Добірка наукової літератури з теми "Choice, Drugs, Abstinence, Neuroscience"

AbstractHeyman's model, paradoxically, predicts that whereas a maximizing approach to drug choice will prevent escalation of drug use it will never yield complete abstinence. We suggest an alternative model that overcomes this difficulty by focusing on changes in drug tolerance. A small modification allows maximization to predict either abstinence or moderation (e.g., social drinking).

AbstractScience has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.

Objectives After initial promising research into acupuncture for withdrawal from drugs of dependence, two large negative trials were published in 2002 and the use of acupuncture in US rehabilitation facilities fell. However, subsequently it has been maintained, despite a lack of support from systematic reviews. This suggests a mismatch between research and clinical observation, which could be due to the acupuncture technique used, choice of controls or outcome measures. This study aims to explore the mismatch. Methods An exploratory review of all 48 clinical trials on alcohol, cocaine, nicotine or opioid dependence included in current reviews. Results Studies with sham controls (that could be active) were less likely to be positive (33%) than those with non-acupuncture controls (75%). Positive results were more likely when measuring craving (56%) or withdrawal symptoms (58%) than when measuring abstinence (31%) or attrition (31%). Three treatment variables appeared to be associated with positive results: (1) body acupuncture, used in 13 studies, was associated with positive outcomes for craving and withdrawal symptoms but not for abstinence or attrition; (2) electroacupuncture, used in seven studies, was associated with positive results with all four outcomes; and (3) bilateral needling in 20 studies was associated with effects on abstinence, craving and withdrawal symptoms. Conclusions The current evidence suggests that acupuncture may have some effects on drug dependence that have been missed because of choice of outcome in many previous studies, and future studies should use outcomes suggested by clinical experience. Body points and electroacupuncture, used in the original clinical observation, justify further research.

Introduction Patients with comorbid cocaine and alcohol dependence have a worse prognosis with lack of adherence to follow-up and treatment, frequent psychosocial problems, and higher rates of relapse [1]. Concurrent use of both substances produces cocaethylene, which is associated with more toxicity than cocaine alone [2]. Objectives To determine the efficacy of disulfiram compared to nalmefene in the treatment of comorbid cocaine and alcohol use. Methods A quasi-experimental open study was designed on 41 outpatients, with a follow-up of at least 1 year at the Mental Health Unit, aged between 18 and 65 years, diagnosed with cocaine and alcohol dependence (ICD-10). A minimum simultaneous weekly consumption of 2 grams of cocaine and 12 SD (Standard Drink) of alcohol during the month before, described by self-records was established. Treatment with oral disulfiram 250mg/day was assigned to 21 patients, and with oral nalmefene 18mg/day to 20 individuals. Observation period was for 6 months. Urinalysis and alcohol breath test were carried out twice a week. Abstinence was defined by obtaining negative results for at least 4 consecutive weeks. Statistical analysis were performed using SPSS v21.0 (significance p<0.05). Results 61.9% of patients treated with disulfiram achieved a minimum of 4 consecutive weeks of abstinence from cocaine and alcohol, compared to 40% in the nalmefene group (χ²=1.188; gl=1; p=0.276). There were no significant differences. Conclusions Disulfiram or nalmefene monotherapy seems clinically ineffective or insufficient in reducing the combined use of cocaine and alcohol. Further research is needed to assess the effect of both drugs simultaneously. Disclosure No significant relationships.

This section discusses the regulation of “lifestyle risks”, a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence – consumption – abuse – addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.

This section discusses the regulation of “lifestyle risks”, a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence – consumption – abuse – addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.

AbstractThis section discusses the regulation of “lifestyle risks” a term that can apply to both substances and behaviours. Lifestyle risks take place along the line of “abstinence - consumption - abuse - addiction”. This can concern substances such as food, alcohol or drugs, as well as behaviours such as gambling or sports. The section also addresses the question of the appropriate point of equilibrium between free choice and state intervention (regulation), as well as the question of when risks can be considered to be acceptable or tolerable. In line with the interdisciplinary scope of the journal, the section aims at updating readers on both the regulatory and the scientific developments in the field. It analyses legislative initiatives and judicial decisions and at the same time it provides insight into recent empirical studies on lifestyle risks.

Relapse to drug use after prolonged abstinence is the key impediment to successful treatment of drug addiction (Wikler, 1973; Jaffe, 1990). It has been known for many years that during abstinence exposure to cues and contexts previously associated with the rewarding effects of drugs can provoke relapse to drug use (Wikler, 1973; O'Brien et al., 1992). Relapse to drug use during abstinence has been the focus of preclinical studies for over 30 years (Stewart and de Wit, 1987). The abstinence period preceding relapse testing in studies using animal models is typically experimenter-imposed or forced; this is achieved either by removal of the laboratory animal from the drug self-administration environment or through extinction training (Shalev et al., 2002; Shaham et al., 2003). However, in humans abstinence is often voluntary due to either the negative consequences of chronic drug use or the presence of alternative non-drug rewards (Katz and Higgins, 2003; Epstein et al., 2006) Based on these considerations, the aim of my thesis was twofold: (1) to develop an animal model of relapse to drug seeking, which incorporates some aspects of the voluntary abstinence, and (2) to explore the neuronal mechanisms underlying this form of relapse. Based on recent studies of Ahmed and colleagues (Lenoir et al., 2007; Cantin et al., 2010; Ahmed et al., 2013b), we first investigated how to achieve voluntary abstinence in rats. We found that by using a mutually exclusive discrete choice procedure, rats voluntarily abstain from methamphetamine because of the presence of a non-drug reward (high carbohydrate palatable food pellets). Indeed, independently of the daily drug access conditions and the withdrawal period, the rats strongly preferred palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage (Caprioli et al., 2015a). Subsequently, we used this choice procedure to develop a rat model of incubation of drug craving in which abstinence is achieved voluntarily (Caprioli et al., 2015b). In this model, we first train rats with free access to ‘animal facility’ nutritionally-balanced food to self-administer palatable food pellets and then to self-administer intravenous methamphetamine. Next, we assess cue-induced methamphetamine seeking in extinctions test during early (day 1) and late (day 14 or 21) abstinence. Between tests, the rats undergo voluntary abstinence in their drug environment; this is achieved via a discrete choice procedure between methamphetamine and palatable food. In this model, cue-induced methamphetamine seeking is higher after 21 abstinence days than after 1 day (incubation of methamphetamine craving). Using this animal model we showed a robust incubation of methamphetamine craving after prolonged periods of choice-based voluntary abstinence (Caprioli et al., 2015b). This effect was observed under two different self-administration procedures that are widely used to model drug addiction: extended daily access drug self-administration procedure (Ahmed and Koob, 1998; Ahmed, 2011) and a long-term training procedure used to identify addicted rats based on DSM-IV criteria (Deroche-Gamonet et al., 2004; Piazza and Deroche-Gamonet, 2013) A question that derives from our study is whether similar or different neurobiological mechanisms control incubation of methamphetamine craving after voluntary versus forced abstinence. For this purpose, we used AZD8529, a new and highly selective positive allosteric modulator (PAM) of metabotropic glutamate receptor 2 (mGluR2) (Justinova et al., 2015). AZD8529 had a similar effect on incubated cue-induced methamphetamine seeking after voluntary and forced abstinence, suggesting mechanistic similarities (Caprioli et al., 2015b). An important question moving forward was which neural mechanisms are critical for the relapse triggered by drug-associated cues after voluntary abstinence. To address this question, we used the neuronal activity marker Fos (Curran and Morgan, 1995) and local dopamine receptor blockade and demonstrated a critical role of central amygdala (CeA) in cue-induced methamphetamine seeking after voluntary abstinence. Moreover, in our follow-up tracing study we used the retrograde tracer cholera toxin subunit b (CTb) in combination with Fos and identified a selective activation of the anterior insula (AI) to CeA projection in this form of relapse. These results are consistent with human imaging studies showing that cue-induced cocaine craving is associated with insula and amygdala activation (Grant et al., 1996; Garavan et al., 2000) and that cue-induced methamphetamine craving is associated with insula activation (Yin et al., 2012).
Relapse to drug use after prolonged abstinence is the key impediment to successful treatment of drug addiction (Wikler, 1973; Jaffe, 1990). It has been known for many years that during abstinence exposure to cues and contexts previously associated with the rewarding effects of drugs can provoke relapse to drug use (Wikler, 1973; O'Brien et al., 1992). Relapse to drug use during abstinence has been the focus of preclinical studies for over 30 years (Stewart and de Wit, 1987). The abstinence period preceding relapse testing in studies using animal models is typically experimenter-imposed or forced; this is achieved either by removal of the laboratory animal from the drug self-administration environment or through extinction training (Shalev et al., 2002; Shaham et al., 2003). However, in humans abstinence is often voluntary due to either the negative consequences of chronic drug use or the presence of alternative non-drug rewards (Katz and Higgins, 2003; Epstein et al., 2006) Based on these considerations, the aim of my thesis was twofold: (1) to develop an animal model of relapse to drug seeking, which incorporates some aspects of the voluntary abstinence, and (2) to explore the neuronal mechanisms underlying this form of relapse. Based on recent studies of Ahmed and colleagues (Lenoir et al., 2007; Cantin et al., 2010; Ahmed et al., 2013b), we first investigated how to achieve voluntary abstinence in rats. We found that by using a mutually exclusive discrete choice procedure, rats voluntarily abstain from methamphetamine because of the presence of a non-drug reward (high carbohydrate palatable food pellets). Indeed, independently of the daily drug access conditions and the withdrawal period, the rats strongly preferred palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage (Caprioli et al., 2015a). Subsequently, we used this choice procedure to develop a rat model of incubation of drug craving in which abstinence is achieved voluntarily (Caprioli et al., 2015b). In this model, we first train rats with free access to ‘animal facility’ nutritionally-balanced food to self-administer palatable food pellets and then to self-administer intravenous methamphetamine. Next, we assess cue-induced methamphetamine seeking in extinctions test during early (day 1) and late (day 14 or 21) abstinence. Between tests, the rats undergo voluntary abstinence in their drug environment; this is achieved via a discrete choice procedure between methamphetamine and palatable food. In this model, cue-induced methamphetamine seeking is higher after 21 abstinence days than after 1 day (incubation of methamphetamine craving). Using this animal model we showed a robust incubation of methamphetamine craving after prolonged periods of choice-based voluntary abstinence (Caprioli et al., 2015b). This effect was observed under two different self-administration procedures that are widely used to model drug addiction: extended daily access drug self-administration procedure (Ahmed and Koob, 1998; Ahmed, 2011) and a long-term training procedure used to identify addicted rats based on DSM-IV criteria (Deroche-Gamonet et al., 2004; Piazza and Deroche-Gamonet, 2013) A question that derives from our study is whether similar or different neurobiological mechanisms control incubation of methamphetamine craving after voluntary versus forced abstinence. For this purpose, we used AZD8529, a new and highly selective positive allosteric modulator (PAM) of metabotropic glutamate receptor 2 (mGluR2) (Justinova et al., 2015). AZD8529 had a similar effect on incubated cue-induced methamphetamine seeking after voluntary and forced abstinence, suggesting mechanistic similarities (Caprioli et al., 2015b). An important question moving forward was which neural mechanisms are critical for the relapse triggered by drug-associated cues after voluntary abstinence. To address this question, we used the neuronal activity marker Fos (Curran and Morgan, 1995) and local dopamine receptor blockade and demonstrated a critical role of central amygdala (CeA) in cue-induced methamphetamine seeking after voluntary abstinence. Moreover, in our follow-up tracing study we used the retrograde tracer cholera toxin subunit b (CTb) in combination with Fos and identified a selective activation of the anterior insula (AI) to CeA projection in this form of relapse. These results are consistent with human imaging studies showing that cue-induced cocaine craving is associated with insula and amygdala activation (Grant et al., 1996; Garavan et al., 2000) and that cue-induced methamphetamine craving is associated with insula activation (Yin et al., 2012).