Molecular Cognition Laboratory, Department of Psychology (M.M.P., S.G.A.) and Program in Neurosciences (S.G.A.), University of California San Diego, La Jolla, California
Molecular Cognition Laboratory, Department of Psychology (M.M.P., S.G.A.) and Program in Neurosciences (S.G.A.), University of California San Diego, La Jolla, California.
Pharmacol Rev. 2019 Jul;71(3):413-449. doi: 10.1124/pr.118.017087.
±3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic, psychoactive drug that is primarily used recreationally but also may have some therapeutic value. At low doses, MDMA produces feelings of relaxation, empathy, emotional closeness, and euphoria. Higher doses can produce unpleasant psychostimulant- and hallucinogen-like adverse effects and therefore are usually not taken intentionally. There is considerable evidence that MDMA produces neurotoxicity and cognitive deficits at high doses; however, these findings may not generalize to typical recreational or therapeutic use of low-dose MDMA. Here, we systematically review 25 years of research on the cognitive effects of MDMA in animals, with a critical focus on dose. We found no evidence that doses of less than 3 mg/kg MDMA-the dose range that users typically take-produce cognitive deficits in animals. Doses of 3 mg/kg or greater, which were administered most often and frequently ranged from 5 to 20 times greater than an average dose, also did not produce cognitive deficits in a slight majority of experiments. Overall, the preclinical evidence of MDMA-induced cognitive deficits is weak and, if anything, may be the result of unrealistically high dosing. While factors associated with recreational use such as polydrug use, adulterants, hyperthermia, and hyponatremia can increase the potential for neurotoxicity, the short-term, infrequent, therapeutic use of ultra low-dose MDMA is unlikely to pose significant cognitive risks. Future studies must examine any adverse cognitive effects of MDMA using clinically relevant doses to reliably assess its potential as a psychotherapeutic.
±3,4-亚甲二氧基甲基苯丙胺（MDMA）是一种合成的、具有精神活性的药物，主要被用作娱乐用途，但也可能具有一定的治疗价值。在低剂量下，MDMA 会产生放松、共情、情感亲近和欣快的感觉。较高的剂量可能会产生不愉快的精神兴奋剂和致幻剂样的不良反应，因此通常不会被故意服用。有大量证据表明，MDMA 在高剂量下会产生神经毒性和认知缺陷；然而，这些发现可能不适用于典型的低剂量 MDMA 娱乐或治疗用途。在这里，我们系统地回顾了 25 年来关于 MDMA 在动物中的认知效应的研究，重点关注剂量。我们没有发现证据表明低于 3 毫克/公斤 MDMA 的剂量——使用者通常服用的剂量范围——会在动物中产生认知缺陷。而 3 毫克/公斤或更高的剂量，最常和频繁使用的剂量范围是平均剂量的 5 到 20 倍，在大多数实验中也没有产生认知缺陷。总的来说，MDMA 引起的认知缺陷的临床前证据是薄弱的，如果有的话，可能是由于剂量不切实际地高造成的。虽然与娱乐用途相关的因素，如多药使用、掺杂物、体温过高和低钠血症，会增加神经毒性的可能性，但短期、偶尔、治疗性使用超低剂量的 MDMA 不太可能对认知造成显著风险。未来的研究必须使用临床相关的剂量来检查 MDMA 的任何不良认知影响，以可靠地评估其作为心理治疗的潜力。
