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

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. Clinical Trial Registration: , identifier NCT02914769.

Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

“…Importantly, we did not find significant increases in depression severity or suicidal ideation from 2-weeks to 4-weeks, suggesting that the positive effects of psychedelics were reliably sustained for at least 1-month post-psychedelic use. These results are in line with clinical studies indicating that psychedelics can lead to decreases in depression severity [e.g., ( 13 , 14 )] and suicidal ideation ( 13 , 15 ) and that these effects are sustained over time [e.g., ( 4 , 6 , 13 )]. Importantly, in both studies, the majority of the participants (Study 1 = 72.2%; Study 2 = 81.9%) exhibited subclinical levels of baseline depression severity.…”

“…Now I know how to deal with my feelings rather than repress them" (1) Serotonergic psychedelics, a class of pharmacological agents that act as serotonin 2A receptor (5-HT2AR) agonists, including psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT; contained in the brew ayahuasca), are currently receiving attention within psychiatry and mental health as novel interventions for a wide range of mental health concerns [for reviews, see (2,3)]. Randomized controlled trials and open-label trials have found promising results for psychedelic therapy in the treatment of distress associated with a life-threatening illness [e.g., (4)(5)(6)], substance use disorders [e.g., (7)(8)(9)(10)], obsessive-compulsive disorder (11), depression [e.g., (12)(13)(14)], and suicidal ideation (13,15).…”

“…Recent research has begun exploring psychedelic therapy as a novel intervention for depression and suicidal ideation. In a randomized controlled trial, among individuals with treatment-resistant major depressive disorder (MDD), administration of ayahuasca was associated with large effect sizes for decreases in depression severity ( 14 ) and suicidal ideation ( 15 ). Similarly, in an open-label trial, individuals with treatment-resistant MDD that received psilocybin therapy showed large decreases in depression severity and suicidal ideation ( 13 ).…”

Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

“…Ayahuasca is an Amazonian brew made with Psychotria viridis , a rubacea containing N, N-DMT, and Banisteriopsis caapi , a vine which contains β-carbolines that are reversible inhibitors of monoamine oxidase and an inhibitor of serotonin reuptake (Palhano-Fontes et al 2014 ). This psychedelic also has been subject to increasing research, which has included effects on mood and addiction in healthy volunteers (McKenna 2004 ; Riba et al 2001 ; Santos et al 2007 ; Uthaug et al 2018 ), as well as clinical trials investigating its psychological and neurobiological antidepressant effects in open-label and double-blind designs (de Almeida et al 2019 ; Dos Santos et al 2011 ; Galvão et al 2018 ; Osorio Fde et al 2015 ; Palhano-Fontes et al 2019 ; Zeifman et al 2019 ).…”

The Use of Classic Hallucinogens/Psychedelics in a Therapeutic Context: Healthcare Policy Opportunities and Challenges

“… 24 Furthermore, an open-label 25 and a placebo-controlled trial 26 showed that ayahuasca administration reduced depression, anxiety, and suicidality in patients with TRD. 27 , 28 …”