Evaluating the relative effectiveness of three aversion therapies designed to reduce craving among cocaine abusers

Crack cocaine use and dependence has been steadily increasing since the mid‐1980s. Treatment approaches vary from simple psychotherapy to intensive medication regimens. One clear phenomenon that has been implicated in the continued use and abuse of crack cocaine is craving. Craving is believed to be a response that has been conditioned with previous drug using episodes, and is elicited by environmental cues. The current study investigated the use of three aversion therapies (chemical, covert sensitization, and faradic) designed to eliminate craving for cocaine. Seventy subjects were randomly assigned to one of three aversion treatments or a relaxation control condition. Results indicate that aversion therapy reduces crack cocaine craving. The use of aversion therapy as an adjunct to traditional treatment programs for reducing craving is discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

INFLUENCES ON COCAINE TOLERANCE ASSESSED UNDER A MULTIPLE CONJUNCTIVE SCHEDULE OF REINFORCEMENT

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate‐decreasing effects of cocaine that has been dependent on schedule‐parameter size in the context of fixed‐ratio (FR) schedules, but not under the context of fixed‐interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key‐pecking responses of White Carneau pigeons maintained under a three‐component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose‐effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response‐rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule‐parameter‐specific tolerance. Tolerance to cocaine was generally independent of FI‐parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.     

Ratio size and cocaine concentration effects on oral cocaine-reinforced behavior.

Monkeys were given a choice between cocaine solutions and water under concurrent fixed-ratio reinforcement schedules. The operant response was spout contact. Six rhesus monkeys served as subjects. The cocaine concentration was varied from 0.0125 to 0.8 mg/ml, and the fixed-ratio value was varied from 8 to 128. Cocaine maintained higher response rates than did water over a wide range of conditions. Response rate and number of cocaine deliveries per session were inverted U-shaped functions of concentration. These functions were shifted to the right as the fixed ratio was increased. The number of cocaine deliveries was more persistent as fixed-ratio value was increased when the unit dose was larger rather than smaller. Cocaine consumption was analyzed as a function of unit price (fixed-ratio value divided by cocaine concentration), and unit price accounted for between 77% and 92% of the variance in cocaine consumption for individual monkeys. The current data support the claim that a drug's reinforcing effects increase directly with dose and underscore the need to gather parametric data when examining the effects of experimental manipulations on a drug-reinforced baseline.     

The psychoanalytic view of phobias. Part I: Freud's theories of phobias and anxiety.

This paper initiates a series of communications on psychoanalytic and current psychiatric approaches to the understanding and treatment of phobic syndromes with a review and discussion of Freud's evolving ideas on phobias and anxiety. A list of issues that any theory of phobic syndromes must address is compiled on the basis of Freud's work.     

Neurobiology of Cocaine-Induced Organic Brain Impairment: Contributions from Functional Neuroimaging

The present review is directed at imparting the current knowledge regarding functional neuroimaging as a tool for enhancing the understanding of cerebrophysiologic and neurobehavioral consequences of stimulant abuse. Stimulants like cocaine are capable of inducing clinically significant neurocognitive impairment through direct action on the brain, and indirectly through other organs that influence cerebral physiology. Neurochemical dysregulation including profound effects on the serotonergic and dopaminergic systems have substantial physiological and neurobehavioral consequences. Brain hemorrhages, transient ischemic attacks, strokes, and seizures frequently follow cocaine use. The residual cerebropathologic consequences of cocaine are seen only in significant or pronounced brain events when structural neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. However, recent research with newer functional neuroimaging techniques such as single photon emission, positron emission tomography, and quantitative electroencephalography have revealed high rates of significant alteration in brain function among cocaine users, with negative structural imaging studies. These findings are often associated with impairment on neuropsychological evaluation, also in the absence of positive findings on CT and MRI. Both cerebral metabolic and hypoperfusion anomalies are seen, especially in anterior and temporal brain regions. Observed changes can persist for months, and for some patients, may represent a permanent change in brain functioning.     

Antipsychotic medication adherence, cocaine use, and recidivism among a parolee sample

This study examined the independent and interactive associations between cocaine use and antipsychotic medication adherence in predicting 12 month criminal recidivism among a sample of mentally ill parolees (N = 200). Consistent with prior research, cocaine use (based on hair assays) was associated with more than a threefold increase (relative to non-cocaine users) in the likelihood of a parolee being returned to custody during the follow-up period. Although medication adherence (based on urine specimens) was not independently associated with a significant reduction in recidivism risk, the interaction between cocaine use and medication adherence was significant, revealing a disproportionate impact of medication adherence specific to cocaine users. Prediction models of recidivism based on self-reported measures of medication adherence and cocaine use revealed only marginally significant trends for cocaine use, no effect for adherence, and no significant interaction between these two predictors.     

Nosologomania: DSM & Karl Jaspers' Critique of Kraepelin

Emil Kraepelin's nosology has been reinvented, for better or worse. In the United States, the rise of the neo-Kraepelinian nosology of DSM-III resuscitated Kraepelin's work but also differed from many of his ideas, especially his overtly biological ontology. This neo-Kraepelinian system has led to concerns regarding overdiagnosis of psychiatric syndromes ("nosologomania") and perhaps scientifically ill-founded psychopharmacological treatment for presumed neo-Kraepelinian syndromes. In the early 20^th century, Karl Jaspers provided unique insights into Kraepelin's work, and Jaspers even proposed an alternate nosology which, though influenced by Kraepelin, also introduced the concept of ideal types. Jaspers' critique of Kraepelin may help us reformulate our current neo-Kraepelinian nosology for the better.     

Issues in prenatal cocaine use research: Problems in identifying users and choosing an appropriate comparison group

Prenatal cocaine exposure has been identified in 11 %–44% of deliveries in this country, and researchers are working to answer many important questions about cocaine-exposed infants. However, the process of discovery takes time, thoughtful planning of studies, and careful interpretation of results. This paper will review recently published data considering the impact on study results of two methodological issues in cocaine use research: identifying a population of users versus nonusers and choosing an appropriate comparison group. Additionally, some thoughts will be presented on the criminalization and sensationalism of prenatal cocaine use and their effect on both researchers and subjects.     

The association between heroin use and anxiety sensitivity among inner-city individuals in residential drug use treatment

The current study represents an initial investigation of the association between heroin use and anxiety sensitivity (AS). Within a sample of 172 inner-city treatment seeking drug users, AS was compared across past year (1) heroin users with no crack/cocaine use (n=12); (2) crack/cocaine users with no heroin use (n=66); (3) users of both heroin and crack/cocaine (n=45); and (4) individuals with no use of heroin or crack/cocaine (n=49). Consistent with expectations, primary heroin users evidenced higher levels of AS than all other groups, with these differences also evidenced for the physical and social subscales. Differences in AS total score and physical subscale score persisted after controlling for demographic variables, depressive symptoms, and primary use of drugs other than heroin and crack/cocaine including alcohol, nicotine, marijuana, and hallucinogens. Findings suggest a unique relationship between AS and heroin, and set the stage for future work explicating the direction of the observed association.     

Activation of amygdaloid PKC pathway is necessary for conditioned cues-provoked cocaine memory performance

Drug-associated cues are critical in reinstating the drug taking behavior even during prolonged abstinence and thus are thought to be a key factor to induce drug craving and to cause relapse. Amygdaloid complex has been known for its physiological function in mediating emotional experience storage and emotional cues-regulated memory retrieval. This study was undertaken to examine the role of basolateral nuclei of amygdala and the intracellular signaling molecule in drug cues-elicited cocaine memory retrieval. Systemic anisomycin treatment prior to the retrieval test abolished the cues-provoked cocaine conditioned place preference (CPP) memory. Likewise, a similar blockade of cues-provoked cocaine CPP performance was achieved by infusion of anisomycin and cycloheximide into the basolateral nuclei of amygdala before the test. Intra-amygdaloid infusion of H89, a protein kinase A inhibitor, or U0126, a MEK inhibitor, did not affect retrieval of the cues-elicited cocaine CPP memory. In contrast, intra-amygdaloid infusion of NPC 15437, a PKC inhibitor, abolished the cues-elicited cocaine CPP expression, while left the memory per se intact. Intra-amygdaloid infusion of NPC 15437 did not seem to affect locomotor activity or exert observable aversive effect. Taken together, our results suggest that activation of PKC signaling pathway and probably downstream de novo protein synthesis in the basolateral nuclei of amygdala is required for the cues-elicited cocaine memory performance. However, temporary inhibition of this signaling pathway does not seem to affect cocaine CPP memory per se.     

Dextrorphan effects on cocaine and brainstem perturbation

Dextrorphan is a noncompetitive blocker of N-methyl-D-aspartate (NMDA) receptors. Since NMDA blockers are known to reduce the locomotor stimulatory and toxic effects of cocaine, it was speculated that dextrorphan would attenuate cocaine-induced behavioral excitatory motor activity associated with and without mechanical perturbation of the brainstem. Technique: Motor activity was recorded following dextrorphan and/or cocaine challenge in 25 SHR rats. Ten were naive subjects. Mini-osmotic pumps delivering cocaine (2.5 mg/0.49 ul/hr) were placed in 15 subjects, and infusion was halted after the third infusion day. On the fifth day either a dextrorphan (25 mg/kg, subcutaneous) or a dextrorphan and cocaine (40 mg/kg, intraperitoneal) challenge was done. Ten rats had bipolar electrode implants in the bilateral brainstem. Five were treated with DC current lesions in each of 12 days over a 3-week period. The effects of brainstem lesions on escape behavior were also evaluated in those five subjects. Results: In the naive subjects, dextrorphan reduced motor activity (P=.0001), whereas combined cocaine and dextrorphan increased motor activity (P=0.04). In lesioned subjects, dextrorphan decreased motor activity (P=0.0001). In electrode implant subjects, combined dextrorphan and cocaine challenge decreased the motor activity (P=0.04). Hyperactivity in the electrode implant group was greater than in the lesioned subjects. Midbrain electrolytic lesions attenuated escape behavior. A variety of behaviors were produced by brainstem lesions. Conclusions: Dextrorphan and brainstem lesions reduced motor hyperactivity and escape behavior. In electrode implant subjects dextrorphan counteracted the expected cocaine excitatory motor effects. Dextrorphan did not activate nor facilitate seizures.     

Cocaine and crack users compared

Because crack use is such a recent phenomenon, little is known about users of this highly addictive drug, the harmful effects of which have been widely publicized. This study hypothesized that crack users would be more depressed and more alienated from family, friends, and school staff than would cocaine users, and would consider as less important reasons not to use crack and cocaine. The authors compared 411 users of cocaine (but not crack) to 156 crack users, all but 22 of whom had also used cocaine. The sample was derived from a larger random survey of 7th- through 12th-grade students in North Carolina. Results indicated that crack users were younger than cocaine users, made poorer grades, were more depressed, and were more likely to be alienated from family and friends. However, cocaine and crack users were equally unlikely to confide in anyone in their school if they had a drinking or drug problem. Further, crack users were more likely to have talked once to a teacher or counselor in the past year about their problems. The implications of these seemingly inconsistent findings are explored. Crack users appear to be a particularly vulnerable population.     

A REVIEW OF COCAINE ABUSE: BEHAVIOR,PHARMACOLOGY, AND CLINICAL APPLICATIONS,EDITED BY S. T. HIGGINS AND J. L. KATZ

This book comprises 17 chapters that deal with a variety of topics related to cocaine and its abuse. Several of the chapters are excellent, and the book in its totality contains a wealth of information. These are major strengths. On the down side, some important topics are ignored, the relevance of several chapters to cocaine abuse is not apparent, and the various chapters are not well integrated. We recommend Cocaine Abuse as a reference volume for scientists with specific training in the areas that it covers. But we do not recommend it for cover‐to‐cover reading as an overview of cocaine abuse.     

Development of the brief Spanish Cocaine Craving Questionnaire-General

Combining two different samples of cocaine users (N = 183), we tested the factor structure of a brief (12-item), Spanish version of the Cocaine Craving Questionnaire-General using confirmatory factor analysis. The four-factor model provided excellent fit to the measure. Moreover, the measure significantly differentiated between recent cocaine users and abstainers, as well as between participants with different levels of severity of drug-use history. Factor 1 expresses highly intense and overwhelming desires, Factor 2 expresses lack of self-control over cocaine use, Factor 3 items express lack of positive reinforcement expectancies, and Factor 4 expresses stimulating expectancies for cocaine use. The results revealed the validity of the CCQ-General brief as an instrument to assess cocaine craving in Spanish and supported the conceptualization of cocaine craving as a multifaceted construct.     

Neurobiology of prenatal cocaine exposure effect on developing monoamine systems

Cocaine and crack belong to a broad category of agents that act primarily as central nervous system stimulants at the level of the monoaminergic neurotransmitter system (dopamine, norepinephrine, and serotonin). These neurotransmitters are involved in the regulation of a number of basic psychological functions including attention and arousal and play a crucial role in the defining of brain structure and neuronal formation. This paper outlines what is currently known about the direct effects of cocaine on the mature and developing central nervous system. Three general points are reviewed: (1) Cocaine has differing effects on structural and functional brain development throughout gestation (e.g., there is not a single, all or none effect); (2) No one area of the brain is singularly affected. Areas related by the monoaminergic system are differentially influenced and affecting one area may result in a functional change in another; and (3) Because substantial brain growth, synaptic formation, and remodeling occur in the first months after birth, ongoing postnatal exposure to cocaine also carries risk for direct effects on brain function. Understanding the developmental neurobiological effects of cocaine provides data to guide studies in infants and young children of how prenatal cocaine exposure may contribute to specific, biologically based areas of neurological vulnerability that will be expressed behaviorally and developmentally in the first 3 to 5 years of life.     

Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food.

The hypothesis that mesolimbic dopamine is selectively involved in cocaine reinforcement was investigated in the rat. Animals were trained under a multiple schedule in which responding was reinforced by intravenous cocaine (0.75 mg/kg/injection) or food (45-mg pellets) under fixed-ratio 15 schedule requirements in alternate 30-min components of a 2-hr daily session. Infusion of the catecholaminergic neurotoxin 6-hydroxydopamine, but not the vehicle solution, into the region of the nucleus accumbens and olfactory tubercle produced selective reductions in cocaine self-administration without significantly altering responding maintained by food within the same sessions. This effect was reproduced in intact animals by substituting saline for cocaine in the self-administration component. These results support the hypothesis that the reinforcing effects of cocaine are dependent upon mesolimbic dopamine and demonstrate that cocaine self-administration can be disrupted in animals without altering behavior maintained by a nondrug reinforcer.     

Tolerance to effects of cocaine on behavior under a response-initiated fixed-interval schedule

Tolerance to effects of cocaine can be modulated by schedules of reinforcement. With multiple ratio schedules, research has shown an inverse relationship between ratio requirement and amount of tolerance that resulted from daily administration of the drug. In contrast, tolerance to the effects of cocaine on behavior under multiple interval schedules generally has developed regardless of interval value. Under interval schedules reinforcement depends on the animal making one response following a time interval. Thus, as time to respond increases, the time to reinforcement decreases. On the other hand, fixed ratio schedules require a specified number of responses to be made prior to reinforcement. Therefore, delaying the initiation of responding does not coincide with a significant decrease in the time to reinforcement. In the current experiment, 6 pigeons were trained to respond under a three-component multiple schedule, with a different tandem fixed-ratio 1 fixed-interval schedule in each component. The multiple schedule required one response, which was followed by one of three fixed-interval values (5, 15, or 60 s). Thus, the multiple schedule was interval-like because after the fixed-ratio 1, only one more response was required for reinforcement, but it was also ratio-like because the length of the pause at the beginning of each interreinforcer interval affected the time until the next reinforcer. Acute administration of cocaine generally resulted in dose-dependent decreases in responding. Chronic (i.e., daily) administration of a rate-decreasing dose resulted in tolerance patterns similar to those usually obtained with multiple ratio schedules. That is, the magnitude of tolerance was related inversely to schedule size. These results suggest that delay to reinforcement from the initial response may play a role in the development of schedule-parameter-related tolerance.     

A cross-cultural study of the structure of comorbidity among common psychopathological syndromes in the general health care setting

This study presents analyses of 7 common psychopathological syndromes in the World Health Organization (WHO) Collaborative Study of Psychological Problems in General Health Care (T. B. Ustun & N. Sartorius, 1995). Data on depression, somatization, hypochondriasis, neurasthenia, anxious worry, anxious arousal, and hazardous use of alcohol were analyzed for 14 countries (Ns for each country ranged from 196 to 800). Four models were evaluated: a 1-factor model; a 2-factor model in which all syndromes except hazardous use of alcohol represented internalizing problems; and two 3-factor models. The 2-factor model fit best. These results extend previous research on the 2-factor model to the current complaints of attendees of general health care clinics, to a new set of syndromes, and to a variety of both Western and non-Western countries.