Cannabinoid tolerance and dependence:: A review of studies in laboratory animals
Cannabinoid tolerance and dependence:: A review of studies in laboratory animals
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DOI：
10.1016/j.pbb.2005.01.028
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发表时间：
2005-06-01
影响因子：
3.6
通讯作者：
Fernández-Ruiz, J
中科院分区：
文献类型：
--
作者：
González, S;Cebeira, M;Fernández-Ruiz, J
从研究角度来看，两个问题是引起更多争议的大麻成瘾问题。第一个与耐受现象的发展有关，特别是在长期吸食大麻素后的依赖状态，当这种情况被中断时会出现戒断症状，这与其他药物观察到的症状相当（或不相当）。第二个有争议的问题是，长期吸食大麻素可能会增加吸食其他成瘾性更强的药物的风险。自20世纪90年代发现内源性大麻素信号系统作为植物源大麻素作用的靶点以来，许多研究在实验室动物中解决了这两个问题，尽管结果在各个方面引起了争议，但以下结论似乎是显而易见的：（i）长时间接触植物衍生物，实验室动物中的合成或内源性大麻素激动剂目前与其大多数药理学作用的耐受性的发展有关，（ii）耐受性主要是由于药效学事件中的适应性现象（大麻素受体的下调/脱敏），尽管存在一些关于额外的药代动力学反应的证据，（iii）在大多数情况下，停止长期大麻素治疗不会自发引起戒断反应，可能是因为大麻素的药代动力学特征，但是这些反应可以在大麻素耐受动物中的大麻素CB 1受体阻断后引发，（iv）这些戒断反应主要包括躯体体征和在对其它药物戒断期间受影响的各种分子过程的变化，尽管这些变化的幅度目前在大麻素的情况下较低，和（v）大麻素耐受动物似乎对吗啡的强化性质并不更脆弱，尽管内源性大麻素信号传导的操纵可能有助于治疗大麻成瘾，特别是对其他药物如酒精、尼古丁或阿片类药物的成瘾。本文将对这些方面进行综述，为今后的研究奠定基础。(c)2005年爱思唯尔公司All rights reserved.
Two are the issues on cannabis addiction that provoke more controversy from a research perspective. The first one is related to the development of tolerance phenomena and, in particular, of a dependence state after chronic cannabinoid consumption, with appearance of withdrawal signs when this is interrupted, that would be (or not) comparable to those observed for other drugs. A second controversial issue is related to the possibility that chronic cannabinoid consumption may increase the risk to consume other drugs of greater addictive power. Since the discovery in the 1990s of the endocannabinoid signaling system as the target for the action of plant-derived cannabinoids, many studies have addressed these two questions in laboratory animals and, although the results have resulted controversial in various aspects, the following conclusions seem evident: (i) prolonged exposure to plant-derived, synthetic or endogenous cannabinoid agonists in laboratory animals is currently associated with the development of tolerance for most of their pharmacological effects, (ii) tolerance is essentially due to adaptative phenomena consisting in pharmacodynamic events (down-regulation/desensitization of cannabinoid receptors), although some evidence exist on additional pharmacokinetic responses, (iii) the discontinuation of chronic cannabinoid treatment does not elicit abstinence responses spontaneously in most of the cases, presumably because the pharmacokinetic characteristics of cannabinoids, but these responses may be elicited after the blockade of cannabinoid CB1 receptors in cannabinoid-tolerant animals, (iv) these abstinent responses include mainly somatic signs and changes in various molecular processes affected during the abstinence to other drugs although the magnitude of these changes was currently lower in the case of cannabinoids, and (v) cannabinoid-tolerant animals do not appear to be more vulnerable to reinforcing properties of morphine, although the manipulation of the endocannabinoid signaling might serve to treat cannabis addiction and, in particular, the addiction to other drugs such as alcohol, nicotine or opioids. The present review article will address all these aspects trying to establish the bases for future research. (c) 2005 Elsevier Inc. All rights reserved.