商业周刊:阻止自杀的药物(3)（在线收听）

In the 1990s he was a psychiatry professor, mentoring then associate professor John Krystal at Yale and trying to figure out how a deficit of serotonin played into depression.

在20世纪90年代，丹尼斯·查尼是一名精神病学教授，指导耶鲁大学当时的副教授约翰·克里斯托，试图弄清楚血清素缺乏如何导致抑郁症。

Back then, depression research was all about serotonin. The 1987 approval of Prozac, the first selective serotonin reuptake inhibitor, or SSRI,

当时，抑郁症研究都关注血清素。1987年批准了抗抑郁药Prozac，这是首款选择性血清素再摄取抑制剂（SSRI），

ushered in an era of what people in the industry call me-too drug development, research that seeks to improve on existing medicines rather than exploring new approaches.

开创了业内人士称之为模仿性跟进的药物开发时代，即研究旨在改善现有药物药效，而不是探索新疗法。

Within this narrow range, pharmaceutical companies churned out blockbuster after blockbuster.

在这个狭窄的研究范畴内，制药公司大量生产出很多畅销药品。

One in eight Americans age 12 and older reported using antidepressants within the past month, according to a survey conducted from 2011 to 2014 by the U.S. Centers for Disease Control and Prevention.

美国疾病控制和预防中心2011年至2014年进行的一项调查显示，八分之一的12岁及以上的美国人在过去一个月内使用过抗抑郁药。

Charney was a depression guy; Krystal was interested in schizophrenia. Their curiosity led them to the same place: the glutamate system, what Krystal calls the "main information highway of the higher brain."

查尼研究抑郁症，而克里斯托对精神分裂症很感兴趣，好奇心把他们引向同一个地方：谷氨酸系统，也就是克里斯托所说的“高阶大脑的主要信息高速公路”。

(Glutamate is an excitatory neurotransmitter, which helps brain cells communicate. It's considered crucial in learning and memory formation.)

（谷氨酸是一种兴奋性神经递质，可以帮助脑细胞进行交流。它被认为是学习和记忆形成的关键。）

They had already used ketamine to temporarily produce schizophrenialike symptoms, to better understand glutamate's role in that condition.

他们已经使用氯胺酮暂时产生类似精神分裂症的症状，以更好地了解谷氨酸在这种情况下的作用。

In the mid-1990s they decided to conduct a single-dose study of ketamine on nine patients (two ultimately dropped out) at the Yale-affiliated VA Connecticut Healthcare System in West Haven to see how depressed people would react to the drug.

20世纪90年代中期，他们决定在西汉文市康涅狄格州附属耶鲁大学退伍军人医疗系统中对9名患者（其中两名患者最终退出试验）进行一次氯胺酮单剂量研究，以了解抑郁症患者对药物的反应。

Outside the field of anesthesiology, ketamine is known, if it's known at all, for its abuse potential.

在麻醉学领域之外，氯胺酮因其存在可能被滥用的风险而广为人知。

Street users sometimes take doses large enough to enter what's known as a "K hole," a state in which they're unable to interact with the world around them.

街头毒品吸食者有时会服用大剂量氯胺酮，进入所谓的“K洞”状态（K是氯胺酮英文首字母），在这种状态下他们无法与周围世界互动。

Over the course of a day, those recreational doses can be as much as 100 times greater than the tiny amount Charney and Krystal were planning to give to patients.

在一天内，用于消遣而服用的氯胺酮剂量可能比查尼和克里斯托计划给病人服用的微量剂量高出100倍。

Nonetheless, they decided to monitor patients for 72 hours—well beyond the two hours that ketamine produces obvious behavioral effects— just to be careful not to miss any negative effects that might crop up.

尽管如此，他们决定对患者进行72小时监测，氯胺酮产生明显行为影响为两小时，他们的监测时间远远超过了这个时间，这样做只是不想错过任何可能产生的负面影响。

"If we had done the typical thing that we do with these drug tests," Krystal says, "we would have completely missed the antidepressant effect of ketamine."

克里斯托说：“如果我们只做有关这些药物测试的常规性工作，我们就无法监测到氯胺酮抗抑郁的药效。”