NIDA Notes: 2011, V23(4), March: Prevention Program Averts Initiation of Alcohol and Tobacco Use

2011·1.4 MB·English

www.drugabuse.gov Volume 23, Number 4 U.S. Department of Health and Human Services | National Institutes of Health
Prevention Program Averts
ALSO IN THIS ISSUE
Initiation of Alcohol and
Research Findings
Tobacco Use
4 HIV Treatment Interruption
Is Pervasive After Release
From Texas Prisons
Communities That Care aids towns in choosing and implementing
7 Combination Therapy
effective activities.
Most Effective for Helping
Smokers Quit
interventions with proven effectiveness; and
BY SHARON REYNOLDS,
9 Cocaine Alters Production
NIDA Notes Contributing Writer implement the interventions with fidelity.
of Hundreds of Proteins
Communities in Canada, the United Kingdom,
In the first randomized trial of Commu- the Netherlands, Germany, and Australia, as
Director’s Perspective
nities That Care (CTC), middle school well as the United States, have adopted CTC.
2 Physical Activity May
students in towns that utilized the preven- However, the current trial, called the Com-
Prevent Substance Abuse
tion system reported less delinquency, munity Youth Development Study (CYDS), is
initiation of alcohol and tobacco use, and binge the first to randomly assign communities to
Research in Brief
drinking than peers in comparison towns. implement either CTC or prevention as usual.
3 Prevention Program
Students in test towns also reported lower rates Earlier analyses of the data showed that CTC
Reduces Later Risky
of current alcohol and smokeless tobacco use in improved communities’ coalition building, as
Sexual Behaviors
the eighth grade. well as their selection and implementation of
• Menthol May Strengthen
CTC provides training and materials to help evidence-based prevention programs. It also
Nicotine Addiction • Brain
communities organize coalitions; identify risks reduced the prevalence of factors associated
Responds to Marijuana
for youth drug use and delinquency, as well as with youth substance abuse. The new findings
Cues in Familiar Manner
protective factors in the community; choose establish that CTC achieved its ultimate goal of
preventing behaviors that pose Bulletin Board
a risk to health.
Students engage in a "mat chat" on bullying through an after-school 14 Dr. Paul Kenny Receives
program chosen by community leaders under the guidance of the Five
the 2010 Waletzky
Town CTC (see box, page 12).
TRAINING COMMUNITIES
Memorial Award • Two
IN PREVENTION SCIENCE
NIDA Grantees Receive
The CTC program was Sarnat Prize • NIDA
designed by Drs. J. David Offers Online Training for
Hawkins and Richard F. Cata- International Community
lano of the Social Develop-
Tearoff
ment Research Group at the
ussell University of Washington. 15 Teenage Marijuana Use Is
N. R “We wanted to help communi- on the Rise
eter ties use prevention science to
P
by guide their actions,” explains What the Numbers Say
hy
ap Dr. Hawkins. “Prevention sci- 16 Fewer Girls Are Smoking,
gr
oto ence tells us that if you want But Change Is Uneven
h
P
[ Continued on page 12 ]
NIDA Notes | Volume 23, Number 4 1
■ DIRECTOR’S PERSPECTIVE By NORA D. VOLKOW, M.D., NIDA Director NIDA Notes
EDITOR
David Anderson
Public Health Advisor, Office of Science Policy
and Communications, National Institute on
Drug Abuse
DEPUTY EDITOR
Physical Activity May Julie Ann Miller, Ph.D.
RTI International
MANAGING EDITOR
Prevent Substance Abuse
Andrew Keegan
RTI International
SENIOR SCIENCE WRITER
Lori Whitten, Ph.D.
F RTI International
rom the minute they arrive at the park, children move constantly. They run,
ASSOCIATE EDITOR
jump, chase, and climb. Wrapped up in their fun, they aren’t thinking about the Debra P. Davis
RTI International
health-promoting effects of exercise. But NIDA scientists are. Staff scientists
DESIGN/LAYOUT
are considering the possibility that exercise—including active play, outdoor
Maggie Bray
adventure, team sports, martial arts, and dance—not only boosts energy and keeps weight RTI International
in check but also helps prevent substance abuse. NIDA has already invested over $4 .3 mil- EDITORIAL BOARD
lion to spur research on this emerging area of addiction science. David Anderson, Chair; Public
Health Advisor, Office of Science Policy
Although people tend to think of exercise as good for the body, it also benefits the brain. and Communications
As it invigorates the heart and lungs, it stimulates the brain’s reward pathway and height- Nicolette Borek, Ph.D., Research
Psychologist, Division of Clinical Neuroscience
ens mood-boosting neurochemicals. Animal research indicates that exercise promotes and Behavioral Research
the formation of blood vessels in the brain, forges connections between cells, enhances Scott Chen, Ph.D. , M.B.A., Scientific Review
Officer, Office of Extramural Affairs
repair of neural tissue, and generates new neurons in memory-formation areas. Through
J.C. Comolli, Public Health Advisor,
its actions on hormones that affect the nervous system, exercise also improves an animal’s
Division of Pharmacotherapies and Medical
tolerance of stress—an observation that is particularly intriguing given the links between Consequences of Drug Abuse
stress and drug abuse. Jennifer Elcano, M.A., Science Writer,
Office of Science Policy and Communications
Such observations may explain why competitive runners experience mood elevations,
Lynda Erinoff, Ph.D., Associate
physical activity sometimes relieves mild depression, and older people who exercise Director, AIDS Research Program, Division
of Epidemiology, Services and Prevention
improve in both mood and cognitive function.
Research
Patterns of drug abuse among teens suggest that physical activity can Petra Jacobs, M.D., Associate Director
strengthen resistance to addiction. Results from the NIDA-funded Monitoring the Future for Program Development, Center for Clinical
Trials Network
survey, for example, indicate that high school students who exercise regularly are less
Jacqueline Lloyd, Ph.D., Health Science
likely than sedentary teens to smoke cigarettes or abuse marijuana (“Lower Rates of Administrator, Division of Epidemiology,
Services and Prevention Research
Cigarette and Marijuana Smoking Among Exercising Teens,” NIDA Notes, Volume 22,
Marsha F. Lopez, Ph.D. , Health Science
Number 4, page 20). The relationship between drugs and exercise, however, may be indi- Administrator, Division of Epidemiology,
Services and Prevention Research
rect. Perhaps students who choose to exercise tend to make healthy decisions in gen-
Ivan Montoya, M.D., M.P.H., Medical
eral. Initiation of substance abuse may also be countered by the support of teammates,
Officer, Division of Pharmacotherapies and
coaches, and family; by other social aspects of participation in organized activities; and by Medical Consequences of Drug Abuse
the time management skills that active teens develop . Mary Pfeiffer, Ph.D., Editor and Writer,
Intramural Research Program
Apart from improving the health of the developing brain, there are many rea-
Kenzie Preston, Ph.D., Chief, Clinical
sons to think that physical activity can be a useful means for preventing substance Pharmacology and Therapeutics Research
Branch
abuse among young people. The best way to grab the attention of children and teens is
Paul Schnur, Ph.D., Deputy Director,
often to offer them a range of appealing challenges. Physical activities—particularly in Division of Basic Neuroscience and Behavioral
Research
natural environments—offer youth healthy opportunities to learn skills, take risks, and
Anna Staton, M.P.A., Public Health
achieve goals.
Analyst, Office of Science Policy and
I run 6 miles a day because I enjoy it. But, as a neuroscientist, I’m intrigued that physi- Communications
cal activity is good for the brain. At NIDA, we look forward to supporting groundbreaking Cora Lee Wetherington, Ph.D.,
Psychologist, Division of Basic Neuroscience
research on the neurobiological, psychological, and social processes by which exercise and Behavioral Research
may promote overall well-being and protect against drug abuse and addiction. ■ This publication was produced and
printed by RTI International under
Contract No. HHSN271200900042C
from the National Institute on Drug
Abuse.
2 NIDA Notes | Volume 23, Number 4
■ RESEARCH IN BRIEF Highlights of recently published NIDA-supported studies
opposed to 32 percent of the them to puff more deeply or either a marijuana pipe or a
control group. The results frequently and thus extract neutral object, in this case a
suggest that school drug more nicotine from each pencil, after going 3 days with-
abuse prevention programs cigarette. In earlier work, the out the drug. While handling
can reduce at least some risky New Jersey group had shown the pipe, the study participants
sexual behavior years later. that smokers of menthol reported more craving for
> Journal of Adolescent Health cigarettes absorb higher levels marijuana, and the brain imag-
45(2):111–117, 2009. of nicotine than smokers of es revealed greater activity in
nonmenthol brands, which the ventral tegmental area,
Menthol May may increase the severity of nucleus accumbens, prefrontal
Prevention Program Strengthen Nicotine addiction and the difficulty of cortex, and other reward- and
Reduces Later Risky Addiction quitting. Of the 1,688 partici- motivation-related areas. In
Sexual Behaviors In a recent NIDA-supported pants in the recent study, 46 other studies, activation of
Teens who participated in study, Latino and African- percent smoked menthol ciga- these neural pathways has
the school-based drug abuse American smokers of menthol rettes, including 81 percent of been associated with crav-
prevention program Project cigarettes benefited less from African-Americans, 65 percent ings for alcohol, nicotine, and
ALERT were less likely than a 1-month smoking cessation of Latinos, and 32 percent of cocaine; the intensity of activa-
peers to engage in risky program than did smokers of Caucasians. tion is considered an indicator
sexual behaviors as young nonmenthol cigarettes. Dur- > International Journal of Clinical of the severity of dependence
adults, report NIDA-funded ing the month following the Practice 63(3):360–367, 2009. on those drugs.
researchers. Dr. Phyllis L. treatment, only 23 percent of As with other addictive
Ellickson and colleagues at Latinos and 30 percent of drugs, the extent of the cue-
RAND Corporation queried African-Americans who induced activity in the brains
1,901 unmarried, sexually smoked menthol cigarettes of the marijuana smokers cor-
active 21-year-old men and achieved a weeklong period related with the number of
women from Midwestern of abstinence, compared problems that the participants
communities. The participants with roughly half of the non- reported, such as family trou-
had attended schools ran- menthol smokers in each bles, work missed, or jobs lost.
domly assigned to use Project group. Caucasian participants According to the researchers,
ALERT, a middle school cur- showed no gap in abstinence the findings suggest that medi-
riculum that motivates young rates between smokers of cation development strategies
people to abstain from drug menthol and of nonmenthol targeting these areas of the
use and teaches resistance cigarettes. Brain Responds to brain may ultimately prove
skills; Project ALERT plus 10 Study leaders Drs. Kunal Marijuana Cues in effective against craving and
booster lessons during high K. Gandhi and Jill M. Wil- Familiar Manner addiction to marijuana, as well
school; or no special program. liams at the University of Cravings triggered by marijuana- as other drugs.
Forty-four percent of Medicine and Dentistry of related cues, such as a mari- > Proceedings of the National
those exposed to either the New Jersey also found that in juana pipe, are associated with Academy of Sciences
106(31):13016–13021, 2009.
core or expanded version of each ethnic group, menthol’s a pattern of brain activity simi-
Project ALERT reported that negative impact on quitting lar to that which accompanies
they had had multiple sex success was most pronounced cravings for other drugs, say
CORRECTION: The article titled
partners during the past year, among participants of low NIDA-funded researchers at
“Study Supports Methadone
compared with 50 percent of socioeconomic status. The the University of New Mexico. Maintenance in Therapeutic
their unexposed peers. Just 27 researchers hypothesized that Dr. Francesca M. Filbey and Communities” (NIDA Notes,
Volume 23, Number 3, page 8)
percent of the Project ALERT smokers who can afford only colleagues obtained functional
should have attributed a 2005
participants reported that they limited cigarette purchases magnetic resonance images of national survey of 380 therapeu-
had engaged in unprotected may prefer menthol cigarettes reward areas in the brains of tic communities to the Institute
for Behavioral Research at the
sex while under the influence because menthol’s soothing 38 regular marijuana smokers
University of Georgia.
of alcohol or illicit drugs, as effects on the throat enable while the participants handled
NIDA Notes | Volume 23, Number 4 3
■ RESEARCH FINDINGS
HIV Treatment Interruption Is
Pervasive After Release From
Texas Prisons
Helping inmates fill out application forms for antiretroviral medication doubles
prescription utilization.
lowing their release, Dr. Baillargeon says. program (see box, page 5) for inmates with
BY LORI WHITTEN,
NIDA Notes Staff Writer As a result, they confront obstacles to con- HIV. Coordinators succeeded in provid-
tinuing treatment at the same time they ing 55 percent of those eligible with formal
Nearly all Texas state prison- face expanded opportunities to initiate or assistance in completing and submitting
ers who receive antiretro- resume injection drug use, unprotected the ADAP application.
viral therapy while incar- sex, and other HIV risk behaviors. Along
cerated experience some with the risks of disease progression and ASSISTANCE INCREASES
treatment interruption following their transmission, discontinuation of antiret- FULFILLMENT
release, according to a new NIDA-funded roviral therapy may lead to medication- The researchers examined all prescrip-
study by Dr. Jacques Baillargeon of the resistant HIV. tions in the Texas ADAP database. They
University of Texas Medical Branch in To examine medication use among found that about 5 percent of released
Galveston. More than two-thirds of these recently released inmates, Dr. Baillar- inmates filled the initial 30-day prescrip-
interruptions last longer than 60 days, geon and colleagues collaborated with tion during the first 10 days after their
during which time ex-prisoners may the Texas Department of Criminal Jus- release, and 18 percent did so during the
develop higher viral loads that increase
their risk of disease progression and trans- Although most HIV-infected inmates receive anti-
mission to others.
retroviral therapy during incarceration, many have
These results highlight a national pub-
extremely limited access to health care systems in
lic health problem, according to Dr. Bail-
the months immediately following their release.
largeon, who notes that prison discharge
planning and community-based HIV
care in Texas is similar to that in other tice, which oversees one of the largest first 30 days. Inmates who received assis-
states. The study also indicated that sim- state prison systems in the United States. tance from a caseworker to complete and
ply helping prisoners with the paperwork Texas administers a federally funded pro- submit the ADAP application filled their
necessary to obtain free federally funded gram, the AIDS Drug Assistance Program prescriptions at rates about double those
antiretroviral therapy can substantially (ADAP), to help ex-prisoners continue who did not receive the help. At 60 days
reduce treatment interruptions. their antiretroviral treatment during the after release, those who had received assis-
time it takes them to locate treatment tance continued to show an advantage—34
A TIME OF INCREASED RISK services in the community. During stan- percent versus 26 percent.
Because rates of HIV infection among dard discharge planning, HIV-infected Although similar percentages of each
inmates are currently several-fold those inmates receive a four-page application ethnic group received assistance with the
of the general population, U.S. pris- form for a free 30-day supply of the medi- ADAP, Hispanic and African-American
ons have become focal sites in efforts to cation through ADAP, along with a 10-day participants were less likely than whites
control the virus. Although most HIV- supply of antiretroviral medication and to continue antiretroviral treatment dur-
infected inmates receive antiretroviral information on accessing community HIV ing the first 10 and 30 days after release.
therapy during incarceration, many have treatment. Those disparities disappeared, however,
extremely limited access to health care Partway through the 4-year study, by 60 days.
systems in the months immediately fol- Texas prisons phased in a new discharge Individuals not on parole filled the
4 NIDA Notes | Volume 23, Number 4
Texas Prison Discharge Planning for Inmates
With HIV
Prisons in Texas adhere to a specific plan for releasing
inmates with HIV. Thirty days before the release of any
inmate, the prison notes whether he or she is receiving
antiretroviral therapy. On the day of release, those who
have been on the therapy receive:
• A copy of recent HIV laboratory test results
• A 10-day supply of antiretroviral medication
• A list of clinicians who provide care to patients with
HIV in the released inmate’s home community
• An application to the AIDS Drug Assistance Program
(ADAP) to receive a 30-day supply of antiretroviral
medication; and, if resources permit, assistance in
completing and submitting the form
Although the federally funded ADAP program has eligibility
• An ADAP medication certification signed by a physician
requirements that include an inability to pay for medica-
• A toll-free phone number and instructions to call an tions, the Texas Department of Corrections found that virtu-
ADAP caseworker for assignment to a local pharmacy. ally every inmate leaving its prison system qualifies.
initial antiretroviral prescription within The study included 2,115 inmates with clinic, suggesting that enhanced discharge
30 and 60 days of release at lower rates HIV released between January 2004 and programs may increase continuity of HIV
than parolees, who had parole officers December 2007. Of the participants, 83 care among newly released inmates.
to encourage them, says Dr. Baillargeon. percent were male, and 58 percent had “Our findings document that a low
Furthermore, participants whose HIV committed a drug-related crime. The percentage of former prisoners access
infection was under control in prison, as study population was 60 percent African- antiretroviral therapy in a timely fash-
indicated by an undetectable viral load, American, 27 percent white, and 13 percent ion after release. This observation may
were more likely to fill the initial prescrip- Hispanic. Although demographic char- underlie the results of prior studies that
tion than those with measurable amounts acteristics of prison inmates vary from reported loss of both immune function
of HIV in their blood. Dr. Baillargeon state to state, Dr. Baillargeon says that he and viral suppression among offenders
notes that some individuals, while in expects the study results to apply across who return to the criminal justice system,”
prison, are better than others at adhering the Nation. says Dr. Baillargeon.
to antiretro viral regimens, and that this In a subsequent analysis of clinical
difference in behavior may continue after data from 1,750 HIV-infected inmates A STEP IN THE RIGHT DIRECTION
release. returning to the community in one Texas The results of the study spurred the
Among those who filled the initial county, Dr. Baillargeon and colleagues Texas Department of State Health Ser-
30-day prescription through ADAP, only found that only 20 percent of former vices to hold a summit on antiretroviral
6 percent accessed the medication for a inmates enrolled in an HIV clinic within therapy continuance after prison release.
second month without interruption. This 30 days of release. Only 28 percent did so Summit participants, including Dr. Bail-
finding suggests that former inmates with within 90 days. At both assessment times, largeon, proposed additional steps public
HIV may need additional assistance coor- those who received enhanced discharge health officials might take—for example,
dinating their health care during the first planning were about 50 percent more providing transportation assistance or
few months after release. likely than those who did not to enroll in a vouchers to facilitate released prisoners’
NIDA Notes | Volume 23, Number 4 5
contact with health care providers. In nent of efforts to improve medication re-entry. Over the next 5 years, the
future research, Dr. Baillargeon’s team continuance. teams will compare different methods of
plans to identify psychosocial and practi- “Followup care after release might fur- identifying HIV-positive offenders and
cal barriers that prevent former prisoners ther enhance the proportion of former engaging and retaining them in treat-
from accessing antiretroviral therapy. The prisoners with HIV who continue medica- ment. Some of the projects will create
team’s goal is to develop interventions to tion,” says Dr. Jones. “Former prisoners and compare systems to better integrate
remove such obstacles. often face many difficulties—including and coordinate HIV management efforts.
“This collaboration between the family estrangement, unemployment, lack The grants will also support randomized
researchers and the Texas Depart- of housing and transportation, and vul- controlled trials among large groups of
ment of Criminal Justice represents nerability to drug relapse—as they try to HIV-positive parolees and probationers,
a step in the right direction toward re-integrate into the community.” comparing various approaches for link-
fighting the HIV epidemic, and NIDA NIDA recently expanded its own ing them to treatment and social services
applauds their effort to address an efforts to fight HIV among prisoners. The in their communities. ■
important public health problem for Institute, along with the National Institute
SOURCES
the Nation,” says Dr. Dionne Jones of Mental Health and the National Institute
Baillargeon, J.G., et al. Enrollment in outpatient care
of NIDA’s Division of Epidemiology, of Allergy and Infectious Diseases, is newly among newly released prison inmates with HIV infec-
Services and Prevention Research. supporting 12 research teams as they tion. Public Health Reports 125 Supplement 1:64–71,
2010.
Because helping inmates complete examine ways to identify persons with
Baillargeon, J.G., et al. Accessing antiretroviral ther-
and submit the ADAP forms was inex- HIV within the criminal justice system and
apy following release from prison. JAMA 301(8):848–
pensive, such assistance may prove link them to effective therapy during peri- 857, 2009.
a cost-effective and valuable compo- ods of incarceration and after community
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6 NIDA Notes | Volume 23, Number 4
■ RESEARCH FINDINGS
Combination Therapy Most Effective
for Helping Smokers Quit
Treatment with a nicotine patch and lozenge outperformed four other
smoking-cessation therapies in a large clinical trial.
BY SHARON REYNOLDS,
NIDA Notes Contributing Writer MANY THERAPIES REDUCE SMOKING Abstinence rates for all treatments peaked at the
8-week assessment. Abstinence was confirmed by breath carbon monoxide levels measured during
visits to the clinic.
In a randomized clinical trial of five
smoking-cessation treatments, a
60
combination of the nicotine patch ng
ki 1 week after quitting
and nicotine lozenge produced the o
m
greatest benefit, relative to placebo treat- m s 50 8 weeks after quitting
mreemnati, nin a hbesltpininegn pt efoopr lea tq lueiat sstm 6o mkinogn tahnsd. ent fro 40 6 months after quitting
n
Current public health guidelines, based sti
b
a
on earlier clinical trials testing individual s 30
nt
smoking-cessation aids, recognize that pa
ci
several medications increase smokers’ arti 20
p
success in kicking the addiction. However, of
the lack of direct comparisons between nt
e 10
c
smoking-cessation aids has made it dif- er
P
ficult for doctors and smokers to choose
0
one treatment over another. Placebo Bupropion Lozenge Patch Bupropion Patch
+ Lozenge + Lozenge
At the start of the study, for example,
there had been only one placebo-controlled
trial of the lozenge’s effectiveness, and
the combinations of lozenge plus either group that included a matching placebo ment designed to mimic one of the five
nicotine patch or bupropion had never for each of the five treatments tested. regimens. Neither the participants nor the
been tested in a clinical trial. The patch, The participants were 1,504 adults who study staff were told who was receiving the
used alone, is currently the most common had smoked more than nine cigarettes active treatments. Varenicline (Chantix),
smoking-cessation aid. a day, on average, for at least the past 6 a more recently introduced smoking ces-
months. They all wanted to quit and had sation aid, was not included in the study.
FIVE TREATMENTS TESTED already tried to do so an average of five The patients began using bupropion
Researchers at the University of Wis- to six times. The smokers were, on aver- and the bupropion placebo 1 week before
consin’s Transdisciplinary Tobacco Use age, moderately dependent on nicotine, their chosen quit date and the other ther-
Research Center designed a compara- according to the Fagerström Test, which apies and their respective placebos on
tive effectiveness trial “to permit more- is commonly used to measure nicotine the quit date. All the treatment regimens
informed decisions about the selection dependence. Each participant was ran- continued for 8 weeks after the quit date
and use of smoking-cessation pharma- domly assigned to receive either one of except for use of the nicotine lozenge and
cotherapies,” explains study leader Dr. five smoking-cessation regimens—the lozenge placebo, which continued for
Megan E. Piper. nicotine lozenge, the nicotine patch, 12 weeks. All participants received two
In the trial, the researchers tested five bupropion, the nicotine patch plus the smoking-cessation counseling sessions
treatments side by side to see how each nicotine lozenge, and bupropion plus before the quit date, one session on the
performed relative to a combined placebo the nicotine lozenge—or a placebo treat- quit date, and three additional sessions
NIDA Notes | Volume 23, Number 4 7
during the following 4 weeks. ing medication after a lapse may reduce the two mechanisms of administration,”
Most of the patients in every group the chance of a relapse. she explains.
avoided smoking for at least 1 day dur- Dr. Piper and colleagues note that if they Dr. Piper says that although the patch
ing the week following their quit dates, had used the criteria employed by studies plus lozenge showed the best results
but those receiving the active medica- that compare a single treatment with pla- relative to placebo, the quit rates in all
tions did so at higher rates than those cebo, all of the active treatments would groups—including those receiving a pla-
on placebos. The patients assigned to have been deemed to outperform the cebo—were unusually high for a smoking-
cessation trial. She speculates that this
The combination of nicotine patch plus lozenge might be attributed to the counseling,
appears to afford smokers the highest chance of which may have been particularly effec-
quitting. tive, or to the high motivation of the par-
ticipants, given that they had agreed to be
three of the active regimens—the patch placebos at all time points, with the excep- part of a 3-year clinical study of the physi-
plus lozenge, bupropion plus lozenge, tion of the lozenge at 1 week after the quit cal and psychological consequences of
and the patch alone—were most likely date. However, only the combination of smoking cessation.
to be abstinent on day 7 and at the end of nicotine patch plus lozenge provided a Dr. Ivan Montoya of NIDA’s Division
the 8-week treatment period (see graph, significant advantage under the stringent of Pharmacotherapies and Medical Con-
page 7). statistical criteria that are appropriate in sequences of Drug Abuse says, “This is
At the 6-month followup interviews, studies making multiple comparisons. This an important study for clinicians because
however, only the group using the patch suggests that the combination of nicotine there is evidence about the best of those
plus lozenge had a significantly higher patch plus lozenge affords smokers the five treatments. Based on these results, if
prevalence of abstinence than the placebo highest chance of quitting. I have a patient who wants to quit smoking,
recipients, 40 percent versus 22 percent. of the five treatment choices, I would try
The patch plus lozenge combination also EFFECTIVENESS ACROSS THE BOARD my patient first on the patch plus lozenge.”
stood out as being one of two regimens— The superiority of the patch plus loz- “This study provides a better under-
with bupriopion plus lozenge—that sig- enge combination seen in this trial has standing of what these treatments can
nificantly increased, relative to placebo, several potential explanations, says Dr. do,” adds Dr. Piper. “To clinicians who
the number of days from the quit date to Piper. One is that this combination ther- think that they don’t have anything to help
relapse, which was defined as smoking on apy provides two different ways to tackle treat smoking, here’s some evidence that
7 consecutive days. All the active medica- withdrawal—a steady dose of nicotine there’s a lot out there that they can use.” ■
tion regimens except the lozenge alone from the patch plus the as-needed lozenge
SOURCE
lengthened the interval between lapsing, to help with transient, strong cravings or
Piper, M.E., et al. A randomized placebo-controlled
defined as taking a first puff on a cigarette challenges induced by an environmental clinical trial of 5 smoking cessation pharmacothera-
after a period of abstinence, and relapsing. cue. “Alternatively, the effect may be due pies. Archives of General Psychiatry 66(11): 1254–1262,
2009.
This latter finding suggests that continu- primarily to the higher nicotine dose from
NIDA Research Report on Marijuana Abuse
This updated NIDA report contains scientific information on the scope, effects,
and consequences of marijuana abuse.
Marijuana Abuse can be viewed at
www.nida.nih.gov/ResearchReports/Marijuana/default.html
and obtained from DrugPubs, NIDA’s Research Dissemination Center.
Place an order at drugpubs.drugabuse.gov
or call 1-877-NIDA-NIH (1-877-643-2644) or 1-240-645-0228 (TDD)
or fax [phone] or e-mail [email protected].
8 NIDA Notes | Volume 23, Number 4
■ RESEARCH FINDINGS
Cocaine Alters Production of
Hundreds of Proteins
Affected proteins include enzymes that influence DNA repair, cell death, stress
resistance, metabolism, and aging.
BY LORI WHITTEN,
NIDA Notes Staff Writer A POWERFUL FAMILY OF ENZYMES IMPLICATED IN COCAINE'S EFFECTS
Sirtuins—also called SIRTs, for “silent information regulators of transcription”— influence a wide
range of functions essential for life. This family of enzymes regulates biological processes including
Chronic cocaine abuse may metabolism, DNA repair, cell specialization and death, stress resistance, and tumor growth. Sirtuin
alter the production of activity has been linked to longevity in worms and fruit flies. Scientists have thus far identified seven
sirtuins in mammals, and SIRT1 has been studied most extensively. Cocaine regulation of sirtuin
more than 1,000 proteins appears to be specific to one brain region.
in the neurons of the brain’s
reward system. The finding by NIDA-
Brain:
funded researchers sets the stage for Liver:
SIRT1
new advances in understanding how the SIRT1

stimulant causes addiction. Each affected
Glucose production Cellular Increases resistance
protein may contribute to the cognitive specialization to neurodegeneration,
Circadian Energy
and behavioral changes that mark the rhythms expenditure influences neuronal
transition from voluntary to compulsive Cell SIRT1 Aging specialization
breakdown
drug taking and provide a lead to new anti- Fat tissue: resSitsrteasnsce
addiction medication strategies. SIRT1 dCeealtl h Pancreas:
Regulation of
Although some of the proteins iden- Fat mobilization, transcription SIRT1
tified in the study have previously been lipid metabolism
Insulin
linked to cocaine’s effects, the great
secretion
majority have not. Among the most
Blood vessel:
intriguing of these, the researchers say, Intestine:
SIRT1
are two enzymes in the large family SIRT1
called sirtuins. In experiments with mice, Growth of
Decreases tumor
chemically boosting the activity of these new vessels
formation
enzymes intensified drug seeking.
ABUNDANT AND SUGGESTIVE
FINDINGS
Dr. Eric Nestler of Mount Sinai School protein products—following a week of ment in a broad range of fundamental pro-
of Medicine and colleagues at the Uni- exposure to cocaine, as compared with a cesses suggests that the cocaine-induced
versity of Texas Southwestern Medical week of exposure to saline. In a smaller— increases in levels of SIRT1 and SIRT2
Center and Florida State University used but still ample—number of other cases, might play important roles in addiction.
a technique called chromatin immunopre- cocaine reduced gene activity. Spurred by this suggestion, Dr. Nes-
cipitation (ChIP)-chip (see box, page 11) The researchers singled out a pair tler and colleagues investigated the rela-
to assess cocaine’s impact on the genes for of sirtuins, SIRT1 and SIRT2, as being tionship between sirtuins and behavioral
20,000 proteins in neurons of the brain of particular interest. Sirtuins regulate responses to cocaine. They administered
area called the nucleus accumbens (NAc) basic biological processes in organisms as the stimulant to mice in one chamber of a
of mice. The results indicated that about diverse as bacteria and humans. Although split cage until the animals began to spend
5 percent of the genes were more active— little is known about the sirtuins’ func- most of their time there, seeking the drug.
likely accelerating manufacture of their tion in the nervous system, their involve- The researchers then removed the mice
NIDA Notes | Volume 23, Number 4 9
One Protein’s Dual Role in Addiction
Chronic exposure to stimulant drugs introduces many • Increasing ∆FosB in drug-naïve rats reduced the produc-
changes in the brain’s reward system. Some are pathological tion of c-Fos in response to a single injection of amphet-
and others appear to be countermeasures to restore neural amine.
health. Recently, Dr. Eric Nestler of Mount Sinai School of
The researchers concluded that ∆FosB attenuates c-Fos manu-
Medicine, New York, with colleagues at the University of
facture by attracting HDAC1 to the promoter region of the c-Fos
Texas Southwestern Medical Center at Dallas revealed how
gene. “In response to repeated amphetamine exposure, brain
one protein that has long been implicated in the develop-
cells mount a counter-response that reverses acute amphet-
ment of addiction to stimulants, such as amphetamines and
amine’s increased production of c-Fos,” says Dr. Nestler.
cocaine, also may contribute to a compensatory effect.
Another ChIP experiment revealed a second adaptive
The protein, ∆FosB, is a transcription factor, one of a family
response to chronic amphetamine exposure that reinforces
of molecules that attach to a gene and accelerate or retard
the suppression of c-Fos production but is independent from
production of its protein. In previous work with animals,
that of ∆FosB. At a location in the c-Fos gene promoter region
Dr. Nestler and others established that chronic exposure to
near to that where ∆FosB accumulates, an enzyme called a
cocaine or amphetamine causes ∆FosB to accumulate in the
histone methyltransferase gathers and reduces access to DNA
brain region called the striatum. This accumulation correlates
by causing a tightening similar to that observed with HDAC1.
with increased drug-seeking behaviors, likely by causing
excesses or shortages of proteins in the nucleus accumbens “Dr. Nestler’s findings point to a new pathway involving ∆FosB
and other areas of the striatum that support cognition and and represent a first step toward determining how this pro-
shape reward-related behaviors. tein represses gene activity,” says Dr. John Satterlee of NIDA’s
Division of Basic Neuroscience and Behavioral Research.
The net result of ∆FosB buildup in the striatum is deleterious,
“Moreover, they show that histone methylation—an estab-
and scientists suspect that it may be pivotal in the transition
lished mechanism underlying changes in gene expression—
from initial stimulant abuse to addiction. However, the effect
plays a role in the brain's response to chronic amphetamine
on one protein, c-Fos, opposes amphetamine’s impact.
exposure.”
Like ∆FosB, to which it is related, c-Fos is a transcription fac-
Dr. Nestler plans to further examine how ∆FosB and c-Fos
tor whose abundance in the striatum correlates with behav-
influence drug seeking and the process of addiction. He also
ioral responses to stimulants. In contrast to ∆FosB, which
emphasizes that ∆FosB’s ability to activate some genes but
responds minimally to acute drug abuse and accumulates
inhibit others highlights the need to identify examples of both
in chronic abuse, c-Fos exhibits a different arc: Its levels
types of actions in the regulation of addictive behaviors.
rise sharply after acute stimulant exposure and wane during
chronic abuse. To Dr. Nestler, these observations suggest that Like some of the brain’s other molecular responses to drugs,
∆FosB suppresses c-Fos production. The recent development ∆FosB augmentation represents an exaggeration of a normal
of ChIP technology (see box, page 11) enabled him and his response to natural rewards such as food. “From an evo-
colleagues to test this proposition. lutionary perspective, accumulation of ∆FosB after natural
rewards was probably adaptive,” Dr. Nestler says. “It likely
The researchers administered daily injections of amphetamine
helped form memories for food and mates and enhanced
or saline to rats for a week followed by 5 days of withdrawal—
motivation to seek these rewards again. Drugs induce an
a time when c-Fos reached its lowest level in striatal neurons
excessive amount of ∆FosB and usurp this process.”
of the animals that had received the drug. The team then used
ChIP to measure ∆FosB binding to the promoter region of the
gene for c-Fos. They observed that:
SOURCES
• More ∆FosB attached in the animals given the drug than Hedges, V.L., et al. Delta FosB overexpression in the nucleus accumbens
those given saline; enhances sexual reward in female Syrian hamsters. Genes, Brain, and
Behavior 8(4):442–449, 2009.
• Increased amounts of bound ∆FosB correlated with
Renthal, W., et al. Delta FosB mediates epigenetic desensitization of the
reduced c-Fos production, as evidenced by lower levels
c-fos gene after chronic amphetamine exposure. Journal of Neuroscience
of c-Fos messenger RNA;
28(29):7344–7349, 2008.
• The ∆FosB attracted an enzyme called histone deacetylase
Wallace, D.L., et al. The influence of DeltaFosB in the nucleus accumbens
1 (HDAC1) that causes DNA to be held more tightly against
on natural reward-related behavior. Journal of Neuroscience 28(41):10272–
its protein scaffolding, resulting in less production of c-Fos; 10277, 2008.
10 NIDA Notes | Volume 23, Number 4