Effects of combined fluoxetine and counseling in the outpatient treatment of cocaine abusers.

Three methods of analysis were used to determine the effects of the combination of counseling with fluoxetine (20, 40, or 60 mg) and "active" placebo (diphenhydramine, 12.5 mg) randomly assigned. Forty-five cocaine-only dependent subjects were treated as outpatients with "interpersonal" counseling, medication, and drug use monitoring three times per week for up to 12 weeks. Treatment effects were analyzed: first, by comparing the three original assignments and placebo; second, by comparing the placebo group to fluoxetine subjects with detectable fluoxetine/norfluoxetine blood levels and those with no detectable medication blood level; third, by examining relapse prevention versus use cessation through stratifying the subjects into four groups according to fluoxetine or placebo assignment and initial urine cocaine positivity or negativity. All three analyses showed improvement on some measures over time regardless of group assignment. The 60-mg fluoxetine group showed least effectiveness, the group with detectable blood levels had less cravings, and the fluoxetine subjects who were abstinent at the start of treatment were somewhat less likely to avoid relapse than those on placebo.

Children of substance abusers: the life experiences of children of opiate addicts in methadone maintenance.

We interviewed 70 substance abusers in methadone maintenance treatment regarding the life experiences of their 188 children. Sixty-four percent of the mothers reported using psychoactive drugs during their pregnancies. Eighty percent of parents reported an arrest during the time the child was growing up, 34% reported receiving treatment for an emotional disorder, and 14% were hospitalized. Four percent of the parents reported that their children had been placed in adoptive care, 9% in foster care, and 1% had a child in a group home. Forty-one percent of the parents reported that at least one of their children repeated a grade in school, 19% were involved in truancy, and 30% had been suspended from school. Twenty percent of parents reported their children's involvement with the law, and 17% reported drug or alcohol use. Problems with the law correlated highly with 1) being held back a grade, 2) truancy, 3) suspension from school, 4) expulsion from school, and 5) treatment for alcohol or drug abuse.

Impulsiveness and subjective effects of intravenous cocaine administration in the laboratory.

Cardiovascular and subjective responses to placebo and 40-mg intravenous (iv) cocaine injections were measured in 29 male iv cocaine users: most subjects received each of these injections on two separate occasions. Most of the subjects also completed various measures of psychopathology and personality. Although the small sample size made any conclusions tentative, an expected significant association between impulsivity and subjective euphoria following 40-mg cocaine administration was obtained, whereas associations of personality measures with cardiovascular responses to cocaine administration were inconsistent.

The development of a cocaine craving questionnaire.

Two versions of a 45-item questionnaire on cocaine craving were administered to 225 cocaine users. The Now version asked about current craving for cocaine, and the General version asked about average craving over the preceding week. Factor analyses showed that a four-factor solution best described the item structure for both versions of the questionnaire. Higher-order analyses indicated that each version was permeated by a single second-order factor. Factor scales derived for each primary and second-order factor had moderate to high reliabilities. Examination of item content, correlations of factors across versions, and external correlates of the factors suggested that both versions were represented by the same hierarchical factor structure. The theoretical and clinical implications of the results from these craving instruments are discussed.

Drug users' self-reports of behaviors and affective states under the influence of alcohol.

This study tested a modified version of the Alcohol-Related Behavior Questionnaire (ARBQ) to investigate the influence of alcohol on negative mood states. The ARBQ asked subjects (substance users and those not misusing drugs or alcohol) to recall various moods and behaviors under three drug conditions: sober, drinking, and drunk. Tests of the ARBQ subscales provided support for its reliability and validity. Scale scores measuring negative affect increased as levels of recalled alcohol intake increased, suggesting that larger amounts of alcohol produced more negative and aggressive feelings. Alcohol-dependent subjects reported more anger and aggression with increasing levels of alcohol intake than nonproblem drinkers. These data further indicated that, among those with alcohol dependence, a history of childhood aggression is an important predictor of negative behaviors and feelings associated with alcohol intake. Among other groups of drug users, a diagnosis of antisocial personality was relatively more important.

Patterns of alcohol, cigarette, and caffeine and other drug use in two drug abusing populations.

Relationships were explored among the frequencies of use of various drugs by a sample of drug-abusing clients of the Addiction Research Foundation (ARF) in Toronto and by drug abusers volunteering to participate in research at the Addiction Research Center (ARC) in Baltimore. The two groups of drug-abusing individuals differed in a number of characteristics. Those from ARF were admitted primarily for diagnosis and possible treatment for alcohol and non-opioid drug problems, whereas those from the ARC were admitted for participation in research on other drugs of abuse, primarily involving opioids. Patterns of use of certain drugs tended to covary in both groups. Of particular interest was the finding that severity of alcoholism was directly related to various measures of tobacco and caffeinated beverage use. In contrast, there was little correlation between the frequency of use among other drugs of abuse (e.g., heroin, cannabis, glue) and the use of tobacco and caffeine. These findings suggest that dependence on nicotine, caffeine, and alcohol may be governed by the same factors and possibly should be considered jointly in the treatment of alcoholic persons. Frequency of use of other drugs examined may be controlled by other factors than those which determine level of use of tobacco and caffeine.

Psychological reactions and retention by cocaine addicts during treatment according to HIV-serostatus: a matched-control study.

We compared retention in treatment and psychological reactions during drug abuse treatment by 22 HIV-antibody positive, physically asymptomatic cocaine addicts to 22 matched HIV-seronegative cocaine addicts. All subjects participated in an outpatient clinical research project. There were no significant differences between groups in sociodemographics and psychiatric symptom scores on entrance or cocaine use except for route of administration (chi 2 = 11.59, df = 2, p less than .005). There were no significant differences among groups regarding being informed of serostatus and beginning treatment. There was a trend (p = .079) for more seropositives to complete treatment. Using end-point analysis to compare 11 seropositive subjects who completed a minimum of 2 weeks of treatment to a matched seronegative comparison groups, there were no significant differences in mood states except for "anger/hostility" (interaction of group x time; F = 2.24, df = 13/260, p less than .05). Informing drug abusers in treatment regarding positive HIV-serostatus was not associated with a lower treatment-retention rate or adverse psychological reactions when counseling regarding HIV issues was integrated with drug abuse treatment.

Cocaine-induced locomotor activity in rats.

Rats were injected SC or IP with a dose of cocaine at 20 mg/kg twice daily or saline (2 ml/kg) for 15 consecutive doses. Horizontal (including ambulatory and repetitive activity) and ambulatory locomotor activities were assessed following the first (acute) and the 15th (chronic) injections. Total locomotor activity (area under curve, AUC) following the acute and the chronic administration of cocaine were comparable, regardless of the route of drug administration. However, the temporal patterns of activity were significantly different; the peak of locomotor activity occurred earlier (chronic vs. acute, 20 vs. 40 min after IP; 130 vs. 180 min after SC) following chronic cocaine administration. Furthermore, the peak activity was significantly higher (3-fold after IP and 50% after SC) in chronically than in acutely treated rats, providing evidence for sensitization. In contrast, activity in the late session (240-280 min after SC) was significantly lower following the chronic SC cocaine administration, providing evidence for desensitization. The absolute slope values of the ascending phase and the descending phase were significantly larger following chronic administration of cocaine than that following the acute dosing. The possibility of changes in locomotor activity with alteration of pharmacokinetics on chronic cocaine treatment is discussed.

Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.

We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.

Geophysical variables and behavior: LXV. Seasonal changes in mood in opioid addicts on the Addiction Research Center Inventory.

Seasonal changes in mood using the Addiction Research Center Inventory (ARCI) were tested in 243 male opioid addicts when they were free of drug and withdrawal effects. No significant changes were found on scales which measure euphoria (MBG), tension-anxiety (LSD), excitement (Ex), or dysphoric effects (SOW). A significant difference between seasons was found for lowered motivation (PCAG) in the summer and spring relative to winter, but these effects were not consistent with a winter seasonal affective disorder. Significant changes were more common for spring-fall and summer seasons relative to winter on items of the inventory.

The prediction of drug dependence from expectancy for hostility while intoxicated.

Three hundred seventy-one male substance-abusing volunteers for drug studies were administered the Buss-Durkee Hostility Inventory (B-D). One hundred nineteen of these subjects were readministered the B-D with the instruction to answer the items in terms of their behavior while drinking alcohol, with 67 of these subjects also completing a heroin use condition. Expectancies for hostility under alcohol or heroin were generally uncorrelated with other measures of personality, psychopathology, antisocial personality, impulsiveness, or criminality; but expectancies for hostility under alcohol were predictive of diagnoses of alcohol, opioid, and marijuana abuse and dependence over and above the influence of these other measures.

The relationship between a diagnosis of antisocial personality and hostility: development of an Antisocial Hostility scale.

An antisocial hostility scale was developed by correlating items of the Buss-Durkee Hostility Inventory with a diagnosis of antisocial personality (ASP) as determined by a computerized version of the DSM-III. Fifty-two male volunteers for drug-related studies at the Addiction Research Center were used for a preliminary test development sample. The scale developed thereby was related significantly to a diagnosis of antisocial personality in a cross-validation sample of 28 drug abusers. A final scale was developed by obtaining correlations between ASP and Buss-Durkee items using the subjects from both of these preliminary samples. Items that comprise the scale were predominantly behaviorally oriented hostility items covered by the Assault scale rather than affective items such as those in the Resentment scale. In a 122 cross-validation sample the scale was related significantly to a diagnosis of antisocial personality. The study confirms the generality of the criterion of overt aggression as a condition for meeting DSM-III criteria for antisocial personality.

Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. A controlled, residential study.

We examined changes over 28 days in mood states, craving for cocaine, and sleep during short-term abstinence reported by 12 male, predominantly intravenous-using, cocaine-addicted subjects residing in a research facility. For comparison, we examined 10 nonaddicted control subjects. There were no significant differences between cocaine addicts and controls regarding demographics and selected DSM-III-R diagnoses other than psychoactive substance use disorder and antisocial personality disorder. There were significantly higher scores of psychiatric symptoms reported by cocaine addicts 1 week before admission. Mood-distress and depression scores recorded at admission and during short-term abstinence were significantly greater than those reported by controls. Addicts' mood-distress scores and craving for cocaine were greatest at admission and decreased gradually and steadily during the 28-day study. There were no significant differences between groups regarding reports of sleep other than difficulty falling asleep and clearheadedness on arising. Although there were significant differences in resting heart rate at admission and over time, there were no significant differences in weight gain or blood pressure. Given the absence of a classic "withdrawal" pattern, "short-term abstinence" may be a more appropriate classification of psychological and physical phenomena experienced by cocaine addicts who initiate abstinence in a controlled environment.

Multidimensional scaling of subjective judgements of drug similarities among ketocyclazocine, morphine, cyclazocine, naloxone and placebo.

Profiles of the subjective and physiologic effects of opioid drugs in man cannot be assigned with precision to specific opioid drug-receptor interactions. We administered a set of training doses of ketocyclazocine, morphine, cyclazocine, naloxone and placebo to 10 drug-using volunteers and obtained similarity judgements between each of 2 test doses of the drugs and a training dose. These data were submitted to multidimensional scaling analysis (INDSCAL) using both neighboring cells estimates and root mean square estimates to estimate missing cells in the data matrices. The results of these analyses are convergent, appear valid and indicate that there are three drug dimensions expressed in this data set: morphine versus placebo and naloxone; cyclazocine and ketocyclazocine versus placebo and naloxone; and ketocyclazocine versus cyclazocine. We interpret this result as supporting evidence that in the set of five drugs studied, three subjective states are induced.

Self-report vs. laboratory measures of aggression as predictors of substance abuse.

Measures of aggressive behavior, antisocial personality, criminality, and impulsivity were obtained on a sample of 85 drug abusing volunteers for studies at the Addiction Research Center in Baltimore. Measures included the Buss-Durkee Hostility Inventory, Diagnostic Interview Schedule Antisocial Personality Disorder diagnosis, Elliott-Huizinga Lifetime Events Scale, Eysenck's Impulsiveness-Venturesomeness-Empathy scales, and a laboratory measure of aggression patterned after the Buss 'aggression machine'. All of the self-report measures of aggression and antisocial personality were moderately correlated with each other, but did not correlate with the laboratory aggression measure. This laboratory measure, nevertheless, made a significant contribution to the prediction of certain substance abuse diagnoses over and above the contributions of the other measures.

EEG and brainstem auditory evoked response potentials in adult male drug abusers with self-reported histories of aggressive behavior.

Auditory brainstem evoked response (BAER) and spontaneous electroencephalogram (EEG) were measured in 124 adult male drug abusers. We examined the relationships among psychiatric diagnoses, paper and pencil measures of aggression and hostility, and electrophysiological features. Subjects meeting criteria for antisocial personality disorder (ASP), as defined by DSM-III, were not significantly different from non-ASP subjects for either BAER or spontaneous EEG measures. The more overtly aggressive subjects had significant delays in BAER latency. Aggressive subjects also had more delta activity and less alpha activity in the spontaneous EEG, as have been observed in "psychopaths" and "criminals." Although ASP and aggression are related, these data indicate that aggressiveness may be a separate, albeit overlapping, trait. As both early aggression and a diagnosis of ASP are predictors of later drug use, the findings that only aggression was associated with EEG slowing and brainstem delays may indicate that ASP and aggression make independent contributions to vulnerability to the development of drug abuse.

Comparison of the characteristics and functioning of cocaine treatment and cocaine research subjects.

Comparisons were made of the functioning and characteristics of cocaine-abusing volunteers to a research ward (N = 25) and to an outpatient treatment program (N = 33) at the same research facility. It was hypothesized that individuals volunteering for clinical studies and for treatment-related studies would represent different segments of the cocaine-abusing population, and that those differences could be significant to an understanding of study findings. Demographic/background variables were assessed through use of the Addiction Severity Index, risk-taking behaviors relative to HIV infection and AIDS through use of a structured interview schedule, intellectual functioning through use of the Shipley Institute for Living Scale, and psychiatric symptoms through use of the Hopkins Symptom Check List (SCL-90R). Significant differences were obtained for criminal activity, needle sharing, and selected psychiatric symptoms. Marital status was particularly important to an understanding of differences between research and treatment groups in that unmarried treatment subjects showed significantly greater psychopathology than research subjects on 3 of 11 symptom scores. Unmarried treatment subjects showed significantly greater deviance than married treatment subjects on 7 of 11 symptom scores. The findings suggest a relationship between marital status and the psychological functioning of treatment clients and indicates that different segments of the cocaine-abusing population volunteer for different types of research.