Pharmacological and Toxicological Aspects of Alkaloid N, N - Dimethyltryptamine (DMT)
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Published:
Mar 11, 2020
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Abstract
N, N - dimethyltryptamine (DMT) is a hallucinogenic alkaloid present in the leaves of Psychotria viridis, a plant widely used in teas that are ingested during some religious ritual, ayahuasca tea is one of the most known. Consider its similarity to the neurotransmitter serotonin (5-HT), DMT acts as an age-agonist at the 5-HT1A, 5-HT2A and 5-HT2C serotonergic receptors, causing several effects such as nausea, tremors and mood changes, some reports indicated system immune changes due to lower levels of CD3 and CD4 lymphocytes. However, recent researches has also pointed out the therapeutic effects of DMT, proving through in vivo tests its antitumor, antidepressant and anxiolytic potential, in addition it helps in the treatment against alcoholism and tobacco. Considering the increasement use of DMT teas, this work aims to describe its main pharmacological and toxicological effects due to limited references and the need to compile data dispersed in the literature. The present study concludes that DMT has potential pharmacological action, but also important adverse effects, including toxicity, which corroborates the need of doing more acute and chronic tests, in addition to epidemiological research focused on its action in which users use.
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1.
Machado LC, da Cruz RH, Higa SS, Silva TRB, Lima TC, Seriani R. Pharmacological and Toxicological Aspects of Alkaloid N, N - Dimethyltryptamine (DMT). Braz. J. Nat. Sci [Internet]. 2020Mar.11 [cited 2024Dec.22];3(1):259. Available from: https://bjns.com.br/index.php/BJNS/article/view/84
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References
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10. Riba J, McIlhenny EH, Valle M, Bouso JC, Barker SA. Metabolism and disposition of N, N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca. Drug testing and analysis. 2012; 4(7-8): 610-616. https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1344.
11. Barbosa PCR, Mizumoto S, Bogenschutz MP, Strassman RJ. Health status of ayahuasca users. Drug testing and analysis. 2012; 4(7-8): 601-609. https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1383.
12. Costa MCM, Figueiredo MC, Cazenave SDOS. Ayahuasca: uma abordagem toxicológica do uso ritualístico. Rev. psiquiatr. Clín.. 2005; 32(6), 310-318. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-60832005000600001&lng=pt&nrm=iso.
13. Souza RC, Zandonadi FS, Freitas DP, Tófoli LF, Sussulini A. Validation of an analytical method for the determination of the main ayahuasca active compounds and application to real ayahuasca samples from Brazil. Journal of Chromatography B. 2019; 1124: 197-203. https://www.sciencedirect.com/science/article/abs/pii/S1570023219301825.
14. Cakic V, Potkonyak J, Marshall A. Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. Drug and alcohol dependence. 2010; 111(1-2): 30-37. https://www.sciencedirect.com/science/article/abs/pii/S0376871610001341.
15. Dos Santos RG, Osorio FL, Crippa JAS, Hallak JE. Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging. Neuroscience & Biobehavioral Reviews. 2016; 71: 715-728. https://www.sciencedirect.com/science/article/abs/pii/S0149763416302354.
16. Da Silva FS, Silva EA, Sousa Jr GMD, Maia-de-Oliveira JP, Soares-Rachetti VDP, de Araujo DB et al. Acute effects of ayahuasca in a juvenile non-human primate model of depression. Brazilian Journal of Psychiatry. 2019; 41(4), 280-288. http://www.scielo.br/scielo.php?pid=S1516-44462018005009104&script=sci_arttext.
17. Pic-Taylor A, da Motta LG, de Morais JA, Junior WM, Santos ADFA, Campos LA et al. Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural processes. 2015; 118: 102-110. https://www.sciencedirect.com/science/article/abs/pii/S0376635715001278.
18. Santos RD, Landeira-Fernandez J, Strassman RJ, Motta V, Cruz APM. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. Journal of ethnopharmacology. 2007; 112(3): 507-513. https://www.sciencedirect.com/science/article/abs/pii/S0378874107002139.
19. Osório FDL, Sanches RF, Macedo LR, Dos Santos RG, Maia-de-Oliveira JP, Wichert-Ana L et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Brazilian Journal of Psychiatry. 2015; 37(1): 13-20. http://www.scielo.br/scielo.php?pid=S1516-44462015000100013&script=sci_arttext&tlng=pt.
20. Cameron LP, Benson CJ, Dunlap LE, Olson DE. Effects of N, N-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS chemical neuroscience. 2018; 9(7): 1582-1590. https://pubs.acs.org/doi/abs/10.1021/acschemneuro.8b00134.
21. Tourino MC, de Oliveira EM, Bellé LP, Knebel FH, Albuquerque RC, Dörr FA et al. Tryptamine and dimethyltryptamine inhibit indoleamine 2, 3 dioxygenase and increase the tumor‐reactive effect of peripheral blood mononuclear cells. Cell biochemistry and Function. 2013; 31(5): 361-364. https://onlinelibrary.wiley.com/doi/abs/10.1002/cbf.2980.
22. Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF et al. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. Journal of neural transmission. 2009; 116(12): 1591. https://link.springer.com/article/10.1007/s00702-009-0308-8.
23. Walter L, Hajnóczky G. Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk. Journal of bioenergetics and biomembranes. 2005; 37(3): 191-206. https://link.springer.com/article/10.1007/s10863-005-6600-x.
24. Jose C, Bellance N, Rossignol R. Choosing between glycolysis and oxidative phosphorylation: a tumor's dilemma?. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2011; 1807(6): 552-561. https://www.sciencedirect.com/science/article/pii/S0005272810007206.
25. Dos Santos RG. Ayahuasca physiological and subjective effects, comparison with d-amphetamine, and repeated dose assessment. Barcelona: Universitat Autònoma de Barcelona, Departament de Farmacologia, Terapèutica i de Toxicologia: 2012.
26. Dos Santos RG. Immunological effects of ayahuasca in humans. Journal of psychoactive drugs. 2014; 46(5): 383-388. https://www.tandfonline.com/doi/abs/10.1080/02791072.2014.960113.
27. Frecska E, Szabo A, Winkelman MJ, Luna LE, Mckenna DJ. A possibly sigma-1 receptor mediated role of dimethyl- tryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission. 2013; 120(9): 1295–303. https://link.springer.com/article/10.1007/s00702-013-1024-y.
28. Szabo A, Kovacs A, Frecska E, Rajnavolgyi E. Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PloS one. 2014; 9(8): e106533. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106533.
29. Gomes MM, Coimbra JB, Clara RO, Dörr FA, Moreno ACR, Chagas JR et al. Biosynthesis of N, N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases. Biochemical pharmacology. 2014; 88(3): 393-401. https://www.sciencedirect.com/science/article/pii/S0006295214000744.
30. Bilhimer MH, Schult RF, Higgs KV, Wiegand TJ, Gorodetsky RM, Acquisto NM. Acute Intoxication following dimethyltryptamine ingestion. Case reports in emergency medicine. 2018; 2018: 1-3. https://www.hindawi.com/journals/criem/2018/3452691/.
31. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. The Ochsner Journal. 2013; 13(4): 533-540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/.
32. Dos Santos, RG. Safety and side effects of ayahuasca in humans - an overview focusing on developmental toxicology. Journal of psychoactive drugs. 2013; 45(1): 68-78. https://www.tandfonline.com/doi/abs/10.1080/02791072.2013.763564.
33. Da Motta LG, de Morais JA, Tavares ACA, Vianna LMS, Mortari MR, Amorim RFB et al. Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats. Reproductive Toxicology. 2018; 77: 143-153. https://www.sciencedirect.com/science/article/pii/S0890623817307037.
34. Gable RS. Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids. Addiction. 2007; 102(1): 24-34. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2006.01652.x.
35. Riba J, Rodríguez-Fornells A, Urbano G, Morte A, Antonijoan R, Montero M. Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology. 2001; 154(1): 85-95. https://link.springer.com/article/10.1007/s002130000606.
2. Almeida DF, Silva ALP, Assis TJCF. Dimethyltryptamine: hallucinogenic alkaloid on the Central Nervous System. Acta Brasiliensis. 2018; 2(1); 28-33. http://www.revistas.ufcg.edu.br/ActaBra/index.php/actabra/article/view/43.
3. De Souza PA. Alcaloides e o chá de ayahuasca: uma correlação dos "estados alterados da consciência" induzido por alucinógenos. Rev. bras. plantas med. 2011; 13 (3): 349-358. http://www.scielo.br/scielo.php?pid=S1516-05722011000300015&script=sci_arttext&tlng=pt.
4. Gomes MM. Dietilamida do ácido lisérgico (LSD) e N,N-dimetiltriptamina (DMT) como substratos de peroxidases: uma possível rota de metabolização [dissertação]. São Paulo: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas; 2008.
5. Carbonaro TM, Gatch MB. Neuropharmacology of N, N-dimethyltryptamine. Brain research bulletin. 2016; 126: 74-88. https://www.sciencedirect.com/science/article/abs/pii/S0361923016300909.
6. McKenna, DJ. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & therapeutics. 2004; 102(2), 111-129. https://www.sciencedirect.com/science/article/abs/pii/S0163725804000464.
7. Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. Journal of Pharmacology and Experimental Therapeutics. 2003; 306(1): 73-83. http://jpet.aspetjournals.org/content/306/1/73.short.
8. Domínguez-Clavé E, Soler J, Elices M, Pascual JC, Álvarez E, de la Fuente Revenga M et al. Ayahuasca: pharmacology, neuroscience and therapeutic potential. Brain research bulletin. 2016; 126: 89-101. https://www.sciencedirect.com/science/article/abs/pii/S0361923016300454.
9. McIlhenny EH, Riba J, Barbanoj MJ, Strassman R, Barker, S. A. Methodology for determining major constituents of ayahuasca and their metabolites in blood. Biomedical Chromatography. 2012; 26(3): 301-313. https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.1657.
10. Riba J, McIlhenny EH, Valle M, Bouso JC, Barker SA. Metabolism and disposition of N, N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca. Drug testing and analysis. 2012; 4(7-8): 610-616. https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1344.
11. Barbosa PCR, Mizumoto S, Bogenschutz MP, Strassman RJ. Health status of ayahuasca users. Drug testing and analysis. 2012; 4(7-8): 601-609. https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1383.
12. Costa MCM, Figueiredo MC, Cazenave SDOS. Ayahuasca: uma abordagem toxicológica do uso ritualístico. Rev. psiquiatr. Clín.. 2005; 32(6), 310-318. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0101-60832005000600001&lng=pt&nrm=iso.
13. Souza RC, Zandonadi FS, Freitas DP, Tófoli LF, Sussulini A. Validation of an analytical method for the determination of the main ayahuasca active compounds and application to real ayahuasca samples from Brazil. Journal of Chromatography B. 2019; 1124: 197-203. https://www.sciencedirect.com/science/article/abs/pii/S1570023219301825.
14. Cakic V, Potkonyak J, Marshall A. Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users. Drug and alcohol dependence. 2010; 111(1-2): 30-37. https://www.sciencedirect.com/science/article/abs/pii/S0376871610001341.
15. Dos Santos RG, Osorio FL, Crippa JAS, Hallak JE. Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging. Neuroscience & Biobehavioral Reviews. 2016; 71: 715-728. https://www.sciencedirect.com/science/article/abs/pii/S0149763416302354.
16. Da Silva FS, Silva EA, Sousa Jr GMD, Maia-de-Oliveira JP, Soares-Rachetti VDP, de Araujo DB et al. Acute effects of ayahuasca in a juvenile non-human primate model of depression. Brazilian Journal of Psychiatry. 2019; 41(4), 280-288. http://www.scielo.br/scielo.php?pid=S1516-44462018005009104&script=sci_arttext.
17. Pic-Taylor A, da Motta LG, de Morais JA, Junior WM, Santos ADFA, Campos LA et al. Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural processes. 2015; 118: 102-110. https://www.sciencedirect.com/science/article/abs/pii/S0376635715001278.
18. Santos RD, Landeira-Fernandez J, Strassman RJ, Motta V, Cruz APM. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. Journal of ethnopharmacology. 2007; 112(3): 507-513. https://www.sciencedirect.com/science/article/abs/pii/S0378874107002139.
19. Osório FDL, Sanches RF, Macedo LR, Dos Santos RG, Maia-de-Oliveira JP, Wichert-Ana L et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Brazilian Journal of Psychiatry. 2015; 37(1): 13-20. http://www.scielo.br/scielo.php?pid=S1516-44462015000100013&script=sci_arttext&tlng=pt.
20. Cameron LP, Benson CJ, Dunlap LE, Olson DE. Effects of N, N-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS chemical neuroscience. 2018; 9(7): 1582-1590. https://pubs.acs.org/doi/abs/10.1021/acschemneuro.8b00134.
21. Tourino MC, de Oliveira EM, Bellé LP, Knebel FH, Albuquerque RC, Dörr FA et al. Tryptamine and dimethyltryptamine inhibit indoleamine 2, 3 dioxygenase and increase the tumor‐reactive effect of peripheral blood mononuclear cells. Cell biochemistry and Function. 2013; 31(5): 361-364. https://onlinelibrary.wiley.com/doi/abs/10.1002/cbf.2980.
22. Cozzi NV, Gopalakrishnan A, Anderson LL, Feih JT, Shulgin AT, Daley PF et al. Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. Journal of neural transmission. 2009; 116(12): 1591. https://link.springer.com/article/10.1007/s00702-009-0308-8.
23. Walter L, Hajnóczky G. Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk. Journal of bioenergetics and biomembranes. 2005; 37(3): 191-206. https://link.springer.com/article/10.1007/s10863-005-6600-x.
24. Jose C, Bellance N, Rossignol R. Choosing between glycolysis and oxidative phosphorylation: a tumor's dilemma?. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2011; 1807(6): 552-561. https://www.sciencedirect.com/science/article/pii/S0005272810007206.
25. Dos Santos RG. Ayahuasca physiological and subjective effects, comparison with d-amphetamine, and repeated dose assessment. Barcelona: Universitat Autònoma de Barcelona, Departament de Farmacologia, Terapèutica i de Toxicologia: 2012.
26. Dos Santos RG. Immunological effects of ayahuasca in humans. Journal of psychoactive drugs. 2014; 46(5): 383-388. https://www.tandfonline.com/doi/abs/10.1080/02791072.2014.960113.
27. Frecska E, Szabo A, Winkelman MJ, Luna LE, Mckenna DJ. A possibly sigma-1 receptor mediated role of dimethyl- tryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission. 2013; 120(9): 1295–303. https://link.springer.com/article/10.1007/s00702-013-1024-y.
28. Szabo A, Kovacs A, Frecska E, Rajnavolgyi E. Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PloS one. 2014; 9(8): e106533. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106533.
29. Gomes MM, Coimbra JB, Clara RO, Dörr FA, Moreno ACR, Chagas JR et al. Biosynthesis of N, N-dimethyltryptamine (DMT) in a melanoma cell line and its metabolization by peroxidases. Biochemical pharmacology. 2014; 88(3): 393-401. https://www.sciencedirect.com/science/article/pii/S0006295214000744.
30. Bilhimer MH, Schult RF, Higgs KV, Wiegand TJ, Gorodetsky RM, Acquisto NM. Acute Intoxication following dimethyltryptamine ingestion. Case reports in emergency medicine. 2018; 2018: 1-3. https://www.hindawi.com/journals/criem/2018/3452691/.
31. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. The Ochsner Journal. 2013; 13(4): 533-540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/.
32. Dos Santos, RG. Safety and side effects of ayahuasca in humans - an overview focusing on developmental toxicology. Journal of psychoactive drugs. 2013; 45(1): 68-78. https://www.tandfonline.com/doi/abs/10.1080/02791072.2013.763564.
33. Da Motta LG, de Morais JA, Tavares ACA, Vianna LMS, Mortari MR, Amorim RFB et al. Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats. Reproductive Toxicology. 2018; 77: 143-153. https://www.sciencedirect.com/science/article/pii/S0890623817307037.
34. Gable RS. Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids. Addiction. 2007; 102(1): 24-34. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1360-0443.2006.01652.x.
35. Riba J, Rodríguez-Fornells A, Urbano G, Morte A, Antonijoan R, Montero M. Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology. 2001; 154(1): 85-95. https://link.springer.com/article/10.1007/s002130000606.