1,276
Views
14
CrossRef citations to date
0
Altmetric
Review Article

Dimethyltryptamine: Endogenous Role and Therapeutic Potential

, &
Pages 299-310 | Received 06 Aug 2018, Accepted 01 Feb 2019, Published online: 25 Apr 2019

References

  • Alonso, J. F., S. Romero, M. A. Mananas, and J. Riba. 2015. Serotonergic psychedelics temporarily modify information transfer in humans. International Journal of Neuropsychopharmacology 18 (8). doi: 10.1093/ijnp/pyv039.
  • Barbosa, P. C., J. S. Giglio, and P. Dalgalarrondo. 2005. Altered states of consciousness and short-term psychological after-effects induced by the first time ritual use of ayahuasca in an urban context in Brazil. Journal of Psychoactive Drugs 37 (2):193–201. doi:10.1080/02791072.2005.10399801.
  • Barbosa, P. C., S. Mizumoto, M. P. Bogenschutz, and R. J. Strassman. 2012. Health status of ayahuasca users. Drug Testing and Analysis 4 (7–8):601–09. doi:10.1002/dta.1383.
  • Barbosa, P. C., R. J. Strassman, D. X. Da Silveira, K. Areco, R. Hoy, J. Pommy, R. Thoma, and M. Bogenschutz. 2016. Psychological and neuropsychological assessment of regular hoasca users. Comprehensive Psychiatry 71:95–105. doi:10.1016/j.comppsych.2016.09.003.
  • Barbosa, P. C. R., L. F. Tofoli, M. P. Bogenschutz, R. Hoy, L. F. Berro, E. A. V. Marinho, K. N. Areco, and M. J. Winkelman. 2018. Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in Psychiatry 9:136. doi:10.3389/fpsyt.2018.00136.
  • Barker, S. A., J. M. Beaton, S. T. Christian, J. A. Monti, and P. E. Morris. 1982. Comparison of the brain levels of N,N-dimethyltryptamine and alpha, alpha, beta, beta-tetradeutero-N-N-dimethyltryptamine following intraperitoneal injection. The in vivo kinetic isotope effect. Biochemical Pharmacology 31 (15):2513–16.
  • Barker, S. A., J. Borjigin, I. Lomnicka, and R. Strassman. 2013. LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate. Biomedical Chromatography : BMC 27 (12):1690–700. doi:10.1002/bmc.2981.
  • Barker, S. A., E. H. McIlhenny, and R. Strassman. 2012. A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955–2010. Drug Testing and Analysis 4 (7–8):617–35. doi:10.1002/dta.422.
  • Barker, S. A., J. A. Monti, and S. T. Christian. 1981. N, N-dimethyltryptamine: An endogenous hallucinogen. International Review of Neurobiology 22:83–110.
  • Benington, F., R. D. Morin, and L. C. Clark Jr. 1965. 5-methoxy-N, N-dimethyltryptamine, a possible endogenous psychotoxin. The Alabama Journal of Medical Sciences 2 (4):397–403.
  • Berry, M. D., R. R. Gainetdinov, M. C. Hoener, and M. Shahid. 2017. Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges. Pharmacology & Therapeutics 180:161–80. doi:10.1016/j.pharmthera.2017.07.002.
  • Blough, B. E., A. Landavazo, A. M. Decker, J. S. Partilla, M. H. Baumann, and R. B. Rothman. 2014. Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology 231 (21):4135–44. doi:10.1007/s00213-014-3557-7.
  • Boeker, H., and R. Kraehenmann. 2018. Neuropsychodynamic approach to depression: Integrating resting state dysfunctions of the brain and disturbed self-related processes. Frontiers in Human Neuroscience 12:247. doi:10.3389/fnhum.2018.00247.
  • Borowsky, B., N. Adham, K. A. Jones, R. Raddatz, R. Artymyshyn, K. L. Ogozalek, M. M. Durkin, P. P. Lakhlani, J. A. Bonini, S. Pathirana, et al. 2001. Trace amines: Identification of a family of mammalian G protein-coupled receptors. Proceedings of the National Academy of Sciences of the United States of America 98 (16):8966–71. doi:10.1073/pnas.151105198.
  • Bouso, J. C., F. Palhano-Fontes, A. Rodriguez-Fornells, S. Ribeiro, R. Sanches, J. A. Crippa, J. E. Hallak, D. B. de Araujo, and J. Riba. 2015. Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology 25 (4):483–92. doi:10.1016/j.euroneuro.2015.01.008.
  • Bunzow, J. R., M. S. Sonders, S. Arttamangkul, L. M. Harrison, G. Zhang, D. I. Quigley, T. Darland, K. L. Suchland, S. Pasumamula, J. L. Kennedy, et al. 2001. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Molecular Pharmacology 60 (6):1181–88.
  • Cakic, V., J. Potkonyak, and A. Marshall. 2010. Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. Drug and Alcohol Dependence 111 (1–2):30–37. doi:10.1016/j.drugalcdep.2010.03.015.
  • Callaway, J. C., D. J. McKenna, C. S. Grob, G. S. Brito, L. P. Raymon, R. E. Poland, E. N. Andrade, E. O. Andrade, and D. C. Mash. 1999. Pharmacokinetics of hoasca alkaloids in healthy humans. Journal of Ethnopharmacology 65 (3):243–56.
  • Callaway, J. C., L. P. Raymon, W. L. Hearn, D. J. McKenna, C. S. Grob, G. S. Brito, and D. C. Mash. 1996. Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca. Journal of Analytical Toxicology 20 (6):492–97.
  • Cameron, L. P., C. J. Benson, L. E. Dunlap, and D. E. Olson. 2018. Effects of N, N-Dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS Chemical Neuroscience 9 (7):1582–90. doi:10.1021/acschemneuro.8b00134.
  • Carbonaro, T. M., and M. B. Gatch. 2016. Neuropharmacology of N,N-dimethyltryptamine. Brain Research Bulletin 126 (Pt 1):74–88. doi:10.1016/j.brainresbull.2016.04.016.
  • Carhart-Harris, R. L., M. Bolstridge, J. Rucker, C. M. Day, D. Erritzoe, M. Kaelen, M. Bloomfield, J. A. Rickard, B. Forbes, A. Feilding, et al. 2016. Psilocybin with psychological support for treatment-resistant depression: An open-label feasibility study. Lancet Psychiatry 3 (7):619–27. doi:10.1016/S2215-0366(16)30065-7.
  • Carlini, E. A. 2003. Plants and the central nervous system. Pharmacology, Biochemistry, and Behavior 75 (3):501–12.
  • Cata-Preta, E. G., Y. A. Serra, E. D. C. Moreira-Junior, H. S. Reis, N. D. Kisaki, M. Libarino-Santos, R. R. R. Silva, T. Barros-Santos, L. C. Santos, P. C. R. Barbosa, et al. 2018. Ayahuasca and its DMT- and beta-carbolines - containing ingredients block the expression of ethanol-induced conditioned place preference in mice: Role of the treatment environment. Frontiers in Pharmacology 9:561. doi:10.3389/fphar.2018.00561.
  • Christian, S. T., R. Harrison, E. Quayle, J. Pagel, and J. Monti. 1977. The in vitro identification of dimethyltryptamine (DMT) in mammalian brain and its characterization as a possible endogenous neuroregulatory agent. Biochemical Medicine 18 (2):164–83.
  • Chu, U. B., S. K. Vorperian, K. Satyshur, K. Eickstaedt, N. V. Cozzi, T. Mavlyutov, A. R. Hajipour, and A. E. Ruoho. 2014. Noncompetitive inhibition of indolethylamine-N-methyltransferase by N,N-dimethyltryptamine and N,N-dimethylaminopropyltryptamine. Biochemistry 53 (18):2956–65. doi:10.1021/bi500175p.
  • Cobos, E. J., J. M. Entrena, F. R. Nieto, C. M. Cendan, and E. Del Pozo. 2008. Pharmacology and therapeutic potential of sigma(1) receptor ligands. Current Neuropharmacology 6 (4):344–66. doi:10.2174/157015908787386113.
  • Cohen, I., and W. H. Vogel. 1972. Determination and physiological disposition of dimethyltryptamine and diethyltryptamine in rat brain, liver and plasma. Biochemical Pharmacology 21 (8):1214–16.
  • Cotter, R., Y. Pei, L. Mus, A. Harmeier, R. R. Gainetdinov, M. C. Hoener, and J. J. Canales. 2015. The trace amine-associated receptor 1 modulates methamphetamine‘s neurochemical and behavioral effects. Frontiers in Neuroscience 9:39. doi:10.3389/fnins.2015.00039.
  • Coutinho, J. F., S. V. Fernandesl, J. M. Soares, L. Maia, O. F. Goncalves, and A. Sampaio. 2016. Default mode network dissociation in depressive and anxiety states. Brain Imaging and Behavior 10 (1):147–57. doi:10.1007/s11682-015-9375-7.
  • Cozzi, N. V., A. Gopalakrishnan, L. L. Anderson, J. T. Feih, A. T. Shulgin, P. F. Daley, and A. E. Ruoho. 2009. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. Journal of Neural Transmission (Vienna) 116 (12):1591–99. doi:10.1007/s00702-009-0308-8.
  • Daumann, J., D. Wagner, K. Heekeren, A. Neukirch, C. M. Thiel, and E. Gouzoulis-Mayfrank. 2010. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis. Journal of Psychopharmacology (Oxford, England) 24 (10):1515–24. doi:10.1177/0269881109103227.
  • Doering-Silveira, E., C. S. Grob, M. D. de Rios, E. Lopez, L. K. Alonso, C. Tacla, and D. X. Da Silveira. 2005. Report on psychoactive drug use among adolescents using ayahuasca within a religious context. Journal of Psychoactive Drugs 37 (2):141–44. doi:10.1080/02791072.2005.10399794.
  • Dominguez-Clave, E., J. Soler, M. Elices, J. C. Pascual, E. Alvarez, M. de la Fuente Revenga, P. Friedlander, A. Feilding, and J. Riba. 2016. Ayahuasca: Pharmacology, neuroscience and therapeutic potential. Brain Research Bulletin 126 (Pt 1):89–101. doi:10.1016/j.brainresbull.2016.03.002.
  • Dos Santos, R. G., J. C. Bouso, and J. E. C. Hallak. 2017. Ayahuasca, dimethyltryptamine, and psychosis: A systematic review of human studies. Therapeutic Advances in Psychopharmacology 7 (4):141–57. doi:10.1177/2045125316689030.
  • Dos Santos, R. G., F. L. Osorio, J. A. Crippa, and J. E. Hallak. 2016. Antidepressive and anxiolytic effects of ayahuasca: A systematic literature review of animal and human studies. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 38 (1):65–72. doi:10.1590/1516-4446-2015-1701.
  • Dos Santos, R. G., M. Valle, J. C. Bouso, J. F. Nomdedeu, J. Rodriguez-Espinosa, E. H. McIlhenny, S. A. Barker, M. J. Barbanoj, and J. Riba. 2011. Autonomic, neuroendocrine, and immunological effects of ayahuasca: A comparative study with d-amphetamine. Journal of Clinical Psychopharmacology 31 (6):717–26. doi:10.1097/JCP.0b013e31823607f6.
  • Drevets, W. C., J. Savitz, and M. Trimble. 2008. The subgenual anterior cingulate cortex in mood disorders. CNS Spectrums 13 (8):663–81.
  • Fabregas, J. M., D. Gonzalez, S. Fondevila, M. Cutchet, X. Fernandez, P. C. Barbosa, M. A. Alcazar-Corcoles, M. J. Barbanoj, J. Riba, and J. C. Bouso. 2010. Assessment of addiction severity among ritual users of ayahuasca. Drug and Alcohol Dependence 111 (3):257–61. doi:10.1016/j.drugalcdep.2010.03.024.
  • Farzin, D., and N. Mansouri. 2006. Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology 16 (5):324–28. doi:10.1016/j.euroneuro.2005.08.005.
  • Fontanilla, D., M. Johannessen, A. R. Hajipour, N. V. Cozzi, M. B. Jackson, and A. E. Ruoho. 2009. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323 (5916):934–37. doi:10.1126/science.1166127.
  • Fortunato, J. J., G. Z. Reus, T. R. Kirsch, R. B. Stringari, L. Stertz, F. Kapczinski, J. P. Pinto, J. E. Hallak, A. W. Zuardi, J. A. Crippa, et al. 2009. Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus. Progress in Neuro-Psychopharmacology & Biological Psychiatry 33 (8):1425–30. doi:10.1016/j.pnpbp.2009.07.021.
  • Francardo, V., F. Bez, T. Wieloch, H. Nissbrandt, K. Ruscher, and M. A. Cenci. 2014. Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain 137 (Pt 7):1998–2014. doi:10.1093/brain/awu107.
  • Franzen, F., and H. Gross. 1965. Tryptamine, N,N-dimethyltryptamine, N,N-dimethyl-5-hydroxytryptamine and 5-methoxytryptamine in human blood and urine. Nature 206 (988):1052.
  • Galvao, A. C. M., R. N. de Almeida, F. A. M. Eads Silva, F. F. Palhano-Fontes, H. Onias, E. Arcoverde, J. P. Maia-de-Oliveira, D. B. de Araujo, B. Lobao-Soares, and N. L. Galvao-Coelho. 2018. Cortisol modulation by ayahuasca in patients with treatment resistant depression and healthy controls. Frontiers in Psychiatry 9:185. doi:10.3389/fpsyt.2018.00185.
  • Garcia-Romeu, A., B. Kersgaard, and P. H. Addy. 2016. Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology 24 (4):229–68. doi:10.1037/pha0000084.
  • Gillin, J. C., J. Kaplan, R. Stillman, and R. J. Wyatt. 1976. The psychedelic model of schizophrenia: The case of N,N-dimethyltryptamine. The American Journal of Psychiatry 133 (2):203–08. doi:10.1176/ajp.133.2.203.
  • Glick, S. D., M. E. Kuehne, J. Raucci, T. E. Wilson, D. Larson, R. W. Keller Jr., and J. N. Carlson. 1994. Effects of iboga alkaloids on morphine and cocaine self-administration in rats: Relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research 657 (1–2):14–22.
  • Gouzoulis-Mayfrank, E., K. Heekeren, A. Neukirch, M. Stoll, C. Stock, M. Obradovic, and K. A. Kovar. 2005. Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): A double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry 38 (6):301–11. doi:10.1055/s-2005-916185.
  • Grandy, D. K. 2007. Trace amine-associated receptor 1-family archetype or iconoclast? Pharmacology & Therapeutics 116 (3):355–90. doi:10.1016/j.pharmthera.2007.06.007.
  • Grob, C. S., D. J. McKenna, J. C. Callaway, G. S. Brito, E. S. Neves, G. Oberlaender, O. L. Saide, E. Labigalini, C. Tacla, C. T. Miranda, et al. 1996. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. The Journal of Nervous and Mental Disease 184 (2):86–94.
  • Halberstadt, A. L., L. Koedood, S. B. Powell, and M. A. Geyer. 2011. Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. Journal of Psychopharmacology (Oxford, England) 25 (11):1548–61. doi:10.1177/0269881110388326.
  • Halpern, J. H. 2004. Hallucinogens and dissociative agents naturally growing in the United States. Pharmacology & Therapeutics 102 (2):131–38. doi:10.1016/j.pharmthera.2004.03.003.
  • Halpern, J. H., A. R. Sherwood, T. Passie, K. C. Blackwell, and A. J. Ruttenber. 2008. Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research 14 (8):SR15–SR22.
  • Hashimoto, K. 2015. Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication. Journal of Pharmacological Sciences 127 (1):6–9. doi:10.1016/j.jphs.2014.11.010.
  • Hayashi, T. 2015. Sigma-1 receptor: The novel intracellular target of neuropsychotherapeutic drugs. Journal of Pharmacological Sciences 127 (1):2–5. doi:10.1016/j.jphs.2014.07.001.
  • Hayashi, T., and T. P. Su. 2007. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival. Cell 131 (3):596–610. doi:10.1016/j.cell.2007.08.036.
  • Heekeren, K., A. Neukirch, J. Daumann, M. Stoll, M. Obradovic, K. A. Kovar, M. A. Geyer, and E. Gouzoulis-Mayfrank. 2007. Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis. Journal of Psychopharmacology (Oxford, England) 21 (3):312–20. doi:10.1177/0269881107077734.
  • Herman, K. S., R. R. Bowsher, and D. P. Henry. 1985. Synthesis of N pi-methylhistamine and N alpha-methylhistamine by purified rabbit lung indolethylamine N-methyltransferase. The Journal of Biological Chemistry 260 (22):12336–40.
  • John, J., P. Kukshal, T. Bhatia, K. V. Chowdari, V. L. Nimgaonkar, S. N. Deshpande, and B. K. Thelma. 2017. Possible role of rare variants in trace amine associated receptor 1 in schizophrenia. Schizophrenia Research 189:190–95. doi:10.1016/j.schres.2017.02.020.
  • Johnson, M. W., and R. R. Griffiths. 2017. Potential therapeutic effects of psilocybin. Neurotherapeutics 14 (3):734–40. doi:10.1007/s13311-017-0542-y.
  • Kaplan, J., L. R. Mandel, R. Stillman, R. W. Walker, W. J. VandenHeuvel, J. C. Gillin, and R. J. Wyatt. 1974. Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive dosages to human subjects. Psychopharmacologia 38 (3):239–45.
  • Katz, M. M., J. L. Tekell, C. L. Bowden, S. Brannan, J. P. Houston, N. Berman, and A. Frazer. 2004. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology 29 (3):566–79. doi:10.1038/sj.npp.1300341.
  • Keiser, M. J., V. Setola, J. J. Irwin, C. Laggner, A. I. Abbas, S. J. Hufeisen, N. H. Jensen, M. B. Kuijer, R. C. Matos, T. B. Tran, et al. 2009. Predicting new molecular targets for known drugs. Nature 462 (7270):175–81. doi:10.1038/nature08506.
  • Kessler, R. C., and E. J. Bromet. 2013. The epidemiology of depression across cultures. Annual Review of Public Health 34:119–38. doi:10.1146/annurev-publhealth-031912-114409.
  • Kirsch, I., B. J. Deacon, T. B. Huedo-Medina, A. Scoboria, T. J. Moore, and B. T. Johnson. 2008. Initial severity and antidepressant benefits: A meta-analysis of data submitted to the food and drug administration. PLoS Medicine 5 (2):e45. doi:10.1371/journal.pmed.0050045.
  • Lawn, W., J. E. Hallak, J. A. Crippa, R. Dos Santos, L. Porffy, M. J. Barratt, J. A. Ferris, A. R. Winstock, and C. J. A. Morgan. 2017. Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: A large, international, self-selecting online survey. Scientific Reports 7 (1):15201. doi:10.1038/s41598-017-14700-6.
  • Liu, J. F., and J. X. Li. 2018. TAAR1 in addiction: Looking beyond the tip of the iceberg. Frontiers in Pharmacology 9:279. doi:10.3389/fphar.2018.00279.
  • Ly, C., A. C. Greb, L. P. Cameron, J. M. Wong, E. V. Barragan, P. C. Wilson, K. F. Burbach, S. Soltanzadeh Zarandi, A. Sood, M. R. Paddy, et al. 2018. Psychedelics promote structural and functional neural plasticity. Cell Reports 23 (11):3170–82. doi:10.1016/j.celrep.2018.05.022.
  • Mandell, A. J., and M. Morgan. 1971. Indole(ethyl)amine N-methyltransferase in human brain. Nature: New Biology 230 (11):85–87.
  • Mavlyutov, T. A., M. L. Epstein, P. Liu, Y. I. Verbny, L. Ziskind-Conhaim, and A. E. Ruoho. 2012. Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N‘-dimethyltryptamine forming enzyme, indole-N-methyl transferase. Neuroscience 206:60–68. doi:10.1016/j.neuroscience.2011.12.040.
  • McKenna, D. J., G. H. Towers, and F. Abbott. 1984. Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and beta-carboline constituents of ayahuasca. Journal of Ethnopharmacology 10 (2):195–223.
  • Moreira-Almeida, A., F. L. Neto, and H. G. Koenig. 2006. Religiousness and mental health: A review. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 28 (3):242–50.
  • Nichols, D. E. 2004. Hallucinogens. Pharmacology & Therapeutics 101 (2):131–81. doi:10.1016/j.pharmthera.2003.11.002.
  • Nichols, D. E. 2018. N,N-dimethyltryptamine and the pineal gland: Separating fact from myth. Journal of Psychopharmacology (Oxford, England) 32 (1):30–36. doi:10.1177/0269881117736919.
  • Niitsu, T., M. Iyo, and K. Hashimoto. 2012. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases. Current Pharmaceutical Design 18 (7):875–83.
  • Nunes, A. A., R. G. Dos Santos, F. L. Osorio, R. F. Sanches, J. A. Crippa, and J. E. Hallak. 2016. Effects of ayahuasca and its alkaloids on drug dependence: A Systematic literature review of quantitative studies in animals and humans. Journal of Psychoactive Drugs 48 (3):195–205. doi:10.1080/02791072.2016.1188225.
  • Oliveira-Lima, A. J., R. Santos, A. W. Hollais, C. A. Gerardi-Junior, M. A. Baldaia, R. Wuo-Silva, T. S. Yokoyama, J. L. Costa, E. L. Malpezzi-Marinho, P. C. Ribeiro-Barbosa, et al. 2015. Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice. Physiology & Behavior 142:28–36. doi:10.1016/j.physbeh.2015.01.032.
  • Osorio Fde, L., R. F. Sanches, L. R. Macedo, R. G. Santos, J. P. Maia-de-Oliveira, L. Wichert-Ana, D. B. Araujo, J. Riba, J. A. Crippa, and J. E. Hallak. 2015. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: A preliminary report. Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) 37 (1):13–20. doi:10.1590/1516-4446-2014-1496.
  • Palhano-Fontes, F., K. C. Andrade, L. F. Tofoli, A. C. Santos, J. A. Crippa, J. E. Hallak, S. Ribeiro, and D. B. de Araujo. 2015. The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network. PloS one 10 (2):e0118143. doi:10.1371/journal.pone.0118143.
  • Palhano-Fontes, F., D. Barreto, H. Onias, K. C. Andrade, M. M. Novaes, J. A. Pessoa, S. A. Mota-Rolim, F. L. Osorio, R. Sanches, R. G. Dos Santos, et al. 2018. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: A randomized placebo-controlled trial. Psychological Medicine 1–9. doi:10.1017/S0033291718001356.
  • Paterson, N. E., W. C. Darby, and P. S. Sandhu. 2015. N,N-Dimethyltryptamine-induced psychosis. Clinical Neuropharmacology 38 (4):141–43. doi:10.1097/WNF.0000000000000078.
  • Penke, B., L. Fulop, M. Szucs, and E. Frecska. 2018. The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases. Current Neuropharmacology 16 (1):97–116. doi:10.2174/1570159X15666170529104323.
  • Pic-Taylor, A., L. G. Da Motta, J. A. de Morais, W. M. Junior, F. Santos Ade, L. A. Campos, M. R. Mortari, M. V. von Zuben, and E. D. Caldas. 2015. Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural Processes 118:102–10. doi:10.1016/j.beproc.2015.05.004.
  • Raab, S., H. Wang, S. Uhles, N. Cole, R. Alvarez-Sanchez, B. Kunnecke, C. Ullmer, H. Matile, M. Bedoucha, R. D. Norcross, et al. 2016. Incretin-like effects of small molecule trace amine-associated receptor 1 agonists. Molecular Metabolism 5 (1):47–56. doi:10.1016/j.molmet.2015.09.015.
  • Reimann, W., and F. Schneider. 1993. The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity. General Pharmacology 24 (2):449–53.
  • Revel, F. G., J. L. Moreau, B. Pouzet, R. Mory, A. Bradaia, D. Buchy, V. Metzler, S. Chaboz, K. Groebke Zbinden, G. Galley, et al. 2013. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Molecular Psychiatry 18 (5):543–56. doi:10.1038/mp.2012.57.
  • Riba, J., E. H. McIlhenny, M. Valle, J. C. Bouso, and S. A. Barker. 2012. Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca. Drug Testing and Analysis 4 (7–8):610–16. doi:10.1002/dta.1344.
  • Riba, J., M. Valle, G. Urbano, M. Yritia, A. Morte, and M. J. Barbanoj. 2003. Human pharmacology of ayahuasca: Subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. The Journal of Pharmacology and Experimental Therapeutics 306 (1):73–83. doi:10.1124/jpet.103.049882.
  • Rickli, A., O. D. Moning, M. C. Hoener, and M. E. Liechti. 2016. Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology 26 (8):1327–37. doi:10.1016/j.euroneuro.2016.05.001.
  • Rousseaux, C. G., and S. F. Greene. 2015. Sigma receptors [sigmaRs]: Biology in normal and diseased states. Journal of Receptor and Signal Transduction Research 1–62. doi:10.3109/10799893.2015.1015737.
  • Rudnick, G., and J. Clark. 1993. From synapse to vesicle: The reuptake and storage of biogenic amine neurotransmitters. Biochimica et biophysica acta 1144 (3):249–63.
  • Rudnick, G., and S. C. Wall. 1992. p-Chloroamphetamine induces serotonin release through serotonin transporters. Biochemistry 31 (29):6710–18.
  • Saavedra, J. M., and J. Axelrod. 1972. Psychotomimetic N-methylated tryptamines: Formation in brain in vivo and in vitro. Science 175 (4028):1365–66.
  • Saavedra, J. M., J. T. Coyle, and J. Axelrod. 1973. The distribution and properties of the nonspecific N-methyltransferase in brain. Journal of Neurochemistry 20 (3):743–52.
  • Sampedro, F., M. de la Fuente Revenga, M. Valle, N. Roberto, E. Dominguez-Clave, M. Elices, L. E. Luna, J. A. S. Crippa, J. E. C. Hallak, D. B. de Araujo, et al. 2017. Assessing the psychedelic “after-glow” in ayahuasca users: Post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 20 (9):698–711. doi:10.1093/ijnp/pyx036.
  • Sanches, R. F., F. de Lima Osorio, R. G. Dos Santos, L. R. Macedo, J. P. Maia-de-Oliveira, L. Wichert-Ana, D. B. de Araujo, J. Riba, J. A. Crippa, and J. E. Hallak. 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. doi:10.1097/JCP.0000000000000436.
  • Santos, R. G., J. Landeira-Fernandez, R. J. Strassman, V. Motta, and A. P. Cruz. 2007. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. Journal of Ethnopharmacology 112 (3):507–13. doi:10.1016/j.jep.2007.04.012.
  • Savoldi, R., D. Polari, J. Pinheiro-da-Silva, P. F. Silva, B. Lobao-Soares, M. Yonamine, F. A. M. Freire, and A. C. Luchiari. 2017. Behavioral changes over time following ayahuasca exposure in Zebrafish. Frontiers in Behavioral Neuroscience 11:139. doi:10.3389/fnbeh.2017.00139.
  • Shi, X., N. A. Walter, J. H. Harkness, K. A. Neve, R. W. Williams, L. Lu, J. K. Belknap, A. J. Eshleman, T. J. Phillips, and A. Janowsky. 2016. Genetic polymorphisms affect mouse and human trace amine-associated receptor 1 function. PLoS one 11 (3):e0152581. doi:10.1371/journal.pone.0152581.
  • Strassman, R. 2001. DMT: The spirit molecule: A doctor‘s revolutionary research into the biology of near-death and mystical experiences. Rochester, Vt.: Park Street Press.
  • Strassman, R. J., and C. R. Qualls. 1994. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry 51 (2):85–97.
  • Strassman, R. J., C. R. Qualls, and L. M. Berg. 1996. Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans. Biological Psychiatry 39 (9):784–95. doi:10.1016/0006-3223(95)00200-6.
  • Strassman, R. J., C. R. Qualls, E. H. Uhlenhuth, and R. Kellner. 1994. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Archives of General Psychiatry 51 (2):98–108.
  • Su, T. P., T. Hayashi, T. Maurice, S. Buch, and A. E. Ruoho. 2010. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends in Pharmacological Sciences 31 (12):557–66. doi:10.1016/j.tips.2010.08.007.
  • Su, T. P., K. Shukla, and T. Gund. 1990. Steroid binding at sigma receptors: CNS and immunological implications. Ciba Foundation Symposium 153:107–13. discussion 113-6.
  • Sulzer, D., T. K. Chen, Y. Y. Lau, H. Kristensen, S. Rayport, and A. Ewing. 1995. Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience 15 (5 Pt 2):4102–08.
  • Szabo, A. 2015. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities. Frontiers in Immunology 6:358. doi:10.3389/fimmu.2015.00358.
  • Szara, S. 1956. Dimethyltryptamin: Its metabolism in man; the relation to its psychotic effect to the serotonin metabolism. Experientia 12 (11):441–42.
  • Szara, S. 2007. DMT at fifty. Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology 9 (4):201–05.
  • Takahashi, T., K. Takahashi, T. Ido, K. Yanai, R. Iwata, K. Ishiwata, and S. Nozoe. 1985. 11C-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions. The International Journal of Applied Radiation and Isotopes 36 (12):965–69.
  • Thomas, G., P. Lucas, N. R. Capler, K. W. Tupper, and G. Martin. 2013. Ayahuasca-assisted therapy for addiction: Results from a preliminary observational study in Canada. Current Drug Abuse Reviews 6 (1):30–42.
  • Thompson, M. A., E. Moon, U. J. Kim, J. Xu, M. J. Siciliano, and R. M. Weinshilboum. 1999. Human indolethylamine N-methyltransferase: CDNA cloning and expression, gene cloning, and chromosomal localization. Genomics 61 (3):285–97. doi:10.1006/geno.1999.5960.
  • Tupper, K. W. 2008. The globalization of ayahuasca: Harm reduction or benefit maximization? The International Journal on Drug Policy 19 (4):297–303. doi:10.1016/j.drugpo.2006.11.001.
  • Valle, M., A. E. Maqueda, M. Rabella, A. Rodriguez-Pujadas, R. M. Antonijoan, S. Romero, J. F. Alonso, M. A. Mananas, S. Barker, P. Friedlander, et al. 2016. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology : The Journal of the European College of Neuropsychopharmacology 26 (7):1161–75. doi:10.1016/j.euroneuro.2016.03.012.
  • Vattai, A., E. Akyol, C. Kuhn, S. Hofmann, H. Heidegger, F. von Koch, K. Hermelink, R. Wuerstlein, N. Harbeck, D. Mayr, et al. 2017. Increased trace amine-associated receptor 1 (TAAR1) expression is associated with a positive survival rate in patients with breast cancer. Journal of Cancer Research and Clinical Oncology 143 (9):1637–47. doi:10.1007/s00432-017-2420-8.
  • Winstock, A. R., S. Kaar, and R. Borschmann. 2014. Dimethyltryptamine (DMT): Prevalence, user characteristics and abuse liability in a large global sample. Journal of Psychopharmacology (Oxford, England) 28 (1):49–54. doi:10.1177/0269881113513852.
  • Yanai, K., T. Ido, K. Ishiwata, J. Hatazawa, T. Takahashi, R. Iwata, and T. Matsuzawa. 1986. In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen, N,N-[11C]dimethyltryptamine. European Journal of Nuclear Medicine 12 (3):141–46.
  • Zucchi, R., G. Chiellini, T. S. Scanlan, and D. K. Grandy. 2006. Trace amine-associated receptors and their ligands. British Journal of Pharmacology 149 (8):967–78. doi:10.1038/sj.bjp.0706948.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.