Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report, Flavia de L. Osorio et al., 2015

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Flavia de L. Osorio, Rafael F. Sanches, Ligia R. Macedo, Rafael G. dos Santos, Joao P. Maia-de-Oliveira, Lauro Wichert-Ana, Draulio B. de Araujo, Jordi Riba, Jose´ A. Crippa, Jaime E. Hallak

Revista Brasileira de Psiquiatria, 2015, 37, 13–20



Objectives : Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich
in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore
have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six
volunteers with a current depressive episode.
Methods : Open-label trial conducted in an inpatient psychiatric unit.
Results : Statistically significant reductions of up to 82% in depressive scores were observed between
baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale
for Depression (HAM-D), the Montgomery-A° sberg Depression Rating Scale (MADRS), and the
Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration
resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking
disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or
hypomania in patients with mood disorders and that modifications in thought content, which could
indicate psychedelic effects, are not essential for mood improvement.
Conclusions : These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in
patients with a depressive disorder.

Keywords : Psychedelic agents; dimethyltryptamine; harmine; monoamine oxidase inhibitors;
therapeutic use


Depression is a highly prevalent disorder and is associated with intense personal suffering, increased mortality, and high morbidity.1,2 Although its etiology is unknown, some theories suggest that biological factors may be implicated.3 One such theory is the monoamine hypothesis, which suggests that an imbalance in cerebral monoamines such as dopamine, norepinephrine, and, especially, serotonin is
responsible for depressive symptomatology.3 The monoamine hypothesis is the theory on which the leading commercially available antidepressants are based.3

Currently available treatments have limitations that can lead to low therapeutic effectiveness, especially related to low response rates, as well as adverse effects and latency to onset of therapeutic action.3 Thus, new interventions, particularly those that with the potential for acute effect, would have a huge impact on the treatment of depression. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, for example, has rapid and potent antidepressant effects in treatmentresistant major depressive disorder (MDD) and bipolar depression, and its use is considered one of the most exciting areas in contemporary psychiatric research.4,5 Ayahuasca (AYA), a botanical hallucinogen traditionally used by indigenous groups of the Northwest Amazon region for ritual and medicinal purposes,6,7 is a potential candidate for this new generation of antidepressant research focusing on new pharmacological treatments that produce immediate and more pronounced effects. AYA is prepared by prolonged decoction of the bark of the vine Banisteriopsis caapi with the leaves of the shrub Psychotria viridis.6,7 B. caapi contains the b-carboline alkaloids harmine, tetrahydroharmine (THH), and harmaline, which act as monoamine oxidase A inhibitors (MAOI), while P. viridis is rich in the psychedelic tryptamine N, N-dimethyl-tryptamine (DMT).6,8-11

The psychoactive effects of AYA are produced by a combined action of peripheral (gastrointestinal and liver) monoamine oxidase A (MAO-A) inhibition by harmine and central 5-HT1A/2A/2C agonist action of DMT on frontal and paralimbic brain areas.8,9,12 Studies conducted among long-term (i.e., years or decades) members of religious groups that use AYA ritually suggest that this population does not present evidence of psychological, neuropsychological, or psychiatric harm caused by AYA.13-15 In fact, there are several reports describing reduced mental health problems in AYA users.13-15 Nevertheless, given the small number of studies, most with a limited number of participants, there is insufficient information to allow a definitive conclusion on this topic, and more studies on the potential long-term toxicity of AYA are required.

An increasing number of studies report antidepressive potential for AYA alkaloids in animals.16-24 Furthermore, a double-blind, placebo-controlled animal study reported reduced hopelessness and panic-related signs after acute AYA administration,25 and preliminary data in humans also support an antidepressive action for AYA.26

The agonist action of AYA alkaloids on serotonergic receptors and its inhibitory effects on MAO-A, associated with field and laboratory evidence suggesting that AYA causes a sensation of well-being, led to the hypothesis that this substance could be useful in the treatment of depression in humans. Thus, the objective of the present preliminary, open-label study was to evaluate the acute effects of a single dose of AYA in patients diagnosed with depression and to test whether AYA administration could produce an acute antidepressant effect.