Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of these two medications has not, however, been directly compared either clinically or preclinically. Further, whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects is unknown. To address these questions, we tested psilocybin, lysergic acid diethylamide (LSD), and ketamine in a rat model for depression. As in humans, a single administration of psilocybin or LSD produced persistent antidepressant-like effects in our model. In contrast, ketamine produced only a transient antidepressant-like effect. Our results indicate that classic psychedelics may have therapeutic efficacy that is more persistent than that of ketamine, and also suggest that a subjective existential experience may not be necessary for therapeutic effects.

中文翻译：

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迷幻药而非氯胺酮在啮齿动物抑郁症研究实验系统中产生持久的抗抑郁药样作用。

在人类临床试验中，仅一次或两次治疗后六个月或更长时间，赛洛西宾就具有缓解抑郁的功效。另一种致幻剂，七氯胺酮，最近已获得美国食品和药物管理局（FDA）的批准，作为一种速效抗抑郁药。psilocybin和氯胺酮的抗抑郁作用的机理基础似乎是保守的。然而，尚未在临床或临床前直接比较这两种药物的功效。此外，尚不清楚深刻的主观存在经验对于psilocybin具有抗抑郁作用是必需的。为了解决这些问题，我们在大鼠抑郁症模型中测试了psilocybin，麦角酸二乙酰胺（LSD）和氯胺酮。和人类一样 在我们的模型中，单次施用psilocybin或LSD会产生持续的抗抑郁样作用。相反，氯胺酮仅产生短暂的抗抑郁样作用。我们的结果表明，经典的迷幻药可能具有比氯胺酮更持久的治疗功效，并且还表明，主观的存在经验对于治疗效果可能不是必需的。