Abstract
As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.
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References
Abrams, D. I. (2016). Integrating cannabis into clinical cancer care. Current Oncology, 23(2), S8–S14. https://doi.org/10.3747/co.23.3099
Andre, C. M., Hausman, J. F., & Guerriero, G. (2016). Cannabis sativa: The plant of the thousand and one molecules. Frontiers in Plant Science, 7, 19. https://doi.org/10.3389/fpls.2016.00019
Aso, E., Sanchez-Pla, A., Vegas-Lozano, E., Maldonado, R., & Ferrer, I. (2015). Cannabis-based medicine reduces multiple pathological processes in AbetaPP/PS1 mice. Journal of Alzheimer’s Disease, 43(3), 977–991. https://doi.org/10.3233/JAD-141014
Attaya, S., Kanthi, Y., Aster, R., & McCrae, K. (2009). Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction. Platelets, 20(1), 64–67. https://doi.org/10.1080/09537100802592676
Augenstein, W. L., Kulig, K. W., & Rumack, B. H. (1988). Captopril overdose resulting in hypotension. JAMA, 259(22), 3302–3305.
Avraham, H. K., Jiang, S., Fu, Y., Rockenstein, E., Makriyannis, A., Zvonok, A., … Avraham, S. (2014). The cannabinoid CB(2) receptor agonist AM1241 enhances neurogenesis in GFAP/Gp120 transgenic mice displaying deficits in neurogenesis. British Journal of Pharmacology, 171(2), 468–479. https://doi.org/10.1111/bph.12478
Barceloux, D. G. (2012). Medical toxicology of drug abuse: Synthesized chemicals and psychoactive plants. Hoboken, NJ: Wiley.
Ben Amar, M. (2006). Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology, 105(1–2), 1–25. https://doi.org/10.1016/j.jep.2006.02.001
Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T., Rhee, M. H., Vogel, Z., … Mechoulam, R. (1998). An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. European Journal of Pharmacology, 353(1), 23–31.
Bilkei-Gorzo, A., Albayram, O., Draffehn, A., Michel, K., Piyanova, A., Oppenheimer, H., … Zimmer, A. (2017). A chronic low dose of Delta9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nature Medicine, 23(6), 782–787. https://doi.org/10.1038/nm.4311
Bravo-Ferrer, I., Cuartero, M. I., Zarruk, J. G., Pradillo, J. M., Hurtado, O., Romera, V. G., … Moro, M. A. (2017). Cannabinoid type-2 receptor drives neurogenesis and improves functional outcome after stroke. Stroke, 48(1), 204–212. https://doi.org/10.1161/STROKEAHA.116.014793
Bregman, T., & Fride, E. (2011). Treatment with tetrahydrocannabinol (THC) prevents infertility in male cystic fibrosis mice. Journal of Basic and Clinical Physiology and Pharmacology, 22(1–2), 29–32. https://doi.org/10.1515/jbcpp.2011.004
Buckholtz, N. S., & Boggan, W. O. (1977). Monoamine oxidase inhibition in brain and liver produced by beta-carbolines: Structure-activity relationships and substrate specificity. Biochemical Pharmacology, 26(21), 1991–1996.
Cannabis-based medicines--GW pharmaceuticals: High CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD. (2003). Drugs R D, 4(5), 306–309.
Cao, C., Li, Y., Liu, H., Bai, G., Mayl, J., Lin, X., … Cai, J. (2014). The potential therapeutic effects of THC on Alzheimer’s disease. Journal of Alzheimer’s Disease, 42(3), 973–984. https://doi.org/10.3233/JAD-140093
Coons, J. C., Barcelona, R. A., Freedy, T., & Hagerty, M. F. (2005). Eptifibatide-associated acute, profound thrombocytopenia. Annals of Pharmacotherapy, 39(2), 368–372. https://doi.org/10.1345/aph.1E244
Dakic, V., Maciel, R. M., Drummond, H., Nascimento, J. M., Trindade, P., & Rehen, S. K. (2016). Harmine stimulates proliferation of human neural progenitors. PeerJ, 4, e2727. https://doi.org/10.7717/peerj.2727
Dakic, V., Nascimento, J. M., Sartore, R. C., Maciel, R. M., de Araujo, D. B., Ribeiro, S., … Rehen, S. K. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine. BioRxiv. https://doi.org/10.1101/108159
Dawson, W. (1934). Studies in the Egyptian medical texts: III. The Journal of Egyptian Archaeology, 20(1/2), 41–46.
Dawson, A. H., Harvey, D., Smith, A. J., Taylor, M., Whyte, I. M., Johnson, C. I., … Roberts, M. J. (1990). Lisinopril overdose. Lancet, 335(8687), 487–488.
de Araujo, D. B., Ribeiro, S., Cecchi, G. A., Carvalho, F. M., Sanchez, T. A., Pinto, J. P., … Santos, A. C. (2012). Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion. Human Brain Mapping, 33(11), 2550–2560. https://doi.org/10.1002/hbm.21381
de Lago, E., Moreno-Martet, M., Cabranes, A., Ramos, J. A., & Fernandez-Ruiz, J. (2012). Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects. Neuropharmacology, 62(7), 2299–2308. https://doi.org/10.1016/j.neuropharm.2012.01.030
de Mello Schier, A. R., de Oliveira Ribeiro, N. P., Coutinho, D. S., Machado, S., Arias-Carrion, O., Crippa, J. A., … Silva, A. C. (2014). Antidepressant-like and anxiolytic-like effects of cannabidiol: A chemical compound of Cannabis sativa. CNS & Neurological Disorders-Drug Targets, 13(6), 953–960.
Di Forti, M., Morgan, C., Dazzan, P., Pariante, C., Mondelli, V., Marques, T. R., … Murray, R. M. (2009). High-potency cannabis and the risk of psychosis. The British Journal of Psychiatry, 195(6), 488–491. https://doi.org/10.1192/bjp.bp.109.064220
Dos Santos, R. G., Grasa, E., Valle, M., Ballester, M. R., Bouso, J. C., Nomdedeu, J. F., … Riba, J. (2012). Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology (Berl), 219(4), 1039–1053. https://doi.org/10.1007/s00213-011-2434-x
Elsohly, M. A., & Slade, D. (2005). Chemical constituents of marijuana: The complex mixture of natural cannabinoids. Life Sciences, 78(5), 539–548. https://doi.org/10.1016/j.lfs.2005.09.011
Fabisiak, A., & Fichna, J. (2017). Cannabinoids as gastrointestinal anti-inflammatory drugs. Neurogastroenterology & Motility, 29(3). https://doi.org/10.1111/nmo.13038
Fadda, P., Robinson, L., Fratta, W., Pertwee, R. G., & Riedel, G. (2004). Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology, 47(8), 1170–1179. https://doi.org/10.1016/j.neuropharm.2004.08.009
Fakhoury, M. (2016). Could cannabidiol be used as an alternative to antipsychotics? Journal of Psychiatric Research, 80, 14–21. https://doi.org/10.1016/j.jpsychires.2016.05.013
Farnsworth, D. L. (1976). What is the evidence for an amotivational syndrome in cannabis users? Annals of the New York Academy of Sciences, 282(1), 1.
Fasinu, P. S., Phillips, S., ElSohly, M. A., & Walker, L. A. (2016). Current status and prospects for cannabidiol preparations as new therapeutic agents. Pharmacotherapy, 36(7), 781–796. https://doi.org/10.1002/phar.1780
Ferreira, S. H. (1965). A bradykinin-potentiating factor (bpf) present in the venom of bothrops jararaca. British Journal of Pharmacology and Chemotherapy, 24(1), 163–169. https://doi.org/10.1111/j.1476-5381.1965.tb02091.x
Fetterman, P. S., & Turner, C. E. (1972). Constituents of Cannabis sativa L. I. Propyl homologs of cannabinoids from an Indian variant. Journal of Pharmaceutical Sciences, 61(9), 1476–1477.
Flather, M. D., Yusuf, S., Kober, L., Pfeffer, M., Hall, A., Murray, G., … Braunwald, E. (2000). Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: A systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet, 355(9215), 1575–1581.
Formukong, E. A., Evans, A. T., & Evans, F. J. (1988). Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. Inflammation, 12(4), 361–371.
Forsyth, A. J. M. (2001). Distorted? A quantitative exploration of drug fatality reports in the popular press. The International Journal of Drug Policy, 12(5–6), 435–453. https://doi.org/10.1016/S0955-3959(01)00092-5
Gallant, M., Odei-Addo, F., Frost, C. L., & Levendal, R. A. (2009). Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes. Phytomedicine, 16(10), 942–949. https://doi.org/10.1016/j.phymed.2009.02.013
Gertsch, J., Pertwee, R. G., & Di Marzo, V. (2010). Phytocannabinoids beyond the Cannabis plant – do they exist? British Journal of Pharmacology, 160(3), 523–529. https://doi.org/10.1111/j.1476-5381.2010.00745.x
Gloss, D. (2015). An overview of products and bias in research. Neurotherapeutics, 12(4), 731–734. https://doi.org/10.1007/s13311-015-0370-x
Guy, G. W., Whittle, B. A., & Robson, P. (2004). The medicinal uses of cannabis and cannabinoids. Chicago, IL: Pharmaceutical Press.
Guzman, M. (2003). Cannabinoids: Potential anticancer agents. Nature Reviews Cancer, 3(10), 745–755. https://doi.org/10.1038/nrc1188
Hamblin, M. W., Leff, S. E., & Creese, I. (1984). Interactions of agonists with D-2 dopamine receptors: Evidence for a single receptor population existing in multiple agonist affinity-states in rat striatal membranes. Biochemical Pharmacology, 33(6), 877–887.
Hookana, E., Ansakorpi, H., Kortelainen, M. L., Junttila, M. J., Kaikkonen, K. S., Perkiomaki, J., & Huikuri, H. V. (2016). Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: A prospective case-control study. Annals of Medicine, 48(1–2), 111–117. https://doi.org/10.3109/07853890.2016.1140225
Hu, S. S., & Mackie, K. (2015). Distribution of the endocannabinoid system in the central nervous system. Handbook of Experimental Pharmacology, 231, 59–93. https://doi.org/10.1007/978-3-319-20825-1_3
Huff, J., & Chan, P. (2000). Antitumor effects of THC. Environmental Health Perspectives, 108(10), A442–A443.
Iurlo, M., Leone, G., Schilstrom, B., Linner, L., Nomikos, G., Hertel, P., … Svensson, H. (2001). Effects of harmine on dopamine output and metabolism in rat striatum: Role of monoamine oxidase-A inhibition. Psychopharmacology (Berl), 159(1), 98–104. https://doi.org/10.1007/s002130100879
Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V., & Mechoulam, R. (2009). Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb. Trends in Pharmacological Sciences, 30(10), 515–527. https://doi.org/10.1016/j.tips.2009.07.006
Jiang, W., Zhang, Y., Xiao, L., Van Cleemput, J., Ji, S. P., Bai, G., & Zhang, X. (2005). Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. The Journal of Clinical Investigation, 115(11), 3104–3116. https://doi.org/10.1172/JCI25509
Jin, K., Xie, L., Kim, S. H., Parmentier-Batteur, S., Sun, Y., Mao, X. O., … Greenberg, D. (2004). Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Molecular Pharmacology, 66(2), 204–208. https://doi.org/10.1124/mol.66.2.204
Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management, 39(2), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008
Johnson, J. R., Lossignol, D., Burnell-Nugent, M., & Fallon, M. T. (2013). An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. Journal of Pain and Symptom Management, 46(2), 207–218. https://doi.org/10.1016/j.jpainsymman.2012.07.014
Keating, G. M. (2017). Delta-9-Tetrahydrocannabinol/Cannabidiol oromucosal spray (Sativex(R)): A review in multiple sclerosis-related spasticity. Drugs, 77(5), 563–574. https://doi.org/10.1007/s40265-017-0720-6
Kekecs, Z., Szollosi, A., Palfi, B., Szaszi, B., Kovacs, K. J., Dienes, Z., & Aczel, B. (2016). Commentary: Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Frontiers in Neuroscience, 10, 155. https://doi.org/10.3389/fnins.2016.00155
Koehler, J. (2014). Who benefits most from THC:CBD spray? Learning from clinical experience. European Neurology, 71(Suppl 1), 10–15. https://doi.org/10.1159/000357743
Labate, B. C., & Cavnar, C. (2013). The therapeutic use of ayahuasca. New York, NY: Springer.
Labate, B. C., & Cavnar, C. (2014a). Ayahuasca shamanism in the Amazon and beyond. New York, NY: Oxford University Press.
Labate, B. C., & Cavnar, C. (2014b). Prohibition, religious freedom, and human rights: Regulating traditional drug use. New York, NY: Springer.
Labigalini, E., Jr., Rodrigues, L. R., & Da Silveira, D. X. (1999). Therapeutic use of cannabis by crack addicts in Brazil. Journal of Psychoactive Drugs, 31(4), 451–455. https://doi.org/10.1080/02791072.1999.10471776
Ladin, D. A., Soliman, E., Griffin, L., & Van Dross, R. (2016). Preclinical and clinical assessment of cannabinoids as anti-cancer agents. Frontiers in Pharmacology, 7, 361. https://doi.org/10.3389/fphar.2016.00361
Letyagin, A. Y., Savelov, A. A., & Polosmak, A. A. (2014). High field magnetic resonance imaging of a mummy from Ak-Alakha-3 mound 1, Ukok plateau, Gorny Altai: Findings and interpretations. Archaeology Ethnology & Anthropology of Eurasia, 42(4), 83–91.
Lewis, D. Y., & Brett, R. R. (2010). Activity-based anorexia in C57/BL6 mice: Effects of the phytocannabinoid, Delta9-tetrahydrocannabinol (THC) and the anandamide analogue, OMDM-2. European Neuropsychopharmacology, 20(9), 622–631. https://doi.org/10.1016/j.euroneuro.2010.04.002
Liu, W. M., Fowler, D. W., & Dalgleish, A. G. (2010). Cannabis-derived substances in cancer therapy--an emerging anti-inflammatory role for the cannabinoids. Current Clinical Pharmacology, 5(4), 281–287.
Lombard, C., Nagarkatti, M., & Nagarkatti, P. S. (2005). Targeting cannabinoid receptors to treat leukemia: Role of cross-talk between extrinsic and intrinsic pathways in Delta9-tetrahydrocannabinol (THC)-induced apoptosis of Jurkat cells. Leukemia Research, 29(8), 915–922. https://doi.org/10.1016/j.leukres.2005.01.014
Maccarrone, M., Maldonado, R., Casas, M., Henze, T., & Centonze, D. (2017). Cannabinoids therapeutic use: What is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others? Expert Review of Clinical Pharmacology, 10(4), 443–455. https://doi.org/10.1080/17512433.2017.1292849
Mckenna, D. J., Towers, G. H. N., & Abbott, F. (1984). Monoamine-oxidase inhibitors in South-American hallucinogenic plants: Tryptamine and beta-carboline constituents of ayahuasca. Journal of Ethnopharmacology, 10, 195–223.
McPartland, J. M., & Guy, G. W. (2004). The evolution of Cannabis and coevolution with the cannabinoid receptor—a hypothesis. In G. Guy, B. A. Whittle, & P. Robson (Eds.), The medicinal use of cannabis and cannabinoids (pp. 71–101). Grayslake, IL: Pharmaceutical Press.
Mechoulam, R., Hanus, L. O., Pertwee, R., & Howlett, A. C. (2014). Early phytocannabinoid chemistry to endocannabinoids and beyond. Nature Reviews Neuroscience, 15(11), 757–764. https://doi.org/10.1038/nrn3811
Moldrich, G., & Wenger, T. (2000). Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides, 21(11), 1735–1742.
Molina-Holgado, F., Pinteaux, E., Moore, J. D., Molina-Holgado, E., Guaza, C., Gibson, R. M., & Rothwell, N. J. (2003). Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. Journal of Neuroscience, 23(16), 6470–6474.
Morgan, C. J., Freeman, T. P., Schafer, G. L., & Curran, H. V. (2010). Cannabidiol attenuates the appetitive effects of Delta 9-tetrahydrocannabinol in humans smoking their chosen cannabis. Neuropsychopharmacology, 35(9), 1879–1885. https://doi.org/10.1038/npp.2010.58
Morgan, C. J., Schafer, G., Freeman, T. P., & Curran, H. V. (2010). Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: Naturalistic study [corrected]. The British Journal of Psychiatry, 197(4), 285–290. https://doi.org/10.1192/bjp.bp.110.077503
Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L., & Nagarkatti, M. (2009). Cannabinoids as novel anti-inflammatory drugs. Future Medicinal Chemistry, 1(7), 1333–1349. https://doi.org/10.4155/fmc.09.93
Nutt, D. J., King, L. A., Phillips, L. D., & Independent Scientific Committee on Drugs. (2010). Drug harms in the UK: A multicriteria decision analysis. Lancet, 376(9752), 1558–1565. https://doi.org/10.1016/S0140-6736(10)61462-6
Ohtsuka, Y., Yoshinaga, H., & Kobayashi, K. (2000). Refractory childhood epilepsy and factors related to refractoriness. Epilepsia, 41(Suppl 9), 14–17.
Osorio, L., Sanches, R. F., Macedo, L. R., Santos, R. G., Maia-de-Oliveira, J. P., Wichert-Ana, L., … Hallak, J. E. (2015). Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A preliminary report. Revista Brasileira de Psiquiatria, 37(1), 13–20. https://doi.org/10.1590/1516-4446-2014-1496
Palhano-Fontes, F. (2017). Os efeitos antidepressivos da ayahuasca, suas bases neurais e relação com a experiência psicodélica [The antidepressant effects of ayahuasca, its neural bases and relation with the psychedelic experience] (Doctoral dissertation). Federal University of Rio Grande do Norte, Natal. Retrieved from https://repositorio.ufrn.br/jspui/handle/123456789/24156
Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M., Pessoa, J., … de Araujo, D. B. (2017). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomised placebo-controlled trial. BioRxiv. https://doi.org/10.1101/103531
Parakh, S., Naik, N., Rohatgi, N., Bhat, U., & Parakh, K. (2009). Eptifibatide overdose. International Journal of Cardiology, 131(3), 430–432. https://doi.org/10.1016/j.ijcard.2007.07.132
Park, H., Purnell, G. V., & Mirchandani, H. G. (1990). Suicide by captopril overdose. Journal of Toxicology: Clinical Toxicology, 28(3), 379–382.
Parker, H. G., Dreger, D. L., Rimbault, M., Davis, B. W., Mullen, A. B., Carpintero-Ramirez, G., & Ostrander, E. A. (2017). Genomic analyses reveal the influence of geographic origin, migration, and hybridization on modern dog breed development. Cell Reports, 19(4), 697–708. https://doi.org/10.1016/j.celrep.2017.03.079
Patti, F. (2016). Health authorities data collection of THC:CBD oromucosal spray (L’Agenzia Italiana del Farmaco Web Registry): Figures after 1.5 years. European Neurology, 75(Suppl 1), 9–12. https://doi.org/10.1159/000444236
Phillips, D. R., & Scarborough, R. M. (1997). Clinical pharmacology of eptifibatide. American Journal of Cardiology, 80(4A), 11B–20B.
Pollan, M. (2001). The botany of desire: A plant’s eye view of the world (1st ed.). New York, NY: Random House.
Price, M. R., Baillie, G. L., Thomas, A., Stevenson, L. A., Easson, M., Goodwin, R., … Ross, R. A. (2005). Allosteric modulation of the cannabinoid CB1 receptor. Molecular Pharmacology, 68(5), 1484–1495. https://doi.org/10.1124/mol.105.016162
Radwan, M. M., Elsohly, M. A., Slade, D., Ahmed, S. A., Wilson, L., El-Alfy, A. T., … Ross, S. A. (2008). Non-cannabinoid constituents from a high potency Cannabis sativa variety. Phytochemistry, 69(14), 2627–2633. https://doi.org/10.1016/j.phytochem.2008.07.010
Rekand, T. (2014). THC:CBD spray and MS spasticity symptoms: Data from latest studies. European Neurology, 71(Suppl 1), 4–9. https://doi.org/10.1159/000357742
Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology, 26(8), 1327–1337. https://doi.org/10.1016/j.euroneuro.2016.05.001
Rimonabant: Depression and suicide. (2009). Prescrire International, 18(99), 24.
Robbe, D., Montgomery, S. M., Thome, A., Rueda-Orozco, P. E., McNaughton, B. L., & Buzsaki, G. (2006). Cannabinoids reveal importance of spike timing coordination in hippocampal function. Nature Neuroscience, 9(12), 1526–1533. https://doi.org/10.1038/nn1801
Rocha e Silva, M. (1963). The physiological significance of bradykinin. Annals of the New York Academy of Sciences, 104, 190–210.
Romeo, B., Choucha, W., Fossati, P., & Rotge, J. Y. (2015). Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry Research, 230(2), 682–688. https://doi.org/10.1016/j.psychres.2015.10.032
Rosenberg, E. C., Tsien, R. W., Whalley, B. J., & Devinsky, O. (2015). Cannabinoids and epilepsy. Neurotherapeutics, 12(4), 747–768. https://doi.org/10.1007/s13311-015-0375-5
Russo, E. B. (2011). Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x
Sanches, R. F., de Lima Osorio, F., Dos Santos, R. G., Macedo, L. R., Maia-de-Oliveira, J. P., Wichert-Ana, L., … Hallak, J. E. (2016). Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A SPECT study. Journal of Clinical Psychopharmacology, 36(1), 77–81. https://doi.org/10.1097/JCP.0000000000000436
Sastre-Garriga, J., Vila, C., Clissold, S., & Montalban, X. (2011). THC and CBD oromucosal spray (Sativex(R)) in the management of spasticity associated with multiple sclerosis. Expert Review of Neurotherapeutics, 11(5), 627–637. https://doi.org/10.1586/ern.11.47
Sawler, J., Stout, J. M., Gardner, K. M., Hudson, D., Vidmar, J., Butler, L., … Myles, S. (2015). The genetic structure of marijuana and hemp. PLoS One, 10(8), e0133292. https://doi.org/10.1371/journal.pone.0133292
Schmits, E., & Quertemont, E. (2013). Les drogues dites “douces”: Cannibas et syndrome amotivationnel [So called “soft” drugs: cannabis and the amotivational syndrome]. Revue Médicale de Liège, 68(5–6), 281–286.
Scott, K. A., Dalgleish, A. G., & Liu, W. M. (2014). The combination of cannabidiol and Delta9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Molecular Cancer Therapeutics, 13(12), 2955–2967. https://doi.org/10.1158/1535-7163.MCT-14-0402
Sherif, M., Radhakrishnan, R., D’Souza, D. C., & Ranganathan, M. (2016). Human laboratory studies on Cannabinoids and psychosis. Biological Psychiatry, 79(7), 526–538. https://doi.org/10.1016/j.biopsych.2016.01.011
Silva, T. B., Balbino, C. Q., & Weiber, A. F. (2015). The relationship between cannabidiol and psychosis: A review. Annals of Clinical Psychiatry, 27(2), 134–141.
Solt, K., Ruesch, D., Forman, S. A., Davies, P. A., & Raines, D. E. (2007). Differential effects of serotonin and dopamine on human 5-HT3A receptor kinetics: Interpretation within an allosteric kinetic model. Journal of Neuroscience, 27(48), 13151–13160. https://doi.org/10.1523/JNEUROSCI.3772-07.2007
Sznitman, S. R., & Lewis, N. (2015). Is cannabis an illicit drug or a medicine? A quantitative framing analysis of Israeli newspaper coverage. International Journal of Drug Policy, 26(5), 446–452. https://doi.org/10.1016/j.drugpo.2015.01.010
Thomas, G., Lucas, P., Capler, N. R., Tupper, K. W., & Martin, G. (2013). Ayahuasca-assisted therapy for addiction: Results from a preliminary observational study in Canada. Current Drug Abuse Reviews, 6(1), 30–42.
Topol, E. J., Bousser, M. G., Fox, K. A., Creager, M. A., Despres, J. P., Easton, J. D., … Investigators, C. (2010). Rimonabant for prevention of cardiovascular events (CRESCENDO): A randomised, multicentre, placebo-controlled trial. Lancet, 376(9740), 517–523. https://doi.org/10.1016/S0140-6736(10)60935-X
Tsou, K., Brown, S., Sanudo-Pena, M. C., Mackie, K., & Walker, J. M. (1998). Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience, 83(2), 393–411.
U’Prichard, D. C. (1980). Multiple CNS receptor interactions of ergot alkaloids: Affinity and intrinsic activity analysis in in vitro binding systems. Advances in Biochemical Psychopharmacology, 23, 103–115.
van Vliet, S. A., Vanwersch, R. A., Jongsma, M. J., Olivier, B., & Philippens, I. H. (2008). Therapeutic effects of Delta9-THC and modafinil in a marmoset Parkinson model. European Neuropsychopharmacology, 18(5), 383–389. https://doi.org/10.1016/j.euroneuro.2007.11.003
Verty, A. N., Evetts, M. J., Crouch, G. J., McGregor, I. S., Stefanidis, A., & Oldfield, B. J. (2011). The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology, 36(7), 1349–1358. https://doi.org/10.1038/npp.2011.19
Wacker, D., Wang, S., McCorvy, J. D., Betz, R. M., Venkatakrishnan, A. J., Levit, A., … Roth, B. L. (2017). Crystal structure of an LSD-bound human serotonin receptor. Cell, 168(3), 377–389. e312. https://doi.org/10.1016/j.cell.2016.12.033
Weber, M., Goldman, B., & Truniger, S. (2010). Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: A randomised, double-blind crossover trial. Journal of Neurology, Neurosurgery & Psychiatry, 81(10), 1135–1140. https://doi.org/10.1136/jnnp.2009.200642
Winkelman, M. (2014). Psychedelics as medicines for substance abuse rehabilitation: Evaluating treatments with LSD, peyote, ibogaine and ayahuasca. Current Drug Abuse Reviews, 7(2), 101–116.
Xapelli, S., Agasse, F., Sarda-Arroyo, L., Bernardino, L., Santos, T., Ribeiro, F. F., … Malva, J. O. (2013). Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures. PLoS One, 8(5), e63529. https://doi.org/10.1371/journal.pone.0063529
Yu, Y. Z., Liu, S., Wang, H. C., Shi, D. Y., Xu, Q., Zhou, X. W., … Huang, P. T. (2016). A novel recombinant 6Abeta15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer’s disease-like pathology, cognitive decline and synaptic loss in aged 3 x Tg-AD mice. Scientific Reports, 6, 27175. https://doi.org/10.1038/srep27175
Zani, A., Braida, D., Capurro, V., & Sala, M. (2007). Delta9-tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors. British Journal of Pharmacology, 152(8), 1301–1311. https://doi.org/10.1038/sj.bjp.0707514
Zarate, C. A., Jr., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., … Manji, H. K. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856–864. https://doi.org/10.1001/archpsyc.63.8.856
Zettl, U. K., Rommer, P., Hipp, P., & Patejdl, R. (2016). Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis. Therapeutic Advances in Neurological Disorders, 9(1), 9–30. https://doi.org/10.1177/1756285615612659
Zuardi, A. W., Crippa, J. A., & Hallak, J. E. (2010). Cannabis sativa: A planta que pode produzir efeitos indesejáveis e também tratá-los [Cannabis sativa: The plant that can induce unwanted effects and also treat them]. Revista Brasileira de Psiquiatria, 32(Suppl 1), S1–S2.
Zuardi, A. W., Crippa, J. A., Hallak, J. E., Bhattacharyya, S., Atakan, Z., Martin-Santos, R., … Guimaraes, F. S. (2012). A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Current Pharmaceutical Design, 18(32), 5131–5140.
Zurier, R. B. (2003). Prospects for cannabinoids as anti-inflammatory agents. Journal of Cellular Biochemistry, 88(3), 462–466. https://doi.org/10.1002/jcb.10291
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Ribeiro, S. (2018). Whole Organisms or Pure Compounds? Entourage Effect Versus Drug Specificity. In: Labate, B., Cavnar, C. (eds) Plant Medicines, Healing and Psychedelic Science. Springer, Cham. https://doi.org/10.1007/978-3-319-76720-8_8
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