The use of new psychoactive substances (NPS) is increasing and currently > 600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization.

We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP).

Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HT₂receptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABA_Areceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure.

Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks.

新的精神活性物质（NPS）的使用正在增加，目前已经报道了> 600 NPS。但是，关于NPS的神经药理和毒理作用的信息有限，妨碍了风险表征。

我们回顾了有关体外神经元作用方式的文献，以获取不同种类的非法药物和NPS的作用指纹图谱。选择了最常报告的NPS进行审查：卡西酮（MDPV，α-PVP，甲吗啡酮，4-MEC，戊酮，甲酮），大麻素（JWH-018），（致卤）苯乙胺（4-氟苯丙胺，苯并呋喃（5-APB ，6-APB），2C-B，NBOMes（25B-NBOMe，25C-NBOMe，25I-NBOMe），芳基环己胺（甲氧西敏）和哌嗪衍生物（mCPP，TFMPP，BZP）。

我们的效果指纹图谱突显了研究的不同NPS的主要作用方式，包括单胺再摄取转运蛋白（卡西酮和非卤代苯乙胺）的抑制和/或逆转，5-HT ₂受体（卤代苯乙胺和哌嗪）的激活，大麻素受体（大麻素）和对NDMA受体的抑制作用（芳基环己胺）。重要的是，我们通过将报告的效应浓度与娱乐使用期间估计的人脑浓度相关联，从而确定了其他目标。这些额外的靶标包括多巴胺受体，α-和β-肾上腺素能受体，GABA _A受体和乙酰胆碱受体，它们在暴露后都可能导致观察到的临床症状。

随着NPS数量的不断增加，还需要其他数据。同样，我们获得的效果指纹仍然不完整，并且在所报告的效果和效果大小方面存在较大差异。专用的体外筛选电池将有助于补充NPS的特效指纹。这些指纹可以在NPS的风险评估中实施，这对于最终采取控制措施以减少公共卫生风险是必需的。