National Institute on Drug Abuse
Director's Report to the National Advisory Council on Drug Abuse
February 1997
Research Findings
Behavioral Research
Decreasing Preferences for Cocaine Dr. Marilyn Carroll and her colleagues
at the University of Minnesota Medical School, Minneapolis MN evaluated
the effects of the opioid partial agonist buprenorphine (0.1 mg/kg) and
concurrent access to either water or a glucose plus saccharin (G+S) solution
in rats self-administering i.v. cocaine (0.4 mg/kg per infusion). Data
obtained indicate that (1) the presence of an alternative non-drug reinforcer
significantly reduced cocaine self-administration, (2) buprenorphine selectively
decreased cocaine, but not water or G+S, self-administration; (3) the decrease
in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine
administration; and (4) expressed as a percentage of baseline conditions,
the combination of buprenorphine and G+S produced a greater decrease in
cocaine self-administration than either buprenorphine or G+S alone. These
results suggest that combined treatment with buprenorphine and concurrent
access to a sweetened solution is a more effective strategy for reducing
cocaine self-administration than either strategy alone. Comer S.D. et al.,
Psychopharmacology, 125, pp. 355-360, 1996.
Increasing Preferences for Cocaine and Lidocaine Dr. John Falk at
Rutgers University has found, in a preference test with rats, that oral
cocaine during a schedule-induced polydipsia procedure was not preferred
over water. However, after pairing a glucose + saccharin (g+s) solution
with cocaine and then fading out the g+s solution, the cocaine did become
preferred over water. Interestingly, this g+s pairing procedure also produced
a preference for lidocaine, which is not an abused drug. (Drug and Alcohol
Dependence, 40, pp. 241-247, 1996). In a follow-up study Dr. Falk found
that these drug preferences that developed after pairing with sweet tastes
were maintained even when drug concentrations were raised to bitter tasting
levels. (Behavioural Pharmacology, In Press). Previous studies in the literature
indicating that oral drug preference established under similar pairing-and-fading
methods now warrant re-examination given that the present research suggests
that drug preference established via these methods may indeed not reflect
pharmacologically reinforcing properties of the substance. These data additionally
suggest that humans may continue to use a drug more because of its prior
pairing with other reinforcing events (e.g., social reinforcers) than because
of its pharmacologic properties.
Smoking and Menstrual Cycle Researchers at the University of Michigan
have found in healthy women smokers that the effects of nicotine administered
intranasally did not vary across menstrual cycle phase. This held true for
both physiological and behavioral (subjective report) dependent measures.
Marks et al., J Substance Abuse, In Press.
ADHD, Smoking and Novelty Seeking It is known that adults with Attention
Deficit Hyperactivity Disorder (ADHD) smoke at nearly twice the rate as
the general population. Based on these findings, researchers at the University
of Michigan asked whether ADHD patients score higher on a standardized test
of novelty-seeking (Cloninger's TPQ). They compared subgroups defined by
smoking status, and also compared groups that lacked the ADHD diagnosis.
Findings showed that among subjects who were smokers, ADHD patients began
smoking at a much earlier age and scored higher on the novelty scale than
non-ADHD. The data showing early age of smoking onset suggest prevention
targeting for youth diagnosed with ADHD. Downey et al., J Substance Abuse,
8, pp. 129-135, 1996.
Job Skills Training Program using a Voucher-Based Reinforcement System
Researchers at the Johns Hopkins School of Medicine recently evaluated the
use of vouchers as incentives to unemployed methadone patients to stay in
a job skills training program. Volunteers were given vouchers with monetary
value which could be exchanged for goods and services for attending two-hour
computer entry training classes. The classes were conducted over a 16 week
period. As part of the study design, the value of the vouchers were escalated
across weeks and then de-escalated, with additional titration of the value
of the vouchers according to class attendance. Five of seven participants
completed all phases of the study. In the escalating value condition, attendance
rates were above 90%. Four of five volunteers stopped attending class in
the descending pay condition when voucher values fell to $6-$9 per class.
Volunteers later positively rated the classes they attended. These data
indicate that a voucher-based system can sustain attendance of chronically
unemployed substance abusers in prolonged job skills training programs.
Silverman et al., Drug and Alcohol Dependence, 41, pp. 197-207, 1996.
Assessment of Buprenorphine's Physical Dependence Potential Researchers
at the Johns Hopkins School of Medicine recently examined the physical dependence
produced by maintaining opioid-dependent volunteers on a clinically relevant
dose of buprenorphine. Eight volunteers were maintained on 8 mg/day sublingual
buprenorphine, during which they received placebo, i.m. naloxone, and p.o.
naltrexone 14 hours after their daily buprenorphine dose. Both naloxone
and naltrexone precipitated withdrawal as indicated by changes in physiological,
and subject- and observer-rated measures. These results indicate that buprenorphine
maintenance produces physical dependence. These results will be important
in guiding the formulation of combination agonist/antagonist medications
for transitioning opioid abusers from buprenorphine to antagonist maintenance.
Eissenberg et al., Journal of Pharmacology and Experimental Therapeutics,
276, pp. 449-459, 1996.
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