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Director's Report to the National Advisory Council on Drug Abuse
May, 2001

Research Findings

Treatment Research and Development

Differences between Methamphetamine and Cocaine Users

At the Matrix Institute on Addictions, in Los Angeles, CA, two large cohorts of cocaine and methamphetamine (MA) users sought outpatient treatment during the same four-year period. The 224 cocaine users spent more money on their drugs, more frequently had severe financial problems or bankruptcy (37.9%), and more frequently used alcohol with their drug of choice (46.9%). The 500 methamphetamine users included a higher proportion of women (40%) and Whites (80.5%), more frequently used their drug on a daily basis (43.6%), more frequently had used marijuana (56.2%) and hallucinogens (6.4%) in the past year, and more frequently had current psychiatric symptoms at admission. However, the two groups did not differ significantly in treatment retention. Retention in treatment for >90 days was most significantly correlated with reported years of heavy drug use. No significant correlation with retention was found for use of methamphetamine, gender, marital status, age, years of education, or prior drug treatment. Rawson, R., Huber, A., Brethen, P., Obert, J., Gulati, V., Shoptaw, S., and Ling, W. Methamphetamine and Cocaine Users: Differences in Characteristics and Treatment Retention. Journal of Psychoactive Drugs, 32(2), pp. 233-238, 2000.

Baseline Urine Test Predicts Cocaine Use during Treatment

At the Philadelphia Veterans Affairs Medical Center, 61 male participants completed a protocol for a 4 week, outpatient treatment for cocaine dependence, using ritanserin or placebo. Altogether, these completers provided an average of more than 11 of their 12 scheduled urine samples. During a 1-3 week baseline placebo period, all participants provided one urine sample, which tested negative or positive for >300 ng/ml benzoylecgonine. Baseline urine was cocaine-positive in 24 men, and cocaine-negative in 37 men. The baseline-positive group had an average of twice as many positive urine samples during treatment as the baseline-negative group. The baseline-positive group also had less than half as many men who were completely abstinent during the 4-week trial, and the group took longer to achieve 3 consecutive cocaine-free urines. These differences in outcome suggest that future evaluations of treatment efficacy should stratify group assignment by results of a baseline urine test. Ehrman, R.N., Robbins, S.J., and Cornish, J.W. Results of a Baseline Urine Test Predict Levels of Cocaine Use during Treatment. Drug and Alcohol Dependence, 62(1), pp. 1-7, 2001.

Propranonol Reduces Symptoms of Cocaine Withdrawal

Dr. Kyle Kampman and colleagues from the University of Pennsylvania have published a paper demonstrating the effectiveness of propranolol in reducing symptoms of cocaine withdrawal and its effectiveness in improving treatment retention and reducing cocaine use in patients with high withdrawal scores. Currently the investigators are evaluating the combination of propranolol and amantadine in the treatment of cocaine dependence. Drug and Alcohol Dependence, 63, pp. 69-78, 2001.

Effects of In-Utero Cocaine Exposure on Brain of Children

Dr. Smith and colleagues at Harbor-UCLA Medical Center investigated the effects of prenatal cocaine exposure on brain metabolism using proton magnetic resonance spectroscopy (1H-MRS). The aim of this work was to examine the possible neurotoxic effects of prenatal cocaine exposure on the developing brain. Cocaine-exposed children and age-matched control subjects were evaluated with structural MRI and localized 1H-MRS. Preliminary findings revealed no structural abnormalities in either group, but children exposed to cocaine in utero had significantly higher (+13%) levels of creatine (Cr, a measure of high-energy phosphate stores) in the frontal white matter, suggesting biochemical alterations may occur in response to early exposure to cocaine. No differences were seen in n-acetyl-containing compounds (NA) that suggest no significant neuronal loss or damage in the basal ganglia or frontal white matter (the two areas assessed in all children). These findings are consistent with findings in abstinent adult cocaine abusers, and these results suggest the clear need to investigate further possible abnormalities of energy metabolism in the brain of children exposed to cocaine prenatally. Smith, L.M. et al. Brain Proton Magnetic Resonance Spectroscopy and Imaging in Children Exposed to Cocaine In-Utero. Pediatrics, 107(2), 2001.

Decision-Making Deficits in Alcohol and Stimulant Abusers Linked to Dysfunctional Ventromedial Prefrontal Cortex

Dr. Bechara and colleagues at the University of Iowa compared the performance of substance abusers, normal controls and patients with ventromedial prefrontal lesions on a decision-making task. This task (Gambling Task) was originally designed to assess cognitive deficits in patients with ventromedial prefrontal lesions. In the task, subjects are presented with 4 decks of cards and told to choose the cards that will yield the best monetary outcome. All of the decks provide immediate reward, but also occasional penalties. Two of the decks yield higher immediate rewards than the other two decks. However, the high-reward decks are disadvantageous in the long run since the penalties eventually outweigh the gains yielding net loss. Unlike neurologically intact subjects who tend to pick more cards from the advantageous, low immediate reward decks, subjects with ventromedial prefrontal lesions tend to persist in choosing the disadvantageous high immediate reward. Substance abusers also tended to pick more cards from the disadvantageous decks, and nearly two thirds of the substance abusers performed as poorly as the ventromedial lesioned patients. Performance of the substance abusers was not related to age, IQ, level of education or performance on other cognitive tasks related to executive or frontal lobe function, but was related to duration of abstinence, years of drug use, number of times of relapse, treatment attempts, and ability to hold gainful employment. These data suggest that drug abuse may be related to dysfunction of the orbitofrontal cortex, at least in a sub-group of drug abusers. Bechara, A. et al. Decision-Making Deficits, Linked to a Dysfunctional Ventromedial Prefrontal Cortex, Revealed in Alcohol and Stimulant Abusers. Neuropsychologia, 39, pp. 376-389, 2001.

Predictability Modulates Human Brain Response to Reward

Dr. Berns and colleagues at Emory University used fMRI to map the responses to predictable and unpredictable delivery of liquid rewards in normal humans. Subjects received small drops of either fruit juice or water under two conditions. In the first condition, juice and water were delivered in a fixed alternating sequence at 10-second intervals. In the second condition, juice and water were delivered in a random sequence at varying intervals. After the sessions were over, subjects stated whether they preferred water or juice (80% preferred juice). This design allowed analysis of brain responses to 1) delivery of the preferred versus non-preferred solution, 2) predictable versus unpredictable delivery, and 3) interaction of preference and predictability. Activity in the nucleus accumbens was associated with unpredictable delivery of liquid, irrespective of whether or not the liquid was preferred. In contrast, only the mouth region of the somatosensory cortex was associated with delivery of the preferred solution. These results provide a new perspective on the functional role of the nucleus accumbens in humans. Rather than being activated in proportion to the hedonic value of stimuli per se as has been previously thought, activity in the nucleus accumbens may reflect attempts to resolve uncertainty about the delivery of rewards. Berns, G.S. Predictability Modulates Human Brain Response to Reward. J. Neuroscience, 21(8), 2001.

The Internet is a Vast New Source of Hallucinogens and Underground Drugs

Drs. Halpern and Pope at McLean Hospital surveyed the information available on the Internet regarding hallucinogens as of December 1998. Using a common search engine (Yahoo), they identified over 80 web sites related to the synthesis, identification, procurement, or subjective effects of hallucinogens. Many of these sites had been heavily accessed; one site had nearly 3 million visitors over the past 3 years, whereas a second site had over 800,000 visitors within the past year. The authors commented on the extraordinary wealth of on-line information about hallucinogenic drugs on the Internet relative to the information available from government or biomedical sources (e.g. MEDLINE). Halpern, J.H. and Pope, H.G. Hallucinogens on the Internet: A Vast New Source of Underground Drug Information. American Journal of Psychiatry, 158, pp. 481-483, 2001.

Cortical Effects of Bromocriptine in Human Subjects Revealed by fMRI

Dr. Kimberg and colleagues at the University of Pennsylvania used fMRI to determine the neurocognitive effects of D-2 receptor stimulation in normal humans. Subjects performed 3 tasks during the fMRI scanning sessions. Two were cognitive tasks related to working memory (two-back) and set-formation and shifting (Wisconsin Card Sorting task). The third task was a simple bimanual motor response task. Subjects were also given a test of reading span during an initial practice session. The effects of bromocriptine on task performance were related to the subject's initial cognitive capacity, as indexed by performance on the reading span task. Bromocriptine improved performance on the Wisconsin Card Sorting task in subjects who had high initial reading span capabilities, but decreased performance in subjects with low reading span scores. There were no effects of bromocriptine or interactions with reading span on the two-back or motor response tasks. The effects on brain activity varied according to the task. The effect of bromocriptine was to attenuate task-related fMRI signals across all three tasks. That is to say, the bromocriptine only affected those brain regions activated during performance of each individual task. Kimberg, D.Y. et al. Cortical Effects of Bromocriptine, a D-2 Dopamine Receptor Agonist, in Human Subjects, Revealed by fMRI. Human Brain Mapping, 12, pp. 246-257, 2001.

Functional Organization of the Brain for Working Memory Differs by Gender

Gender differences in brain activation during working memory tasks were examined with fMRI. Seventeen right-handed adult subjects were studied with four different verbal working memory tasks of varying difficulty using whole brain echo-planar fMRI. Consistent with prior studies, activation of the lateral prefrontal cortices (LPFC), the parietal cortices (PC), and additionally caudate activation was observed in both sexes. The volume of activated brain tissue increased with increasing task difficulty. For all tasks, the males showed bilateral activation or right-sided dominance (LPFC, PC and caudate), whereas females showed activation predominantly in the left hemisphere. Performance data demonstrated higher accuracy and slightly slower reaction times for females. Results show highly significant gender differences in the functional organization of the brain for working memory. These variations in functional organization of the brain may be due to gender-differences in problem solving strategies or in neurodevelopment. Therefore, gender matching or stratification is necessary for studies of brain function using imaging techniques. Speck, O., Ernst, T., Braun, J., Koch, C., Miller, E., Chang, L. Gender Differences in the Functional Organization of the Brain for Working Memory. Neuroreport, 11(11), pp. 2581-2585, 2000.

Cerebral Perfusion Abnormalities in Abstinent Cocaine Abusers

Drs. Ernst, Chang and colleagues at Harbor-UCLA Medical Center used perfusion magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) to evaluate regional cerebral blood flow abnormalities in abstinent cocaine abusers. Abnormalities were evaluated and compared in 25 asymptomatic abstinent cocaine users and 15 healthy controls without a history of drug use. After co-registration of SPECT with MRI, the relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were determined in 10 brain regions in each hemisphere. There was a statistically significant interaction between drug use and brain region on SPECT alone (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on perfusion MRI alone. There also was a significant interaction among gender, drug use, and brain region. Compared to the controls, abstinent cocaine abusers showed increased rCBF in the frontal white matter and in the globus pallidus, and decreased rCBF in the putamen and the temporal cortex. Female, but not male, cocaine abusers showed significantly reduced relative rCBF in the parietal gray matter and increased relative rCBF in the frontal and temporo-parietal white matter, whereas male, but not female, cocaine abusers showed significantly increased rCBF in the thalamus. SPECT and perfusion MRI detect a regional pattern of rCBF abnormalities in cocaine users that is consistent across the two methods. The hypoperfusion in the cortex and deep gray matter of the cocaine users is consistent with previous results. The increased rCBF in the white matter of cocaine users may be due to the presence of reactive glia. Ernst, T., Chang, L., Oropilla, G., Gustavson, A., Speck, O. Cerebral Perfusion Abnormalities in Abstinent Cocaine Abusers: A Perfusion MRI and SPECT Study. Psychiatry Research: Neuroimaging, l99(2), pp. 63-74, 2000.

Effects of Route of Administration on Cocaine-Induced Dopamine Transporter Blockade Using PET

Dr. Volkow and colleagues at the Brookhaven National Laboratory assessed differences in the efficacy of cocaine to block the dopamine transporter (DAT) as a function of route of administration. Positron emission tomography (PET) was used to compare the levels of DAT blockade induced by intravenous, smoked, or intranasal cocaine administration in 32 current cocaine abusers. They found that the levels of blockade were comparable across all routes of administration, and a dose effect was observed for intravenous and intranasal cocaine but not for smoked cocaine. For equivalent levels of cocaine in plasma and DAT blockade, smoked cocaine induced significantly greater self-reports of "high" than intranasal cocaine and showed a trend for a greater effect than intravenous cocaine. The time to reach peak subjective effect was significantly faster for smoked (1.4 min) than for intravenous cocaine (3.1) or for intranasal cocaine (14.6 min). It was found that differences in the reinforcing effects of cocaine as a function of the route of administration were not due to differences in the efficacy of cocaine to block the dopamine transporters. The faster time course for the subjective effects for smoked than intravenous and for intravenous than for intranasal cocaine highlights the importance of the speed of cocaine's delivery into the brain on its reinforcing effects. Volkow, N.D. et al. Effects of Route of Administration on Cocaine Induced Dopamine Transporter Blockade in the Human Brain. Life Sciences, 67, pp. 1507-1515, 2000.

An fMRI Study Reveals Sex Differences in Response to Visual Stimulation: Implications for Dopamine System Function

Drs. Cowan, Renshaw and colleagues at McLean Hospital investigated the visual system response to blue light as a marker of CNS dopamine tone. Given that numerous sex-related differences in CNS dopamine function have been found previously, it was predicted that blue (470 nm) and red (660 nm) light stimulation would produce sex-specific patterns of response in the primary visual cortex using the blood oxygen level dependent (BOLD) functional magnetic resonance (fMRI) method. BOLD response to red and blue light was analyzed in male and female volunteers. Results showed that near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase to blue light stimulation when compared to females. These findings support a sex- and color-dependent differential pattern of primary visual cortical response to photic stimulation and further suggest a viable method for assessing the influence of specific dopamine agonist/antagonist medications on visual function. Cowan, R.L. et al., Sex Differences in Response to Red and Blue Light in Human Primary Visual Cortex: A BOLD fMRI Study. Psychiatry Research: Neuroimaging, 100, pp. 129-138, 2000.

Effects of Nicotine and Caffeine on EEG Topography and Other Measures

The effects of nicotine and caffeine were assessed separately and in combination, in 12 male habitual smokers (aged 19-31 yrs) using a repeated-measures design. Caffeine (0-mg versus two 150-mg doses were administered in a decaffeinated/sugar-free cola drink following baseline and 90 min later) and was crossed with nicotine (ad libitum, self dosing versus 1.00-mg machine-delivered dose versus 0.05-mg machine-delivered dose). Subjects smoked 5 cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on EEG power; however, these effects were modulated by whether the eyes were open or closed, the other drug, and the electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs. Gilbert, D.G, Dibb, W.D., Plath, L.C., and Hiyane, S.G. Effects of Nicotine and Caffeine, Separately and in Combination, on EEG Topography, Mood, Heart Rate, Cortisol, and Vigilance. Psychophysiology, 37(5), pp. 583-595, 2000.

Impact of Temperature on METH-Induced Neurotoxicity via DAT

Hyperthermia exacerbates and hypothermia attenuates methamphetamine (METH)-induced dopamine (DA) neurotoxicity. The mechanisms underlying these temperature effects are unknown. Given the essential role of the DA transporter (DAT) in the expression of METH-induced DA neurotoxicity, it was hypothesized that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT. To test this hypothesis, the effects of small, physiologically relevant temperature changes on DAT function were evaluated in two types of cultured neuronal cells: (1) a neuroblastoma cell line stably transfected with human DAT cDNA and (2) rat embryonic mesencephalic primary cells that naturally express the DAT. Temperatures for studies of DAT function were selected based on core temperature measurements in animals exposed to METH under ambient (22o C) and hypothermic (6o C) temperature conditions, where METH neurotoxicity was fully expressed and blocked, respectively. DAT function, determined by measuring accumulation of radiolabeled DA and 1-methyl-4-phenyl-pyridinium (MPP+), was found to directly correlate with temperature, with higher levels of substrate uptake at 40o C, intermediate levels at 37o C, and lower levels at 34o C. DAT-mediated accumulation of METH also directly correlated with temperature, with greater accumulation at higher temperatures. These findings indicate that relatively small, physiologically relevant changes in temperature significantly alter DAT function and intracellular METH accumulation, and suggest that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT. Xie, T., McCann, U.D., Kim, S., Yuan, J., and Ricaurte, G. Effect of Temperature on Dopamine Transporter Function and Intracellular Accumulation of Methamphetamine: Implications for Methamphetamine-Induced Dopaminergic Neurotoxicity. Journal of Neuroscience, 20(20), pp. 7838-7845, 2000.

Strongest Evidence to Date Demonstrates a Single Nucleotide Polymorphism in DβH Structural Gene Accounts for 35-52% of the Variation of Plasma Activity of Dopamine-beta hydroxylase

Dr. Joseph Cubells and colleagues at Yale have analyzed the dopamine beta-hydroxylase (DβH) gene in samples of African Americans, European Americans and Japanese and found that individuals with low levels of DβH activity have two copies (i.e., are homozygous) of the polymorphism in which there is a substitution of tyrosine for cytosine (C→T) in the 5' flanking region (-1021C→T). Individuals with only one copy (heterozygotes) had intermediate activity compared to the homozygotes who both had the unsubstituted allele. DβH catalyzes the conversion of dopamine to norepinephrine and released from sympathetic neurons into the circulation. While the clinical significance of low DβH activity is not settled, it is believed that it is a disease-modifying gene and may be related to addiction as well as other psychopathology. These results offer a new tool for testing hypotheses along this line. Zabetian, C.P., Anderson, G.M., Buxbaum, S.G., Elston, R.C., Ichinose, H., Nagatsu, T., Kim. K-S., Kim, C-H., Malison, R.T., Gelernter, J., and Cubells, J.F. A Quantitative-Trait Analysis of Human Plasma-Dopamine Beta-Hydroxylase Activity: Evidence for a Major Functional Polymorphism at the DβH Locus. Am. J. Hum. Genet. 68, pp. 515-522, 2001.

Heritability of Use and Abuse of Illicit Substances in Adolescents

Iacono and colleagues found in their longitudinal study on twins (Minnesota Twin Family Study, MTFS) that heritability of illicit substances was only 25% or less with heritability of tobacco use and nicotine dependence to be substantially higher: 40% and 60%, respectively. These estimates are lower than others found in adult twin studies and suggest a larger influence of environment at this younger age. Indeed, the contribution to the shared environment turned out to be a substantial 41% and 66% for illicit substance use and abuse, respectively. It was also found that, in general, these heritabilities were not different between males and females. McGue, M., Elkins, I., and Iacono, W.G.. Genetic and Environmental Influences on Adolescent Substance Use and Abuse. Am. J. Med. Genet. 96(5), pp. 671-677, 2000.

Identifying a Multivariate Endophenotype for Substance Use Disorders Using Psychophysiological Measures

Iacono and associates have achieved modest success in identifying individuals with substance dependence using performance on two uncorrelated psychophysiological measures: P300 evoked potentials and electrodermal modulation. These measures had been associated with risk for substance abuse in the past. Now subjects were selected based on their scores and compared for presence of abuse. In the high-risk group, defined as low P300 amplitudes and good electrodermal modulation, significantly more had "any" substance abuse (including alcohol) and significantly more nicotine dependence. There were no differences for illicit substances that may be due to low incidence in this adolescent cohort as well as low numbers of subjects. These data provide suggestions for physiological markers - endophenotypes - that characterize people who abuse psychoactive substances. Iacono, W.G., Carlson, S.R., and Malone, S.M. Identifying a Multivariate Endophenotype for Substance Use Disorders Using Psychophysiological Measures. Intl. J. Psychophysiol. 38(1), pp. 81-96, 2000.

Withdrawal Symptoms were Observed During 28-day Abstinence from Heavy, Chronic Marijuana Use

Drs. Kouri and Pope documented a number of behavioral changes reported in daily diaries by individuals who were temporarily abstaining from heavy marijuana smoking compared to controls, who either were never users or who were heavy marijuana users but who had quit at least 6 months prior to the study. Compared to baseline (day 0 for current users), anxiety, physical tension, and irritability increased; mood decreased over the length of the period. Scores on the Hamilton Depression Scale were maximal at about 1 week into abstinence. Appetite declined for the first few days and then resumed to baseline. Increases in physical symptoms were reported intermittently. This is the first prospective naturalistic investigation demonstrating a variety of symptoms in withdrawal from marijuana use. Kouri, E.M. and Pope, H.G. Abstinence Symptoms during Withdrawal from Chronic Marijuana Use. Exp. Clin. Psychopharm., 8(4), pp. 483-492, 2000.

Upregulation of Serotonin Transporters (SERT) in Chronic Cocaine Users

Mash and associates assessed the status of the serotonin transporter (SERT) in post-mortem tissue of cocaine overdose deaths. Significant increases were seen in the nucleus accumbens, anterior and posterior sectors of the striatum, and in areas of the orbitofrontal gyrus including the anterior portion of the insular cortex and cingulate gyrus. Also investigated were SERT changes in overdose victims who also were determined premorbidly to have excited delirium. In contrast to other victims, elevation was not seen in the substantia nigra and posterior striatum suggesting a distinct phenotype for these individuals. Mash, D.C., Staley, J.K., Izenwasser, S., Basile, M., and Ruttenber, A.J. Serotonin Transporters Upregulate with Chronic Cocaine Use. J. Chem. Neuroanat., 20(3-4), pp. 271-280, 2000.

Procaine Challenge Produced a Bilateral Activation of the Orbitofrontal Cortex in Cocaine-Addicted Subjects

Adinoff and colleagues are trying to determine if repeated cocaine use induces permanent hyperexcitability in the limbic system, not unlike the kindling effect in an animal model. Using procaine as a probe and SPECT measures of regional cerebral blood flow, the cocaine patients demonstrated an increase in the orbitofrontal cortex while comparison subjects showed activation of the anterior cingulate, bilateral insula, and right amygdala. Of interest, the cocaine patients had a significantly lower activation in the orbitofrontal cortex after placebo. This pattern of findings in the cocaine patients was interpreted to be similar to the pattern of interictal hypoperfusion and ictal hyperperfusion that has been observed in subjects with epilepsy and thus may represent evidence of localized (orbitofrontal) sensitization. Adinoff, B., Devous, M.D., Best, S.M., George, M.S., Alexander, D., and Payne, K. Limbic Responsiveness to Procaine in Cocaine-Addicted Subjects. Am. J. Psychiatry, 158, pp. 390-398, 2001.

Prognostic Significance of Antisocial Personality Disorder in Cocaine-Dependent Patients Entering Continuing Care

Dr. McKay and colleagues at the University of Pennsylvania examined the relationship of antisocial personality disorder (APD) to response to continuing care treatments in cocaine-dependent patients (N=127). Patients with and without APD were randomly assigned to 20-week standard group or individualized relapse prevention continuing care interventions after the completion of an initial treatment episode and followed up at 3, 6, and 12 months. Patients with and without APD did not differ on retention in continuing care, substance use outcomes, social function outcomes, or experiences before or during cocaine relapse episodes. A diagnosis of APD was also not a predictor of differential response to the two continuing care interventions in the study. However, APD patients had worse medical psychiatric problem severity than non-APD patients at entrance to continuing care and during follow-up. The results suggest that cocaine patients with APD who are in the continuing care phase of outpatient rehabilitation might benefit from additional medical and psychiatric treatment services. McKay, J.R., Alterman, A.I., Cacciola, J.S., Mulvaney, F.D. and O'Brien, C.P. The Journal of Nervous and Mental Disease, 188, pp. 287-296, 2000.

Factors Accounting for Cocaine Use Two Years Following Initiation of Continuing Care

This study examined the relationship between various interpersonal, intrapersonal and situational factors assessed at 6, 12, and 18 months after entrance to continuing care, and cocaine use in subsequent periods. Cocaine-dependent male veterans (n=132) were randomly assigned to either 12 -step focused group treatment or to an individualized relapse prevention continuing care. Measurements of motivation, coping and mood, social support, co-morbid problem severity, treatment attendance, self-help participation and cocaine use were made at each follow-up. In multivariate analyses, degree of self-help participation emerged as the strongest and most consistent predictor of cocaine use. Continued self-help participation and early achievement of cocaine abstinence appear to be important factors in the maintenance of good cocaine use outcomes over extended periods. McKay, J.R., Merikle, E., Mulvaney, F.D., Weiss, R.V., and Koppenhaver. Addiction, 96, pp. 213-225, 2001.

Behavioral Couples Therapy for Male Methadone Maintenance Patients: Effects on Drug-Using Behavior and Relationship Adjustment

A total of 36 drug-abusing men entering methadone maintenance treatment were randomly assigned either to individual skill-based counseling or to behavioral couples therapy (BCT). Men participating in BCT had significantly fewer positive drug screens during treatment and reported greater reduction in drug use from baseline to post-treatment than did men participating in individual counseling. Further, although both groups showed significant reductions in drug-abuse severity and psychiatric symptoms after treatment, men receiving BCT also reported fewer family and social problems after treatment than did men receiving individual counseling. These findings suggest that BCT is an effective intervention for reducing both substance and family problems. Fals-Stewart, O'Farrell, and Birchler, Behavior Therapy, 32, pp. 391-411, 2001.

Predictors of Engagement in Adolescent Drug Abuse Treatment

Drs. Dakof, Tejeda, and Liddle from the University of Miami Center for Treatment Research on Adolescent Drug Abuse studied 224 adolescents referred for drug abuse treatment and their parents. These researchers compared adolescents considered to be successfully engaged in treatment (n = 118) to those not successfully engaged (n = 106), defining successful engagement as participation in four or more sessions. Both parent and adolescent perceptions distinguished between successful and unsuccessful engagement. Adolescents who were successfully engaged in treatment had parents who described them as exhibiting significantly more "externalizing behavior", including delinquency and aggression, than adolescents who were not successfully engaged. Also, parents of successfully-engaged adolescents reported significantly higher expectations of academic success for their child than did unsuccessfully-engaged adolescents. Finally, adolescents who reported higher degrees of family conflict were more likely to be engaged successfully in treatment than adolescents who reported less family conflict. These results suggest a particular family profile at higher risk for treatment dropout, and inform clinical interventions aimed to engage drug-abusing adolescents and their families in treatment. Dakof, Tejeda, and Liddle, Journal of the American Academy of Child and Adolescent Psychiatry, 40, pp. 274-281, 2001.

Methods for Enhancing Transition of Substance Dependent Patients from Inpatient to Outpatient Treatment

Drs. Chutuape, Katz, and Stitzer at Johns Hopkins University examined methods for increasing the transition of substance dependent patients from inpatient detoxification to outpatient aftercare. One hundred and ninety-six patients were randomly assigned to, 1) standard referral (standard); 2) standard referral with an incentive (incentive); or 3) staff escort from detoxification to aftercare with an incentive (escort + incentive). Incentives (worth US $13.00) were dispensed for completing aftercare intake procedures on the day of discharge from detoxification. More escort + incentive participants (76%) than those in the incentive (44%) or standard conditions (24%) completed intake. The escort + incentive procedure may be useful for improving transition from detoxification to aftercare. Chutuape, M.A., Katz, E.C., and Stitzer, M. Drug and Alcohol Dependence, 61(2), pp. 137-143, 2001.

Development of a Skill Training Program for Parents of Substance-Abusing Adolescents

Dr. Neil McGillicuddy and colleagues at the Research Institute on Addictions, State University of New York at Buffalo, have developed a coping skill training program for parents of substance abusing adolescents. The behavioral-analytic model of program development was used to sample representative problematic situations experienced by parents of substance abusing adolescents, obtain an effectiveness-scaling of responses to these situation, and derive alternate forms of a situational role-play measure of parental coping. These situations and scoring guidelines were then used to create the skill training program. Parents of substance abusing adolescents not in treatment subsequently were randomly assigned in a pilot investigation to either a skill training or delayed treatment condition. Skill training resulted in significant improvement in parental coping skills relative to delayed treatment. Moderate to large improvement in the parent's report of their own functioning, family communication, and the teen's marijuana use also favored the skill training group. McGillicuddy, N.B., Rychtarik, R.G., Duquette, E.T., and Morsheimer, E.T. J Substance Abuse Treatment (20), pp. 59-68, 2001.

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