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. Author manuscript; available in PMC: 2026 Feb 20.
Published before final editing as: J Psychoactive Drugs. 2025 Feb 20:1–11. doi: 10.1080/02791072.2025.2465800

Long-term mental health and wellbeing outcomes associated with naturalistic ayahuasca consumption

BA Pagni 1,2, A Halman 3, J Sarris 4, R Chenhall 3, MP Bogenschutz 2, D Perkins 3,4,5,*
PMCID: PMC12353293  NIHMSID: NIHMS2059532  PMID: 39980134

Abstract

The durability of ayahuasca’s effects on mental health and the influence of clinical diagnoses on therapeutic response is unclear. Adults with no prior exposure to ayahuasca (n=66) participating in neo-shamanic ayahuasca ceremonies completed questionnaires at baseline, 7 days, and 1, 6, and 12 months. Mixed models were used to characterize temporal trajectories in mental health, alcohol and cannabis use, affect, personality, spirituality, and relationships; and examine the longevity of effects in individuals with and without a depressive or anxiety disorder. After multiple comparison correction, ayahuasca use was associated with decreases in depression, anxiety, stress, negative affect, negative emotionality, accepting external influence, and self-alienation at all time points. Improvements in mental health, self-efficacy, and spirituality were observed up to 12 months post-ceremony. Individuals with depression and anxiety diagnoses maintained significant symptom reductions, whereas those without a diagnosis experienced short-term benefits. Decreases in alcohol and cannabis use were only observed at month one. Naturalistic ayahuasca use was associated with persisting improvements in mental health and wellbeing, with the largest magnitude of symptom reduction observed in those diagnosed with a depressive or anxiety disorder. Differing trajectories of change were identified across psychological constructs, suggestive of both enhancement and attenuation of gains over time.

Keywords: ayahuasca ceremony, DMT, psychedelic, depression, anxiety, mental health, alcohol, cannabis, personality

Introduction

Ayahuasca is a psychedelic plant decoction that has emerged as a promising candidate for the psychiatric treatment of mental health conditions. Ayahuasca contains the psychoactive compound N,N-dimethyltryptamine (DMT), and several harmala alkaloids which render DMT orally bioavailable (Werneck et al., 2020). Clinical trials, prospective observational studies, and large cross-sectional surveys of ayahuasca users suggest that ayahuasca use can lead to rapid, robust, and enduring improvements in symptoms of depression and anxiety.

In a double-blind clinical trial, Palhano-Fontes et al. (2019) randomised patients with major depressive disorder (MDD) to ayahuasca or an active placebo with purgative effects. Significant antidepressant response was observed seven days after dosing, with remission rates of 64% in the ayahuasca group and 27% in the placebo group (Palhano-fontes et al., 2019). Prospective observational studies have found reductions in anxiety and depression symptoms out to 6-months in mixed samples, and reductions in depression in patients with MDD out to 12-months after administration, but a separate study did not find therapeutic effects 4 to 7 years later (Jiménez-Garrido et al., 2020; Ruffell et al., 2021; Santos et al., 2018; van Oorsouw et al., 2022a).

Cross-sectional research has found only slight, or nil associations between the number of years since ayahuasca was last drunk and better mental health, and reduced alcohol/drug/tobacco use, suggesting effects may be highly durable or diminish at a very slow rate over longer time scales (Daldegan-Bueno et al., 2022; Perkins, Opaleye, et al., 2021, 2023; Perkins, Schubert, et al., 2021). Other clinically relevant changes have been observed, including increases in life satisfaction, mindfulness, cognitive flexibility, empathy, and connection to self, others, and nature, and alterations to personality traits, which are consistent with enhanced resiliency (Kiraga et al., 2021; Murphy-Beiner & Soar, 2020; Ruffell et al., 2023; van Oorsouw et al., 2022a). Corroborating these relationships, cross-sectional survey studies have found that regular ayahuasca users report better general well-being and cognitive performance, fewer diseases and symptoms of psychopathology, and healthier lifestyles relative to normative samples (Bouso et al., 2012; Kohek et al., 2023; Lawn et al., 2017).

Despite the health benefits reported in these studies, it is unclear how long psychological changes persist over time, whether negative long-term consequences arise after the purported short-term benefits, and whether effects are specific to individuals with clinical diagnoses. We previously published an analysis of data from a prospective observational study which identified increases in relationship satisfaction, nature relatedness, spirituality, authenticity, self-efficacy, and body connection one month after a neo-shamanic ayahuasca ceremony in first-time users of ayahuasca (Perkins et al., 2022). In this report, we characterise mental health and psychological outcomes and trajectories in this sample over a 12-month period. We also evaluate whether clinical diagnosis of a depressive or anxiety disorder impacts the longevity of antidepressant or anxiolytic effects, respectively. This study contributes important longitudinal data to better understand the time course of changes in mental health and psychological wellbeing associated with naturalistic ayahuasca use.

Methods

Participants

Ayahuasca naïve participants (n = 66) were recruited using convenience sampling from two independent ayahuasca churches in North America from 2019 to 2021. Inclusion criteria for participating in the study were being 18 years of age or older, an English speaker, and having never used ayahuasca in the past. See Perkins et al. (2022) for a detailed description of recruitment and enrolment procedures. The research team was not involved in recruitment, administration of ayahuasca, or conducting the ceremony - all of which were performed by the ayahuasca church sites. All participants provided written informed consent. The study protocol was approved by the University of Melbourne Human Research Ethics Committee (HREC number 1852071.1). As part of the churches’ intake processes, independent of this study, all attendees with a confirmed or suspected diagnosis of a psychotic disorder or using a contraindicated medication use (e.g., antipsychotics, antidepressants, etc.) were excluded.

Design and Setting

Ayahuasca ceremonies were conducted in a neo-shamanic mestizo-styled setting at both church sites between November 2018 and December 2019. The churches were not organisationally affiliated. At each site participants attended a 1-day, 2-day, or 3-day ceremony led by a facilitator. For more information on the ceremonial setting, see Perkins et al. (2022).

Measures

Mental Health

Participants reported lifetime mental health diagnoses, including depression and anxiety disorders. The DASS-21 (Depression, Anxiety and Stress Scale) and Positive and Negative Affect Scale (PANAS) were administered at baseline (BL), day 7 (D7), 1 month (1m), 6 months (6m), and 12 months (12m). The DASS-21 is a 21-item survey with subdomain scores for depression, anxiety, and stress (Lovibond & Lovibond, 1995). The PANAS is a 10-item survey with subscale scores for positive and negative affect (Watson et al., 1988). The Short-Form Health Survey (SF-12) was administered at BL, 1m, 6m and 12, and features a mental health and physical health summary score (Ware et al., 2009).

Alcohol and Cannabis Use

The 8-item World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to calculate a total risk score for alcohol and cannabis use at BL, 1m, 6m and 12m (Humeniuk et al., 2008). Three categorical items were used in the Alcohol Use Disorder Identification Test (AUDIT) that evaluated the 1) frequency of alcohol use, 2) average amount of alcohol consumed on a drinking day, and 3) and frequency of binge-related drinking episodes at BL, 1m, 6m, and 12m (Bradley et al., 1998).

Wellbeing and Personality

All wellbeing measures were collected at BL, 1m, 6m, and 12m. The 10-item General Self-efficacy Scale (GSE) total score was used to measure general perceived self-efficacy (Schwarzer & Jerusalem, 1995); the 30-item Barratt Impulsivity Scale (BIS-30) total scores was used to measure impulsivity (Vasconcelos et al., 2012); the 15-item short form Big Five Inventory-2 (BFI-2-XS) was used to measure the personality traits Extraversion, Agreeableness, Conscientiousness, Negative Emotion, and Open-mindedness (Soto & John, 2017). Quality of interpersonal relationships was measured using the 7-item Relationship Satisfaction Scale (RS) (Wooden et al., 2002). Interpersonal and intrapersonal influence was measured using the 12-item Authenticity Scale (AS), which contains the subscales Authentic Living, External Influence, and Self-alienation (Wood et al., 2008). Bodily awareness was measured using the 20-item Scale of Body Connection (SBC), which contains the subscales Body Awareness and Bodily Dissociation (Price et al., 2017). Relationships with nature were measured using the 21-item Nature Relatedness Scale (NR), which contains the subscales Self, Perspective, and Experience (Nisbet et al., 2008). Spirituality was measured using the 6-item Intrinsic Spirituality Scale (ISS) (Hodge, 2003). Fruit and vegetable consumption was collected with the question “Approximately how many servings of vegetables/fruit do you eat on a usual day?”. Body Mass Index was calculated using the formula: weight (kg) / [height (m)]2.

Statistical analysis

Data were collected and managed using the REDCap data collection tool hosted at the University of Melbourne. All records were imported into R statistical software version 4.1.2 where data analysis was conducted. Linear Mixed Models (LMM) through lmerTest package was used to test differences between groups and between time points within groups for all instruments unless stated otherwise (Kuznetsova et al., 2017). In all LMM models, an individual was set as a random effect. Fixed effects included time point and whether an individual had consumed ayahuasca after the initial treatment period. The impact of each predictor was assessed by generating ANOVA results from the LMM with Satterthwaite’s method for estimating degrees of freedom. LMMs were utilised due to being well-suited to handling partially missing data, thus reducing potential bias due to differences between responders and non-responders. To analyse results involving ordinal scales, Cumulative Link Mixed Models (CLMM) were employed, utilising functionalities from the ordinal and RVAideMemoire packages in R (Christensen, 2019). The model implemented used the same fixed and random effects as LMM. Furthermore, odds ratios (ORs) were calculated using the ordinal package (Christensen, 2019). Effect sizes were measured by using effect size R package and partial eta-squared (ηp2) with 95% confidence intervals (Ben-Shachar et al., 2020). Effect sizes are considered small from 0.01 to 0.06, medium from 0.06 to 0.14, and large 0.14 or above (Miles & Shevlin, 2001). Multiplicity across measures was controlled for with false discovery rate (FDR) correction using the Benjamani-Hochberg method (Benjamani and Hochberg, 1995). FDR correction was performed using the p-values from the main effects of time (the primary effect of interest) for all 42 measures. Post-hoc pairwise comparisons using Holm-Bonferroni’s adjustment were conducted to examine significant simple effects of time. Those comparisons were performed using R’s emmeans package and the results are reported with estimated marginal means (EMM), mean difference scores (Mdiff) and their corresponding standard error (SE) (Lenth & others, 2022). P-values less than 0.05 after FDR correction were considered significant.

Results

Participants

The sample sizes for the linear mixed models for each respective instrument and time point are presented in Supplemental Table S1. The baseline sample size was 66 participants (26 men and 40 women) with a mean age of 37.56 (SD: 10.16, range 19–64). Among this sample, the vast majority of participants were US citizens (97%), with relatively high levels of education: almost half (49.9%) reported a bachelor’s degree or above (bachelor’s degree, 30.3%; a masters or other professional degree, 12.1%; doctoral degree, 6.1%). Twenty-four participants reported previously receiving a depressive disorder diagnosis (e.g. major depression) and fifteen reported receiving an anxiety disorder diagnosis (e.g. generalized anxiety disorder) (Table S1). During the follow-up period, 27 participants reported additional instances of drinking ayahuasca, and 39 participants did not.

Mental Health

Depression, Anxiety, and Stress

Significant main effects of time were detected on the DASS-21 subscales for Depression (ηp2 = 0.20), Anxiety (, ηp2 = 0.16), and Stress (ηp2 = 0.33), all of which survived correction (p-FDR<0.001). Relative to baseline, depressive symptoms were reduced across the full sample by 75% at 7d, 59% at 1m, and 51% at 12m (Figure 1A, Table S2). Relative to baseline, anxiety and stress symptoms were reduced across the full sample by 57% and 63% at 7d, 55% and 54% at 1m, 50% and 36% at 6m, and 47% and 46% at 12m, respectively (Figure 1C and 1E, Table S2). Symptoms of depression and stress were statistically higher at 6m compared to 7d, suggesting a temporary attenuation of therapeutic gains (Figure 1A and 1E, Table S2).

Figure 1:

Figure 1:

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DASS-21 scores for (A) depression, (B) depression by depressive diagnosis, (C) anxiety, (D) anxiety by anxiety diagnosis (E) stress. SF-12 score for (F) mental health summary. PANAS scores for (G) negative affect and (H) positive affect. Scores were measured at baseline, 7 days (7d), 1 month (1m), 6 months (6m) and 12 months (12m) post-ayahuasca ceremony, except for (F), where 7d was not collected. Estimated marginal means (EMM) with standard errors (SE) are shown with asterisks representing statistical significance levels of * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. Colors on the Y-axis of (B) and (D) correspond to the severity of either depression or anxiety, with normal (green), mild (yellow), moderate (orange), severe (light red) and extremely severe (dark red). Purple asterisks show differences between groups.

When the categorical variable for lifetime history of a depressive disorder was included in the model for the DASS-21 depression subscale, a main effect of diagnosis was detected (ηp2 = 0.07). When the categorical variable for lifetime history of an anxiety disorder was included in the model for the DASS-21 anxiety subscale, a main effect of diagnosis was detected (ηp2 = 0.08). In these two models, main effects of time were retained for depression (ηp2 = 0.24) and anxiety (ηp2 = 0.25). At baseline, those with clinical diagnoses exhibited statistically greater values than those without diagnoses on the DASS-21 depression and anxiety subscales, suggesting the diagnostic cut-off segregated those with lower and higher baseline symptomatology. In those with a diagnosis of depression or anxiety, reductions in depressive or anxiety symptoms were evident at all follow-up time points relative to baseline, with the 12m follow-up point showing a 60% and 64% reduction in depression and anxiety, respectively (Figure 1B and 1D, Table S2). Notably, individuals with either depression or anxiety diagnosis showed significant improvement, with symptoms improving from a moderate to a normal range. They maintained reductions within a normal range throughout the follow-up period, closely approximating the symptom levels of the group without the diagnosis.

Negative and Positive Affect

Significant main effects of time were detected on the PANAS subscales Negative Affect (ηp2 = 0.27) and Positive Affect (ηp2 = 0.09; Table S2), which survived correction (p-FDR<0.01). Relative to baseline, Negative Affect was significantly diminished by 33% at 7d, 32% at 1m, 21% at 6m, and 27% at 12m compared to baseline (Figure 1G). Relative to baseline, Positive Affect was only statistically higher at 7d (Figure 1H, Table S2).

General mental and physical health

A significant main effect of time was detected on the SF-12 Mental Health Component Score (MCS) (ηp2 = 0.21), but not Physical Health Component Score, (p = 0.37). MCS survived correction (p-FDR<0.001). Relative to baseline, significant improvements in mental health were found at 1m, 6m, and 12m. Additionally, mental health showed a significant drop in scores from 1m to 6m but remained significantly higher than baseline at 6m (Figure 1F, Table S3).

Alcohol and Cannabis Use

Significant main effects of time were detected on the ASSIST alcohol risk (ηp2 = 0.16) and cannabis risk scores (ηp2 = 0.20), which survived correction (p-FDR<0.01). Relative to baseline, reductions in alcohol and cannabis total risk scores were detected at 1m, but not subsequent time points (p > 0.38) (Figure 2A–B, Table S3). An effect of time was found on the AUDIT for frequency of alcohol consumption (p-FDR<0.01), which was significantly reduced at 1m and 6m, but not 12m (p > 0.05) (Table S3). An effect of time was also detected on the AUDIT for average alcohol beverages but is not interpreted since there were no significant changes between specific time points (p > 0.29) and it did not survive correction (p-FDR=0.08). No effect of time was observed on the AUDIT for frequency of binge drinking episodes.

Figure 2:

Figure 2:

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ASSIST for (A) Alcohol and (B) Cannabis; BFI for (C) Agreeableness, (D) Negative Emotionality, (E) Open-mindedness, (F) Extraversion, and (G) Conscientiousness; AS for (H) Authentic Living, (I) External Influence, and (J) Self-alienation; (K) GSES total; SBC for (L) Body Awareness and (M) Body Dissociation; (N) Intrinsic Spirituality Scale total; NRS for (O) Total, (P) Self subscale, (Q) Perspective subscale, and (R) Experience subscale; Relationship Satisfaction for (S) Partner, (T) Friends, (U) Children, (V) Parents, (W) Partner’s Parents, (X) Other Family, and (Y) Former Partner. Scores were measured at baseline (BL), and 1 month (1m), 6 months (6m) and 12 months (12m) post-ceremony. BFI = Big Five Inventory; AS = Authenticity Scale; GSES = General Self-efficacy Scale; SBC = Scale of Body Connection; NRS = Nature Relatedness Scale. Estimated marginal means (EMM) with standard errors (SE) are shown with asterisks representing statistical significance levels of * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Wellbeing

Personality

Main effects of time were identified for the BFI personality traits Agreeableness (ηp2 = 0.06), Negative Emotionality (ηp2 = 0.17), and Open-Mindedness (ηp2 = 0.06). Negative Emotionality survived correction (p-FDR<0.001), but Agreeableness (p-FDR=0.066) and Open-Mindedness (p-FDR=0.073) did not. Relative to baseline, trait Agreeableness was significantly higher at 12m; trait Negative Emotionality was significantly lower at 1m, 6m, and 12m; and Open-mindedness was significantly higher at 1m (Figures 2C–G, Table S3).

Generalized Self-efficacy

A main effect of time was detected on the GSES (ηp2 = 0.12) that survived correction (p-FDR<0.01). Relative to baseline, significant increases in self-efficacy were found at 1m and 12m, but not 6m (Figure 2K, Table S3).

Impulsivity

No significant main effects of time were found on the BIS Total Score (p = 0.13) or the BIS subscales Cognitive Impulsivity and Behavioural Impulsivity (p > 0.05).

Relationship Satisfaction

Main effects of time were detected for relationship satisfaction with: friends (ηp2 = 0.08) and partner’s parents (ηp2 = 0.14). Relationship satisfaction with friends survived correction (p-FDR=0.042), but satisfaction with partner’s parents did not (p-FDR=0.066). Relative to baseline, improvements relationship satisfaction with friends and partner’s parents were found at 12m (Figure 2S–Y, Table S3).

Authenticity

Main effects of time were identified on the AS subscales Authentic Living (ηp2 = 0.06), External Influence (ηp2 = 0.09), and Self-alienation (ηp2 = 0.17). External Influence and Self-Alienation survived correction (p-FDR=0.01 and p-FDR<0.001, respectively), but Authentic Living did not (p-FDR=0.063). Relative to baseline, Authentic Living was increased at 12m; External Influence was reduced at 1m, 6m, and 12m; and Self-alienation was reduced at 1m, 6m, and 12m, showing a 50% reduction at 12m (Figure 2H–J; Table S3).

Body Connection

A significant main effect of time was identified on the SBC subscale Body Dissociation (ηp2 = 0.10), but not Body Awareness (p = 0.06) (Figure 2L–M). Body Dissociation survived correction (p-FDR=0.011). Relative to baseline, Body Dissociation was statistically lower at 1m (Table S3).

Relationship with Nature

Significant main effects of time were detected on the NRS subscales Self (ηp2 = 0.08) and Experience (ηp2 = 0.11), but not Perspective (p = 0.09; Figure 2P–R). Experience survived correction (p-FDR=0.032), but Self did not (p-FDR=0.074). Relative to baseline, Self was increased at 6m and Experience was increased at 12m (Table S3).

Spirituality

Significant main effects of time were detected on the ISS (ηp2 = 0.12), which survived correction (p-FDR=0.003). Relative to baseline spirituality was significantly increased at 1m, 6m, and 12m (Figure 2N, Table S3)

Lifestyle

No significant main effects of time were found on BMI (p = 0.14), or vegetable (p = 0.07) or fruit (p = 0.32) consumption (Table S3).

Effects of further ayahuasca use

Significant differences between those reporting/not reporting further ayahuasca consumption were identified in the models for negative emotionality (ηp2 = 0.09), relationship satisfaction (with an intimate partner [ηp2 = 0.13] and parents [ηp2 = 0.10], and fruit (ηp2 = 0.09) and vegetable consumption (ηp2 = 0.24). However, the only significant difference from baseline was in those with no further ayahuasca consumption, who reported greater relationship satisfaction with parents at 12m. Only between-group differences were observed for vegetable consumption and relationship satisfaction. Those who consumed more ayahuasca reported higher vegetable intake at all time points, including baseline, and reported higher parental relationship satisfaction at baseline and the 1-month follow-up (p < 0.05).

Effect sizes

Large effect sizes were observed for depression, anxiety, stress (DASS), and overall mental health (SF12-MCS). Of the well-being measures, constructs encompassing negative mood demonstrated large effect sizes, including subscales for negative affect (PANAS), negative emotionality trait (BFI), body dissociation (SBC), and self-alienation (AS). Additionally, large effect sizes were observed for alcohol and cannabis risk scores (ASSIST), self-efficacy (GSES) and relationships with partner’s parents (RS). Medium effect sizes were observed for other measures of well-being, including positive affect (PANAS), agreeableness and openness (BFI), authentic living and external influence (AS), nature relatedness (NRS), spirituality, and relationships with friends (RS).

Discussion

Despite growing observational evidence for the therapeutic potential of naturalistic ayahuasca consumption, the breadth and durability of improvements remain unclear. This study identified large improvements in mental health and wellbeing that were sustained over a 12-month follow-up period in ayahuasca naive participants. Particularly novel to this study, we found that reductions in depression and anxiety associated with ayahuasca consumption were maintained longer in individuals with a lifetime diagnosis of a depressive or anxiety disorder relative to those without. Ayahuasca use was also associated with a short-term enhancement of positive affect and a sustained reduction in negative affect.

Trajectories of change across the psychological measures were varied, with some effects diminishing, some growing, and others remaining stable over the one-year follow-up period. For example, Body Dissociation was only significantly altered at 1 month, while Nature Relatedness and Relationship Satisfaction were only significantly different from baseline at later assessments. Significant changes in Negative Emotionality, External Influence, Self-alienation, and Spirituality were maintained across the entire follow-up duration, raising the possibility that these are stable (trait) changes. The effect sizes for most of these well-being measures were moderate in magnitude, and generally not as robust as the large effect sizes observed on the mental health measures.

Our findings contribute to the literature suggesting that structured use of ayahuasca may have therapeutic effects on psychopathology. Clinical and naturalistic studies have reported antidepressant and anxiolytic effects in healthy and psychiatric samples, ranging from 7 days to 6 months after consumption (Jiménez-Garrido et al., 2020; Palhano-fontes et al., 2019; Ruffell et al., 2021). One small study identified reductions in depression symptoms up to 12 months in clinically depressed patients (van Oorsouw et al., 2022b). Another study at the Takiwasi ayahuasca center in Peru reported significant reductions in depression, anxiety, and alcohol use at 12 months (Rush et al., 2023), but was confounded by the multifactorial treatment program and long length of treatment (27.9 weeks). Cross-sectional research supports a negative relationship between frequency of ayahuasca consumption and level of alcohol and drug use, but longitudinal studies are scant (Perkins, Opaleye, et al., 2023). Although decreases in alcohol and cannabis use were detected one month after ceremony, none of the subsequent time points were significant from baseline. Participants exhibited low-risk alcohol use and moderate-risk cannabis use at baseline, which may have presented floor effects. Combined with the small sample size, the analysis may have been underpowered but the effect sizes hint toward large effects.

Changes across wellbeing measures were in a direction associated with adaptive functioning and improved mental health. For instance, links have been established between mental health and lower Neuroticism and greater Agreeableness (Strickhouser & Zell, 2017); wellbeing and Nature Relatedness (Grabowska-Chenczke et al., 2022); life satisfaction and Interpersonal Relationships (Froh et al., 2007); and lower prevalence of mental illness and Self-efficacy (Andersson et al., 2014). Similarly, the Authenticity Scale subscales correlate strongly with mental health challenges, with External Influence and Self-alienation being positively correlated, and Authentic Living being negatively correlated (Grijak, 2017). Thus, the observed decreases in Negative Emotionality, External Influence, and Self-Alienation, and contemporaneous increases in Relationship Satisfaction, Nature Relatedness, and Self-efficacy might reflect a pattern of improved adaptive functioning and mental health. For example, reduced self-alienation and greater relationship satisfaction support meaningful social connections that foster resiliency toward changing environmental, social, and economic conditions. Further, reduced external influence and greater self-efficacy and connection to nature may improve one’s ability to handle stress, recover from adversity, and maintain overall mental health.

Multiple studies have reported alterations in personality structure after naturalistic ayahuasca use characterized by increases in Agreeableness, Open-mindedness, Conscientiousness, and Extraversion, and decreases in Neuroticism (analogous to Negative Emotionality) (Kiraga et al., 2021; Netzband et al., 2020; Perkins et al., 2022; Weiss et al., 2021). Our findings are partially consistent with these reports, although we did not observe significant changes in Conscientiousness or Extraversion, and increases in Open-mindedness and Agreeableness did not survive correction. Here, we found that personality traits undergo dynamic shifts across time, with numerical increases in Open-mindedness only at the 1 month assessment, increases in Agreeableness only at the 12 month assessment, and significant decreases in Negative Emotionality across the entire follow-up duration. Personality traits qualitatively displayed distinct linear, quadratic, and cubic relationships with time (see Figure 2).

Ayahuasca has also been associated with changes in other psychological constructs and health-related behaviours. Studies point toward enhanced spirituality, nature relatedness, self-efficacy, body connection, and interpersonal relationships (Bathje et al., 2021; Harris & Gurel, 2012; Kaasik & Kreegipuu, 2020; Perkins, Ruffell, et al., 2023; Ruffell et al., 2024), and positive lifestyle and health-related behaviours, including diet (Perkins, Opaleye, et al., 2023). The present study extends this work by demonstrating persisting increases in self-efficacy, nature relatedness, and relationship satisfaction with friends that lasted up to 12 months. Nonsignificant changes in body awareness and impulsiveness suggest some constructs may not be affected by ayahuasca treatment. Further, the absence of changes in some health-related behaviours (i.e., body mass index, vegetable and fruit consumption, and physical activity) is in contrast to several cross-sectional studies (Kohek et al., 2023; Perkins, Opaleye, et al., 2023).

Limitations

This study has notable limitations. First, a comparison group was not utilised and therefore the potential influence of demand characteristics and elapsed time on treatment effectiveness cannot be ruled out. Non-pharmacological factors (e.g., ceremony, community, etc.), likely contribute to the effects observed in this study (Perkins, Schubert, et al., 2021; Uthaug et al., 2021). Selection and attrition biases are inherent to research and restrict the generalisability of results. Partially mitigating this concern, 81.8% and 63.6% of the original sample were retained for primary mental health measures at months 1 and 12, respectively. Further, linear mixed models were fitted for missing outcome data and have been shown to provide correct inferences (Schafer & Graham, 2002). Another limitation is the use of self-report measures and lack of expectancy data and total frequency of ayahuasca use, which preclude conclusive evidence. However, broad coverage and converging results across mental health measures support the validity of these findings.

Future Research

Randomized clinical trials using objective measures are needed to elucidate psychological mediators and moderators of therapeutic action, and to disentangle the temporal dynamics and causal mechanisms of ayahuasca-induced trait changes.

Conclusion

This study identified long-term improvements in mental health and wellbeing outcomes following naturalistic ayahuasca consumption among first-time users with relatively poor mental health at baseline.

Supplementary Material

1

Acknowledgements

We thank the facilitators and participants of this study for their time and effort in taking part in the research.

Declaration of Funding

BAP is a postdoctoral fellow in the NYU Langone Psychedelic Medicine Research Training program and was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number TL1TR001447. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. MPB has received research funding from Mind Medicine, Inc., Tilray Canada, MAPS-PBC, B.More, Inc., the Heffter Research Institute, the Turnbull Family Foundation, the Fournier Family Foundation, Dr. Bronner’s Family Foundation, Bill Linton, and the Riverstyx Foundation. MPB is director of the NYU Langone Center for Psychedelic Medicine Research and Training Program, funded by MindMed.

Footnotes

Declaration of Conflicting Interests

DP, JS and AH hold equity in a commercial entity, Psychae Therapeutics, which is undertaking research with psychedelic compounds and DP and JS are co-CEOs of the same organisation. MPB serves on the Advisory Board of Ajna Labs LLC, Journey Colab, and Bright Minds Biosciences, Inc. MPB is named as inventor on patent applications relating to the use of psilocybin for alcohol use disorder but has waived all rights and has no prospect of financial benefit.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, DP, upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

1
NIHMS2059532-supplement-1.pdf (270.2KB, pdf)

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, DP, upon reasonable request.

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