Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects.
Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide in Healthy Subjects.
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DOI：
10.1007/s40262-017-0513-9
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发表时间：
2017-10
影响因子：
4.5
通讯作者：
Liechti ME
中科院分区：
文献类型：
--
作者：
Dolder PC;Schmid Y;Steuer AE;Kraemer T;Rentsch KM;Hammann F;Liechti ME
麦角酰二乙胺（LSD）用于娱乐和临床研究。本研究的目的是描述口服LSD的药代动力学和剂量-效应关系。我们分析了来自两项已发表的安慰剂对照、双盲、交叉研究的药代动力学数据，这些研究分别在24名和16名受试者中使用口服LSD 100和200 µg。首次显示100 µg剂量的药代动力学，重新分析并纳入200 µg剂量的数据。重复评估LSD的血浆浓度、主观效应和生命体征。使用房室模型确定药代动力学参数。使用药代动力学-药效学模型描述浓度-效应关系。100和200 µg LSD给药后1.4和1.5 h，几何平均（95%置信区间）最大血药浓度值分别达到1.3（1.2-1.9）和3.1（2.6-4.0）ng/mL。血浆半衰期为2.6 h（2.2-3.4 h）。100和200 µg LSD剂量组的主观效应持续时间（平均值±标准差）分别为8.2 ± 2.1和11.6 ± 1.7小时。LSD 100和200 µg给药后分别在2.8和2.5 h达到主观峰值效应。观察到LSD浓度和受试者的主观反应之间存在密切关系，具有中度逆时针滞后。半数最大有效浓度值在1 ng/mL范围内。在最大血药浓度或接近最大血药浓度的受试者之间以及剂量组内，未发现血浆LSD浓度与LSD效应之间存在相关性。目前的药代动力学数据对于评价临床研究结果（例如，功能性磁共振成像研究）和LSD中毒的解释。口服LSD呈现剂量比例药代动力学和一级消除长达12小时。LSD的作用与血浆浓度随时间的变化有关，没有急性耐受性的证据。试验注册：NCT 02308969、NCT 01878942。本文的在线版本（doi：10.1007/s40262-017-0513-9）包含补充材料，可供授权用户使用。
Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure–response relationship of oral LSD. We analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Geometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2–1.9) and 3.1 (2.6–4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2–3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups. The present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related to changes in plasma concentrations over time, with no evidence of acute tolerance. Trial registration: NCT02308969, NCT01878942. The online version of this article (doi:10.1007/s40262-017-0513-9) contains supplementary material, which is available to authorized users.
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影响因子：
4.3
作者：
Dolder, Patrick C.;Liechti, Matthias E.;Rentsch, Katharina M.
通讯作者：
Rentsch, Katharina M.
影响因子：
4.1
作者：
Gasser, Peter;Kirchner, Katharina;Passie, Torsten
通讯作者：
Passie, Torsten
影响因子：
2.5
作者：
Klette, KL;Horn, CK;Anderson, CJ
通讯作者：
Anderson, CJ
影响因子：
2.1
作者：
Martin, Rafaela;Schuerenkamp, Jennifer;Koehler, Helga
通讯作者：
Koehler, Helga
DOI：
10.1073/pnas.1518377113
发表时间：
2016-04-26
影响因子：
11.1
作者：
Carhart-Harris, Robin L.;Muthukumaraswamy, Suresh;Nutt, David J.
通讯作者：
Nutt, David J.