National Institute on Drug Abuse
Director's Report to the National Advisory Council on Drug Abuse
September, 1996
Research Findings
Clinical and Services Research
Contribution of ADHD Symptoms to Substance Problems and Delinquency
in Conduct-Disordered Adolescents
Researchers examined adolescents with conduct disorder (CD) and substance
abuse problems to determine if those with attention deficit hyperactivity
disorder (ADHD) symptomatology had more severe delinquency and substance
involvement. The study sample consisted of 171 adolescent boys, 13-17 years
of age, enrolled in a residential program for substance abusers with behavioral
problems. ADHD symptomatology was assessed by self-reports using the Diagnostic
Interview Schedule for Children (DISC) and by the use of DISC plus reports
of others (parents, program staff, and program teacher). Results showed
that boys with either self- or multi-source ADHD had more conduct disorder
symptoms, earlier age of conduct disorder onset, more substance dependence
diagnoses, and more co-morbid depression and anxiety. Thompson, L.L., Riggs,
P.D., Mikulich, S.K., and Crowley, T.J. Journal of Abnormal Child Psychology,
24(3): pp. 325-347, 1996.
An Open Trial of Pemoline in Drug-Dependent Delinquents with Attention-Deficit
Hyperactivity Disorder
Research shows that adolescents with conduct disorder and substance use
disorders have high rates of co-morbid attention deficit hyperactivity disorder
(ADHD). Further, ADHD may contribute to the severity and persistence of
substance use disorders and antisocial behaviors. A study was conducted
to examine if adolescents with ADHD and substance use disorders could be
successfully treated. The study sample consisted of 13 male adolescents
with CD, substance use disorder, and ADHD, in a residential program. Patients
were treated with pemoline, schedule IV stimulant medication but with a
known low abuse potential, at a standard daily dose of 37.5 mg, that was
increased over the subsequent 3 weeks to a total of 112.5 to 185.5 mg (=1.2-3.3
mg/kg maximal dosing). All patients took this maximal dose for at least
1 week prior to post-treatment assessment of motility, CHI (Connors Hyperactivity
Index), and CPT (Continuous Performance Score). Results showed that hyperactivity
and motility declined significantly by 13.9% and 7%, respectively, with
pemoline treatment. However, the continuous performance scores did not change.
These data indicate that pemoline may be a useful treatment for ADHD in
substance-dependent delinquents. Riggs, P.D., Thompson, L.L., Mikulich,
S.K., Whitmore, E.A., and Crowley, T.J. Journal of American Academy of Child
and Adolescent Psychiatry, 35(8): pp. 1015-1024, August 1996.
Frontal P300 Decrements, Childhood Conduct Disorder, Family History,
and the Prediction of Relapse Among Abstinent Cocaine Abusers
Antisocial personality disorder is a frequent co-morbid diagnosis in cocaine
dependent patients. A study was conducted in 49 cocaine dependent patients,
abstinent for 1-5 months, to examine the following: (1) the neurophysiological
effects of pre-morbid antisocial personality symptoms (ASPD; e.g., conduct
disorder) occurring before age 15 versus co-morbid or post-morbid ASP symptoms
occurring after age 15, (2) comparison of ASPD in patients with a family
history of alcoholism and in cocaine dependent patients, (3) to examine
the usefulness of P300 in predicting relapse, and (4) examine the time course
of P300 decrements in cocaine abusers, with or without ASPD. Patients were
assigned according to the presence/absence of a DSM-IIIR diagnosis of ASPD.
Analysis of P300 recorded during a visual selective attention task revealed
reduced amplitudes at frontal electrode sites among patients with ASPD,
relative to the ASPD negative patient and control groups. The frontal P300
decrement was significantly correlated with the number of childhood conduct
disorder symptoms, but not with the presence/absence of a family history
of alcoholism. Further, discriminant function analysis revealed that P300
amplitude alone accurately identified 71% of the patients who later relapsed,
and 53% of the patients who did not. Bauer, L.O., Drug and Alcohol Dependence,
In Press.
Safety Dose-Response Study on Lofexidine
Elmer Yu, M.D., from the Philadelphia Medications Development Research Unit,
has initiated a safety dose-response study on the alpha-2-noradrenergic
agonist, lofexidine, for the alleviation of opiate withdrawal symptoms in
opiate dependent individuals. The potential importance of this study is
that lofexidine, unlike clonidine, has not historically been associated
with decreases in blood pressure that limit the usefulness of clonidine.
Other preclinical researchers are determining if lofexidine binds to a different
set of receptor subtypes than clonidine.
Impaired Regulation of Arousal in Infants Prenatally-Exposed to Cocaine
Researchers at Yale University have provided evidence of impaired arousal
regulation in 3-month old infants prenatally-exposed to cocaine and other
drugs. Behavioral state, affective expressiveness, and attention to novel
stimuli were the measures of arousal. There were no differences in baseline
behavioral state or affective expression prior to stimulus presentation
across two groups of 3-month old infants (36 infants prenatally-exposed
to cocaine and other drugs, and 27 not exposed to cocaine prenatally). However,
the exposed infants were more likely to exhibit a crying state and to display
negative affect when novel stimuli were presented. There was no difference
in looking time between the two groups. These group results were found when
sociodemographic and perinatal factors were controlled. The investigators
discuss these findings as to possible sources of differences in arousal
regulation, and relative to predictive implications for social and cognitive
development. Mayes, L.C., et al., Development and Psychopathology, 8: pp.
29-42, 1996.
Prediction of Treatment Success in Alcohol and/or Cocaine Use Disorders
by qEEG
NIDA-funded researcher, Dr. Henry D. Abraham, from the Butler Hospital in
Providence, Rhode Island has assessed the ability of quantitative electroencephalography
(qEEG) to predict relapse following inpatient treatment for alcohol and/or
cocaine use disorders in 27 subjects. Subjects were studied in a drug-free
state following treatment and were followed for an assessment of sobriety.
At one year after discharge, 39.3% of the subjects had maintained abstinence,
and 60.7% had relapsed. Three qEEG variables derived a year earlier predicted
relapse with 88.2% sensitivity and 90.0% specificity (p < .0001). Dr.
Abraham hypothesized that these preliminary findings may lead to markers
for diverse etiologies of relapse.
Changes in Brain Metabolism in Chronic Marijuana Users
Dr. Nora D. Volkow of the Brookhaven National Laboratory and her colleagues
recently reported on the effects of chronic marijuana use on brain glucose
metabolism. Eight chronic marijuana abusers were evaluated with positron
emission tomography (PET). At baseline, the marijuana abusers had significantly
lower baseline cerebellar metabolic values than normal subjects. Metabolic
response to THC administration revealed an increase in relative cerebellar
metabolism in all subjects, but only the marijuana abusers showed metabolic
increases in prefrontal cortex, orbitofrontal cortex, and basal ganglia.
For the normals, THC either did not change or decreased metabolism in these
areas. These results suggest that the lower baseline cerebellar metabolic
activity in chronic marijuana abusers could reflect changes in cannabinoid
receptors in the cerebellum (a brain structure rich in cannabinoid receptors).
Also, the THC-induced activation of the orbitofrontal cortex and basal ganglia
in abusers could be one of the underlying neural mechanisms leading to the
drive and compulsion to self-administer the drug in addicted individuals.
Volkow et al., Brain Glucose Metabolism in Chronic Marijuana Users at Baseline
and During Marijuana Intoxication. Psychiatry Research, 67, pp. 29-38,
1996.
Sex Differences in Plasma Cocaine Levels and Subjective Effects after
Acute Cocaine Administration
Scott Lukas and colleagues at the Alcohol and Drug Abuse Research Center,
McLean Hospital and Harvard Medical School reported that male occasional
cocaine users achieved significantly faster peak plasma cocaine levels after
an intranasal dose of cocaine hydrochloride. They also reported
a greater number of intense effects. Women also differed in their menstrual
cycle where peak plasma levels of cocaine were lower in the luteal compared
to the follicular phase; subjective reports did not differ. However, heart
rates did not differ between males and females, suggesting that females
with the lower plasma cocaine had more sensitive cardiovascular sensitivity.
These data demonstrate differential effects between the sexes for use of
cocaine. Psychopharmacology, 125, pp. 346-354, 1996.
Sleep Improvement by Low Doses of Buprenorphine in Recovering, Dual
Dependent (Cocaine and Opiates) Drug Abusers
Dr. Lukas and colleagues have also been studying the disturbed sleep of
recovering dual-dependent drug abusers. Findings indicate delays in sleep
onset, multiple awakenings and reduced total sleep time with little or no
Stage 3 or Stage 4 sleep. Low dose (4 mg/day) significantly increased sleep
time, reduced latency, and increased Stage 3 sleep whereas only sleep latency
was significantly reduced with a larger dose (8 mg/day).
Cocaine-Associated Agitated Delirium
An increasing number of deaths due to cocaine are characterized by delirium
and seemingly violent behavior requiring restraint. NIDA grantee, Dr. Deborah
Mash of the University of Miami School of Medicine, together with colleagues
in the medical examiners office, are studying the underlying causes of delirium-associated
deaths which constitute about 10% of the deaths due to cocaine overdose.
They describe in a recent report that victims are most often male, succumbing
in the warmer months. Work so far has shown that these psychotic victims
have marked reduction of D2 dopamine receptors within the temperature regulatory
centers of the hypothalamus and no increases in dopamine recognition sites
on the striatal dopamine transporter. It was also pointed out that cocaine
per se may not be the sole cause since a similar syndrome was described
nearly 150 years ago. Also cocaine-induced changes of dopamine sites may
not be the sole cause; other factors such as stress of restraint may exacerbate
the situation. American Journal of Emergency Medicine, In Press.
Increase of D3 Dopamine Receptors in Human Cocaine Fatalities
Dr. Mash has also recently reported a 1 to 3 fold increase in the number
of D3 receptor binding sites over particular sectors of the striatum and
substantia nigra in cocaine overdose victims compared to age-matched and
drug-free controls. This receptor has been shown to play a pivotal role
in the reinforcing effects of cocaine in, for example, self-administering
but not naive, rhesus monkeys. Since this receptor is such an integral
part of the brain's reward circuitry in chronic cocaine abusers, it may
be a potential site for therapeutic intervention. Journal of Neuroscience,
In Press.
Treatment Effects of Acupuncture for Cocaine Abuse
Dr. Milton Bullock and colleagues at the Hennepin County Medical Center
in Minneapolis conducted two linked studies to evaluate the potential usefulness
of auricular acupuncture (Ac) in the treatment of cocaine addiction. In
Study I, residential clients were randomized to true Ac, sham Ac and conventional
treatment without Ac. Sham acupuncture consisted of needles in ear points
considered to be non-specific for the treatment of substance abuse. Subjects
in the specific and non-specific acupuncture groups were blinded to their
treatment assignment. In Study II, day treatment clients received conventional
psychosocial treatment and were randomized to one of three dose levels of
true Ac (28, 16, and 8 treatments). Sham points were not used in Study
II. Data were collected from research assistants blinded to the subjects'
treatment assignment. Multivariate analyses were performed both to determine
outcomes related to placebo and sham treatment factors and to the various
Ac conditions. Outcomes examined included cocaine use and craving, treatment
effect sizes, treatment attrition rates and health, psychological and social
status. The results of this study indicate that Ac did not provide any
significant therapeutic benefit for any of the parameters tested over the
improvement obtained by conventional psychosocial therapy.
Marijuana Use and Treatment Outcome in Cocaine-Dependent Patients
Dr. Budney and associates at the University of Vermont assessed marijuana
use in 186 persons seeking cocaine dependence treatment. Comparisons were
made between clients who did and did not report using marijuana, and between
marijuana users who did and did not meet diagnostic criteria for marijuana
dependence. A high rate of current marijuana use (59%) was observed at
intake and the majority of the marijuana users (74%) used marijuana at some
point during treatment. Marijuana use at intake was associated with increased
psychosocial impairment and substance-use severity. However, no significant
adverse relations were observed between marijuana use and any of the treatment
outcome measures. That is, regular marijuana use did not interfere with
cocaine abstinence during or following treatment. These findings challenge
the common assertion that drug-dependent patients must simultaneously cease
use of all drugs of abuse to succeed in treatment. Alternative treatment
strategies for addressing polydrug use warrant consideration. Budney, A.J.,
Higgins, S.T., and Wong, C.J. Experimental and Clinical Psychopharmacology,
In Press.
Matching Patients to Smoking Treatments
Relatively little is known about individual variation in withdrawal, or
the determinants of such variation. Dr. Baker and colleagues at the University
of Wisconsin reported findings showing that the course of smoking withdrawal
symptoms varies greatly across smokers. Results from two studies reveal
that 35-50% of smokers in cessation programs experience withdrawal that
follows an "atypical" course over the first 2 months after a quit
attempt. Dynamic cluster analysis revealed two clusters of subjects that
experienced either a late exacerbation of withdrawal, or a prolonged maintenance
of withdrawal symptoms. Women were more likely than men to belong to an
atypical cluster, and membership in such a cluster was associated with a
higher risk of relapse. This research may identify an important individual
difference that predicts relapse vulnerability and may also reveal an important
target for future treatments. Piasecki, T.M., Fiore, M.C., Baker, T.B.
Profiles in Discouragement: Two studies of Variability in the Time Course
of Smoking Withdrawal Symptoms, Submitted to Journal of Abnormal Psychology.
Economic Evaluation of Drug Abuse Treatment Programs
Dr. Michael T. French at the Community-based, Health Services Research Center
has published an important review article for the drug abuse treatment field.
This study presents a simplified economic evaluation methodology that can
be followed by program staff and researchers. The evaluation methodology
includes aspects of cost-and-outcome analysis, cost-effectiveness analysis,
and benefit-cost analysis. Methods and findings from most of the major
economic evaluation studies of drug and alcoholism treatment are discussed.
Guidelines for conducting future economic evaluations are presented along
with suggestions for how the results can be used for policy purposes and
program planning. French, M. Economic Evaluation of Drug Abuse Treatment
Programs: Methodology and Findings. Am J Drug Alcohol Abuse, 21: pp. 111-135,
1995. Relatively little is known about individual variation in withdrawal,
or the determinants of such variation. Dr. Baker and colleagues at the
University of Wisconsin reported findings showing that the course of smoking
withdrawal symptoms varies greatly across smokers. Results from two studies
reveal that 35-50% of smokers in cessation programs experience withdrawal
that follows an "atypical" course over the first 2 months after
a quit attempt. Dynamic cluster analysis revealed two clusters of subjects
that experienced either a late exacerbation of withdrawal, or a prolonged
maintenance of withdrawal symptoms. Women were more likely than men to
belong to an atypical cluster, and membership in such a cluster was associated
with a higher risk of relapse. This research may identify an important
individual difference that predicts relapse vulnerability and may also reveal
an important target for future treatments. Piasecki, T.M., Fiore, M.C.,
Baker, T.B. Profiles in Discouragement: Two studies of Variability in the
Time Course of Smoking Withdrawal Symptoms, Submitted to Journal of Abnormal
Psychology.
Economic Evaluation of Drug Abuse Treatment Programs
Dr. Michael T. French at the Community-based, Health Services Research Center
has published an important review article for the drug abuse treatment field.
This study presents a simplified economic evaluation methodology that can
be followed by program staff and researchers. The evaluation methodology
includes aspects of cost-and-outcome analysis, cost-effectiveness analysis,
and benefit-cost analysis. Methods and findings from most of the major
economic evaluation studies of drug and alcoholism treatment are discussed.
Guidelines for conducting future economic evaluations are presented along
with suggestions for how the results can be used for policy purposes and
program planning. French, M. Economic Evaluation of Drug Abuse Treatment
Programs: Methodology and Findings. Am J Drug Alcohol Abuse, 21: pp. 111-135,
1995.
Methadone Dosing Practices
An important finding from a long-term study by Thomas D'Aunno concerns methadone
dosing practices. Preliminary results, which have not yet been published,
indicate that average methadone dose levels have improved in comparison
to data from 1988 and 1990. The average dose increased from 46 mg/day in
1990 to 59 mg/day in 1995, and the upper dose limit increased from 82 mg/day
in 1990 to 94 mg/day in 1995. Consistent with earlier findings (D'Aunno
and Vaughn, 1992), treatment programs more likely to have lower dose levels
and shorter times in treatment treat higher percentages of clients who are
unemployed, African American, young, and male. Units staffed with more physicians
are likely to have higher dose levels.
For additional information about NIDA send e-mail to Information@nida.nih.gov
[NIDA Home Page][Office
of the Director][Report Index][Previous
Report Section] [Next Report Section]
|
|
