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Ibogaine in the treatment of substance dependence. 伊博格因在药物依赖治疗中的应用。
Pub Date : 2013-03-01 DOI: 10.2174/15672050113109990001
Thomas Kingsley Brown

Ibogaine is a psychoactive alkaloid derived from Tabernanthe iboga, a plant used in initiatory rituals in West Central Africa. Largely because of ibogaine's status as a Schedule I substance in the U.S., the development of ibogaine's use in the treatment of drug addiction took place outside conventional clinical and medical settings. This article reviews the history of ibogaine's use in the treatment of drug addiction, and discusses progress made towards, and obstacles blocking, the establishment of controlled clinical trials of ibogaine's efficacy. Preclinical research has generally supported anecdotal claims that ibogaine attenuates withdrawal symptoms and reduces drug cravings. Concerns about ibogaine's safety, as well as a dearth of solid data from human studies, have hampered progress in its development as an approved medication. This article outlines major findings from preclinical studies, discusses concerns about ibogaine's safety, and details previous and ongoing research on ibogaine's use as an anti-addictive treatment for humans.

伊博格碱是一种精神活性生物碱,它是从西非中部的一种入会仪式中使用的植物Tabernanthe iboga中提取的。很大程度上是因为伊波加因在美国属于一级管制药物,所以伊波加因在药物成瘾治疗中的应用是在传统的临床和医疗环境之外发展起来的。本文回顾了伊博格因治疗药物成瘾的历史,并讨论了伊博格因疗效对照临床试验的进展和障碍。临床前研究普遍支持伊博加因减轻戒断症状和减少药物渴望的轶事说法。对伊博加因安全性的担忧,以及缺乏可靠的人体研究数据,阻碍了其作为一种批准药物的发展进程。本文概述了临床前研究的主要发现,讨论了对伊博格因安全性的担忧,并详细介绍了以前和正在进行的关于伊博格因用于人类抗成瘾治疗的研究。
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引用次数: 88
Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin. 研究经典致幻剂治疗酒精中毒的效果:原理、方法和目前的裸盖菇素研究。
Pub Date : 2013-03-01 DOI: 10.2174/15733998113099990002
Michael P Bogenschutz

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

经典致幻剂研究的最新进展,加上对旧文献的重新评估,重新引起了人们对这些药物可能的治疗应用的兴趣,特别是它们在成瘾治疗中的应用。本文将首先对裸盖菇素和麦角酸二乙胺(LSD)等经典致幻剂治疗成瘾的可能疗效提供直接和间接支持的研究文献进行简要综述。在为这一领域的临床研究提供了基本原理之后,我们讨论了使用经典致幻剂的临床试验中的设计问题,其中一些是该类药物所独有的。然后,我们讨论了这一研究领域的现状和未来随机试验的设计考虑。
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引用次数: 42
Cognitive function in ecstasy naive abstinent drug dependants and MDMA users. 摇头丸初次戒断药物依赖者和MDMA使用者的认知功能。
Pub Date : 2013-03-01 DOI: 10.2174/1874473711306010008
Adam Potter, Luke Downey, Con Stough

Introduction/aims: 'Hidden' symptoms, or subtle cognitive deficits and long-term changes in mood, have been linked to the recreational use of 3, 4-methylenedioxymethamphetamine/MDMA, and are notionally present in non-heavy polydrug users. This study assessed the cognitive functioning and mood profiles of clinically diagnosed drug dependents who had never consumed MDMA, recreational drug users that had previously consumed MDMA, with both groups having not consumed illicit drugs for 6-months, and a control group with limited illicit drug use and no MDMA usage in their past.

Methods: Cognitive functioning was assessed using the Cognitive Drug Research computerised cognitive assessment system and participants completed the Profile of Mood States and Beck Depression Inventory to assess their current mood and depression.

Results: Participants in the clinically diagnosed drug dependent group scored significantly worse on the 'Quality of Working Memory' cognitive factor score than both the MDMA and control group (F (2, 33) = 5.75, p = 0.007). The control and clinical groups also differed on depression scores (U [16] = 13.00, p = 0.016) and Tension/Anxiety scores (U [16] = 16.00, p = 0.034), with the clinical group scoring significantly higher in both cases. The MDMA group did not differ from the control group on the measures of cognition or mood.

Discussion/conclusions: These results suggest that despite a 6-month prolonged abstinence the cognitive deficits ostensibly caused by 'heavy' usage or the dependence on or abuse of illicit drugs are not reversed by abstinence.

介绍/目的:“隐性”症状,或微妙的认知缺陷和情绪的长期变化,与娱乐性使用3,4 -亚甲基二氧甲基苯丙胺/MDMA有关,并且在非重度多种药物使用者中理论上存在。本研究评估了临床诊断为从未服用过MDMA的药物依赖者和之前服用过MDMA的娱乐性药物使用者的认知功能和情绪特征,两组都有6个月没有服用非法药物,对照组有有限的非法药物使用,过去没有使用过MDMA。方法:采用认知药物研究计算机化认知评估系统对参与者的认知功能进行评估,并完成情绪状态量表和贝克抑郁量表来评估他们当前的情绪和抑郁状况。结果:临床诊断为药物依赖组的“工作记忆质量”认知因子得分明显低于MDMA组和对照组(F (2,33) = 5.75, p = 0.007)。对照组和临床组在抑郁评分(U [16] = 13.00, p = 0.016)和紧张/焦虑评分(U [16] = 16.00, p = 0.034)上也存在差异,临床组和对照组得分均显著高于对照组。在认知和情绪方面,服用MDMA的小组与对照组没有什么不同。讨论/结论:这些结果表明,尽管有6个月的长期戒断,但表面上由“大量”使用或依赖或滥用非法药物引起的认知缺陷并没有被戒断所逆转。
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引用次数: 9
Salvia divinorum: a psychopharmacological riddle and a mind-body prospect. 鼠尾草:一个心理药理学之谜和身心前景。
Pub Date : 2013-03-01 DOI: 10.2174/18744737112059990004
Jose-Luis Diaz

The multidisciplinary research on Salvia divinorum and its chemical principles is analyzed concerning whether the ethnobotany, phytochemistry, mental effects, and neuropharmacology of this sacred psychoactive plant and main principle clarify its experienced effects and divinatory uses. The scientific pursuit spans from the traditional practices, continues with the botanical identification, isolation of active molecules, characterization of mental and neural effects, possible therapeutic applications, and impinges upon the mind-body problem. The departure point is ethnopharmacology and therefore the traditional beliefs, ritual uses, and mental effects of this Mazatec sacred mint recorded during a 1973- 1983 field research project are described. A water potion of crushed leaves produced short-lasting light-headedness, dysphoria, tactile and proprioceptive sensations, a sense of depersonalization, amplified sound perception, and an increase visual and auditory imagery, but not actual hallucinations. Similar effects were described using questionnaires and are attributable to salvinorin A, but cannot be explained solely by its specific and potent brain kappa-opioid receptor agonist activity. Some requirements for a feasible classification and mechanism of action of consciousness-altering products are proposed and include the activation of neural networks comprising several neurochemical systems. Top-down analyses should be undertaken in order to characterize such neural networks and eventually allowing to explore the differential ethnic effects. As is the case for other consciousness-altering preparations, a careful and encompassing research on this plant and principle can be consequential to endeavors ranging from the mind-body problem, a better understanding of shamanic ecstasy, to the potential generation of analgesic, antidepressant, and drug-abuse attenuating products.

从民族植物学、植物化学、心理作用、神经药理学、主要原理等方面分析了丹参及其化学原理的多学科研究。科学的追求跨越了传统的实践,继续进行植物学鉴定,活性分子的分离,精神和神经效应的表征,可能的治疗应用,以及对身心问题的影响。出发点是民族药理学,因此,在1973年至1983年的实地研究项目中,描述了这种马扎特克神圣薄荷的传统信仰,仪式用途和心理影响。一种由碎叶子制成的水药水会产生短暂的头晕、不安、触觉和本体感觉、人格解体感、声音感知放大、视觉和听觉图像增加,但不是真正的幻觉。通过问卷调查也描述了类似的效果,并归因于salvinorin A,但不能仅仅通过其特异性和有效的脑kappa-阿片受体激动剂活性来解释。提出了意识改变产物的可行分类和作用机制的一些要求,包括由多个神经化学系统组成的神经网络的激活。应该进行自上而下的分析,以表征这种神经网络,并最终允许探索不同种族的影响。就像其他改变意识的制剂一样,对这种植物及其原理进行仔细而全面的研究,可以对从身心问题、更好地理解萨满狂喜,到潜在的镇痛药、抗抑郁药和药物滥用减弱产品的产生产生重大影响。
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引用次数: 18
Buprenorphine and buprenorphine/naloxone intoxication in children - how strong is the risk? 儿童丁丙诺啡和丁丙诺啡/纳洛酮中毒的风险有多大?
Pub Date : 2013-03-01 DOI: 10.2174/18744737112059990010
Michael Soyka

Opioid maintenance therapy with methadone or buprenorphine is an established and first-line treatment for opioid dependence. Risk of diversion and toxicity of opioid prescription drugs, including buprenorphine, causes significant concerns. This is particularly the case in the United States, where the number of related emergency visits is increasing, especially in children. A systematic literature research (Medline, Pubmed) was performed to assess the risk associated with buprenorphine. The search, which was not limited to particular publication years, was performed with the key words buprenorphine AND toxicity (114 counts ) AND children (4 counts) and buprenorphine AND mortality AND children (5 counts). In addition, the author obtained information from relevant websites (NIDA, SAMSHA) and pharmacovigilance data from the manufacturer of buprenorphine. Clinical and toxicological data suggest a low risk for fatal intoxications associated with bupreorphine in adults. Data from emergency units indicate a dramatic, 20-fold increase in buprenorphine exposure in children over the past decade, mostly in those under 6. The US 'Researched Abuse, Diversion and Addiction-Related Surveillance' (RADARS) system indicates a lower risk of severe opioid intoxications with buprenorphine than with other opioids, with no fatal outcomes recorded. Correspondingly, data from spontaneous reports to the surveillance programme of the manufacturer of buprenorphine (13,600 buprenorphine exposures, 4879 of these in children under six) show a serious medical outcome in 34% of children under the age of six but only one fatal outcome. Although exposure to buprenorphine and other opioids remains a significant concern in children, the drug seems rather to be safe with respect to severe outcomes, in particular death.

美沙酮或丁丙诺啡维持阿片类药物治疗是阿片类药物依赖的一线治疗方法。阿片类处方药(包括丁丙诺啡)的转移风险和毒性引起了重大关注。美国的情况尤其如此,相关的急诊数量正在增加,尤其是儿童。进行了系统的文献研究(Medline, Pubmed)来评估丁丙诺啡的相关风险。检索不限于特定出版年份,检索关键词丁丙诺啡与毒性(114项)、儿童(4项)和丁丙诺啡与死亡率和儿童(5项)。此外,笔者从相关网站(NIDA、SAMSHA)获取信息,从丁丙诺啡生产企业获取药物警戒数据。临床和毒理学数据表明,成人丁丙奥啡致死性中毒的风险较低。急诊部门的数据表明,在过去十年中,儿童丁丙诺啡接触量急剧增加了20倍,其中大多数是6岁以下儿童。美国“研究滥用、转移和成瘾相关监测”(雷达)系统表明,丁丙诺啡严重阿片类药物中毒的风险低于其他阿片类药物,没有致命的结果记录。相应地,向丁丙诺啡制造商监测方案自发报告的数据(13,600次丁丙诺啡接触,其中4879例为6岁以下儿童)显示,34%的6岁以下儿童出现严重的医疗后果,但只有1例死亡。虽然接触丁丙诺啡和其他类阿片仍然是儿童的一个重大问题,但就严重后果,特别是死亡而言,该药物似乎是相当安全的。
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引用次数: 8
Cigarette smoking in methadone maintained patients: an up-to-date review. 美沙酮维持患者吸烟:最新综述。
Pub Date : 2013-03-01 DOI: 10.2174/1874473711306010009
Ali Zirakzadeh, Charles Shuman, Erinn Stauter, J Taylor Hays, Jon O Ebbert

Tobacco dependence is the leading cause of preventable death and disability in the United States. While smoking prevalence among U.S. adults is 19.3%, the prevalence of smoking among methadone-maintained patients ranges between 73.5% and 94%. Most methadone-maintained smokers (76%-80%) desire to quit smoking; however only a minority of these smokers receive cessation treatment or referrals for smoking cessation intervention. Smoking cessation treatment in methadone-maintained patients has generally been successful in reducing the daily number of cigarettes smoked. Unfortunately, sustained cessation rates using nicotine replacement therapy and behavioral interventions have generally been low (0%-11%). Poor cessation outcomes may be partially explained by pharmacodynamic interactions between nicotine and methadone leading to increased reinforcement of smoking behavior. Further research is needed to improve smoking cessation rates in methadone-maintained patients.

在美国,烟草依赖是导致可预防的死亡和残疾的主要原因。美国成年人的吸烟率为19.3%,而美沙酮维持患者的吸烟率为73.5%至94%。大多数美沙酮维持吸烟者(76%-80%)希望戒烟;然而,这些吸烟者中只有少数人接受戒烟治疗或转诊进行戒烟干预。在维持美沙酮的患者中,戒烟治疗通常在减少每日吸烟数量方面是成功的。不幸的是,使用尼古丁替代疗法和行为干预的持续戒烟率通常很低(0%-11%)。戒烟效果不佳的部分原因可能是尼古丁和美沙酮之间的药效学相互作用导致吸烟行为的增强。需要进一步的研究来提高美沙酮维持患者的戒烟率。
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引用次数: 44
Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada. 死藤水辅助成瘾治疗:来自加拿大初步观察研究的结果。
Pub Date : 2013-03-01 DOI: 10.2174/15733998113099990003
Gerald Thomas, Philippe Lucas, N Rielle Capler, Kenneth W Tupper, Gina Martin

Introduction: This paper reports results from a preliminary observational study of ayahuasca-assisted treatment for problematic substance use and stress delivered in a rural First Nations community in British Columbia, Canada.

Methods: The "Working with Addiction and Stress" retreats combined four days of group counselling with two expert-led ayahuasca ceremonies. This study collected pre-treatment and six months follow-up data from 12 participants on several psychological and behavioral factors related to problematic substance use, and qualitative data assessing the personal experiences of the participants six months after the retreat.

Findings: Statistically significant (p < 0.05) improvements were demonstrated for scales assessing hopefulness, empowerment, mindfulness, and quality of life meaning and outlook subscales. Self-reported alcohol, tobacco and cocaine use declined, although cannabis and opiate use did not; reported reductions in problematic cocaine use were statistically significant. All study participants reported positive and lasting changes from participating in the retreats.

Conclusions: This form of ayahuasca-assisted therapy appears to be associated with statistically significant improvements in several factors related to problematic substance use among a rural aboriginal population. These findings suggest participants may have experienced positive psychological and behavioral changes in response to this therapeutic approach, and that more rigorous research of ayahuasca-assisted therapy for problematic substance use is warranted.

引言:本文报告了在加拿大不列颠哥伦比亚省的一个农村第一民族社区进行的死藤水辅助治疗问题物质使用和压力的初步观察研究的结果。方法:“与成瘾和压力一起工作”静修结合了为期四天的小组咨询和两次专家主持的死藤水仪式。本研究收集了12名参与者的治疗前和6个月的随访数据,包括与问题物质使用有关的几个心理和行为因素,以及评估参与者在撤退后6个月的个人经历的定性数据。结果:在评估希望、授权、正念和生活质量、意义和前景的量表上,有统计学意义(p < 0.05)的改善。自我报告的酒精、烟草和可卡因使用情况有所下降,但大麻和鸦片剂的使用情况没有下降;据报告,有问题的可卡因使用的减少在统计上是显著的。所有的研究参与者都报告了参加静修后积极而持久的变化。结论:这种形式的死藤水辅助治疗似乎与农村土著人口中与问题物质使用相关的几个因素的统计学显著改善有关。这些发现表明,参与者可能经历了积极的心理和行为变化,作为对这种治疗方法的反应,死藤水辅助治疗问题物质使用的更严格的研究是有必要的。
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引用次数: 247
Editorial: Second International Conference on Novel Psychoactive Substances (NPSs): keynote addresses and conference abstracts. 社论:第二届新型精神活性物质国际会议:主题演讲和会议摘要。
Pub Date : 2013-01-01 DOI: 10.2174/187447370604140616121012
A C Parrott, O Corazza, F Schifano, P Griffiths, R Sedefov, A Gallegos, R M Murray, Z Demetrovics, V Curran, G Bersani, L T Singer
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引用次数: 1
Editorial: Can hangover immunity be really claimed? 社论:宿醉免疫真的可以宣称吗?
Pub Date : 2013-01-01 DOI: 10.2174/187447370604140616120736
Joris C Verster, Suzanne de Klerk, Adriana C Bervoets, L Darren Kruisselbrink
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引用次数: 27
Editorial: Cognitive enhancement: are we barking up the wrong tree? 社论:认知增强:我们找错对象了吗?
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040001
Andrew Scholey, Con Stough, Joris C Verster
There are surprisingly few studies directly comparing the effects of nutraceutical and pharmaceuticals. However, a recent comparison of effects sizes (Cohen's d) from studies on modafinil and ginseng (and the long term benefits of Bacopa) was conducted [16]. In non sleep deprived individuals modafinil was associated with effect sizes ranging from d = 0.083 to d = 0.774. The latter was for accuracy of Visual Spatial Memory. For Ginseng there was larger variation in the effect sizes across mood and cognitive domains, ranging from d = -.340 (from a high dose of Ginseng) to d = 1.396. The latter related to reversal of self-rated mental fatigue during intense cognitive processing. In the context of cognitive processing the largest effect size (d = 0.860) was for simple reaction time. Thus it appears that herbal extracts may be at least as promising as pharmaceuticals as cognitive enhancers. Perhaps this is not so surprising when one considers that most pharmaceutical approaches to cognitive enhancement rely on the "magic bullet" approach to brain function. That is, they tend to target one neurotransmitter (or neurotransmitter family). It does seem unlikely that a phenomenon as complex as human cognitive function will benefit greatly from such an approach. Herbal extracts on the other hand, may contain multiple active components. These may exert multiple subtle effects which individually either have positive or negative effects on behaviour, but together may affect multiple neuronal, metabolic and hormonal systems which underpin behavioural processes. This polypharmacological approach may offer more promise in the context of cognitive enhancement.
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引用次数: 2
期刊
Current drug abuse reviews
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