Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Neuropsychology & Psychopharmacology, Faculty of Psychology & Neuroscience, Maastricht University, Maastricht, The Netherlands.
Clin Pharmacol Ther. 2021 Mar;109(3):658-666. doi: 10.1002/cpt.2057. Epub 2020 Oct 18.
"Microdoses" of lysergic acid diethylamide (LSD) are used recreationally to enhance mood and cognition. Increasing interest has also been seen in developing LSD into a medication. Therefore, we performed a pharmacokinetic-pharmacodynamic study using very low doses of LSD. Single doses of LSD base (5, 10, and 20 µg) and placebo were administered in a double-blind, randomized, placebo-controlled crossover study in 23 healthy participants. Test days were separated by at least 5 days. Plasma levels of LSD and subjective effects were assessed up to 6 hours after administration. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-subjective effect relationships were described using pharmacokinetic-pharmacodynamic modeling. Mean (95% confidence interval) maximal LSD concentrations were 151 pg/mL (127-181), 279 pg/mL (243-320), and 500 pg/mL (413-607) after 5, 10, and 20 µg LSD administration, respectively. Maximal concentrations were reached after 1.1 hours. The mean elimination half-life was 2.7 hours (1.5-6.2). The 5 µg dose of LSD elicited no significant acute subjective effects. The 10 µg dose of LSD significantly increased ratings of "under the influence" and "good drug effect" compared with placebo. These effects began an average of 1.1 hours after 10 µg LSD administration, peaked at 2.5 hours, and ended at 5.1 hours. The 20 µg dose of LSD significantly increased ratings of "under the influence," "good drug effects," and "bad drug effects." LSD concentrations dose-proportionally increased at doses as low as 5-20 µg and decreased with a half-life of 3 hours. The threshold dose of LSD base for psychotropic effects was 10 µg.
“微剂量”的麦角酸二乙酰胺（LSD）被用于娱乐目的，以改善情绪和认知。人们对将 LSD 开发成药物的兴趣也越来越大。因此，我们进行了一项使用非常低剂量 LSD 的药代动力学-药效学研究。在 23 名健康参与者中进行了双盲、随机、安慰剂对照交叉研究，单次给予 LSD 碱（5、10 和 20μg）和安慰剂。测试日至少间隔 5 天。在给药后 6 小时内评估 LSD 的血浆水平和主观效应。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-主观效应关系。5、10 和 20μg LSD 给药后 LSD 的平均（95%置信区间）最大浓度分别为 151pg/mL（127-181）、279pg/mL（243-320）和 500pg/mL（413-607）。最大浓度在 1.1 小时后达到。平均消除半衰期为 2.7 小时（1.5-6.2）。5μg LSD 剂量不会引起明显的急性主观效应。与安慰剂相比，10μg LSD 剂量显著增加了“受影响”和“良好药物效应”的评分。这些作用在 10μg LSD 给药后平均 1.1 小时开始，在 2.5 小时达到峰值，在 5.1 小时结束。20μg LSD 剂量显著增加了“受影响”、“良好药物效应”和“不良药物效应”的评分。LSD 浓度在 5-20μg 的剂量范围内呈剂量比例增加，半衰期为 3 小时。LSD 碱产生精神作用的阈值剂量为 10μg。
