Showing papers on "Addiction published in 2006"

NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

Abstract: Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.

Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction.

Abstract: The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [11C]raclopride (dopamine D2 receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [11C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [11C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction.

Behavioural assessment of drug reinforcement and addictive features in rodents: an overview.

Abstract: Some psychoactive drugs are abused because of their ability to act as reinforcers. As a consequence behavioural patterns (such as drug-seeking/drug-taking behaviours) are promoted that ensure further drug consumption. After prolonged drug self-administration, some individuals lose control over their behaviour so that these drug-seeking/taking behaviours become compulsive, pervading almost all life activities and precipitating the loss of social compatibility. Thus, the syndrome of addictive behaviour is qualitatively different from controlled drug consumption. Drug-induced reinforcement can be assessed directly in laboratory animals by either operant or non-operant self-administration methods, by classical conditioning-based paradigms such as conditioned place preference or sign tracking, by facilitation of intracranial electric self-stimulation, or, alternatively by drug-induced memory enhancement. In contrast, addiction cannot be modelled in animals, at least as a whole, within the constraints of the laboratory. However, various procedures have been proposed as possible rodent analogues of addiction's major elements including compulsive drug seeking, relapse, loss of control/impulsivity, and continued drug consumption despite negative consequences. This review provides an extensive overview and a critical evaluation of the methods currently used for studying drug-induced reinforcement as well as specific features of addictive behaviour. In addition, comic strips that illustrate behavioural methods used in the drug abuse field are provided given for free download under http://www.zi-mannheim/psychopharmacology.de.

‘Internet Addiction’: A Critical Review

Abstract: It has been alleged by some academics that excessive Internet use can be pathological and addictive. This paper reviews what is known from the empirical literature on ‘Internet addiction’ and its derivatives (e.g., Internet Addiction Disorder, Pathological Internet Use, etc.) and assesses to what extent it exists. Empirical research into ‘Internet addiction’ can roughly be divided into five areas: (1) survey studies that compare excessive Internet users with non-excessive users, (2) survey studies that have examined vulnerable groups of excessive Internet use, most notably students, (3) studies that examine the psychometric properties of excessive Internet use, (4) case studies of excessive Internet users and treatment case studies, and (5) correlational studies examining the relationship of excessive Internet use with other behaviours (e.g., psychiatric problems, depression, self-esteem, etc.). Each of these areas is reviewed. It is concluded that if ‘Internet addiction’ does indeed exist, it affects a relatively small percentage of the online population. However, exactly what it is on the Internet that they are addicted to still remains unclear.

Theory of Addiction

Abstract: An understanding of addiction theory is vital to understanding addiction itself. Theory of Addiction takes theory development from a simple â?~rational addiction modelâ?T, adding elements such as compulsion, self-control and habit, to explain the â?~big observationsâ?T in the field. As well as explaining and evaluating the arguments of each of the prevailing schools of thought, the book develops a new, synthetic theory of addiction that brings together the diverse elements of current models. Designed to enable students, practitioners and researchers to establish a starting point in the labyrinthine world of addiction theory, Theory of Addiction supports abstract thinking with concrete and realistic scenarios, underlining the centrality of theoretical understanding to working with addiction. â?¢ Presents a digest of major existing theories in one volume â?¢ Develops a new synthetic theory of addiction â?¢ Recognises the diversity of the experience of addiction â?¢ Discusses factors at the level of both the individual and populations â?¢ Provides key recommendations for the development of effective interventions

Preference for Immediate over Delayed Rewards Is Associated with Magnitude of Ventral Striatal Activity

Abstract: Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

Mindfulness meditation and substance use in an incarcerated population

Abstract: Despite the availability of various substance abuse treatments, alcohol and drug misuse and related negative consequences remain prevalent. Vipassana meditation (VM), a Buddhist mindfulness-based practice, provides an alternative for individuals who do not wish to attend or have not succeeded with traditional addiction treatments. In this study, the authors evaluated the effectiveness of a VM course on substance use and psychosocial outcomes in an incarcerated population. Results indicate that after release from jail, participants in the VM course, as compared with those in a treatment-as-usual control condition, showed significant reductions in alcohol, marijuana, and crack cocaine use. VM participants showed decreases in alcohol-related problems and psychiatric symptoms as well as increases in positive psychosocial outcomes. The utility of mindfulness-based treatments for substance use is discussed.

The Addiction Severity Index at 25: origins, contributions and transitions.

Abstract: The Addiction Severity Index (ASI) is a multi-dimensional interview used to measure the substance use, health, and social problems of those with alcohol and other drug problems, both at admission to treatment and subsequently at follow-up contacts. This article first discusses the conceptual and practical importance of the ASI's multi-dimensional approach to measuring addiction severity, as illustrated by two case presentations. The second section of the paper reviews how this measurement approach has led to some important findings regarding the prediction and measurement of addiction treatment effectiveness. The third section describes the historical and practical considerations that have changed the instrument over time, details the problems with the instrument, and describes our efforts to correct those problems with the ASI-6. Finally, some recent ASI data collected from over 8,400 patients admitted to a nationally representative sample of U.S. addiction treatment programs are presented.

Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors.

Abstract: The development of addiction and vulnerability to relapse following withdrawal is proposed to be the result of neuroadaptive processes within the central nervous system that oppose the acute reinforcing actions of drugs of abuse. These changes lead to impairment in the mechanisms that mediate positive reinforcement and the emergence of affective changes such as anxiety, dysphoria, and depression during withdrawal. Considerable evidence exists implicating perturbations in DA and 5-HT transmission in the nucleus accumbens--neurochemical systems that are activated by cocaine and ethanol self-administration and deficient during withdrawal--as potential substrates for these affective changes. In addition, growing evidence suggests that enhanced CRF release in the central nucleus of the amygdala represents a mechanism underlying the anxiogenic and stress-like consequences of withdrawal that are common to all drugs of abuse. A growing body of evidence also implicates dysregulation of the non-neuroendocrine CRF stress system within the central nucleus of the amygdala as a common factor in the anxiogenic and aversive consequences of withdrawal from drugs of abuse. Moreover, a possible link may exist between long-lasting abnormalities in CRF function in the CeA and vulnerability to relapse during protracted abstinence. Another presumably critical element contributing to the chronic relapsing nature of drug addiction is the learned responses to drug-related stimuli. The long-lasting efficacy of drug- and alcohol-associated contextual stimuli in eliciting drug-seeking behavior in animal models of relapse resembles the endurance of conditioned cue reactivity and cue-induced cocaine craving in humans and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. With cocaine, D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala may be important substrates for the motivating effects of drug-related environmental stimuli. With ethanol, available data suggest a role for opioid receptors in the mediation of conditioned drug-seeking behavior. Finally, conditioning factors (i.e., exposure to drug-associated stimuli) and stress can interact to augment vulnerability to relapse. This finding emphasizes that it will be important to consider the simultaneous effects of multiple environmental triggers for relapse in the development of treatment and medication strategies.

Psychiatric Comorbidity Assessed in Korean Children and Adolescents Who Screen Positive for Internet Addiction

Abstract: Objectives This study aimed to evaluate clinical comorbidity in children and adolescents with Internet addiction by using structured interview. Method The study was performed in 2 stages. We screened for the presence of Internet addiction among 455 children (mean +/- SD age = 11.0 +/- 0.9 years) and 836 adolescents (mean +/- SD age = 15.8 +/- 0.8 years) using Young's Internet Addiction Scale. These subjects also completed a measure of psychopathology for comparison between addicted and nonaddicted subjects. Sixty-three children (13.8%) and 170 adolescents (20.3%) screened positive for Internet addiction. Of these, 12 children (male, N = 9; female, N = 3) and 12 adolescents (male, N = 11; female, N = 1) were randomly selected for evaluation of current psychiatric diagnoses. Structured interviews used were K-SADS-PL-K for children and SCID-IV for adolescents. Data were collected and interviews were conducted from August 2003 through October 2004. Results In the child group, 7 were diagnosed with attention-deficit/hyperactivity disorder (ADHD) not otherwise specified including those with subthreshold levels. Mean DuPaul's ADHD Rating Scale scores were more than 20% higher than the mean in Korean children for 6 subjects. In the adolescent group, 3 subjects had major depressive disorder, 1 had schizophrenia, and 1 had obsessive-compulsive disorder. Conclusion By structured interview, we found that Internet-addicted subjects had various comorbid psychiatric disorders. The most closely related comorbidities differ with age. Though we can not conclude that Internet addiction is a cause or consequence of these disorders, clinicians must consider the possibility of age-specific comorbid psychiatric disorders in cases of Internet addiction.

The neurobiology of addiction: a neuroadaptational view relevant for diagnosis.

Abstract: AIMS: The purpose of this review is to provide a synthesis of our knowledge of the neurobiological bases of addiction relevant for the diagnosis of addiction. METHODS: A heuristic framework of neuroadaptive changes within key brain neurocircuitry responsible for different stages of the addiction cycle is outlined and linked to human studies to provide important future translational links for diagnosis. RESULTS: Animal studies have revealed dysregulation of specific neurochemical mechanisms (dopamine, opioid peptides) in the brain reward systems and recruitment of brain stress systems (corticotropin-releasing factor) during the development of dependence that convey vulnerability to relapse. Animal studies have implicated the prefrontal cortex and basolateral amygdala in drug- and cue-induced relapse, respectively, and the brain stress systems in stress-induced relapse. Genetic studies suggest roles for the genes encoding the neurochemical elements involved in both the brain reward and stress systems in the vulnerability to addiction, and molecular studies have identified transduction and transcription factors that may mediate dependence-induced reward dysregulation. Human imaging studies reveal similar neurocircuits involved in acute intoxication, chronic drug dependence and vulnerability to relapse. CONCLUSIONS: Major neurobiological changes in substance abuse disorders common to human and animal studies relevant for diagnosis include a compromised reward system, overactivated brain stress systems and compromised orbitofrontal/prefrontal cortex function. No biological markers of substance abuse disorders currently exist, but there are many promising neurobiological features of substance abuse disorders that will eventually aid in the specific diagnoses of substance use, misuse and dependence.

Neurobiology of addiction. Toward the development of new therapies.

Abstract: Drug addiction is a chronic relapsing brain disorder characterized by neurobiological changes that lead to a compulsion to take a drug with loss of control over drug intake. The hypothesis outlined here is that knowledge of the neurochemical systems involved in the transition from drug use to the compulsive use of addiction will provide the rational basis for development of pharmacotherapies for drug addiction. Much evidence has been obtained in identifying the midbrain-basal forebrain neural elements involved in the positive reinforcing effects of drugs of abuse and more recently in the neural elements involved in the negative reinforcement associated with drug addiction. Key elements for the acute reinforcing effects of drugs of abuse include a macrostructure in the basal forebrain called the extended amygdala that contains parts of the nucleus accumbens and amgydala and involves key neurotransmitters such as dopamine, opioid peptides, serotonin, GABA, and glutamate. Withdrawal from drugs of abuse is associated with subjective symptoms of negative affect, such as dysphoria, depression, irritability and anxiety, and dysregulation of brain reward systems involving some of the same neurochemical systems implicated in the acute reinforcing effects of drugs of abuse. In addition, acute withdrawal is accompanied by recruitment of the brain stress neurotransmitter system, corticotropin-releasing factor. Animal models of craving involve not only conditioning models but also models of excessive drug intake during prolonged abstinence, post-acute withdrawal, that may reflect continued dysregulation of drug reinforcement that could lead to vulnerability to relapse and represent an important focus for pharmacotherapy. Such changes have been hypothesized to involve a change in set point for drug reward that may represent an allostatic state contributing to vulnerability to relapse and re-entry into the addiction cycle. Elucidation of the specific neuropharmacological changes contributing to this prolonged functional dysregulation will be the challenge of future research on the neurobiology of drug addiction.

The neurobiology of substance and behavioral addictions.

Abstract: Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.

Implicit Cognition and Addiction

Abstract: Extensive recent research has begun to unravel the more implicit or automatic cognitive mechanisms in addiction. This effort has increased our understanding of some of the perplexing characteristics of addictive behaviors. The problem, often, is not that substance abusers do not understand that the disadvantages of continued use outweigh the advantages; rather, they have difficulty resisting their automatically triggered impulses to use their substance of abuse. Existing interventions may help to moderate these impulses. In addition, new techniques aimed at directly modifying implicit cognitive processes in substance abuse are being developed.

Tridimensional personality of adolescents with internet addiction and substance use experience.

Abstract: Objective:This study aimed to examine the differences in personality characteristics between adolescents with and without Internet addiction and substance use experience as defined by the Tridimens...

Methadone‐Related Opioid Agonist Pharmacotherapy for Heroin Addiction: History, Recent Molecular and Neurochemical Research and Future in Mainstream Medicine

Abstract: In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and persistence of, as well as relapse to, use of addictive drugs.

Genetic and environmental influences on the development of alcoholism: resilience vs. risk.

Abstract: : The physiological changes of adolescence may promote risk-taking behaviors, including binge drinking. Approximately 40% of alcoholics were already drinking heavily in late adolescence. Most cases of alcoholism are established by the age of 30 years with the peak prevalence at 18–23 years of age. Therefore the key time frame for the development, and prevention, of alcoholism lies in adolescence and young adulthood. Severe childhood stressors have been associated with increased vulnerability to addiction, however, not all stress-exposed children go on to develop alcoholism. Origins of resilience can be both genetic (variation in alcohol-metabolizing genes, increased susceptibility to alcohol's sedative effects) and environmental (lack of alcohol availability, positive peer and parental support). Genetic vulnerability is likely to be conferred by multiple genes of small to modest effects, possibly only apparent in gene–environment interactions. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. In addition, a common Met158 variant in the catechol-O-methyltransferase (COMT) gene can confer both risk and resilience to alcoholism in different drinking environments. It is likely that a complex mix of gene(s)—environment(s) interactions underlie addiction vulnerability and development. Risk–resilience factors can best be determined in longitudinal studies, preferably starting during pregnancy. This kind of research is important for planning future measures to prevent harmful drinking in adolescence.