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Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study
Open accessAbstract
Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.
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“While similar in distribution, the magnitude of the CBF response in depression patients was distinctly less than that in the study of healthy volunteers by Riba et al. [141].”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [142]
In the citing paper
“Parametric mapping of CBF changes indicated increases in some very small clusters (<50 voxels) localized to the left nucleus accumbens, right insula, and left cingulate cortex, which the authors felt to be regions activated by antidepressant treatments.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [142]
In the citing paper
“the mean Hamilton depression rating scales declined from 25 to 15 in the three hours after administration, and remained around 10 during the following three weeks.”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [142]
In the citing paper
“These open label [22–24] and randomised control [21] trials have suggested that ayahuasca may produce rapid and significant reductions in depression symptoms in as little as 1 day.”
From The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol (2022) · cites this paper as [23]
In the citing paper
“Several studies, including one RCT, have highlighted a similar rapid onset and sustained antidepressant effect after a single ingestion in patients diagnosed with treatment-resistant depression (3, 36).”
From Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects (2024) · cites this paper as [36]
In the citing paper
“Similarly, ayahuasca's anti-depressive potential has been demonstrated in pilot studies and replicated in a RCT on patients with treatment-resistant depression (33, 36, 63).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [33]
In the citing paper
“Most of these studies however suffer from low methodological validity and are mostly open-label, yet they have yielded preliminary evidence for the capacity of psychedelic substances for treating addiction, depression, anxiety, and eating disorders (29–35).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [33]
In the citing paper
“For example, enhanced activation of the ACC and other prefrontal regions was observed in novice and experienced meditators (120–122), and as a result of ayahuasca administration (33, 63).”
From Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy (2021) · cites this paper as [33]
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Metadata
- Authors
- Sanches, R. F., de Lima Osório, F., dos Santos, R. G., Macedo, L. R. H., Maia-de-Oliveira, J. P., Wichert-Ana, L., de Araujo, D. B., Riba, J., Crippa, J. A. S., & Hallak, J. E. C.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Sanches, Rafael Faria
- Macedo, Ligia R.H.
- Crippa, José Alexandre S.
- Hallak, Jaime E.C.
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2016-02
- Volume
- 36
- Issue
- 1
- Pages
- 77-81
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2419844652
- Cited by
- 466
- References
- 26
- Citations by year
- 2026: 31 · 2025: 34 · 2024: 63 · 2023: 55 · 2022: 68 · 2021: 59 · 2020: 39 · 2019: 28 · 2018: 41 · 2017: 31 · 2016: 14
- FWCI
- 35.96
- Type
- journal article
- Language
- en
- Open access
- green
- repositorio.ufrn.br
- Licence
- other-oa
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ayahuasca, recurrent depression, antidepressant effects, dimethyltryptamine, harmine, 5-HT2A receptor agonism, monoamine oxidase A inhibition, regional cerebral blood flow, nucleus accumbens, insula, dissociative states, adverse effects, single-dose administration
- MeSH terms
- Administration, Oral, Adult, Antidepressive Agents, Brain, Major Depressive Disorder, Female, Hallucinogens, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Recurrence, Time Factors, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Plant Preparations, Banisteriopsis
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