@article{2c67f1b6c7ad4105b1ca347ed4d0852c,
title = "Metabolomics predicts the pharmacological profile of new psychoactive substances",
abstract = "BACKGROUND:: The unprecedented proliferation of new psychoactive substances (NPS) threatens public health and challenges drug policy. Information on NPS pharmacology and toxicity is, in most cases, unavailable or very limited and, given the large number of new compounds released on the market each year, their timely evaluation by current standards is certainly challenging.AIMS:: We present here a metabolomics-targeted approach to predict the pharmacological profile of NPS.METHODS:: We have created a machine learning algorithm employing the quantification of monoamine neurotransmitters and steroid hormones in rats to predict the similarity of new drugs to classical ones of abuse (MDMA (3,4-methyl enedioxy methamphetamine), methamphetamine, cocaine, heroin and Δ9-tetrahydrocannabinol).RESULTS:: We have characterized each classical drug of abuse and two examples of NPS (mephedrone and JWH-018) following alterations observed in the targeted metabolome profile (monoamine neurotransmitters and steroid hormones) in different brain areas, plasma and urine at 1 h and 4 h post drug/vehicle administration. As proof of concept, our model successfully predicted the pharmacological profile of a synthetic cannabinoid (JWH-018) as a cannabinoid-like drug and synthetic cathinone (mephedrone) as a MDMA-like psychostimulant.CONCLUSION:: Our approach allows a fast NPS pharmacological classification which will benefit both drug risk evaluation policies and public health.",
keywords = "CANNABINOIDS, DOPAMINE, DRUG DISCOVERY, JWH-018, MEPHEDRONE, METABOLISM, PHARMACOKINETICS, SEROTONIN, TRYPTOPHAN, Targeted metabolomics, URINE, new psychoactive substances, predicted pharmacology",
author = "Eul{\`a}lia Olesti and {De Toma}, Ilario and Ramaekers, {Johannes G} and Brunt, {Tibor M} and Carb{\'o}, {Marcel L{\'i}} and Cristina Fern{\'a}ndez-Avil{\'e}s and Patricia Robledo and Mag{\'i} Farr{\'e} and Mara Dierssen and Pozo, {{\'O}scar J} and {de la Torre}, Rafael",
note = "Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the European Commission (Drugs Policy Initiatives, Justice Programme 2014–2020, contract no. HOME/2014/JDRU/AG/DRUG/7082, Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology). Support by the Red de Trastornos Adictivos RTA RD12/0028/0006 and the DIUE of the Generalitat de Catalunya (2014 SGR 680; SGR 2014/1125) and the Program of Excellence Severo Ochoa (SEV-2012-0208) is also acknowledged. The Spanish Health National System is acknowledged for the contract of O.J.P. (CPII16/00027). This work was supported by a grant (I.D.T.) from the Impulse post-doctoral Marie-Curie co-funded program from CRG. Funding Information: The authors are very grateful to Rafael Maldonado and Andr?s Ozaita for their valuable assistance during ?9-THC experiments. The valuable involvement of Mariona Cabanas and Josep Rodr?guez-Morat? is also acknowledged. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the European Commission (Drugs Policy Initiatives, Justice Programme 2014?2020, contract n o. HOME/2014/JDRU/AG/DRUG/7082, Predicting Risk of Emerging Drugs with In silico and Clinical Toxicology). Support by the Red de Trastornos Adictivos RTA RD12/0028/0006 and the DIUE of the Generalitat de Catalunya (2014 SGR 680; SGR 2014/1125) and the Program of Excellence Severo Ochoa (SEV-2012-0208) is also acknowledged. The Spanish Health National System is acknowledged for the contract of O.J.P. (CPII16/00027). This work was supported by a grant (I.D.T.) from the Impulse post-doctoral Marie-Curie co-funded program from CRG. Publisher Copyright: {\textcopyright} The Author(s) 2018.",
year = "2019",
month = mar,
doi = "10.1177/0269881118812103",
language = "English",
volume = "33",
pages = "347--354",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",
number = "3",
}