Trial PaperTreatment-Resistant Depression (TRD)SuicidalityBorderline Personality Disorder (BPD)Depressive DisordersPersonality DisordersMajor Depressive Disorder (MDD)Public Health, Prevention & Behaviour ChangeAyahuascaPlacebo

The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial.

This secondary analysis of a double-blind, parallel-arm, randomised placebo-controlled trial (n=29) investigates the impact of ayahuasca on suicidality (SI) in individuals with treatment-resistant depression (TRD). It found that ayahuasca may show potential as a fast-acting and innovative intervention for SI, but didn't find significant results (only a trend with a large effect size). This is the first study to investigate the use of ayahuasca for SI.

Authors

  • Jamie Hallak
  • Richard Zeifman
  • Fernanda Palhano-Fontes

Published

Frontiers in Pharmacology
individual Study

Abstract

Suicide is a major public health problem. Given increasing suicide rates and limitations surrounding current interventions, there is an urgent need for innovative interventions for suicidality. Although ayahuasca has been shown to target mental health concerns associated with suicidality (i.e., depression and hopelessness), research has not yet explored the impact of ayahuasca on suicidality. Therefore, we conducted secondary analyses of a randomized placebo-controlled trial in which individuals with treatment-resistant depression were administered one dose of ayahuasca (n = 14) or placebo (n = 15). Suicidality was assessed by a trained psychiatrist at baseline, as well as 1 day, 2 days, and 7 days after the intervention. A fixed-effects linear mixed model, as well as between and within-groups Cohen's d effect sizes were used to examine changes in suicidality. Controlling for baseline suicidality, we found a significant effect for time (p < .05). The effect of the intervention (i.e., ayahuasca vs. placebo) trended toward significance (p = .088). At all time points, we found medium between-group effect sizes (i.e., ayahuasca vs. placebo; day 1 Cohen's d = 0.58; day 2 d = 0.56; day 7 d = 0.67), as well as large within-group (ayahuasca; day 1 Cohen's d = 1.33; day 2 d = 1.42; day 7 d = 1.19) effect sizes, for decreases in suicidality.Conclusions: This research is the first to explore the impact of ayahuasca on suicidality. The findings suggest that ayahuasca may show potential as an intervention for suicidality. We highlight important limitations of the study, potential mechanisms, and future directions for research on ayahuasca as an intervention for suicidality.

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Research Summary of 'The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial.'

Blossom's Take

Although promising, this study doesn't find a significant effect of ayahuasca on suicidal ideation. One thing that becomes clear from visually observing Figure 1 is the mismatch between the suicidality score (MADRS-SI) at the baseline between the ayahuasca and placebo groups (the former being much higher and then dropping just below the latter).

Introduction

Suicide is described as a major and growing public health problem, particularly among people with major depressive disorder (MDD) and those with comorbid MDD and borderline personality disorder (BPD). The authors note limitations of existing interventions for suicidality — including delayed onset of effect, limited availability, adverse effects, the need for ongoing administration, and substantial non-response among some patients — and highlight the unmet need for fast-acting, durable, and safe novel treatments. Previous experimental work with ketamine shows rapid reductions in suicidality but concerns remain regarding durability and abuse potential; observational and some open-label studies of psychedelics (including psilocybin and ayahuasca) suggest associations with lower suicidality and improvements in related constructs such as depression and hopelessness, but experimental placebo-controlled data on suicidality are lacking. Jha and colleagues therefore report secondary analyses of a double-blind, randomised, placebo-controlled trial in individuals with treatment-resistant unipolar MDD, testing whether a single dose of ayahuasca reduces clinician-assessed suicidality. The primary hypothesis was that ayahuasca would produce reductions in suicidality that were sustained from 1 to 7 days post-administration. The investigators also planned exploratory analyses of the relationship between changes in suicidality and changes in non-suicide-related depressive symptoms.

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The Impact of Ayahuasca on Suicidality: Results... — Research Summary & Context | Blossom