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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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