National Institute on Drug Abuse
Director's Report to the National Advisory Council on Drug
Abuse
May, 1997
Research Findings
Behavioral Research
Individual Differences in Drug Discrimination
To test the effects on operant food responding via discrimination and
generalization of internal amphetamine cues on high versus low behavioral
responders, several different operant pre-test screening methodologies for
behavioral response to novelty/stress were used. Based on measures of activity,
rats were grouped into high versus low responders. Both groups were then
trained to discriminate amphetamine versus saline in a two lever procedure
using food maintained responding. Following this training, amphetamine generalization
tests were conducted across a range of doses. In the first of these two
tests, the high responders to novelty were found to be more sensitive than
the low responders to the bar-press suppressant effects of amphetamine.
In the second generalization test, high responders were also more sensitive
to the discriminative effects of amphetamine (i.e., lower median effective
dose). These results are discussed in terms of identifying the processes
common to the screens (e.g. stress and novelty). Bevins, R.A., Klebaur,
J.E., and Bardo, M.T. Individual Differences in Response to Novelty, Amphetamine-Induced
Activity and Drug Discrimination in Rats. Behavioral Pharmacology, In press.
Drug Combinations: Caffeine + Triazolam is not Caffeine + Buspiron
The drug discrimination paradigm has become a standard method by which
many behaviorally active compounds are classified in animal research. Researchers
from the University of Vermont adapted this procedure to humans to ask:
Can the stimulus properties of caffeine, a methylxanthine CNS stimulant,
be altered by the two chemically distinct anxiolytic compounds triazolam
and buspiron? They found that triazolam given in combination with caffeine
blocked the subject's ability to discriminate caffeine. By contrast, buspiron
given in combination with caffeine had no effect on volunteers' ability
to discriminate caffeine from placebo. These results demonstrate the utility
of drug discrimination paradigms for studying the effects of drug combinations
in humans. Furthermore, these results suggest triazolam and caffeine share
a common neurosubstrate for detection of their stimulus properties that
are distinct from the neurosubstrate associated with buspiron detection.
Oliveto, A.H., et al. Behavioural Pharmacology, In press.
Neonatal Withdrawal Syndrome in Infants Exposed to Cocaine and Methadone
The effect of concomitant cocaine and methadone use on neonatal withdrawal
was examined in 68 infants born to methadone-maintained mothers. Fifty-three
(78%) of these mothers reported regular cocaine use during pregnancy and/or
had positive urine screens. Methadone dose in the last weeks of pregnancy
was positively correlated with withdrawal severity. Infants exposed to both
cocaine and methadone had higher first withdrawal scores; however, cocaine-exposed
infants did not require more medication for withdrawal management, nor were
they more likely to show retarded growth in the uterus, prematurity, or
early perinatal complications. These data do not support a common view among
women in methadone maintenance that cocaine will either minimize their infant's
methadone withdrawal or will decrease the length of hospitalization after
birth. Such incorrect beliefs may be contributing to the high frequency
of cocaine use in the present sample of women. Mayes, C., & Carroll,
K.M. Substance Use and Misuse, 3, pp. 241-253, 1996.
False Feedback about Work Performance Reduces Methamphetamine Intake
Researchers at Columbia University tested whether research volunteers
who are told that d amphetamine impairs research task performance and reduces
monetary earnings would actually decrease their d-amphetamine self-administration
in the laboratory. With no performance feedback, volunteers chose d-amphetamine
over placebo 78% of the time, and increased amphetamine choices when they
were given feedback that their performance had improved. By contrast, d-amphetamine
self-administration decreased significantly to 25% when subjects were told
that it impaired their performance on work tasks and resulted in reduced
earnings. In reality, d-amphetamine had little effect on work task performance.
With regard to subjective effects, d amphetamine significantly increased
ratings of "Stimulated" and "Good Drug Effect" and significantly
decreased ratings of "Tired" and "Sleepy." These results
demonstrate that d amphetamine served as a reinforcer under conditions in
which drug self-administration did not influence monetary earnings, but
that d-amphetamine self-administration could be modified by feedback/monetary
earnings. Thus, contingencies associated with performance have important
implications for drug use in the workplace. Comer, S.D., Haney, M., Foltin,
R.W., Fischman, M.W., Psychopharmacology, 127, pp. 39-46, 1996.
The Noradrenergic System May Not be Involved in Morphine Discriminative
Effects
Since studies suggest that the noradrenergic system is involved in the
analgesic effects of opioids and in physical signs of opioid withdrawal,
is the noradrenergic system involved in the discriminative effects of morphine?
First, a range of doses of morphine (0.3-10.0 mg/kg) produced dose-dependent
increases in morphine-appropriate responding in rats without substantial
decreases in response rate. In several experiments, neither the alpha 2
agonist clonidine (0.003 0.1 mg/kg), the alpha 1 antagonist prazosin (0.1-10.0
mg/kg), the alpha 2 antagonist yohimbine (0.1-10.0 mg/kg), the beta 2 agonist
salbutamol (0.03-10.0 mg/kg), nor the beta antagonist propranolol (1.0-10.0
mg/kg) substituted for morphine nor altered the discriminative-stimulus
effects of morphine when administered in combination. These data suggest
that the noradrenergic system is not involved in the discriminative-stimulus
effects of 5.6 mg/kg morphine in rats. Hughes, C.E., Habash, T., Dykstra,
L.A., Picker, M.J. Pharmacol. Biochem. Behav. 53, pp.979-986, 1996.
Gender and Vulnerability Factors in Cigarette Abstinence
Dr. David Gilbert from Southern Illinois University is investigating
the role of individual differences in physiological and psychological responses
to smoking abstinence among females as they relate to individual differences
in personality and nicotine dependence and comparing responses of this female
sample to a recently collected all-male sample. Large individual differences
in response to quitting have been found to correlate with personality, psychopathology,
and nicotine dependence. Preliminary data indicate that neuroticism and
depressive trait measures predict degree of smoking cessation induced negative
affect and depressive state. These findings are consistent with the PI's
hypothesis that individuals scoring high in trait depression and neuroticism
smoke to self-medicate their temperamental disposition toward negative affect.
The data, when complete, will lead to new knowledge that will have implications
for how to individualize smoking cessation programs to maximize successful
long-term abstinence.
Behavioral Methods for Cigarette Smoking Cessation
Dr. Maxine Stitzer at Johns Hopkins University conducted a study to understand
the role of nicotine in the maintenance of cigarette smoking. Volunteers
compared their own brand (mean nicotine yield = 1.07 mg; mean tar = 15.8
mg), a "light" cigarette (nicotine yield = 0.7 mg; tar = 10 mg),
or a denicotinized cigarette (nicotine <0.1; tar = 10.8 mg) in random
order on three separate days. Subjective ratings for the denicotinized and
light cigarettes were comparable. They were rated as similar in strength
and satisfaction (both were rated as lower than their own brand). Desire
to smoke scores declined after smoking and rose gradually over the next
90 mins with similar profiles across the three cigarette types. The results
suggest that acute subjective effects of smoking in experienced smokers
may be determined more by tar and/or sensory characteristics than by nicotine
levels. Pharmacology, Biochemistry and Behavior, In press.
Gender Differences in Psychiatric and Substance Use Comorbidity among
Treatment-Seeking Opioid Abusers
Psychiatric and substance use comorbidity was assessed in 716 opioid
abusers (47.2% women) seeking methadone maintenance during a 5-year period.
Rates of co-occurring mental disorders and personality traits were compared
by gender. Although rates of comorbidity were similar in women and men (47%
vs 48%), women were less likely than men to have a DSM-III-R personality
disorder (28.4% vs 40.5%) or an antisocial personality (15.4% vs 33.9%)
but more likely to have a mood disorder (27.5 % vs 11.4%) and 7 times more
likely to have a borderline personality (9.5% vs 1.3%). Although all patients
had at least one substance use diagnosis beyond opioid dependence, most
often cocaine dependence, women were less likely than men to have a life-time
cannabis, alcohol, or hallucinogen disorder or a current cannabis (12.1%
vs 19.8%) or alcohol dependence (19.5% vs 29.4%). Brooner, R.K., King, V.L.,
Kidorf, M., Schmidt, C.W., and Bigelow, G.E. Psychiatric and Substance Use
Comorbidity Among Treatment-Seeking Opioid Abusers. Arch. Gen. Psychiatry,
54(1), pp. 71 80, 1997.
Contingent Reinforcement of Group Participation Versus Abstinence
in a Methadone Maintenance Program
This study evaluated the relative efficacy of two strategies for reducing
illicit substance use in a methadone maintenance setting: urinalysis-contingent
reinforcement versus participation in Training in Interpersonal Problem
Solving groups (TIPS), an 8 week manualized psychoeducational group designed
to promote problem-solving skills. Three months after admission, 66 methadone
patients were randomly assigned to either the Urinalysis contingent condition
in which take-home medication doses were received based on drug free urines
or to the psychoeducational group in which take-home medication doses were
received based on group attendance. During the 24 week intervention period,
the urinalysis-contingent group showed greater improvement in rates of abstinence
from illicit drugs and better met criteria for clinical improvement than
the psychoeducational group. It appears that reinforcement of the psychoeducational
group attendance is not as effective for reducing illicit drug use among
methadone maintenance patients as is urinalysis-contingent reinforcement.
These findings support the efficacy of contingency interventions targeted
specifically at the drug using behavior. Iguchi, M. et al., Journal of Experimental
and Clinical Psychopharmacology, 4(3), pp. 315-321, 1996.
Reinforcing Operants Other Than Abstinence in Drug Abuse Treatment:
An Effective Alternative for Reducing Drug Use
This study evaluated the efficacy of Treatment Plan Based Reinforcement
(a task-oriented behavioral intervention) compared with a standard treatment
control and a more traditional contingency management intervention in reinforcing
the provision of drug-free urines. Following a six-week stabilization phase,
103 subjects in methadone maintenance treatment were randomly assigned to
either the standard treatment control, the urinalysis-based reinforcement
or the treatment plan reinforcement. The intervention period lasted 12 weeks.
Participants in the Treatment Plan group earned vouchers for completing
objectively defined and clearly verifiable treatment plan tasks and were
not reinforced for the provision of drug-free urines. The vouchers had an
exchange value of 50 cents and could only be redeemed for expenses related
to treatment plan goals (maximum value, $15 per week). The Treatment Plan
group earned more vouchers than the Urinalysis-Contingent group and the
number of vouchers earned bore a direct relationship to the number of drug
free urines submitted. Only the Treatment plan group demonstrated improvement
in abstinence rates that were maintained after the intervention was discontinued.
The results from this study suggest that reinforcement of clearly defined
behavioral tasks targeted to treatment plan goals increases involvement
in behaviors inconsistent with drug use among methadone maintenance patients.
Iguchi, M. et al. Journal of Consulting and Clinical Psychology, In press.
The NIDA Collaborative Cocaine Treatment Study
Investigators recently reported on the prevalence and pretreatment psychiatric,
drug use, and demographic correlates of DSM-III-R personality disorders
in a sample of 289 cocaine dependent outpatients accepted into the pilot
phase of a randomized, multisite, clinical trial comparing different psychotherapy
and drug counseling treatments. Results showed that 48% of the patients
had at least one personality disorder and 18% had two or more. Of those
with a personality disorder, 65% had a cluster B disorder with antisocial
and borderline personality disorders being the most common. Men were significantly
more likely to be diagnosed with antisocial personality disorder than women.
Patients with personality disorders were significantly more likely to receive
an another Axis 1 diagnosis and to have more severe psychiatric symptoms.
However, the groups did not differ on other measures of drug use severity
or demographic variables. While the prognostic significance of these findings
is yet to be determined, the results suggest that personality disorders
are apt to play an important role in the treatment of cocaine dependence.
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]
|