NIDA Notes: 2003, V18(5), December: Addictive Drugs and Stress Trigger Similar Change in Brain Cells, Animal Study Finds

16 Pages·2003·0.44 MB·English

Volume 18, Number 5
Addictive Drugs and Stress Trigger Similar
Change in Brain Cells, Animal Study Finds
By Patrick Zickler, NIDA NOTES Staff Writer
PP reventing relapse is
Addictive Drugs and Stress Increase Sensitivity of
the most formidable
challenge to success- Dopamine Cells in Mice
ful treatment of drug
addiction. After months or 0.82
0.8
efovremne yr euasres ros fm aabys tienxepnecrei-, atio 00..67 0.70 0.70 0.68 0.67 0.64
ence powerful cravings DA R0.5 0.42 0.46 0.44 0.44 0.41 0.46
that lead to resumption of M0.4
N
drug abuse. A single expo- PA/0.3
M
sure to drugs, an environ- A0.2
mental cue associated with 0.1
pstarests sdfurul ge vtaeknitn cga, no rp raecipi- 0.0 Saline CocaineAmphetamine Saline Morphine Nicotine Alchohol Saline FluoxetiCnaerbemazepine Saline Stress
tate renewed, uncontrol- Addictive Drug Non-Addictive Drug Stress
lable drug seeking and
Researchers injected mice with either saline, an addictive drug (cocaine, amphetamine, morphine, nicotine, or
abuse.
alcohol), or a nonaddictive drug that is active in the brain (carbemazepine or fluoxetine). Twenty-four hours
Susceptibility to
later, the scientists measured the electrical properties of dopamine cells from the animals’ ventral tegmental
relapse, like the onset of area (VTA). Cells from mice exposed to addictive drugs exhibited a higher ratio of AMPA to NMDA currents
addiction, is in part a con- than did those of mice exposed to nonaddictive drugs or saline, indicating establishment of long-term potenti-
sequence of changes to ation (LTP), a condition that causes the cells to release dopamine more abundantly than they previously would
have. The researchers also exposed mice to stress, but not to any drugs, and found the same LTP “fingerprint”
nerve cells in the brain.
when they examined VTA cells 24 hours later.
In recent experiments aimed at increasing understanding of
the nature of these changes, NIDA researchers have estab-
What’s Inside
lished that most major drugs of abuse can induce long-
term potentiation (LTP) in dopamine-releasing cells in an
DUAL CHALLENGE OF SUBSTANCE ABUSE
area of the brain called the VTA (ventral tegmental area).
AND MENTAL DISORDERS
LTP primes these cells to react more strongly—and release
in the Director’s Column . . . . . . . . . . . . . . . . . . . .3 dopamine more abundantly—in response to future expo-
sures to the drug. Because dopamine’s roles include alert-
HARD-TO-TREAT SMOKERS
may benefit from Parkinson’s medication . . . . . . .11 ing the mind that something important is happening or
about to happen and triggering feelings of pleasure, this
KIDS AT HIGH RISK FOR SUBSTANCE USE
finding could help explain addiction’s extraordinary and
respond to prevention program . . . . . . . . . . . . . .12
long-lasting hold over people. The researchers showed that
continued on page 6
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESnNATIONAL INSTITUTES OF HEALTH
IN THIS ISSUE
Research Findings
Addictive Drugs and Stress Trigger Similar Change in
Brain Cells, Animal Study Finds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Early Use of Drugs May Lead to Later Psychiatric Disorders . . . . . . . . . . . . . . . . . 5
Cognitive Deficits in Marijuana Smokers Persist After
Use Stops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Hard-to-Treat Smokers May Benefit From Medication
That Acts on Dopamine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
School Prevention Program Effective With Youths at
Marijuana’s Persistent Impact on High Risk for Initiating Substance Use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Cognition, p. 8
Research News
Researchers, Practitioners “Blend” Knowledge to Enhance
Drug Abuse Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Director’s Column
The Dual Challenge of Substance Abuse and
Mental Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Bulletin Board
You’ve Got Mail: NIDA NOTES Online Delivery Coming Soon . . . . . . . . . . . . . . 14
Electronic Delivery of NIDA Tearoff
NOTES, p. 14
Researcher-Practitioner Dialogue Continues in NIDA Journal . . . . . . . . . . . . . . . 15
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2 Volume 18, Number 5 NIDA NOTES
DIRECTOR’S COLUMN
The Dual Challenge of Substance
Abuse and Mental Disorders
By NIDA Director Nora D. Volkow, M.D.
AA s many as 6 in 10 people who “Early Use of Drugs May Lead to Later
abuse drugs and alcohol also Psychiatric Disorders,” p. 5).
suffer from mental illnesses, Multidisciplinary research studies
according to epidemiological studies. can give us a better understanding of
Conversely, some 25 to 60 percent of the origins and progression of comor-
individuals with mental illnesses also bid mental and substance abuse disor-
have substance abuse disorders. The ders that will enable us to respond
overwhelming reality of these concur- effectively to the problem. Thus,
rent disorders presents huge chal- NIDA and NIMH are increasing
lenges for drug abuse research, pre- research to identify genetic variations
vention, and treatment. that increase vulnerability to mental
Our attempts to understand sub- and substance abuse disorders and
stance abuse and mental illness clarify how individual, social, and
comorbidity are complicated by the environmental factors influence the
Multidisciplinary research
many ways these complex conditions development and course of comorbid-
can develop. Research suggests that ity. This research has the potential to
studies can give us a better some people’s genetic makeup may bolster our ongoing efforts to develop
put them at higher risk for psychiatric effective approaches to preventing
understanding of the and substance use disorders. In some comorbidity and treating the vast
instances, individuals with mental ill- majority of substance abuse patients
origins and progression of ness may begin to abuse drugs in who suffer from this devastating con-
attempts to alleviate distressing symp- dition.
toms of the disease, putting them- MDD, other mood disorders, con-
comorbid substance abuse
selves at risk for addiction. In other duct and personality disorders, post-
cases, substance abuse and its associ- traumatic stress disorder (PTSD), and
and mental disorders that
ated neurobiological changes appear schizophrenia are mental disorders
to increase vulnerability to and possi- that often accompany substance
will enable us to respond
bly trigger mental disorders. Research abuse. However, mood disorders are
funded by the National Institute of among the most commonly diagnosed
effectively to the problem. Mental Health (NIMH) and NIDA that mental illnesses in people who abuse
followed more than 700 individuals substances. Basic research has found
from early childhood into their late that drug-dependent individuals and
twenties recently concluded that early people with depression exhibit similar
substance abuse is associated with alterations in brain activity. For exam-
and significantly predicts later occur- ple, drug withdrawal symptoms such
rence of psychiatric disorders, includ- as irritability, dysphoric mood, and an
ing major depressive disorder (MDD). inability to experience pleasure are
The study’s findings suggest that there associated with changes in neuro-
are common risk factors for both sub- transmission regulated by the chemi-
stance abuse and MDD and that once cal messengers dopamine and sero-
abuse begins, it becomes an addi- tonin and the stress-related peptide
tional risk factor for MDD (see, corticotropin-releasing factor.
continued on page 4
Volume 18, Number 5 NIDA NOTES 3
The Dual Challenge of ment needs of substance-dependent
Substance Abuse and patients with concurrent mental ill-
To help patients whose
Mental Disorders ness. Overlapping symptoms of the
coexisting disorders greatly increase
continued from page 3 problems fall within our
the difficulty of diagnosing and
Research has documented similar treating either separately. However,
health missions, NIDA and
changes in the activity of these neuro- NIDA-funded research suggests that
transmitters in depression. To clarify integrating pharmacological or behav-
NIMH have joined hands to
the role such changes play in drug ioral therapies for mental disorders
abuse and mood disorders, NIDA and support research that will with drug abuse treatment may
NIMH recently awarded more than a improve outcomes for both illnesses.
dozen research grants to spur the increase fundamental Researchers have found, for instance,
development of new imaging com- that giving antidepressant medications
pounds that will enable further explo- knowledge about drug to adult patients in methadone treat-
ration of the neurochemical receptors ment reduced their craving for drugs
and brain regions associated with abuse and mental health and their drug use as well as their
substance abuse and mental disor- comorbid mood disorder (see “Treating
ders. This important research could comorbidity, advance efforts Mood Disorders in Drug Abuse
pave the way for the development of Patients Yields Improvement in Both
new medication strategies to treat to prevent this destructive Conditions,” NIDA NOTES, Vol. 13,
both conditions. No. 6). Combining an effective behav-
combination, and treat
Increased understanding of how ioral therapy for PTSD with cognitive
biological and environmental factors behavioral therapy for cocaine abuse
those already afflicted.
affect mentally ill individuals’ suscep- also has been found to produce sub-
tibility to substance abuse is central to stantial improvement in both disor-
developing new programs to prevent ders (see “Joint Treatment of PTSD
comorbidity. We know from decades NIDA program that has been explor- and Cocaine Abuse May Reduce
of drug abuse research that modifying ing the links between childhood psy- Severity of Both Disorders,” NIDA
factors known to foster initial drug chopathology and subsequent sub- NOTES, Vol. 18, No. 1).
use can prevent it from occurring and stance abuse has established the sci- That most individuals with sub-
reduce the risk of progression to entific basis for tackling this question. stance abuse disorders also struggle
more severe drug abuse. We also Last year, the program culminated in with mental illnesses is today’s reality.
know from NIDA’s extensive program a joint NIDA/NIMH request for It does not have to be tomorrow’s. To
of drug abuse vulnerability research research aimed at identifying risk fac- help these patients whose problems
that childhood conduct disorders, tors, causal mechanisms, and child- fall within our health missions, NIDA
anxiety disorders, and other psychi- hood mental health interventions that and NIMH have joined hands to sup-
atric disorders may increase the risk may prevent or inhibit later substance port research that will increase funda-
of later substance abuse. While we use. This year, the Institutes will mental knowledge about drug abuse
don’t know if early intervention with jointly fund roughly 10 new studies and mental health comorbidity,
children with such disorders can pre- under this initiative. These studies advance efforts to prevent this
vent substance abuse from occurring should enhance our understanding of destructive combination, and treat
during adolescence, several studies how biological vulnerability and envi- those already afflicted. NIDA’s broad
have found that treating children with ronmental challenges in these chil- program of scientific investigation
attention-deficit/hyperactivity disorder dren’s lives contribute to the chain of into the origins and pathways of
(ADHD) with stimulant medications events that results in coexisting men- comorbidity promises new prevention
reduces their likelihood of developing tal health and substance abuse disor- and treatment vehicles that can reduce
substance abuse disorders later in ders. In turn, this information will the incidence of both diseases among
life (see “Studies Link Stimulant provide the basis for new and more vulnerable individuals and put those
Treatment of ADHD in Childhood to effective prevention strategies. who already suffer from dual disorders
Lower Risk of Later Substance Abuse.” While striving to find ways to on the road to recovery.
NIDA NOTES, Vol. 18, No.1). prevent comorbidity, NIDA continues
For the last 5 years, an ongoing to support research to meet the treat-
4 Volume 18, Number 5 NIDA NOTES
RESEARCH FINDINGS
Early Use of Drugs May Lead to Later
Psychiatric Disorders
By Jill Schlabig Williams, NIDA NOTES Contributing Writer
OO ne of the challenges of Researchers
Early Substance Abuse Increases Likelihood of
research into comorbidity— from the City
Developing Psychiatric Disorders in Late Twenties
the co-occurrence of sub- University of
stance abuse and mental disorders—is New York ran-
determining the order in which these domly selected
disorders occur and the factors that 736 survey par- tric 80% MDD
tltohhneanyg its7uh0da0ir neina. ldR isevtucidedunyat ltfish nafrdt oifnmogl lsoe awfrroleymd c mhaioldre- t1oi9cf i7ap5na naestfs f poianrtr tt o d of Psychiae Twenties 567000 ADSleUcpoDehsnodlence
hood into their late twenties now identify the ooLat 40
cthoen ficDromrm. sJo uordbniitedh i stSye. q cBuoernonuocnked aorunf mde v.D ern. tsD ianvid hoAfel bacalhtnhily dn raeenendd isn ed Likelihorders in 2300
ss
W. Brook of New York’s Mount Sinai Saratoga, New eaDi 10
r
c
School of Medicine and Dr. Patricia York. The ratio n 0
I Tobacco Alcohol Marijuana Other Illicit
Cohen of Columbia University, also in of boys to girls Drugs
New York, provide evidence that sub- in the study Substances Abused in Childhood, Adolescence,
and/or Early Twenties
stance abuse significantly predicts the reflected that of
later occurrence of psychiatric disor- the population Longitudinal study participants who abused tobacco, alcohol, marijuana,
ders, including major depressive dis- of children in and other illicit substances in earlier years were more likely to have
order (MDD), alcohol dependence, both cities, as diagnoses of major depressive disorder (MDD), alcohol dependence, or
substance use disorders (SUDs) in their late twenties.
and substance use disorders (SUDs). did the level of
Moreover, their findings suggest that family intactness, family income, and controlled for age, sex, parents’ edu-
there are common risk factors for parents’ education level. The children cation level, family income, and
both substance abuse and MDD and were, on average, 6 years old when episodes of prior psychiatric symp-
that once abuse begins, it becomes an the study began. toms,” says Dr. Brook. “The cumula-
additional risk factor for MDD. Eight years later, Dr. Judith S. tive frequency of substance abuse
“Most studies obtain data on psy- Brook and Dr. Cohen acquired the from childhood through early adult-
chiatric disorders and drug abuse original data set and study population hood is strongly associated with
simultaneously, so it’s almost impossi- with support from NIDA and the episodes of MDD, alcohol depend-
ble to determine which came first,” National Institute of Mental Health ence, and SUDs in the late twenties.”
says Dr. Judith Brook. “This longitudi- (NIMH). Subsequent interviews were Earlier marijuana and tobacco use
nal data set is unique because it fol- completed at approximately 5-year were each more strongly related to
lows one group of people through intervals. Participants were asked participants’ development of MDD in
their lives, collecting data roughly about tobacco, alcohol, marijuana, their late twenties than more recent
every 5 years on drug abuse patterns, and other illicit drug abuse during use of these substances. However, the
psychiatric disorders, and other fac- each set of interviews, and psychiatric opposite was true for alcohol use and
tors. This approach allows us to study disorders were measured. other illicit drug use—recent use was
the progression of drug abuse, how it “Overall, alcohol and substance more strongly related to development
affects a person’s functioning, and abuse during the early years was sig- of MDD in the late twenties. The rela-
how it relates to subsequent psychi- nificantly related to later psychiatric tionship between earlier use of all
atric disorders.” disorders, even after we statistically four substances—tobacco, alcohol,
continued on page 13
Volume 18, Number 5 NIDA NOTES 5
Addictive Drugs and Stress When a drug or other stimulus estab- alcohol. There was no increase, how-
Trigger Similar Change in lishes LTP, however, subsequent ever, after exposure to the nonaddic-
Brain Cells, Animal Study exposures to it generate higher AMPA tive medications fluoxetine (an antide-
Finds currents and more copious dopamine pressant) or carbemazepine (an anti-
release. seizure medication).
continued from page 1
The increase in AMPA activity that “These observations are an
signifies LTP is confirmed experimen- intriguing followup to the results the
stress also induces LTP in VTA cells, a tally by showing an increased ratio of research group found when they
possible clue to the long-observed AMPA current to the current gener- looked at the impact of cocaine
connection between stress and ated by another cell component, alone,” says Dr. Susan Volman of
relapse. NIDA’s Division of Neuroscience and
Behavioral Research. “The study’s
Addictive Drugs and LTP finding that dissimilar addictive drugs
Dr. Robert Malenka at Stanford act in a similar way to usurp an
University in Palo Alto, California, and important neurobiological process
The finding that stress alone
colleagues at Stanford and the supports the hypothesis that LTP
University of California, San plays a role in the transition from
Francisco, first demonstrated that a can induce changes similar drug abuse to addiction and might
single exposure to cocaine can estab- contribute to relapse.”
lish LTP in the brain cells of mice to those caused by drugs
(see “Altered Cellular Activity May Be Stress and LTP
First Step in Progression to Cocaine Laboratory studies have shown
in VTA cells indicates the
Addiction,” NIDA NOTES Vol. 16, that stress can cause reinstatement of
No. 5). Subsequently, the researchers drug taking in animals, and
possibility of a priming
set out to determine whether other researchers believe that for some peo-
addictive drugs have a similar effect ple, stress may play a role in the initi-
on dopamine cells in the VTA. mechanism that could ation of drug use or relapse to use
Dr. Malenka explains, “We found that after a period of abstinence. To exam-
amphetamine, morphine, nicotine, make someone who has ine this relationship, Dr. Malenka and
and alcohol, each of which is addic- his colleagues investigated whether
tive but has its own molecular mecha- stress in the absence of drug taking
experienced stress much
nisms of action, all trigger the same can induce LTP. Mice that had not
change that we saw with cocaine. We been exposed to drugs were forced to
more vulnerable to
also found that medications that are swim for several minutes in a water
active in the brain but not addictive tank with no escape. When investiga-
do not have this effect.” addiction. tors examined the animals’ VTA cells
In their studies, the investigators 24 hours later, they found the same
demonstrated LTP by documenting an increased AMPA:NMDA ratios they
increase in the electrical activity in a had observed in mice exposed to
VTA cell component called the AMPA addictive drugs.
receptor. When stimulated, AMPA called the NMDA receptor. The association of stress with LTP
receptors generate an electrical cur- Dr. Malenka and his colleagues helps explains what seems at first to
rent that prompts the cell to release measured AMPA:NMDA ratios in be a puzzling relationship between
dopamine, with the strength of the mouse VTA cells before and after a stress and the development of addic-
current determining how much single exposure to an addictive drug tion, Dr. Volman observes. “Stress is
dopamine is released. In general, a or a psychoactive medication. The unpleasant, a negative stimulus.
repeated application of the same stim- ratios increased, indicating LTP had Addictive drugs, on the other hand,
ulus will result in the same amount of been established after exposure to have a pleasurable effect, at least ini-
AMPA current and dopamine release. amphetamine, morphine, nicotine, or tially. The finding that stress alone
6 Volume 18, Number 5 NIDA NOTES
Long-Term Potentiation in Dopamine Cells
Long-term potentiation (LTP) is one of
the brain’s key mechanisms for registering
VTA Dopamine Cell Before LTP
experience and using it to shape future
responses, as in learning and remembering.
us NMDA rio en When an experience or other stimulus induces
Stimul Receptors eseRrv imapo LtoT Pfu itnu rae ceexlpl,o tshuer ecse tlol rtehsep osanmdse mstoimreu slutrso.n Fgolyr
ate Currents ne Dd example, if you hit a fast ball for a home run,
m mi es LTP is part of the reason you might get excited
a a a
Glut AReMcPeAptors Dpo eleR the next time you are at the plate and see a
fast ball coming.
The images at left illustrate how LTP
occurs, using the example of dopamine cells
in the brain’s ventral tegmental area (VTA).
Top image: The process begins when a drug
or other stimulus raises the level of the brain
chemical glutamate. The glutamate in turn
VTA Dopamine Cell With LTP stimulates specific sites, called AMPA recep-
tors and NMDA receptors, on the dopamine
cells. The two receptors then interact to
us NMDA rio en
Stimul Receptors eseRrv imapo pdroopdaumcien ea nt oe lfleocwtri cfraolm c utrhree ncte tlhl’sa tr ecsaeursveosir
mate Currents nmei Ddes tohurtosuidgeh tthhee cceellll.’ sB motetommb riamnea gien:t o O thnec es pLaTcPe
Gluta AReMcPeAptors Dpao ealeR hthaes sbaemene setsitmabulliussh ereds, uslutsb sine qau henigth eexrp AoMsuPrAe to
current than occurred in response to the
initial exposure, resulting in greater dopamine
release.
can induce changes similar to those “Reinstatement and relapse are like represent a potentially important tar-
caused by drugs in VTA cells indicates reawakening a learned behavior. It is get for therapeutic intervention in the
the possibility of a priming mecha- possible that the effect of stress, like treatment of addictive disorders.”
nism that could make someone who that of drugs, plays a role in this
has experienced stress much more reawakening,” Dr. Volman says. Source
vulnerable to addiction,” says Dr. “The changes we see in • Saal, D.; Dong, Y.; Bonci, A.;
Volman. dopamine cells in the VTA may be a Malenka, R. Drugs of abuse and stress
LTP could also be part of a neu- key neural adaptation that contributes trigger a common synaptic adaptation
robiological mechanism that explains not only to addiction, but also to the in dopamine neurons. Neuron
the observed association between interaction of stress with drug abuse 37(4):577-582, 2003.
stress and drug reinstatement in ani- and addiction,” concludes Dr.
mals or relapse by humans. Malenka. “This adaptation may also
Volume 18, Number 5 NIDA NOTES 7
Cognitive Deficits in Marijuana Smokers
Persist After Use Stops
By Jill Schlabig Williams, NIDA NOTES Contributing Writer
NNIDA-funded scientists have neurocognitive tests, even after 28 days the concept of cognitive reserve,” says
found that cognitive impair- of abstinence. The measures on which Dr. Bolla. “People with higher IQs do
ments resulting from smoking the heavy abusers had comparative better than those with lower IQs; the
marijuana can last up to at least 28 days deficits included verbal and visual fewer cognitive reserves you have, the
after an individual last smoked the memory, executive functioning, visual more impact you will see from a slight
drug. The more a person had smoked perception, psychomotor speed, and change in brain function.”
prior to abstinence, the more profound manual dexterity. On some tests, quan- The results of this study are consis-
this impairment, with marijuana smok- tity of marijuana use accounted for tent with study findings obtained by Dr.
ers with lower IQs faring worse than more than half the variance in test Harrison Pope, Jr., at Harvard University
their higher IQ peers, even if the latter scores. “We found a dose-response rela- McLean Hospital in Belmont,
had routinely smoked more of the tionship,” says Dr. Bolla. “The more Massachusetts (see NIDA NOTES, Vol.
drug. marijuana people used, the worse they 11, No. 3). Dr. Pope and his colleagues
NIDA-funded researchers performed on the tests, especially those found that memory and learning prob-
Dr. Karen Bolla from the Johns for memory.” lems caused by heavy marijuana smok-
Hopkins University School of Medicine “We know a lot about the acute ing lasted for at least a week after use
in Baltimore and Dr. Jean Lud Cadet effects of marijuana use, but researchers stopped, although the problems disap-
from NIDA’s Intramural Research are just now beginning to look at the peared within a month. “Since mari-
Program (IRP) admitted marijuana long-term effects,” says Dr. Jag Khalsa juana has a half-life of 4 days, the neu-
smokers to IRP’s Clinical Inpatient of NIDA’s Center on AIDS and Other rocognitive effects seen in Dr. Pope’s
Research Unit on Hopkins’ Bayview Medical Consequences of Drug Abuse. study after 7 days indicate that mari-
campus, tested them to ensure they “This study demonstrates that marijuana juana does have residual effects,” says
abstained from marijuana use through- smoking has chronic, dose-related Dr. Khalsa. “Study differences in longer
out their 4-week stay, and gave them a effects on cognitive impairments up to term effects could be explained by dif-
battery of neurocognitive tests at the 28 days after last use. But how long do ferences in the study population.”
end of the study. these effects persist beyond that point? “In the Harvard study,” Dr. Bolla
Twenty-two individuals partici- That’s something we have to examine.” notes, “participants were older, ranging
pated. Their average age was 22, 86 “We have shown that marijuana use from age 30 to 55; had higher IQs;
percent were male, and all reported is associated with persistent detrimental were more affluent; and were more
consuming fewer than 14 alcoholic cognitive effects,” explains Dr. Bolla. likely to be employed. Our inpatient
drinks a week. The researchers esti- “These results are not attributable to study was conducted in the inner city
mated that the group had been smok- use of other drugs, because participants with a younger, poorer population that
ing marijuana for an average of 4.8 were excluded for current or past used marijuana more heavily. Plus, Dr.
years. Based on participants’ reports of history of significant use of other Pope measured lifetime episodes of
their current levels of marijuana use, substances, including alcohol. Marijuana smoking marijuana, not the current
the researchers grouped them as appears to be harmful when smoked number of joints smoked per week.” In
light, medium, or heavy smokers. in very large quantities.” Dr. Bolla’s study, duration of use was
“Determining an exposure index—how The study results also suggested associated with a decrease in perform-
many joints participants smoked per that some people are at higher ance on just one neurocognitive test,
week—and looking at the range of use cognitive risk from smoking marijuana which measured participants’ ability to
in the study population strengthened than others. Cognitive performance copy a complex figure.
our ability to make causal inferences,” in individuals with lower IQ scores
says Dr. Bolla. decreased as the number of joints Source
Very heavy abusers smoked an smoked per week increased, while • Bolla, K.I., et al. Dose-related neu-
average of 94 joints a week and scored those with higher IQ scores had fewer rocognitive effects of marijuana use.
worse than light abusers (average 11 decrements even as marijuana use Neurology 59(9):1337-1343, 2002.
joints per week) on 24 of the 35 increased. “This finding demonstrates
8 Volume 18, Number 5 NIDA NOTES
Severity of Cognitive Deficits Varies by Level of Marijuana Use
Verbal Memory. In tests of logical memory, partici- Logical Memory RAVLT
50 15
pants were read a paragraph and then asked questions
about it immediately and again after 30 minutes. The 40 Immediate
Delayed
Rey Auditory Verbal Learning Test (RAVLT) involved 10
listening to 15 words and then repeating them either ores30 ores
c c
immediately (Trial 1) or after 30 minutes. The response S20 S
5 Trial 1
patterns suggest difficulty with information recall, not Delayed
10
with the acquisition or retention of information, accord-
ing to the researchers. 0 Light Medium Heavy 0 Light Medium Heavy
Level of Use Level of Use
Heavy marijuana users scored below light users on all measures of
Visual Memory. In the Symbol-Digit Paired Associate
verbal memory, although they had no problems recognizing previ-
Learning test, seven flash cards featuring a symbol and ously learned material.
a number were displayed; test subjects were then shown
only the symbol and asked to supply the number that
Executive Cognitive
originally accompanied that symbol. In the Rey Complex
Functioning.In the
Figure tests, participants were shown a complex figure and Executive Cognitive
asked to draw it from memory. Wisconsin Card Sorting 40 Functioning (WCST)
Test (WCST), participants
are asked to sort cards by 30
Symbol-Digit Paired
Rey Complex Figure
25 Associate Learning 40 three different concepts s
e
that the tester changes. This or 20 Errors
20 30 exercise tests the subject’s Sc
es15 es ability to switch cognitive 10 Categories completed
or or20
Sc10 Sc sets based on feedback. 0
Poor performance indicates Light Medium Heavy
10
5 Level of Use
difficulty incorporating
0 Light Medium Heavy 0 Light Medium Heavy feedback to guide and Greater marijuana use was
Level of Use Level of Use change incorrect response associated with lesser executive
selection. cognitive functioning.
Heavy marijuana use affected visual learning and memory.
Psychomotor Speed.
Manual Dexterity.
Manual Dexterity
Participants were given the PsychomotorSpeed
c For this test, partici-
e 500
California Computerized ms pants were asked to tap 50
Assessment Package d in 400 a finger on their left 0 s40
ptal(Cei sgsbAyhtu,cLt thtCtflhooAaenmsPy h ow)w .t thooReer er mneas pcetaehtasieeoskduyen. rd setI ai ntmtwo ht e ehhaiiirst ction Time Elapse 123000000 hwn1au0anm ssd ebd.c eeMorte noardmnf sut.ianaple sdd m ebxaytde trehi teiyn # of Finger Taps/1123000
a
measured the milliseconds Re 0 Light Medium Heavy 0
Light Medium Heavy
that elapsed between the Level of Use
Level of Use
light flashing and the
Heavy marijuana users showed
participant hitting the Heavy marijuana use was associ-
slower reaction times on a test of
button. ated with lower performance on
simple reaction time.
manual dexterity measures.
Volume 18, Number 5 NIDA NOTES 9
RESEARCH NEWS
Researchers, Practitioners “Blend” Knowledge to
Enhance Drug Abuse Treatment
By Mary Beth Hatem, NIDA NOTES Contributing Writer
SS eptember’s 2-day NIDA confer- organization for
ence, “Blending Clinical Practice publicly funded
and Research: Forging treatment in
Partnerships in the Rocky Mountain Colorado.
States to Enhance Drug Abuse Twelve topi-
Treatment,” drew an overflow crowd cal workshops
of 680 drug abuse researchers, admin- facilitated
istrators, and treatment providers to research-practice
Westminster, Colorado. This was the partnerships by
third in the conference series estab- highlighting
lished by NIDA to help narrow the research findings
gap between clinical practice and and implications,
clinical research. as well as con-
“Blending is NIDA’s short name siderations for
for some of its most important work,” putting research
explained NIDA Director Nora D. into practice and
Volkow, M.D. “By blending, we mean for future
the integrated research-practice part- research. Each
nership so necessary to achieve our workshop pre-
full potential and relieve the suffering sented critical
NIDA Director Nora D. Volkow, M.D., presented the keynote address
and waste of human life caused by issues and to nearly 700 participants at the 2003 Blending Conference.
drug abuse and addiction.” opportunities
Conference co-sponsors included facing the drug abuse treatment and imperative. “Knowledge is not a lux-
NIDA and the Rocky Mountain research communities, including ury,” she commented. “Science that is
Clinical Trials Network (CTN) Node, assessment and treatment of psychi- not used is useless.” Dr. Volkow
one of 17 regional research and train- atric comorbidity, new brain research reviewed recent scientific investiga-
ing centers within NIDA’s nationwide on craving and decision making, and tions that are enhancing our under-
CTN system. CTN, now in its fifth treatment of opioid dependence with standing of drug abuse and addiction
year, was developed to test the buprenorphine/Nalaxone combination and providing new treatment options
effectiveness of new and improved tablets. Issues specific to Colorado through painstaking study of the
interventions in community-based were also on the agenda, including workings of genes, protein expres-
treatment settings with diverse popu- blending research and practice in sion, neurological circuitry, human
lations. The CTN has completed five Native American populations and behavior, and social networks.
clinical studies, and 21 other studies ruralizing urban treatment. At the “Understanding drug abuse and
are underway or in development. conclusion of the conference, clinical addiction requires a systems approach
Other key conference partners were skills training workshops were held . . . and treatment requires a multi-
the University of Colorado Health on evidence-based treatment pronged approach,” she said.
Sciences Center, home of the Rocky approaches. Although advances in science are
Mountain CTN node; the Colorado In her keynote address, Dr. leading to improved treatment
State Office of Alcoholism and Volkow drew on her dual clinical and options, Dr. Volkow observed, much
Substance Abuse Services; the research backgrounds in discussing more work is needed to ensure that
Alcoholism and Substance Abuse progress in integrating drug abuse they are used in community treatment
Providers of Colorado; the Mountain research into clinical practice. The settings. Toward that end, she said,
West Addiction Technology Transfer gap between research and practice NIDA will be increasing funding
Center; and Signal Behavioral Health, exists in every medical field, she for research on translating research
Inc., the largest managed services noted, but closing that gap is findings into clinical practice and
continued on page 14
10 Volume 18, Number 5 NIDA NOTES