Maida Nunzia La, Papaseit Esther, Martínez Lucia, Pérez-Mañá Clara, Poyatos Lourdes, Pellegrini Manuela, Pichini Simona, Pacifici Roberta, Ventura Mireia, Galindo Liliana, Busardò Francesco Paolo, Farré Magí
Department of Excellence of Biomedical Science and Public Health, University "Politecnica delle Marche" of Ancona, Via Tronto 71, 60124 Ancona, Italy.
Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), 08916 Badalona, Spain.
Biology (Basel). 2021 Mar 24;10(4):257. doi: 10.3390/biology10040257.
Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 ( = 8) or cannabis flowering tops containing 10 or 20 mg THC ( = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.
合成大麻素（SCs）是欧盟早期预警系统和世界卫生组织监测的最常见的新型精神活性物质类别之一。相对于CB2受体，UR-144对CB1受体的亲和力相对较低。与其他大麻素受体激动剂一样，自2012年以来，欧盟早期预警系统一直在监测其对消费者的严重不良反应。由于UR-144人体药理学数据非常有限，因此进行了一项观察性研究，以评估其使用大麻烟卷给药后的急性药理作用，并以此作为比较依据。在口腔液中研究了UR-144和δ-9-四氢大麻酚（THC）的代谢情况。16名志愿者吸食了用烟草和1或1.5毫克剂量的UR-144（n = 8）或含有10或20毫克THC的大麻花枝（n = 8）制成的烟卷。测量了包括收缩压和舒张压、心率和皮肤温度在内的生理变量。使用一组视觉模拟量表（VAS）、成瘾研究中心量表（ARCI）-49项简短版和具有滥用潜力物质主观效应评估量表（VESSPA-SSE）来评估主观效应。在基线、吸烟后10、20、40分钟以及1、2、3和4小时采集口腔液，用于监测UR-144或THC浓度。结果显示，吸食UR-144和大麻后，收缩压和舒张压以及心率均有显著统计学升高。两种物质均使与兴奋样和快感相关的VAS得分升高，但大麻给药后的得分显著更高。未观察到致幻作用。口腔液中UR-144和THC的最大浓度分别出现在吸烟后20分钟和10分钟。口腔液中UR-144的存在构成了合成大麻素消费的非侵入性生物标志物。这项观察性研究的结果提供了UR-144药理作用的宝贵初步数据，显示与THC相比，其心血管效应相似，但主观效应强度较低。我们的结果必须通过更大样本的研究来证实，以广泛阐明UR-144的药理作用和健康风险概况。
