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National Institute on Drug Abuse

Director's Report to the National Advisory Council on Drug Abuse
February, 1999

Research Findings

Behavioral Research

The Economics of Polydrug Abuse

Researchers at the University of Vermont are examining polydrug abuse in heroin abusers. In a simulation, where drugs were not actually given, heroin abusers were asked to purchase various drugs in a simulated market place. The researchers discovered that as the price of heroin increased, purchases decreased. Interestingly however, as the price of heroin increased, purchases of Valium and cocaine increased indicating that for heroin addicts these drugs substituted for heroin. Other results indicated that when income rose in the simulation, the demand for heroin and cocaine increased proportionally more than the rise in income. However, purchases of marijuana, alcohol and Valium did not change as income increased. Drug choices in the simulation were related to actual real-world drug use to the extent that volunteers who said they would purchase large quantities of valium, alcohol and cocaine in the simulation were found to actually use these drugs in real life. These results show that simulations are useful for understanding the relationship between the price of a drug and consumption, and polydrug abuse in the natural setting. Petry, N.M., Bickel, W.K. NBER Working Paper Series, Paper 6415, February 1998.

Does Nicotine Improve Memory?

Kenneth Perkins and his colleagues at the University of Pittsburgh studied how environmental context can mediate the effects of nicotine on working memory by introducing a distractor during the memory task. Smokers and non-smokers were administered nicotine (aerosol spray) or placebo. In comparison to non-smokers, or to conditions with no distractions, nicotine in the presence of the distracting stimuli improved smokers' short-term memory. These results suggest that environmental conditions, such as the presence of a distracting stimulus, may play an important role in mediating the effects of nicotine. Grobe, J.E. Perkins, K. et al. Experimental & Clinical Psychopharmacology 6, pp. 209-216, 1998.

Do Cigarette Cravings Reduce Language Ability?

Rolf Zwaan at Florida State University asked whether cigarette smoking urges interfere with language comprehension, perhaps by taking up working memory resources. Smokers (but not non-smokers) who heard a smoking urge script showed less accuracy during a sentence comprehension task. Also, smokers read the sentences significantly faster than nonsmokers. These results indicate again that smoking urges and cravings interfere with cognitive processing. Zwaan, R., Truitt, T. Experimental & Clinical Psychopharmacology, 6, pp. 325-330, 1998.

Do Addicts Have Altered Perceptions of Future Events?

Warren Bickel and his colleagues at the University of Vermont studied whether heroin addicts show shortened time horizons and decreased sensitivity to future consequences of their behavior compared with nondrug users. Heroin addicts enrolled in a buprenorphine treatment clinic were tested on the Stanford Time Perception Inventory (STPI) personality questionnaire, the Future Time Perspective (FTP) task, and the Bechara card task (which measures preferences for decks of cards that vary delayed and immediate rewards and punishers). Heroin addicts in comparison to controls: 1) scored lower on the STPI indicating less future orientation; 2) were less likely to predict events far into the future and less likely to systematically organize events in the future on the FTP scale; and 3) in the card task, were less likely to win money than controls because they more often played from a deck that contained greater immediate gains, but that resulted in large, delayed punishers and overall net losses. Petry, N., Bickel, W., Arnett, M. Addiction, 93, pp. 729-738, 1998.

Acute Effects of Alprazolam in Women with Premenstrual Dysphoric Disorder (PMS)

Research by Dr. Suzette Evans and colleagues at New York State Psychiatric Institute suggests that acute administration of alprazolam is not a useful treatment for PMS. Double-blind testing of mood and performance changes under varying doses of alprazolam and placebo during the luteal and follicular phases of subjects with confirmed PMS indicated substantial changes in mood as a function of the cycle phase. Alprazolam, however, failed to improve negative mood, but instead increased negative mood in the follicular phase and it impaired task performance in both phases. Subjective measures indicative of abuse liability did not increase following alprazolam administration. Alprazolam's failure to improve negative mood premenstrually, its increase in negative mood in the follicular phase, and its impairment of task performance in both phases argue against its clinical usefulness when administered acutely. Evans, S.M, Haney, M., Levin, F.R., Foltin, R.W., Fischman, M.W. Neuropsycho-pharmacology, 19, pp. 499-516, 1998.

Contingency-Management for Treating Drug Abuse in Individuals with Schizophrenia

Dr. John Roll and his colleagues at the University of Vermont examined the feasibility of using contingency-management interventions for the treatment of drug abuse in individuals with schizophrenia using cigarette smoking as an example of drug use. The first and third weeks of the three-week study served as the baseline for 11 individuals with schizophrenia. In the second week, during which patients could earn money by abstaining from cigarette smoking, abstinence was significantly greater than during the two baseline weeks. These results illustrate the potential sensitivity of drug use to reinforcement contingencies in this population, suggesting that contingency-management interventions are a feasible option for treating drug abuse of individuals with schizophrenia. Roll, J.M., Higgins, S.T., Steingard, S., McGinley Experimental and Clinical Psychopharmacology, 6, pp. 157-161, 1998.

Alcohol Enhances Oral Methadone Self-Administration

Alcoholism has been implicated in relapse to opiate dependence in methadone-maintenance patients. Few animal studies, however, have examined the effects of methadone-alcohol interactions. Dr. Richard Meisch at the University of Texas Health Science Center found that rhesus monkeys who did not readily self-administer methadone did consume significant amounts of a methadone-alcohol drug combination (in comparison to a choice of water). In this combination condition, methadone was consumed on the order of 4.8 to 6.8 mg/kg, well above the range of maintenance doses used in an opiate dependent population. Previous studies with methadone maintenance patients have found that supplemental methadone beyond the normal maintenance dose can serve as a reinforcer. Since the availability of oral ethanol has been demonstrated to enhance drug intake with other classes of abused drugs in animal self-administration studies, these results suggest that alcohol may enhance the reinforcing properties of methadone. Shelton, K.L., Macenski, M.J., Meisch, R.A. Pharm., Biochem. & Behav., 61, pp. 367-374, 1998.

Methylphenidate's Subjective Effects and Similarity to D-Amphetamine

Methylphenidate (Ritalin) is self-administered by non-human primates and may have significant abuse potential in man. Few studies have directly compared the subjective effects of methylphenidate with the potent addictive compound, d-amphetamine despite their structural and neuropharmacological similarities and the overlap in their behavioral effects. Dr. Craig Rush from the University of Mississippi Medical Center in Jackson, Mississippi has compared these two psychostimulant drugs. Research volunteers were tested for their ability to distinguish between the intero-ceptive effects of 20 mg of d-amphetamine and various doses of oral methylphenidate. The study found that subjects reported a similarity of subjective effects between the two drugs. Moreover, the two drugs produced similar dose-response functions on self-report rating of effects such as "alert/energetic", "elated" and "like drug". Rush, C.R., Kollins, S.H. Pazzaglia, P.J. Exp. Clin. Psychopharm., 6, pp. 32-44, 1998.

Effect of Clonidine on Stress- and Drug-induced Relapse to Heroin and Cocaine Seeking

This presentation demonstrated evidence that in rats both clonidine and lofexidine (alpha-2 nor-adrenergic agonists) block footshock stress-induced cocaine and inhibit heroin reinstatement. Implications are that clonidine and lofexidine may be useful in decreasing the relapse to cocaine or heroin associated with stress that may occur in the longterm outpatient post detoxification period where the incidence of relapse to abused drugs is so high. Lofexidine may offer greater clinical utility than clonidine as a medication for relapse, as recent published double-blind controlled trials of lofexidine v. clonidine in opiate withdrawal suggest significantly less hypotensive effects of lofexidine at equieffective doses for withdrawal. Erb, S., Mueller, D., Shaham, Y., Leung, S. and Stewart, J. Effect of Clonidine on Stress- and Drug-induced Relapse to Heroin and Cocaine Seeking. Soc. for Neurosci., 24, p. 498, 1998.

Generalization Between Cocaine's Effects and a Stress "Cue"

Dr. Nick Goeders at Louisiana State University Medical Center in Shreveport, LA has been studying similarities between internal states due to stress and the internal states associated with cocaine. Experimenter-induced stress has been observed to induce a relapse to drug self-administration in an animal model, but the mechanism for this effect is unknown. Rats responded to restraint stress as if they had received cocaine, suggesting that the stress produced an internal state resembling the interoceptive stimulus properties of cocaine. The investigators speculate that this stress-induced internal state may mimic the anxiogenic properties of cocaine shown in other behavioral paradigms, or may resemble the drug's positive subjective effects if the internal state reflects "freedom from restraint". Mantsch, J.R., Goeders, N.E. Psychopharmacology, 135, pp. 423-426, 1998.

Cognition and Nicotine Metabolism

Cotinine is the major and persistent metabolite resulting from cigarette smoking, and its possible effects on memory and attention during or following smoking have not been fully explored. A report by Dr. Neal Benowitz and associates has indicated that cotinine administered orally to non-smokers resulted in decreased reaction time and a decline in recall memory. It was suggested that cotinine may play a role in the withdrawal symptoms seen during smoking abstinence. Herzig, K.E., Callaway, E., Halliday, R., Naylor, H., Benowitz, N.L. Psychopharmacology, 135, pp. 127-132, 1998.

Effects of THC and Anandamide Administration

Recent research by Dr. William Martin and associates has focused on the effects of D9-THC and on physical dependence and withdrawal. In one study, the acute administration of these compounds produced behavioral effects that were substantially reversed by pretreatment with a cannabinoid antagonist (SR141716A). The behavioral effects of anandamide were distinguishable from those of D9-THC, with anandamide inducing less ataxia. Following ten days of D9-THC, a challenge with SR141716A produced evidence of physical withdrawal. In contrast to the D9-THC effects, the authors reported only limited behavioral effects from withdrawal of anandamide, its precursor arachidonic acid, or a fluorinated methylanandamide chosen for its metabolic stability. Lichtman, A.H., Wiley, J.L., LaVecchia, K.L., Neviaser, S.T., Arthur, D.B., Wilson, D.M. and Martin, B.R. Eur. J.Pharm., 357, pp. 39-48, 1998; Aceto, M.D., Scates, S.M., Razdan, R.K., and Martin, B.R. J. Pharm.& Exp. Ther., 287, pp. 598-605, 1998.

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