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Director's Report to the National Advisory Council on Drug Abuse
May, 1995


Research Findings

Clinical and Services Research

Nosology, Diagnosis and Clinical Assessment

Since her project began in 1988, Dr. Linda Cottler and her colleagues, Washington University School of Medicine, have been examining the inter-rater reliability and clinical validity of substance use disorder diagnoses according to the criteria of the Diagnostic and Statistical Manual, Third Edition, Third Edition Revised, and Fourth Edition [DSM-III, -III-R, and -IV] (American Psychiatric Association) and the International Classification of Diseases, Tenth Edition [ICD-10] (World Health Organization). The Substance Abuse Module (SAM), an expanded version of the substance use disorder sections of the Composite International Diagnostic Interview (CIDI), is the structured diagnostic assessment used in this study. Validity measures have included urine, informant interviews, and clinician interviews using the semi-structured WHO Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Comparisons of DSM-III, -III-R, -IV, and ICD-10 have shown good agreement for dependence diagnoses among alcohol, nicotine, cannabis, and cocaine users, but less agreement between systems for abuse (DSM) and harmful use (ICD). Comparison between the lay-administered SAM and the clinician-administered SCAN has indicated good agreement for ICD-10 alcohol, opiate, and cocaine dependence and poor agreement for cannabis. (Cottler, LB; Robins, LN; and Helzer, JE. Agreement Between DSM-III and DSMIII-R Substance Use Disorders. Drug and Alcohol Dependence, 29:17-25, 1991; Cottler, LB. Comparing DSM-III-R and ICD-10 Substance Use Disorders. British Journal of Addiction, 88:689-696, 1993. Cottler, LB et al. Subjective Reports of Withdrawal Among Cocaine Users: Recommendations for DSM-IV; Drug and Alcohol Dependence, 33:97-104, 1993; Cottler, LB et al. The Discrepancy Interview Protocol: A Method for Evaluating and Interpreting Discordant Survey Responses. International Journal of Methods in Psychiatric Research, 4:173-182, 1994.


Identification of Subtypes of Antisocial Personality Disorder

In a study focused on high risk behaviors, comorbidity and drug use conducted by Dr. Linda B. Cottler and her colleagues, new subtypes of Antisocial Personality Disorder (ASPD) were identified among 405 adult drug users admitted to treatment. To meet criteria for ASPD, a person must have exhibited irresponsible, socially non-conforming behaviors as an adult as well as a pattern of childhood conduct disorder (CD). Results of the study showed that a substantial proportion of injecting drug users met criteria for Adult Antisocial Behavior (AAB) without the childhood trajectory of CD. Using the Diagnostic Interview Schedule, a fully diagnosed ASPD group (with history of CD) was distinguishable from an AAB-only group (without history of CD). The findings identify a distinct subtype of ASPD, especially among women, and suggest a modification in the concept of ASPD.


Pattern Shift VEPs in Abstinent Cocaine Dependent, Alcohol Dependent, and Codependent Patients

Bauer and Easton (1994, submitted) of the University of Connecticut Health Center evaluated pattern shift evoked potential (PSVEP) amplitudes and latencies in four groups of subjects (controls, 10; cocaine-dependent, 10; alcohol dependent, 11; and cocaine+alcohol codependent, 11). The subjects were given two psychiatric interviews (the Semistructured assessment for the Genetics of Alcoholism and the Addiction Severity Index) and these met the DSM-IIIR criteria for drug dependence. Drug use or abstinence was verified by urine toxicology. There were abnormal PSVEPs evoked by checkerboard reversal among cocaine abusers abstinent for an average of 3 months. The abstinent alcoholics and those with codependency, also abstinent for 3 months, did not exhibit this abnormality. Data suggest that cocaine may impair visual nervous system function at the level of retina, optic nerve, lateral geniculate, and/or primary visual cortex (Bauer LO and Easton C. Submitted for Publication, 1994).


Neuropsychological Correlates of Urine Toxicology Results

Easton and Bauer (1994) report neuropsychological decrements associated with cocaine use. Four groups of men and women, aged 15 to 61 years, who had used drugs recently [cocaine (n=12), cannabis (n=14), multiple drugs (n=7) or no drug (n=21)], were assessed for neuropsychological function. The use of drugs was confirmed by standard urine toxicology. The battery of tests included the Wechsler Adult Intelligence Scale (WAIS), the Trail making Tests, and Porteus Maze Test. The cocaine positive group exhibited statistically significant impairments in verbal IQ, and on information, comprehension and vocabulary subtests. These individuals also exhibited decrements on the Trail B and Picture Completion subtests, implying impaired cognitive flexibility and attention/concentration. The other experimental groups did not differ from the urine negative group (Easton C and Bauer LO, submitted for publication, 1994).


Pharmacodynamic Effects of Supraphysiologic Doses of Testosterone Enanthate on the Pituitary-Testicular Axis of Young Healthy Male Volunteers: Preliminary Report

Dr. Perry and colleagues at the University of Iowa report that follicular stimulating hormone (FSH) is more sensitive to exogenous testosterone (TE) pituitary-testicular axis (PTA) suppression than luteinizing hormone (LH) in healthy male volunteers. TE was administered intramuscularly at doses of 100 mg (n=4), 250 mg (n=4), or 500 mg (n=2) once weekly for 14 weeks after baseline studies and 2 weeks of placebo. Serum LH, FSH, free and total testosterone, and markers of spermatogeneses were measured at 1 or 2 weeks intervals during and up to 12 weeks after dosing ceased. Dose-response curves showed that FSH was more rapidly sensitive to the effects of supraphysiologic doses of TE than LH, and the effect on sperm count varied markedly between subjects. The time to maximal effect (9-11 weeks) on LH and FSH secretion was delayed compared to maximal free and total testosterone (Scott SD, Perry PJ, MacIndoe JH, Yates WR, Holman TL, and Ellingrod VL. Presented at the European Conference on Specificity and Variability in Drug Metabolism, Besancon, May 1995).


Smoking Cessation for Depressed Patients

Smokers with a history of major depressive disorder constitute a significant proportion of smokers who present for cessation treatment. These smokers experience more frequent and intense depressive symptoms upon initial cessation and relapse at higher rates than other smokers. New and innovative interventions are needed to address the needs of these more recalcitrant smokers who may be unable to quit with standard interventions which are not matched or tailored to their particular needs.

Dr. Richard Brown, a NIDA investigator in Providence, Rhode Island, examined whether adding cognitive-behavioral treatment for depression to a standard smoking cessation protocol will enhance the achievement and maintenance of smoking cessation in smokers with a history of major depressive disorder. Preliminary results suggest that the addition of cognitive-behavioral treatment for depression (to standard smoking cessation treatment) results in superior rates of abstinence for smokers with a history of major depressive disorder, relative to standard smoking cessation treatment alone.

Dr. Arthur Garvey of the Harvard School of Dental Medicine found depressed smokers given nicotine gum were more likely to remain abstinent compared to depressed smokers receiving placebo gum. Although nicotine replacement appears to aid depressed smokers in their attempts to quit, this population may require a combination of nicotine replacement with other methods (antidepressants, mood management therapy) to elevate abstinence rates.


Acute Thermogenic Effects of Nicotine Combined with Caffeine During Light Physical Activity in Male and Female Smokers

Perkins et al. (1994) studied the thermogenic effects of nicotine (15 ug/kg) and caffeine (5 mg/kg) alone or in combination, during physical activity (lowintensity cycle ergometer riding) compared with rest in male and female smokers (n=10 each). The energy expenditure was measured by indirect calorimetry while subjects engaged lowintensity cycle ergometer riding (activity) or were in quiet rest. There were significant thermogenic effects of nicotine and caffeine individually, while the combination of both produced additive effects. The energy expenditure attributable to nicotine, caffeine, or the combination significantly increased during activity compared with rest, but only in males. These differences in energy expenditure were not explained by the increased plasma levels of nicotine and caffeine during activity. The gender differences in the thermogenic effects of nicotine and caffeine during casual physical activity explained some of the apparent individual variability in expenditure due to tobacco smoking. In addition, eating played a more substantial role in the influence of nicotine on body weight in women than in men (Perkins KA, Sexton JE, Epstein LH, DiMarco A, Fonte C, Stiller RL, Scierka A, and Jacob RG. American Journal Clinical Nutrition, 60: 312-319, 1994).
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