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[Addiction characteristics as prognostic factors in opiate dependence treated with naltrexone].

INTRODUCTION: Addiction characteristics as prognostic factors in opiate dependence treatment were studied. Thus, several factors related to previous opiate consumption record were considered (current heroin route, amount of heroin, onset age of heroin consumption, time of heroin consumption, other drug consumption record). OBJECTIVE: To establish the prognostic value of addiction characteristics in a naltrexone program for opiate dependence. METHODS: To achieve this objective, an observational, retrospective study was designed with a design of a treatment group with no control group. 945 subjects diagnosed of opiate dependence who were consecutively hospitalized voluntarily in the naltrexone program of the Hospital Ramon y Cajal of Madrid during 1991-1995 form a part of the study population. Descriptive and survival techniques were used to analyze the data. RESULTS: Previous intravenous heroin route, chronic heroin consumption record, onset age of heroin use younger than 17 or older than 25, and other drug consumption especially benzodiazepine and also cocaine provide a prognostic value for a worse outcome. High quantities of heroin consumption also tend to be associated with a poorer evolution. CONCLUSIONS: Several addiction characteristics (current previous route, onset age of heroin consumption, quantity of heroin consumption, time of heroin consumption, other drug consumption) have a prognostic value for treatment evolution. Further studies are necessary to provide a more complete knowledge of addiction characteristics as prognosis factors in opiate dependence treatment.

Adolescent↗

Imbalance between drug and non-drug reward availability: a major risk factor for addiction.

Laboratory animals self-administer most, though not all, drugs of abuse. Recent evidence shows that with increased drug availability, most laboratory rats develop all the major behavioral signs of addiction, including: 1) drug intake escalation, 2) increased motivation for the drug, 3) difficulty to abstain, 4) decreased reward function, and 5) inflexible drug use. The large prevalence of addicted rats may suggest that they are particularly vulnerable to develop compulsive drug use. I review evidence showing that this apparent vulnerability results in large part from the lack of positive (i.e., alternative non-drug rewards) and negative (i.e., costs) incentives capable of turning animals away from the pursuit of drugs. In particular, most animals seem to take drugs and eventually become addicted, not because drugs are intrinsically addictive, but more likely because drugs are the only significant sources of reward available in the laboratory. Laboratory animals would therefore represent more of a model of high-risk human groups than of the general population. Consequently, they should be more suited for searching factors that protect from, rather than predispose to, drug addiction. Reconsidering the environmental background of drug self-administration experiments in laboratory animals raises intriguing implications for understanding the initial demand for drug consumption and the transition to drug addiction, and for extrapolation from laboratory animals to humans.

Animals↗

D1-receptor drugs and cocaine-seeking behavior: investigation of receptor mediation and behavioral disruption in rats.

RATIONALE: Dopamine D1-receptor antagonists and agonists both attenuate cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains unclear whether these effects are D1-receptor mediated. OBJECTIVES: The present study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether behavioral disruption is involved in these effects. METHODS: Rats trained to press a lever for cocaine reinforcement with light and tone cues paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus complex was available). After responding diminished, the effects of the D1 antagonist on the dose-response functions of the D1 agonist for reinstatement of cocaine-seeking behavior by response-contingent cue presentations or cocaine priming were examined. A separate experiment assessed the effects of the agonist on the dose-response function of the antagonist for cue reinstatement. Stereotyped behavior and activity were also measured during each test session. RESULTS: The attenuating effects of SKF-81297 on cocaine-seeking behavior during cocaine-primed reinstatement were reversed by co-administration of SCH-23390. However, no evidence for reversal of the attenuation during cue reinstatement was found even though agonist-induced stereotypy and antagonist-induced hypoactivity were reversed by co-administration of the two drugs during the same test session. CONCLUSIONS: The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.

Animals↗

Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects.

Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens. But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine. Addicts showed reduced dopamine release in the striatum, the brain region where the nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.

Adult↗

Behavioral risk factors and human immunodeficiency virus (HIV) prevalence among intravenous drug users in Puerto Rico.

This study reports on four empirical models likely to contribute to understanding the behaviors linked with human immunodeficiency virus (HIV) among intravenous drug users. The sample comprises 1,637 intravenous drug users recruited between May 1989 and June 1990 in San Juan, Puerto Rico. Adjusting for sociodemographics, four logistic regression models were constructed to assess the association of risk behaviors with HIV seropositivity. In model 1, the variables found to be significantly associated with HIV seropositivity were injecting four times a day, injection as the only route of consuming drugs, and years of injection. In model 2, the only risk behavior significantly associated with HIV seropositivity was injecting drugs in shooting galleries. In model 3, all sex risk variables failed to meet the adjusted level of significance. In model 4, pneumonia, hepatitis, and syphilis were significantly linked with HIV infection. In order to assess the individual effects of the significant variables in each one of the four models, a logistic regression analysis was performed simultaneously controlling for all of the variables. After adjustment for the Bonferroni correction, age group 25-34 years, injection as the only route of using drugs, number of years of injection, and syphilis were the only significant variables remaining.

Age Factors↗

Characteristics of problem gambling in a Canadian context: a preliminary study using a DSM-IV-based questionnaire.

OBJECTIVE: To develop a self-report instrument to assess diagnostic criteria and associated features of pathological gambling in order to learn more about the characteristics of individuals who seek treatment for gambling problems in a Canadian setting. METHOD: Fifty-seven adults seeking treatment for gambling problems at the Addictions Foundation of Manitoba were assessed. RESULTS: There was substantial variation in the endorsement of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms. Lying to family members or friends and "chasing" previous gambling losses were frequently reported, while more serious consequences (for example, relationship breakup, job losses) were less frequent. DSM-IV ratings were correlated (r = 0.59) with the South Oaks Gambling Screen. Many individuals reported gambling as a way to alleviate dysphoric mood, and 30% reported receiving mental health services in the past. Approximately 50% reported suicidal ideation, although recent suicide attempts were not common. CONCLUSION: These preliminary results of Canadian adults seeking treatment for gambling problems suggest a somewhat different profile from many United States studies, which often rely on older male pathological gamblers. More systematic investigation of the presence of major depression and other psychiatric disorders is warranted. Consistent with demographic data collected at the Addictions Foundation of Manitoba, it appears that video lottery terminals play a major role in the type of problem gambling experience seen in Canadian settings.

Adult↗

Cannabinoids and reward: interactions with the opioid system.

There is currently substantial evidence that Cannabis sativa derivates act on brain reward in a way very similar to other drugs of abuse and exert numerous pharmacological effects through their interaction with various neurotransmitters and neuromodulators. Among them, the endogenous opioids seem to play an important role in modulating the addictive properties of cannabinoids. Given the plethora of research activity on such a topic, this brief review is necessarily focused on cannabinoid/opioid interaction in reward-related events and restricted to the recent literature. Recent findings from our and other laboratories concerning cannabinoid reinforcing effects as revealed by behavioral animal models of addiction are here summarized. Evidence is then provided demonstrating a functional cross-talk between the cannabinoid and opioid systems in the mutual modulation of the addictive behavior; accordingly, very recent data from transgenic mice lacking either the cannabinoid CB1 or opioid receptors are also presented. Finally, the role of the endogenous cannabinoid system in relapse to opioids is investigated by means of extinction/reinstatement animal models following a period, even prolonged, of drug abstinence. Altogether, the reviewed studies provided a better understanding of the neurobiological mechanisms involved in cannabinoid actions and revealed a bidirectional interaction between the endogenous cannabinoid and opioid systems in reward that extends to central mechanisms underlying relapsing phenomena. Challenges for the future involve elucidation of the neuroanatomical substrates of cannabinoids action, even in light of the therapeutic potential of these compounds.

Animals↗

Are some children and adolescents in Louisiana addicted to tobacco? The Bogalusa Heart Study.

The US Surgeon General concluded that nicotine in tobacco is addictive. Few studies actually explore the nature of nicotine addiction in youth. In Bogalusa, Louisiana, surveys to assess tobacco usage were administered to 11-18 year olds according to a standardized protocol developed in 1976. In 1991-92, a special substudy explored the nature of nicotine addiction in youth. Overall, 14.7% were current cigarette smokers; however, as many as 44.3% of white females, ages 15-16, indicated they were current smokers. Twelve percent of the surveyed population purchased single cigarettes. Thirty-two percent of current smokers reported they smoke a cigarette within 30 minutes after waking up. Thirty-one percent said they would find it difficult to refrain from smoking in places where it is forbidden. And 23% said they continue to smoke cigarettes when they are ill. From the findings in this study, it is clear there are young people who are addicted to tobacco. It is important to develop prevention of tobacco usage in childhood. Those who are addicted require a carefully developed intervention program to assist them with their cessation efforts.

Adolescent↗

Neurochemical characterization of individual vulnerability to addictive drugs in rats.

Rats exposed to a low-light, low-noise, novel environment exhibit differences in individual locomotor response to the novelty stressor. The categorization of rats in a locomotor screening procedure as low- (LR) or high-responders (HR), where LRs are in the low locomotor range while HRs belong to the high locomotor range, is significant in that HRs show higher activity in mesencephalic dopaminergic projection neurons, and also show a higher propensity to self-administer psychostimulants and other drugs of abuse compared with LRs. In this study, we examined the neurobiological basis of dopaminergic hyperactivity by comparing in HRs and LRs the steady-state differences in regulatory inputs to mesencephalic (substantia nigra and ventral tegmental area: VTA) dopaminergic neurons. In particular, using in situ hybridization, we studied levels of mRNA for tyrosine hydroxylase (TH) and cholecystokinin (CCK) in the mesencephalon, and for preprodynorphin (DYN), preproenkephalin (PPE), and preprotachykinin (PPT) in the striatum and nucleus accumbens (Acb). We also evaluated TH levels by radioimmunocytochemistry (TH-RIC) in striatal, accumbal and mesencephalic regions. HRs versus LRs had lower levels of neurochemicals belonging to the intrinsic inhibitory input to dopaminergic neurons in the VTA, e.g. lower TH-RIC (-25%) and CCK-mRNA (-48%). In contrast, HRs showed higher levels of parameters belonging to extrinsic facilitating inputs, e.g. higher PPE-mRNA (+37%). In addition, HRs had higher DYN-mRNA in Acb (+61%), which has been shown to be positively correlated with higher dopaminergic activity. These results enhance our knowledge of the neurobiological correlates of individual rats' propensities to develop drug-intake and provide some putative mechanisms for the dopaminergic hyperactivity that characterizes drug-prone animals.

Animals↗

Preventing fetal alcohol exposure: a cognitive behavioral approach.

Fetal alcohol exposure is a serious social and public health problem. However, most prevention programs in this area are solely informational. Important gaps in both understanding processes which underlie alcohol consumption during pregnancy and in the design of interventions to prevent fetal alcohol exposure are discussed. We argue that an important group missed by current interventions are women for whom abstinence is difficult, but who are not physically addicted. Cognitive behavioral interventions are proposed as appropriate for this target group. Recommendations for future directions in the area of fetal alcohol exposure are discussed.

Adult↗

Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction.

An understanding of drug addiction requires knowledge of the effective drug concentrations to which receptors in the nervous system are exposed. It has often been thought that smoking of abused substances such as nicotine or cocaine produces much higher drug concentrations in the arterial blood than those achieved following any other route of administration. However, to date no studies have sampled arterial blood following cigarette smoking with the rapidity necessary to evaluate this hypothesis. We measured arterial plasma nicotine concentrations in samples collected every 5 s from 13 cigarette smokers during cigarette smoking and during administration of nicotine by intravenous injections. Our results show that, for both routes of administration, concentrations of nicotine in arterial blood were more than 10 times lower than expected. Thus, the delivery of nicotine into arterial blood is substantially slower than would be predicted if nicotine were absorbed as rapidly as has generally been assumed. A plausible explanation of these results is that lung uptake of nicotine considerably slows the entry of nicotine into the systemic circulation, as has been shown for other amines. These results have significant implications for theories of addiction to nicotine as well as other drugs such as cocaine that may be subject to binding by lung tissue.

Adult↗

Addiction: a disease of volition caused by a cognitive impairment.

The common etiology of substance and behavioural addictions is one that suggests faulty volition caused by a cognitive impairment. A cognitive impairment that minimizes the recall of the negative effects of the addictive behaviour is viewed as necessary and causal to all addictions. The proposed definition for addiction clarifies the confusion associated with addictive disorders, explains the many variable presentations, and provides an explanation of comorbidity and treatment outcomes. In addition, this paper suggests why this process has not been previously identified.

Attitude↗

Nicotine dependence in women.

Cigarette smoking is the most preventable cause of death in the United States, accounting for the deaths of approximately 140,000 women annually. Despite the known health risks, women continue to begin and continue smoking at high rates. Like other addictive drugs, nicotine becomes reinforcing with repeated use, induces euphoric sensations, and is self-administered. Tolerance to nicotine's effects develops rapidly and leads to increased use. Reducing or suppressing tobacco consumption produces a withdrawal syndrome characterized by irritability, difficulty concentrating, cognitive impairments, and weight gain. These withdrawal symptoms, along with other factors, lead to relapse rates comparable to those following cessation from other addictive drugs. This review article discusses the pathogenesis of nicotine addiction compared to other addictive substances such as cocaine and heroin with an effort to provide comparative data for men and women.

Adolescent↗

A cross-cultural study of gambling behaviour among adolescents.

This study investigated whether the prevalence of weekly and problem gambling among youth varied according to cultural affiliation. A convenience sample of 1,265 Quebec high school students aged 12-18 was divided into three linguistic groupings: Anglophone (English), Francophone (French), and Allophone (other). Results revealed that the Allophone grouping contained the highest proportion of youth who gambled on a weekly basis and who reported gambling problems, followed by the Anglophone, and finally the Francophone groupings. Acculturation difficulties were associated with problem gambling. Few meaningful between-group differences were found with respect to factors related to problem gambling (i.e., comorbidity with other risk factors, coping, family functioning and resiliency). The results are discussed with respect to the influence of cultural background on gambling behavior.

Adolescent↗

Clinical and translational research: introduction to the special issue.

This special issue represents an effort by the journal Experimental and Clinical Psychopharmacology to emphasize its interdisciplinary mission by encouraging the writing of articles on clinical research and the interchange between basic and clinical research on mental illness and the addictions. This special issue opens with a commentary from A. I. Leshner (2002), retired director of the National Institute on Drug Abuse, which emphasizes the importance of translating research findings into clinical practice. Four review articles and 12 original research reports provide a broad sampling of contemporary clinical research, including behavioral therapy, pharmacotherapy, psychiatric comorbidity, and special populations, and also illustrate linkages between clinical research and basic fields of inquiry, including behavioral theory, neuropsychology, neuropharmacology, and statistics.

Behavior, Addictive↗

Clinical uses of naltrexone: a review of the evidence.

The implication of the opioidergic system in the pathogenesis of various substance use disorders has led to renewed interest in expanding the clinical uses of naltrexone, an opioid antagonist. This article examines the evidence for the efficacy of naltrexone in a variety of substance use and psychiatric disorders. Naltrexone can be an effective treatment for alcohol and opioid dependence if issues of compliance are adequately addressed. Thus far, no definitive role has been found for naltrexone in the treatment of other psychiatric disorders. Further research needs to be done in self-injurious behavior, gambling, cocaine, and nicotine dependence.

Alcoholism↗