370
Views
5
CrossRef citations to date
0
Altmetric
Review

Ayahuasca, a potentially rapid acting antidepressant: focus on safety and tolerability

ORCID Icon, , , ORCID Icon, , & ORCID Icon show all
Pages 789-801 | Received 28 Jan 2022, Accepted 14 Mar 2022, Published online: 23 Mar 2022

References

  • Sartorius N. The economic and social burden of depression. J Clin Psychiatry. 2001;62 Suppl 15(15):8–11.
  • Malhi GS, Mann JJ. Depression. Lancet. 2018 Nov 24;392(10161):2299–2312.
  • Penn E, Tracy DK. The drugs don’t work? antidepressants and the current and future pharmacological management of depression. Ther Adv Psychopharmacol. 2012 Oct;2(5):179–188.
  • Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357–1366.
  • Feltes KP, Doorduin J, Klein HC, et al. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy. J Psychopharmacol. 2017 Sep;31(9):1149–1165.
  • Dos Santos RG, Bouso JC, Alcázar-Córcoles M, et al. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev Clin Pharmacol. 2018 Sep;11(9):889–902.
  • Psiuk D, Nowak E, Cholewa K, et al. The Potential Role of Serotonergic Hallucinogens in Depression Treatment. Life (Basel, Switzerland). 2021 Jul 29;11(8). DOI:10.3390/life11080765
  • Dos Santos RG, Osório FL, Crippa JA, et al. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Braz J Psychiatry. 2016 Mar;38(1):65–72.
  • Riba J, Valle M, Urbano G, et al. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J Pharmacol Exp Ther. 2003 Jul;306(1):73–83.
  • Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, et al. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998 Dec 1;9(17):3897–3902.
  • Schmid Y, Enzler F, Gasser P, et al. Acute effects of lysergic acid diethylamide in healthy subjects. Biol Psychiatry. 2015 Oct 15;78(8):544–553.
  • Preller KH, Pokorny T, Hock A, et al. Effects of serotonin 2A/1A receptor stimulation on social exclusion processing. Proc Natl Acad Sci U S A. 2016 May 3;113(18):5119–5124.
  • Fortunato JJ, Réus GZ, Kirsch TR, et al. Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1425–1430.
  • Fortunato JJ, Réus GZ, Kirsch TR, et al. Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus. J Neural Transm (Vienna). 2010 Oct;117(10):1131–1137.
  • Fortunato JJ, Réus GZ, Kirsch TR, et al. Effects of beta-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: further evidence of antidepressant properties. Brain Res Bull. 2010 Mar 16;81(4–5):491–496.
  • Grob CS, McKenna DJ, Callaway JC, et al. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis. 1996 Feb;184(2):86–94.
  • Barbosa PC, Giglio JS, Dalgalarrondo P. 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. J Psychoactive Drugs. 2005 Jun;37(2):193–201.
  • Da Silveira DX, Grob CS, de Rios Md, et al. Ayahuasca in adolescence: a preliminary psychiatric assessment. J Psychoactive Drugs. 2005 Jun;37(2):129–133.
  • Bouso JC, González D, Fondevila S, et al. Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study. PLoS One. 2012;7(8):e42421.
  • Uthaug MV, van Oorsouw K, Kuypers KPC, et al. Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution. Psychopharmacology (Berl). 2018 Oct;235(10):2979–2989.
  • Ona G, Kohek M, Massaguer T, et al. Ayahuasca and public health: health status, psychosocial well-being, lifestyle, and coping strategies in a large sample of ritual ayahuasca users. J Psychoactive Drugs. 2019 Apr-Jun;51(2):135–145.
  • Jiménez-Garrido DF, Gómez-Sousa M, Ona G, et al. Effects of ayahuasca on mental health and quality of life in naïve users: a longitudinal and cross-sectional study combination. Sci Rep. 2020 Mar 5;10(1):4075.
  • Giovannetti C, Garcia Arce S, Rush B, et al. Pilot evaluation of a residential drug addiction treatment combining traditional Amazonian medicine, ayahuasca and psychotherapy on depression and anxiety. J Psychoactive Drugs. 2020 Nov-Dec;52(5):472–481.
  • Osório Fde L, Sanches RF, Macedo LR, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry. 2015 Jan-Mar;37(1):13–20.
  • Sanches RF, de Lima Osório F, Dos Santos RG, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J Clin Psychopharmacol. 2016 Feb;36(1):77–81.
  • Zeifman RJ, Wagner AC, Watts R, et al. Post-psychedelic reductions in experimental avoidance are associated with decreases in depression severity and suicidal ideation. Front Psychiatry. 2020;11:782–783.
  • Palhano-Fontes F, Barreto D, Onias H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019 Mar;494:655–663.** First randomized, double-blind, placebo-controlled trial of ayahuasca in treatment-resistant major depressive disorder
  • de Almeida Rn, Galvão ACDM, da Silva Fs, et al. Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca: observation from a randomized controlled trial. Front Psychol. 2019;10:1234.
  • Galvão-Coelho NL, de Menezes Galvão AC, de Almeida RN, et al. Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca. J Psychopharmacol. 2020;34(10):1125–1133.
  • Dos Santos RG, Balthazar FM, Bouso JC, et al. The current state of research on ayahuasca: a systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging. J Psychopharmacol. 2016 Dec;30(12):1230–1247.
  • Dos Santos RG, Hallak JE. Effects of the natural β-carboline alkaloid harmine, a main constituent of ayahuasca, in memory and in the hippocampus: a systematic literature review of preclinical studies. J Psychoactive Drugs. 2017 Jan-Mar;49(1):1–10.
  • Katchborian-Neto A, Santos WT, Nicácio KJ, et al. Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson’s disease. J Ethnopharmacol. 2020 Jun 12;255:112743.
  • Morales-García JA, de la Fuente Revenga M, Alonso-Gil S, et al. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Sci Rep. 2017 Jul 13;7(1):5309.
  • Inserra A; Inserra A. Hypothesis: the psychedelic ayahuasca heals traumatic memories via a sigma 1 receptor-mediated epigenetic-mnemonic process. Front Pharmacol. 2018;9:330.
  • Callaway JC, McKenna DJ, Grob CS, et al. Pharmacokinetics of Hoasca alkaloids in healthy humans. J Ethnopharmacol. 1999 Jun;65(3):243–256.
  • Riba J, Rodriguez-Fornells A, Urbano G, et al. Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers. Psychopharmacology (Berl). 2001 Feb;154(1):85–95.
  • Dos Santos RG, Valle M, Bouso JC, et al. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine. J Clin Psychopharmacol. 2011 Dec;31(6):717–726.
  • Dos Santos RG, Grasa E, Valle M, et al. Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology (Berl). 2012 Feb;2194:1039–53. * First and Only study to evaluate the effects of two consecutive doses of ayahuasca.
  • Dos Santos RG, Osorio FL, Rocha JM, et al. Ayahuasca improves self-perception of speech performance in subjects with social anxiety disorder: a pilot, proof-of-concept, randomized, placebo-controlled trial. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):540–550.
  • Rocha JM, Rossi GN, de Lima Osorio F, et al. Effects of ayahuasca on the recognition of facial expressions of emotions in naive healthy volunteers: a pilot, proof-of-concept, randomized controlled trial. J Clin Psychopharmacol. 2021 May-Jun 01;41(3):267–274.
  • Durante I, Dos Santos RG, Bouso JC, et al. Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects. Braz J Psychiatry. 2021 Jul-Aug;43(4):362–369.
  • Muller F, Borgwardt S. Acute Effects of Lysergic Acid Diethylamide (LSD) on Resting Brain Function. Swiss Med Wkly. 2019 Sep 23;149:w20124.
  • Bienemann B, Ruschel NS, Campos ML, et al. Self-reported negative outcomes of psilocybin users: a quantitative textual analysis. PLoS One. 2020;15(2):e0229067.
  • Mertens LJ, Preller KH. Classical psychedelics as therapeutics in psychiatry - Current clinical evidence and potential therapeutic mechanisms in substance use and mood disorders. Pharmacopsychiatry. 2021 Jul;54(4):176–190.
  • Goldberg SB, Shechet B, Nicholas CR, et al. Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis. Psychol Med. 2020 Dec;50(16):2655–2666.
  • Wieckiewicz G, Stoklosa I, Piegza M, et al. Lysergic acid diethylamide, psilocybin and dimethyltryptamine in depression treatment: a systematic review. Pharmaceuticals (Basel). 2021 Aug 12;14(8):793.
  • Pasquini L, Palhano-Fontes F, Araujo DB. Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. J Psychopharmacol. 2020 Jun;34(6):623–635.
  • Riba J, Rodriguez-Fornells A, Barbanoj MJ. Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively. Psychopharmacology (Berl). 2002 Dec;165(1):18–28.
  • Riba J, Romero S, Grasa E, et al. Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant. Psychopharmacology (Berl). 2006 May;186(1):93–98.
  • Dos Santos RG, Landeira-Fernandez J, Strassman RJ, et al. Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members. J Ethnopharmacol. 2007 Jul 25;112(3):507–513.
  • Tort S, Urrútia G, Nishishinya MB, et al. Monoamine oxidase inhibitors (MAOIs) for fibromyalgia syndrome. Cochrane Database Syst Rev. 2012; Apr 18(4):Cd009807. DOI:10.1002/14651858.CD009807
  • Brubacher JR, Ravikumar PR, Bania T, et al. Treatment of toad venom poisoning with digoxin-specific Fab fragments. Chest. 1996 Nov;110(5):1282–1288.
  • Ermakova AO, Dunbar F, Rucker J, et al. A narrative synthesis of research with 5-MeO-DMT. J Psychopharmacol. 2021;36(3):273–294.
  • Stoyek MR, Jonz MG, Smith FM, et al. Distribution and chronotropic effects of serotonin in the zebrafish heart. Auton Neurosci. 2017 Sep;206:43–50.
  • Watts SW, Morrison SF, Davis RP, et al. Serotonin and blood pressure regulation. Pharmacol Rev. 2012 Apr;64(2):359–388.
  • Paredes S, Cantillo S, Candido KD, et al. An association of serotonin with pain disorders and Its modulation by estrogens. Int J Mol Sci. 2019 Nov 15;20(22):5729.
  • Rizzoli P, Mullally WJ. Headache. Am J Med. 2018 Jan;131(1):17–24.
  • Labate B, de Rose I, Dos Santos R. Ayahuasca religions: a comprehensive bibliography and critical essays. Santa Cruz: Multidisciplinary Association for Psychedelic Studies; 2009.
  • Serrano-Dueñas M, Cardozo-Pelaez F, Sanchez-Ramos J. Effects of Banisteriopsis caapi extract on Parkinson’s disease. Sci Rev Alternative Med. 2001 06 /01;.;5:127–132.
  • Djamshidian A, Bernschneider-Reif S, Poewe W, et al. Banisteriopsis caapi, a forgotten potential therapy for Parkinson’s disease? Mov Disord Clin Pract. 2015;3(1):19–26.
  • Banerjee R, Kumar M, Gaurav I, et al. In-silico prediction of the beta-carboline alkaloids harmine and harmaline as potent drug candidates for the treatment of Parkinson’s disease. Antiinflamm Antiallergy Agents Med Chem. 2021;20(3):250–263.
  • Pennes HH, Hoch PH. Psychotomimetics, clinical and theoretical considerations: harmine, win-2299 and nalline. Am J Psychiatry. 1957 Apr;113(10):887–892.
  • Khan H, Patel S, Kamal MA. Pharmacological and toxicological profile of harmane-β-carboline alkaloid: friend or foe. Curr Drug Metab. 2017;18(9):853–857.
  • Brito-da-Costa AM, Dias-da-silva D, Gomes NGM, et al. Toxicokinetics and toxicodynamics of ayahuasca alkaloids N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine: clinical and forensic impact. Pharmaceuticals. (Basel, Switzerland). 2020;13(11): 334.
  • Houle SKD, Evans D, Carter CA, et al. Ayahuasca and the traveller: a scoping review of risks and possible benefits. Travel Med Infect Dis. 2021 Nov-Dec;44:102206.
  • Zhao T, He YQ, Wang J, et al. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res. 2011 Nov;25(11):1671–1677.
  • Li S-P, Wang Y-W, Qi S-L, et al. Analogous β-carboline alkaloids harmaline and harmine ameliorate scopolamine-induced cognition dysfunction by attenuating acetylcholinesterase activity, oxidative stress, and inflammation in mice. Front Pharmacol. 2018;9:346.
  • Jiang B, Meng L, Zou N, et al. Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: challenge on monoamine oxidase and acetylcholinesterase inhibition. Phytomedicine. 2019 Sep;62:152967.
  • Orsolini L, Chiappini S, Papanti D, et al. How does ayahuasca work from a psychiatric perspective? Pros and cons of the entheogenic therapy. Hum Psychopharmacol. 2020 May;35(3):e2728.
  • Orsolini L, Chiappini S, Papanti D, et al. The bridge between classical and “synthetic”/chemical psychoses: towards a clinical, psychopathological, and therapeutic perspective. Front Psychiatry. 2019;10:851.
  • Szmulewicz AG, Valerio MP, Smith JM. Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report. Int J Bipolar Disord. 2015;3(1):4.
  • Zellner N, Zellner T, Warninghoff J. Ayahuasca-induced psychosis in a patient with bipolar disorder. Nervenarzt. 2019 Nov;90(11):1154–1155.

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.