Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial

This analysis of an earlier open-label study (n=15) on ayahuasca (one session), found significant (Hedges’ g = 1.75) and sustained decreases in suicidality in people with depression (MDD).

Abstract

“Rationale: Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality.

Objective: To examine the acute and post-acute effect of ayahuasca on suicidality among individuals with MDD.

Methods: We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received a single dose of ayahuasca (N = 17). Suicidality was assessed at baseline; during the intervention; and 1, 7, 14, and 21 days after the intervention.

Results: Among individuals with suicidality at baseline (n = 15), there were significant acute (i.e., 40, 80, 140, and 180 min after administration) and post-acute (1, 7, 14, and 21 days after administration) decreases in suicidality following administration of ayahuasca. Post-acute effect sizes for decreases in suicidality were large (Hedges’ g = 1.31-1.75), with the largest effect size 21 days after the intervention (g = 1.75).

Conclusions: When administered in the appropriate context, ayahuasca may lead to rapid and sustained reductions in suicidality among individuals with MDD. Randomized, double-blind studies with larger sample sizes are needed to confirm this early finding.“

Authors: Richard J. Zeifman, Nikhita Singhal, Rafael G. Dos Santos, Rafael F. Sanches, Flávia de Lima Osório, Jaime E. C. Hallak & Cory R. Weissman

Notes

The data used came from Sanches and colleagues (2016) who analysed the antidepressant effects of a single dose of ayahuasca.

Summary

Preliminary evidence indicates that ayahuasca may decrease depressive symptoms and reduce suicidality among individuals with major depressive disorder.

We conducted a secondary analysis of an open-label trial in which individuals with recurrent MDD received ayahuasca. The results showed that there were significant acute and post-acute decreases in suicidality following administration of ayahuasca.

Ayahuasca may reduce suicidality among individuals with MDD when administered in the appropriate context.

Introduction

Suicide is among the leading causes of death worldwide. While first-line interventions for major depressive disorder (MDD), such as selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT), lead to limited decreases in suicidality, ketamine is one rapid-acting pharmacological agent that is currently being researched for its anti-suicidal effects.

Ayahuasca as a potential novel intervention for suicidality

Ayahuasca, a psychoactive brew composed of the plants Banisteriopsis caapi and Psychotria viridis, may show promise as a treatment for suicidality. However, additional research is needed to determine the effects of ayahuasca on suicidality.

Participants

Participants were recruited via local advertisements and by referral from private psychiatric clinics. They were required to have failed at least one previous antidepressant treatment and to have denied prior use of illicit substances or ayahuasca.

Procedure

The study took place in an inpatient psychiatric unit in Brazil, and participants were given a single 2.2 ml/kg dose of ayahuasca containing 0.8 mg/ml DMT, 0.21 mg/ml harmine, and no harmaline. No psychological intervention was performed during the session.

Suicidality was assessed at baseline, 40, 80, 140, and 180 min after ayahuasca administration, and 1, 7, 14, and 21 days post-intervention.

Measures

The Montgomery-sberg Depression Rating Scale (MADRS) is a clinician-administered 10-item measure of depressive symptoms. It includes one item assessing current suicidality (item 10; MADRS-suicidality item; MADRS-SI), and the sum of the remaining 9 items is used to measure non-suicide-related depressive symptoms.

Data analysis

We used fixed-effects linear mixed models to examine acute and post-acute changes in suicidality as indexed by the MADRS-SI. Within-group comparison t tests were conducted comparing baseline and each subsequent time point, and Pearson correlation coefficients were calculated to examine the relationship between acute and post-acute changes.

Demographics

The total sample of the trial included 17 individuals. Two individuals did not exhibit suicidality at baseline, and one individual exhibited a small increase in suicidality 1 day after the intervention.

Clinical outcomes

Acute changes in suicidality were significant for time and for each time point during the acute phase. There was a significant association between changes in suicidality and changes in non-suicide-related depressive symptoms.

The linear mixed model showed that time affected post-acute changes in suicidality. Within-subject t tests indicated that suicidality decreased at all time points and was lowest 21 days after administration.

Discussion

We explored the effects of a single dose of ayahuasca on suicidality among individuals with recurrent MDD. We found that the effects of ayahuasca were rapid and sustained, and that there was a significant relationship between acute and post-acute changes in suicidality and non-suicide-related depressive symptoms.

We found that ayahuasca administration led to acute and sustained reductions in suicidality up to 21 days after the administration. This finding is consistent with other studies finding therapeutic benefits for depression and suicidality.

How might ayahuasca lead to decreases in suicidality?

The integrated motivational-volitional model suggests that entrapment (i.e., the belief that one is unable to change one’s undesirable internal and external life circumstances) plays a key role in suicidality and that psychedelics reduce entrapment and experiential avoidance, which may be mechanisms through which ayahuasca reduces suicidality.

Ayahuasca’s acute and post-acute effects on suicidality may be modulated by the pharmacological effects of the -carbolines and/or DMT, including increases in hippocampal brain-derived-neurotrophic factor (BDNF) and neurogenesis, as well as its agonism of cortical 5-HT2A receptors and subsequent increases in glutamatergic tone.

Limitations and future directions

This study was limited by its small sample size, open-label design, and use of a single item from a depression scale to assess suicidality. Future studies should include randomized, controlled designs that specifically recruit individuals that are high in suicidality and assess suicidality as a primary outcome.