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Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Pharmacological Reviews ( IF 21.1 ) Pub Date : 2021-01-01 , DOI: 10.1124/pharmrev.120.000056
Antonio Inserra 1 , Danilo De Gregorio 1 , Gabriella Gobbi 2
Affiliation  

Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food and Drug Administration in a new class of antidepressants, and 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin and lysergic acid diethylamide (LSD) are being investigated in several phase II and phase I clinical trials. Hence, the concept of psychedelics as therapeutics may be incorporated into modern society. Here, we discuss the main known neurobiological therapeutic mechanisms of psychedelics, which are thought to be mediated by the effects of these compounds on the serotonergic (via 5-HT2A and 5-HT1A receptors) and glutamatergic [via N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors] systems. We focus on 1) neuroplasticity mediated by the modulation of mammalian target of rapamycin–, brain-derived neurotrophic factor–, and early growth response–related pathways; 2) immunomodulation via effects on the hypothalamic-pituitary-adrenal axis, nuclear factor ĸB, and cytokines such as tumor necrosis factor-α and interleukin 1, 6, and 10 production and release; and 3) modulation of serotonergic, dopaminergic, glutamatergic, GABAergic, and norepinephrinergic receptors, transporters, and turnover systems. We discuss arising concerns and ways to assess potential neurobiological changes, dependence, and immunosuppression. Although larger cohorts are required to corroborate preliminary findings, the results obtained so far are promising and represent a critical opportunity for improvement of pharmacotherapies in psychiatry, an area that has seen limited therapeutic advancement in the last 20 years. Studies are underway that are trying to decouple the psychedelic effects from the therapeutic effects of these compounds.

中文翻译:

精神病学中的迷幻药:神经可塑性、免疫调节和神经递质机制

越来越多的证据表明迷幻化合物作为精神病学中潜在的新型疗法的安全性和有效性。氯胺酮已被美国食品和药物管理局批准用于一类新型抗抑郁药,3,4-亚甲二氧基甲基苯丙胺 (MDMA) 正在接受治疗创伤后应激障碍的 III 期临床试验。赛洛西宾和麦角酸二乙胺 (LSD) 正在几项 II 期和 I 期临床试验中进行研究。因此,迷幻药作为治疗的概念可能会被纳入现代社会。在这里,我们讨论迷幻药的主要已知神经生物学治疗机制,这些机制被认为是由这些化合物对血清素能(通过 5-HT 2A和 5-HT 1A受体)和谷氨酸能 [通过Ñ甲基d天冬氨酸(NMDA)和α ] -氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体系统。我们关注 1) 由哺乳动物雷帕霉素靶标、脑源性神经营养因子和早期生长反应相关通路的调节介导的神经可塑性;2) 通过对下丘脑-垂体-肾上腺轴、核因子 ĸB 和细胞因子(如肿瘤坏死因子)的影响进行免疫调节和白介素 1、6 和 10 的生产和释放;3) 调节血清素能、多巴胺能、谷氨酸能、GABA能和去甲肾上腺素能受体、转运蛋白和周转系统。我们讨论了出现的问题以及评估潜在神经生物学变化、依赖性和免疫抑制的方法。尽管需要更大的队列来证实初步发现,但迄今为止获得的结果是有希望的,并且代表了改进精神病学药物治疗的关键机会,该领域在过去 20 年中的治疗进展有限。正在进行研究,试图将迷幻效果与这些化合物的治疗效果分开。
更新日期:2020-12-17
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