Mckenna44. McKenna DJ, Towers GH, Abbott F. Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and β-carboline constituents of ayahuasca. J Ethnopharmacol. 1984;10:195-223. |
1984 |
Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and ß-carboline constituents of ayahuasca |
Showed MAOI effect in vitro. |
Original proposal regarding DMT deamination prevention via MAOI in harmala alkaloids from P. viridis.
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Proposes that inhibition experiments using mixtures of ß-carbolines indicate that their effects in combination are additive, rather than synergistic or antagonistic. |
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Callaway1717. Callaway JC, Airaksinen MM, McKenna DJ, Brito GS, Grob CS. Platelet serotonin uptake sites increased in drinkers of ayahuasca. Psychopharmacology (Berl). 1994;116:385-7. |
1994 |
Platelet serotonin uptake sites increased in drinkers of ayahuasca |
Increased number of serotonin mRNA transporter sites in regular ayahuasca drinkers against control group. |
-Shows an increased number of binding sites in platelets. -No evidence of this for DMT alone, which is suggestive of a synergistic effect. |
Strassman55. Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R. Dose-response study of N, N-dimethyltryptamine in humans: II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994;51:98-108. |
1994 |
Dose-response study of N, N-dimethyltryptamine in humans |
-Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration and were negligible at 30 minutes. -DMT dose-dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of ß-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. -Threshold doses for significant effects relative to placebo were also hallucinogenic (> 0.2 mg/kg) -Subjects exposed five or more times to 3,4-methylenedioxymethamphetamine had less robust pupil diameter effects than those exposed two times of less. -Evidence that DMT is unique in the inability to develop tolerance to its psychological effects. |
Dose-response data for IV DMT fumarate, neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. |
Smith1818. Smith RL, Canton H, Barrett RJ, Sanders-Bush E. Agonist properties of N, N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors. Pharmacol Biochem Behav. 1998;61:323-30. |
1998 |
Agonist properties of N, N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors |
-DMT fully substituted for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors. -DMT was a partial agonist at 5-HT2C receptors in this native preparation. -DMT behaves as an agonist at both 5-HT2A and 5-HT2C receptors. -One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time (suggestive of limited application for repeat prescription). |
Evidence of DMT 5HT2a(c) agonism. |
Callaway1919. Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, et al. Pharmacokinetics of Hoasca alkaloids in healthy humans. J Ethnopharmacol. 1999;65:243-56. |
1999 |
Pharmacokinetics of Hoasca alkaloids in healthy humans |
-THH shows PK profile independent to harmine. -Affinities and other PK values provided. |
-Evidence that THH alone may be a weak SSRI. -Implies further synergistic effects on the serotonin system. |
Ott2020. Ott J. Pharmahuasca: human pharmacology of oral DMT plus harmine. J Psychoactive Drugs. 1999;31:171-7. |
1999 |
Pharmahuasca: human pharmacology of oral DMT plus harmine |
-MAO inhibition from simultaneous ingestion of ß-carbolines confirmed by eight self-experimenters. -Results of a total of some 70 bioassays are summarized and the literature on this subject is reviewed. |
-Evidence that DMT and harmine in tablet form create similar effects to ayahuasca, further reinforcing the DMT MAOI interaction. -When orally ingested, DMT without harmine is non-active. |
Glennon2121. Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, et al. 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;60:121-32. |
2000 |
Binding of ß-carbolines and related agents at serotonin (5-HT2 and 5-HT1A), dopamine (D2) and benzodiazepine receptors |
Affinity scores at 5-HT2 for harmine/harmaline. |
Shows that other harmala alkaloids also bind to the 5HT2 receptors, further suggesting synergistic potential in the serotonergic system. |
Riba2222. 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. J Pharmacol Exp Ther. 2003;306:73-83. |
2003 |
Human pharmacology of ayahuasca |
-Diastolic blood pressure significant increase. -Heart rate moderate increase. -Increased urinary normetanephrine excretion. -Deaminated monoamine metabolite levels did-not decrease (contrary to typical MOAI effect profile). -The negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. |
-Double-blind placebo controlled clinical trial using freeze-dried ayahuasca. -PK angle. -Small sample size (n=18). |
Riba2323. Riba J, Romero S, Grasa E, Mena E, Carrió I, Barbanoj MJ. Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl). 2006;186:93-8. |
2006 |
Increased frontal and paralimbic activation following ayahuasca |
-Significant activation of frontal and paralimbic brain regions. -Increased blood perfusion observed bilaterally in anterior insula, gather intensity in right hemisphere, and anterior cingulate/frontal medial cortex of right hemisphere. -Increases observed in left amygdala/parahippocampal gyrus. -Concludes that ayahuasca interacts with neural systems that are central to interoception and emotional processing. |
-Double-blind placebo controlled clinical trial using freeze-dried ayahuasca. -Neuroimaging angle. -Used SPECT. |
Fortunato2424. Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, et al. Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus. J Neural Transm (Vienna). 2010;117:1131-7. |
2010 |
Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus |
-Increased BDNF protein levels in rat hippocampus. -Concludes that findings within support the hypothesis that harmine could bring about behavioral and molecular effects. |
Further evidence that the synergistic mechanisms of DMT + harmine are more than just effects of MAOIs. |
dos Santos2525. dos Santos RG, Valle M, Bouso JC, Nomdedéu JF, Rodríguez-Espinosa J, McIlhenny EH, et al. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine. J Clin Psychopharmacol. 2011;31:717-26. |
2011 |
Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with D-amphetamine |
-Significant increases in prolactin. -Percentage of CD3/4 were decreased, natural killer cells increased. -Maximum changes occurred around 2 hours, returned to baseline after 24 hours. -Ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and time-dependent modulatory effect on cell-mediated immunity. |
Focuses on the synergistic effects of ayahuasca rather than individual action of compounds. |
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Immunological, rather than neuropsychological, perspective. |
McIlhenny2626. McIlhenny EH, Riba J, Barbanoj MJ, Strassman R, Barker SA. Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine. Biomed Chromatogr. 2011;25:970-84. |
2011 |
Methodology for determining the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine |
-Showed that the major metabolite of a DMT is the corresponding DMT-NO, the first time this metabolite has been described in in vivo studies in humans. -Very little DMT detected in urine, despite the MAOI. -Major alkaloid excreted was THH.-List of other products and metabolites quantified. |
-Provides methodology for identifying and quantifying constituents of ayahuasca in human urine. -PK data of tested samples provided.Excretion and metabolism of THH should be further investigated. |
McIlhenny2727. McIlhenny EH, Riba J, Barbanoj MJ, Strassman R, Barker SA. Methodology for determining major constituents of ayahuasca and their metabolites in blood. Biomed Chromatogr. 2012;26:301-13. |
2012 |
Methodology for determining major constituents ofayahuasca and its metabolites in blood |
-DMT concentrations lower than DMT-NO at all time points. -Plasma DMT-NO concentrations three to four times higher than DMT. -DMT-NO forms rapidly after drug administration. -THH levels peaked at around 4.5 hours. -Harmine and harmaline present in most samples. |
-Single methodology combining HPLC and gas chromatography to identify ayahuasca constituents in blood following oral consumption.-First report of presence of DMT-NO in human blood following ayahuasca/DMT administration. -Method for the most complete profile of DMT, harmala alkaloids, and metabolite concentrations. |
Riba1313. 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 Test Anal. 2012;4:610-6. |
2012 |
Metabolism and disposition of N, N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca |
-Less than 1% of DMT excreted unchanged. -Fifty per cent was recovered as indole-3-acetic acid or DMT-NO. -Ten per cent was other MAO-independent compounds. -Recovery of DMT plus metabolites reached 68%. -Harmol, harmalol, and THH conjugates were abundant in urine. -The recovery of each harmala alkaloid plus its 0-demethylated metabolite varied greatly (between 9 and 65%). |
-PK study with implications regarding alternative metabolic routes for DMT other than biotransformation by MAO. -Freeze-dried ayahuasca. -Urine samples obtained. -Small sample (n=10). |
Morales-Garcia2828. Morales-García JA, de la Fuente Revenga M, Alonso-Gil S, Rodríguez-Franco MI, Feilding A, Perez-Castillo A, et al. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Sci Rep. 2017;7:5309. |
2017 |
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen ayahuasca, stimulate adult neurogenesis in vitro
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Significant neurogenesis in adult hippocampal cells in vitro with harmine. |
Suggests that ayahuasca brew may have more complex synergistic properties than we currently understand. Shows that harmine alone could be partially responsible for the neurological changes seen in ayahuasca users. |
Sampedro2929. Sampedro F, de la Fuente Revenga M, Valle M, Roberto N, Domínguez-Clavé E, Elices M, et al. Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities. Int J Neuropsychopharmacol. 2017;20:698-711. |
2017 |
Assessing the psychedelic “after-glow” in ayahuasca users: post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities |
-Magnetic resonance spectroscopy showed post-acute reductions in glutamate + glutamine, creatine, and N-acetylaspartate+N- acetylaspartylglutamate in the posterior cingulate cortex. -Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. -Glutamate + glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire-Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. -Post-acute neural changes predicted sustained elevations in nonjudging 2 months later. |
-DMN activity decrease and increased neural connectivity to other areas of the brain. -Supported by other studies on 5HT2a agonists. -Long-term neurological differences found after ayahuasca administration. |