Cocaine addiction: psychology and neurophysiology.

Cocaine was considered incapable of producing dependence in 1980 but was recently proclaimed the drug of greatest national health concern. Recent clinical and preclinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from those of other major abused drugs and suggest that long-term cocaine abuse produces neurophysiological alterations in specific systems in the central nervous system that regulate the capacity to experience pleasure. It will be necessary to develop clinically pertinent research models before these findings can be considered definitive, but these evolving ideas have already led to applications of promising experimental treatments for cocaine abuse.

Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate.

We conducted an open clinical trial of desipramine hydrochloride or lithium carbonate as adjuncts to psychotherapy in cocaine abusers. Subjects who were treated with desipramine hydrochloride showed marked decreases in a measure of cocaine craving after two to three weeks of treatment and became abstinent regardless of whether an affective disorder was also present. Lithium carbonate was effective only in cyclothymic subjects. Other subjects treated with lithium carbonate, as well as nonpharmacologically treated subjects, continued their cocaine use.

Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations.

Abstinence symptoms and psychiatric diagnoses were evaluated in 30 chronic cocaine abusers. Structured diagnostic interviews were done within an experimental design intended to maximize differentiation of enduring symptoms from symptoms linked to binges of cocaine use. Longitudinal evaluations showed a three-phase sequence of post-cocaine abuse abstinence symptoms. Over half the sample also met criteria for ed 3 DSM-III, axis I psychiatric disorders. The findings present specific implications for treatment design.

Outpatient treatment of 'crack' cocaine smoking with flupenthixol decanoate. A preliminary report.

"Crack" cocaine abuse often produces severe cocaine dependence that is refractory to available pharmacological and outpatient psychotherapeutic treatments. We conducted two preliminary investigations evaluating the efficacy of flupenthixol decanoate, a depot xanthene requiring infrequent intramuscular administration, in the treatment of cocaine withdrawal. Ten outpatient crack cocaine smokers with poor prognoses were administered flupenthixol decanoate in an open-label, open-ended trial. Flupenthixol decanoate was well tolerated and appeared to decrease cocaine craving and use markedly and rapidly, producing a 260% increase in the average time retained in treatment among these subjects. These promising but preliminary data, combined with the magnitude of problems presented by crack, warrant rapid, expanded double-blind assessment of flupenthixol decanoate in cocaine-abuse treatment.

Desipramine facilitation of initial cocaine abstinence.

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.

Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.

BACKGROUND: At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers. METHODS: One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment. RESULTS: First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management. CONCLUSION: These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.

Seasonal cocaine abuse.

The authors describe two patients with seasonal affective disorder characterized by fluctuations in cocaine craving that paralleled seasonal dysphoria. This extends the range of axis I disorders associated with cocaine self-administration.

Clinical features of cocaine-induced paranoia.

OBJECTIVE: The authors' objective was to assess the frequency and nature of cocaine-induced paranoia. METHOD: They interviewed 50 cocaine-dependent men consecutively admitted to a 28-day rehabilitation program. RESULTS: Thirty-four (68%) of the 50 men reported highly distressing transient paranoid states in the context of cocaine use. The men who experienced paranoia did not differ from those who did not in age, race, or measures of cocaine use. The mean duration and amount of cocaine use before development of paranoia of the men who reported paranoia were not significantly different from the mean lifetime duration and amount of cocaine used by the men who did not report paranoia. Paranoia became more severe and developed more rapidly with continued cocaine use. CONCLUSIONS: The transient paranoid state appears to be a common feature of cocaine dependence and does not seem to be simply a result of exceeding a threshold of use. Rather, affected individuals might possess a predisposition to this drug-induced state. The fact that paranoia became more severe and developed more rapidly with continued drug use is consistent with a sensitization model of cocaine-induced paranoia. In vulnerable individuals, limbic sensitization may underlie its expression, but localization to a specific brain region is speculative. Quantity of use and route of administration do not appear directly to predispose to this phenomenon. Future investigations must be aimed at uncovering the markers and meaning of vulnerability to transient paranoia in heavy cocaine users.

Intravenous cocaine challenges during desipramine maintenance.

Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.

Chronic neuropharmacology of cocaine: progress in pharmacotherapy.

Cocaine dependence has long been thought of as a psychological addiction without a physiological withdrawal syndrome. In animals, chronic cocaine administration produces multiple neurophysiological adaptations that may decrease activity in brain reward pathways. Recent clinical research suggests that cocaine abstinence symptoms include anhedonia, which is consistent with the decreased reward in preclinical studies. Thus, severe cocaine abuse appears to produce a neurophysiological addiction having a primarily psychological clinical expression. Recent research has produced encouraging preliminary data on general pharmacological therapies for cocaine abuse and on specific agents for treating cocaine abusers who have coexisting axis I psychiatric disorders.

The spectrum of cocaine abuse and its treatment.

There is as yet no definitive treatment for cocaine abusers, nor is there consensus as to their degree of psychopathology. Some researchers have found a high incidence of major affective and bipolar disorders, while others have not. Psychological treatment consists of behavioral, supportive, and psychodynamic approaches, with the choice based on the severity of the cocaine abuse. Experimental pharmacologic approaches using tricyclic antidepressants, lithium, or stimulants are being tried both as diagnosis-specific agents and as general treatment adjuncts, but no adequate controlled trials have yet been published.

A preliminary study of desipramine in the treatment of cocaine abuse in methadone maintenance patients.

Intravenous cocaine use is a major problem in methadone maintenance programs. In this pilot study of 16 cocaine-abusing methadone maintenance patients, 8 received desipramine and 8 received no medication other than methadone. During an 8-week open trial the desipramine patients reported significantly less cocaine craving and had less cocaine use than the other patients.

Neuroleptic reduction of cocaine-induced paranoia but not euphoria?

Central dopaminergic activation is hypothesized to underly schizophrenia and, paradoxically, stimulant euphoria. Four cocaine abusers with histories of stimulant-induced paranoid psychoses reported selective reduction in psychotic symptoms but not euphoria when treated with dopamine blockers. This provides preliminary evidence against efficacy of neuroleptics in cocaine abuse prevention, and suggests euphoria and paranoia may have discriminable neurophysiological substrates.

Double-blind evaluation of the effect of acute amantadine on cocaine craving.

Single doses of amantadine hydrochloride and placebo were administered in a double-blind cross-over design on separate days to ten actively craving cocaine abusers in treatment. Pharmacological treatment did influence cocaine craving, but amantadine was less effective than placebo.

The face of craving? Facial muscle EMG and reported craving in abstinent and non-abstinent cocaine users.

We studied 12 subjects, half of whom were current cocaine users and half of whom were abstinent former users, using facial EMG before and after subjects completed questionnaires describing cocaine use, craving and mood. Changes in zygomatic EMG tone before and after cocaine questionnaire completion correlated with reported craving in current users. This preliminary study suggests that facial EMG correlates with cocaine craving in current users.

Gender differences in cocaine use and treatment response.

Much of our understanding of treatment efficacy in drug abuse is based on male drug abusers. In order to determine if there are gender differences in baseline drug use and treatment response, we compared male and female cocaine abusers who participated in an outpatient randomized clinical trial (RCT) evaluating pharmacotherapies for cocaine abuse. Although females had more severe drug problems at intake, they were as successful as males in the RCT and more successful at 6-month follow-up.

Cocaine abuse and addiction.

The National Institute on Drug Abuse now considers cocaine the "drug of greatest national public health concern." Lower prices and a new administration route, cocaine smoking, have increased the potential for addiction. An estimated 2 million individuals in the United States may be addicted to cocaine, or four times the number addicted to heroin. Contrary to population representations of the intractable power of cocaine addiction, cocaine dependence is a treatable disorder. The primary care physician must become familiar with signs of dependence and with therapeutic approaches to cocaine abuse, with particular attention to emerging advances in both psychotherapy and pharmacotherapy.