This review summarizes research published within the past year that pertains to the pharmacotherapy of cocaine dependence. Included are clinical trials, cocaine challenges in the presence of pharmacological agents, and studies that shed light on research strategies by investigating brain reward mechanisms. Reversal of targeted cocaine-induced neuroadaptations, particularly those involving the dysregulation of dopamine, glutamate, and dynorphin systems, might represent the most promising strategy for this impervious condition. (C) 2002 Lippincott Williams Wilkins.

Central stimulants have been abused since their inception and we are currently in the midst of a cocaine epidemic that challenges our resources and capabilities. Through their actions on powerful endogenous reward centers, central stimulants produce intense euphoria that reinforces subsequent usage and eventual dependence. Considerable evidence indicates that the activation of dopamine circuits mediates stimulant reward. With regard to cocaine, it has been hypothesized that depletion of central dopamine leads to craving. Euphoria and craving, the key dynamics of stimulant addiction, may therefore result largely from neurochemical alterations of dopamine systems in the brain's reward center. Progressive deterioration of the stimulant addict involving medical, psychiatric, and psychosocial impairment occurs rapidly, underscoring the addiction potential of these agents. Tolerance, sensitization and withdrawal phenomena are discussed from clinical and neurochemical perspectives.

Alcohol and drug addiction are defined in behavioral terms as the preoccupation with, compulsive use of, and relapse to drugs that are descriptive and confirmatory. The basis of addiction may involve neurochemical changes in the brain that distort and redirect the drive states (instincts). Tolerance and dependence may only be incidentally associated with addiction as a result of a nonspecific adaptation by the body to the presence of a drug. The cellular adaptation may be the same in all organs. Addiction to alcohol and drugs may have no specific relationship to tolerance and dependence. Addiction occurs in the absence of observable tolerance and dependence to alcohol and drugs. Alcohol and drug addiction is probably more complex than tolerance and dependence. Addiction is difficult to study because of the variability of behavioral phenomena and the underlying intricacies of the neurosubstrates. Tolerance and dependence are still useful as they are indicators of drug use. It is a misconception that long term chronic use is necessary for tolerance and dependence to develop. Some studies have shown that tolerance can develop within hours and days to a single dose of alcohol or other drugs. Anxiety, depression and insomnia can occur after a single dose of ethanol in humans. These symptoms of withdrawal from the alcohol or drug constitute dependence. Redefining the criteria for addiction tolerance and dependence to alcohol and other drugs may be in order. A neurochemical model may provide a more definitive and uniform basis for considering addiction, tolerance, and dependence to alcohol and drugs.

Thirteen hospitalized cocaine addicts complaining of cocaine craving were given a single dose of bromocriptine, a dopamine agonist, in a randomized, double-blind, placebo-controlled study design. Compared to placebo, bromocriptine caused a significant reduction in craving ratings. These data suggest that bromocriptine may be effective as a new, nonaddictive pharmacological treatment for cocaine addicts and support the notion that functional dopamine depletion occurs with chronic cocaine use. Open trials indicate that low-dose bromocriptine may be useful in cocaine detoxification.

In order to determine the sensitivity of the dexamethasone suppression test (DST) for major depression in alcoholics, we administered this test to 27 alcoholics with major depression. Sixteen of 27 had abnormal DST results, yielding a 59% sensitivity for depression in alcoholics. When combined with previously reported specificity findings of 100%, the DST significantly (p < 0.001) distinguished depressed from nondepressed alcoholics.

This paper reviews certain clinical and neurochemical aspects of cocaine abuse. Once entrenched patterns of addiction have developed, cocaine addicts suffer progressive financial, medical, psychiatric and psychosocial deterioration that results, to some extent, from cocaine-induced neurochemical alterations in the brain. While cocaine produces euphoria through its stimulatory effect on dopamine neurons, several lines of evidence suggest that dopamine depletion occurs after chronic cocaine abuse. The dopamine neurotransmitter system is therefore a natural starting point for understanding the biology of cocaine addiction and selecting suitable adjunctive pharmacological agents. Furthermore, the dopamine depletion hypothesis implies that cocaine is "physically" addictive and provides a biological framework for understanding this disease and refining present therapeutic approaches.

The persistence of untreated depression was evaluated in 49 severely depressed alcoholics. After 2 weeks of sobriety, 80% of patients with initial major depression by Research Diagnostic Criteria were no longer depressed. These patients improved without antidepressant medications, suggesting the need for a 2-week period of sobreity before psychopharmacotherapy for depression is instituted. Many severe depressions in actively drinking or recently sober alcoholics may represent alcohol-induced organic affective syndromes which, unlike major depressive illness, remit spontaneously with sobriety.

Hyperprolactinemia and sexual dysfunction occurred in 7 of 10 chronic cocaine users. Two of these 7 patients who underwent rehabilitation for cocaine abuse and developed hyperprolactinemia and decreased libido are described. One patient developed galactorrhea. These adverse effects were reversed by bromocriptine. The pathophysiology of cocaine abuse and the central dopaminergic influence on sexual function are discussed.

Despite the high incidence of substance abuse, it remains a common cause of misdiagnosis. In patients who have abused or who are currently abusing drugs, symptoms of a psychiatric illness may be mimicked by either the drug's presence or absence. The laboratory can aid in making a differential diagnosis and eliminating drugs from active consideration as a cause of psychosis, depression, mania, and personality changes. Treatment planning and prevention of serious medical consequences often rest on the accuracy of the admission drug screen. Testing is widely used to assess improvement in substance abuse in both inpatient and outpatient settings. In occupational settings, testing has been used as an early indicator that a problem exists and as a successful prevention tool. The appropriate use of analytic technology in drug abuse testing requires an understanding of available test methodologies. These include drug screens by thin-layer chromatography, comprehensive testing using enzyme immunoassay, and computer-assisted gas chromatography-mass spectrometry (GC-MS). Testing for specific drugs considered likely causes or precipitants of "psychiatric" complaints is available with enzyme assays, radioimmunoassay, or definitive forensic-quality testing using GC-MS.

Back to table of contents Previous article Next article ArticleNo AccessAbnormal Dexamethasone Suppression Test: Result of Tolerance to Opioids?EDE FRECSKAEDE FRECSKAPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.143.1.119-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Abnormal Dexamethasone Suppression Test: Result of Tolerance to Opioids?." American Journal of Psychiatry, 143(1), pp. 119-a–119 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Register for access Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byFair Oaks Clinical Research Center13 February 2010 | British Journal of Addiction, Vol. 84, No. 6 Volume 143Issue 1 January 1986Pages 119-a-119 Metrics PDF download History Published online 1 April 2006 Published in print 1 January 1986

Back to table of contents Previous article Next article ArticleNo AccessPropranolol and StutteringJAMES A. COCORES, CHARLES A. DACKIS, ROBERT K. DAVIES, and MARK S. GOLDJAMES A. COCORES, CHARLES A. DACKIS, ROBERT K. DAVIES, and MARK S. GOLDPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.143.8.1071-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "Propranolol and Stuttering." American Journal of Psychiatry, 143(8), pp. 1071-a–1072 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byStuttering Treatment Research 1970–2005: II. Systematic Review Incorporating Trial Quality Assessment of Pharmacological ApproachesAmerican Journal of Speech-Language Pathology, Vol. 15, No. 4Journal of Clinical Psychopharmacology, Vol. 18, No. 1Fluency Changes in Persons Who Stutter Following a Double Blind Trial of Clomipramine and DesipramineJournal of Speech, Language, and Hearing Research, Vol. 38, No. 3Journal of Fluency Disorders, Vol. 18, No. 2-3Journal of Fluency Disorders, Vol. 18, No. 2-3The pharmacology of stuttering: a critical review1 April 2006 | American Journal of Psychiatry, Vol. 148, No. 10The Lancet, Vol. 335, No. 8683Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 29, No. 5Addiction, Vol. 84, No. 6 Volume 143Issue 8 August 1986Pages 1071-a-1072 Metrics PDF download History Published online 1 April 2006 Published in print 1 August 1986

The aim of this paper is to review and explore the psychopharmacology of cocaine from two divergent points of view--the chronic user and the laboratory. Cocaine's behavioral effects will be correlated with neurophysiological, neurochemical events, and reports by users of consequences of chronic use. These studies and reports when pieced together offer considerable promise in the development of a natural history of compulsive cocaine use. Additional neurochemical and neurophysiological research investigations are needed to allow for the development of non-addicting treatments for detoxification (à la clonidine) and prophylaxis (à la naltrexone). In the absence of these data cocaine treatment programs have been developed borrowing heavily from self help, contingency contracting and inpatient programs for working addicts.

Euphoric properties of cocaine lead to the development of chronic abuse, and appear to involve the acute activation of central DA neuronal systems. This is based upon known effects of cocaine on DA neurons, and the role played by DA in reward states and self-stimulation behavior. With chronic cocaine use, neurotransmitter and neuroendocrine alterations occur. DA depletion is hypothesized to result from overstimulation of these neurons and excessive synaptic metabolism of the neurotransmitter. DA depletion may underlie dysphoric aspects of cocaine abstinence, and cocaine urges. Neurochemical disruptions caused by cocaine are consistent with the concept of “physical” rather than “psychological” addiction. Possible pharmacological interventions in cocaine addiction are outlined and the psychological approach to these patients is discussed.