de Sousa Fernandes Perna Elizabeth B, Theunissen Eef L, Dolder Patrick C, Mason Natasha L, Hutten Nadia R P W, Toennes Stefan W, Kuypers Kim P C, Ramaekers Johannes G
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands.
Department of Forensic Toxicology, Institute of Legal Medicine, Goethe University Frankfurt, Frankfurt, Germany.
Front Pharmacol. 2018 Jul 6;9:713. doi: 10.3389/fphar.2018.00713. eCollection 2018.
Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers ( = 12) who received single doses of 100 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions. Overall, 4-FA produced a strong elevation in blood pressure up until 4-5 h after administration that was followed by a sustained increase in heart rate. After an interim review of safety data from five participants, a decision was taken to cancel administration of 150 mg. We subsequently obtained complete datasets for placebo and 100 mg 4-FA treatments only. Effects of 4-FA on mood and neurocognitive function were most distinct at 1 h post drug and included significant elevations of vigor, friendliness, elation, arousal, positive mood, as well as improvements in attention and motor performance. Negative affect was also reported as time progressed in the acute phase and even more so during the subacute phase. Overall, the influence of 4-FA on vital signs, mood, and neurocognition was similar to that observed with other stimulants. Present findings confirm clinical observations of acute toxicity among 4-FA users and warrant warnings about potential health risks associated with 4-FA use.
在过去几年中，新型精神活性物质（NPS）的可得性呈指数级增长。由于缺乏针对人类健康参数的药理学研究，对NPS的风险评估受到阻碍。本研究的目的是评估健康志愿者（n = 12）在单次服用100毫克和150毫克4-氟苯丙胺（4-FA）后的安全性和神经认知功能，4-FA是一种与严重心血管和脑血管并发症相关的苯乙胺。该研究被设置为一项安慰剂对照、受试者内的1期试验，因为这是首次在受控条件下给人类施用4-FA。总体而言，4-FA在给药后4至5小时内导致血压大幅升高，随后心率持续增加。在对五名参与者的安全数据进行中期审查后，决定取消150毫克剂量的给药。我们随后仅获得了安慰剂和100毫克4-FA治疗的完整数据集。4-FA对情绪和神经认知功能的影响在服药后1小时最为明显，包括活力、友好度、兴高采烈、觉醒、积极情绪显著升高，以及注意力和运动表现改善。在急性期随着时间推移也报告了消极情绪，在亚急性期更为明显。总体而言，4-FA对生命体征、情绪和神经认知的影响与其他兴奋剂观察到的影响相似。目前的研究结果证实了4-FA使用者急性毒性的临床观察结果，并证明有必要对与使用4-FA相关的潜在健康风险发出警告。
