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Synthetic cannabinoids and synthetic cathinones are the most reported groups of NPSs. Despite NPSs being widely studied, due to their structural diversity and the constant emergence of novel compounds with unknown properties, the development of new techniques is required to clarify their mode of action and evaluate their toxicological effects. Metabolomics has been a useful tool to evaluate the metabolic effects of several xenobiotics. Herein, a systematic review was performed, following PRISMA guidelines, regarding metabolomic studies on synthetic cathinones and synthetic cannabinoids to evaluate their effects in cellular metabolism. In the studies, in vivo models were the most employed (86%) and the analysis mostly followed untargeted approaches (75%) using LC-MS techniques (67%). Both groups of NPSs seem to primarily interfere with energy metabolism-related pathways. Even though this type of study is still limited, metabolomics holds great promise as a tool to clarify mechanisms of actions, identify biomarkers of exposure, and explain the toxicological effects of NPSs.<\/jats:p>","DOI":"10.3390\/molecules30020290","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T09:49:17Z","timestamp":1736761757000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the Metabolic Footprint of New Psychoactive Substances by Metabolomics: A Systematic Review"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-1854","authenticated-orcid":false,"given":"Ana Sofia","family":"Almeida","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-5700","authenticated-orcid":false,"given":"Paula Guedes de","family":"Pinho","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-9163","authenticated-orcid":false,"given":"Carla","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"ref_1","unstructured":"Watson, R.R., and Zibadi, S. (2017). Chapter 29\u2014Novel Psychoactive Substances: A New Behavioral and Mental Health Threat. Addictive Substances and Neurological Disease, Academic Press."},{"key":"ref_2","unstructured":"Preedy, V.R. (2016). Chapter 63\u2014Treating the Phenomenon of New Psychoactive Substances: Synthetic Cannabinoids and Synthetic Cathinones. Neuropathology of Drug Addictions and Substance Misuse, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/bs.irn.2015.02.009","article-title":"Chapter Thirteen\u2014\u201cLegal Highs\u201d\u2014An Emerging Epidemic of Novel Psychoactive Substances","volume":"Volume 120","author":"Taba","year":"2015","journal-title":"International Review of Neurobiology"},{"key":"ref_4","unstructured":"EMCDDA (2024, November 06). New Psychoactive Substances\u2014The Current Situation in Europe (European Drug Report 2024). Available online: https:\/\/www.euda.europa.eu\/publications\/european-drug-report\/2024\/new-psychoactive-substances_en."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11419-017-0385-6","article-title":"The newest cathinone derivatives as designer drugs: An analytical and toxicological review","volume":"36","author":"Majchrzak","year":"2018","journal-title":"Forensic Toxicol."},{"key":"ref_6","first-page":"37","article-title":"Emerging drugs of abuse: Current perspectives on substituted cathinones","volume":"5","author":"Cesbron","year":"2014","journal-title":"Subst. Abus. Rehabil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0091-3057(93)90110-F","article-title":"Cocaine-stimulus generalization to two new designer drugs: Methcathinone and 4-methylaminorex","volume":"45","author":"Young","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00204-013-1163-9","article-title":"Khat and synthetic cathinones: A review","volume":"88","author":"Valente","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.lfs.2013.07.023","article-title":"Bath salts and synthetic cathinones: An emerging designer drug phenomenon","volume":"97","author":"German","year":"2014","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1080\/10408444.2019.1679087","article-title":"Synthetic cathinones: An evolving class of new psychoactive substances","volume":"49","author":"Alves","year":"2019","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/SAR.S73586","article-title":"Emerging drugs of abuse: Current perspectives on synthetic cannabinoids","volume":"6","author":"Debruyne","year":"2015","journal-title":"Subst. Abus. Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.7150\/ijms.27087","article-title":"Cannabinoids: From pot to lab","volume":"15","author":"Papaseit","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/10408444.2020.1762539","article-title":"The synthetic cannabinoids phenomenon: From structure to toxicological properties. A review","volume":"50","author":"Alves","year":"2020","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_14","unstructured":"EMCDDA (2024, April 21). Synthetic Cannabinoids in Europe (Perspectives on Drugs). Available online: https:\/\/www.emcdda.europa.eu\/topics\/pods\/synthetic-cannabinoids_en."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"de Oliveira, M.C., Vides, M.C., Lassi, D.L.S., Torales, J., Ventriglio, A., Bombana, H.S., Leyton, V., P\u00e9rico, C.A., Negr\u00e3o, A.B., and Malbergier, A. (2023). Toxicity of Synthetic Cannabinoids in K2\/Spice: A Systematic Review. Brain Sci., 13.","DOI":"10.3390\/brainsci13070990"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Almeida, A.S., Silva, B., Pinho, P.G., Remi\u00e3o, F., and Fernandes, C. (2022). Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation Methods. Molecules, 27.","DOI":"10.3390\/molecules27072057"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3390\/psychoactives3020018","article-title":"New Psychoactive Substances: Health and Legal Challenges","volume":"3","author":"Santos","year":"2024","journal-title":"Psychoactives"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, A.M., Carvalho, F., Guedes de Pinho, P., and Carvalho, M. (2021). Toxicometabolomics: Small Molecules to Answer Big Toxicological Questions. Metabolites, 11.","DOI":"10.3390\/metabo11100692"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/jat.2874","article-title":"Review: Toxicometabolomics","volume":"33","author":"Bouhifd","year":"2013","journal-title":"J. Appl. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"209","DOI":"10.14573\/altex.2013.2.209","article-title":"Metabolomics in toxicology and preclinical research","volume":"30","author":"Ramirez","year":"2013","journal-title":"Altex"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.dmpk.2015.10.002","article-title":"Application of metabolomics to toxicology of drugs of abuse: A mini review of metabolomics approach to acute and chronic toxicity studies","volume":"31","author":"Zaitsu","year":"2016","journal-title":"Drug. Metab. Pharmacokinet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s00204-020-02949-2","article-title":"In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV)","volume":"95","author":"Carvalho","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Manier, S.K., Keller, A., Sch\u00e4per, J., and Meyer, M.R. (2019). Untargeted metabolomics by high resolution mass spectrometry coupled to normal and reversed phase liquid chromatography as a tool to study the in vitro biotransformation of new psychoactive substances. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-39235-w"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/dta.2389","article-title":"Targeted and non-targeted metabolite identification of MAM-2201 in human, mouse, and rat hepatocytes","volume":"10","author":"Kim","year":"2018","journal-title":"Drug Test. Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105039","DOI":"10.1016\/j.arabjc.2023.105039","article-title":"Pharmacokinetics and metabolomics of the new psychoactive substance 4-chloroethylcathinone","volume":"16","author":"Wang","year":"2023","journal-title":"Arab. J. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hemmer, S., Wagmann, L., Pulver, B., Westphal, F., and Meyer, M.R. (2022). In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS\/MS. Metabolites, 12.","DOI":"10.3390\/metabo12121209"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152503","DOI":"10.1016\/j.tox.2020.152503","article-title":"Effect of temperature on 3,4-Methylenedioxypyrovalerone (MDPV)-induced metabolome disruption in primary mouse hepatic cells","volume":"441","author":"Bastos","year":"2020","journal-title":"Toxicology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Steuer, A.E., Kaelin, D., Boxler, M.I., Eisenbeiss, L., Holze, F., Vizeli, P., Czerwinska, J., Dargan, P.I., Abbate, V., and Liechti, M.E. (2020). Comparative Untargeted Metabolomics Analysis of the Psychostimulants 3,4-Methylenedioxy-Methamphetamine (MDMA), Amphetamine, and the Novel Psychoactive Substance Mephedrone after Controlled Drug Administration to Humans. Metabolites, 10.","DOI":"10.3390\/metabo10080306"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1177\/0269881118812103","article-title":"Metabolomics predicts the pharmacological profile of new psychoactive substances","volume":"33","author":"Olesti","year":"2019","journal-title":"J. Psychopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1007\/s00204-020-02742-1","article-title":"Toxicometabolomics of the new psychoactive substances \u03b1-PBP and \u03b1-PEP studied in HepaRG cell incubates by means of untargeted metabolomics revealed unexpected amino acid adducts","volume":"94","author":"Manier","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1007\/s00204-019-02566-8","article-title":"Metabolic signature of methylone in primary mouse hepatocytes, at subtoxic concentrations","volume":"93","author":"Carvalho","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shestakova, K.M., Mesonzhnik, N.V., Markin, P.A., Moskaleva, N.E., Nedorubov, A.A., Brito, A., Appolonova, E.G., Kuznetsov, R.M., Bochkareva, N.L., and Kukharenko, A. (2021). Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070668"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Markin, P.A., Brito, A., Moskaleva, N.E., Tagliaro, F., La Frano, M.R., Savitskii, M.V., and Appolonova, S.A. (2021). Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 243.","DOI":"10.1016\/j.cbpc.2021.109000"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, R.S., Fukumori, R., Takeda, T., Song, Y., Morimoto, S., Kikura-Hanajiri, R., Yamaguchi, T., Watanabe, K., Aritake, K., and Tanaka, Y. (2019). Elevation of endocannabinoids in the brain by synthetic cannabinoid JWH-018: Mechanism and effect on learning and memory. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-45969-4"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.lfs.2015.05.013","article-title":"Metabolome disruption of the rat cerebrum induced by the acute toxic effects of the synthetic cannabinoid MAM-2201","volume":"137","author":"Zaitsu","year":"2015","journal-title":"Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-030-51652-9_2","article-title":"NMR-Based Metabolomics","volume":"1280","author":"Raftery","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Emwas, A.H., Roy, R., McKay, R.T., Tenori, L., Saccenti, E., Gowda, G.A.N., Raftery, D., Alahmari, F., Jaremko, L., and Jaremko, M. (2019). NMR Spectroscopy for Metabolomics Research. Metabolites, 9.","DOI":"10.3390\/metabo9070123"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wishart, D.S., Cheng, L.L., Copi\u00e9, V., Edison, A.S., Eghbalnia, H.R., Hoch, J.C., Gouveia, G.J., Pathmasiri, W., Powers, R., and Schock, T.B. (2022). NMR and Metabolomics-A Roadmap for the Future. Metabolites, 12.","DOI":"10.3390\/metabo12080678"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Crook, A.A., and Powers, R. (2020). Quantitative NMR-Based Biomedical Metabolomics: Current Status and Applications. Molecules, 25.","DOI":"10.3390\/molecules25215128"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zeki, \u00d6.C., Eylem, C.C., Re\u00e7ber, T., K\u0131r, S., and Nemutlu, E. (2020). Integration of GC-MS and LC-MS for untargeted metabolomics profiling. J. Pharm. Biomed. Anal., 190.","DOI":"10.1016\/j.jpba.2020.113509"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1039\/C9RA08985C","article-title":"Mass spectrometry-based metabolomics in health and medical science: A systematic review","volume":"10","author":"Zhang","year":"2020","journal-title":"RSC Adv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jpba.2014.12.017","article-title":"Metabolomics for laboratory diagnostics","volume":"113","author":"Bujak","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Szeremeta, M., Pietrowska, K., Niemcunowicz-Janica, A., Kretowski, A., and Ciborowski, M. (2021). Applications of Metabolomics in Forensic Toxicology and Forensic Medicine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063010"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/164_2018_178","article-title":"Neuropharmacology of Synthetic Cathinones","volume":"252","author":"Baumann","year":"2018","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"218","DOI":"10.2174\/1570163813666160114093140","article-title":"From in vitro Experiments to in vivo and Clinical Studies; Pros and Cons","volume":"12","author":"Saeidnia","year":"2015","journal-title":"Curr. Drug. Discov. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1089\/omi.2012.0090","article-title":"Cell metabolomics","volume":"17","author":"Zhang","year":"2013","journal-title":"Omics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/toxsci\/kfp149","article-title":"Are in vitro tests suitable for regulatory use?","volume":"111","author":"Hartung","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1007\/s00204-015-1653-z","article-title":"3,4-Methylenedioxypyrovalerone (MDPV): In vitro mechanisms of hepatotoxicity under normothermic and hyperthermic conditions","volume":"90","author":"Valente","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.tox.2017.06.004","article-title":"Mechanisms of hepatocellular toxicity associated with new psychoactive synthetic cathinones","volume":"387","author":"Luethi","year":"2017","journal-title":"Toxicology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-319-47656-8_2","article-title":"Collection and Preparation of Clinical Samples for Metabolomics","volume":"965","author":"Chetwynd","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Smith, L., Villaret-Cazadamont, J., Claus, S.P., Canlet, C., Guillou, H., Cabaton, N.J., and Ellero-Simatos, S. (2020). Important Considerations for Sample Collection in Metabolomics Studies with a Special Focus on Applications to Liver Functions. Metabolites, 10.","DOI":"10.3390\/metabo10030104"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.clnu.2010.02.005","article-title":"Amino acid and protein metabolism in the human kidney and in patients with chronic kidney disease","volume":"29","author":"Garibotto","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0896-6273(01)00247-1","article-title":"Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals","volume":"29","author":"Maejima","year":"2001","journal-title":"Neuron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.neuropharm.2016.06.027","article-title":"Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: Behavioral, electrophysiological and neurochemical evidence","volume":"109","author":"Barbieri","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1093\/brain\/awg143","article-title":"Cannabis and the brain","volume":"126","author":"Iversen","year":"2003","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18150","DOI":"10.1073\/pnas.1113444108","article-title":"The major central endocannabinoid directly acts at GABA(A) receptors","volume":"108","author":"Sigel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"235","DOI":"10.4274\/tjps.galenos.2018.40820","article-title":"Psychoactive Bath Salts and Neurotoxicity Risk","volume":"17","author":"Altun","year":"2020","journal-title":"Turk. J. Pharma. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1007\/s00204-018-2314-9","article-title":"GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA)","volume":"92","author":"Bastos","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/nbm.1352","article-title":"Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat","volume":"22","author":"Perrine","year":"2009","journal-title":"NMR Biomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nature20153","article-title":"The effects of \u0394(9)-tetrahydrocannabinol on the dopamine system","volume":"539","author":"Bloomfield","year":"2016","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s00210-004-0921-x","article-title":"Differential effects of acute cannabinoid drug treatment, mediated by CB1 receptors, on the in vivo activity of tyrosine and tryptophan hydroxylase in the rat brain","volume":"369","author":"Moranta","year":"2004","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e664","DOI":"10.1038\/cddis.2013.151","article-title":"Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells","volume":"4","author":"Dando","year":"2013","journal-title":"Cell Death Dis."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/2\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:27:53Z","timestamp":1759919273000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/2\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,13]]},"references-count":64,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["molecules30020290"],"URL":"https:\/\/doi.org\/10.3390\/molecules30020290","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,13]]}}}