Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers
Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers
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DOI：
10.1080/02791072.2019.1593560
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发表时间：
2019-04-11
影响因子：
2.8
通讯作者：
Mendelson, John E.
中科院分区：
文献类型：
--
作者：
Baggott, Matthew J.;Garrison, Kathleen J.;Mendelson, John E.
诱惑剂，如3，4-亚甲基二氧基甲基苯丙胺(MDMA，“Molly”，“摇头丸”)似乎有不寻常的，潜在的治疗，情感影响。了解它们的机制可以从相关药物的临床实验中受益。然而，已知的第一种具有这种特性的药物--3，4-亚甲基二氧基苯丙胺(MDA)--的研究仍然很少，其在人体内的药代动力学尚不清楚。我们对1.4 mg/kg的消旋丙二醛进行了受试者内、双盲、安慰剂对照研究，并将结果与先前的1.5 mg/kg口服消旋MDMA的类似研究结果进行了比较。参与者对丙二醛的耐受性良好。丙二醛引起心率和血压的强劲增加，以及皮质醇和催乳素的增加，程度与MDMA相似。丙二醛自我报告的效果与MDMA以及经典迷幻剂的共同特征。丙二醛的自我报告效应持续时间长于MDMA，在8h时持续升高，而MDMA效应在6h后消失，丙二醛的Cmax和AUC(0无穷大)分别为229+/-39(均值+/-SD)和3636+/-958mUg/L，代谢产物4-羟基-3-甲氧基苯丙胺(HMA)为92+/-61和1544+/-741mU/L。受试者之间的MDA/HMA比率有相当大的差异。丙二醛和MDMA药代动力学的相似性表明，丙二醛作用的持续时间更长是由于药效学而不是药代动力学。
Entactogens such as 3,4-Methylenedioxymethamphetamine (MDMA, "molly", "ecstasy") appear to have unusual, potentially therapeutic, emotional effects. Understanding their mechanisms can benefit from clinical experiments with related drugs. Yet the first known drug with such properties, 3,4-Methylenedioxyamphetamine (MDA), remains poorly studied and its pharmacokinetics in humans are unknown. We conducted a within-subjects, double-blind, placebo-controlled study of 1.4 mg/kg oral racemic MDA and compared results to those from our prior similar studies with 1.5 mg/kg oral racemic MDMA. MDA was well-tolerated by participants. MDA induced robust increases in heart rate and blood pressure and increased cortisol and prolactin to a similar degree as MDMA. MDA self-report effects shared features with MDMA as well as with classical psychedelics. MDA self-report effects lasted longer than those of MDMA, with MDA effects remaining elevated at 8 h while MDMA effects resolved by 6 h. Cmax and AUC(0-infinity) for MDA were 229 +/- 39 (mean +/- SD) and 3636 +/- 958 mu g/L for MDA and 92 +/- 61 and 1544 +/- 741 mu g/L for the metabolite 4-hydroxy-3-methoxyamphetamine (HMA). There was considerable between-subject variation in MDA/HMA ratios. The similarity of MDA and MDMA pharmacokinetics suggests that the greater duration of MDA effects is due to pharmacodynamics rather than pharmacokinetics.