{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T20:02:16Z","timestamp":1776715336701,"version":"3.51.2"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T00:00:00Z","timestamp":1568160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T00:00:00Z","timestamp":1568160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We have developed the Computational Analysis of Novel Drug Opportunities (CANDO) platform to infer homology of drug behaviour at a proteomic level by constructing and analysing structural compound-proteome interaction signatures of 3,733 compounds with 48,278 proteins in a shotgun manner. We applied the CANDO platform to predict putative therapeutic properties of 428 psychoactive compounds that belong to the phenylethylamine, tryptamine, and cannabinoid chemical classes for treating mental health indications. Our findings indicate that these 428 psychoactives are among the top-ranked predictions for a significant fraction of mental health indications, demonstrating a significant preference for treating such indications over non-mental health indications, relative to randomized controls. Also, we analysed the use of specific tryptamines for the treatment of sleeping disorders, bupropion for substance abuse disorders, and cannabinoids for epilepsy. Our innovative use of the CANDO platform may guide the identification and development of novel therapies for mental health indications and provide an understanding of their causal basis on a detailed mechanistic level. These predictions can be used to provide new leads for preclinical drug development for mental health and other neurological disorders.<\/jats:p>","DOI":"10.1038\/s41598-019-49515-0","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T06:03:02Z","timestamp":1568181782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Computational chemoproteomics to understand the role of selected psychoactives in treating mental health indications"],"prefix":"10.1038","volume":"9","author":[{"given":"Jonathan","family":"Fine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram","family":"Samudrala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-7898","authenticated-orcid":false,"given":"Gaurav","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,9,11]]},"reference":[{"key":"49515_CR1","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1586\/epr.09.65","volume":"6","author":"N Bonander","year":"2009","unstructured":"Bonander, N. & Bill, R. M. Relieving the first bottleneck in the drug discovery pipeline: using array technologies to rationalize membrane protein production. Expert Rev. Proteomics 6, 501\u2013505 (2009).","journal-title":"Expert Rev. Proteomics"},{"key":"49515_CR2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.2174\/157489111796064641","volume":"6","author":"SH Gillespie","year":"2011","unstructured":"Gillespie, S. H. & Singh, K. XDR-TB, what is it; how is it treated; and why is therapeutic failure so high. Recent Pat. Antiinfect. Drug Discov. 6, 77\u201383 (2011).","journal-title":"Recent Pat. Antiinfect. Drug Discov."},{"key":"49515_CR3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/9781118098141.ch13","volume-title":"Polypharmacology in Drug Discovery","author":"Jeremy A. Horst","year":"2012","unstructured":"Horst, J. A., Laurenzi, A., Bernard, B. & Samudrala, R. Computational Multitarget Drug Discovery. In Polypharmacology in Drug Discovery 263\u2013301, https:\/\/doi.org\/10.1002\/9781118098141.ch13 (John Wiley & Sons, Inc., 2012)."},{"key":"49515_CR4","doi-asserted-by":"publisher","first-page":"749","DOI":"10.4155\/fmc.09.53","volume":"1","author":"LV Sacks","year":"2009","unstructured":"Sacks, L. V. & Behrman, R. E. Challenges, successes and hopes in the development of novel TB therapeutics. Future Med. Chem. 1, 749\u2013756 (2009).","journal-title":"Future Med. Chem."},{"key":"49515_CR5","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.drudis.2011.02.016","volume":"16","author":"S Ekins","year":"2011","unstructured":"Ekins, S., Williams, A. J., Krasowski, M. D. & Freundlich, J. S. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov. Today 16, 298\u2013310 (2011).","journal-title":"Drug Discov. Today"},{"key":"49515_CR6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/bib\/bbr006","volume":"12","author":"K Xu","year":"2011","unstructured":"Xu, K. & Cote, T. R. Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases. Brief. Bioinform. 12, 341\u2013345 (2011).","journal-title":"Brief. Bioinform."},{"key":"49515_CR7","first-page":"1487","volume":"294","author":"E Jenwitheesuk","year":"2005","unstructured":"Jenwitheesuk, E. & Samudrala, R. Identification of Potential Multitarget Antimalarial Drugs. JAMA 294, 1487 (2005).","journal-title":"JAMA"},{"key":"49515_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.tips.2007.11.007","volume":"29","author":"E Jenwitheesuk","year":"2008","unstructured":"Jenwitheesuk, E., Horst, J. A., Rivas, K. L., Van Voorhis, W. C. & Samudrala, R. Novel paradigms for drug discovery: computational multitarget screening. Trends Pharmacol. Sci. 29, 62\u201371 (2008).","journal-title":"Trends Pharmacol. Sci."},{"key":"49515_CR9","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1016\/j.drudis.2014.06.018","volume":"19","author":"M Minie","year":"2014","unstructured":"Minie, M. et al. CANDO and the infinite drug discovery frontier. Drug Discovery Today 19, 1353\u20131363 (2014).","journal-title":"Drug Discovery Today"},{"key":"49515_CR10","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/bib\/bbr028","volume":"12","author":"SJ Swamidass","year":"2011","unstructured":"Swamidass, S. J. Mining small-molecule screens to repurpose drugs. Brief. Bioinform. 12, 327\u2013335 (2011).","journal-title":"Brief. Bioinform."},{"key":"49515_CR11","doi-asserted-by":"publisher","first-page":"W441","DOI":"10.1093\/nar\/gkq400","volume":"38","author":"J Ren","year":"2010","unstructured":"Ren, J., Xie, L., Li, W. W. & Bourne, P. E. SMAP-WS: a parallel web service for structural proteome-wide ligand-binding site comparison. Nucleic Acids Res. 38, W441\u2013W444 (2010).","journal-title":"Nucleic Acids Res."},{"key":"49515_CR12","doi-asserted-by":"publisher","first-page":"e721","DOI":"10.1371\/journal.pntd.0000721","volume":"4","author":"JM Costin","year":"2010","unstructured":"Costin, J. M. et al. Structural Optimization and De Novo Design of Dengue Virus Entry Inhibitory Peptides. PLoS Negl. Trop. Dis. 4, e721 (2010).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"49515_CR13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.antiviral.2010.11.008","volume":"89","author":"CO Nicholson","year":"2011","unstructured":"Nicholson, C. O. et al. Viral entry inhibitors block dengue antibody-dependent enhancement in vitro. Antiviral Res. 89, 71\u201374 (2011).","journal-title":"Antiviral Res."},{"key":"49515_CR14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1177\/0022034512449837","volume":"24","author":"JA Horst","year":"2012","unstructured":"Horst, J. A. et al. Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries. Adv. Dent. Res. 24, 86\u201393 (2012).","journal-title":"Adv. Dent. Res."},{"key":"49515_CR15","doi-asserted-by":"publisher","first-page":"705","DOI":"10.2174\/1389557515666150219145148","volume":"15","author":"G Sethi","year":"2015","unstructured":"Sethi, G., Chopra, G. & Samudrala, R. Multiscale Modelling of Relationships between Protein Classes and Drug Behavior Across all Diseases Using the CANDO Platform. Mini Rev. Med. Chem. 15, 705\u2013717 (2015).","journal-title":"Mini Rev. Med. Chem."},{"key":"49515_CR16","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1021\/acsmedchemlett.6b00468","volume":"8","author":"X Ma","year":"2017","unstructured":"Ma, X. et al. Identification of New FLT3 Inhibitors That Potently Inhibit AML Cell Lines via an Azo Click-It\/Staple-It Approach. ACS Med. Chem. Lett. 8, 492\u2013497 (2017).","journal-title":"ACS Med. Chem. Lett."},{"key":"49515_CR17","doi-asserted-by":"crossref","unstructured":"Hernandez-Perez, M. et al. Inhibition of 12\/15-Lipoxygenase Protects Against \u03b2 Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes. Diabetes (2017).","DOI":"10.2337\/db17-0215"},{"key":"49515_CR18","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nrd1824","volume":"4","author":"R Pink","year":"2005","unstructured":"Pink, R., Hudson, A., Mouri\u00e8s, M.-A. & Bendig, M. Opportunities and Challenges in Antiparasitic Drug Discovery. Nat. Rev. Drug Discov. 4, 727\u2013740 (2005).","journal-title":"Nat. Rev. Drug Discov."},{"key":"49515_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.lfs.2005.09.012","volume":"78","author":"MJ Balunas","year":"2005","unstructured":"Balunas, M. J. & Kinghorn, A. D. Drug discovery from medicinal plants. Life Sci. 78, 431\u2013441 (2005).","journal-title":"Life Sci."},{"key":"49515_CR20","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1039\/c3np20111b","volume":"30","author":"M Hur","year":"2013","unstructured":"Hur, M. et al. A global approach to analysis and interpretation of metabolic data for plant natural product discovery. Nat. Prod. Rep. 30, 565 (2013).","journal-title":"Nat. Prod. Rep."},{"key":"49515_CR21","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1021\/np9604893","volume":"60","author":"GM Cragg","year":"1997","unstructured":"Cragg, G. M., Newman, D. J. & Snader, K. M. Natural products in drug discovery and development. Journal of Natural Products 60, 52\u201360 (1997).","journal-title":"Journal of Natural Products"},{"key":"49515_CR22","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.drudis.2015.01.009","volume":"21","author":"E Patridge","year":"2016","unstructured":"Patridge, E., Gareiss, P., Kinch, M. S. & Hoyer, D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discovery Today 21, 204\u2013207 (2016).","journal-title":"Drug Discovery Today"},{"key":"49515_CR23","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235\u2013242 (2000).","journal-title":"Nucleic Acids Res."},{"key":"49515_CR24","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/prot.340090107","volume":"9","author":"C Sander","year":"1991","unstructured":"Sander, C. & Schneider, R. Database of homology-derived protein structures and the structural meaning of sequence alignment. Proteins Struct. Funct. Bioinforma. 9, 56\u201368 (1991).","journal-title":"Proteins Struct. Funct. Bioinforma."},{"key":"49515_CR25","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.2174\/1381612822666160325121943","volume":"22","author":"G Chopra","year":"2016","unstructured":"Chopra, G. & Samudrala, R. Exploring Polypharmacology in Drug Discovery and Repurposing Using the CANDO Platform. Curr. Pharm. Des. 22, 3109\u201323 (2016).","journal-title":"Curr. Pharm. Des."},{"key":"49515_CR26","doi-asserted-by":"publisher","first-page":"4297","DOI":"10.1093\/bioinformatics\/bti694","volume":"21","author":"ACR Martin","year":"2005","unstructured":"Martin, A. C. R. Mapping PDB chains to UniProtKB entries. Bioinformatics 21, 4297\u20134301 (2005).","journal-title":"Bioinformatics"},{"key":"49515_CR27","doi-asserted-by":"publisher","unstructured":"Fine, J., Konc, J., Samudrala, R. & Chopra, G. CANDOCK: Chemical atomic network based hierarchical flexible docking algorithm using generalized statistical potentials. bioRxiv, https:\/\/doi.org\/10.26434\/chemrxiv.7187540.v1 (2018).","DOI":"10.26434\/chemrxiv.7187540.v1"},{"key":"49515_CR28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/prot.22323","volume":"76","author":"B Bernard","year":"2009","unstructured":"Bernard, B. & Samudrala, R. A generalized knowledge-based discriminatory function for biomolecular interactions. Proteins Struct. Funct. Bioinforma. 76, 115\u2013128 (2009).","journal-title":"Proteins Struct. Funct. Bioinforma."},{"key":"49515_CR29","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.3390\/molecules21121537","volume":"21","author":"G Chopra","year":"2016","unstructured":"Chopra, G., Kaushik, S., Elkin, P. L. & Samudrala, R. Combating Ebola with repurposed therapeutics using the CANDO platform. Molecules 21, 1537 (2016).","journal-title":"Molecules"},{"key":"49515_CR30","first-page":"299","volume":"40","author":"E Jenwitheesuk","year":"2003","unstructured":"Jenwitheesuk, E. et al. Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations. BMC Struct. Biol. 2003 31 40, 299\u2013309 (2003).","journal-title":"BMC Struct. Biol. 2003 31"},{"key":"49515_CR31","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1006\/jmbi.1997.1479","volume":"275","author":"R Samudrala","year":"1998","unstructured":"Samudrala, R. & Moult, J. An all-atom distance-dependent conditional probability discriminatory function for protein structure prediction 1 1Edited by F. Cohen. J. Mol. Biol. 275, 895\u2013916 (1998).","journal-title":"J. Mol. Biol."},{"key":"49515_CR32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1006\/jmbi.1998.1689","volume":"279","author":"R Samudrala","year":"1998","unstructured":"Samudrala, R. & Moult, J. A graph-theoretic algorithm for comparative modeling of protein structure. J. Mol. Biol. 279, 287\u2013302 (1998).","journal-title":"J. Mol. Biol."},{"key":"49515_CR33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1006\/jmbi.2000.3835","volume":"300","author":"Y Xia","year":"2000","unstructured":"Xia, Y., Huang, E. S., Levitt, M. & Samudrala, R. Ab initio construction of protein tertiary structures using a hierarchical approach. J. Mol. Biol. 300, 171\u2013185 (2000).","journal-title":"J. Mol. Biol."},{"key":"49515_CR34","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/(SICI)1097-0134(1999)37:3+<194::AID-PROT24>3.0.CO;2-F","volume":"Suppl 3","author":"R Samudrala","year":"1999","unstructured":"Samudrala, R., Xia, Y., Huang, E. & Levitt, M. Ab initio protein structure prediction using a combined hierarchical approach. Proteins Suppl 3, 194\u20138 (1999).","journal-title":"Proteins"},{"key":"49515_CR35","doi-asserted-by":"publisher","first-page":"e1002503","DOI":"10.1371\/journal.pcbi.1002503","volume":"8","author":"F Cheng","year":"2012","unstructured":"Cheng, F. et al. Prediction of drug-target interactions and drug repositioning via network-based inference. PLoS Comput. Biol. 8, e1002503 (2012).","journal-title":"PLoS Comput. Biol."},{"key":"49515_CR36","doi-asserted-by":"publisher","first-page":"e41064","DOI":"10.1371\/journal.pone.0041064","volume":"7","author":"F Cheng","year":"2012","unstructured":"Cheng, F., Zhou, Y., Li, W., Liu, G. & Tang, Y. Prediction of chemical-protein interactions network with weighted network-based inference method. PLoS One 7, e41064 (2012).","journal-title":"PLoS One"},{"key":"49515_CR37","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/nar\/gkg056","volume":"31","author":"GD Bader","year":"2003","unstructured":"Bader, G. D., Betel, D. & Hogue, C. W. V. BIND: The Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248\u2013250 (2003).","journal-title":"Nucleic Acids Res."},{"key":"49515_CR38","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tips.2005.02.007","volume":"26","author":"P Csermely","year":"2005","unstructured":"Csermely, P., \u00c1goston, V. & Pongor, S. The efficiency of multi-target drugs: The network approach might help drug design. Trends in Pharmacological Sciences 26, 178\u2013182 (2005).","journal-title":"Trends in Pharmacological Sciences"},{"key":"49515_CR39","doi-asserted-by":"publisher","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, https:\/\/doi.org\/10.1176\/appi.books.9780890425596 (2013).","DOI":"10.1176\/appi.books.9780890425596"},{"key":"49515_CR40","doi-asserted-by":"publisher","first-page":"350","DOI":"10.7196\/SAMJ.7863","volume":"104","author":"Z Mohamed-Kaloo","year":"2014","unstructured":"Mohamed-Kaloo, Z. & Laher, S. Perceptions of mental illness among Muslim general practitioners in South Africa. South African Med. J. 104, 350 (2014).","journal-title":"South African Med. J."},{"key":"49515_CR41","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1177\/0004867412438873","volume":"46","author":"N R\u00fcsch","year":"2012","unstructured":"R\u00fcsch, N., Evans-Lacko, S. & Thornicroft, G. What is a mental illness? Public views and their effects on attitudes and disclosure. Aust. New Zeal. J. Psychiatry 46, 641\u2013650 (2012).","journal-title":"Aust. New Zeal. J. Psychiatry"},{"key":"49515_CR42","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/S0011-393X(00)80049-1","volume":"61","author":"L Skaer","year":"2000","unstructured":"Skaer, L., Robison, M., Sclar, A. & Galin, S. Treatment of depressive illness among children and adolescents in the United States. Curr. Ther. Res. 61, 692 (2000).","journal-title":"Curr. Ther. Res."},{"key":"49515_CR43","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jad.2015.12.005","volume":"192","author":"A Bauer","year":"2016","unstructured":"Bauer, A., Knapp, M. & Parsonage, M. Lifetime costs of perinatal anxiety and depression. J. Affect. Disord. 192, 83\u201390 (2016).","journal-title":"J. Affect. Disord."},{"key":"49515_CR44","doi-asserted-by":"publisher","first-page":"777","DOI":"10.2105\/AJPH.2012.301056","volume":"103","author":"C Henderson","year":"2013","unstructured":"Henderson, C., Evans-Lacko, S. & Thornicroft, G. Mental illness stigma, help seeking, and public health programs. Am. J. Public Health 103, 777\u201380 (2013).","journal-title":"Am. J. Public Health"},{"key":"49515_CR45","unstructured":"Medco Health Solutions. America\u2019s state of mind (2011)."},{"key":"49515_CR46","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1176\/appi.ajp.159.4.561","volume":"159","author":"MJ Sernyak","year":"2002","unstructured":"Sernyak, M. J., Leslie, D. L., Alarcon, R. D., Losonczy, M. F. & Rosenheck, R. Association of Diabetes Mellitus With Use of Atypical Neuroleptics in the Treatment of Schizophrenia. Am. J. Psychiatry 159, 561\u2013566 (2002).","journal-title":"Am. J. Psychiatry"},{"key":"49515_CR47","unstructured":"National Alliance on Mental Illness. Mental Health Facts. National Institute of Mental Health Available at, https:\/\/www.nami.org\/NAMI\/media\/NAMI-Media\/Infographics\/Children-MH-Facts-NAMI.pdf (2018)."},{"key":"49515_CR48","unstructured":"National Alliance on Mental Illness. What is mental illness: Mental illness facts, Www.Nami.Org 1\u20132 (2013)."},{"key":"49515_CR49","doi-asserted-by":"crossref","unstructured":"Cox, G. R. et al. Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database of Systematic Reviews 2014 (2014).","DOI":"10.1002\/14651858.CD008324.pub3"},{"key":"49515_CR50","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.cell.2016.10.027","volume":"167","author":"G Sharon","year":"2016","unstructured":"Sharon, G., Sampson, T. R., Geschwind, D. H. & Mazmanian, S. K. The Central Nervous System and the Gut Microbiome. Cell 167, 915\u2013932 (2016).","journal-title":"Cell"},{"key":"49515_CR51","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.neubiorev.2017.08.019","volume":"84","author":"H Akil","year":"2018","unstructured":"Akil, H. et al. Treatment resistant depression: A multi-scale, systems biology approach. Neurosci. Biobehav. Rev. 84, 272\u2013288 (2018).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"49515_CR52","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.drudis.2015.03.015","volume":"20","author":"X Zheng","year":"2015","unstructured":"Zheng, X., Zhang, X., Wang, G. & Hao, H. Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder. Drug Discov. Today 20, 562\u2013568 (2015).","journal-title":"Drug Discov. Today"},{"key":"49515_CR53","doi-asserted-by":"crossref","first-page":"355","DOI":"10.31887\/DCNS.2007.9.4\/macrocq","volume":"9","author":"MA Crocq","year":"2007","unstructured":"Crocq, M. A. Historical and cultural aspects of man\u2019s relationship with addictive drugs. Dialogues in Clinical Neuroscience 9, 355\u2013361 (2007).","journal-title":"Dialogues in Clinical Neuroscience"},{"key":"49515_CR54","unstructured":"Shulgin, A. & Shulgin, A. Phenethylamines I Have Known And Loved: A Chemical Love Story. Transform 1\u20131188 (1991)."},{"key":"49515_CR55","unstructured":"Shulgin, A. & Shulgin, A. Tryptamines I Have Known And Loved. (Transform, 1997)."},{"key":"49515_CR56","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1586\/14737175.2016.1121098","volume":"16","author":"MC Paolino","year":"2016","unstructured":"Paolino, M. C., Ferretti, A., Papetti, L., Villa, M. P. & Parisi, P. Cannabidiol as potential treatment in refractory pediatric epilepsy. Expert Review of Neurotherapeutics 16, 17\u201321 (2016).","journal-title":"Expert Review of Neurotherapeutics"},{"key":"49515_CR57","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1056\/NEJMc1512758","volume":"374","author":"J Killestein","year":"2016","unstructured":"Killestein, J. Cannabinoids in the Treatment of Epilepsy. N. Engl. J. Med. 374, 94\u201395 (2016).","journal-title":"N. Engl. J. Med."},{"key":"49515_CR58","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.neuropharm.2017.12.041","volume":"142","author":"L Roseman","year":"2018","unstructured":"Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J. & Carhart-Harris, R. L. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology 142, 263\u2013269 (2018).","journal-title":"Neuropharmacology"},{"key":"49515_CR59","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.neuropharm.2016.05.010","volume":"112","author":"TH Pham","year":"2017","unstructured":"Pham, T. H. et al. Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB\/cJ mice. Neuropharmacology 112, 198\u2013209 (2017).","journal-title":"Neuropharmacology"},{"key":"49515_CR60","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.neuropharm.2017.12.040","volume":"142","author":"JJH Rucker","year":"2018","unstructured":"Rucker, J. J. H., Iliff, J. & Nutt, D. J. Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology 142, 200\u2013218 (2018).","journal-title":"Neuropharmacology"},{"key":"49515_CR61","doi-asserted-by":"publisher","first-page":"14003","DOI":"10.1038\/npjschz.2014.3","volume":"1","author":"JM Nascimento","year":"2015","unstructured":"Nascimento, J. M. & Martins-de-Souza, D. The proteome of schizophrenia. npj Schizophr. 1, 14003 (2015).","journal-title":"npj Schizophr."},{"key":"49515_CR62","doi-asserted-by":"publisher","first-page":"249","DOI":"10.4306\/pi.2015.12.2.249","volume":"12","author":"J Lee","year":"2015","unstructured":"Lee, J. et al. Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses. Psychiatry Investig. 12, 249 (2015).","journal-title":"Psychiatry Investig."},{"key":"49515_CR63","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1002\/prca.201400139","volume":"9","author":"L Carboni","year":"2015","unstructured":"Carboni, L. The contribution of proteomic studies in humans, animal models, and after antidepressant treatments to investigate the molecular neurobiology of major depression. Proteomics - Clinical Applications 9, 889\u2013898 (2015).","journal-title":"Proteomics - Clinical Applications"},{"key":"49515_CR64","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1177\/0269881109106931","volume":"25","author":"R Taurines","year":"2011","unstructured":"Taurines, R. et al. Review: Proteomic research in psychiatry. Journal of Psychopharmacology 25, 151\u2013196 (2011).","journal-title":"Journal of Psychopharmacology"},{"key":"49515_CR65","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1586\/14789450.5.2.293","volume":"5","author":"FH Kobeissy","year":"2008","unstructured":"Kobeissy, F. H., Sadasivan, S., Liu, J., Gold, M. S. & Wang, K. K. W. Psychiatric research: Psychoproteomics, degradomics and systems biology. Expert Review of Proteomics 5, 293\u2013314 (2008).","journal-title":"Expert Review of Proteomics"},{"key":"49515_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1517\/21678707.2016.1120664","volume":"4","author":"BE Bloom","year":"2016","unstructured":"Bloom, B. E. Recent successes and future predictions on drug repurposing for rare diseases. Expert Opin. Orphan Drugs 4, 1\u20134 (2016).","journal-title":"Expert Opin. Orphan Drugs"},{"key":"49515_CR67","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1208\/s12248-012-9390-1","volume":"14","author":"TI Oprea","year":"2012","unstructured":"Oprea, T. I. & Mestres, J. Drug Repurposing: Far Beyond New Targets for Old Drugs. AAPS J. 14, 759\u2013763 (2012).","journal-title":"AAPS J."},{"key":"49515_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-181","volume":"14","author":"R Xu","year":"2013","unstructured":"Xu, R. & Wang, Q. Large-scale extraction of accurate drug-disease treatment pairs from biomedical literature for drug repurposing. BMC Bioinformatics 14, 181 (2013).","journal-title":"BMC Bioinformatics"},{"key":"49515_CR69","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.drudis.2015.12.007","volume":"21","author":"A Lavecchia","year":"2016","unstructured":"Lavecchia, A. & Cerchia, C. In silico methods to address polypharmacology: Current status, applications and future perspectives. Drug Discovery Today 21, 288\u2013298 (2016).","journal-title":"Drug Discovery Today"},{"key":"49515_CR70","doi-asserted-by":"crossref","unstructured":"Brown, R. A. et al. Depression Among Cocaine Abusers in Treatment: Relation to Cocaine and Alcohol Use and Treatment Outcome. Depression Among Cocaine Abusers In 155 (1998).","DOI":"10.1176\/ajp.155.2.220"},{"key":"49515_CR71","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1212\/WNL.67.12_suppl_4.S45","volume":"67","author":"JCM Brust","year":"2006","unstructured":"Brust, J. C. M. Seizures and substance abuse: treatment considerations. Neurology 67, S45\u2013S48 (2006).","journal-title":"Neurology"},{"key":"49515_CR72","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/1520-6394(2000)12:1+<2::AID-DA2>3.0.CO;2-4","volume":"12","author":"KJ Ressler","year":"2000","unstructured":"Ressler, K. J. & Nemeroff, C. B. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety 12, 2\u201319 (2000).","journal-title":"Depression and Anxiety"},{"key":"49515_CR73","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/eat.20522","volume":"41","author":"EY Chen","year":"2008","unstructured":"Chen, E. Y., Matthews, L., Allen, C., Kuo, J. R. & Linehan, M. M. Dialectical behavior therapy for clients with binge-eating disorder or bulimia nervosa and borderline personality disorder. Int. J. Eat. Disord. 41, 505\u2013512 (2008).","journal-title":"Int. J. Eat. Disord."},{"key":"49515_CR74","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jfca.2015.09.013","volume":"45","author":"AB Cerezo","year":"2016","unstructured":"Cerezo, A. B. et al. Quality control and determination of melatonin in food supplements. J. Food Compos. Anal. 45, 80\u201386 (2016).","journal-title":"J. Food Compos. Anal."},{"key":"49515_CR75","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.mce.2015.01.024","volume":"418","author":"P Kumar Jha","year":"2015","unstructured":"Kumar Jha, P., Challet, E. & Kalsbeek, A. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals. Molecular and Cellular Endocrinology 418, 74\u201388 (2015).","journal-title":"Molecular and Cellular Endocrinology"},{"key":"49515_CR76","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.jsmc.2015.08.006","volume":"10","author":"KJ Reid","year":"2015","unstructured":"Reid, K. J. & Abbott, S. M. Jet lag and shift work disorder. Sleep Med. Clin. 10, 523\u2013535 (2015).","journal-title":"Sleep Med. Clin."},{"key":"49515_CR77","unstructured":"Zisapel, N. & Laudon, M. Derivating of tryptamine and analgous compounds and pharamaceutical formulations containing them (2004)."},{"key":"49515_CR78","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/0091-3057(85)90295-3","volume":"22","author":"MD Schechter","year":"1985","unstructured":"Schechter, M. D. & Glennon, R. A. Cathinone, cocaine and methamphetamine: similarity of behavioral effects. Pharmacol. Biochem. Behav. 22, 913\u2013916 (1985).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"49515_CR79","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.mehy.2013.06.007","volume":"81","author":"K Blum","year":"2013","unstructured":"Blum, K. et al. Hypothesizing that designer drugs containing cathinones (\u2018bath salts\u2019) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption. Med. Hypotheses 81, 450\u2013455 (2013).","journal-title":"Med. Hypotheses"},{"key":"49515_CR80","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S0924-977X(02)00020-2","volume":"12","author":"G Ellison","year":"2002","unstructured":"Ellison, G. Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry. European Neuropsychopharmacology 12, 287\u2013297 (2002).","journal-title":"European Neuropsychopharmacology"},{"key":"49515_CR81","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/B978-0-12-420118-7.00005-6","volume":"69","author":"FI Carroll","year":"2014","unstructured":"Carroll, F. I. et al. Bupropion and bupropion analogs as treatments for CNS disorders. Adv. Pharmacol. 69, 177\u2013216 (2014).","journal-title":"Adv. Pharmacol."},{"key":"49515_CR82","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.2165\/00003495-200059040-00019","volume":"59","author":"KJ Holm","year":"2000","unstructured":"Holm, K. J. & Spencer, C. M. Bupropion: A review of its use in the management of smoking cessation. Drugs 59, 1007\u20131024 (2000).","journal-title":"Drugs"},{"key":"49515_CR83","first-page":"402","volume":"49","author":"AE Vento","year":"2013","unstructured":"Vento, A. E. et al. Bupropion perceived as a stimulant by two patients with a previous history of cocaine misuse. Ann. Ist. Super. Sanita 49, 402\u2013405 (2013).","journal-title":"Ann. Ist. Super. Sanita"},{"key":"49515_CR84","doi-asserted-by":"publisher","unstructured":"Sullivan, M. & Evans, E. Abuse and misuse of antidepressants. Subst. Abuse Rehabil. 107, https:\/\/doi.org\/10.2147\/sar.s37917 (2014).","DOI":"10.2147\/sar.s37917"},{"key":"49515_CR85","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s13181-012-0228-0","volume":"8","author":"C Chomchai","year":"2012","unstructured":"Chomchai, C. & Manaboriboon, B. Stimulant Methamphetamine and Dextromethorphan Use Among Thai Adolescents: Implications for Health of Women and Children. J. Med. Toxicol. 8, 291\u2013294 (2012).","journal-title":"J. Med. Toxicol."},{"key":"49515_CR86","doi-asserted-by":"publisher","first-page":"23","DOI":"10.7326\/0003-4819-119-1-199307010-00004","volume":"119","author":"EC Strain","year":"1993","unstructured":"Strain, E. C., Stitzer, M. L., Liebson, I. A. & Bigelow, G. E. Dose-Response Effects of Methadone in the Treatment of Opioid Dependence. Ann. Intern. Med. 119, 23 (1993).","journal-title":"Ann. Intern. Med."},{"key":"49515_CR87","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S0024-3205(01)01152-3","volume":"69","author":"HC Kim","year":"2001","unstructured":"Kim, H. C. et al. Dextromethorphan affects cocaine-mediated behavioral pattern in parallel with a long-lasting Fos-related antigen-immunoreactivity. Life Sci. 69, 615\u2013624 (2001).","journal-title":"Life Sci."},{"key":"49515_CR88","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0014-2999(96)00970-3","volume":"321","author":"L Pulvirenti","year":"1997","unstructured":"Pulvirenti, L., Balducci, C. & Koob, G. F. Dextromethorphan reduces intravenous cocaine self-administration in the rat. Eur. J. Pharmacol. 321, 279\u2013283 (1997).","journal-title":"Eur. J. Pharmacol."},{"key":"49515_CR89","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/S0304-3940(00)01188-5","volume":"288","author":"WK Jhoo","year":"2000","unstructured":"Jhoo, W. K. et al. Dual effects of dextromethorphan on cocaine-induced conditioned place preference in mice. Neurosci. Lett. 288, 76\u201380 (2000).","journal-title":"Neurosci. Lett."},{"key":"49515_CR90","first-page":"627","volume":"19","author":"HC Kim","year":"1997","unstructured":"Kim, H. C., Park, B. K., Hong, S. Y. & Jhoo, W. K. Dextromethorphan alters the reinforcing effect of cocaine in the rat. Methods Find Exp Clin Pharmacol 19, 627\u2013631 (1997).","journal-title":"Methods Find Exp Clin Pharmacol"},{"key":"49515_CR91","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1254\/jphs.11R02CR","volume":"116","author":"E-J Shin","year":"2011","unstructured":"Shin, E.-J. et al. Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs. J. Pharmacol. Sci. 116, 137\u2013148 (2011).","journal-title":"J. Pharmacol. Sci."},{"key":"49515_CR92","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.supflu.2010.09.011","volume":"55","author":"H Perrotin-Brunel","year":"2010","unstructured":"Perrotin-Brunel, H. et al. Solubility of non-psychoactive cannabinoids in supercritical carbon dioxide and comparison with psychoactive cannabinoids. J. Supercrit. Fluids 55, 603\u2013608 (2010).","journal-title":"J. Supercrit. Fluids"},{"key":"49515_CR93","doi-asserted-by":"crossref","unstructured":"Marsaglia, G., Tsang, W. W. & Wang, J. Evaluating Kolmogorov\u2019s Distribution. J. Stat. Softw. 8 (2015).","DOI":"10.18637\/jss.v008.i18"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-49515-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-49515-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-49515-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T08:33:02Z","timestamp":1671265982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-49515-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,11]]},"references-count":93,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["49515"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-49515-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.6148940.v1","asserted-by":"object"},{"id-type":"doi","id":"10.26434\/chemrxiv.6148940","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,11]]},"assertion":[{"value":"18 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"13155"}}