Ayahuasca (AYA) is a psychotropic plant from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that AYA may have therapeutic potential in the treatment of mental health disorders like depression – a common life-disrupting, highly recurrent disorder – that is among the leading causes of disability worldwide.

The aim of this exploratory study is to gather and assess scientific evidence about clinical effects of AYA in the treatment and symptomatological expression of patients with depression.

A literature research was conducted on PubMed, starting from the MeSH terms: “Banisteriopsis” and “Depression”. Results corresponding to investigations using AYA, and based on an adult population with depressive disorders, were selected for our analysis.

The research provided 8 results, of which 6 met the defined criteria. Different types of studies with variable samples were considered, including retrospective and prospective observational studies, meta-analysis and a narrative review. Overall, evidence about the use of AYA in depressive disorders is associated to reductions in depression scales, to significant antidepressant effects and in mediating improvement of grief symptoms. AYA administration increased introspection and positive mood, self-acceptance, empathy, openness and potentiated improvements in emotional processing. The underlying potential mechanisms, adverse effects and the current limitations related to its study and use are analysed and discussed.

The use of AYA in depression shows promising results that should be further explored in controlled trials with larger sample sizes, in order to better evaluate its clinical effects, safety profile and related short and long-term effects.

No significant relationships.

Ayahuasca is an hallucinogenic tea prepared from the Amazonian vine Banisteriopsis caapi and the leaves of the plant Psychotria Viridis. Banisteriopsis caapi contains monoamine oxidase inhibitors (MAO) that render the N, N-dimethyltryptamine (DMT) of Psychotria Viridis active. This brew is being used as a sacrament in syncretic religions in urban areas of Brazil and worldwide with the purpose of enabling a spiritual experience as well as healing for a variety of conditions such as drug addiction, depression and anxiety disorders.

This work aims to provide an understanding on the potential benefits of ayahuasca in psychiatric symptoms, as well as its neuropsychological functioning, neuroimaging and adverse events.

A non-systematic review was performed on PubMed database and Google Scholar, using the key words “Ayahuasca, Drug Addiction, Psychedelics, DMT, Neuroplasticity”. The review included experimental studies in humans, observational studies, systemic review articles and clinical trials.

In a randomized placebo-controlled trial, ayahuasca had a significant antidepressant effect when compared to the placebo group. Long term ayahuasca usage was associated with structural alterations in the medial parts of the brain with no evidence of increased psychopathology or worse neuropsychological functioning. According to reviewed studies the incident of prolonged psychotic reaction among ayahuasca users is rare and the causal relation with ayahuasca is sometimes difficult to establish.

Despite the promising results, more controlled double-blinded studies with larger populations are necessary to better understand the therapeutic potentials and side effects of ayahuasca.

No significant relationships.

Ayahusca has potential therapeutic beneffits.

Expose the potential beneffits of ayahuasca from neuropharmacology and clinical existing evidence.

A literature review was carried out in the databases pubmed, clinical key and texts of scientific dissemination.

There´s scientific literature about the potential therapeutic use of ayahuasca in dependencies, anxiety symtoms and depression, near death experiences and terminal illnesses. Possible benefit is postulated in impulsivity and personality disorders. It induces an introspective state, triggered by thoughts, emotions and autobiographical memories, which promotes reflection on personal issues, allowing new perspectives on certain life issues. It is common for users to describe it as analogous to a psychotherapeutic intervention. 5HTA2 agonists stimulate the expression of genes that encode transcription factors such as c-fos, egr 1, egr 2 and brain-derived neurotrophic factor (BDNF), which influence neuronal plasticity and are associated with cognitive aspects such as memory and attention. MAOIs and 5HT2A agonism have anxiolytic and antidepressant effects. Sigma -1 agonism promotes neuroplasticity. Decrease and remission in the consumption of alcohol and cocaine has been reported in patients with abuse and dependence. There has been significant decrease in depressive symptomatology, in observational studies, cases and controls and double blind compared with placebo. Improvement in different domains measured with mindfulness scales, similar to those observed in meditators, suggests an association between mindfulness techniques and experiences with ayahuasca.

There is existing evidence about potential therapeutical uses of ayahuasca. More studies are needed with biger samples, to establish it´s clinical use.

No significant relationships.

Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.

We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.

A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.

High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.

To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.

We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).

To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).