When LSD binds to serotonin receptors, it pulls a “lid” closed behind it, locking it in place for hours, and explaining its long-lasting effects. Christopher Intagliata reports.
当LSD与五羟色胺受体结合，它在身后拉上了一个闭合的“盖子”，在几小时内把自己锁在里面，这解释了它能够产生了长时间作用的原因。克里斯托弗·因塔利亚塔报道。
撰文/播音：克里斯托弗·因塔利亚塔（Christopher Intagliata）
翻译：郭鑫鹏
审校：丁可含
LSD is one of the most potent hallucinogenic drugs-active at just around 100 micrograms…a miniscule amount. That fact has fascinated pharmacologists for decades. Namely, how can it have such long-lasting effects…12 hours or more…at such tiny doses?
LSD是一种最能强力致幻的药物——仅仅100毫克这样的微量就能起作用。这项事实让药理学家们着迷了几十年。也就是说，它为什么如此小剂量就能有12个小时或者更长这样持久的作用？
To find out, researchers legally obtained LSD. And built copies of the receptors it binds to in the brain-serotonin receptors. They mixed the LSD and the receptors together, and crystallized the result. They then imaged the structure, using x-ray crystallography.
为了找出原因，研究者们合法地取得了LSD。他们复制了大脑中LSD能够与之结合的受体——五羟色胺受体。他们把LSD和受体混合在一起，让其结晶。然后他们使用X射线对其结构进行晶体学成像。
And they found that when LSD linked up with the serotonin receptor, a sort of “lid” formed over it. Almost like the drug went in, then pulled the door shut behind it. “You could think of the top part of LSD as a hand, holding onto the latch and pulling it down.” Bryan Roth, a pharmacologist at University of North Carolina in Chapel Hill involved in the research.
他们发现当LSD与五羟色胺受体结合后，受体则产生了一个“盖子”盖住了自己。就像当药物进入，然后在它身后关上了门。“你可以想象LSD顶部是一只手，抓住了门闩把它拉了下来。“参与了这项研究的北卡罗来纳大学教堂山分校药理学家布赖恩·罗特说。
“This explains why LSD is so potent, why such a small amount of it is active, and secondly why it lasts for such a long period of time. Because basically once it gets in there it takes hours to come off the receptor.” The study is in the journal Cell. [Daniel Wacker et al., Crystal Structure of an LSD-Bound Human Serotonin Receptor]
“这解释了为什么LSD这样强力，很小剂量就能起作用，还有为什么它能这么持久。因为当它进入后，要几时才会离开受体。“这项研究发表在期刊《细胞》上。
The result may also explain why microdosing-taking even smaller amounts of LSD, at sub-psychedelic levels-might work as a mood enhancer, as some users have reported. “It’s clear from the data we have that these small doses can engage these receptors, and of course we know that the receptors that LSD interacts with, they’re the same receptors that are thought to be involved in antidepressant drug action.”
这个结果也能解释为什么微剂量——使用更少的，低于迷幻剂量的LSD——能够稳定情绪，像一些使用者报告的那样。“从数据上我们很清楚这些小剂量可以与受体结合，我们也知道LSD影响的这些受体，也是抗抑郁药物影响的受体。
Roth does not advocate trying it out. But he says the discovery of the “lid” might someday lead to the development of novel antidepressants-ones with long-lasting effects, at just the tiniest of doses.
罗特并不提倡去尝试。但是他说这个“盖子”机制的发现有一天会促进新型抗抑郁药物的发展——让它们可以在极小剂量产生持久的效果。
-Christopher Intagliata
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