National Institute on Drug Abuse
Director's Report to the National Advisory Council on Drug Abuse
September, 1998
Research Findings
Clinical and Services Research
Matching Coping Styles and Treatment Strategies
Dr. Edward Gottheil at Thomas Jefferson University in Philadelphia is conducting a study designed to estimate the relative contributions of treatment, client and counselor factors in determining the response of polysubstance abusers to brief individual counseling. The two counseling styles being employed are 1) high-structure, behaviorally-oriented individual counseling (HSB); and 2) low-structure, facilitative style (LSF). Treatment outcomes are being compared for clients whose coping styles are matched to treatments with those whose styles are mismatched. In a sample of 60, there were no differences in treatment benefit for the LSF and HSB clients. However, clients with more severe pretreatment drug problems did better in HSB counseling, while those with less severe problems fared better in LSF treatment. These findings provide some support for the notion that treatment benefit for substance abuse patients can be improved through appropriate patient-treatment matching on the basis of addiction severity. Thornton C.C., Gottheil E., Weinstein, S.P. Kerachsky, R.S. Patient-Treatment Matching in Substance Abuse: Drug Addiction Severity. Journal of Substance Abuse Treatment, 15(2), pp. 1-7, 1998.
Modeling and Modifying Motivation for Change
Dr. William Miller at the University of New Mexico is testing the efficacy of a promising therapeutic procedure, Motivation Enhancement Therapy (MET), for enhancing motivation for change in heroin and cocaine addicts. Preliminary findings support the effectiveness of motivation interviewing as an additive adjunct to treatment for drug dependence. Data from 85 subjects show a significant difference in the rate of urine drug screens (UDS) positive for cocaine or opiates, between intake and the first follow-up at 3 months. Clients entering treatment for drug problems without having received motivational interviewing showed a 15.8% decrease in the frequency of UDS positive for these illicit drugs, which were the primary problem drugs precipitating treatment. Clients who first received a motivation interview and then proceeded into the same treatment programs showed a 42.2% decrease in UDS positives, a highly significant difference. Yahne, C.E., Miller, W.R., & Harris, R.J. Motivational Interviewing in Drug Abuse Services: Preliminary Results on a Self-Report Measure and a Laboratory Measure. Poster presented at the Eighth International Conference on Treatment of Addictive Behaviors, Santa Fe, New Mexico, January, 1998.
Stop Smoking Treatment for Drug/Alcohol Abuse Inpatients
Dr. Thomas Burling at the American Institutes for Research in California has completed a large scale, controlled, clinical trial examining the impact of smoking cessation treatments on substance dependent inpatients. Two smoking treatments specifically designed for newly recovering substance abusers were compared. One treatment used multiple, intensive, stop-smoking procedures to address the high-level of nicotine dependence found in this population. The second treatment used the same procedures, but promoted generalization of cessation and relapse prevention skills from cigarettes to drugs and alcohol. Both treatments were expected to be equally successful in terms of smoking outcomes, however the "generalization" treatment was expected to produce better drug and alcohol outcomes. Analyses examined both smoking and drug/alcohol outcomes with respect to abstinence and relapse rates. Findings suggest that subjects who receive the "smoking-focused" treatment had better smoking outcomes (not significant) and better drug and alcohol outcomes (significant) than those who received the "generalization" treatment. The results indicate that providing a focused smoking treatment concurrent with drug/alcohol treatment can be effective and better in terms of drug/alcohol outcomes than a combined smoking and drug/alcohol treatment. Burling, T.A., Seidner, A.L. (Presenter), & Ramsey, T.G. A Controlled Clincal Trial of Stop-Smoking Treatment for Drug/Alcohol Dependent Inpatients. Paper presented at the Society of Behavioral Medicine Annual Convention, April, 1997.
A Comparison of Daily and 3-Day Buprenorphine/Naloxone Dosing Schedules
Dr. Leslie Amass an MDD sponsored grantee, compared the clinical efficacy of the combination tablet of buprenorphine and naloxone administered daily with that of two different 3-day dosing schedules. Under one 3-day schedule (3-day clinic), clients ingested 16, 16, and 24 mg of the combination tablet at the clinic each Monday, Wednesday and Friday, respectively. On the other 3-day schedule (3-day take-home), clients received an 8 mg tablet every Monday, Wednesday and Friday and 8 mg tablets to take at home on days between clinic visits. The data showed that there were no significant differences across conditions in rates of illicit drug use. Subjects "liked" both 3-day schedules significantly more than the daily schedule (p=.002), and ratings of "good" were significantly higher for the 3-day take-home as opposed to 3-day clinic condition (p=.04). The data suggest that reducing clinic attendance improves medication compliance and increases client satisfaction without impacting illicit drug use.
Predictive Validity of Cocaine, Sedative, and Alcohol Dependence Diagnoses
Dr. Kidorf and colleagues at the Johns Hopkins University School of Medicine examined the predictive validity of the Structured Clinical Interview for DSM-III-Revised-based substance dependence diagnoses (e.g, cocaine; sedative; alcohol) for 518 opioid-dependent outpatients entering a methadone maintenance program that included daily methadone substitution, individual and group counseling, and random urine screens 1-4 times per month. Patients were followed for over one year of treatment. Unlike a co-occurring diagnosis of sedative and/or alcohol dependence, results of the study indicate that a comorbid diagnosis of cocaine dependence at intake predicted an early dropout from the program. Kidorf, M., Brooner, R.K., King, V.L., Stoller, K.B., and Wertz, J. Journal of Consulting and Clinical Psychology, 66(1), pp. 168-173, 1998.
Prenatal Cocaine Exposure and Stimulus-Seeking Behaviors in Infants
Robert L. Freedland, Ph.D. and colleagues at the New York State Institute for Basic Research, Staten Island, NY, have investigated orientation sensitivity to complex perceptual patterns in groups of normal, brain-injured and cocaine-exposed infants. Previous studies with newborns revealed that normal neonates were able to modulate attention to stimulation depending on their arousal pattern, but brain-injured and cocaine-exposed neonates demonstrated poorer attention modulation. Brain-injured newborns preferred less stimulation even when more aroused (stimulus avoiding) and cocaine-exposed newborns preferred more stimulation even when more aroused (stimulus seeking). Current studies evaluated these differences in older infants (at four and seven months of age), using age-appropriate, complex visual perceptual tasks. These cocaine-exposed infants appear to be most sensitive to oblique orientations presented in a complex, herringbone visual pattern. The inference is that these older cocaine-exposed infants were responding to complex stimuli differently than non-cocaine-exposed, age-matched infants. Novelty responses of cocaine-exposed infants seem to be driven by the orientation of the stimulation-rich elements within the complex visual pattern, which may demonstrate a further instance of arousal-based "stimulation-seeking" behavior. Stimulus-seeking behavior in these older cocaine-exposed infants appeared to continue in development with the more advanced perceptual tasks. These findings are helpful in establishing a basis for the effects of cocaine exposure on infants and for determining if the effects persist. Further, the results suggest differential effects on the development of early sensory organization in cocaine-exposed infants after the first six months of life. The differences in responses to more advanced stimuli with respect to perceptual organization suggest an enduring drug-mediated effect in the sensory encoding of visual information in cocaine pre-exposed infants. Freedland, R.L., Karmel, B.Z., Gardner, J. M., & Lewkowicz, D.J. Prenatal Cocaine Exposure and Stimulus-seeking Behaviors during the First Year of Life. Annals of the New York Academy of Sciences, 846, pp. 386-390, 1998.
Activation of Specific Brain Areas with Cue-induced Craving in Cocaine Addicts
Dr. Scott Lukas and colleagues at McLean Hospital in Belmont, Massachusetts demonstrated cerebral activation in the anterior cingulate and left dorsolateral prefrontal cortex after audiovisual stimuli in cocaine-using patients. The activation was specific to cues related to cocaine and not to neutral cues. The method used was blood-oxygenation-level-dependent (BOLD) functional activation. The results of this study demonstrate that this form of functional MRI can be useful to study the neurobiological basis of cue-induced craving. Maas, L.C., Lukas, S.E., Kaufman, M.J., Weiss, R.D., Daniels, D.L., Rogers, V.W., Kukes, T.J., and Renshaw, P.F. Functional Magnetic Resonance Imaging of Human Brain Activation During Cue-induced Cocaine Craving. Am. J. Psychiatry, 155(1), pp. 124-126, 1998.
Sex Differences in fMRI with Primary Visual Stimulation
Dr. Jonathan M. Levin and colleagues at the Brain Imaging Center at McLean Hospital in Belmont, Massachusetts conducted a study to determine the effect of sex on a non-cognitive, primary sensory activation task using the well-characterized, blood-oxygenation-level-dependent (BOLD) functional MRI response. BOLD signal response was measured in the primary visual cortex in response to binocular photic stimulation. It was found that women had a significantly lower (about 38%) mean BOLD signal response than men, and the influence of hemisphere revealed that women were more symmetrical than men in their response. This finding might reflect sex-based differences in the anatomy of the visual cortex, differences in visual processing, differences in regional oxygen utilization with activation, differences in vascular response to activation, or differences in baseline physiological measures related to BOLD contrast (e.g., hemoglobin level). In addition to functional implications, these results demonstrate the importance that the effect of sex might have when considering both the design and interpretation of functional MRI studies. Levin, J.M., Ross, M. H., Mendolson, J.H., Mello, N.K., Cohen, B.M., and Renshaw, P.F. Sex Differences in Blood-oxygenation-level-dependent Functional MRI with Primary Visual Stimulation. Am. J. Psychiatry, 155(3), pp. 434-436, 1998.
Neurochemical Alterations in Asymptomatic Abstinent Cocaine Users
Using proton magnetic resonance spectroscopy, Dr. Linda Chang and colleagues at the Harbor-UCLA Medical Center in Torrance, California investigated the effects of cocaine on brain neurochemistry in abstinent cocaine users using proton magnetic resonance spectroscopy. They found that the brain metabolites, creatinine and myo-inositol, were both elevated in the (temporoparietal) white matter, with a strong trend toward elevated creatinine in the gray matter. Further, there was a significant and positive correlation between creatinine, as well as myo-inositol, and the frequency and duration of cocaine use in the white matter, with a similar trend in the gray matter. Glutamine and glutamate levels were moderately elevated in the gray matter of cocaine users, with a significant correlation between level and duration of cocaine use. This finding suggests a perturbation of the glutaminergic system. N-acetyl-containing compounds (of which n-acetyl-aspartate, a marker of neuronal damage or loss, mostly comprises) were not different between cocaine abusers and controls in the areas assessed, thus revealing no differences in neuronal damage or cell loss. Overall, these findings demonstrate neurochemical abnormalities in the nonneuronal cells of subcortical brain regions in asymptomatic cocaine users, and these abnormalities exist in the absence of any visible structural changes as assessed by MRI. Chang, L., Mehringer, C.M., Ernst, T., Melchor, R., Myers, H., Forney, D., and Satz, P. Neurochemical Alterations in Asymptomatic Abstinent Cocaine Users: A Proton Magnetic Resonance Spectroscopy Study. Biol. Psychiatry, 42, pp. 1105-1114, 1997.
Differential Cognitive Functioning in 9-12 Years Olds Relative to Prenatal Cigarette and Marijuana Exposure
In an examination of cognitive performance of 131 9-12 year-old children participating in a Carleton University longitudinal study since birth, discriminant function analysis indicated a dose-dependent association between higher prenatal cigarette exposure in utero and lower performance on global intelligence test scores, with the verbal subtests of the intelligence test discriminating maximally among levels of in utero exposure. In contrast, prenatal marijuana exposure was not associated with global intelligence or the verbal subtests, but rather was negatively related to executive function tasks that require impulse control and visual analysis/hypothesis testing, and with a number of the intelligence subtests requiring these same abilities. The cigarette results extend observations made in this sample and others at earlier ages. The marijuana findings, combined with results observed at earlier ages, lead the authors to suggest that in utero exposure to marijuana may have a negative impact on aspects of neurocognitive competence that fall under the domain of executive function. Fried, P.A., Watkinson, B.M. and Gray, R. Neurotoxicology and Teratology, 20 (3), pp. 293-306, 1998.
Mechanisms of Cardiovascular Effects of Cocaine in Humans
Cocaine use is associated with catastrophic cardiovascular events, ranging from cardiomyopathies, myocardial infarction to sudden death. Victor and his colleagues at the University of Texas Southwestern Medical Center conducted studies to understand the underlying mechanisms of cardiovascular effects of cocaine in humans. In their earlier studies, they found that intranasal cocaine (2 mg/kg-systemic route) increased myocardial oxygen demand and decreased oxygen supply. Later they (Jacobsen et al. 1997) showed that intranasal cocaine increased the sympathetic nerve discharge (recorded via intraneural microelectrodes in the peroneal nerve) to the skeletal muscle vascular bed. The authors hypothesized that the sinoaortic baroreflexes may be playing a pivotal role in modulating the cocaine-induced sympathetic excitation, and that the interplay between these excitatory and inhibitory neural influences determines the net effect of cocaine on sympathetic discharge targeted to the human skeletal muscle circulation. On the other hand, intracoronary infusion of cocaine at high concentrations (1 mg/min over a 15 min period, total dose of 15 mg cocaine) caused a deterioration of LV systolic and diastolic performance in humans (Pitts et al. 1998) without producing any epicardial coronary arterial vasoconstriction or alterations in the blood flow suggesting myocardial effects of cocaine (Daniel et al. 1996). Effects of Intracoronary Infusion of Cocaine on Coronary Arterial Dimensions and Blood Flow in Humans, Daniel, W.C., Lange, R., Landau, C.,Willard, J. and Hills, D. Am J Cardiol., 78, pp. 288-291, 1996; Effects of Intranasal Cocaine on Sympathetic Nerve Discharge in Humans, Jacobsen, T.N., Grayburn, P.A., Snyder, R.W., II, Hansen, J., Chavoshan, B., Landau, C., Lange, R.A., Hills, D., and Victor, R., J. Clin Invest., 99, pp. 628-634, 1997; Effects of Intracoronary Infusion of Cocaine on Left Ventricular Systolic and Diastolic Function in Humans, Pitts, W., Vongpatanasin, W., Cigarroa, J.E., Hills, D., and Lange, R. Circulation, 97, pp. 1270-1273, 1998.
A Comparison of Daily and 3-Day Buprenorphine/Naloxone Dosing Schedules
Dr. Leslie Amass an MDD sponsored grantee, compared the clinical efficacy of the combination tablet of buprenorphine and naloxone administered daily with that of two different 3-day dosing schedules. Under one 3-day schedule (3-day clinic), clients ingested 16, 16, and 24 mg of the combination tablet at the clinic each Monday, Wednesday and Friday, respectively. On the other 3-day schedule (3-day take-home), clients received an 8 mg tablet every Monday, Wednesday and Friday and 8 mg tablets to take at home on days between clinic visits. The data showed that there were no significant differences across conditions in rates of illicit drug use. Subjects "liked" both 3-day schedules significantly more than the daily schedule (p=.002), and ratings of "good" were significantly higher for the 3-day take-home as opposed to 3-day clinic condition (p=.04). The data suggest that reducing clinic attendance improves medication compliance and increases client satisfaction without impacting illicit drug use.
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