Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects.
Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects.
复制标题
DOI：
10.1038/s41386-020-00883-6
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Liechti ME
中科院分区：
文献类型：
--
作者：
Holze F;Vizeli P;Ley L;Müller F;Dolder P;Stocker M;Duthaler U;Varghese N;Eckert A;Borgwardt S;Liechti ME
在精神病学研究和治疗中使用麦角酰二乙胺（LSD）的兴趣越来越大。然而，没有现代研究评估了不同的和药学上明确定义的剂量的LSD的主观和自主效应。我们在16名健康受试者（8名女性，8名男性）中使用双盲、随机、安慰剂对照、交叉设计，这些受试者接受了6次25小时的治疗，并在给予5-羟色胺-2A（5-HT 2A）受体拮抗剂酮色林（40 mg）后1小时接受了安慰剂、LSD（25、50、100和200 μg）和200 μg LSD。测试日间隔至少10天。结果测量包括自我评定量表，评估主观效应、自主效应、不良反应、血浆脑源性神经营养因子水平和24小时内的药代动力学。评价药代动力学-主观反应关系。从25 µg剂量开始，LSD显示出剂量比例性药代动力学和一级消除以及剂量依赖性诱导的主观反应。在100 µg时观察到良好药物效应的天花板效应。200 μg剂量的LSD比100 μg剂量的LSD引起更大的自我溶解，并引起显著的焦虑。随着25-200 µg剂量的增加，主观效应的平均持续时间从6.7小时增加到11小时。LSD适度增加血压和心率。Ketanserin有效地阻止了对200 µg LSD的反应。LSD剂量反应曲线显示主观良好效果的天花板效应，自我溶解和焦虑在剂量超过100 μg时进一步增加。这些结果可能有助于未来LSD研究的剂量发现。LSD的全部迷幻作用主要由5-羟色胺5-HT 2A受体激活介导。
Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25–200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose–response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.
登录
查看更多内容
DOI：
10.1038/npp.2017.86
发表时间：
2017-10
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Liechti ME
通讯作者：
Liechti ME
影响因子：
4.5
作者：
Dolder PC;Schmid Y;Steuer AE;Kraemer T;Rentsch KM;Hammann F;Liechti ME
通讯作者：
Liechti ME
影响因子：
8.8
作者：
Ly C;Greb AC;Cameron LP;Wong JM;Barragan EV;Wilson PC;Burbach KF;Soltanzadeh Zarandi S;Sood A;Paddy MR;Duim WC;Dennis MY;McAllister AK;Ori-McKenney KM;Gray JA;Olson DE
通讯作者：
Olson DE
影响因子：
4.3
作者：
Dittrich, A
通讯作者：
Dittrich, A
影响因子：
3.4
作者：
Kraehenmann, Rainer;Pokorny, Dan;Vollenweider, Franz X.
通讯作者：
Vollenweider, Franz X.