Showing papers on "Addiction published in 1993"

The pharmacology and neural circuitry of sensitization to psychostimulants.

Abstract: Behavioral sensitization to amphetamine-like psychostimulants is manifest as a progressive increase in drug-induced anxiety and paranoia which can culminate in psychopathologies, such as paranoid psychosis and panic attacks. Sensitization may also mediate the facilitation of drug relapse in addicts by increasing the reinforcing value of acute drug administration. The primary animal model for psychostimulant-induced psychopathologies involves repeated, non-contingent administration of drug to rodents, which can produce a progressive and enduring augmentation in motor activity and increased susceptibility to drug self-administration. Because of the mature literature implicating mesoaccumbens dopamine transmission in the acute motor and reinforcing effects of amphetamine-like stimulants, investigation into the neural basis of behavioral sensitization has focused on this projection. Over the last decade, with a few exceptions, the neurochemical and molecular literature that has emerged from this effort is replete with inconsistencies. In contrast, the presence of behavioral sensitization is a highly replicable event. It is proposed that behavioral sensitization arises from an alteration in the neural circuitry that subserves the translation of motivationally relevant stimuli into adaptive motor responses. The mesoaccumbens dopamine projection is embedded in this circuit and an enduring change in dopamine transmission may alter the functional state of the circuit to produce behavioral sensitization. However, combinations of alterations in other connections within the circuit can also support behavioral sensitization. The specific changes in the circuit that promote behavioral sensitization are under the control of experimental parameters, such as the drug employed, dosage regimen, withdrawal period and the presence of conditioning cues. Thus, the profile of neurochemical alterations observed after exposure to repeated psychostimulants may vary depending upon the experimental protocol and strain of animals, even though all laboratories report the presence of behavioral sensitization.

Nicotine delivery kinetics and abuse liability.

Abstract: It is well established that nicotine meets all criteria of a highly addictive drug. However, as recognized by the U.S. surgeon general, the nicotine delivery system itself is an important determinant of the toxic and addictive effects engendered by nicotine use. Therefore, altering the form of nicotine dosing may allow for selective therapeutic action in efforts to develop safer and less addictive nicotine replacement therapies. While it is the case that initial tobacco use often escalates to compulsive use accompanied by tolerance and physical dependence, this is not usually observed with nicotine replacement therapies. These observations are consistent with laboratory data indicating that (a) nicotine polacrilex and transdermal systems deliver nicotine more slowly and at lower dose levels than tobacco-based forms, and (b) human data suggesting that the abuse liability of these systems is substantially lower than that of the tobacco-based nicotine delivery systems. Because the drug dosage form can be systematically manipulated and evaluated, further research in developing alternative nicotine delivery forms may hold substantial promise in the treatment of tobacco dependence. Psychological research methods can play an important part in their evaluation.

Vietnam veterans' rapid recovery from heroin addiction: a fluke or normal expectation?

Abstract: Between 1972 and 1974, the outcomes of army enlisted men who had served in Vietnam during 1970-71 were evaluated and compared with that of a matched group. This paper reports the major findings of that study with respect to frequency of narcotic addiction in and after Vietnam, and the major risk factors for Vietnam addiction and later relapse. Extraordinary access to records facilitated drawing the sample, locating it, and verifying interview responses. The surprisingly low levels of readdiction and the rarity of addiction to narcotics alone as compared with poly-substance dependence are findings still not entirely incorporated into public and scientific views of heroin addiction. Some defenses against that incorporation are examined.

Behavioral frequency and psychological commitment: Necessary concepts in the study of excessive exercising

Abstract: Efforts to understand the associations among exercising, personality factors, and disordered eating have been the focus of much debate. However, research has been plagued by inconsistent findings, and there is evidence that classification and measurement differences are fundamental to these problems. To date, there are no studies which have defined exercise as a multifaceted construct. The purposes of this study were to establish the factor structure of a questionnaire developed to assess the core features believed to characterize excessive exercisers and to assess relationships between exercise (operationally defined as a function of behaviors and attitudes) and a number of putative risk factors. Results indicated that exercise was strongly related to weight preoccupation among women and men and that, among men, obsessive-compulsiveness was also positively related--findings which support claims that exercising and dieting tend to coexist, and they are associated with an obsessive-compulsive personality profile.

Clinical Pharmacology and Toxicology of Cocaine

Abstract: Cocaine abuse has produced a major epidemic health problem in North America in the 1980s. The abuse of cocaine is maintained by the drug's effects on brain reward systems, mediated at least in part by its dopaminergic action. The patterns and consequences of use are best understood by considering the pharmacokinetics (rapid absorption and delivery to the brain, relatively short half-life) and the pharmacodynamics (intense central and peripheral neural stimulation). Cocaine is used therapeutically as a topical and local anaesthetic. Toxicity occurs primarily in cocaine abusers, but also occasionally after therapeutic dosing. Medical complications reflect primarily excessive central nervous system stimulation and excessive vasoconstriction, the latter resulting in severe hypertension and/or organ ischaemia with associated organ injury. Most deaths that result from medical complications of cocaine intoxication are sudden and occur before medical intervention is possible. Other complications of cocaine abuse with severe personal and social consequences include traumatic deaths and injuries, and reproductive disturbances, as well as transmission of infectious diseases, especially AIDS. Cocaine addiction is clearly a problem, although the number of addicts is unknown. Pharmacologic treatment of cocaine addiction has as yet been unsuccessful. Psychosocial approaches remain the mainstay of therapy.

Smoking cessation, clonidine, and vulnerability to nicotine among dependent smokers

Abstract: Objective This study examines the efficacy of clonidine in smoking cessation and the influence of gender, history of major depression, and measures of nicotine dependence. Methods The study was designed as a 10-week double-blind randomized comparison stratified for gender and major depression. Three hundred subjects who smoked cigarettes heavily were enrolled in the study. Abstinence from smoking was evaluated by self-report and verified by serum cotinine levels. Results Gender, major depression recurrent type, and measures of nicotine addiction were risk factors for treatment failure. There was no clonidine effect in men, but there was a modest effect in women (odds ratio, 2.01; 95% confidence interval, 1.00 to 4.10) that was most pronounced (odds ratio, 8.5; 95% confidence interval, 1.67 to 43.62) among women with the highest risks. Conclusion Measures of addiction and major depression predict treatment failure. Together they are stronger predictors of outcome than drug. Clonidine is a limited aid in cessation, and drug effects come primarily from women at high risk for treatment failure. An increased risk for psychiatric complications after smoking cessation was apparent among smokers with histories of major depression, particularly bipolar disease. Clinical Pharmacology and Therapeutics (1993) 54, 670–679; doi:10.1038/clpt.1993.205

Alcoholism in treatment-seeking cocaine abusers: clinical and prognostic significance.

Abstract: Two hundred ninety-eight treatment-seeking and 101 community cocaine abusers were interviewed using the Schedule for Affective Disorders and Research Diagnostic Criteria. Alcoholism was the most frequently diagnosed current and lifetime psychiatric disorder in both samples. Several findings from this study converge with recent evidence which suggests a particularly strong relationship between cocaine abuse and alcoholism that may differ from other types of alcohol-drug comorbidity. First, rates of alcoholism among cocaine abusers doubled those of comparable samples of opioid addicts. Second, while virtually all cocaine abusers in this sample reported some alcohol use during the past month, a lifetime diagnosis of alcoholism was associated with more severe cocaine dependence. Third, the onset of alcoholism followed the onset of drug dependence for the majority of alcoholic cocaine abusers, a pattern which contrasts that typically seen in other types of drug-alcohol comorbidity and suggests that cocaine abu...

Diagnosis and treatment of sexual addiction

Abstract: Following a brief introduction to the concept of addiction, the definition of and diagnostic criteria for sexual addiction are presented A theoretical framework for treatment of sexual addiction is then outlined, based on an understanding of the underlying addictive process: the compulsive dependence on external actions as a means of regulating one's internal states Effective treatment addresses both addictive behavior and the addictive process Addictive sexual behavior is addressed through behavioral symptom management, which includes relapse prevention and other cognitive-behavioral techniques The addictive process is addressed by enhancing self-regulatory functions through individual psychotherapy, therapeutic group experience, and pharmacotherapy (medication treatment, when indicated) An integrated system for treatment of sexual addiction, which brings together these therapeutic methods in one theoretically coherent, clinically unified approach, is outlined

Cellular responses to chronic treatment with drugs of abuse.

Abstract: This review focuses on the long-term adaptations opiates and cocaine induce in specific regions of the nervous system that underlie the additive actions of the drugs, and the mechanisms by which such adaptations are achieved. To date, opiate and cocaine regulation of post-receptor, intracellular messenger pathways has shed considerable light on the mechanisms underlying chronic drug action. Of particular interest is the up-regulation of the cyclic AMP pathway observed in the locus coeruleus (LC), a brain region involved in physical opiate addition, in response to chronic opiate administration. Up-regulation of the cyclic AMP pathway has been shown to contribute to the opiate tolerance, dependence, and withdrawal exhibited by these neurons electrophysiologically. A similar up-regulation of the cyclic AMP pathway in response to chronic opiate and chronic cocaine treatments has been observed in the mesolimbic dopamine system, which is implicated in the psychological aspects of drug addiction. Several lines of evidence suggest the possibility that these biochemical adaptations may contribute to opiate and cocaine regulation of this neural pathway. Related studies in inbred rat strains raise the additional possibility that similar adaptations may contribute to individual genetic vulnerability to drug addition. Current studies are aimed at investigating opiate and cocaine regulation of transcription factors in these discrete brain regions to identify the molecular mechanisms involved in drug action. The investigations have focused on the Fos-Jun family of immediate early gene transcription factors, and the CREB family of transcription factors, as possible mediators of the effects of chronic opiate and cocaine exposure on regulation of neuronal gene expression. Ultimately, more direct analyses are needed that make use of methods for detecting changes in target gene expression in vivo. Together, these studies of opiate and cocaine action will help define the precise mechanisms, at the molecular level, by which these drugs of abuse alter the expression of specific genes in particular neuronal cell types and thereby produce physical and psychological aspects of drug addition.

Perinatal substance abusers. Psychological and social characteristics

Abstract: Forty perinatal substance abusers were administered multiple psychosocial, addiction, and psychological measures before beginning treatment. Results indicate that these patients are limited intellectually, educationally, financially, and emotionally. Psychiatric comorbidity was high, with 45% having non-substance abuse axis I diagnoses and 75% having confirmed (by two or more tests) axis II pathology. The most frequently identified axis I disorders were depression and anxiety. The most frequently detected personality disorders were antisocial, borderline, paranoid, and dependent. The average IQ was 87 (low average range) and nearly one third of the sample were found to be somewhat impaired intellectually. These data suggest that treatment programs must take psychological characteristics into account if they are going to succeed in helping these women achieve and maintain abstinence.

Drug effect expectancies and addictive behavior change.

Abstract: While expectancies are considered an important factor in the etiology of addiction, less is known about expectancies for drugs other than alcohol, and there has been little effort to systematically incorporate expectancies into programs designed to change addictive behavior. This report reviews the expectancy construct and the role of expectancies in the development of substance abuse. Cognitive and behavioral strategies for changing substance use expectancies and the means by which expectancies may facilitate changes in addictive behaviors are described. Examples of strategies to incorporate expectancy-based change efforts into clinical intervention for addictive behavior are presented.

Psychomotor-stimulant sensitization: a unitary phenomenon?

Abstract: Repeated intermittent treatment with psychomotor stimulants or opiates sensitizes animals to the locomotor activating effects of these drugs. Whereas such sensitization may have important implications for the understanding of addiction, mental illness, and the cellular basis of memory, its mechanisms remain only partially understood. Psychomotor-stimulant sensitization can result in relatively permanent changes in the response of the mesolimbic dopamine system to these agents and to a variety of stressors, but the process does not depend upon simple activation of dopaminergic neurons. Psychomotor sensitization can be produced by direct (apomorphine, bromocriptine) and indirect (amphetamine, cocaine) dopamine agonists that inhibit the firing of dopaminergic neurons and thus reduce impulse-dependent dopamine release. Moreover, some treatments that cause dopaminergic activation and dopamine (DA)-dependent locomotion fail to cause robust psychomotor sensitization. While nucleus accumbens injections of amphetamine cause DA release and enhanced locomotion, they do not sensitize the animals to subsequent systemic amphetamine. On the other hand, ventral tegmental injections of amphetamine inhibit the DA system and DA-dependent locomotion but none the less sensitize the animal to subsequent systemic amphetamine treatment. While some drugs (cocaine, amphetamine, morphine, heroin) cross-sensitize animals to each other, other drugs (bromocriptine, quinpirole) sensitize animals to themselves and each other but not to cocaine or heroin. While some cases of sensitization involve Pavlovian association of environmental cues with the drug state, others seem largely independent of such conditioning. Thus it appears that there is more than one phenomenon and more than one mechanism of psychomotor sensitization.

Negative addiction in male and female runners and exercisers

Abstract: 72 male and 26 female runners and 60 male and 30 female exercisers were tested on the Negative Addiction Scale of Hailey and Bailey along with demographic questions to examine the relationships among gender, age, years of exercise experience, and addiction to exercise. Analysis showed no differences in addiction scores by age, gender, or type of activity. A trend showed longer involvement in physical activity was associated with higher addiction scores.

Network therapy for addiction: a model for office practice.

Abstract: Individual therapists in office practice are often considered to have limited effectiveness in treating alcohol and drug dependence. In this article the author describes network therapy, an approach developed to assure greater success in such treatment. It uses psychodynamic and behavioral therapy while engaging the patient in a support network composed of family members and peers. A cognitive-behavioral model of addiction, based on the role of conditioned withdrawal in relapse, is described. Related techniques for securing abstinence are then reviewed; they augment individual psychotherapy to help patients avoid relapse caused by the affective and environmental cues that precipitate drug seeking. The role of social cohesiveness as a vehicle for engaging patients in treatment is outlined next, along with a related technique for enhancing an addicted patient's commitment to the therapy. This is done by using the patient's family and peers as a therapeutic network to join the patient at intervals in therapy sessions. The network is managed by the therapist to provide cohesiveness and support, undermine denial, and promote compliance with treatment. The author presents applications of the network technique designed to sustain abstinence and describes means of stabilizing members' involvement. Applications of network therapy to ambulatory detoxification, disulfiram and naltrexone administration, relapse prevention, and contingency contracting are reviewed.

Guidelines for treating depressive illness with antidepressants: A statement from the British Association for Psychopharmacology.

Abstract: Depression is a common illness which affects some 3% of the population per year. At least 25% of those with marked depression do not consult their general practitioner and in half of those who do the illness is not detected. Depression is easy to recognize when four or five of the core symptoms have been present for 2 weeks which often coincides with some occupational and social impairment. The core symptoms are depressed mood, loss of interest or pleasure, loss of energy or fatigue, concentration difficulties, appetite disturbance, sleep disturbance, agitation or retardation, worthlessness or self blame and suicidal thoughts. A diagnosis of depression is made when five of these core symptoms, one of which should be depressed mood or loss of interest or pleasure, have been present for 2 weeks. Four core symptoms are probably sufficient. Response to antidepressants is good in those with more than mild symptoms. When there are only few or very mild depressive symptoms evidence of response to antidepressants is more uncertain. Antidepressants are effective, they are not addictive and do not lose efficacy with prolonged use. The newer antidepressants have fewer side effects than the older tricyclics, they are better tolerated and lead to less withdrawals from treatment. They are less cardiotoxic and are safer in overdose. Antidepressants should be used at full therapeutic doses. Treatment failure is often due to too low a dose being used in general practice. It may be difficult to reach the right dose with the older tricyclics because of side effects. To consolidate response, treatment should be continued for at least 4 months after the patient is apparently well. Stopping the treatment before this is ill-advised as the partially treated depression frequently returns. Most depression is recurrent. Long-term antidepressant treatment is effective in reducing the risk of new episodes of depression and should be continued to keep the patient well.

Cigarette Smoking, Nicotine Addiction, and Its Pharmacologic Treatment

Abstract: Cigarette smoking is the most prevalent modifiable risk factor for increased morbidity and mortality in the United States and perhaps the world. Not only does the smoker incur medical risks attributable to smoking, passive smokers and society also bear ill effects and increased economic costs attributable to the smoker's habit. These risks of morbidity and mortality have been shown to be related to the addictive component of tobacco smoke, so that pharmacologic therapies have been studied in an attempt to modify the addiction, aid in smoking cessation, and prevent relapse. Presently, nicotine polacrilex and transdermal nicotine show some efficacy. Clonidine's efficacy has been equivocal. In addition, the combination of nicotine substitution and clonidine may be useful but will need formal investigation. Nicotine agonists and antagonists have not proven helpful. Antidepressants are being studied at this time. Nonpharmacologic modalities are briefly mentioned but play a major role in helping the smoker quit. (Arch Intern Med. 1993;153:34-48)

Psychostimulant drugs and a dopamine hypothesis regarding addiction: update on recent research.

Abstract: Evidence that psychostimulant drugs interact principally with monoamines, and in particular with the mesolimbic pathway that utilizes dopamine as the neurotransmitter, has prompted the dopamine hypothesis of psychostimulant addiction. This hypothesis proposes that enhancement of dopamine neurotransmission in the mesolimbic pathway is fundamental to the reinforcing properties of many drugs of abuse. Cocaine, the best characterized psychostimulant, is seen to fulfil this hypothesis by blocking dopamine transporters, thereby preventing re-uptake of the neurotransmitter and enhancing its synaptic concentration (Fig. 1). This biochemical mechanism is supported by behavioural data. For example, concordance between binding to the transporter and changes in locomotor activity has been demonstrated for a large series of cocaine analogues. The dopamine hypothesis suggests possible pharmacotherapeutic strategies to combat psychostimulant use, and these approaches, including available human data and future directions of pharmacological treatments are discussed in this paper. The limitations of the dopamine hypothesis with respect to psychostimulant dependence and abuse liability are also summarized, to provide a broad perspective of the current status of this hypothesis.