Dolder Patrick C, Grünblatt Edna, Müller Felix, Borgwardt Stefan J, Liechti Matthias E
Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel and University of BaselBasel, Switzerland.
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of ZurichZurich, Switzerland.
Front Pharmacol. 2017 Jun 28;8:423. doi: 10.3389/fphar.2017.00423. eCollection 2017.
Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes and in rat and mouse brains through 5-HT receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT receptor gene () and genes. mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. LSD did not alter the expression of the or genes 1.5 and 24 h after administration compared with placebo. No changes were observed in the gene expression of LSD's primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans.
在精神病学研究和实践中，人们对使用麦角酸二乙酰胺（LSD）的兴趣再度兴起。反复使用LSD会导致耐受性，据信这是由血清素（5-HT）5-HT受体下调引起的。在大鼠中，连续4天每日给予LSD会降低额叶皮质5-HT受体结合。此外，单次给予LSD可通过5-HT受体刺激在大鼠和小鼠大脑中急性增加早期生长反应基因和的表达。尚未有关于LSD对基因表达影响的人类数据报道。因此，我们研究了单次给予LSD对5-HT受体基因（）和基因表达的影响。在一项随机、双盲、安慰剂对照、交叉研究中，对15名健康受试者在给予LSD（100μg）和安慰剂之前以及给药后1.5小时和24小时，分析全血中作为外周生物标志物的mRNA表达水平。与安慰剂相比，LSD在给药后1.5小时和24小时并未改变或基因的表达。在LSD的主要靶受体基因或涉及其下游效应的基因的基因表达中未观察到变化。长期给予LSD是否会改变人类的基因表达仍不清楚。
