Biomedical subjects
Publications and source records attributed to T N Alim.
The visual scanning of 19 recently abstinent crack cocaine-dependent men was assessed while they viewed a picture of a cocaine cue and a picture of a neutral cue. Cocaine craving scores were inversely correlated with the number of preattentive fixations and saccades and were positively correlated with the number of attentive fixations.
Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double-blind, placebo-controlled trial. Forty-six abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg doses of diethylpropion. Patients were tested at baseline and again after 9-14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests.
Cocaine-induced paranoia (CIP) remains an important drug-induced model of idiopathic paranoia for which no psychophysiologic marker has yet emerged. Measures of pupillary oscillation were able to significantly distinguish a group of abstinent crack cocaine abusers endorsing past CIP (n = 32) from another group of crack addicts who denied past CIP (n = 29).
The Wide Range Achievement Test (Revised) (WRAT-R) reading test, demographic variables and drug use severity were used to develop prediction equations to estimate premorbid ability in 92 cocaine abusers. WRAT-R reading was correlated significantly with full scale, verbal and performance IQ. Stepwise regression indicated that only WRAT-R reading score and age accounted for 23% of the variance in Full Scale IQ (FSIQ) and 28% in Verbal IQ (VIQ). Abstinence and severity of use variables did not correlate with nor predict IQ. Actual and predicted IQ scores were correlated significantly and did not differ based on within group t-tests. Thus, these formulas accurately estimate premorbid functioning in cocaine-dependent research patients with FSIQs in the average to low average range, replicating the results in normal adults with average IQs.
Fifty cocaine-dependent patients completed a 2-week double-blind, double-dummy, parallel-group comparison of four dosage levels of diethylpropion and placebo. This clinical trial was designed to evaluate both diethylpropion's ability to attenuate cocaine cue-induced craving and its potential for development as a medication with cocaine-agonist properties. The results indicated that diethylpropion was not superior to placebo and confirmed earlier reports that craving for cocaine diminishes over the course of an inpatient hospitalization. Moreover, the results showed that the cocaine cue-induced craving paradigm employed is effective in stimulating craving for cocaine. Medications that are effective in attenuating this type of "conditioned" craving may have relevance to the breaking of the cycle of relapse and long-term treatment of cocaine dependence. Diethylpropion may not be an appropriate candidate for future medication development because of its lack of obvious therapeutic efficacy and the emergence of a significant number of side effects. However, a cocaine-agonist medication strategy may be appropriate for a subgroup of cocaine-dependent patients with coexisting attention deficit-hyperactivity disorder.
There has been the clinical impression that people with higher levels of anxiety and central arousal are more prone to develop cocaine-induced paranoia (CIP), but this notion has not been formally studied. In the current study, we examined the differences between 28 CIP-endorsing and 16 CIP-denying chronic cocaine users in their levels of state and trait anxiety as measured by the Spielberger State-Tait Anxiety Inventory. We also studied levels of central arousal and reactivity using pupil size measures both during exposure to neutral, abstract, non-drug cues, and after exposure to a cocaine cue. Levels of trait (but not state) anxiety were significantly higher in the CIP group than in the non-CIP group. Moreover, while there were no significant pupil size differences or changes between the two groups while viewing neutral, abstract video images, the CIP group had significantly greater pupillary dilation in response to a video image of crack cocaine than did the non-CIP group. These significant differences remained even after covarying for anxiety scores. The study findings seem relevant to studies of autonomic reactivity in response to drug cues in cocaine-dependent patients; such studies might remain attentive to potential cue reactivity differences between patients endorsing and those denying CIP. Finally, this is the first study showing higher trait anxiety in patients with CIP.
Epidemiologic Cachment Area Survey (ECAS) results suggest that cocaine abusing patients are at increased risk for the later development of Obsessive Compulsive Disorder (OCD), and a need for attention in laboratory and clinical research to the 'cocaine-OCD hypothesis' has been described. Analysis of the ECAS data, however, could not rule out the possibility of a 'distinctive OCD-like syndrome' related to cocaine use. Such an OCD-like syndrome in cocaine dependent individuals has been recently described, where some cocaine dependent patients compulsively forage for cocaine, especially after a cocaine binge. To further explore a possible relationship between cocaine dependence and OCD, the performance on an antisaccade task of 32 cocaine dependent individuals was compared to a group of 15 individuals without neuropsychiatric or substance abusing histories. OCD patients have been described as having a greater frequency of reflexive glances (i.e., increased saccadic distractibility) during the antisaccade task than normals. No statistically significant differences in antisaccade performance were observed between the cocaine dependent patients and a normal comparison group. However, when the cocaine using group was divided into those endorsing and those not endorsing significant cocaine-induced compulsive foraging, statistically significant differences emerged. Cocaine-induced compulsive foragers had the poorest antisaccade performance. While the small sample sizes and the lack of an OCD control group limit the conclusions that can be drawn from the present study, the results seem to suggest that a cocaine-OCD link might be particularly relevant for those cocaine addicts endorsing compulsive foraging.
Recent preclinical studies suggest utility for voltage-sensitive calcium channel blockers (VSCCBs) in the treatment of cocaine addiction. The following double-blind placebo-controlled study examined the role of the VSCCB nimodipine in attenuating cocaine craving in 66 recently abstinent cocaine-dependent patients on an inpatient substance abuse treatment unit utilizing an intensive 12-step milieu-oriented psychosocial therapy. While the medication was well tolerated, the dose of nimodipine used in this study (90 mg q.d.) was not superior to placebo in reducing background or cue-induced cocaine craving over the 3 weeks of the study. There was the suggestion that nimodipine might attenuate the severity of some cocaine-induced brain deficits, as detected by evaluation of smooth pursuit eye movement function. A rationale for evaluating higher doses of nimodipine for the treatment of cocaine addiction is presented. As nimodipine might have anticraving and mood-stabilizing properties and cardio- and neuroprotective properties in the face of cocaine intoxication and might possibly even reverse some cocaine-induced brain deficits, further investigation of the role of nimodipine (and other VSCCBs) in cocaine addiction appears an attractive avenue of future medication development.
Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizopherenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., "anti-stimulant" versus "anti-PCP") might address different aspects of the positive symptom picture in schizophrenia.
Two prominent behavioral syndromes associated with chronic cocaine use that have been described in the literature are cocaine-induced paranoia (CIP) and cocaine-induced compulsive foraging (CICF) for cocaine. To help to clarify the relationship between the two cocaine-induced syndromes, the concordance and sequence of onset of the two cocaine-induced behaviors over the course of the patients' lifetime use of cocaine and during the course of a binge was examined in 62 crack cocaine-dependent men. Thirty-four (54.8%) reported experiencing both CIP and CICF. In 18 (29%) of the patients, only one of these cocaine-induced behavioral syndromes was reported. Ten (16.1%) of the subjects reported neither CIP nor CICF. Patterns of cocaine or other substance use and degrees of tolerance to cocaine were not significantly different between the groups endorsing different patterns of cocaine-induced behaviors. CIP typically preceded the onset of CICF both over the course of the patients' lifetime use of cocaine and over the course of a binge. The study results suggest varying thresholds for the expression of these behaviors in chronic cocaine-abusing individuals.
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Compulsive foraging behavior associated with use of crack cocaine involves compulsively searching the environment for possibly misplaced pieces of crack. Of 41 crack cocaine addicts evaluated, 33 (80.5%) reported at least some compulsive foraging associated with use of crack; 21 (51.2%) reported such behavior as always associated with crack use. The mean length of time spent in compulsive foraging was 90 minutes. Cocaine-induced foraging may represent a drug-induced model of a type of compulsive behavior.