use," says Dr. Jag Khalsa of NIDA's Center onAIDS and Other Medical Consequences of Drug Abuse.Treatment providers may not address the problem of
Severity of Symptoms During Marijuana Use Versus Abstinence
Sleep Difficulty20
1 4 5 8 7 8 9 12 13 14 15 16
Aggression
2.0
Study Day
1 4 5 6 7 8 9 12 13 14 15 16
Study Day
Rated from 0 (not at all),I (mild), 2 (moderate), to 3 (severe)
DuringMarijuanaUse
Craving for Marijuana20 -
1.6
1.2
0.8
0.4
01 4 5
Irritability2.0
1.6
1.2
0.8
0.4
6 7 8 9 12 13 14 15 18
Study Day
1 4 5 6 7 8 9 12 13 14 15 16
DuringAbstinencefrom Marijuana
Study Day
Marijuana smokers living at home reported "clinically significant" withdrawal symptoms such as sleep difficulty marijuanacraving, aggression, and irritabilityduring 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.
3 8
marijuana withdrawal because the condition is not cur-rently included in the Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition (DSM-M, the standardreference published by the American PsychiatricAssociation.
Dr. Budney and his colleagues evaluated withdrawalsymptoms in 12 adult marijuana smokers (7 male, 5female, average age 30 years) over 3-day abstinence peri-ods that followed 5-day periods when participants couldsmoke marijuana at will. "We found consistent emotionaland behavioral symptoms that increased during abstinenceand dramatically decreased when marijuana smokingresumed, suggesting that these types of symptoms are thehallmark of acute marijuana withdrawal," Dr. Budneysays. "The symptoms most closely resembled many ofthose observed during nicotine withdrawal."
During the study, participants lived at home and madedaily records rating the intensity of withdrawal symptoms(on a scale from 0, "not at all," to 3, "severe") over thepreceding 24 hours. In addition, each participant desig-nated an observera friend or family member who spentat least 2 hours each day with the participantto providean independent rating of the participant's withdrawalsymptoms. The participants made daily laboratoryvisits during which their abstinence was confirmed byurine tests.
During the abstinence periods, participants reportedincreases in the severity of craving and sleep difficulty,decreased appetite, and increased aggression, anger, andirritability. In addition, participants reported an increasein "strange dreams" during the second abstinence period.Observers reported increased irritability and restlessnessamong the participants during abstinence.
"Marijuana withdrawal doesn't include dramatic physicalsymptoms such as the pain, nausea, heavy sweating, andcramps associated with opiate withdrawal. Nevertheless,the symptoms of marijuana withdrawal appear clinicallysignificant. It seems clear now that withdrawal from mari-juana produces identifiable behavioral and emotional dis-tress that may be as important as, if not more importantthan, physical symptoms in the development of depen-dence and undermining attempts to quit using the drug,"Dr. Budney says.
"Confirming withdrawal as part of marijuana dependencewill increase the likelihood that treatment providerswill alert patients to its symptoms and will help themcope with it through behavioral or pharmacologicaltreatments," says Dr. Khalsa.
Source
Budney, A.J.; Hughes, J.R.; Moore, B.A.; Novy, P.L.Marijuana abstinence effects in marijuana smokersmaintained in their home environment. Archives ofGeneral Psychiatry 58(10):917-924, 2001. IME
9
4
NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVol 17, No. 3 (October 2002)
Cannabinoid Antagonist Reduces Marijuana's Effects in HumansBy Patrick Zickler, NIDA NOTES Staff Writer
Marijuana smokers treated with an experimental com-pound reported reduced highs and had smaller heart rateincreases than untreated smokers in a recent study atNIDA's Intramural Research Program (IRP) in Baltimore.The finding confirms the pivotal role played in marijuanaintoxication by certain structurescalled cannabinoidreceptorson brain cells. In addition, the study suggeststhat the compound, called SR141716, may be useful as amedication to help marijuana smokers quit. (See also,"Study Opens Promising New Approach to DevelopingMedications To Prevent Relapse to Cocaine Use," in thisissue).
Marijuana, like other psychoactive drugs, achieves itseffects by attaching to nerve cells in the brain and alteringtheir function. The main psychoactive component ofmarijuana, tetrahydrocannabinol (THC), attaches tocannabinoid receptors. Animal studies have led scientiststo believe that a particular type of cannabinoid receptor isthe site at which THC initiates the effects that producemarijuana intoxication.
"Studies have shown in laboratory animals that the CB-1cannabinoid receptors, which are found in high densitiesin regions of the brain associated with attention, motorcontrol, and reasoning, play a major role in the effects ofmarijuana. However, until our study, this had not beenconfirmed in humans," says Dr. Marilyn Huestis, anIRP researcher.
To evaluate the role of human CB-1 receptors, Dr. Huestisand her colleagues studied the effects of SR141716 in 63adult men with a history of smoking marijuana. Thecompound was developed by Sanofi -Synthelabo, Inc., ofMalvern, Pennsylvania, and clinical testing of the com-pound in marijuana users was conducted through aCooperative Research and Development Agreement withNIDA. SR141716 has effectively blocked the effects ofmarijuana at CB-1 receptors in studies involving rats,pigeons, and monkeys. Participants in the NIDA researchreceived doses of 1, 3, 10, 30, or 90 mg SR141716 orplacebo. Two hours later, they smoked a marijuana ciga-rette containing THC or a marijuana cigarette withoutTHC. Immediately after smoking and up to 65 minuteslater, participants rated the strength of marijuana's effectson a scale ranging from 0 (no effect at all) to 100(extremely strong effect).
"Participants who received the 90-mg dose of SR141716reported 40 to 75 percent less drug effect than those who
Compound Reduces Marijuana Effects
eo
70
60015 50
140cc
30
E 20
10
0Feeling
High
0Aarljusne Orly
FeelingStoned
30
16 25
c 20
15
11 10
5
strength ot-1'Drug Effect
1.4arljuene and SR141716
HeartRate
Participants received either placebo or active SR141716 beforesmoking marijuana and were then asked to describe, on a scalefrom 0 (not at all) to 100 (extremely), "How high do you feelnow?" "How stoned on marijuana are you now?" and "How strongis the drug effect you feel now?" SR141716 (90 mg) reduced themaximum mean rating of the drug effects. Participants whoreceived SR141716 also experienced smaller increases in heart rateafter smoking marijuana.
didn't receive the compound. Those who received lowerdoses of the compound also reported less drug effect," Dr.Huestis says. "This demonstrates, first, that CB-1 recep-tors play a major role in THC's effects in humans and,second, that SR141716 can be used to at least partiallyblock the drug's effects."
In addition to its psychological effects on humans,marijuana increases the heart rate. Heart rates of men whosmoked marijuana with THC but received no SR141716increased by roughly 30 percent above baseline within 10minutes of smoking marijuana and were 15 percent higherat 1 hour after smoking. Increases in heart rate after mari-juana with THC was smoked were diminished in a dose-related manner by SR141716.
Blood tests showed that men who smoked marijuana withTHC and who received 90 mg SR141716 had blood con-centrations of THC similar to those of participants whodid not receive SR141716. This demonstrates that reduc-tion of marijuana's effects is attributable not to any effectof SR141716 on THC concentration, but to blockade ofCB-1 receptors, Dr. Huestis says.
Because SR141716 partially blocks THC's intoxicatingeffects, the compound may prove valuable in treating
510 BEST COPY AVAILfiALE
marijuana addiction, the researchers say. If marijuana doesnot provide its usual high, patients in treatment would beless tempted to smoke it and less vulnerable to relapse. Toevaluate the compound's role as a medication, NIDAresearchers currently are studying SR141716's ability toreduce the effects of THC when given in repeated dosesover 2 weeks. Other NIDA-supported research suggeststhat a different formulation of the compound may beeffective in treatment of cocaine addiction (see this issue's"Study Opens Promising New Approach to DevelopingMedications To Prevent Relapse to Cocaine Use").
In addition, Sanofi-Synthelabo is investigating thecompound's possible effects on other disorders related tocannabinoid receptors, such as increased appetite and foodintake, and in smoking cessation treatment.
Source
Huestis, M.A., et al. Blockade of effects of smokedmarijuana by the CB1-selective cannabinoid receptorantagonist SR141716. Archives of General Psychiatry58(4):322-328, 2001. ME
11
NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVol 17, No 3 (October 2002)
New Research Report Presents Marijuana Facts
The latest in NIDA'sResearch Report series is"Marijuana Abuse," aneight-page pamphletthat summarizes currentscientific knowledge ofmarijuana and itseffects. "Today's mari-juana is far more potentthan the marijuana of30 years ago," saysNIDA Acting DirectorDr. Glen R. Hanson."The drug can producea range of adverse physi-cal and emotional
effects, andcontrary to what many people believeitcan be addictive."
Acute Effects of Marijuana Use
Marijuana's effects start as soon as the drug enters thebrain. The drug's mind-altering effects are caused bytetrahydrocannabinol (THC). Just a few minutes afterinhalation of marijuana smoke, the user's heart rate accel-erates, bronchial passages relax, and blood vessels in theeyes enlarge. Soon the user feels euphoric, experiencingpleasant sensations, colors, and sounds more intenselythan usual. He or she may develop a dry mouth and feelvery hungry or thirsty. When the euphoria passes, the usermay feel sleepy or depressed. Sometimes marijuana useproduces anxiety, fear, or panic in the wake of euphoria.
During marijuana intoxication, a user may have difficultyforming memories. THC also interferes with parts of thebrain that control balance, posture, and coordinationof movement.
With high doses of marijuana, the user may suffer toxicpsychosis, including hallucinations, delusions, and a lossof the sense of personal identity. The specific causes areunknown, but toxic effects are more likely when a strongdose of THC is consumed in food or drink ratherthan smoked.
Long-Term Effects On Health
Marijuana has negative effects on memory and learningskills that are persistent but may not be permanent. Other
effects of long-term abuse are cumulative and may lastindefinitely. Regular marijuana smokers may have many ofthe same respiratory problems that tobacco smokers do:daily cough and phlegm production, frequent respiratoryillness, a tendency toward obstructed airways, and aheightened risk of lung infections. Data suggest also thatmarijuana smoke increases the likelihood that head andneck cancers will develop, and it has the potential topromote lung cancer.
Some adverse effects may result from THC's impairing theimmune system. In studies with mice, those exposed toTHC or related substances were more likely than theunexposed animals to develop bacterial infections andtumors. In studies that used both animal and humancells exposed to marijuana ingredients, the normal disease-preventing actions of immune cells were inhibited.
A serious risk of long-term marijuana use is addictioncompulsive use of the drug, even though it interferes withfamily, school, and work. Withdrawal symptoms and drugcraving can make it hard for long-term marijuana users tostop the drug. There are no medications to treat marijuanaaddiction, but behavioral therapies are available.Researchers are focusing on the most effective forms ofcounseling and incentives for abstinence.
Effects on School, Work, and Social Life
Students who smoke marijuana get lower grades thanthose who don't. Workers who smoke it are more likely tohave problems on the job. Depression, anxiety, and per-sonality disturbances are all associated with marijuana use.Marijuana interferes with a person's ability to learn andremember information, so frequent users may fall behindin developing intellectual, job, or social skills. Researchwith students has shown that marijuana use is linked to areduction in the psychological skills that enable individu-als to maintain confidence and persist in their pursuitof goals.
For More Information
"Marijuana Abuse" can be ordered from the NationalClearinghouse for Alcohol and Drug Information; call800-729-6686 (800-487-4889 for the deaf) or orderonline at www.health.org. Ask for publication#PHD940.
II. 27
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11
Shortened Family Prevention Programs Yield Long-LastingReductions in Adolescent Drug AbuseBy Robert Mathias, NIDA NOTES Staff Writer
Two brief family-focused drug abuse preventionprograms have produced long-term reductions insubstance abuse among adolescents in rural Iowapublic schools who were assigned to the programs inthe sixth grade, a study funded by NIDA and theNational Institute of Mental Health has shown.The programs may offer communities a practicalapproach to effective family-based drug abuseprevention.
The longer of the two programs reduced the propor-tion 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 shorterprogram decreased alcohol use among 10th-graderssignificantly, along with reducing lifetime substanceuse behaviors.
"The study demonstrates that brief family interven-tions can reduce drug use among young people dur- Lower percentages of ISFP and PDFY 10th-graders than control studentsing the high-risk years when they are making the had initiated a number of substance abuse behaviors involving use oftransition from childhood to adolescence," says Dr. alcohol, cigarettes, and marijuana 4 years after they had received theRichard Spoth of Iowa State University in Ames, programs in the 6th grade.who led the study. Reducing the number of children Staff members from the Iowa Cooperative State Research,who begin substance use during these years may have Education, and Extension Service of the U.S. Departmentimportant public health benefits because early initial use is of Agriculture worked with community facilitators toassociated with higher rates of substance dependence in implement either PDFY or ISFP in a total of 22 schoolslater adolescence and young adulthood, he says. with 459 families whose family, school, and communityA total of 667 families of sixth-graders from 33 public characteristics had previously been assessed. Eleven schoolsschools in Iowa were recruited for the study. The children's with 208 comparable families were assigned to a controlschools were randomly assigned to either a five-session group that was mailed leaflets on adolescent developmentprogram called Preparing for the Drug Free Years (PDFY), and parent-child relationships. The programs were deliv-a seven-session Iowa Strengthening Families Program ered in weekly evening sessions to participating families at(ISFP), or a control group. The two programs were the schools. Parents in PDFY attended four sessions anddesigned for families with young adolescents. The ISFP were joined by their children for a final joint session. Inwas adapted from a more extensive program that had pre- the relatively more intensive ISFP, parents and childrenviously been evaluated in a variety of settings and with attended both separate and joint sessions for 6 weeks andseveral racial and ethnic groups. a final joint session. The weekly PDFY and ISFP sessions
"The purpose of modifying longer programs and trying to sought to improve how parents and children functioned
replicate their results in new settings is to make them individually and as a family in a variety of situations. Both
more practical for communities to implement and for programs taught skills such as effective parenting, appro-priate management of family conflicts, and how to resistfamilies to participate in them," notes Dr. Elizabethpeer pressure. The development of such skills has beenRobertson of NIDA's Division of Epidemiology, Services as
land Prevention Research. "The fact that the adapted pro- linked to delayed onset or reduction of substance abuse.
grams achieved very positive results indicates they can be Four years after 6th-grade students had received the pro-whittled down and still maintain their effectiveness," grams, the researchers interviewed them and found thatshe says.
Substance Use Behaviors Among10th-Grade Students
Ever Used Alcohol
Without Parents'Permission
8
Brief Family Programs Reduce Rates of MarijuanaInitiation Over 4-Year Study
e
0
ISFP= Iowa Strengthening Families Program
PDFY= Preparing for the Drug-Free Years
0 Control
Control
PDFY
ISFP
0 Months 6 Months(6th Grade)
18 Months(7th Grade)
30 Months(8th Grade)
Time After Initial Assessment
48 Months(10th Grade)
Initiation of marijuana use occurred at a slower rate among students who participated in the ISFPand PDFY programs than among those in the control group.
significantly lower percentages of ISFP than control10th-graders had ever initiated any of five substance abusebehaviors. Specifically, lower percentages of ISFP studentsthan controls had begun to use alcohol, cigarettes, ormarijuana; had ever used alcohol without parental permis-sion; or had become drunk. The proportion of newmarijuana users in the control group was 2.4 times greaterthan it was among ISFP youths. Similarly, the proportionof controls who had been drunk or smoked cigarettes were1.7 and 1.5 times greater than they were among ISFPyouths. Participants in the PDFY program also showedlower rates of initiation of all five substance use behaviorsthan controls, but only the differences in lifetime drunk-enness and marijuana use approached statistical signifi-cance. Nevertheless, the rates of new marijuana use andever getting drunk were 1.5 and 1.2 times greater for con-trols than they were for PDFY youths. Actual rates of sub-stance use behaviors among 10th-graders in all threegroups are shown in the illustration on the preceedingpage.
Among those 10th-graders in the three groups who hadbegun to use alcohol, tobacco, or marijuana, the studyfound lower proportions of PDFY and ISFP students thancontrols had used alcohol and tobacco in the precedingmonth and marijuana during the preceding year. Forexample, frequency of past-month alcohol use among
PDFY and ISFP students wasabout two-thirds that of con-trols. Among ISFP students,past-month cigarette use wasapproximately half that of con-trol group students.
"Developmental timing is animportant factor in the long-term effects of these interven-tions," Dr. Spoth says."Intervening at this time, inthe sixth grade when kids areexperimenting with substances,probably contributes greatly tothe positive effects," he says.The careful design of the inter-ventions with their theory-based focus on parenting andfamily interactions also isimportant, he adds.
The critical element affected byboth programs is the parent component, says NIDA's Dr.Robertson. "When you provide parents with informationabout what to expect of children at that age, what is typi-cal and what is not, and how to deal with some of theproblems, you are shaping how parents relate to their chil-dren. Changing the family context can have a long-lastingeffect because you are positively influencing the day-to-day environment of the child over a long period of time,"she says.
Whether the findings of this study would apply to morediverse populations in other settings remains an openquestion, Dr. Robertson says. However, the original pro-grams from which the critical elements in these programswere derived have been successfully tested in a variety ofsettings, she notes. In addition, the ISFP has been adaptedfor and is now being tested with urban and rural African-Americans and Native American families.
Source
Spoth, R.L.; Redmond, C.; and Shin, C. Randomizedtrial of brief family interventions for general popula-tions: Adolescent substance use outcomes 4 years fol-lowing baseline. Journal of ConsultAand ClinicalPsychology 69(4):627-642, 2001.
4
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9
NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVol. 17, No. 1 (April 2002)
Chronic Marijuana Abuse May Increase Risk of Stroke
Dr. Ronald I. Herning and Dr. Jean Lud Cadet, withcolleagues at NIDA's Intramural Research Program inBaltimore, report preliminary evidence suggesting thatchronic abuse of marijuana can restrict blood flow to thebrain and increase the risk of stroke for young men aged18 to 30.
The investigators used transcranial Doppler sonography, anoninvasive technology that uses sound waves to take mea-surements and create images, to calculate the pulsatilityindexa measure of resistance to blood flowin cerebralarteries of 35 male participants, 16 long-term marijuanausers and 19 nonusers of marijuana. Marijuana users hadhigher resistance to blood flow to their brains than did
nonusers upon initial measurement, and the deficits per-sisted after the marijuana abusers remained abstinent for amonth, well past the time when acute withdrawal symp-toms were reported. As a result, the deficits do not appearto be related to a temporary withdrawal syndrome.
The findings suggest that, at least within the first 4 weeksof marijuana abstinence, blood flow in the brain in youngmarijuana abusers is comparable to that of 60-year-olds,which may be of clinical importance because advancingage increases the risk of stroke. Ma
The study was published in the June 2001 Annals of theNew York Academy of Science.
15
10
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II
Cognitive Deficits Associated With Heavy Marijuana Use AppearTo Be ReversibleBy Margi Grady, NIDA NOTES Contributing Writer
Memory and learning problems caused byheavy marijuana smoking persist for at least aweek after cessation of use of the drug, butthey appear to resolve completely within amonth, a NIDA-supported study shows."Cognitive impairment from heavy mari-juana use may linger for a week or longer,but it does not appear to be permanent," saysDr. Harrison Pope, Jr., who led the study atHarvard University's McLean Hospital inBelmont, Massachusetts. "Even if userssmoke a lot, these tests suggest they caneventually recover," he says. As a followup tothis research, Dr. Pope and his colleagues areusing functional magnetic resonance imagingto determine whether the more sensitiveassessment tool reveals cognitive effects thathis pencil-and-paper tests could not detect.
"Even though our study suggests that heavyusers recover from cognitive deficits after 4weeks of abstinence, it doesn't follow that marijuana is abenign substance," says Dr. Pope. He notes that the studyrevealed some startling demographic differences betweenlong-term heavy users and a control group. Data collectedon participants when they joined the study showed thatthose who had used marijuana heavily for many years hadmarkedly lower income and education levels than thecontrol group, regardless of whether they were still usingthe drug.
Dr. Pope and his colleagues examined cognitive functionin 180 participants, including 63 current heavy marijuanausers, 45 former heavy users, and 72 control subjects.Current heavy users had smoked marijuana a minimum of5,000 times during their lives (the equivalent of at leastonce a day for 13 years) and were smoking at least 7 timesa week at the beginning of the study. Former heavy usershad also smoked at least 5,000 times in their lives but nomore than 12 times during the previous 3 months. Thecontrol subjects had smoked at least once but no morethan 50 times during their lives and no more than once inthe previous year. Participants ranged in age from 30 to55. All three groups were carefully screened for unrelatedcharacteristics that might affect the study results.
All participants were required to remain abstinent frommarijuana and other drugs for the course of the 28-day
Heavy Marijuana Users Report Lower IncomeAnd Less Education Than Control Subjects
Education, High School or Less 29% 0%13%Mother's Education, High School or Less 61 40 58Father's Education, High School or Less 46 50 38
,-,71= ,:,,a ,40 z----, ---
51 51 26Household Income Less Than $30,000Parents' Household Income Less Than $30,000 25 44 18
Information gathered on the Harvard study's participants revealed that bothcurrent and former long-term heavy users of marijuana had markedly lower incomeand less education than control subjects, even though the education and incomeof the two groups' parents were similar, says Dr. Harrison Pope, Jr., the study'slead investigator.
study and submit urine specimens that were used toconfirm their abstinence. Their cognitive function wasevaluated through standardized neuropsychological testsat study entry and on the 1st, 7th, and 28th days of thestudy. On study entry (day 0) and days 1 and 7, currentheavy marijuana users scored significantly lower thancontrol subjects on tests of verbal learning and memory.This finding confirms and extends the findings of previ-ous studies by Dr. Pope's group and others that haveshown impaired cognitive skills in heavy marijuana usersfor up to 3 days after use is stopped. By day 28, the differ-ence between the scores of the control group and those ofcurrent heavy marijuana users disappeared.
Income and education data suggestconsequences of heavy marijuana use.
Two findings allowed the researchers to conclude that thecognitive deficits were associated with recent heavy userather than total lifetime use. First, former heavy usersshowed no significant difference from the control subjectson any of the tests on any of the testing days. Also, theresearchers found a clear relationship between lower test
1BEST COPY AVAILABLE
scores and higher levels of marijuana residues in urine atthe beginning of the study, but no relationship betweentest scores and total lifetime marijuana use.
"This study is particularly significant for treatment,"says Dr. Steven Grant of NIDA's Division of TreatmentResearch and Development. "By stopping drug use, heavymarijuana users are able to regain their memory andlearning functions. Still, we cannot say there are noconsequences to heavy marijuana use: The income andeducation data suggest the opposite."
Sources
Fletcher, J.M., et al. Cognitive correlates of long-termcannabis use in Costa Rican men. Archives of GeneralPsychiatry 53(11):1051-1057, 1996.
Pope, H.G., Jr., et al. Neuropsychological perfor-mance in long-term cannabis users. Archives ofGeneral Psychiatry 58(10):909-915, 2001.
Pope, H.G., Jr., and Yurgelun-Todd, D. The residualcognitive effects of heavy marijuana use in college stu-dents. Journal of the American Medical Association275(7):521-527, 1996.
Solowij, N. Cannabis and Cognitive Functioning.Cambrid e, UK: Cambridge University Press,1998.
1 7
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Adolescent Treatment Programs Reduce Drug Abuse,Produce Other ImprovementsBy Kimberly R. Martin, NIDA NOTES Contributing Writer
In the first large-scale study designed to evaluate drugabuse treatment outcomes among adolescents in age-specific treatment programs, NIDA-supported researchershave found that longer stays in these treatment programscan effectively decrease drug and alcohol use and criminalactivity as well as improve school performance andpsychological adjustment.
The study, part of NIDA's ongoing Drug Abuse TreatmentOutcome Studies for Adolescents (DATOS-A), analyzeddata from 23 community-based adolescent treatmentprograms that addressed peer relationships, educationalconcerns, and family issues such as parent-child relation-ships and parental substance abuse. Successful elements ofadult treatment programs, such as participation in grouptherapy and participation in a 12-step program, were alsoincluded in treatment plans.
"The results of this study are particularly impressive inlight of the fact that the adolescents had multiple prob-lems," says Dr. Christine Grella of the University ofCalifornia, Los Angeles (UCLA), Drug Abuse ResearchCenter, one of the study's investigators. "Although this isalso typical of many adults in treatment, timely resolutionof these problems is even more critical for adolescents.These young people are in the process of developingvalues, making lifestyle decisions, and preparing to assumeadult roles and responsibilities, such as family and work;whereas when many adults enter treatment, they havecompleted this process."
Treatment Programs Varied
Dr. Yih-Ing Hser, also of UCLA, led the research teamthat evaluated the treatment outcomes for 1,167 adoles-cents, age 11 to 18, who were admitted to one of thetreatment programs between 1993 and 1995. Thetreatment centers, located in Pittsburgh, Pennsylvania;Minneapolis, Minnesota; Chicago, Illinois; and Portland,Oregon, included eight residential programs, nine outpa-tient drug-free programs, and six short-term inpatient pro-grams.
The 418 adolescents in the residential treatment programsreceived education, individual and group counseling, andinterventions to develop social responsibility. The 292
Behaviors of Adolescents Before andOne Year After Treatment
DRUG USEBefore After
;,;;lircentage
Weekly Marijuana Use 80.4% 43.8%Heavy Drinking 33.8 20.3Hallucinogen Use 31.0 26.8Stimulant Use 19.1 15.3
SCHOOL PERFORMANCE
62.6 74.0Regular AttendanceGrades Average or Better 53.4 79.6
CRIMINAL ACTIVITIES
75.6 52.8Any Arrest 50.3 33.9
An evaluation of more than 1,100 adolescents who receivedsubstance abuse treatment in residential, short-term inpatient, ordrug free outpatient programs found improvement in rates of druguse and social behavior. Some 53 percent of those treated met orexceeded the minimum recommended stay in treatment.
adolescents in the outpatient drug-free programs receivededucation, skills training, and individual and groupcounseling. The 467 adolescents in short-term inpatientprograms received counseling and a 12-step program.Family therapy was strongly emphasized, and adolescentsin these programs were referred to continued outpatienttreatment. The average length of treatment for adolescentsin the residential, outpatient drug-free, and short-terminpatient programs was 5 months, 1.6 months, and 18days, respectively.
The adolescents were interviewed when they began treat-ment and again 1 year after discharge by professionalinterviewers who were not employed by the treatmentcenters. Problem severity was determined at the initialinterview according to a number of criteria. Dependenceon drugs or alcohol was determined from standardizeddiagnostic measures. To validate self-reports of drug use,one-quarter of the participants were selected randomly tosubmit urine samples during the posttreatment interview.
Before treatment, 25 percent of the participants used threeor more drugs, 36 percent were dependent on alcohol,
1-4
13
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In the year following treatment,more adolescents attended school
and reported average orbetter-than-average grades.
64 percent were dependent on marijuana, and 10 percentwere dependent on cocaine. In addition to substanceabuse problems, 63 percent were diagnosed with a mentaldisorder and 67 percent were criminally active.
Outcomes Overall
Research has indicated that in general the rate of drug andalcohol use tends_to increase during adolescence. In thepresent study, however, improvements were observed inmany of the areas evaluated, although some of theparticipants did not complete their treatment program.Comparing the year before treatment to the year aftertreatment, the adolescents showed significant declines inthe use of marijuana and alcohol, which are considered tobe the major drugs of abuse for this age group. Weekly ormore frequent marijuana use dropped from 80 percent to44 percent, and abstinence from any use of other illicitdrugs increased from 52 percent to 58 percent. Heavydrinking decreased from 34 percent to 20 percent, andcriminal activity decreased from 76 percent to 53 percent.Adolescents also reported fewer thoughts of suicide, lowerhostility, and higher self-esteem. In the year followingtreatment, more adolescents attended school and reportedaverage or better-than-average grades. Some exceptions tothe general pattern of improvement were that overall,cocaine and hallucinogen use did not improve during theyear after treatment.
Treatment Length and Outcomes
Previous research indicates that a minimum of 90 days oftreatment for residential and outpatient drug-freeprograms, and 21 days for short-term inpatient programs ispredictive of positive outcomes for adults in treatment.Better treatment outcomes were reported among adoles-cents who met or exceeded these minimum lengths oftreatment than for those who did not. Among the treat-ment participants, 58 percent of those in residentialprograms, 27 percent in outpatient drug-free programs,and 64 percent in short-term inpatient programs met orexceeded the minimum stay. In the year following treat-ment, those who met or exceeded the minimum treatmentwere 1.52 times more likely to abstain from drug andalcohol use and 1.2 times more likely to not be involvedin criminal activity. In addition, these adolescents were1.34 times more likely to have average or better-than-average grades.
This study confirms that community-based drug treat-ment programs designed for adolescents can reduce sub-stance abuse and have a positive impact on many otheraspects of their life, says Dr. Tom Hilton of NIDA'sDivision of Epidemiology, Services and PreventionResearch. These results justify new research to identify thekey elements common to effective treatment programs foradolescents, he noted.
Source
Hser, Y-I.; Grella, C.E.; Hubbard, R.L.; et al. An eval-uation of drug treatment for adolescents in four U.S.cities. Archives of General Psychiatry 58(7):689-695,2001. ME
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As- A Ss- II
Television Public Service Announcements Decrease Marijuana Usein Targeted TeensBy Kimberly R. Martin, NIDA NOTES Contributing Writer
NIDA-supported researchers havehelped clarify the necessary elements ineffective anti-drug public serviceannouncements (PSAs) directed athigh-sensation-seeking adolescents.
NIDA researchers have previouslyshown that high-sensation-seekersindividuals characterized by their needfor new, emotionally intense experi-ences and the willingness to take risksto obtain these experiencesare atgreater risk for using marijuana andother drugs and for using them at anearlier age than other individuals.
Using a prevention approach developedfrom previous NIDA-supportedstudies, the researchers produced fiveanti-marijuana PSAs. The dramaticand attention-getting PSAs were airedduring programs that appealed tohigh-sensation-seekers such as action-oriented television shows. The media Drs. Philip Palmgreen (left) and Lewis Donohew
supported by paid asplacement was review.a public service announcement at the
well as donated advertising to ensure University of Kentucky.
the most effective outreach to the target audience.
"To appealappeal to high-sensation-seekers, a PSA must bedramatic, intense, and highly original," says Dr. PhilipPalmgreen, the research team leader at the University ofKentucky in Lexington. "An effective PSA needs to showthe negative consequences that can occur as a direct resultof drug use. For example, high-sensation-seekers need tosee that they can end up in a wheelchair, lose their job, orlose their girlfriend or boyfriend as a result of drug use.We found that the threat of death is not a deterrentbecause high-sensation-seekers do not believe that death isa real possibility," he says.
The PSAs were aired from January through April 1997 inFayette County, Kentucky, and from January throughApril 1998 in Fayette County and Knox County,Tennessee. One hundred students in 7th through 10thgrade were selected each month by random phone calls
seeking teens by 26.7
and asked to participate in thestudy. The students were inter-viewed to determine whether theysaw the PSAs and their attitudestoward and whether they usedmarijuana and other drugs.Questions also were asked to deter-mine their degree of sensation-seeking. More than 70 percent ofthe targeted age groups watched atleast three PSAs per week, theresearchers' say.
Marijuana use declined substantial-ly among teens during the cam-paigns in both counties and resid-ual effects of the campaigns wereevident for several months.According to Dr. Palmgreen, thesecond campaign in FayetteCounty had a "booster effect,"resulting in further declines.Overall, marijuana use decreasedby 38 percent in Fayette County.In Knox County, marijuana usedeclined among high-sensation-
percent.
"We have shown that, for PSAs to be effective, they mustbe designed for a specific audience and must air frequentlyduring programs watched by that audience," says Dr.Palmgreen. "PSAs typically are shown during donated air-time. However, the trend toward paid placements of PSAs,as in various campaigns across the country, is a verypositive approach."
Source
Palmgreen, P.; Donohew, L.; Lorch, E.P.; Hoyle, R.;and Stephenson, M.T. Television campaigns and ado-lescent marijuana use: Tests of sensation seeking tar-geting. American Journal of Public Health 91 (2):292-296, 2001. ME
15
NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 16, Number 3 (August 2001)
Adding Vouchers to Behavioral Therapies Improves MarijuanaTreatment Results
Enhancing behavioral treatments by adding the opportu-nity to earn vouchers for remaining drug-free has beenshown to improve abstinence rates among cocaine- andopiate-addicted patients. Now, a NIDA-funded study hasshown that the combination of behavioral interventionsand voucher-based incentives also can improve treatmentresults for heavy marijuana abusers.
Researchers at the University of Vermont in Burlington,led by Dr. Alan J. Budney, recruited 60 heavy marijuanausers who wanted to quit. Most of the study participantshad long histories of marijuana abuse, smoked marijuanaalmost daily, and smoked more than once a day. Theywere randomly assigned to one of three treatments:motivational enhancement therapy, motivational enhance-ment plus behavioral coping skills therapy, or motivationalenhancement plus coping skills plus voucher-based incen-tives. Throughout the study, each participant gave urinesamples twice weekly to be tested for marijuana use. Ifpatients in the incentives group tested negative, theyearned vouchers that they could exchange for retail goodsor services, such as movie passes, sporting equipment,or vocational classes. Patients in the other two treatmentgroups did not receive such tangible rewards forabstinence.
Over the 14-week study, 40 percent of patients in theincentives group achieved at least 7 weeks of continuousabstinence from marijuana, compared with 5 percent of
Marijuana Abstinence at End of Treatment
ao
35
30
25
ao
is
10
5
35%Motivational enhancement plus coping
1---J skills plus voucher-based incentives
0 Motivational enhancement plusbehavioral coping skills therapy
0 Motivational enhancement therapy
10%
5%
Adding voucher-based incentives to behavioral and motivationaltreatments more than tripled the percentage of patients whostopped using marijuana by the end of treatment.
patients in each of the other groups. At the end of thetreatment period, 35 percent of the incentives group hadstopped using marijuana, compared to 10 percent of themotivational enhancement plus coping skills group and 5percent of the motivational enhancement group.
The study was published in the December 2000 issue ofthe Journal of Consulting and Clinical Psychology.
16
NIBANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 15, Number 4 (September 2000)
Gender Differences in Prevalence of Drug Abuse Traced toOpportunities to UseBy Patrick Zickler, NIDA NOTES Staff Writer
Males are more likely than females to abuse drugs.According to the 1999 National Household Survey onDrug Abuse (NHSDA)-an annual Substance Abuse andMental Health Services Administration survey of morethan 25,000 respondents-8.1 percent of males and 4.5percent of females older than age 12 had used illicit drugswithin the past month, and this ratio has remained fairlyconstant throughout the 29-year history of the survey.
s 1. 0./059.0%
43.9%
Boys Girls
A
2.771,28.7%
18.3%
compared with 43.9 percent of females; to use cocaine,28.7 percent of males and 18.3 percent of females; to usehallucinogens, 18.6 percent of males and 10 percent offemales; and to use heroin, 7.8 percent of males and 3.2percent of females.
Once presented with an opportunity to use drugs, 44.2percent of males and 42 percent of females began usingmarijuana within 1 year; 37.7 percent of males and 33.2
Having Opportunity to Use Drugs
3 f.239.2% I
28.7%
7g.h7.8%
3.2%
Boys Girls
NI 5.14.5%
Actual Drug Use
0
8.5% 1.4% 0.8%
Marijuana Cocaine Hallucinogens Heroin Marijuana Cocaine Hallucinogens Heroin
According to the 1993 National Household Survey on Drug Abuse, boys are more likely to abuse drugs than girls. The graphabove shows the estimated percentage of boys and girls using each drug and the percentage having the opportunity to use each drug.
Research by Dr. James Anthony, a NIDA-supportedscientist at the Johns Hopkins University School ofHygiene and Public Health in Baltimore, shows that thesegender differences in drug abuse are not related to genderdifferences in susceptibility. Instead, they have their foun-dation in the very first stage of drug involvement-theopportunity to use drugs. Once given the opportunity touse, males and females are equally likely to use drugs.
Dr. Anthony and his colleagues analyzed NHSDA data for1993 to look for information that might explain the gen-der difference in rates of drug abuse. "Males are morelikely than females to have an opportunity to use drugs.There is no male-female difference with respect to trying adrug once an opportunity to do so has been experienced,"Dr. Anthony says.
The findings are consistent for marijuana, cocaine, hallu-cinogens, and heroin, Dr. Anthony says. The proportionof opportunities to use marijuana was 59 percent of males
percent of females began using cocaine; 50.5 percent ofmales and 50 percent of females began using hallucino-gens; and 14.6 percent of males and 22.1 percent offemales began using heroin.
Dr. Anthony found that females were likely to get theirfirst opportunity to use cocaine at an earlier age than weremales (age 19 for females, age 20 for males) but thatthere were no differences among males and females in ageof first opportunity to use marijuana, heroin, orhallucinogens.
One benefit of improved understanding of the linkbetween opportunity and eventual use is that counselorsor 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 aboutthe opportunity to use drugs rather than a question aboutactual drug use, because the opportunity is less likely tobe illegal or particularly sensitive," Dr. Anthony says.
r) 217
idEST COPY AVAILABLE
Boys Girls
Use
7- 710
Within 1 Year of First Opportunity
'11°4
Boys Girls
Eventual
'3 °A
Drug Use
( 7%125.6%
.1,5%, 04
MK= Drug
1.1 t...2
65.
10.10.:444
66.8% 65.5% 677.14/.7%61.1%
50.5% 50.0% 50.6%14646.3%44.2
42.0%37.7%1
32.2%
14.b, 22.1%
17.7%4.6%
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 girlsto eventually use drugs, given the opportunity.
Understanding the differences in opportunities to usedrugs may also help shape prevention efforts, according toDr. Cora Lee Wetherington, NIDA's Women and GenderResearch Coordinator. "The prevalence of drug abuse isgreater for males than for females even though, given theinitial opportunity to use drugs, males and females areequally likely to move on to drug use. It appears that theopportunities themselves play a very important role indrug abuse and need more investigation. Understandingthe sex differences in opportunities could make it possibleto develop prevention programs that reduce the opportu-nities and, therefore, the higher rate of drug abuse amongmales. In fact, NIDA-supported research into sex differ-ences in opportunities (see this issue's "Boys and GirlsEncounter Different Drug Offers, Use Different Refusal
Strategies") raises the possibility that gender-specificprevention interventions that focus on drug opportunitiescould serve to reduce drug use by both males andfemales," Dr. Wetherington says.
Sources
Van Etten, M.L., and Anthony, J.C. Comparativeepidemiology of initial drug opportunities andtransitions to first use: Marijuana, cocaine,hallucinogens and heroin. Drug and AlcoholDependence 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. =I
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18.
A 111
Cocaine, Marijuana, and Heroin Abuse Up, MethamphetamineAbuse DownBy Robert Mathias, NIDA NOTES Staff Writer
Cocaine abuse indicators increased in many U.S. metro-politan areas during 1998 and the first half of 1999,according to a NIDA-supported network of drug abuseresearchers who regularly report data on drug abuse in theUnited States. The rise follows several years of stable ordeclining use, the researchers reported at the December1999 meeting of the Community Epidemiology WorkGroup (CEWG).
CEWG researchers meet twice a year to report on suchdrug abuse indicators as drug-related deaths, hospitalemergency department (ED) visits, and treatment admis-sions. Data from 20 cities presented at the Decembermeeting indicate that marijuana and heroin abuse alsocontinued to increase in most areas of the country.However, methamphetamine abuse declined in mostcities, including some areas that have been hardest hit bythe problem. Highlights from the meeting's advancereport are:
Cocaine. Indicators of cocaine abuse increased in half ofthe 20 CEWG cities, remained stable or mixed in 8, anddecreased in 2. Five cities reported significant increases incocaine-related ED incidents and 9 cities reported largeincreases in the number of cocaine-related deaths.
Heroin. Heroin abuse indicators increased in 10 CEWGcities, were stable or mixed in 9, and decreased in 1.Heroin abuse and snorting of the drug continued toincrease among younger populations, such as college stu-dents. These trends were particularly apparent in EastCoast cities where pure forms of white powder heroin,which can be snorted, are most available. Heroin-relateddeaths also increased in many areas of the country.
Marijuana. Seventeen CEWG cities reported increases inproblems associated with marijuana abuse. The percentageof drug abusers whose primary drug of abuse wasmarijuana continued to increase in many cities. Rates ofmarijuana-related ED visits also continued the consistent,often dramatic, increases shown over the last 6 years.Increases in marijuana-related problems may be tied toincreased availability, higher potency, and lower prices forthe drug along with perceptions that marijuana abuse isless risky than abuse of other drugs, the report indicates.
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Cities With SignificantChanges in Drug-RelatedEmergency Room Visits
I BEI I 1 I
Cocaine Heroin Marijuana Methamphetamine
-59%
Dallas45%
65%17%
Denver
Los Angeles23%
-36%
-44%
Miamitez 29%
New Orleans24%
16%
Philadelphia1E116%
17%
Phoenix1111%
-26%
San Diego16%
San Francisco91,?..,91
-39%
-44%Seattle
Washington, D.C.15%
25%
60%
Many CEWG citiesreported statisticallysignificant increases from1997 to 1998 in hospitalemergency department(ED) visits due tococaine, heroin, andmarijuana use. However,methamphetamine-related ED visits declinedsharply in most citieswhere rates had previouslybeen highest. Source:Substance Abuse andMental Health ServicesAdministration, DrugAbuse Warning Network,1998 (July 1999Update).
Methimphetamine. Indicators of methamphetamineabuse decreased in West Coast and Southwest areas whereabuse of the drug has been a major problem for years.Sharp declines in methamphetamine-related ED visitswere reported in 1998 in six CEWG areas. Several areasalso reported that methamphetamine treatment admis-sions, hospital mentions, and deaths continued to declinein the first half of 1999. Researchers cited several possiblereasons for these decreases, including initiation of nationaland community methamphetamine abuse prevention pro-grams and enactment of laws that make it more difficultto obtain the chemicals needed to produce the drug.
Club Drugs. Thirteen cities reported problems withMDMA (ecstasy) abuse. The drug is available at raves andnightclubs in most areas. Ecstasy abuse also is increasingin other settings, such as college campuses. Nine areasreported GHB (gamma-hydroxybutyrate) abuse at ravesand clubs. Numerous medical emergencies and severaldeaths were associated with GHB abuse.
For More Information
The CEWG "Advance Report, Epidemiologic Trends inDrug Abuse, December 1999," is available from NIDA'sWeb site, www.drugabuse.gov.
20
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Evidence Accumulates That Long-Term Marijuana UsersExperience WithdrawalBy Patrick Zickler, NIDA NOTES Staff Writer
Laboratory studies have shown that animals exhibitsymptoms of drug withdrawal after cessation of prolongedmarijuana administration. Some human studies have alsodemonstrated withdrawal symptoms such as irritability,stomach pain, aggression, and anxiety after cessation oforal administration of tetrahydrocannabinol (THC),marijuana's principal psychoactive component. Now,NIDA-supported researchers at McLean Hospital inBelmont, Massachusetts, and Columbia University inNew York City have shown that individuals who regularlysmoke marijuana experience withdrawal symptoms afterthey stop smoking the drug.
"These studies suggest that in real-world situations absti-nence from daily marijuana smoking creates withdrawalsymptoms similar to those of other drugs of abuse," saysDr. Jag Khalsa of NIDA's Center on AIDS and OtherMedical Consequences of Drug Abuse. "Marijuanasmokers may continue to use the drug to prevent theirritability and discomfort they experience when theystop."
Aggression
Dr. Elena Kouri and her colleagues at the BiologicalPsychiatry Laboratory at McLean Hospital found thatlong-term heavy marijuana users became more aggressiveduring abstinence from marijuana than did former orinfrequent users. Previous studies of withdrawal symptomshave relied largely on patients' subjective reports of a rangeof symptoms, Dr. Kouri notes. "We studied measurablechanges in one specific symptomaggression," she says.
The researchers recruited two groups of male and femalevolunteers: 17 current long-term users of marijuana and acontrol group of 20 infrequent or former users. Currentlong-term users were smoking marijuana daily at the timeof recruitment and had smoked marijuana at least 5,000timesthe equivalent of smoking once each day for morethan 13 years. The infrequent or former users had notsmoked more than 50 times in their life and had smokedless than once per month in the past year, or had formerlysmoked at least daily but had not smoked more than onceper week for the past 3 months.
At the beginning of the study, all participants wereinstructed to refrain from any marijuana use for 28 days.
Abstinence was monitored by analysis of daily observedurine sampling. Cigarette smokers were allowed tocontinue their usual tobacco use.
"The results demonstrate thatabstinence is associated
with unpleasant behavioralsymptoms that may contribute to
continued drug use."
Aggression was measured on the first day of the study andafter 1, 3, 7, and 28 days of abstinence. To measureaggression, the researchers used a 20-minute computerizedtest that participants were told would measure motor skillsand other physiological characteristics. Participants weretold that pressing one button in a certain pattern wouldadd points to their score and that pressing another buttonwould subtract points from the score of their opponent,who could similarly add or subtract points.
In fact, Dr. Kouri says, there was no human opponent; thecomputer was programed to subtract points randomly in
Abstinence Elicits Aggressive Behavior in
Long-Term Marijuana Smokers
Long-Term Daily Smokers (17)CI Infrequent or Former Smokers (20)
During the first weeks of abstinence, long-term current marijuana smokers made more aggres-sive responses on a computerized game than did infrequent or former smokers. The graphshows the average number of aggressive responses in 17 long-term daily (1) and 20 infre-quent or former a marijuana smokers. (it = significantly different from former smokers.)
21
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order to give the illusion of a human opponent. At theend of each session, aggressive responsesthose thatsubtracted from the supposed opponent's pointswerecompared with nonagressive responsesthose that addedto the participant's points. Dr. Kouri notes that studiesinvolving parolees with a history of violent behavior haveshown a close correlation between performance on thisgame and actual aggression.
After 1, 3, and 7 days of abstinence, current marijuanausers registered significantly more aggressive responsesmore than twice as many on days 3 and 7than thecontrol group. By the 28th day, there was no significantdifference between groups. Aggressive behavior was limit-ed to responses in the test situation, Dr. Kouri notes; par-ticipants did not display overt hostility. "At this point wedo not know exactly how these findings reflect changes inaggressive behavior outside the laboratory," Dr. Kouri says."But the results demonstrate that abstinence is associatedwith unpleasant behavioral symptoms that may contributeto continued drug use."
Other Withdrawal Symptoms
Studies at Columbia University in New York City havedemonstrated that, in addition to aggression, marijuanasmokers experience other withdrawal symptoms such asanxiety, stomach pain, and increased irritability duringabstinence from the drug. "These results suggest thatdependence may be an important consequence of repeateddaily exposure to marijuana," says NIDA-supportedresearcher Dr. Margaret Haney.
Dr. Haney and her colleagues investigated the effects ofabstinence on 12 adult males with an average age of 28years who, in the laboratory, smoked marijuana withTHC concentrations of 3.1 percent or 1.8 percent, ormarijuana cigarettes containing no active THC. All partic-ipants smoked inactive marijuana during the first 4 daysof the study followed by either the high concentration,low concentration, or inactive marijuana on alternating4-day periods. Three times each day, the participants com-pleted a 50-item checklist that rated physical conditionssuch as hunger, dizziness, and headache and aspects of
their mood, for example, anxiety, talkativeness, friendliness,or depression.
"The withdrawal symptoms are not asdramatic as those associated withwithdrawal from opiates or alcohol,
but are still significant."
Abstinence from either high- or low-concentration mari-juana resulted in reduced hunger, decreased ratings of"friendly" and "content," and increased ratings of "irri-tability," "stomach pain," and "anxiety." Moreover, Dr.Haney notes, participants receiving high-concentrationmarijuana rated the drug's effects higher ("good drugeffect," "stimulated," "high") on the first day of exposurethan on the fourth day, indicating the development oftolerance to THC.
"It appears likely that the onset of the withdrawalsymptoms we observed in this study may contribute tomaintaining chronic marijuana use," Dr. Haney says."The withdrawal symptoms are not as dramatic as thoseassociated with withdrawal from opiates or alcohol, butare still significant to the individual marijuana user. Thesesymptoms must be taken into account in order to developeffective treatment programs for marijuana abuse."
Sources
Kouri, E.M.; Pope, H.G.; and Lukas, S.E. Changes inaggressive behavior during withdrawal from long-termmarijuana use. Psychopharmacology, 143:302-308,1999.
Haney, M.; Ward, A.S.; Corner, S.D.; Foltin, R.W.;and.Fischman, M.W. Abstinence symptoms followingsmoked marijuana in humans. Psychopharmacology,141:395-404, 1999. IME
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Marijuana-Like Compound in Womb May Influence Early PregnancyBy Steven Stocker, NIDA NOTES Contributing Writer
Ever since scientists began discovering in the early 1990sthat marijuana-like compounds are normally produced invarious parts of the body, they have been investigating thefunction of these compounds. Research has suggested thatin the brain, the compounds, called endocannabinoids,inhibit pain perception and help to regulate movement. Inthe spleen and blood, endocannabinoids seem to be partlyinvolved in suppressing inflammation and other responsesof the immune system. Now NIDA-funded researchershave discovered that in the female mouse reproductivetract, one of these endocannabinoids, called anandamide,appears to help regulate the early stages of pregnancy.
Dr. Sudhansu K. Dey and his colleagues at the Universityof Kansas Medical Center in Kansas City, Kansas, havefound that the mouse uterus contains the highest anan-damide levels yet discovered in any mammalian tissue. Attimes, parts of the uterus contain anandamide levels thatare more than 100 times higher than those in the brain.The researchers have also found that mouse embryos con-tain cannabinoid receptorsproteins on the cell surfacesthat latch on to endocannabinoids in the vicinityagain,at levels that exceed those of the brain.
To find out why the uterus contains anandamide and theembryo contains cannabinoid receptors, the scientists firstexamined the effects of anandamide on embryo develop-ment. When they placed embryos from mice in cell cul-ture, about 90 percent proceeded to the next stage ofembryonic development, the blastocyst, which normallyimplants into the wall of the uterus and eventuallybecomes a fetus. With the addition of anandamide, only36 percent proceeded to the blastocyst stage. However, ifthese embryos were then placed in cell culture withoutanandamide, most started developing again.
In addition to inhibiting the growth of embryos prior toimplantation, anandamide probably also inhibits implan-tation itself, the researchers found. They determined thatadministering compounds similar to anandamide prevent-ed blastocysts from implanting in the uterine wall.
Functions of Anandamide
Anandamide may be serving at least three functions beforeand during implantation, suggests Dr. Dey. First, thecompound may be involved in synchronizing the develop-ment of the embryo with the preparation of the uterus forreceiving it. For example, anandamide secreted into thefluid of the uterine tubes might retard embryo develop-ment until the uterus is ready to receive the implantingblastocyst and to sustain it once it has implanted.
Second, anandamide may be involved in embryo selection."In the mouse, about 15 percent of embryos neverimplant, and in humans, as many as 60 percent eitherdon't implant or don't survive after implantation," saysDr. Dey. "Perhaps these rejected embryos are inferior insome way, and high anandamide levels in the uterine wallmay prevent them from implanting or surviving afterimplantation."
Finally, Dr. Dey suggests, anandamide may prevent asecond blastocyst from implanting nearby one that hasalready implanted. After the first one implants, theanandamide level in the surrounding area increases again,which prevents other blastocysts from implanting at thesame site.
Understanding how anandamide acts in the female repro-ductive tract may lead to an explanation for some cases ofinfertility in women, if anandamide is found to exist inthe human uterus, suggests Dr. Dey. In these infertilewomen, excessive uterine levels of anandamide may bedisrupting embryo development and implantation, saysDr. Dey.
This research may also lead to the development of newcontraceptives that can inhibit embryo developmentand implantation in the same manner as anandamide.Conversely, it could also lead to the development offertility agents that act in ways opposite to those ofanandamide.
23
Sources
Paria, B.C.; Das, S.K.; and Dey, S.K. The preimplan-tation mouse embryo is a target for cannabinoid lig-and-receptor signaling. Proceedings of the NationalAcademy of Sciences 92:9460-9464, 1995.
Paria, B.C., et al. Fatty-acid amide hydrolase isexpressed in the mouse uterus and embryo during theperiimplantation period. Biology of Reproduction60:1151-1157, 1999.
Schmid, P.C., et al. Changes in anandamide levels inmouse uterus are associated with uterine receptivityfor embryo implantation. Proceedings of the NationalAcademy of Sciences 94:4188-4192, 1997.
Yang, Z-M; Paria, B.C.; and Dey, S.K. Activation ofbrain-type cannabinoid receptors interferes withpreimplantation mouse embryo develament. Biologyof Reproduction 55:756- 761, 1996.
24
NalANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 14, Number 4 (November 1999)
Twin Studies Help Define the Role of Genes in Vulnerability toDrug AbuseBy Patrick Zickler, NIDA NOTES Staff Writer
Some individuals who use drugs become drug abusersthey continue taking drugs even though doing so causesserious problems in their lives. Others avoid abuse oraddiction. By studying patterns of drug use in pairs oftwins, NIDA-supported researchers are beginning toclarify the role that genes play in predisposing individualsto drug abuse.
"Twin studies explore the roles and interrelationship ofgenetic and environmental risk factors in the developmentof drug use, abuse, and dependence," says Dr. NaimahWeinberg of NIDA's Division of Epidemiology, Services,and Prevention Research.
In twin studies, researchers interview both members ofidentical (monozygotic) and fraternal (dizygotic) twinpairs, who typically are exposed to common environmen-tal influences. If genes influence their risk for drug abuse,identical twin pairs, who share the same genes, will tendto be concordantthat is, both will abuse drugs or notabuse drugs. Fraternal twin pairs, on the other hand, areno more similar genetically than non-twin siblings, and sowill be less concordantthere will be more pairs in whichone twin abuses drugs and the other does not. By compar-ing the degree of concordance in identical and fraternaltwins, researchers can estimate the extent to which genesinfluence vulnerability to drug abuse.
If genes influence the risk for drug abuse, identical twin pairs,who share the same genes, will tend to be concordantthat is,both will abuse drugs or both will not abuse drugs.
Marijuana and Cocaine Abuse Among Female Twins
NIDA-supported researchers Dr. Kenneth Kendler andDr. Carol Prescott at the Medical College of Virginia in
Richmond have examined the patterns of marijuana andcocaine use by female twins and found that genetic factorsplay a major role in the progression from drug use toabuse and dependence. The researchers interviewed 1,934twins, ranging in age from 22 to 62, recruited from theVirginia Twin Registry, a database compiled fromCommonwealth birth records.
Drug Use, Abuse, and DependenceAmong Female Twin Pairs
Use' Abuse
Cocaine
- Marijuana
Ajogirldweinnstical
/ (CIA 24/ /Fraternal
Dependence
For marijuana, use more than 10 times in any month; for cocaine, any use.I No instance in which both twins were dependent.2 Only 2 instances (1 identical pair fraternal pair) in which both twins were dependent.
Percentages of pairs in which both twins used, abused, or weredependent on marijuana or cocaine were higher in identicaltwins than in paternal twins.
In the study, drug "use" involved at least one nonpre-scribed use of a drug; "abuse" was based on the definitionprovided in the Diagnostic and Statistical Manual ofMental Disorders, Fourth Edition (DSM -I1'9, whichincludes symptoms such as recurrent use in situationswhere it presents a physical danger, failure to meet obliga-tions at work or school, or recurrent social or interperson-al problems caused by effects of the drug; and "depen-dence" was based on the DSM- IVdefinition and includedcharacteristics such as physical symptoms of tolerance orwithdrawal, taking larger amounts of the drug or using itover a longer period than intended, or spending large
25 3 0 BEST COPY AVAILABLE
amounts of time seeking, obtaining, and recovering fromthe effects of the drug.
"Our research supports other studies that indicate familyand social environmental factors are influential in deter-mining whether an individual begins using these drugs,"Dr. Kendler says. "But our findings suggest that the pro-gression from the use of cocaine or marijuana to abuse ordependence was due largely to genetic factors."
In addition, Dr. Kendler says, the study found that con-cordance rates-both twins using, abusing, or being depen-dent on drugs-were higher for identical than fraternaltwins (see chart). For cocaine use, concordance was 54percent in identical twins and 42 percent in fraternaltwins; for abuse, 47 percent in identical twins and 8 per-cent in fraternal twins; and for dependence, 35 percent inidentical twins and zero for fraternal twins.
"Abuse and dependence are highly heritable," Dr. Kendlersays. "For both cocaine and marijuana, genetic factors areresponsible for roughly 60 to 80 percent of the differencesin abuse and dependence between fraternal and identicaltwin pairs."
Genetic Risk Factors Differ Among Drugs andBetween Males and Females
Dr. Ming Tsuang, a NIDA-supported researcher atHarvard University in Cambridge, Massachusetts, hasfound that, in males, genetic influences are stronger forabuse of some drugs than for others. Dr. Tsuang and hiscolleagues studied drug use in 1,874 identical male twinpairs and 1,498 fraternal male twin pairs recruited fromthe Vietnam Era Twin Registry, a database compiled fromDepartment of Defense records. The average age ofparticipants was 45.
The researchers found evidence to suggest that geneticinfluences contribute to a common vulnerability for abus-ing marijuana, sedatives, stimulants, heroin or opiates, andpsychedelics. "There is some characteristic of the individ-ual that imparts vulnerability to the abuse of all categoriesof drugs. Abusing any category of drugs was associatedwith a marked increase in the probability of abusing everyother category of drugs," Dr. Tsuang says. In addition tothis shared vulnerability, the researchers found differentvulnerabilities for different drugs. "Each category of drugswe looked at, except psychedelics, had unique geneticinfluences," Dr. Tsuang says. "The genetic influence forabuse was greater for heroin than for any other drug."
NIDA-supported studies involving male and female twinssuggest that genetic factors for drug abuse are stronger inmales than in females. Dr. Marianne van den Bree and Dr.Roy Pickens of NIDA's Intramural Research Program andtheir 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 fraternalmale pairs, 38 identical female pairs, and 28 fraternalfemale pairs. Participants were interviewed to determinedrug use (five times or more) and clinical diagnosis(according to DSM-IV criteria) of drug abuse, dependence,or both for sedatives, stimulants, opiates, marijuana, orcocaine. For most drugs, clinical diagnosis of abuse,dependence, or both was more strongly influenced bygenetic factors than was drug use. In addition, for mostdrugs, genetic influences for abuse or dependence weregreater for males than for females.
"The progression from the useof cocaine or marijuana to abuseor dependence was due largely
to genetic factors."
"For females, genetic influences accounted for 47 percentof the differences between identical and fraternal twins inabuse, dependence, or both for any drug, compared with79 percent for males," Dr. van den Bree says. The impactof genetic factors also seems to differ for specific drugs,she notes. The researchers found no evidence for geneticinfluence for opiate or sedative abuse, dependence, orboth in females, but in males genetic influences were gen-erally larger than environmental influences.
"The results we see from these twin studies are makingimportant advances in our understanding of the role ofgenetic influences in drug abuse," observes NIDA's Dr.Weinberg. "Although the studies can't tell us anythingabout the risk for a particular individual, they are of enor-mous value in helping define the variations in drug abusevulnerability in the population."
Sources
American Psychiatric Association. Diagnostic andStatistical 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 offemale twins. American Journal of P.sychiatry155(8):1016-1022, 1998.
Kendler, K., and Prescott, C. Cocaine use, abuse, anddependence in a population-based sample of femaletwins. British Journal of Psychiatry 173:345-350, 1998.
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Tsuang, M., et al. Co-occurrence of abuse of differentdrugs in men. Archives of General Psychiatry 55:967-972, 1998.
3 2
Van den Bree, M.; Johnson, E.; Neale, M.; andPickens, R. Genetic and environmental influences ondrug use and abuse/dependence in male and femaletwins. Drmil and Alcohol Dependence 52(3):231-241,1998.
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NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 14, Number 4 (November 1999)
Student Use of Marijuana Linked to Perceptions of Risk
Many American teenagers today do not believe thatsmoking marijuana is dangerous. That was one of theconclusions of a recent study, by Dr. Jerald G. Bachmanand colleagues at the University of Michigan in AnnArbor, that examined changing attitudes of high schoolstudents toward the use of marijuana. The study is basedon an extensive review of data from NIDA-supportedannual surveys of 8th-, 10th-, and 12th-graders. Thesurveys, which together make up the ongoing Monitoringthe Future project, have collected data on drug use fromhigh school seniors since 1975. Data from 8th- and 10th-graders have been collected since 1991.
The percentage of high school seniors who used marijuanaat least once during the past year decreased from 50.8 per-cent in 1979 to 21.9 percent in 1992, before rising steadilyto 37.5 percent in 1998. While use rose, the perceptionof harm from use declined from 76.5 percent in 1992 to58.5 percent in 1998. Those who disapproved strongly ofregular use dropped from 90.1 percent in 1992 to 81.2percent in 1998.
Dr. Bachman's group's statistical analysis showed that thesimultaneous rise in use and decline in perceived harm-fulness during the mid-1990s was more than simplecoincidence. To account for this waning concern aboutthe dangers of marijuana, the researchers suggest thatthe decline in drug use in the 1980s may have led to a"lowering of the guard" of government, schools, massmedia, and families. News coverage of drug issues fellsubstantially in the early 1990s, and fewer antidrugmessages were aired during prime-time televisionprograms, the researchers note.
Young people pay close attention to realistically andcreatively presented information about the risks of druguse, the researchers suggest. "Presenting this kind of infor-mation on the risks and consequences of marijuana useonly once does not do the job," says Dr. Bachman."The message must be repeated regularly so we don'tlose students from one year to the next." LEE
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NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 14, Number 3 (September 1999)
Ethnic Identification and Cultural Ties May Help Prevent Drug UseBy Patrick Zickler, NIDA NOTES Staff Writer
Among Puerto Ricans, African Americans, and Asians,cultural influences and ethnic identification may signifi-cantly influence drug use. Studies conducted by NIDAresearchers in New York City suggest that Puerto Ricanand African-American adolescents who strongly identifywith their communities and cultures are less vulnerable torisk factors for drug use and benefit more from protectivefactors than do adolescentswithout this identification.In San Francisco, NIDA-supported research demon-strated different patterns of,drug use among differentsubgroups of the Asian com-munity. These findings
"For example, strong identification with Puerto Rican cul-tural factors offsets drug risks such as a father's drug use,peer tolerance of drugs, and the availability of drugs.Identification with Puerto Rican friends offsets risks asso-ciated with family tolerance for drug use and drug avail-ability," Dr. Brook notes.
Adolescents who stronglyidentify with their communities and
cultures are less vulnerable torisk factors for drug use.
suggest that incorporatingethnic and cultural compo-nents into drug abuse prevention programs can makethese programs more effective.
In one study, Dr. Judith Brook at the Mount Sinai Schoolof Medicine in New York City examined the extent towhich ethnic and cultural factors influenced drug-relatedbehavior in Puerto Rican adolescents. She and her col-leagues interviewed 275 males and 280 females aged 16 to24. The researchers asked the participants to describe theimportance in their lives of cultural and ethnic factorssuch as observation of Hispanic holidays and customs,preference for speaking Spanish or English, feelings ofattachment to their ethnic group, ethnic affiliation of theirfriends, and the value placed on the family. The partici-pants also answered questions designed to assess theirpersonal risk for drug use; these risk factors included theuse of drugs by parents or siblings, peer use or toleranceof drug use, perception of the riskiness of drug use, andthe availability of illegal drugs in their environment. Theparticipants were categorized into stages of drug use: noreported drug use, used alcohol or tobacco only, usedmarijuana but no other illicit drug, or used illicit drugsother than or in addition to marijuana.
"Other studies have looked at ethnic identification inisolation, not as an interactive part of a young person'scultural and social context," Dr. Brook says. "We wantedto determine the extent to which ethnic and culturalfactors might mitigate risk factors or enhance protective
factors and lead to lower stages of drug use. We foundthat strong ethnic identification acts to offset some risks,resulting in less drug use.
Ethnic identification also servesto amplify the effect of protec-tive factors, Dr. Brook says. Forexample, among participantswhose siblings were not drugusers, those with a strongPuerto Rican affiliation weresignificantly more likely to bein a lower stage of drug usethan those whose affiliationwas weaker.
In a related study that focused on late-adolescent AfricanAmericans in New York City, Dr. Brook and hercolleagues found a similar interaction between ethnic andcultural identification and drug use. The study involved627 participants-259 male and 368 femaleaged 16 to25 years.
The researchers found that components of ethnic identitysuch as awareness of African-American history andtradition, identification with African-American friends, orparticipation in African-American cultural activities suchas Kwanzaainteracted with other factors to reduce riskor to enhance protection.
"In isolation, few specific components of ethnic identityplay a role as main effects on drug use. Instead, they act incombination with family, personality, or peer influences toblunt the negative impact of risk factors and magnify thepositive value of protective factors," Dr. Brook says.
"Together, the research with Puerto Rican and African-American populations points out the importance ofincorporating ethnic identity into drug programs,"Dr. Brook concludes. "It can be a valuable part of drugprevention programs in communities and can also beapplied to individual treatment programs."
Cultural Differences Lead to Different Patterns ofDrug Use
In another NIDA-supported study, Dr. Tooru Nemotoand his colleagues at the University of California, San
D4
Francisco, have identified patterns of drug use amongAsian drug users that are unique to ethnicity, gender, agegroup, and immigrant status.
"Large multiracial studies have not distinguished betweenAsian ethnic groups," Dr. Nemoto says. "The purpose ofour study was to describe the patterns of drug use inChinese, Filipino, and Vietnamese groups and to assessthe relationship between cultural factors and drug useamong the groups."
The San Francisco study was based on qualitative inter-views with 35 Chinese, 31 Filipino, and 26 Vietnamesedrug users who were not enrolled in treatment programs.All participants were 18 years or older, with an average ageof 32.5, and had used illicit drugs more than three timesper week during the preceding 6 months. Overall, immi-grants and women represented 66 percent and 36 percent,respectively. However, all Vietnamese were immigrants.
Overall, participants born in the U.S. began using drugsat an earlier age-15 yearsthan did immigrant Asians-19 yearsand were more likely than immigrants to usemore than one drug. In general, women started drug useat about the same age as menabout 17.5 yearsbutethnic groups showed a varied pattern. Chinese womenbegan earlierat 15.2 yearsthan Chinese menat 18.5years. Filipino women began using drugs laterat 15.5yearsthan Filipino menat 13.1 years. Vietnamesewomen in the study started drug use much laterat 27.8yearsthan did Vietnamese menat 19.9 years.
Dr. Nemoto and his colleagues identified differences indrug use among the ethnic groups. Filipino drug userswere most likely to have begun drug use with marijuana,while Vietnamese drug users in the study most often
started with crack or powder cocaine. Chinese andVietnamese were twice as likely as Filipinos to be usingcrack as their current primary drug. Filipinos were fourtimes more likely to be using heroin than were Chinese orVietnamese. Filipino study participants were more likelythan Chinese or Vietnamese to be injecting and less likelyto be smoking drugs. There were also significant differ-ences in the characteristics of drug user networks amongthe ethnic groups. For example, Filipinos were more thantwice as likely as Chinese or Vietnamese participants touse drugs in groups that included members of other racesor ethnic groups.
"These differences among ethnic groups have importantimplications for the way we design programs aimed atAsian drug users," Dr. Nemoto says. "Prevention programsshould address the common factors among Asian drugusers, such as stigma associated with injection drug use,but we should also be careful to incorporate factors thatare unique to each target group."
Sources
Brook, J.S., et al. Drug use among African Americans:Ethnic identity as a protective factor. PsychologicalReports 83:1427-1446, 1998.
Brook, J.S.; Whiteman, M.; Balka, E.B.; Win, RT.;and Gursen, M.D. Drug use among Puerto Ricans:Ethnic identity as a protective factor. Hispanic Journalof Behavioral Sciences 20(2):241-254, 1998.
Nemoto, T, et al. Drug use behaviors among Asiandrug users in San Francisco. Addictive Behavior(in press). ME
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NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 14, Number 1 (April 1999)
MERIT Award Research Helps Reveal Long-term andDevelopmental Impact of Drug AbuseBy Patrick Zickler, NIDA NOTES Staff Writer
Identifying the long-term impact of drugs is crucial tounderstanding drug abuse and addiction. Chronic use ofdrugs by adults may have effects that last long after druguse has stopped. In children, exposure to drugs mayimpair development or contribute to behavioral disorders.But understanding these long-term effects requires well-designed research projects that may last decades. Threerecent MERIT Award recipients are carrying out investiga-tions that will provide answers to important questionsabout the long-term impact of drug use.
Studying the Long-term Consequences of PrenatalExposure to Marijuana and Cigarettes
Dr. Peter A. Fried
For more than 15 years, Dr. Peter A.Fried, professor of psychology atCarleton University in Ottawa,Canada, has studied mother-childpairs to determine whether prenatalexposure to marijuana, cigarettes, orboth affects the development andbehavior of children and adolescents.Dr. Fried's MERIT Award will allowhim to continue to follow themother-child pairs as the children
develop through their teenage years.
"Dr. Fried's research represents an immense opportunityto obtain previously unattainable information on the long-term consequences of prenatal exposure to marijuana andcigarettes," says Dr. Vincent Smeriglio of NIDA's Centerfor AIDS and Other Medical Consequences of DrugAbuse. "His research already has made a significant contri-bution not only to documenting infancy and childhoodconsequences, but also to exploring possible mechanismsfor those consequences."
Dr. Fried's research involves more than 150 children bornin the Ottawa area who were exposed before birth to ciga-rettes, marijuana, or both. Dr. Fried and his colleaguesevaluated the children several hours after birth and at4 days, 7 days, 9 days, 30 days, 6 months, and 1 year.The researchers have evaluated the children annually sincetheir first year to look for developmental and behavioralproblems that might be related to prenatal exposure tomarijuana or cigarettes. The researchers' findings suggestthat marijuana exposure is associated with impaired execu-tive functioningthe ability to make decisions and plan
for the futurein the children at 9 to 12 years of age."The major finding in this study about regular marijuanause during pregnancy is that marijuana can have animpact that may prevent a child from achieving his or herfull potential," Dr. Fried says.
Children born to women who smoked cigarettes duringpregnancy showed, from infancy through early adoles-cence, a reduction in auditory-based abilities. From ages 9to 12, children who were exposed prenatally to tobaccosmoke showed a reduction in language scores and poorerperformance in tests involving the auditory aspects ofreading compared with children born to nonsmokers, withthe most heavily exposed children performing worse thanthose exposed to smaller amounts. "The continuity, overapproximately 12 years, of the relationship between audi-tory and language variables and prenatal exposure tocigarette smoke suggests that these important aspects ofbehavior are directly affected by maternal smoking,"Dr. Fried says.
The MERIT Award will simplify the continuation of thisresearch through a crucial period of the children's develop-ment, Dr. Fried notes. "Testing the children at midadoles-cence is particularly critical. Subtle learning difficulties aremost likely to manifest themselves at this stage of develop-ment, which involves complex behaviors requiring focusedattention and cognitive skills," he says.
Investigating the Effects of Chronic HeavyMarijuana Use
Research has shown that heavy and long-term marijuanausers suffer impaired cognitivefunction during and immediatelyfollowing periods of marijuana use.But does this impairment last, andfor how long, if marijuana use isdiscontinued?
Answers to these questions may comefrom NIDA-supported researchunder way at the McLean HospitalBiological Psychiatry Laboratory inBelmont, Massachusetts.
The research is part of the work being done by Dr.Harrison Pope, Jr., who recently received a NIDA MERITAward to continue his investigations.
4,
Dr. Harrison Pope, Jr.
356
Dr. Pope's research focuses on 30- to 54-year-oldindividualsincluding both men and women andrepresenting a range of ethnic and socioeconomicgroupswho have smoked marijuana at least 5,000 times.This rate of use is equivalent to having smoked marijuanaat least once daily for more than 13 years. The study par-ticipants will be given a series of neuropsychological testsduring a 28-day period of abstinencemonitored byanalysis of observed daily urine collectionsfrom mari-juana and other drugs.
Using similar neuropsychological tests, Dr. Pope demon-strated that college-age heavy marijuana users performedmore poorly than light users on memory, learning, andattention tests following a 24-hour period of supervisedabstinence. "Testing after a longer abstinence period inour new study will allow us to distinguish betweenprolonged impairment that results from marijuananeurotoxicity and temporary impairment that mightsimply be the result of marijuana residues or withdrawaleffects," Dr. Pope says.
"This unique research will allow us to get a much clearerunderstanding of the residual effects of chronic heavymarijuana use on brain function," says Dr. Jag Khalsa ofNIDA's Clinical Medicine Branch. "Equally important isthe MERIT Award's potential for expanding the currentresearch using this rich database."
Looking for Links Between Substance Dependence andAdolescent Conduct Disorder
Dr. Thomas Crowley
Dr. Crowley, at the University ofColorado School of Medicine's Addiction Research andTreatment Service in Denver, has spent more than 20years treating adolescents referred by criminal justiceagencies. "Among the patients diagnosed with conductdisorder, 80 percent are also dependent on marijuana, andmore than half are dependent on nicotine," Dr. Crowleysays. He found that conduct disorders preceded substancedependence in the majority of the adolescents referred to
Many adolescents who suffer fromconduct disorder are also substancedependent, and the two disorderstogether represent a major healthproblem for adolescents. Researchbeing conducted by MERIT Awardrecipient Dr. Thomas Crowley willhelp clarify the critical relationshipbetween conduct disorders andsubstance dependence.
his program with both conditions. Although many of thepatients began their substance useusually with marijuanaor alcoholas early as age 12, in 75 percent of thepatients conduct disorders began even earlier.
"Conduct disorder is a major contributor to substancedependence in these patients, and our work suggests thatconduct disorders will coexist with most substance depen-dence that begins early in adolescence," Dr. Crowley says.
Dr. Crowley says his MERIT-supported research will allowhim to investigate more fully the relationship betweenconduct disorder, attention deficit/hyperactivity disorder,and substance dependence. In addition, Dr. Crowley andhis colleagues will examine the possible role of genetic andfamilial factors in patients suffering from both conditions.
"Antisocial drug dependencethat is, substance depen-dence combined with conduct disorder or antisocialpersonality disordermay be due in part to genetic influ-ences and may need special treatment," Dr. Crowley says.He and other researchers will use behavioral studies andbrain imaging to investigate the action of tetrahydro-cannabinol, the principal psychoactive component inmarijuana, in the brains of adolescents with coexistingconduct disorder and marijuana dependence. "We willidentify and quantify the characteristic of comorbidity inthese patients and use that information to investigate theunderlying behavioral genetics," Dr. Crowley says.
"Dr. Crowley and his research team are one of the veryfew groups in the country who are addressing this clinicalpopulation. Their MERIT-supported studies will be ofcrucial importance in understanding the psychopathologyof conduct disorder, attention deficit/hyperactivity disor-der, and antisocial behavior in young adolescents with,substance dependence disorder," says NIDA's Dr. Khalsa.
Sources
Crowley, T.J., et al. Substance dependent, conduct-disordered adolescent males: Severity of diagnosis pre-dicts 2-year outcome. Drug and Alcohol Dependence49:225-237, 1998.
Crowley, T.J.; Macdonald, M.J.; Whitmore, E.A.; andMikulich, S.K. Cannabis dependence, withdrawal,and reinforcing among adolescents with conductsymptoms and substance use disorder. Drug andAlcohol Dependence 50:27-37, 1998.
Fried, P.A. Cigarette smoke exposure and hearing loss.Journal of the American Medical Association280(11):963, 1998 MI
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I
a a
Tracking Trends in Teen Drug Abuse Over the Years
In 1975, shortly after NIDA was established, NIDA's firstMonitoring the Future study (MTF) began to collect dataon drug use among the Nation's high school seniors.In 1991, 8th- and 10th-grade students were added tothe annual study to examine drug use among youngeradolescents.
Over the course of its 24-year history, MTF has chartedsome significant changes in illicitdrug use among America's school-aged children. For example, sometrends in annual useuse in thepast yearinclude:
Annual use of any illicit drug byhigh school seniors peaked at54.2 percent iri 1979, declinedto a low of 27.1 percent in1992, then climbed steadily to42.4 percent in 1997. Seniors'use of any illicit drug has beenstable since then.
Annual marijuana use amonghigh school seniors crested in1979 at 50.8 percent, thendeclined to 21.9 percent in
' 1992, before rising steadily to38.5 in 1997. Marijuana use by
'I 'seniors has remained steadysince then.
Annual cocaine use more than doubled among highschool seniors from 5.6 percent in 1975 to 13.1 per-cent in 1985 then declined sharply to 4.9 percent in1996. Seniors' cocaine use has been stable since then.
-
Heroin use always has been relatively low amongschool children. However, in recent years, the avail-ability of cheap, high-purity heroin that enables usersto get high by snorting the drug rather than injectingit has contributed to heroin use approximately dou-bling among high school seniors from 0.4 percent in1991 to 1.0 percent in 1998.
Past-year Use of Drugs by High School Seniors
The Monitoring the Future study is Anded by NIDA and conducted by the University ofMichigan's Institute for Social Research.
Marijuana, cocaine, and heroin use bottomed out inthe early 1990s but has since risen among childrenat all grade levels. MTF figures for 1997 and 1998suggest this trend toward increased illicit drug use isleveling off and may be in the process of reversing.
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Institute Launches Science Education Campaign forMiddle SchoolersBy Barbara Cire, NIDA NOTES Associate Editor
NIDA has launched a new science education campaign toprovide middle school students with information abouthow drugs work in the brain. "NIDA Goes to School," acompilation of resource materials, is being mailed toscience teachers at 18,084 public and private middleschools across the country and 256 Department ofDefense schools overseas. Thecampaign, undertaken in partner-ship with the National Associationof Biology Teachers, wasannounced in November at theNational Leadership Forum of theCommunity Anti-Drug Coalitionsof America in Washington, D.C.In December, at a national pressconference about teen drug use,Health and Human ServicesSecretary Dr. Donna E. Shalalacited the campaign as an effectivetool for teaching young peoplehow drugs damage their mindsand bodies and helping them toresist drugs.
classes. `NIDA Goes to School' provides teachers withtools they can use to explain the neurobiology of sub-stance abuse. We also hope that teachers will use NIDAas a source for additional fact-based informationabout drugs."
HHS Secretary Dr. Donna E. Shalala praised the"NIDA Goes to School" campaign at a recent national
press conference on teen drug use.
"Science-based education about drug abuse should be aprominent part of the curriculum for all students," saysNIDA Director Dr. Alan I. Leshner. "This new initiativeprovides teachers easily usable, student-oriented materialsto help achieve this goal."
The "NIDA Goes to School" kit contains a variety ofresearch-based materials for teachers and students aboutdrugs and how they affect the brain. (See "A Toolbox forTeachers.") In addition, a "NIDA Goes to School" Website has been established at NIDA's home page on theWorld Wide Web. Students and teachers can use thisinteractive Web site to get additional information aboutdrugs of abuse. The site also will serve as a major source offeedback from students, teachers, and parents. As newscience education materials are developed, they will beadded to the site.
"We are very excited about this project," says Dr. CathrineSasek, science education coordinator in NIDA's Office ofScience Policy and Communications. "Science teacherswant information and resources that they can use in their
Many of the materials are writtenspecifically for students in grades 5through 9. Seven Mind OvirMatter magazines feature theadventures of Sara Bellum, a girlwho explores the brain's responseto particular drugs and introduceskey concepts in neuroscience.The series includes magazines onmarijuana, opiates, stimulants, hal-lucinogens, inhalants, steroids, andnicotine. Each magazine unfoldsinto a poster with a quote from anoted scientist superimposed on avivid color image of a brain area orneuron. For example, on thereverse side of the magazine oninhalants is a quote from Nobel
Prize winner Albert von Szent-Gyorgyi (1893-1986):"Discovery consists of seeing what everybody has seen andthinking what nobody thought."
Also included in the materials is an interactive CD-ROMthat features information on drugs of abuse in a variety oftelevision show formats. Called ATOD-TVATODstands for alcohol, tobacco, and other drugsthe CD-ROM was developed by Dr. Danny Wedding of theMissouri Institute of Mental Health with a NIDA ScienceEducation Drug Abuse Partnership Award. In eachATOD-TV show, human and animated characters playout scenarios that illustrate different aspects of drug abuseand addiction. For example, "Neuronet" is a news pro-gram that provides information about the brain and howit is affected by drugs. "The Torn and the Troubled" is asoap opera that challenges myths about drugs and addic-tion. "Wheels of Misfortune" uses a game-show format' tosupply statistical information about drug use by differentpopulations. An accompanying teacher's guide suggestsstudent activities and provides a comprehensive list ofresources for further information.
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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.
"Our goal for this campaign is to enhance science educa-tion, increase science literacy, and encourage young peopleto pursue careers in the sciences," says Dr. Sasek. "Byintroducing students to the science of drug abuse, wehope to stimulate their interest in neuroscience andsubstance abuse research."
1 do.
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To Receive This Resource
All materials in the "NIDA Goes to School" kit, with theexception of the ATOD-TV CD-ROM and teacher'sguide, are available free from the National Clearinghousefor Alcohol and Drug Information. The materials also canbe downloaded from NIDA's home page on the WorldWide Web at http://www.nida.nih.gov/. The "NIDAGoes to School" Web site can be accessed from NIDA'shome page.
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NIDANATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 12, Number 6 (November/December 1997)
Research Must Determine Medical Potential of Marijuana,NIH Expert Panel ConcludesBy Robert Mathias, NIDA NOTES Staff Writer
A National Institutes of Health (NIH) panel of expertshas concluded that critical questions about the therapeuticusefulness of marijuana remain largely unanswered bystudies that have been conducted to date. The panel calledfor NIH to facilitate rigorous, well-designed clinical stud-ies to evaluate marijuana's potential to treat a variety ofmedical conditions. Such studies must address the manypotential short- and long-term hazards of smoked marijuana,the panel stressed.
The panel of eight experts, who have broad experience inclinical studies and therapeutics, expressed their opinionsin a 37-page report that NIH issued in August 1997. NIHhad convened the experts at a 2-day meeting earlier in theyear to consider wide-ranging claims about the therapeuticusefulness of marijuana, particularly smoked marijuana,and the need for and feasibility of additional research.At the meeting, the panel reviewed the published scientificdata on the medical use of marijuana and consideredcomments, including those from patients andadvocacy groups.
Under U.S. law, marijuana has been classified in the mostrestrictive category of controlled substances since 1970.This means that the drug in its usual form has a highpotential for abuse and has no commonly acceptedmedical use in this country. However, advocates for themedical use of smoked marijuana claim it is effective insuch areas as reducing nausea associated with cancerchemotherapy, counteracting the wasting syndrome associ-ated with AIDS, and treating glaucoma. An oral form ofmarijuana's principal active ingredient, delta-9-tetrahydro-cannabinol (THC), called dronabinol, is approved as atreatment for nausea and vomiting related to cancerchemotherapy. Dronabinol also is used to stimulate theappetite of AIDS patients.
Any studies of marijuana's medicalpotential need to consider boththe short- and long-term risks
associated with smoked marijuana,the panel stressed.
The NIH panel noted that the current debate over usingmarijuana as a medicine centers on claims that smokedmarijuana offers therapeutic advantages over dronabinoland that it has potential to treat other conditions, such aspain and glaucoma. However, little data from clinical trialsare available to support or refute these claims, the panel'sreview showed.
Most previous studies of marijuana's therapeutic potentialhave used THC in capsule form. Such studies do notanswer questions about the potential benefits or risks ofsmoked marijuana, which has substantially different doseabsorption and pharmacological activity from the oraldosage form, the panel noted. In addition, although THCis the principal psychoactive component of the cannabisleaf, other compounds in the leaf may have therapeuticproperties, the panel said.
The panel called for more studies to properly evaluatemarijuana's medical potential in five areas: analgesia, orpain relief; neurological and movement disorders; nauseaand vomiting associated with cancer chemotherapy; glau-coma; and appetite stimulation to counteract weight loss inpatients with AIDS or cancer. In addition to droriabinol;effective treatments already are available for many of the*indications, the panel noted. For example, a number ofmedications can treat pain without risking marijuana'sadverse effects.
However, even where effective medications exist, marijuanacould be studied for its potential to offer relief to patientswho do not respond fully to such treatments, the panelstated. Other reasons for studying marijuana's medicalpotential include determining whether it is useful in treat-ing diseases or conditions for which treatments are notcurrently available, such as nerve pain caused by disease ortissue injury, and whether it could enhance the therapeuticeffects of currently available treatments.
Any studies of marijuana's medical potential need toconsider both the short- and long-term risks associatedwith smoked marijuana, the panel stressed. Among theshort-term risks cited by the panel are cardiovasculareffects, effects on the lungs, and undesirable mental andbehavioral effects. Other concerns would come into play ifmarijuana were used to treat patients with chronic dis-eases, such as the possibility that frequent and prolongedmarijuana use might significantly impair the functioning
4136
of, the body's immune system. Examining that aspect isparticularly important for patients who already havecompromised immune systems, such as cancer patientsundergoing chemotherapy and HIV/AIDS patients, thepanel noted.
To address health concerns about using smoked marijuanafor longer term therapy, the panel suggested thatresearchers strive to develop alternative dosage forms formarijuana, such as a smoke-free inhaled delivery system.
42
Such a system could deliver purer forms of THC andrelated cannabinoids and permit better control of doses,the panel stated.
For More Information
The full text of the expert panel's report on the medicalutility of marijuana is available athttp://www.nih.govinews/medmarijuana/MedicalMarijuana.htm 1321
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New NIDA Drug Abuse Education Materials for MiddleSchool Students
NIDA has released a new series of drug abuse educationmaterials called Mind Over Matter. Designed for studentsin grades five through nine, the series consists of six full-color glossy magazines that unfold into posters. Thepackage also includes a comprehensive teacher's guide. Ineach magazine, a girl named Sara Belluma play on"cerebellum," a section of the brain that helps controlcoordinationexplores the brain's response to a particulardrug and introduces key concepts in neuroscience.
The magazines teach students about the adverse effects ofmarijuana, opiates, stimulants, hallucinogens, inhalants,and steroids. A seventh in the series, which will discussnicotine, will be available early in 1998. The magazinesare designed to excite students about science in generaland neuroscience in particular.
The series uses illustrations and cartoons to provide usefulinformation. Some illustrations show Sara Bellum scubadiving in the depths of the brain, watching drug mole-cules alter nerve cell activity. The cartoons often depict anerve cell or body organ performing abnormally under theinfluence of drugs. For example, a heart playing drums ina rock band loses its rhythm due to cocaine
The posters on the reverse side of each magazine can beseen after the magazine is unfolded. Each 18- by 38-inch
poster has a quote from a well-known scientist superim-posed over a vivid color photograph of a brain image orneuron. For example, on the back side of the opiatesmagazine and superimposed over a photograph of neuronsin the brain is a quote from Jacob Bronowski, the lateBritish mathematician, which reads, "The essence ofscience: Ask an impertinent question, and you are on theway to a pertinent answer."
The teacher's guide provides detailed information onthe brain and how drugs of abuse affect it. It also listsresources and suggests activities to help students rememberthe principles discussed in the magazines.
Mind Over Matter is a product of NIDA's ScienceEducation Program, which funds programs to interestchildren in pursuing careers in science and to increaseknowledge about drug abuse and addiction among thegeneral public. The six magazine-posters and the teacher'sguide are available free. To order copies, contact theNational Clearinghouse for Alcohol and DrugInformation, P.O. Box 2345, Rockville, MD 20847-2345,(800) 729-6686 or (301) 468-2600; TDD number:(800) 487-4889; fax: (301) 468-6433; e-mail:[email protected]. MM
Following are the six magazines and their subjects:
The Brain's Response to Marijuana shows how marijuana affects emotions, memory, judgment, bal-ance, and coordination.
The Brain's Response to Opiates discusses how opiates such as heroin act on many places in the brainand spinal cord and how addiction and withdrawal affect neurons.
The Brain's Response to Stimulants demonstrates how cocaine and amphetamines change the wayneurons 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 thesenses by disrupting the actions of chemical messengers in the brain.
The Brain's Response to Inhalants illustrates how inhalants break down the electrical insulation sur-rounding 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 theoutside and yet cause extensive damage on the inside.
VOW, SW .0
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NI NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 12, Number 4 (July/August 1997)
NIDA-Supported Research Shows...
Promising Advances Toward Understanding the Genetic Rootsof AddictionBy June R. Wyman, NIDA NOTES Staff Writer
This, is the second article in a new series, "NIDA-SupportedResearch Shows," that will appear periodically in NIDANOTES. The series will explain broad scientific concepts indrug abuse research and describe how NIDA researchers areusing these concepts to develop more effective ways to preventand treat drug abuse and addiction. The first article, "Rateand Duration of Drug Activity Play Major Roles in DrugAbuse, Addiction, and Treatment," appeared in NIDANOTES, March/April 1997.
At a major scientific meeting, a scientist announced to aspellbound audience that he had identified some of thegenes associated with drug abuse. He described the muta-tions in those genes that lead people to abuse marijuana,heroin, cocaine, and other drugs. His landmark discoverybrought scientists a giant step closer to dramatically curb-ing drug abuse. Although some drug abuse researchers arepredicting this tale could come true as early as the next 5to 10 years, for now it is fiction.
Currently, scientists agree that genetics is involved in drugabuse, but the consensus ends there. Many genes arethought to act together to make someone more likely toabuse drugs. But exactly which genes those are and whatthey do are the subject of a lively scientific debate.Further, since drug addiction appears to be the productof both heredity and environment, the roles of the twoare hard to separate.
At ,NIDA, a Genetics Workgroup is trying to sort outthese issues. The group's mission is to assess the state ofthe science, identify research gaps, and decide what studiesare needed to untangle, the genetic roots of addiction. Itsmembers consult with experts from around the countryto get advice on what directions NIDA should take,according to Dr. Jonathan Pollock of NIDA's Divisionof Basic Research, who chairs the group.
Meanwhile, amid the debate, new scientific information isemerging, giving scientists leads that may generate newstrategies for drug abuse prevention and treatment.
Family Resemblances
Whether or not someone feels good after smoking mari-juana is strongly influenced by heredity, report NIDA-funded grantees from Harvard Medical School. Their
conclusion comes from a study of 352 pairs of identicalmale twins and 255 pairs of fraternal male twins, all ofwhom had smoked marijuana more than five times intheir lives. Identical twins have exactly the same genes,while in fraternal twins about half the genes are identical.
Dr. Ming Tsuang, Dr. Michael Lyons, and their colleaguescompared the identical twins' answers with the fraternaltwins' answers to a set of questions about how good orbad they felt after smoking marijuana. The identical twins'answers were significantly more alike than those of the fra-ternal twins. The researchers interpret their data to meanthat genetic factors have a significant impact on whethersomeone will enjoy marijuana.
It is this kind of research that begins the search for drugabuse genes. Although studies of twins and families can-not pinpoint specific genes related to drug addiction, theycan look closely at people who share a drug abuse disorderand a common genetic makeup. "Twin studies are promis-ing because they ask exactly what is heritable," says Dr.Harold Gordon of NIDA's Division of Clinical andServices Research. Then, using blood samples, molecularbiologists can examine these individuals' genetic material,or DNA, to locate shared genetic characteristics, he says.
To advance such work, NIDA has expanded funding toepidemiologists who work with large numbers of twins orfamilies but have not previously studied addiction todrugs other than nicotine and alcohol. For example, Dr.Kenneth Kendler of Virginia Commonwealth Universityin Richmond has been studying the genetic basis of nico-tine dependence in a large database of twins and siblingsin Virginia. NIDA's support has allowed him to launch anepidemiologic survey of those twins that will flag vulnera-bility to a wide range of drugs including nicotine, cocaine,barbiturates, opiates, inhalants, and marijuana. To mea-sure gender differences, he is doing separate analyses offemale/female twins and male/male twins.
Dr. Roy Pickens of NIDA's Division of IntramuralResearch (DIR) in Baltimore, with colleagues at JohnsHopkins University in Baltimore and the University ofMinnesota in Minneapolis, also has been studying twins.Their study looked at same-sex twins, half identical andhalf fraternal, with coexisting, or comorbid, drug addic-tion, alcohol abuse, and/or mental health problems. Theresearchers' analyses suggest that common genetic factors
are involved in drug and alcohol abuse and certainpsychological disorders in men. They speculate that thismay account for some of the comorbidity among thesedisorders. Genetic influences were not identified inwomen, probably because there were not enough womenin the study, says Dr. Pickens.
1 Identical twinshave exactly thesame genes.
Scientists studytwins to look forthe genetic basis ofdisorders such asdrug abuse.
Likely Candidate Genes
Meanwhile, geneticists are homing in on particular drugabuse genesa daunting task, given that humans havearound 100,000 genes and, of those, more than 40,000may be expressed in the brain, where drugs of abuse act.Still, many scientists are optimistic. "We've known for along time that genetics is an important part of an individ-ual's response to drugs of abuse," says Dr. John Crabbe, aNIDA grantee at Oregon Health Sciences University inPortland. "What we're able to do now is get our hands onspecific candidate genes."
Of particular interest are genes that control the brainchemical dopamine, which is associated with movementand pleasure, including pleasure from drug use. "Genes inthe dopamine circuit are likely candidates, and most ofthese have been examined at least to some degree," saysDr. George Uhl, chief of DIR's Molecular NeurobiologyBranch. This work is being done in mice, which havecritical genetic similarities to humans. Also, scientistsknow more about the genetic makeup of mice thanthat of any other mammal except humans.
One approach to studying the genes that may influencedrug responses is to remove, or "knock out," a candidategene in mice and see what happens. For example, DIRScientific Director Dr. Barry Hoffer and scientists fromtwo Swedish laboratories recently used genetic engineeringtechniques to knock out the gene for a protein calledNurr 1. The brains of these mice lacked the two majorgroups of dopamine neurons and, thus, could not produceany dopamine.
The scientists conclude that in mice Nurr 1 is critical fornormal development of dopamine-containing nerve cells,and they speculate that development of those cells may beabnormal in people who are vulnerable to substanceabuse. "These people may be abusing drugs in an attemptto counteract the deficiency," says Dr. Hoffer, who did thestudy with scientists from the Karolinska Institute and theLudwig Institute for Cancer Research, both in Stockholm.
r alOPRI1 Pirtinn7//: !MEM?? 5.5IV .
"Medications could be developed that interact with Nurr 1and thus regulate dopamine levels in the brain," Dr.Hoffer speculates. "These medications could be useful intreating an underlying disorder that might make somepeople more likely to abuse drugs."
Another approach to studying the genetics of addiction isto study responses to drugs in genetically identical strainsof mice. At Oregon Health Sciences University and thePortland Veteran's Administration Medical Center, Dr.Crabbe and Dr. John K. Belknap have studied more than25 strains of these inbred mice. "There are big differencesamong strains in whether they self-administer differentdrugs," Dr. Crabbe observes. For example, a strain calledDBA/2 refuses most drugs of abuse, while C57BL/6 miceseem to like almost everything, including alcohol, mor-phine, cocaine, phenobarbital, and diazepam. Otherinbred strains fall between these extremes. "This workshows that specific genes cause animals to like particulardrugs, so that vulnerability to drug abuse is partly undergenetic control," says NIDA's Dr. Pollock.
So the evidence from animal studies is compelling. Butfinding equally strong evidence in humans for a geneticinfluence on drug addiction has proved trickier. Althougha number of genes have been implicated, none has beenclearly linked to drug addiction.
At DIR, Dr. David Vandenbergh, Dr. Uhl, and their coin-vestigators are looking for genes that may be involved indrug abuse by comparing DNA from drug abusers to that of
NIDA's Dr. George Uhl examines a gene that codes for a typeof dopamine receptora molecule to which the brain chemicaldopamine attaches itself. The inset shows a particular gene fromnine different people; each column represents one person. Columns6 and 9, which have two dark blotsare genetically different fromthe others. Researchers are hying to determine whether geneticdifferences such as these relate to drug abuse.
40 4 5 'BEST COPY AVAILABLE
people who do not abuse drugs. So far the strongest can-didate is a variant of a gene that tells the body to producean enzyme called COMT (catechol-o-methyltransferase).Widespread throughout the body, this enzyme helps breakdown and inactivate dopamine and related substances.COMT occurs in two genetically determined forms: lowactivity and high activity. "We found that the high-activityforms of the gene and the enzyme are found more often indrug abusers," Dr. Vandenbergh says. If further work con-firms this finding, then drugs that lower COMT activitycould be tested as treatments for drug addiction, he says.
Gene Hunters
What will it take to locate the particular genes involved inhuman drug addiction? Some scientists think that the bestbet is what scientists call a genome-wide scan. Thismethod, which was recently used to identify the geneticdefect for Parkinson's disease, entails several steps:
find families with high rates of the disorder;
analyze blood samples from these people to locate thegenetic markers, or stretches of DNA, that familymembers with the disorder seem to share that are dif-ferent from those who do not have the disorder;
scan all known human genes using sources such as theNational Institutes of Health's Human GenomeProject, and try to find some connectionfor exam-ple, a gene on the chromosome that is known to regu-late dopamine levels; and
go back to the blood samples to look for shared muta-tions in those genes.
But applying this method to drug addiction will not bestraightforward. "What should we look at? Drug abuse perse? Sensation seeking? Specific biological markers? Wereally don't know," says Dr. Gordon.
"These genes could operate in many ways. They mightmake you seek sensations or make it hard to withdrawonce you start abusing drugs or make you get higher than
other people. Or maybe you need all of these to become adrug abuser," says Dr. Pickens.
Dr. Crabbe in Portland is one of those researchers whothinks that identifying some of the genes involved in drugabuse and addiction is in sight. "That's the big thing thatwill happen in this field in the next 5 to 10 years. We'llturn the theory that genes influence addiction into theidentification of specific genes," he predicts.
Sources
Crabbe, J.C.; Belknap, J.K.; and Buck, K.J. Geneticanimal models of alcohol and drug abuse. Science264:1715-1723, 1994.
Gordon, H.W. Human neuroscience at NationalInstitute on Drug Abuse: Implications for geneticsresearch. American Journal of Medical Genetics54:300-303, 1994.
Lyons, M.J.; Toomey, R.; Meyer, J.M.; Green, A.I.;Eisen, S.A.; Goldberg, J.; True, W.R.; and Tsuang,M.T. How do genes influence marijuana use? The roleof subjective effects. Addiction 92(4):409-417, 1997.
Pickens, R.W.; Svikis, D.S.; McGue, M.; and LaBuda,M.C. Common genetic mechanisms in alcohol, drug,and mental disorder comorbidity. Drug and AlcoholDependence 39:129-138, 1995.
Uhl, G.R.; Gold, L.H.; and Risch, N. Genetic analy-ses of complex behavioral disorders. Proceedings of theNational Academy of Sciences 94:2785-2786, 1997.
Vandenbergh, D.; Rodriguez, L.R.; Miller, I.T.; Uhl,G.R.; and Lachman, H.M. High-activity catechol-o-methyltransferase allele is more prevalent in polysub-stance abusers. American Journal of Medical Genetics74:439-442, 1997.
Zetterstrom, R.H.; Solomin, L.; Jansson, L.; Hoffer,B.J.; Olson, L.; and Perlmann, T. Dopamine neuronagenesis in Nurrl-deficient mice. Science 276:248-250, 1997. ME
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NIDANATIONAL INSTITUTE
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Research FindingsVolume 12, Number 1 (January/February 1997)
Smoking Any Substance Raises Risk of Lung InfectionsBy Michael D. Mueller, NIDA NOTES Staff Writer
Smoking any substancetobacco, marijuana, or "crack,"a smokable form of cocaineincreases a smoker's risk ofdeveloping bacterial pneumonia and other infections ofthe lungs, according to the findings of drug abuse,smoking and health, and AIDS researchers.
Although some drugs seem to have specific damagingeffects when smoked, smoking anything appears to dam-age or paralyze the cilia, the hair-like projections in thelungs that sweep out microbes and other matter that cancause disease, according to NIDA-funded studies.Damaging the lung's cilia, the respiratory system's first lineof defense, can have severe consequences for people withweak immune systems, the studies note.
A NIDA workshop held inAugust 1995 examined currentresearch at that time on thecardio-pulmonary complicationsof crack cocaine use. In a reportsummarizing the major findingspresented at the workshop,Dr. Pushpa V. Thadani, a phar-macologist in NIDA's Divisionof Basic Research, notes thatsmoking cocaine appears toweaken the crack smoker's nat-ural resistance to infection in the lungs.
"Pulmonary alveolar macrophagescells that protect thelungs from infectious agentsare exposed to the highestconcentrations of cocaine," says Dr. Thadani. NIDA-funded studies show that alveolar macrophages fromcrack cocaine smokers are less active than are alveolarmacrophages from nonsmokers in destroying Staphylo-coccus aureus, a common cause of bacterial lung infection.Preliminary findings also indicate that alveolar macro-phages of cocaine smokers are more susceptible to HIV-related infections than are alveolar macrophages of peoplewho do not smoke cocaine.
"Much remains unknown about the effects of cracksmoking on the alveolar macrophages and other cells ofdefense in the lungs," says Dr. Thadani. "However, itappears that there are profound effects, and this needs tobe further explored," she says.
Dr. Donald P. Tashkin, a professor of medicine at theUniversity of California at Los Angeles School ofMedicine, and his colleagues recently examined the effects
that habitual smoking of tobacco, marijuana, and/orcocaine has on the lining of the lung's air passages. TheNIDA-funded study included 53 nonsmokers, 14 smokersof crack cocaine only, 40 smokers of marijuana only, and31 regular tobacco smokers. In addition, there were 16smokers of both cocaine and marijuana, 12 smokers ofcocaine and tobacco, and 44 smokers of bothmarijuana and tobacco. Thirty-one patients smoked allthree substances.
The researchers found that smoking either marijuana ortobacco produces significant damage to the cilia in thelining of the airways. Among smokers of both marijuanaand tobacco, it appears that the effects of marijuana addto the effects of tobacco, and vice versa. "The damage to
the ciliated cells in the lin-ing of the airways caused
Smoking anything appears todamage or paralyze the cilia, thehair-like projections in the lungs
that sweep out microbes and othermatter that can cause disease.
by smoking tobacco,and/or marijuana weakensthe ability of the lungs toremove inhaled particles,making the lungs morevulnerable to infection,"says Dr. Tashkin.
Cocaine smokers had fewersignificant abnormalities
than marijuana or tobacco smokers didbut more abnor-malities than were detected among nonsmokers, Dr.Tashkin says. Among people who smoke both tobacco andcocaine, cocaine smoking appears to produce injury to themucosal lining of the airways beyond that caused bysmoking tobacco alone.
A NIDA-supported study by Dr. Waleska T Caiaffa andher colleagues at Johns Hopkins University in Baltimorecompared the medical records of 40 HIV-positive inject-ing drug users (IDUs) who had suffered from one bout ofbacterial pneumonia with those of 197 HIV-positive IDUswith no history of bacterial pneumonia. The study foundthat HIV-positive IDUs who smoked illicit drugs werealmost twice as likely to develop bacterial pneumonia aswere their counterparts who did not smoke illicit drugs.This association was independent of age, degree to whichthe natural immune system had been suppressed, andcigarette smoking. Among the 77 HIV-positive IDUs whoreported smoking drugs, 87.9 percent indicated that theyhad smoked marijuana, 25.9 percent said that they hadused cocaine, and 9.1 percent admitted smoking crack.
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Smoking is a serious issue among AIDS patients,according to several NIDA-supported studies. The healtheffects of smoking illicit drugs are above and beyond thosecaused by smoking cigarettes, the studies note. Peoplewith AIDS often die of pneumonia and other lungproblems, and smoking tobacco and/or illicit drugsincreases the risks for these diseases.
"The effect that smoking has on the lungs is more seriousthan most people realize. Smoking anything is bad foryour health, especially if your immune system has beenweakened," says Dr. Tashkin.
Sources
Caiaffa, WT; Vlahov, D.; Graham, N.M.;Astemborski, J.; Solomon, L.; Nelson, K.E.; and
Munoz, A. Drug smoking, Pneumo-cystis cariniipneumonia, and immunosuppression increase risk ofbacterial pneumonia in human immunodeficiencyvirus-seropositive injection drug users. Am. J. ofRespiratory 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. Tracheobronchialhistopathology in habitual smokers of cocaine, mari-juana, and/or tobacco. Chest, in press.
Thadani, P.V., et al. NIDA conference report on car-diopulmonary complications of "crack" cocaine use:Clinical manifestations and pathophysiology. Chest110:1072-1076, 1996. [ME
4843
NIDANATIONAL INSTITUTEON DRUG ABUSE
Research FindingsVolume 11, Number 3 (May/June 1996)
Studies Show Cognitive Impairments Linger in HeavyMarijuana UsersBy Robert Mathias, NIDA NOTES Staff Writer
Students who smoke marijuana heavily may be limitingtheir ability to learn, according to a NIDA-funded study.The study found that college students who used marijuanaregularly had impaired skills related to attention, memory,and learning 24 hours afterthey had last used the drug.The finding supports theresults of previous NIDA-funded research that reportedthat adults who were chronicheavy marijuana users showedresidual impairment incognitive abilities a day afterthey had last used marijuana.
"Now we know that forstudents who smoke marijuanaheavily, the ability to learn isaffected not just while they arehigh, but for at least a dayafter," says NIDA DirectorDr. Alan I. Leshner. Togetherwith other NIDA-fundedresearch that has shown amarked increase in daily marijuana use among young peo-ple in recent years, this finding underlines the importanceof the Marijuana Use Prevention Initiative launched byHealth and Human Services Secretary Dr. Donna Shalalalast year, Dr. Leshner says. NIDA is playing a leading rolein the initiative by providing science-based information toeducate the public about the consequences of marijuanause. (For more information, "Marijuana ConferenceAdvances HHS Secretary's Marijuana Initiative," V10-6Novevember/December 1995, and "Facts AboutMarijuana and Marijuana Use," V11-1, March/April1996.)
Regular heavy marijuana use compromises the ability tolearn and remember information primarily by impairingthe ability to focus, sustain, and shift attention, saysDr. Harrison Pope, Jr., of McLean Hospital in Belmont,Massachusetts, who directed the recent study. Noting thatthe actual ability to recall information remains relativelyunaffected, Dr. Pope says, "If you could get heavy users tolearn an item, then they could remember it; the problemwas getting them to learn it in the first place."
In the study conducted among college students, Dr. Popeand Dr. Deborah Yurgelun-Todd, also of McLeanHospital, tested the cognitive functioning of 65 heavycannabis users, most of whom had smoked marijuana at
least 27 out of the previousJ 30 days. The researchers com-
pared the heavy users' cogni-tive functioning to that of acomparison group of 64 lightusers, most of whom hadsmoked marijuana on no morethan 3 of the previous 30 days.Heavy users ranged in agefrom 18 to 24 years and lightusers from 18 to 28 years. Thetwo groups were similar demo-graphically and had compara-ble numbers of men andwomen. Subjects in bothgroups had smoked marijuanafor at least 2 years, and nonehad smoked regularly for morethan a decade.
Using the Wisconsin Card Sorting Test, shown here,Dr. Harrison Pope, Jr. (left) found that 24 hours after theystopped using the drug, heavy marijuana smokers made agreater number of errors than light users made in sorting cardsinto different categories.
To ensure that the subjects did not smoke marijuana oruse other illicit drugs or alcohol during the study,researchers monitored them for 19 to 24 hours. Then thesubjects performed a battery of standard tests designed toassess their ability to pay attention, learn, and recall newinformation. The tests indicated that heavy marijuanausers had more difficulty than light users in sustaining andshifting attention and hence in registering, organizing, andusing information. Heavy users exhibited these cognitivedeficits by being less able than light users were to learnword lists; by making a greater number of errors in sortingcards by different characteristics, such as by color orshape; and by making more errors when the rules for sort-ing the cards were changed without warning. Men in theheavy users group showed somewhat greater impairmentthan women in the same group.
While the residual cognitive impairments detected in thestudy were not severe, they could be significant in the day-to-day life of chronic users, Dr. Pope says. The diminishedability to pay attention and decreased mental flexibilityexhibited in these tests may cause chronic marijuana users
44
important difficulties in adapting to intellectual and inter-personal tasks, he says.
"This is a fairly definitive study because it was method-ologically sound and controlled for a wide number of fac-tors, including the possible confounding effects of alcoholand other drug use," says Dr. Jagjitsing Khalsa of NIDA'sDivision' of Clinical and Services Research.
Previous studies have produced mixed findings aboutthe residual effects of heavy marijuana use on neuropsy-chological performance, notes Dr. Khalsa. Methodologicalproblems such as ambiguous terminology, failing to takeinto account cognitive differences in study participantsprior to initiation of marijuana use, and failing to note thepossible effect of alcohol and other drugs have raisedquestions about the results of many of these studies.(For more information about methodological issues, seethe Pope, Gruber, and Yurgelun-Todd article listed below.)
The study joins a growing body ofresearch that indicates protractedcognitive impairment among heavy
marijuana users.
The study by Dr. Pope and Dr. Yurgelun-Todd joins agrowing body of well-controlled and well-designed studiesthat indicate protracted cognitive impairment amongheavy marijuana users, says Dr. Khalsa. For example, in1993, Dr. Robert Block of the University of Iowa Collegeof Medicine compared adult heavy marijuana users andnonusers ranging in age from 18 to 42 years who hadbeen matched on the basis of their intellectual functioningbefore the onset of drug use. Subjects who used marijuanafrequently-7 or more times weekly for at least 2 yearsshowed deficits in mathematical skills and verbal expres-sion and selective impairments in memory retrievalprocesses, the study reported. Although the two studiesused different neuropsychological tests, "in general, both
studies showed some impairments in cognitive abilitiesamong heavy marijuana users," Dr. Block says.
It remains unclear whether marijuana's short-term residualcognitive impairments are due either to a residue of thedrug that remains in the brain after marijuana's acuteeffects have dissipated, to a withdrawal effect from abruptdiscontinuation of the drug, or to a neurotoxic effect ofthe drug on brain structure or function. Research has yetto demonstrate conclusively that chronic heavy marijuanause results in cognitive deficits that persist after a pro-longed period of abstinence. However, NIDA-supportedanimal studies do show structural damage to the hip-pocampus, a structure critical in learning and memory,from the principal psychoactive ingredient in marijuana.
To help answer these and other questions about the long-term effects of marijuana, both Dr. Pope and Dr. Blockplan followup studies to examine the effects of chronicheavy marijuana use on cognition and brain function afterlonger periods of abstinence. Dr. Block proposes to useneuroimaging techniques to look at heavy users' brainswhile they perform cognitive tasks to determine whetherbrain function or structure is altered after abstinence frommarijuana for a minimum of 30 hours. Dr. Pope is plan-ning a study to determine if cognitive impairments persistin long-time heavy marijuana users for up to 28 days afterthey have stopped using marijuana.
Sources
Block, R.I., and Ghoneim, M.M. Effects of chronicmarijuana 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 AlcoholDependence 38:25-34, 1995.
Pope, H.G., Jr., and Yurgelun-Todd, D. The residualcognitive effects of heavy marijuana use in collegestudents. JAMA 275(7):521-527, 1996. ME
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111
arij ana Um airs riving-Related Skills andrk lace Perfor 3 ante
By Robert Mathias, NIDA NOTES Staff Writer
Marijuana use impairs driving-related functions and islinked to a pattern of behaviors that leads to poor jobperformance, according to two NIDA-supported studieson the effects of marijuana on human performance.Findings from the studies were presented at NIDA's firstNational Conference on Marijuana Use.
"Driving and marijuana do not mix; that's the bottomline," said Dr. Stephen J. Heishman, a research psycholo-gist in the Clinical Pharmacology Branch of NIDA'sDivision of Intramural Research. Figures from previousstudies of automobile accident victims show that from 6to 12 percent of nonfatally injured drivers and 4 to 16percent of fatally injured drivers had tetrahydrocannabinol(THC), the psychoactive ingredient in marijuana, in theirbloodstream, Dr. Heishman said. One study showed that32 percent of drivers in a shock trauma unit in Baltimorehad marijuana in their bloodstream, he noted. However,in most of these studies, the majority of subjects whotested 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 ResearchCenter in Baltimore that controlled for alcohol's con-founding effect, Dr. Heishman tested marijuana's effectson the functional components of driving. Study subjectssmoked a marijuana cigarette, waited 10 minutes, thensmoked another cigarette. Both cigarettes contained either0, 1.8, or 3.6 percent THC. Twenty minutes after smok-ing the cigarettes, the subjects were given a standardsobriety test similar to a roadside sobriety test. The testshowed that marijuana significantly impaired their abilityto stand on one leg for 30 seconds or touch their finger totheir nose. As the dose of THC increased, the subjectsswayed more, raised their arms, and had to put their feetdown in an attempt to maintain their balance. Subjectsalso committed 2.5 times more errors when they attemptedto touch their nose with their finger.
The data from these laboratory studies show that marijuanaimpairs balance and coordinationfunctional componentsimportant to drivingin a dose-related way, saidDr. Heishman. These effects may be related to reportedmarijuana-induced impairment of automobile driving,he stated.
Highway and urban driving studies conducted in theNetherlands show less impact on actual driving. However,
. ar
At NIDA's National Conference on MarijuanaUse, Dr. Stephen Heishman presented data fromlaboratory studies showing that marijuanaimpairs functions important to driving.
these driving studies used very low doses of marijuana forsafety reasons, Dr. Heishman said. Future research usingappropriate safety measures should test the effect of higherdoses of marijuana on driving as well as the combinedeffect of marijuana and alcohol on driving, he concluded.
In another study, Dr. Wayne Lehman of Texas ChristianUniversity looked at how marijuana affects job perfor-mance. A series of surveys he conducted among.4,600municipal employees in four cities in the Southwest indi-cated that 8 percent of employees had smoked marijuanain the past year, and a large percentage of these users hadsmoked marijuana in the past month, Dr. Lehman said.
"Employees who report marijuana use are different fromnonusers," said Dr. Lehman. They are much more likelythan nonusers to have arrest histories, low self-esteem,high rates of depression, and friends who are deviant.Many marijuana smokers also have alcohol-relatedproblems. One-third of marijuana users in the surveysreported they drank frequently, one-half said they gotdrunk, and 60 percent reported a problem with alcoholuse, according to Dr. Lehman.
This behavioral pattern in the personal backgrounds ofmarijuana-smoking employees was associated with nega-tive attitudes toward work and job performance, Dr.Lehman said. The surveys found that marijuana users wereless likely than nonusers to commit to the organization,had less faith in management, and experienced low jobsatisfaction. These workers reported more absenteeism,tardiness, accidents, workers' compensation claims, andjob turnover than workers who had not used marijuana.They were also more likely to report to work with a hang-over, miss work because of a hangover, and be drunk oruse drugs at work.
These data indicate that marijuana use is stronglyassociated with problematic alcohol use and a pattern ofgeneral deviance that leads to impaired behaviors and poorworkplace performance, Dr. Lehman concluded. ME
46
IP
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NIDA Conference Advances HHS Secretary's Marijuana Initiative
Approximately 570 marijuana researchers, treatment andprevention services providers, and educators met inArlington, Virginia, July 19-20, to learn about newmarijuana research findings. The occasion was NIDA'sConference on Marijuana Use: Prevention, Treatment,and Research, the firstnational conference everheld on the topic.
The conference was a keycomponent of the MarijuanaUse Prevention Initiative, amultifaceted campaign beingspearheaded by theDepartment of Health andHuman Services. The confer-ence furthered the Initiative'score objective of using sci-ence-based information toeducate the public about theconsequences of marijuanause. (For more about theInitiative, see "HHS Secretary Sends MarijuanaInformation to the Nation's Schools," and "NIDAExpands Its Marijuana Research Agenda." )
"The marijuana issue is about the costs to society of drug-related auto wrecks, accidents, property damage, truancyand school failure, on-the-job mishaps, and lost produc-tivity," Health and Human Services Secretary Dr. DonnaE. Shalala told conference participants. "At the core of our
agenda must be a clear andconsistent message: Marijuanais illegal, dangerous,unhealthy, and wrong."
During the 2-day conference,more than 60 speakersdiscussed marijuana topicsranging from current patterns
/ of use and perceptions of riskto physical and behavioraleffects and prevention andtreatment approaches. Amongthe research results presented:
Dr. Billy Martin of theMedical College of Virginia at
Virginia Commonwealth University released newresearch showing that marijuana produces drugdependency in animals (see "Marijuana AntagonistReveals Evidence of THC Dependence in Rats").
f
NIDA's 2-day Conference on Marijuana Use drew some 570researchers, treatment and prevention services providers, andeducators from across the Nation to hear the latest researchfindings on marijuana.
NIDA Expands Its Marijuana Research Agenda
In conjunction with the Marijuana Use PreventionInitiative, NIDA has expanded its marijuana researchagenda. Its new Marijuana/Cannabis Abuse ResearchProgram Announcement (PA 95-076) is encouragingresearch on the entire spectrum of marijuana abuse.Research areas of interest include etiology, epidemio-logy, prevention, treatment, and clinical and basicscience.
Receipt dates for grant applications are February 1,June 1, and October 1 of each year. For further infor-mation on programmatic issues, contact
Dr. Lynda ErinoffNIDA6001 Executive BlvdBethesda, Maryland 20892(301) 443-1263Internet: lerinoff @aoada.ssw.dhhs.gov
Copies of program announcements and informationregarding fiscal issues may be obtained from
Dr. Gary FlemingNIDA6001 Executive BlvdBethesda, Maryland 20892(301) 443-6710Internet: [email protected]
From NIDA NOTES, November/December, 1995
47
Dr. Donald Tashkin of the University of California atLos Angeles reported his findings on the pulmonaryconsequences of habitual marijuana use, whichinclude symptoms of chronic bronchitis, an increasedfrequency of acute chest illnesses, a heightened risk ofpulmonary infection, and an apparently increased riskof disease in both the upper airway and the lungs.
Preliminary findings presented by Dr. Peter Fried ofCarleton University in Ottawa suggest that, in 9- to12-year-olds, prenatal marijuana exposure is associatedwith impaired executive function, the intellectual abil-ity that involves decisionmaking and planning.
Dr. Stephen Heishman of NIDA's Division ofIntramural Research discussed his recent study,which showed that marijuana significantly impairedperformance in standardized sobriety tests conductedin controlled laboratory conditions.
Dr. Judith Brook at the Mt. Sinai School of Medicinein New York City presented findings from a multi-generational study showing certain factors associatedwith marijuana use among young people. Studyresults indicate that children who are aggressive andhave a distant relationship with their parents are morelikely than other children to use marijuana as youngadults, and that adolescents at risk for marijuana useexhibit rebelliousness, poor school achievement, anddifficulty in family relationships.
Conference proceedings and audio cassettes of conferencesessions are available. Proceedings may be ordered fromthe National Clearinghouse for Alcohol and DrugInformation (NCADI), P.O. Box 2345, Rockville, MD20847-2345, (800) 729-6686 or (301) 468-2600.Information on ordering audio cassettes. MM
HHS Secretary Sends Marijuana Informationto the Nation's Schools
With the distribution of NIDA developedmaterials on marijuana to 16,000 U.S. schooldistricts in October, the national Marijuana UsePrevention Initiative delivered a new wave ofscience based information to the Nation's school-aged children and their parents.
The materials were accompanied by a letter fromHealth and Human Services Secretary Dr.Donna E. Shalala, who launched the Initiative atthe end of last year in response to disturbingincreases in teenage use of marijuana reported inNIDNs 1994 Monitoring the Future survey.
The school districts received a 13 minute infor-mational video for parents-"Marijuana: WhatCan Parents Do?"
Two question-and-answer brochures accompa-nied the video: "Marijuana: Facts for Teens" and"Marijuana: Facts Parents Need to Know."
In addition, full -color posters bearing themessages "Drugs Have No Place in a HealthyLife!" and "Marijuana Can Mess You Up!"were distributed as supplements to "My WeeklyReader" and a number of other educationalperiodicals used in the school systems.
In developing the Marijuana Use PreventionInitiative, NIDA collaborated with the Centerfor Substance Abuse Prevention and the Centerfor Substance Abuse Treatment, both agencies ofthe Substance Abuse and Mental Health ServicesAdministration, and the Partnership for aDrug-Free America, a communications industrycoalition to reduce the demand for illicit drugs.
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NI NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 10, Number 6 (November/December 1995)
Marijuana Antagonist Reveals Evidence ofTHC Dependence in RatsBy Neil Swan, NIDA NOTES Contributing Writer
For the first time, researchers have demonstrated thatmarijuana may cause drug dependency in animals. Thisfinding was made possible by the recent development of apotent marijuana antagonistan agent that blocks manyeffects of the drug. The marijuana antagonist appears toact like an on-off switch, allowing researchers to controlthe effects of withdrawal from delta-9-tetrahydrocannabi-nol (THC), the principal psychoactive ingredientof marijuana.
Dr. Billy Martin, a NIDA-funded marijuana researcher atVirginia Commonwealth University's Medical College ofVirginia, who conducted one of two initial studies, pre-sented his findings at NIDA's National Conference onMarijuana Use: Prevention, Treatment, and Research lastsummer. During his research, rats were exposed to THCfor 4 days, then given a dose of the THC antagonist SR141716A, which was developed by French scientists lastyear. The rats immediately and "dramatically" exhibitedclassic rodent behavioral withdrawal symptoms, indicatingthat they were dependent on THC, Dr. Martin said.
Within 10 minutes after administration of the marijuanaantagonist, the rats exhibited behavior that included "wet-dog shakes" and facial rubbing, which constitute "definiteevidence of withdrawal" from the effects of THC, said Dr.Martin. This behavior mimics long-observed opiate with-drawal symptoms in rodents.
The shakes and rubbing were so striking and frequent thatthey could be quantified by trained observers. Other, lessfrequent withdrawal-like behaviors included head shakes,biting, drooping eyelids, retropulsion (backing away), eartwitching, chewing, licking, and arching the back,Dr. Martin said.
The wet-dog shakes were dose-dependent, meaning theybecame more pronounced as dose levels of the antagonistwere increased in the THC-exposed animals.
Dr. Martin acknowledged that such behavior is not likeany marijuana withdrawal syndrome in humans.
"The fact that people do seek treatment for marijuanadependence is evidence of marijuana withdrawal inhumans, but, even among those seeking treatment, we donot see dramatic withdrawal symptoms," said Dr. Martin.
Dr. Billy Martin found that when ratsthat are adminstered the main psychoactiveingredient in marijuana are then given dosesof a compound that blocks the action of thisingredient, the rats "dramatically" exhibitclassic rodent withdrawal symptoms.
"That's because the withdrawal process in humans is solong and drawn out, evidenced chiefly by mild distress oranxiety. But with the rats, using SR 141716A as aneffective antagonist, we compress and accentuate thatwithdrawal process.
"The challenge for us now is to use these animal data todesign human studies-to determine how small a dose ofTHC is needed to become dependent on marijuana," saidDr. Martin.
Dr. Martin, senior investigator Dr. Mario D. Aceto, andcolleagues at the Department of Pharmacology andToxicology of Virginia Commonwealth University havepublished the results of their research.
"We have been searching for a marijuana antagonist formany years," said Dr. Martin, who has been a marijuanaresearcher for 22 years.
Sources
Aceto, M.D.; Scates, S.M.; Lowe, J.A.; and Martin,B.R. Canna-binoid-precipitated withdrawal by aselective antagonist: SR 141716A. Eur. J. Pharmacol.282(1-3):R1-R2, 1995.
Rinaldi-Carmona, M., et al. SR 141716A, a potentand selective antagonist of the brain cannabinoidreceptor. FEBS (Federation of European BiochemicalSocieties) Letters 350(2-3):240-244, 1994.
Tsou, K.; Patrick, S.; and Walker, M.J. Physicalwithdrawal in rats tolerant to delta-9-tetrahydro-cannabinol precipitated by a cannabinoidreceptor antagonist. Eur. J. Pharmacol.280:R13-R15, 1995. IME
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NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 10, Number 4 (July/August 1995)
NIDA Takes a Lead Role in National Marijuana InitiativeBy Neil Swan, NIDA NOTES Contributing Writer
NIDA is taking a lead role in the Marijuana UsePrevention Initiative announced by Health and HumanServices Secretary Donna E. Shalala. The Institute isproviding the scientifically based messages aboutmarijuana that are designed to dispel myths, increasepublic awareness of rising trends in marijuana use amongteens, and educate the public about the conse-quences of marijuana use, especially emphasiz-ing the consequences for young people.
To kick off the Initiative, this summer NIDAsponsored the National Conference onMarijuana Use: Prevention, Treatment, andResearch. Leading marijuana researchers madepresentations on the conse-quences and effects of marijuanause, changing trends in its use,what it does to the body, andhow marijuana use can progressfrom initiation to dependence orthe use of other drugs. They dis-cussed the effects of its psychoac-tive ingredient on the brain, onthe disease-fighting immune sys-tem, and on children of womenwho smoke marijuana duringpregnancy. They outlined howmarijuana use, often in combina-tion with alcohol, is associatedwith increased risks of autoaccidents and the spread ofAIDS.
Keynote addresses for this first national conferencefocusing on marijuana were delivered by Secretary Shalalaand Dr. Lee P. Brown, director of the White House Officeof National Drug Control Policy, following a welcomingaddress by NIDA Director Dr. Alan I. Leshner.
To support the Marijuana Initiative, NIDA is alsopreparing science-based materials on how marijuanaaffects the brain, including learning and memory, and thebody. The materials include question-and-answer bookletswritten for both parents and teenagers; a one-page factsheet on the drug; "Marijuana Use: What Parents CanDo," a videotape for parents and other adults presentingscience-based facts about marijuana; and a science educa-tion series for elementary school students. Advance copiesof the booklets and a short version of the video werepresented at the conference.
NIDA is working in collaboration with the Center forSubstance Abuse Prevention and the Partnership for aDrug-Free America, a voluntary alliance of advertisingagencies, in developing materials, videos, and programsto support the Secretary's Marijuana Use PreventionInitiative.
Marijuana:-
Parents Need
marijuana:
,1
What
o Know
The Initiative was prompted lastDecember when NIDA's Monitoring theFuture survey reported disturbing trendsshowing increases in drug use amongteenagers as young as 13.
The survey showed that, during the last3 years, marijuana use among 8th-gradersdoubled and use among 10th- and 12th-graders increased significantly. "Current"usewithin the past 30 daysofmarijuana among high school seniorsincreased by 38 percent during the sameperiod.
Along with increased use of marijuanaand other drugs, the NIDA-sponsored survey also found asignificant erosion in antidrugperceptions among youngpeople. The proportion of thosewho believe occasional or regu-lar marijuana use is harmful hasdeclined by 22 percent over thelast 3 years, according to thesurvey.
In announcing the Initiative,Secretary Shalala and other officials noted the proliferationof drug-culture images in movies and other media.
In addition to spearheading the Marijuana Initiative, theInstitute is also expanding its marijuana research agendawith supplements to current research grants and a newmarijuana research program announcement issued in July.
NIDA also continues to promote its antidrug campaigntargeting teens and young adults. With the collaborationof the Advertising Council, the Institute is nowproducing the next phase of its "Get High, Get Stupid,Get AIDS" national media campaign. The campaignincludes new TV announcements targeting both teensand young adults. ME
NIDA is preparing ques-tion and answer bookletswritten for both parentsand teenagers that pre-sent information to helpcorrect widespread publicmisconceptions aboutmarijuana use.
50
A-
S
Marijuana Initiative Features Scientifically Accur. te9Credible MessagesBy NIDA Director Dr. Alan I. Leshner
NIDA's most recent Monitoring the Future survey ofteenage drug use revealed truly-alarming trends. The sur-vey of 8th-, 10th-, and 12th-grade students found druguse increasing in virtually all categories of drugs and at allage levels. Most disturbing to me was the finding that, forthe third year in a row, there was a significant increase inmarijuana use among 8th-grade students.Over the past 3 years, annual use ofmarijuana by 8th-graders has nearly dou-bled. In 1994, 13 percent said they hadsmoked marijuana at least once during theprevious year.
These are 8th-graders-13-year-olds.
The NIDA-sponsored survey also found thatantidrug perceptions were deteriorating.Fewer students than before now believesmoking marijuana occasionallyor evenregularlyis harmful to their health.
Unless we, as a Nation, do something tocorrect teens' perceptions and the trend toward increasinglevels in the use of marijuana and other drugs, we're head-ed for serious problems. Marijuana is often the introduc-tion to progressive drug use patterns. For more than 20years, NIDA-funded long-range studies repeatedly haveshown that children and teenagers who use tobacco, alco-hol, and particularly marijuana are at increased risk ofusing other drugs.
When Health and Human Services Secretary Donna E.Shalala announced the 1994 Monitoring the Futuresurvey results last December, she called them an urgentwarning of a disturbing trend in drug use among thecountry's adolescents. In response to this warning, sheannounced plans for the Secretary's Marijuana UsePrevention Initiative, a nationwide campaign to provideinformation to teens and parents that would counteractthe drug-glamorizing messages our youth now receivefrom movies, TV, and pop music.
That Marijuana Initiative is now under way (see "NIDATakes a Lead Role in National Marijuana Initiative"), andI am gratified that NIDA has been designated to play akey part in providing carefully crafted messages based onscientifically sound knowledge.
All of us involved in the campaign know it is critical thateach of its messages be solidly based on scientific research
I
findings. To be convincing to teenagers we must fully andhonestly present the scientific evidence. And the informa-tion must be presented in ways that are readily under-standable and convincing to adolescents and applicable totheir world. This scientific documentation and communi-cation are at the heart of NIDA's mission.
Media efforts, involving national TV net-works and other print and broadcast media,will provide information on the dangers ofmarijuana use and how parents and childrencan address the problem in their homes,schools, and communities. The campaign isa joint effort in the Department of Healthand Human Services involving the Office ofthe Secretary, NIDA, and the Center forSubstance Abuse Prevention. The privatesector is also involved, through thePartnership for a Drug-Free America, whichmakes available the communications exper-tise of major advertising agencies for public
service campaigns against drug abuse.
NIDA has already prepared informational booklets forboth parents and teens warning of the risks of marijuanause. Also in the works are a videotape, "Marijuana Use:What Parents Can Do," and a science-education series ofmaterials for elementary school students.
The Marijuana Use Prevention Initiative will showyoung children, teenagers, and their parents that marijuanais a serious threat to the health and well-being ofouryouth. Too many parentswho may have themselvesexperimented with marijuana in their youthoften find itdifficult to talk to their children about marijuana use or tolay out strict rules against its use.
But marijuana-use circumstances now are different fromthose remembered by today's parents. These parentsshould realize that today's children are starting marijuanause at a younger age and that more potent forms of thedrug are now available. Parents need to understand thatmarijuana poses a serious threat to their children's vitalityand potential. They need to tell their children not touse it.
The Initiative will show how marijuana is harmful bypresenting the facts. Real-world scenarios based on scien-tific evidence will dramatize the risks involved with its use.
51
For example, many people don't realize the extent towhich marijuana can interfere with the physical andmental skills needed to safely drive a car, increasing therisk of auto accidents. Youngsters often drink beer orother alcoholic drinks while smoking marijuana, whichincreases still further the risk of automobile accidents.
As NIDA has already shown in its continuing nationwidemedia campaign for young people, "Get High, GetStupid, Get AIDS," the Marijuana Initiative will showteens, in the language and media formats that they relateto, the high-risk connection between drug use and thespread of AIDS.
The messages will show children and teenagers that if theybegin to use marijuana they become vulnerable to impair-ments in thinking, speaking, listening effectively, problemsolving, and forming concepts. They will graphically
demonstrate that marijuana can cripple the skills andfunctions they need to achieve their full potential or evento get a job. They will feature research showing thatstudents do not retain knowledge when they are highfrom smoking a joint and that their motivation and cogni-tion may be altered by marijuana, hampering their abilityto learn.
We know that drug abuse is closely tied to increasing ratesof crime and violence, family disintegration and relatedchildhood developmental barriers, and death anddiseaseincluding the spread of AIDS. In its myriadmanifestations, drug abuse can rob young people oftheir chance for a happy, healthy life. That's why we areundertaking this Initiative that targets an early, formativeaspect of drug abusemarijuana use among childrenand teenagers. ZIE
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NIDA Survey Provides First National Data on Drug UsePregnancyBy Robert Mathias, NIDA NOTES Staff Writer
More than 5 percent of the 4 million women who gavebirth in the United States in 1992 used illegal drugs whilethey were pregnant, according to the first nationally repre-sentative survey of drug use among pregnant women. TheNIDA-sponsored survey, which was released last fall, pro-vides the best estimates to date of the number of womenwho use drugs during pregnancy, their demographic char-acteristics, and their patterns of drug use.
"Information from NIDA's National Pregnancy andHealth Survey can help to guide public health policymak-ers who have to make decisions about prevention andtreatment programs aimed at reducing the problem ofdrug abuse during pregnancy," said NIDA Director Dr.Alan I. Leshner. Dr. Leshner reported the survey's findingsat a press briefing held during NIDA's conference onDrug Addiction Research and the Health of Women lastSeptember.
The survey gathered self-report data from a national sam-ple of 2,613 women who delivered babies in 52 urban andrural hospitals during 1992. Based on these data, an esti-mated 221,000 women who gave birth in 1992 used illicitdrugs while they were pregnant. Marijuana and cocainewere the most frequently used illicit drugs-2.9 percent,or 119,000 women, used marijuana and another 1.1percent, or 45,000 women, used cocaine at some timeduring their pregnancy.
The survey found a high incidence of cigarette and alco-hol use among pregnant women. At some point duringtheir pregnancy, 20.4 percent, or 820,000, pregnantwomen smoked cigarettes and 18.8 percent, or 757,000,drank alcohol.
"We know for certain that these [legal] substances affectthe health of the fetus and a woman during and afterpregnancy," said Dr. Loretta D. Finnegan, NIDA'sformer senior advisor on women's issues. Health care prac-titioners should ask women about their use ofcigarettes and alcohol during prenatal checkups andeducate them about the health risks of licit drugs, said Dr.Finnegan, who now directs the Women's Health Initiativeat the National Institutes of Health.
The survey also uncovered a strong link betweencigarette smoking and alcohol use and the use of illicitdrugs in this population. Among those women who usedboth cigarettes and alcohol, 20.4 percent also used
urin
marijuana and 9.5 percent took cocaine. Conversely, ofthose women who said they had not used cigarettes oralcohol, only 0.2 percent smoked marijuana and 0.1 per-cent used cocaine. "This finding reinforces the need forhealth practitioners to monitor the status of both licit andillicit drug use during pregnancy," said Dr. Leshner.
Besides providing the first national estimates of drug useduring pregnancy, the survey also examined differences inthe amount and types of drugs used by several racial andethnic groups of women. Overall, 11.3 percent of African-American women, 4.4 percent of white women, and4.5 percent of Hispanic women used illicit drugs whilepregnant. While African Americans had higher rates ofdrug use, in terms of actual numbers of users, mostwomen who took drugs while they were pregnant werewhite. The survey found that an estimated 113,000 whitewomen, 75,000 African-American women, and 28,000Hispanic women used illicit drugs during pregnancy.
Drug Use During Pregnancy*Among Racial and Ethnic Grou s
BlacksAny Illicit Drug 11.3%
Marijuana 4.6%
Cocaine 4.5%
Alcohol 15.8%
Cigarettes 19.8%
WhitesAny Illicit Drug 4.4%
Marijuana 3.0%
Cocaine 11 0.4%
Alcohol
Cigarettes
22.7%
His anicsAny Illicit Drug I 1 4.5%
Marijuana 1.5%
Cocaine 0 0.7%
Alcohol
Cigarettes
,8.7%
5.8%
24.4%
'Percent of American women who gavebirth in 1992 end used drugs during pregnancy
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The survey found that an estimated113,000 white women,
75,000 African-American women, and28,000 Hispanic women
used illicit drugs during pregnancy.
The survey also described different patterns of licit andillicit drug use among white women and ethnic minorities.African-American women had the highest rates of cocaineuse, mainly "crack," during pregnancy. About 4.5 percentof African-American women used cocaine compared with0.4 percent of white women and 0.7 percent of Hispanicwomen who did so.
White women had the highest rates of alcohol and cigaretteuse. Nearly 23 percent of white women drank alcohol and24.4 percent smoked cigarettes. By comparison, 15.8percent of African-American women and 8.7 percent ofHispanic women drank alcohol and 19.8 percent of
African-American women and 5.8 percent of Hispanicwomen smoked cigarettes. "These findings point to theimportance of attending to cultural issues in drug abuseprevention and treatment efforts," said Dr. Finnegan.
Although women who used drugs during pregnancy gen-erally decreased their rates of drug use throughout theirpregnancy, they did not discontinue drug use, Dr. Leshnernoted. "This finding indicates how gripping an illnessdrug addiction can be, even in the face of what may seemto be the ultimate incentive to stay drug free," Dr.Leshner said. Nevertheless, "it is a disease that can betreated and managed with appropriate interventions,"he stressed.
"With the information the survey provides about the pat-terns of drug use by women during pregnancy, we will bebetter able to identify priorities we must address," said Dr.Finnegan. This will enable researchers to develop and testmore effective approaches to the differential drug abusetreatment and prevention needs of women of childbearingage, she concluded. 221
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NI NATIONAL INSTITUTE
ON DRUG ABUSE
Research FindingsVolume 10, Number 1 (January/February 1995)
Early Childhood Behavior and Temperament Predict LaterSubstance UseBy Neil Swan, NIDA NOTES Contributing Writer
By the first grade, or earlier, children show temperamentand behavior traits that are powerful indicators of theirinclination to use and abuse drugs in their teenage andadult years. Researchers have identified not only commonchildhood risk factors and behaviors that predict drugabuse potential but also protective factors that shield somechildren from influences to use drugs.
A number of long-range NIDA-funded studies have tracedat-risk children into adulthood and parenthood, trying todetermine why some children are able to resist persistentinfluences to use substances of abuse. Studies have zeroedin on several important factors in predicting a first-grader'ssubsequent use of substances: shyness, aggressiveness,rebelliousness, and gender. External risk factors includesubstance use among peers, drug use by parents, andtroubles with the police. Protective factors includeachievement in school or after-school activities and closefamily ties. The researchers are now designing drug abuseprevention and intervention strategies based on thesefindings made over 20 or more years.
Some of the earliest studies, by Dr. Margaret E.Ensminger and Dr. Sheppard G. Kellam and colleaguesof Johns Hopkins University, started in the 1960s withfirst-graders and their families in Woodlawn, a poor,urban African-American community on the South Sideof Chicago.
Today the researchers are following about 1,000 of the1,242 original first-graders to continue to identify andmonitor early childhood factors affecting later drug useand symptoms of psychiatric problems. These first-gradersare now 32 or 33 years old.
Interviews in 1993 show that key risk factors such asaggressive behavior and shy-aggressive behavior identified26 years ago continue to hold and are valid predictors ofthe subjects' current levels of cocaine use as adults.
During their studies, Dr. Ensminger and her colleaguesrated each first-grader's mental health using two criteria:social adaptation and psychological health. To measurepupils' social adaptation to school, researchers usedteachers' ratings of children's classroom social performance
and intelligence as well as the results of standardized tests.Psychological health was determined by a number ofcriteria, including psychological symptoms, abnormalbehavior, and level of self-esteem.
Two important risk factors identified as predictors of laterdrug use are shy behaviordescribed by the teachers assitting alone, having few friends, and not speaking up inclassand aggressiondescribed as fighting with othersor breaking rules. Shyness and aggression are types of poorsocial adaptation distinct from symptoms of anxiety ordepression, which are internal feelings, noted theresearchers.
A number of long range NIDA-fundedstudies have traced at-risk children
into adolescence and beyondtrying to determine why some of them
are able to resist influences to usesubstances of abuse
While shyness and aggressiveness are key predictors ofdrug use, a complex relationship exists between the twofactors. Among boys, aggressive behavior in the first gradeleads to increased teenage substance abuse, while first-grade shyness alone without aggressiveness leads to lowerlevels of substance abuse as teenagers. However, thecombination of shyness and aggressiveness leads to evenhigher levels of adolescent substance use among boys thanaggressiveness without shyness does, the studies found.
Boys whose teachers said they had problems concentratingin class had higher levels of later substance abuse becauseconcentration problems appear to be closely related toaggressiveness, the studies reported. By contrast, neitheraggressiveness, nor shyness, nor concentration problems inthe first grade were associated with later substance useamong girls.
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Understanding Gender Differences
Shyness and aggressiveness may be less important pre-dictors of substance use among females than among malesbecause girls' peer groups are smaller and less important tothem, she adds. These gender-based considerations arenow being studied in drug abuse prevention programs,says Dr. Ensminger, who was among the first researchersto urge colleagues to stop dismissing gender as a possiblekey consideration in predicting children'ssubsequent drug use.
For both sexes, higher scoreson first-grade IQ and
readiness-for-school tests wereassociatedwith higher levels of
beer or wine, hard liquor,and marijuana use 10 years later.
When the first-graders reached age 16 or 17, girls usedsmaller amounts of beer, wine, liquor, and marijuana andother illicit drugs but not cigarettes than boys did. Forboth sexes, higher scores on first-grade IQ and readiness-for-school tests were associated with higher levels of beeror wine, hard liquor, and marijuana use 10 years later, theresearchers found. "This tells us that the children who aremost ready for school are also those most ready toexperiment with drugs," says Dr. Ensminger.
Psychological well-being and family relationships in thefirst grade seemed more important to girls than to boys interms of influencing psychiatric symptoms 10 years later.Mothers had an important effect on the psychologicalstatus of their daughters but not of their sons. Mothers'expectations of how far daughters would go in school andmothers' own psychological health were positive factors intheir daughters' psychological well-being 10 years later, thestudy found. Girls with strong family bonds tend to usedrugs less than other girls do, but the same family influenceis not so apparent with boys, said Dr. Ensminger.
Results from the Woodlawn study served as the basis forprevention programs started in Baltimore in the 1980s byDr. Kellam and colleagues. That prevention effort focusedon aggressive behavior because of its relationship to laterdrug use and on underachievement because of itsrelationship to depressed feelings.
Recent data gathered on the Woodlawn study subjectsshow that early childhood aggression is still a valid pre-dictor of drug abuse when measured against the now-adult
subjects' levels of use of cocaine, Dr. Ensminger reports.Those data are now being prepared for publication.
Examining Protective Factors
Another long-term study of drug-use predictors focuses onchildren in Northeastern States. For 20 years, Dr. JudithS. Brook of Mt. Sinai School of Medicine has studied riskfactors identified in early childhood and in adolescencethat are related to drug use during adolescence. She isconducting a study of 1,000 children and their mothersthat began in 1975 in two communities representative ofthe population of the Northeastern United States. In thecontinuing research, Dr. Brook is examining not only riskfactors but also protective factors that help shield childrenand adolescents from these risk factors.
Dr. Brook and her colleagues have identified a number ofrisk factors for subsequent drug use such as childhoodaggression, which includes anger, aggression toward sib-lings, noncompliance, temper, and nonconforming behav-ior. Other risk factors are unconventionalityan attitudeof deviance, rebelliousness, and evasion of responsibilitythe extent of drug use among peers, and parental sociopa-thy, that is, parents' problems with drinking, drugs, or thepolice.
Dr. Brook's group examined the risk factors and theirimplications during childhood, ages 5 to 10; middleadolescence, ages 13 to 18; and late adolescence, ages 15to 20. They found that childhood aggression and parentalsociopathy predicted increased levels of drug use in lateadolescence. They also determined that unconventionalityduring the early years of adolescence had an "importantand pervasive impact on all aspects of middle and lateadolescent functioning," including increased drug use.
The research team is now observing the original subjects'children, beginning at age 2, and interviewing both parentsof these children to collect data on the new generation."So we're now studying the third generationthe grand-children of the mothers [of the original subjects] initiallystudied in 1975," says Dr. Brook. 'And we're finding agreat deal of consistency down through the generations inregards to personality and family characteristics," includingtraits that are drug-use risk factors.
The researchers also have studied interactions among riskfactors and their implications for subsequent drug use asthe children grow older. In addition to childhood aggres-sion, they found three additional factors that influencelate-adolescent drug useunconventionality and drug usein middle adolescence and parental sociopathy duringchildhood. They found that little or no drug use inmiddle adolescence when combined with conventionalityduring the same age span resulted in the least amount ofsubsequent drug use.
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As expected, parental sociopathy is related to late-teendrug use. Parents who drink or use drugs or both may bethe most strict with their children, telling them, "Do as Isay, not as I do," according to Dr. Brook's study. Theseadmonitions might be effective in middle adolescence,when children are more likely to be influenced by parentaldemands, but not in later adolescence, when the familyhas less control and the parents' own display of negativebehaviors becomes a drug-use risk factor, she says.
Dr. Brook agrees with other researchers that there arechildhood protective factors that can be very powerfulshields to safeguard children and adolescents from therecognized risk factors. These protective factors includeachievement, religious commitment, strong family bonds,and a solid attachment to and emulation of a wholesomerole model, she says.
"Some of these children are remarkably resilient," says Dr.Brook. Among those who become successful, she foundevidence of protective factors such as church attendance,childhood achievement in school or in extracurricularactivities, or close ties to brothers and sisters.
"Many of these kids go on to lead successful, productivelives, yet we tend to focus on the ones that don't," says Dr.Brook. "I want to learn more about what makes those thatdo well do so."
Family Relationships Critical
Still another continuing study of predictive factors fordrug use focuses on a different population segmentat-risk children of white families living in small andmedium-sized communities in Oregon. The study byDr. Hyman Hops and colleagues of the Oregon ResearchInstitute examines family and peer-group influences onadolescent substance use and is now in its 10th year.About 500 subjects were ages 11 through 15 at their firstassessment in 1984 and will be 21 through 25 at their lastassessment this year.
Among those studied, 90 percent of subjects who pro-gressed from one substance of abuse to another did so inthe following sequenceabstinence, alcohol, cigarettes,marijuana, and hard drugs. The most dramatic increase indrug use occurred between the ages of 13 and 14, whenadolescents are going from middle to high school.
Parents' use of substances, including cigarettes, is animportant predictive factor influencing their children'sdrug use. Within two-parent families, Dr. Hops foundthat fathers' drinking appears to have a greater impactthan mothers' drinking on both girls and boys, whilemothers' drinking has an effect only on adolescents under14, before they enter high school. Parents who use
cigarettes and alcohol may influence not only theirchildren's use of the same substances but illicit substancesas well, he says.
Family conflict and strife are strongly associated withincreased substance abuse, based on the researchers' directobservations of problem-solving scenarios between parentsand adolescents. Their findings suggest that families withsubstance-abusing children typically are unable to easilyresolve problems and that the resulting confrontationsnegatively affect drug use.
In examining peer influences, the Oregon researchers bal-anced each study subject's self-reports of levels of substanceuse against reports of his or her substance use level fromthe child's best friend. The scientists reported that theamount of both family cohesion and peer encouragementto use drugs was predictive of initial levels of substanceabuse. A good family relationship may play a powerfulrole as a protective factor in middle and late adolescence,they say. On the other hand, peer encouragement to usesubstances plays a stronger role across the age range andalso suggests that early peer influences may encouragehigher levels of drug use at later ages.
"These findings underscore the importance of familyinfluences on substance abuse throughout adolescenceand suggest greater attention to the family, as well as thepeer group, in designing prevention strategies," saysDr. Hops. "You've got to have a healthy family relation-ship to counter the very powerful peer influences thatkids face today."
Sources
Andrews, J.A.; Hops, H.; Ary, D.; Tildesley, E.; andHarris, J. Parental influence on early adolescent sub-stance use: Specific and nonspecific effects. Journal ofEarly Adolescence 13:285-310, 1993.
Brook, J.S.; Whiteman, M.; Cohen, P.;and Tanaka, J.S. Childhood precursors of adolescentdrug use: A longitudinal analysis. Genetic, Social, andGeneral Psychology Monographs 118(2):195-213, 1991.
Brook, J.S.; Whiteman, M.; Gordon, A.S.; andBrook, D.W. The psychosocial etiology of adolescentdrug use: A family interactional approach. Genetic,Social, and General Psychology Monographs116(2):113-267, 1990.
Brook, J.S.; Whiteman, M.; Hamburg, B.A.; andBalka, E.B. African-American and Puerto Rican druguse: Personality, familial, and other environmental riskfactors. Genetic, Social, and General PsychologyMonographs 118(4):417-438, 1992.
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Ensminger, M.E. Sexual activity and problem behav-iors among black, urban adolescents. ChildDevelopment 61:2032-2046, 1990.
Ensminger, M.E.; Brown, C.H.; and Kellam, S.G.Sex differences in antecedents of substance use amongadolescents. Journal of Social Issues 38(2):25 -42, 1982.
Hops, H.; Tildesley, E.; Lichtenstein, E.; Ary, D.; andSherman, L. Parent-adolescent problem-solving inter-actions and drug use. American Journal of Drug andAlcohol Abuse 16:239-258, 1990.
Kellam, S.G.; Brown, C.H.; Rubin, B.R.; andEnsminger, M.E. Paths leading to teenage psychiatricsymptoms and substance use: Developmentalepidemiological studies in Woodlawn. In: Guze, S.B.;Earls, F.J.; and Barrett, J.E., eds. ChildhoodPsychopathology and Development. New York: Raven,1983. pp. 17-51.ME
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