Science2014-06-13 12:05 PM

孕烯醇酮能够有效地消除大麻引发的“极度兴奋” Pregnenolone Can Protect the Brain from Cannabis Intoxication

论文摘要 

研究人员发现了一种自然产生的叫作孕烯醇酮的类固醇激素,它能减少脑中I型大麻素受体(CB1)的活性,有效地消除了由四氢大麻酚(THC)引发的“极度兴奋”,THC是大麻中的具有精神活性的成分。这些研究人员并非试图让人扫兴;他们的发现可带来新的治疗大麻中毒及成瘾的方法,而且它可让研究人员在阻断大麻对行为及躯体效应的同时分离出大麻的药用特性。Monique Vallée 及其同事对小鼠和大鼠进行了研究以观察主要的被滥用的药物——如可卡因、吗啡、尼古丁及酒精——是如何影响神经类固醇,或在这些啮齿类动物的脑中直接产生类固醇的。他们发现,THC尤其会通过激活这些啮齿动物的CB1受体而导致孕烯醇酮急剧增加——这是一种神经类固醇的构建模块。反过来,他们说,孕烯醇酮减弱了在这些动物中的THC效应——如记忆损害及过度进食。这些发现揭示了一个先前未被认识到的负反馈回路,该回路看来能保护大脑不受CB1的过度刺激。

Abstract 

Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa(marijuana), ∆9-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.

Counteracting Cannabis

What is the role of steroid hormones in vulnerability to addiction? Working with rodents, Vallée et al. (p. 94) found that all major drugs of abuse (morphine, cocaine, alcohol, nicotine) increase neurosteroid levels, with the active ingredient in cannabis (THC) inducing a particularly large increase. THC and other drugs increased levels of pregnenolone, long thought to be an inactive precursor of downstream active steroids. Pregnenolone antagonized most of the known behavioral and somatic effects of THC.

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