Potential therapeutic use of ayahuasca: A literature review

COSTA, Salvana Priscylla Manso; CARVALHO, Keith Cardoso; GOMES, Isabella Nunes; CALAZANS, Carine Lopes; SILVA, Morganna Thinesca Almeida; MIRANDA, Joseneide de Alves; BARRETO, Ighor Costa; MELO, Matheus Vinícius Guimarães de; HOLANDA, Keyla Emanuelle Ramos de; ALENCAR FILHO, José Marcos Teixeira de

doi:10.1590/1809-4392202301821

home Sumário navigate_before Anterior Atual Seguinte navigate_next

home Sumário

CHEMISTRY AND PHARMACOLOGY | REVIEW • Acta Amaz. 54 (2) • Apr-Jun 2024 • https://doi.org/10.1590/1809-4392202301821 linkcopy

Potential therapeutic use of ayahuasca: A literature review

Potencial uso terapêutico da ayahuasca: Uma revisão da literatura

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Ayahuasca is a psychoactive decoction originally used in indigenous Amazonian culture. It consists of a dense brown liquid that most frequently results from the decoction of two plants native to the Amazon rainforest, Psychotria viridis (Rubiaceae) and Banisteriopsis caapi (Malpighiaceae). The composition of the decoction is variable, as several plant species can be used in its preparation. Its psychoactive effect occurs due to the presence of N,N-dimethyltryptamine (DMT), an agonist at serotonergic receptors (5-HT_1A/2A/2C) that is metabolized by the enzyme monoamine oxidase type A (MAO-A), and also the presence of β-carbolines, which are reversible MAO-A inhibitors. This joint interaction promotes a sequence of psychedelic neurochemical effects. Due to the current expansion of research on psychedelic substances and the growing public interest in the benefits of ayahuasca beyond its traditional use in the Amazon, academic research on its therapeutic capacity has been increasing. This study aimed to carry out a literature review on the scientific evidence for the therapeutic potential of ingesting ayahuasca. The review covered the period 2012-2022, and resulted in evidence on the therapeutic effects of ayahuasca on depression/anxiety, chemical dependency/alcoholism and Parkinson’s disease, as well as neuropsychological effects, and possible toxic effects on reproduction/embryonic development, among other adverse effects. The highest number of publications in the searched period dealt with the effects of ayahuasca on depression and anxiety. Further studies need to address the detailed mechanism of action of ayahuasca, as well as its potential toxicity, in order to demonstrate its safety.

KEYWORDS:
Psychotria viridis; Banisteriopsis caapi; medicinal effects; N,N-dimethyltryptamine

Substance	Molecular formula	Classification	Structural similarity	Mechanism of action
Dimethyltryptamine (DMT)	C₁₂H₁₆N₂	Indole alkaloid with psychedelic effects	Similar to serotonin and melatonin, derivatives of the amino acid tryptophan. Chemical structure similar to sumatriptan (Schripsema and Dagnino 2017)	Non-selective serotonin receptor agonist (Brito-da-Costa et al. 2020)
Harmine (HRM)	C₁₃H₁₂N₂O	ꞵ-carboline	Similar to indole amines such as serotonin (Schripsema and Dagnino 2017)	MAO inhibitors (inhibit the intestinal desamination of DMT, allowing it to reach the brain). Increase in serotonin, dopamine and norepinephrine levels in the brain. (Brito-da-Costa et al. 2020)
Harmaline (HRL)	C₁₃H₁₄N₂O	ꞵ-carboline
Tetrahydroharmine (THH)	C₁₃H₁₆N₂O	ꞵ-carboline		Serotonin reuptake transporter inhibitor (Brito-da-Costa et al. 2020)

Evaluated aspect	Type of study	Effects	Identified substances	Concentration (mg mL^-1)	Source
Acute effects on neuropsychological performance (memory)	Clinical trial	Mixed effects, negatively affecting work memory, but not interfering with stimulus response.	-	-	Bouso et al. (2013)
Toxicity and behavioral functions	Animal models (rats)	Decrease in locomotor activity and activation of brain areas involved in interpretation and emotional process.	-	-	Pic-Taylor et al. (2015)
Alcoholism	Animal models	Inhibition in ethanol-induced hyperlocomotion.	-	-	Oliveira-Lima et al. (2015)
Depression	Open preliminary study	Significant and fast reduction of depressive symptoms and hopelessness.	DMT HRM	0.8 0.21	Osório et al. (2015)
Depression	Clinical trial	Increase in brain blood perfusion and fast sustained antidepressive effects regardless of severity of patient current depressive episode.	DMT HRM	0.8 0.21	Sanches et al. (2016)
Effects on animal reproduction	Animal models (rats)	Significant increase in total serum testosterone, decrease in spermatic transit time and spermatic reserves in the epididymis caudae with 4× dose (13.2 mg kg^-1 harmine, 1.04 mg kg^-1 harmaline, 1.24 mg kg^-1 DMT), but not with highest dose. No significant changes in other reproductive endpoints (spermatozoid motility and morphology, total spermatozoid count, daily sperm production), and histology of testis and epididymis.	DMT HRM HRL	0.146 1.56 0.12	Santos et al. (2017)
Chemical dependency	Qualitative ethnographic analysis	Effectiveness in treatment of substance dependency was demonstrated.	-	-	Talin and Sanabriab (2017)
Toxicity and behavioral evaluation	Animal models (zebrafish)	Anomalies in embryos at highest concentration, including hatching delay, loss of equilibrium, edema and accumulation of red blood cells. Embryo significantly decreased locomotor activity.	DMT HRM HRL	0.141 1.56 0.122	Andrade et al. (2018)
Fetal toxicity and embryonic development	Animal models (rats)	50% mortality at higher doses, and neuronal loss, kidney injuries, intrauterine growth retardation, embryo death and anomalies in fetuses.	DMT HRM HRL	0.141 1.56 0.122	Motta et al. (2018)
Depression	Animal models	Behavioral and physiological improvements. Increase in cortisol levels (hormone involved in depression etiology).	DMT HRM HRL THH	0.01 0.11 0.03 0.05	Silva et al. (2019)
Depression	Double- blinded placebo- controlled study	Rapid antidepressant effect after single dosing session compared with placebo. Depression severity changed significantly but differently for ayahuasca and placebo groups. Significantly higher improvement in psychiatric scales in the ayahuasca group compared to placebo at all time points.	DMT HRM HRL THH	0.01 0.11 0.24 0.05	Palhano-Fontes et al. (2019)
Prolonged grief disorder	Observational study (no control)	Significant decrease in grief symptoms and severity with ceremonial use. Improvement in psychosocial well-being. Participants responded to online survey that included the Texas Revised Inventory of Grief, Symptom Assessment-45, WHO Quality of Life-Bref, Acceptance and Action Questionnaire, and Decentering.	DMT HRM HRL THH	2.0 2.0 0.37 1.0	Gonzales et al. (2020)
Suicidal tendency in individuals with major depressive disorder (MDD)	Open-label trial	Rapid and sustained reductions in suicidality among individuals with major depressive disorder (MDD). Decrease in suicidality highest 21 days after intervention.	DMT HRM	0.8 0.21	Zeifman et al. (2020)
Inflammatory biomarkers of depression	Double- blinded placebo- controlled study	Significant reduction of C-reactive protein levels across time in patients and controls, but not in placebo. Significant correlation between decrease in C-reactive protein and decrease in depressive symptoms 48 h after substance ingestion (Montgomery-Åsberg Depression Rating Scale).	DMT HRM HRL THH	0.36 1.86 0.24 1.20	Galvao-Coelho et al. (2020)
Mental health	Observational study	Associatuon of mental health with non-pharmacological factors that cause placebo response and dose-dependent pharmacological contribution of AYA.	DMT HRM HRL	2.01 5.57 0.38	Uthaug et al. (2021)
Adverse effects	Transversal study	Mild and tolerable adverse effects in individuals after AYA use, pending care with drug interactions.	-	-	Durante et al. (2021)
Depression and anxiety	Observational study	Most participants believed that they were cured or became better after AYA ingestion. A small part reported worsening of the symptoms.	-	-	Sarris et al. (2021)
State of conciousness	Observational study	Unbalance in circulating concentrations of aromatic amino acids involved in neurotransmission.	DMT HRM HRL THH	0.14 4.5 0.51 2.10	Madrid-Gambin et al. (2022)
Chemichal dependency	Animal models	Increase in locomotor activity relative to control during acquisition of sensitization.	DMT	1.76 mg kg^-1	Almeida et al. (2022)
Parkinson’s disease	In vitro model	MAO inhibitory activity by β-carbolines with potential to treat parkinsonism due to dopamin degradation prevention in brain cells.	DMT HRM	4.5 1.5	Katchborian-Neto et al. (2020)

vertical_align_top show_chart

more_horiz close
- image
- translate
- link
- article
- vertical_align_top
- file_download
- show_chart
- image
- translate
- link
- article

location_on

Instituto Nacional de Pesquisas da Amazônia Av. André Araujo, 2936 Aleixo, 69060-001 Manaus AM Brasil, Tel.: +55 92 3643-3030, Fax: +55 92 643-3223 - Manaus - AM - Brazil
E-mail: acta@inpa.gov.br

rss_feed Acompanhe os números deste periódico no seu leitor de RSS