Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Neuropsychopharmacology. 2017 Oct;42(11):2114-2127. doi: 10.1038/npp.2017.86. Epub 2017 Apr 27.
All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.
本文综述了近 25 年来，使用经典致幻剂麦角酸二乙酰胺（LSD）对健康受试者或患者进行的所有现代临床研究。其中包括五项在健康参与者中进行的近期研究和一项在患者中进行的研究。在对照环境下，LSD 可诱发欣快、视听联觉、知觉意义改变、现实解体、人格解体和神秘体验。这些 LSD 的主观效应是由 5-HT 受体介导的。LSD 增加了与他人的亲近感、开放性、信任感和暗示性。LSD 损害了对悲伤和恐惧面孔的识别，降低了左杏仁核对恐惧面孔的反应性，并增强了情感同理心。LSD 增加了对音乐的情感反应和音乐的意义。LSD 可急性导致感觉运动门控缺陷，类似于精神分裂症的观察结果。LSD 对自主神经系统有微弱的刺激作用，可升高血浆皮质醇、催乳素和催产素水平。静息态功能磁共振研究表明，LSD 可急性降低功能脑网络的完整性，并增加正常情况下更分离的网络之间的连通性。LSD 增加了丘脑皮质的功能连接和初级视觉皮层与其他脑区的功能连接。后一种效应与主观幻觉有关。LSD 可急性诱导大脑整体熵增加，这与 14 天后更大的特质开放性相关。在患有危及生命疾病相关焦虑的患者中，两次 LSD 剂量后，焦虑可缓解 2 个月。在医疗环境中，未观察到 LSD 给药的并发症。这些数据应有助于进一步研究 LSD 在精神病学中的治疗潜力。
