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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Therapeutic Potential of Natural Psychoactive Drugs for Central Nervous System Disorders: A Perspective from Polypharmacology

Author(s): Genís Oña and José Carlos Bouso*

Volume 28, Issue 1, 2021

Published on: 12 December, 2019

Page: [53 - 68] Pages: 16

DOI: 10.2174/0929867326666191212103330

Price: $65

Abstract

In the drug development, the formation of highly selective ligands has been unsuccessful in the treatment of central nervous system disorders. Multi-target ligands, from the polypharmacology paradigm, are being proposed as treatments for these complex disorders, since they offer enhanced efficacy and a strong safety profile. Natural products are the best examples of multi-target compounds, so they are of high interest within this paradigm. Additionally, recent research on psychoactive drugs of natural origin, such as ayahuasca and cannabis, has demonstrated the promising therapeutic potential for the treatment of some psychiatric and neurological disorders. In this text, we describe how research on psychoactive drugs can be effectively combined with the polypharmacology paradigm, providing ayahuasca and cannabis research as examples. The advantages and disadvantages are also discussed.

Keywords: Polypharmacology, multi-target, psychoactive, ayahuasca, cannabis, plant, therapeutic.

[1]
Vigo, D.; Thornicroft, G.; Atun, R. Estimating the true global burden of mental illness. Lancet Psychiatry, 2016, 3(2), 171-178.
[http://dx.doi.org/10.1016/S2215-0366(15)00505-2] [PMID: 26851330]
[2]
Biotechnology Innovation Organization (BIO) Clinical development success rates 2006-2015. Available at. https://www.bio.org/sites/default/filesClinical%20Development%20Success%20Rates%202006-2015%20-%20BIO%20Biomedtracker,%20Amplion%202016.pdf (Accessdate: 7 August2019.
[3]
van Gerven, J.; Cohen, A. Vanishing clinical psychopharmacology. Br. J. Clin. Pharmacol., 2011, 72(1), 1-5.
[http://dx.doi.org/10.1111/j.1365-2125.2011.04021.x] [PMID: 21651614]
[4]
Horrobin, D.F. A new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E). Prog. Drug Res., 2002, 59, 171-199.
[http://dx.doi.org/10.1007/978-3-0348-8171-5_6] [PMID: 12458967]
[5]
Insel, T.R. Disruptive insights in psychiatry: transforming a clinical discipline. J. Clin. Invest., 2009, 119(4), 700-705.
[http://dx.doi.org/10.1172/JCI38832] [PMID: 19339761]
[6]
Hyman, S.E. Revolution stalled. Sci. Transl. Med., 2012, 4(155)155cm11
[http://dx.doi.org/10.1126/scitranslmed.3003142] [PMID: 23052291]
[7]
Athauda, D.; Foltynie, T. The ongoing pursuit of neuroprotective therapies in Parkinson disease. Nat. Rev. Neurol., 2015, 11(1), 25-40.
[http://dx.doi.org/10.1038/nrneurol.2014.226] [PMID: 25447485]
[8]
Yiannopoulou, K.G.; Papageorgiou, S.G. Current and future treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disorder., 2013, 6(1), 19-33.
[http://dx.doi.org/10.1177/1756285612461679] [PMID: 23277790]
[9]
Médicaments de la maladie d'Alzheimer: enfin non remboursables en France! Rev. Prescrire, 2018, 38(416).Available at:. https://english.prescrire.org/en/81/168/55126/0/ NewsDetails.aspx (Access date: 7 August, 2019.
[10]
Treede, R.D.; Rief, W.; Barke, A.; Aziz, Q.; Bennett, M.I.; Benoliel, R.; Cohen, M.; Evers, S.; Finnerup, N.B.; First, M.B.; Giamberardino, M.A.; Kaasa, S.; Kosek, E. Lavandʼhomme, P.; Nicholas, M.; Perrot, S.; Scholz, J.; Schug, S.; Smith, B.H.; Svensson, P.; Vlaeyen, J.W.; Wang, S.J. A classification of chronic pain for ICD-11. Pain, 2015, 156(6), 1003-1007.
[http://dx.doi.org/10.1097/j.pain.0000000000000160] [PMID: 25844555]
[11]
Gilron, I.; Baron, R.; Jensen, T. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin. Proc., 2015, 90(4), 532-545.
[http://dx.doi.org/10.1016/j.mayocp.2015.01.018] [PMID: 25841257]
[12]
Vanderah, T.W. Delta and kappa opioid receptors as suitable drug targets for pain. Clin. J. Pain, 2010, 26(10)(Suppl. 10), S10-S15.
[http://dx.doi.org/10.1097/AJP.0b013e3181c49e3a] [PMID: 20026960]
[13]
Merlos, M.; Romero, L.; Zamanillo, D.; Plata-Salamán, C.; Vela, J.M. Sigma-1 receptor and pain. Handb. Exp. Pharmacol., 2017, 244, 131-161.
[http://dx.doi.org/10.1007/164_2017_9] [PMID: 28275913 ]
[14]
Dos Santos, R.G.; Bouso, J.C.; Alcázar-Córcoles, M.Á.; Hallak, J.E.C. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev. Clin. Pharmacol., 2018, 11(9), 889-902.
[http://dx.doi.org/10.1080/17512433.2018.1511424] [PMID: 30102078]
[15]
Horrobin, D.F. Modern biomedical research: an internally self-consistent universe with little contact with medical reality? Nat. Rev. Drug Discov., 2003, 2(2), 151-154.
[http://dx.doi.org/10.1038/nrd1012] [PMID: 12563306]
[16]
Hopkins, A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[17]
Hughes, J.P.; Rees, S.; Kalindjian, S.B.; Philpott, K.L. Principles of early drug discovery. Br. J. Pharmacol., 2011, 162(6), 1239-1249.
[http://dx.doi.org/10.1111/j.1476-5381.2010.01127.x] [PMID: 21091654]
[18]
Roth, B.L.; Sheffler, D.J.; Kroeze, W.K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov., 2004, 3(4), 353-359.
[http://dx.doi.org/dx.doi.or g/10.1038/nrd1346] [PMID: 15060530]
[19]
Viayna, E.; Sola, I.; Di Pietro, O.; Muñoz-Torrero, D. Human disease and drug pharmacology, complex as real life. Curr. Med. Chem., 2013, 20(13), 1623-1634.
[http://dx.doi.org/10.2174/0929867311320130002] [PMID: 23410162]
[20]
Escott-Price, V.; Nalls, M.A.; Morris, H.R.; Lubbe, S.; Brice, A.; Gasser, T.; Heutink, P.; Wood, N.W. H ardy, J.; Singleton, A.B.; Williams, N.M. International Parkinson’s disease genomics consortium; IPDGC consortium members. Polygenic risk of Parkinson disease is correlated with disease age at onset. Ann. Neurol., 2015, 77(4), 582-591.
[http://dx.doi.org/10.1002/ana.24335] [PMID: 25773351]
[21]
Hagenaars, S.P.; Radaković, R.; Crockford, C.; Fawns-Ritchie, C.; Harris, S.E.; Gale, C.R.; Deary, I.J. International FTD-genomics consortium (IFGC). Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function. PLoS One, 2018, 13(6)e0198187
[http://dx.doi.org/10.1371/journal.pone.0198187] [PMID: 29856801]
[22]
Purcell, S.M.; Wray, N.R.; Stone, J.L.; Visscher, P.M.; O’Donovan, M.C.; Sullivan, P.F.; Sklar, P. International Schizophrenia consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 2009, 460(7256), 748-752.
[http://dx.doi.org/10.1038/nature08185] [PMID: 19571811]
[23]
Chadman, K.K.; Yang, M.; Crawley, J.N. Criteria for validating mouse models of psychiatric diseases. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2009, 150B(1), 1-11.
[http://dx.doi.org/10.1002/ajmg.b.30777] [PMID: 18484083]
[24]
Cryan, J.F.; Slattery, D.A. Animal models of mood disorders: recent developments. Curr. Opin. Psychiatry, 2007, 20(1), 1-7.
[http://dx.doi.org/10.1097/YCO.0b013e3280117733] [PMID: 17143074]
[25]
Setola, V.; Roth, B.L. Why mice are neither miniature humans nor small rats: a cautionary tale involving 5-hydroxytryptamine-6 serotonin receptor species variants. Mol. Pharmacol., 2003, 64(6), 1277-1278.
[http://dx.doi.org/10.1124/mol.64.6.1277] [PMID: 14645656]
[26]
Bolognesi, M.L. Polypharmacology in a single drug: multitarget drugs. Curr. Med. Chem., 2013, 20(13), 1639-1645.
[http://dx.doi.org/10.2174/0929867311320130004] [PMID: 23410164]
[27]
Csermely, P.; Agoston, V.; Pongor, S. The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol. Sci., 2005, 26(4), 178-182.
[http://dx.doi.org/10.1016/j.tips.2005.02.007] [PMID: 15808341]
[28]
Tang, J.; Aittokallio, T. Network pharmacology strategies toward multi-target anticancer therapies: from computational models to experimental design principles. Curr. Pharm. Des., 2014, 20(1), 23-36.
[http://dx.doi.org/10.2174/13816128113199990470] [PMID: 23530504]
[29]
Agoston, V.; Csermely, P.; Pongor, S. Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example. Phys. Rev. E Stat. Nonlin. Soft Matter Phys., 2005, 71(5 Pt 1)051909
[http://dx.doi.org/10.1103/PhysRevE.71.051909] [PMID: 16089573]
[30]
Anighoro, A.; Bajorath, J.; Rastelli, G. Polypharmacology: challenges and opportunities in drug discovery. J. Med. Chem., 2014, 57(19), 7874-7887.
[http://dx.doi.org/10.1021/jm5006463] [PMID: 24946140]
[31]
Yildirim, M.A.; Goh, K.I.; Cusick, M.E.; Barabási, A.L.; Vidal, M. Drug-target network. Nat. Biotechnol., 2007, 25(10), 1119-1126.
[http://dx.doi.org/10.1038/nbt1338] [PMID: 17921997]
[32]
Jalencas, X.; Mestres, J. On the origins of drug polypharmacology. MedChemComm, 2012, 4(1), 80-87.
[http://dx.doi.org/10.1039/C2MD20242E]
[33]
Hu, Y.; Bajorath, J. High-resolution view of compound promiscuity. F1000 Res., 2013, 2, 144.
[http://dx.doi.org/10.12688/f1000research.2-144.v1] [PMID: 24358872]
[34]
Lu, J.J.; Pan, W.; Hu, Y.J.; Wang, Y.T. Multi-target drugs: the trend of drug research and development. PLoS One, 2012, 7(6)e40262
[http://dx.doi.org/10.1371/journal.pone.0040262] [PMID: 22768266]
[35]
Straube, A.; Aicher, B.; Fiebich, B.L.; Haag, G. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics? BMC Neurol., 2011, 11, 43.
[http://dx.doi.org/10.1186/1471-2377-11-43] [PMID: 21453539]
[36]
Talevi, A. Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front. Pharmacol., 2015, 6, 205.
[http://dx.doi.org/10.3389/fphar.2015.00205] [PMID: 26441661]
[37]
Aixalà, M.; Ona, G.; Parés, Ò.; Bouso, J.C. Patterns of use, desired effects, and mental health status of a sample of natural psychoactive drug users. Drugs Educ. Prev. Policy, 2019, 27(3), 191-198.
[http://dx.doi.org/10.1080/09687637.2019.1611739]
[38]
Iserson, K.V. “Go Ask Alice”: The case for researching Schedule I drugs. Camb. Q. Healthc. Ethics, 2019, 28(1), 168-177.
[http://dx.doi.org/10.1017/S0963180118000518] [PMID: 30570473]
[39]
Kyzar, E.J.; Nichols, C.D.; Gainetdinov, R.R.; Nichols, D.E.; Kalueff, A.V. Psychedelic drugs in biomedicine. Trends Pharmacol. Sci., 2017, 38(11), 992-1005.
[http://dx.doi.org/10.1016/j.tips.2017.08.003] [PMID: 28947075]
[40]
Mithoefer, M.C.; Grob, C.S.; Brewerton, T.D. Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. Lancet Psychiatry, 2016, 3(5), 481-488.
[http://dx.doi.org/10.1016/S2215-0366(15)00576-3] [PMID: 27067625]
[41]
Ona, G.; Bouso, J.C. Can psychedelics be the treatment for the crisis in psychopharmacology?; Preprints, 2019, p. 2019010249.
[http://dx.doi.org/10.20944/preprints201901.0249.v1 ]
[42]
Berthoux, C.; Barre, A.; Bockaert, J.; Marin, P.; Bécamel, C. Sustained activation of postsynaptic 5-HT2A receptors gates plasticity at prefrontal cortex synapses. Cereb. Cortex, 2019, 29(4), 1659-1669.
[http://dx.doi.org/10.1093/cercor/bhy064] [PMID: 29917056]
[43]
Ly, C.; Greb, A.C.; Cameron, L.P.; Wong, J.M.; Barragan, E.V.; Wilson, P.C.; Burbach, K.F.; Soltanzadeh Zarandi, S.; Sood, A.; Paddy, M.R.; Duim, W.C.; Dennis, M.Y.; McAllister, A.K.; Ori-McKenney, K.M.; Gray, J.A.; Olson, D.E. Olson, D.E. Psychedelics promote structural and functional neural plasticity. Cell Rep., 2018, 23(11), 3170-3182.
[http://dx.doi.org/10.1016/j.celrep.2018.05.022] [PMID: 29898390]
[44]
Bouso, J.C.; Palhano-Fontes, F.; Rodríguez-Fornells, A.; Ribeiro, S.; Sanches, R.; Crippa, J.A.; Hallak, J.E.C.; de Araujo, D.B.; Riba, J. Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. Eur. Neuropsychopharmacol., 2015, 25(4), 483-492.
[http://dx.doi.org/10.1016/j.euroneuro.2015.01.008] [PMID: 25637267]
[45]
Apud, I.; Romaní, O. Medicine, religion and ayahuasca in Catalonia. Considering ayahuasca networks from a medical anthropology perspective. Int. J. Drug Policy, 2017, 39, 28-36.
[http://dx.doi.org/10.1016/j.drugpo.2016.07.011] [PMID: 27768991]
[46]
Calvey, T.; Howells, F.M. An introduction to psychedelic neuroscience.. Prog. Brain Res; , 2018, 242, pp. 1-23.
[http://dx.doi.org/10.1016/bs.pbr.2018.09.013] [PMID: 30471677]
[47]
Schindler, E.A.D.; Wallace, R.M.; Sloshower, J.A.; D’Souza, D.C. Neuroendocrine associations underlying the persistent therapeutic effects of classic serotonergic psychedelics. Front. Pharmacol., 2018, 9, 177.
[http://dx.doi.org/10.3389/fphar.2018.00177] [PMID: 29545753]
[48]
Chu, M.; Chen, X.; Wang, J.; Guo, L.; Wang, Q.; Gao, Z.; Kang, J.; Zhang, M.; Feng, J.; Guo, Q.; Li, B.; Zhang, C.; Guo, X.; Chu, Z.; Wang, Y. Polypharmacology of berberine based on multi-target binding motifs. Front. Pharmacol., 2018, 9, 801.
[http://dx.doi.org/10.3389/fphar.2018.00801] [PMID: 30087614]
[49]
Gonçalves, P.B.; Romeiro, N.C. Multi-target natural products as alternatives against oxidative stress in chronic obstructive pulmonary disease (COPD). Eur. J. Med. Chem., 2019, 163, 911-931.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.020] [PMID: 30612088]
[50]
Koeberle, A.; Werz, O. Multi-target approach for natural products in inflammation. Drug Discov. Today, 2014, 19(12), 1871-1882.
[http://dx.doi.org/10.1016/j.drudis.2014.08.006] [PMID: 25172801]
[51]
Ganesan, A. The impact of natural products upon modern drug discovery. Curr. Opin. Chem. Biol., 2008, 12(3), 306-317.
[http://dx.doi.org/10.1016/j.cbpa.2008.03.016] [PMID: 18423384]
[52]
Rishton, G.M. Natural products as a robust source of new drugs and drug leads: past successes and present day issues. Am. J. Cardiol., 2008, 101(10A), 43D-49D.
[http://dx.doi.org/10.1016/j.amjcard.2008.02.007] [PMID: 18474274]
[53]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[54]
Esatbeyoglu, T.; Huebbe, P.; Ernst, I.M.; Chin, D.; Wagner, A.E.; Rimbach, G. Curcumin--from molecule to biological function. Angew. Chem. Int. Ed. Engl., 2012, 51(22), 5308-5332.
[http://dx.doi.org/10.1002/anie.201107724] [PMID: 22566109]
[55]
Hsiao, W.L.; Liu, L. The role of traditional Chinese herbal medicines in cancer therapy--from TCM theory to mechanistic insights. Planta Med., 2010, 76(11), 1118-1131.
[http://dx.doi.org/10.1055/s-0030-1250186] [PMID: 20635308]
[56]
Tasneem, S.; Liu, B.; Li, B.; Choudhary, M.I.; Wang, W. Molecular pharmacology of inflammation: Medicinal plants as anti-inflammatory agents. Pharmacol. Res., 2019, 139, 126-140.
[http://dx.doi.org/10.1016/j.phrs.2018.11.001] [PMID: 30395947]
[57]
Deng, Y.H.; Wang, N.N.; Zou, Z.X.; Zhang, L.; Xu, K.P.; Chen, A.F.; Cao, D.S.; Tan, G.S. Multi-target screening and experimental validation of natural products from Selaginella plants against Alzheimer’s disease. Front. Pharmacol., 2017, 8, 539.
[http://dx.doi.org/10.3389/fphar.2017.00539] [PMID: 28890698]
[58]
Kim, J.; Lee, H.J.; Lee, K.W. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J. Neurochem., 2010, 112(6), 1415-1430.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06562.x] [PMID: 20050972]
[59]
Shan, C.S.; Zhang, H.F.; Xu, Q.Q.; Shi, Y.H.; Wang, Y.; Li, Y.; Lin, Y.; Zheng, G.Q. Herbal medicine formulas for Parkinson’s disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled clinical trials. Front. Aging Neurosci., 2018, 10, 349.
[http://dx.doi.org/10.3389/fnagi.2018.00349] [PMID: 30467472]
[60]
Russo, M.; Spagnuolo, C.; Tedesco, I.; Bilotto, S.; Russo, G.L. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem. Pharmacol., 2012, 83(1), 6-15.
[http://dx.doi.org/10.1016/j.bcp.2011.08.010] [PMID: 21856292]
[61]
Singh, B.N.; Shankar, S.; Srivastava, R.K. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem. Pharmacol., 2011, 82(12), 1807-1821.
[http://dx.doi.org/10.1016/j.bcp.2011.07.093] [PMID: 21827739]
[62]
Domínguez-Clavé, E.; Soler, J.; Elices, M.; Pascual, J.C.; Álvarez, E.; de la Fuente Revenga, M.; Friedlander, P.; Feilding, A.; Riba, J. Ayahuasca: Pharmacology, neuroscience and therapeutic potential. Brain Res. Bull., 2016, 126(Pt 1), 89-101.
[http://dx.doi.org/10.1016/j.brainresbull.2016.03.002] [PMID: 26976063]
[63]
Nichols, D.E. Psychedelics. Pharmacol. Rev., 2016, 68(2), 264-355.
[http://dx.doi.org/10.1124/pr.115.011478] [PMID: 26841800]
[64]
Santos, M.C.; Navickiene, S.; Gaujac, A. Determination of tryptamines and β-carbolines in ayahuasca beverage consumed during Brazilian religious ceremonies. J. AOAC Int., 2017, 100(3), 820-824.
[http://dx.doi.org/10.5740/jaoacint.16-0337] [PMID: 28105971]
[65]
Robinson, E.S.; Anderson, N.J.; Crosby, J.; Nutt, D.J.; Hudson, A.L. Endogenous beta-carbolines as clonidine-displacing substances. Ann. N. Y. Acad. Sci., 2003, 1009, 157-166.
[http://dx.doi.org/10.1196/annals.1304.018] [PMID: 15028582]
[66]
Herraiz, T.; González, D.; Ancín-Azpilicueta, C.; Arán, V.J.; Guillén, H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem. Toxicol., 2010, 48(3), 839-845.
[http://dx.doi.org/10.1016/j.fct.2009.12.019] [PMID: 20036304]
[67]
Cao, R.; Peng, W.; Wang, Z.; Xu, A. beta-Carboline alkaloids: biochemical and pharmacological functions. Curr. Med. Chem., 2007, 14(4), 479-500.
[http://dx.doi.org/10.2174/092986707779940998] [PMID: 17305548]
[68]
Moura, D.J.; Richter, M.F.; Boeira, J.M.; Pêgas Henriques, J.A.; Saffi, J. Antioxidant properties of beta-carboline alkaloids are related to their antimutagenic and antigenotoxic activities. Mutagenesis, 2007, 22(4), 293-302.
[http://dx.doi.org/10.1093/mutage/gem016] [PMID: 17545209]
[69]
Riba, J.; Valle, M.; Urbano, G.; Yritia, M.; Morte, A.; Barbanoj, M.J. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J. Pharmacol. Exp. Ther., 2003, 306(1), 73-83.
[http://dx.doi.org/10.1124/jpet.103.049882]] [PMID: 12660312]
[70]
Nasehi, M.; Piri, M.; Nouri, M.; Farzin, D.; Nayer-Nouri, T.; Zarrindast, M.R. Involvement of dopamine D1/D2 receptors on harmane-induced amnesia in the step-down passive avoidance test. Eur. J. Pharmacol., 2010, 634(1-3), 77-83.
[http://dx.doi.org/10.1016/j.ejphar.2010.02.027] [PMID: 20188725]
[71]
Glennon, R.A.; Dukat, M.; Grella, B.; Hong, S.; Costantino, L.; Teitler, M.; Smith, C.; Egan, C.; Davis, K.; Mattson, M.V. Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors. Drug Alcohol Depend., 2000, 60(2), 121-132.
[http://dx.doi.org/10.1016/S0376-8716(99)00148-9] [PMID: 10940539]
[72]
Husbands, S.M.; Glennon, R.A.; Gorgerat, S.; Gough, R.; Tyacke, R.; Crosby, J.; Nutt, D.J.; Lewis, J.W.; Hudson, A.L. beta-carboline binding to imidazoline receptors. Drug Alcohol Depend., 2001, 64(2), 203-208.
[http://dx.doi.org/10.1016/S0376-8716(01)00123-5] [PMID: 11543990]
[73]
Farouk, L.; Laroubi, A.; Aboufatima, R.; Benharref, A.; Chait, A. Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved. J. Ethnopharmacol., 2008, 115(3), 449-454.
[http://dx.doi.org/10.1016/j.jep.2007.10.014] [PMID: 18054186]
[74]
Akhtar, M.S.; Iqbal, Z.; Khan, M.N.; Lateef, M. Anthelmintic activity of medicinal plants with particular reference to their use in animals in the Indo-Pakistan subcontinent. Small Rumin. Res., 2010, 38(2), 99-107.
[http://dx.doi.org/10.1016/S0921-4488(00)00163-2]
[75]
Moloudizargari, M.; Mikaili, P.; Aghajanshakeri, S.; Asghari, M.H.; Shayegh, J. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacogn. Rev., 2013, 7(14), 199-212.
[http://dx.doi.org/10.4103/0973-7847.120524] [PMID: 24347928]
[76]
Beringer, K. Ueber ein neues, auf das extrapyramidalmotorische System wirkendes Alkaloid (Banisterin). Nervenarzt, 1928, 1, 265-275.
[77]
Lewin, L. Sur une substance enivrante, la banistérine, extraite de Banisteria Caapi. C. R. Hebd. Seances Acad. Sci., 1928, 186, 469-471.
[78]
Djamshidian, A.; Bernschneider-Reif, S.; Poewe, W.; Lees, A.J. Banisteriopsis caapi, a forgotten potential therapy for Parkinson’s disease? Mov. Disord. Clin. Pract. (Hoboken), 2015, 3(1), 19-26.
[http://dx.doi.org/10.1002/mdc3.12242] [PMID: 30713897]
[79]
Fisher, R.; Lincoln, L.; Jackson, M.J.; Abbate, V.; Jenner, P.; Hider, R.; Lees, A.; Rose, S. The effect of Banisteriopsis caapi (B. caapi) on the motor deficits in the MPTP-treated common marmoset model of Parkinson’s disease. Phytother. Res., 2018, 32(4), 678-687.
[http://dx.doi.org/10.1002/ptr.6017] [PMID: 29368409]
[80]
Morales-García, J.A.; de la Fuente Revenga, M.; Alonso-Gil, S.; Rodríguez-Franco, M.I.; Feilding, A.; Perez-Castillo, A.; Riba, J. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Sci. Rep., 2017, 7(1), 5309.
[http://dx.doi.org/10.1038/s41598-017-05407-9] [PMID: 28706205]
[81]
Barker, S.A.N. N-Dimethyltryptamine (DMT), an endogenous hallucinogen: past, present, and future research to determine its role and function. Front. Neurosci., 2018, 12, 536.
[http://dx.doi.org/10.3389/fnins.2018.00536] [PMID: 30127713]
[82]
Keiser, M.J.; Setola, V.; Irwin, J.J.; Laggner, C.; Abbas, A.I.; Hufeisen, S.J.; Jensen, N.H.; Kuijer, M.B.; Matos, R.C.; Tran, T.B.; Whaley, R.; Glennon, R.A.; Hert, J.; Thomas, K.L.; Edwards, D.D.; Shoichet, B.K.; Roth, B.L. Predicting new molecular targets for known drugs. Nature, 2009, 462(7270), 175-181.
[http://dx.doi.org/10.1038/nature08506] [PMID: 19881490]
[83]
Nichols, D.E.; Nichols, C.D. Serotonin receptors. Chem. Rev., 2008, 108(5), 1614-1641.
[http://dx.doi.org/10.1021/cr078224o] [PMID: 18476671]
[84]
Carbonaro, T.M.; Gatch, M.B. Neuropharmacology of N,N-dimethyltryptamine. Brain Res. Bull., 2016, 126(Pt 1), 74-88.
[http://dx.doi.org/10.1016/j.brainresbull.2016.04.016] [PMID: 27126737]
[85]
Fontanilla, D.; Johannessen, M.; Hajipour, A.R.; Cozzi, N.V.; Jackson, M.B.; Ruoho, A.E. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science, 2009, 323(5916), 934-937.
[http://dx.doi.org/10.1126/science.1166127] [PMID: 19213917]
[86]
Collier, T.L.; Waterhouse, R.N.; Kassiou, M. Imaging sigma receptors: applications in drug development. Curr. Pharm. Des., 2007, 13(1), 51-72.
[http://dx.doi.org/10.2174/138161207779313740] [PMID: 17266588]
[87]
Revel, F.G.; Moreau, J.L.; Gainetdinov, R.R.; Ferragud, A.; Velázquez-Sánchez, C.; Sotnikova, T.D.; Morairty, S.R.; Harmeier, A.; Groebke Zbinden, K.; Norcross, R.D.; Bradaia, A.; Kilduff, T.S.; Biemans, B.; Pouzet, B.; Caron, M.G.; Canales, J.J.; Wallace, T.L.; Wettstein, J.G.; Hoener, M.C. Trace amine-associated receptor 1 partial agonism reveals novel paradigm for neuropsychiatric therapeutics. Biol. Psychiatry, 2012, 72(11), 934-942.
[http://dx.doi.org/10.1016/j.biopsych.2012.05.014] [PMID: 22705041]
[88]
Sánchez, C.; Bouso, J.C. Ayahuasca: from the Amazon to the global village.Transnational Institute, 2015. Accessed at:, https://www.tni.org/files/publication-downloads/dpb_ 43_eng_web_19122015.pdf(Access date: 7 August,2019.
[89]
Riba, J.; Barbanoj, M.J. Ayahuasca.Tratado SET de trastornos adictivos; Peris, J.C.; Zurián, J.C.; Martínez, G.C; Valladolid, G.R.Ed. Médica Panamericana; Madrid, 2006, pp. 321-324.
[90]
Palhano-Fontes, F.; Barreto, D.; Onias, H.; Andrade, K.C.; Novaes, M.M.; Pessoa, J.A.; Mota-Rolim, S.A.; Osório, F.L.; Sanches, R.; Dos Santos, R.G.; Tófoli, L.F.; de Oliveira Silveira, G.; Yonamine, M.; Riba, J.; Santos, F.R.; Silva-Junior, A.A.; Alchieri, J.C.; Galvão-Coelho, N.L.; Lobão-Soares, B.; Hallak, J.E.C.; Arcoverde, E.; Maia-de-Oliveira, J.P.; Araújo, D.B. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol. Med., 2019, 49(4), 655-663.
[http://dx.doi.org/10.1017/S0033291718001356] [PMID: 29903051]
[91]
Osório. Fde.L.; Sanches, R.F.; Macedo, L.R.; Santos, R.G.; Maia-de-Oliveira, J.P.; Wichert-Ana, L.; Araujo, D.B.; Riba, J.; Crippa, J.A.; Hallak, J.E.C. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Br. J. Psychiatry, 2015, 37(1), 13-20.
[http://dx.doi.org/10.1590/1516-4446-2014-1496] [PMID: 25806551]
[92]
Sanches, R.F.; de Lima Osório, F.; Dos Santos, R.G.; Macedo, L.R.; Maia-de-Oliveira, J.P.; Wichert-Ana, L.; de Araujo, D.B.; Riba, J.; Crippa, J.A.; Hallak, J.E.C. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J. Clin. Psychopharmacol., 2016, 36(1), 77-81.
[http://dx.doi.org/10.1097/JCP.0000000000000436] [PMID: 26650973]
[93]
Franquesa, A.; Sainz-Cort, A.; Gandy, S.; Soler, J.; Alcázar-Córcoles, M.Á.; Bouso, J.C. Psychological variables implied in the therapeutic effect of ayahuasca: a contextual approach. Psychiatry Res., 2018, 264, 334-339.
[http://dx.doi.org/10.1016/j.psychres.2018.04.012] [PMID: 29674223]
[94]
Soler, J.; Elices, M.; Franquesa, A.; Barker, S.; Friedlander, P.; Feilding, A.; Pascual, J.C.; Riba, J. Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities. Psychopharmacology (Berl.), 2016, 233(5), 823-829.
[http://dx.doi.org/10.1007/s00213-015-4162-0] [PMID: 26612618]
[95]
Barbosa, P.C.; Cazorla, I.M.; Giglio, J.S.; Strassman, R. A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naïve subjects. J. Psychoactive Drugs, 2009, 41(3), 205-212.
[http://dx.doi.org/10.1080/02791072.2009.10400530] [PMID: 19999673]
[96]
Ona, G.; Troncoso, S. Long-lasting analgesic effect of the psychedelic drug change: a case report. J. Psychedelic Studies, 2019, 3(1), 7-13.
[http://dx.doi.org/10.1556/2054.2019.001]
[97]
Gable, R.S. Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids. Addiction, 2007, 102(1), 24-34.
[http://dx.doi.org/10.1111/j.1360-0443.2006.01652.x] [PMID: 17207120]
[98]
Lima, F.A.S.; Tófoli, L.F. An epidemiological surveillance system by the UDV: mental health recommendations concerning the religious use of hoasca. The internationalization of ayahuasca; Labate, B.C; Jungaberle, H., Ed.; , 2011, pp. 185-200.
[99]
Dos Santos, R.G.; Bouso, J.C.; Hallak, J.E.C. Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies. Ther. Adv. Psychopharmacol., 2017, 7(4), 141-157.
[http://dx.doi.org/10.1177/2045125316689030] [PMID: 28540034]
[100]
Gouzoulis-Mayfrank, E.; Heekeren, K.; Neukirch, A.; Stoll, M.; Stock, C.; Obradovic, M.; Kovar, K.A. Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry, 2005, 38(6), 301-311.
[http://dx.doi.org/10.1055/s-2005-916185] [PMID: 16342002]
[101]
Geyer, M.A.; Vollenweider, F.X. Serotonin research: contributions to understanding psychoses. Trends Pharmacol. Sci., 2008, 29(9), 445-453.
[http://dx.doi.org/10.1016/j.tips.2008.06.006] [PMID: 19086254]
[102]
Riba, J.; Rodríguez-Fornells, A.; Urbano, G.; Morte, A.; Antonijoan, R.; Montero, M.; Callaway, J.C.; Barbanoj, M.J. Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology (Berl.), 2001, 154(1), 85-95.
[http://dx.doi.org/10.1007/s002130000606] [PMID: 11292011]
[103]
Barbosa, P.C.; Strassman, R.J.; da Silveira, D.X.; Areco, K.; Hoy, R.; Pommy, J.; Thoma, R.; Bogenschutz, M. Psychological and neuropsychological assessment of regular hoasca users. Compr. Psychiatry, 2016, 71, 95-105.
[http://dx.doi.org/10.1016/j.comppsych.2016.09.003] [PMID: 27653781]
[104]
Bouso, J.C.; González, D.; Fondevila, S.; Cutchet, M.; Fernández, X.; Ribeiro Barbosa, P.C.; Alcázar-Córcoles, M.Á.; Araújo, W.S.; Barbanoj, M.J.; Fábregas, J.M. Riba, J. Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study. PLoS One, 2012, 7(8)e42421
[http://dx.doi.org/10.1371/journal.pone.0042421] [PMID: 22905130]
[105]
Grob, C.S.; McKenna, D.J.; Callaway, J.C.; Brito, G.S.; Neves, E.S.; Oberlaender, G.; Saide, O.L.; Labigalini, E.; Tacla, C.; Miranda, C.T.; Strassman, R.J.; Boone, K.B. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J. Nerv. Ment. Dis., 1996, 184(2), 86-94.
[http://dx.doi.org/10.1097/00005053-199602000-00004] [PMID: 8596116]
[106]
Halpern, J.H.; Sherwood, A.R.; Passie, T.; Blackwell, K.C.; Ruttenber, A.J. Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament. Med. Sci. Monit., 2008, 14(8), SR15-SR22.
[PMID: 18668010]
[107]
Li, H.L. An archaeological and historical account of cannabis in China. Econ. Bot., 1974, 28(4), 437-448.
[http://dx.doi.org/10.1007/BF02862859]
[108]
Grotenhermen, F.; Müller-Vahl, K. The therapeutic potential of cannabis and cannabinoids. Dtsch. Arztebl. Int., 2012, 109(29-30), 495-501.
[http://dx.doi.org/10.3238/arztebl.2012.0495] [PMID: 23008748]
[109]
Noel, C. Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment Health Clin, 2018, 7(1), 29-38.
[http://dx.doi.org/10.9740/mhc.2017.01.029] [PMID: 29955495]
[110]
ElSohly, M.; Gul, W. Constitutens of Cannabis sativa.Handbook of cannabis; Pertwee, R.G., Ed.; Oxford University Press: Oxford, 2014, pp. 3-22.
[http://dx.doi.org/10.1093/acprof:oso/9780199662685.003.0001]
[111]
Russo, E.B. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol., 2011, 163(7), 1344-1364.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01238.x] [PMID: 21749363]
[112]
Hindocha, C.; Freeman, T.P.; Schafer, G.; Gardener, C.; Das, R.K.; Morgan, C.J.; Curran, H.V. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users. Eur. Neuropsychopharmacol., 2015, 25(3), 325-334.
[http://dx.doi.org/10.1016/j.euroneuro.2014.11.014] [PMID: 25534187]
[113]
Ben-Shabat, S.; Fride, E.; Sheskin, T.; Tamiri, T.; Rhee, M.H.; Vogel, Z.; Bisogno, T.; De Petrocellis, L.; Di Marzo, V.; Mechoulam, R. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur. J. Pharmacol., 1998, 353(1), 23-31.
[http://dx.doi.org/10.1016/S0014-2999(98)00392-6] [PMID: 9721036]
[114]
Benbadis, S.R.; Sanchez-Ramos, J.; Bozorg, A.; Giarratano, M.; Kalidas, K.; Katzin, L.; Robertson, D.; Vu, T.; Smith, A.; Zesiewicz, T. Medical marijuana in neurology. Expert Rev. Neurother., 2014, 14(12), 1453-1465.
[http://dx.doi.org/10.1586/14737175.2014.985209] [PMID: 25427150]
[115]
Blasco-Benito, S.; Seijo-Vila, M.; Caro-Villalobos, M.; Tundidor, I.; Andradas, C.; García-Taboada, E.; Wade, J.; Smith, S.; Guzmán, M.; Pérez-Gómez, E.; Gordon, M.; Sánchez, C. Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer. Biochem. Pharmacol., 2018, 157, 285-293.
[http://dx.doi.org/10.1016/j.bcp.2018.06.025] [PMID: 29940172]
[116]
Pamplona, F.A.; da Silva, L.R.; Coan, A.C. Potential clinical benefits of CBD-rich cannabis extracts over purified CBD in treatment-resistant epilepsy: observational data meta-analysis. Front. Neurol., 2018, 9, 759.
[http://dx.doi.org/10.3389/fneur.2018.00759] [PMID: 30258398]
[117]
Vigil, J.M.; Stith, S.S.; Diviant, J.P.; Brockelman, F.; Keeling, K.; Hall, B. Effectiveness of raw, natural medical cannabis flower for treating insomnia under naturalistic conditions. Medicines (Basel), 2018, 5(3)E75
[http://dx.doi.org/10.3390/medicines5030075] [PMID: 29997343]
[118]
Ibeas Bih, C.; Chen, T.; Nunn, A.V.; Bazelot, M.; Dallas, M.; Whalley, B.J. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics, 2015, 12(4), 699-730.
[http://dx.doi.org/10.1007/s13311-015-0377-3] [PMID: 26264914]
[119]
Di Marzo, V.; Piscitelli, F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics, 2015, 12(4), 692-698.
[http://dx.doi.org/10.1007/s13311-015-0374-6] [PMID: 26271952]
[120]
Maccarrone, M.; Bab, I.; Bíró, T.; Cabral, G.A.; Dey, S.K.; Di Marzo, V.; Konje, J.C.; Kunos, G.; Mechoulam, R.; Pacher, P.; Sharkey, K.A.; Zimmer, A. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol. Sci., 2015, 36(5), 277-296.
[http://dx.doi.org/10.1016/j.tips.2015.02.008] [PMID: 25796370]
[121]
Piscitelli, F.; Di Marzo, V. “Redundancy” of endocannabinoid inactivation: new challenges and opportunities for pain control. ACS Chem. Neurosci., 2012, 3(5), 356-363.
[http://dx.doi.org/10.1021/cn300015x] [PMID: 22860203]
[122]
Deng, H.; Verrico, C.D.; Kosten, T.R.; Nielsen, D.A. Psychosis and synthetic cannabinoids. Psychiatry Res., 2018, 268, 400-412.
[http://dx.doi.org/10.1016/j.psychres.2018.08.012] [PMID: 30125871]
[123]
Morrison, P.D.; Zois, V.; McKeown, D.A.; Lee, T.D.; Holt, D.W.; Powell, J.F.; Kapur, S.; Murray, R.M. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol. Med., 2009, 39(10), 1607-1616.
[http://dx.doi.org/10.1017/S0033291709005522] [PMID: 19335936]
[124]
Bonaccorso, S.; Ricciardi, A.; Zangani, C.; Chiappini, S.; Schifano, F. Cannabidiol (CBD) use in psychiatric disorders: a systematic review. Neurotoxicology, 2019, 74, 282-298.
[http://dx.doi.org/10.1016/j.neuro.2019.08.002] [PMID: 31412258]
[125]
Bloomfield, M.A.P.; Ashok, A.H.; Volkow, N.D.; Howes, O.D. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature, 2016, 539(7629), 369-377.
[http://dx.doi.org/10.1038/nature20153] [PMID: 27853201]
[126]
Rubino, T.; Zamberletti, E.; Parolaro, D. Adolescent exposure to cannabis as a risk factor for psychiatric disorders. J. Psychopharmacol., 2012, 26(1), 177-188.
[http://dx.doi.org/10.1177/0269881111405362] [PMID: 21768160]
[127]
Fischer, B.; Russell, C.; Sabioni, P.; van den Brink, W.; Le Foll, B.; Hall, W.; Rehm, J.; Room, R. Lower-risk cannabis use guidelines: a comprehensive update of evidence and recommendations. Am. J. Public Health, 2017, 107(8), e1-e12.
[http://dx.doi.org/10.2105/AJPH.2017.303818] [PMID: 28644037]
[128]
Cox, P.; Roche, D. Directive 2004/24/EC of the European Parliament and of the Council. Official Journal of the European Union, 2004. Available at: , https://eur-lex. europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:136:0085:0090:en:PDF(Access date: 7 August, 2019.
[129]
Mechoulam, R.; Ben-Shabat, S. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat. Prod. Rep., 1999, 16(2), 131-143.
[http://dx.doi.org/10.1039/a703973e] [PMID: 10331283]
[130]
Elfawal, M.A.; Towler, M.J.; Reich, N.G.; Weathers, P.J.; Rich, S.M. Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. Proc. Natl. Acad. Sci. USA, 2015, 112(3), 821-826.
[http://dx.doi.org/10.1073/pnas.1413127112] [PMID: 25561559]
[131]
Gasser, P.; Holstein, D.; Michel, Y.; Doblin, R.; Yazar-Klosinski, B.; Passie, T.; Brenneisen, R. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J. Nerv. Ment. Dis., 2014, 202(7), 513-520.
[http://dx.doi.org/10.1097/NMD.0000000000000113] [PMID: 24594678]
[132]
Johnson, M.; Richards, W.; Griffiths, R. Human hallucinogen research: guidelines for safety. J. Psychopharmacol., 2008, 22(6), 603-620.
[http://dx.doi.org/10.1177/0269881108093587] [PMID: 18593734]
[133]
Studerus, E.; Kometer, M.; Hasler, F.; Vollenweider, F.X. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J. Psychopharmacol., 2011, 25(11), 1434-1452.
[http://dx.doi.org/10.1177/0269881110382466] [PMID: 20855349]
[134]
Gallily, R.; Yekhtin, Z.; Hanuš, L.O. Overcoming the Bell-shaped dose-response of cannabidiol by using cannabis extract enriched in cannabidiol. Pharmacol. Pharm., 2015, 6, 75-85.
[http://dx.doi.org/10.4236/pp.2015.62010]
[135]
Interamerican Court of Human Rights. Case of the Kichwa indigenous people of Sarayaku v.Ecuador, Merits and Reparations 2012. Available at, http://www.worldcourts. com/iacthr/eng/decisions/2012.06.27_Kichwa_Indigenous_People_of_Sarayaku_v_Ecuador.pdf (Access date: 7 August, 2019.)
[136]
CESR. General Comment No.14: The Right to the Highest Attainable Standard of Health (art. 12) 2000. Available at:. https://www.refworld.org/pdfid/4538838d0.pdf (Access date: 7 August,2019)

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