Pharmacological options for management of opioid dependence

Methadone is currently the only opioid available for the pharmacotherapy of opioid dependence. Cross-tolerance between methadone and other opioids constitutes the pharmacological basis for substitution and attenuating the effects of illicit opioid use. However, these principles limit the utility of methadone. Potential alternative opioids include long-acting partial agonists such as buprenorphine and pure antagonists such as naltrexone. Buprenorphine is an alternative to methadone with intermediate intrinsic efficacy. It has a large margin of safety, yet displays some agonist actions similar to methadone. It has greater potential than methadone to safely and effectively block the actions of illicit opioids. Naltrexone is a safe, convenient opioid-antagonist for use following detoxification from opioid agonists. Its main use is to block the actions of other opioids, thereby attenuating or eliminating illicit use during treatment. However, it is poorly accepted by many clients, limiting its application to a sub-group who are highly motivated to detoxify. The distinct pharmacological properties of these opioids can overcome some of the drawbacks of methadone, but other limitations may emerge. Non-opioid adjuncts such as alpha2-adrenoceptor agonists can also have a role during detoxification. These drugs might be of use for specific groups of opioid users, providing therapists with the flexibility to tailor pharmacotherapy to the individual needs of clients.     

Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal

The activity of mesolimbic dopaminergic neurons was investigated in rats at various times after a chronic regimen of morphine, which produced, upon suspension, a marked somatic withdrawal syndrome. Single-cell extracellular recording techniques, coupled with antidromic identification from the nucleus accumbens, were used to monitor neuronal activity while behavioural observations allowed quantification of the somatic signs of morphine withdrawal. Temporal correlation of electrophysiological indices, such as firing rate and burst firing, with scores obtained through behavioural assessments proved negative, in that somatic signs were pronounced at 24 h after suspension of treatment and then subsided to control values at 72 h after the last morphine injection. In contrast, the firing rate and burst firing of mesolimbic dopaminergic neurons were found to be reduced at 1, 3 and 7 days after morphine withdrawal. After 14 drug-free days, electrophysiological analysis revealed an apparent normalization of various parameters. However, at this time, intravenous administration of morphine produced an increment of electrical activity which was significantly higher than that obtained in control (saline treated) rats. Further, administration of the opiate antagonist naltrexone, administered without prior morphine, at 3, 7 and 14 days after the last morphine administration, failed to alter dopaminergic neuronal activity. The results indicate: (i) that the activity of mesolimbic dopaminergic neurons remains reduced well after somatic signs of withdrawal have disappeared; (ii) after 14 days of withdrawal, the augmented magnitude of the electrophysiological response to exogenous morphine suggests an increased sensitivity of opiate receptors; and (iii) the lack of relationship between dopaminergic activity and somatic signs of withdrawal corroborates the notion that dopaminergic activity in the mesolimbic system does not participate in the neurobiological mechanisms responsible for somatic withdrawal. The present results may be relevant to the phenomenon of drug addiction in humans and consequent relapse after drug-free periods.     

Running and cocaine both upregulate dynorphin mRNA in medial caudate putamen

Physical activities such as long-distance running can be habit forming and associated with a sense of well-being to a degree that justifies comparison with drug-induced addictive behaviours. To understand molecular similarities and dissimilarities controlling these behaviours in humans we compared the effects of running in running wheels to the effects of chronic cocaine or morphine administration on mRNA levels in brain reward pathways in the inbred Fischer and Lewis rat strains. These strains are both inbred from the Sprague-Dawley strain; Lewis rats display a higher preference towards addictive drugs and running than do Fischer rats. After chronic cocaine or running a similar increase of dynorphin mRNA in medial caudate putamen was found in the Lewis rat, suggesting common neuronal adaptations in this brain region to both cocaine and running. Fischer and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after running, possibly reflecting the much higher degree of running by the Lewis strain as compared to the Fischer strain. Moreover, the running-induced upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist naloxone. We suggest that running increases dynorphin mRNA by a mechanism that involves endogenous opioids. The voluntary wheel-running model in rats might be used to study natural reward and compulsive behaviours and possibly also to screen candidate drugs for treatment of compulsive disorders.     

美沙酮合并丁丙诺啡和东莨菪碱脱毒治疗

目的：比较美沙酮脱毒疗程早期改用丁丙诺啡合并东莨若碱替代治疗与单用美沙酮替代治疗方法之优劣。方法：108例符合DSM—IV阿片类依赖的戒毒者随机分为试验组和对照组，试验组于美沙酮脱毒疗程早期(第四天)改用丁丙诺啡合并东莨若碱替代治疗，对照组则单用美沙酮替代治疗。采用《阿片类药物戒断症状量表》(owS)评定疗效。结果：试验组和对照组的脱毒率分别为94．4％和74％，有显著性差异(P＜0．01＝。owS量表总分在治疗d1—4无显著性差异(P＞0．05)；在治疗d5—8，试验组总分平稳下降，与对照组逐日比较有显著性差异(P＜0．05或P＜0．01＝；治疗药物停用48h后试验组症状未见波动，而对照组症状波动，owS总分两组间有显著性差异(P＜0．01＝。结论：美沙酮脱毒疗程早期改用丁丙诺啡合并东莨若碱替代治疗优于单用美沙酮，是快速脱毒、提高脱毒成功率的较好方法。     

The Role of Therapeutic Alliance in Network Therapy: A Family and Peer Support-Based Treatment for Cocaine Abuse

The therapeutic alliance is a well-studied construct factor that is important to outcome in many forms of individual therapy. Therapeutic alliance has been rarely studied in group therapy and results in addiction treatment have been mixed. In this paper, we studied the presence of a therapeutic alliance in Network Therapy: an approach that uses peer and family support in addiction treatment. Twenty-one participants undergoing Network Therapy for cocaine addiction were observed on videotape, and were rated on therapeutic alliance using the Working Alliance Inventory and the Penn Helping Alliance Rating Scale. Results showed a significant positive correlation between therapeutic alliance and outcome as measured by the percentage of cocaine-free urine toxicology screens and by eight consecutive cocaine-free urines.     

Assault,PTSD, Family Substance Use,and Depression as Risk Factors for Cigarette Use in Youth: Findings from the National Survey of Adolescents

A national household probability sample of 4,023 adolescents aged 12 to 17 years was surveyed by telephone via structured clinical interview to determine the impact of familial substance use, sexual and physical assault, witnessed violence, depression and posttraumatic stress disorder (PTSD) on risk of smoking. Results indicated that familial substance use increased risk of smoking only for boys and sexual assault or depression increased risk of smoking only for girls. Age, Caucasian ethnicity, and experiencing physical assault or witnessing violence elevated risk of current cigarette use for both genders. By contrast, PTSD per se was not associated with increased risk of smoking, after the effects of other variables were controlled.     

静脉药瘾者心内膜炎11例临床分析

目的探讨静脉药瘾并发感染性心内膜炎(infective endocarditis IE)的特征。方法回顾分析11例静脉药瘾并发IE的临床资料。结果静脉药瘾并发IE者多为青年男性,男女比例10∶1,平均年龄26岁,无基础心脏病。临床特点起病为发热,体温38~40℃,为不规则发热,全身乏力,面色苍白,咳嗽气促,合并肺感染(91%);血细菌培养阳性以金黄色葡萄球菌多见(45.3%);超声心动图显示右心系统感染(三尖瓣受累)最为常见(81%),其次二尖瓣(18%)。结论静脉药瘾并发IE者临床特征为发热、咳嗽、气促,心脏杂音,血细菌培养阳性合并肺感染,超声心动图检查对右心感染有重要价值。     

大学生网络成瘾及影响因素分析

目的：探讨大学生网络成瘾及其影响因素,了解网络对医学生带来的负效应,及早发现网络成瘾者,进一步采取干预措施.方法：于2005年2月到4月,对沈阳三所大学一年级至三年级的本科生采用统一的调查表,进行了不记名问卷调查.结果：在1 883名医学生中有1 642名学生上网,上网率87.2%,199名网络成瘾者,成瘾发生率为12.1%.网络成瘾发生有关的主要因素有学生性别、生源地、上网目的和对网恋的态度.结论：互联网的使用在医学生中已经普及,且对医学生已产生了的负面影响.对大学生开展有针对性的健康教育,培养良好的兴趣爱好,摆脱网瘾,达到促进健康的目的.     

网络成瘾少年家庭关怀及干预措施研究

目的探讨网络成瘾少年家庭关怀度并有针对性提出干预措施。方法对89例住院网络成瘾少年进行家庭关怀度指数问卷调查,并与普通在校学生进行对照。有针对性地运用认知行为治疗理论,利用“戒网课堂”、“戒网网吧”、“戒网同盟”、“戒网日记”、“戒网军训课”、“戒网旅游”等进行干预。结果95%的家长表示能与孩子面对面地进行有效沟通,孩子能主动面对父母讲出自己对父母的愧疚,向父母谈起自己的过去,并对父母表示感恩之心,与父母谈论有关网络方面的知识。结论家庭关怀及干预能提高住院网瘾少年家庭关怀度,提高认知水平。