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急性给予合成大麻素 JWH-018 后的神经认知和主观体验:一项 1 期、安慰剂对照、初步研究。

Neurocognition and subjective experience following acute doses of the synthetic cannabinoid JWH-018: a phase 1, placebo-controlled, pilot study.

机构信息

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.

Department of Forensic Toxicology, Institute of Legal Medicine, Goethe University of Frankfurt, Frankfurt, Germany.

出版信息

Br J Pharmacol. 2018 Jan;175(1):18-28. doi: 10.1111/bph.14066. Epub 2017 Nov 29.

Abstract

BACKGROUND AND PURPOSE

Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to their easy access and portrayed safety. Controlled studies on the behavioural effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds.

EXPERIMENTAL APPROACH

This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration. JWH-018, 2 and 3 mg, was administered to six healthy cannabis-experienced volunteers in a placebo-controlled, cross-over study following an escalating dosing schedule. Participants were monitored for 12 h after drug administration, and several neurocognitive measures and subjective questionnaires were taken.

KEY RESULTS

Serum concentrations of JWH-018 were highest after the 2 mg dose but generally low after administration of both doses. Both doses of JWH-018 were well tolerated, and no serious side effects were reported. Participants reported feeling more 'high' at 1 and 2 h after administration, particularly after the 2 mg dose. Behavioural impairments also emerged despite the low serum concentrations of JWH-018. The low dose of JWH-018 impaired performance on the tracking, divided attention and stop signal task.

CONCLUSION AND IMPLICATIONS

JWH-018 dosing in the present study resulted in drug concentrations that were generally low and not fully representative of common use. Yet initial impairments of neurocognitive function and subjective feelings of high did emerge despite low levels of JWH-018 in serum. Higher doses are needed to obtain a more representative risk profile of JWH-018.

摘要

背景与目的

合成大麻素(通常以香料或 K2 的形式出售)由于其易于获取和所谓的安全性,已成为大麻的一种非常受欢迎的替代品。目前缺乏对合成大麻素行为影响的对照研究,这阻碍了对这些化合物的风险评估。

实验方法

这是首次尝试评估合成大麻素 JWH-018 在受控给药后对人类神经认知和主观体验的影响。JWH-018 2 和 3 毫克,在递增剂量方案后,在一项安慰剂对照、交叉研究中,给予六名有经验的大麻使用者。给药后 12 小时内对参与者进行监测,并进行了几项神经认知测试和主观问卷。

主要结果

JWH-018 的血清浓度在 2 毫克剂量后最高,但两种剂量后通常较低。两种剂量的 JWH-018 均耐受良好,未报告严重副作用。参与者报告在给药后 1 和 2 小时感觉更“高”,尤其是在 2 毫克剂量后。尽管 JWH-018 的血清浓度较低,但仍出现了行为障碍。低剂量的 JWH-018 会损害跟踪、分散注意力和停止信号任务的表现。

结论与意义

本研究中的 JWH-018 剂量导致药物浓度通常较低,不完全代表常见用途。然而,尽管血清中的 JWH-018 水平较低,但仍出现了神经认知功能和主观高感的初始损害。需要更高的剂量来获得更具代表性的 JWH-018 风险概况。

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