Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities
This observational study (n=25) found that ayahuasca intake led to significant increases in mindfulness comparable to those obtained after extensive mindfulness practice. The authors argue that this effect may be the mediating factor responsible for ayahuasca's observed therapeutic potential.
Abstract
Background: Ayahuasca is a psychotropic plant tea used for ritual purposes by the indigenous populations of the Amazon. In the last two decades, its use has expanded worldwide. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested its therapeutic potential, reporting that its use has helped individuals abandon the consumption of addictive drugs. Furthermore, recent open-label studies in patients with treatment-resistant depression found that a single ayahuasca dose induced a rapid antidepressant effect that was maintained weeks after administration. Here, we conducted an exploratory study of the psychological mechanisms that could underlie the beneficial effects of ayahuasca.Methods: We assessed a group of 25 individuals before and 24 h after an ayahuasca session using two instruments designed to measure mindfulness capacities: The Five Facets Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ).Results: Ayahuasca intake led to significant increases in two facets of the FFMQ indicating a reduction in judgmental processing of experiences and in inner reactivity. It also led to a significant increase in decentering ability as measured by the EQ. These changes are classic goals of conventional mindfulness training, and the scores obtained are in the range of those observed after extensive mindfulness practice.Conclusions: The present findings support the claim that ayahuasca has therapeutic potential and suggest that this potential is due to an increase in mindfulness capacities.
Research Summary of 'Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities'
Introduction
Ayahuasca is a traditional Amazonian psychotropic brew made from Banisteriopsis caapi (containing MAO-inhibiting β-carbolines such as harmine and tetrahydroharmine) combined with leaves that contain N,N-dimethyltryptamine (DMT). The β-carbolines prevent gastrointestinal breakdown of DMT, allowing oral psychoactivity; DMT acts at 5-HT2A and 5-HT1A receptors and interacts with the sigma-1 receptor. Interest in ayahuasca has grown because acute administration produces introspective, dream-like experiences with visions and autobiographical emotional memory retrieval, and observational and open-label studies have reported potential benefits for substance use disorders and treatment‑resistant depression. However, the psychological mechanisms underlying these putative therapeutic effects are poorly understood. Soler and colleagues designed an exploratory study to test whether a single ayahuasca session acutely enhances mindfulness-related capacities. The investigators hypothesised that aspects of the ayahuasca experience—particularly a detached perspective on thoughts and emotions—overlap with constructs targeted by secular mindfulness practice, such as non-judgement, non-reactivity, and decentering; they therefore assessed mindfulness measures before and 24 hours after ayahuasca intake to examine short-term changes in these capacities.
Methods
Participants were recruited via networks of ayahuasca users and acquaintances, yielding 25 volunteers (14 females) with mean age 43.6±12 years and mean education 15±4 years. Exclusion criteria included current psychiatric disorder, alcohol or substance use disorders, and significant medical illness; no formal screening for past psychiatric diagnoses was reported. Twenty-three participants had prior ayahuasca experience (mean 79 prior uses, range 1–500) and two were ayahuasca‑naïve. All participants abstained from ayahuasca for at least 15 days prior to assessment and avoided alcohol, medications, and other drugs on the day before and for 24 hours after the session. The study took place in a non-religious, dimly lit setting with recorded music; experimenters were present and administered questionnaires before and after the session. Participants recorded the total ingested volume and provided samples for alkaloid analysis. Alkaloid concentrations were measured using liquid chromatography–electrospray ionisation–tandem mass spectrometry. Based on assays, the mean ingested DMT dose was 43.6 mg (range 28.82–69.81 mg), described by the authors as a moderate dose relative to their laboratory studies. Psychological assessments were completed during the 24 hours before the session (participants were instructed to answer as they normally felt in the absence of psychoactive substances) and again covering the 24 hours after the session. Mindfulness-related outcomes comprised the Five Facet Mindfulness Questionnaire (FFMQ), which yields subscales for Observe, Describe, Acting with Awareness, Non-judging, and Non-reacting, and the Experiences Questionnaire (EQ), which measures decentering. Internal consistency in this sample was reported: FFMQ Cronbach's α 0.83 pre- and 0.86 post-intake, EQ α 0.88 pre- and 0.94 post-intake. The investigators also calculated the MINDSENS Composite Index, a combined score of FFMQ and EQ items previously shown to be sensitive to meditation practice. For analysis, scores on MINDSENS, the five FFMQ subscales, and EQ were compared before versus after ayahuasca using repeated-measures ANOVAs with session (pre vs post) as the within-subjects factor. Given variability in prior ayahuasca exposure, a secondary analysis introduced the number of previous ayahuasca uses as a covariate in the repeated-measures ANOVA. The study was exploratory and no correction for multiple comparisons was applied; significance was set at p<0.05.
Results
The MINDSENS composite index increased significantly 24 hours after the ayahuasca session (F(1,24)=6.78, p=0.016). On the EQ, which measures decentering, scores also showed a significant pre-to-post increase (F(1,24)=8.55, p=0.007). Within the FFMQ, two subscales demonstrated significant increases after ayahuasca: Non-judging of inner experience (Non-Judge; F(1,24)=7.86, p=0.010) and Non-reactivity to inner experience (Non-React; F(1,24)=5.06, p=0.034). The remaining three FFMQ facets did not show significant change in the reported analyses. When prior experience with ayahuasca was entered as a covariate, the overall pattern of findings remained. The MINDSENS effect persisted (F(1,23)=5.26, p=0.031). Inclusion of prior use altered the test statistics for other outcomes: EQ scores retained a statistically significant pre‑to‑post increase (F(1,23)=6.45, p=0.018), while the significance of the FFMQ Non-Judge and Non-React comparisons increased (Non-Judge F(1,24)=8.39, p=0.008; Non-React F(1,24)=5.06, p=0.009). The authors report that despite shifts in F and p values, the overall pattern—acute increases in decentering and in acceptance-related facets—was unchanged.
Discussion
Soler and colleagues interpret their findings as evidence that a single ayahuasca session can produce rapid increases in several mindfulness-related capacities, specifically reductions in judgmental processing and in inner reactivity, together with enhanced decentering. They propose that these changes—attitudinal aspects of mindfulness often described as acceptance and defusion from thoughts and emotions—may constitute a psychological mechanism contributing to previously reported therapeutic effects of ayahuasca in addiction and depression. The investigators note that their sample was not affiliated with ayahuasca religions and that the results therefore support the possibility that ayahuasca itself, rather than ritual membership, can enhance mindfulness capacities. They compare post‑ayahuasca scores with values reported for experienced meditators and observe close correspondence on several measures (for example, EQ and MINDSENS scores), arguing that pharmacological intervention may produce changes similar to those of formal meditation practice. The authors further situate their results within broader psychedelic research, noting parallels with findings on psilocybin and LSD and with neuroimaging evidence of acute modulation in regions such as the amygdala and anterior cingulate cortex; they also reference structural differences reported in long-term ayahuasca users in default mode network regions such as the posterior cingulate cortex. Key limitations acknowledged by the authors include the exploratory design, small and self-selected sample, and substantial prior ayahuasca exposure in most participants, which could produce ceiling effects or limit generalisability. They also highlight the absence of a control group, the lack of rigorous exclusion for past psychiatric diagnoses, and the fact that only a single dose was tested despite dose-dependent subjective effects. The authors argue that FFMQ facets and decentering are relatively stable over time, making spontaneous fluctuation an unlikely explanation for the observed changes, but recommend future randomised controlled trials, dose–response studies, and investigations of the durability of effects and efficacy in clinical populations. Overall, the study team concludes that the data provide preliminary support for ayahuasca's therapeutic potential via increases in mindfulness-related capacities and call for further research to corroborate and extend these findings.
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INTRODUCTION
Ayahuasca is a psychotropic beverage prepared by infusing in water the stalk of Banisteriopsis caapi together with the leaves of Psychotria viridis (Rubiaceae) or Diplopterys cabrerana (Malpighiaceae). This tea has been used for centuries in Amazonian traditions for ritual and medical purposes, and more recently, its use has extended to North American and European countries. B. caapi contains β-carboline alkaloids, mainly harmine, tetrahydroharmine (THH), and to a lesser extent, harmaline. These alkaloids show monoamine-oxidase (MAO) inhibiting properties, while THH is also a serotonin reuptake inhibitor. The leaves of P. viridis and D. cabrerana, the most common admixtures used in ayahuasca preparation, contain the psychedelic indole N,N-dimethyltryptamine or DMT. DMT is structurally related to the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) and shows agonist activity at the 5-HT 2A and 5-HT 1A receptors. More recently, it has been shown that DMT also interacts with the sigma-1 receptor. DMT induces intense modifications of the ordinary state of awareness when administered parenterally, but it is devoid of psychoactivity when ingesteddue to degradation by MAO) and cytochrome-dependent mechanisms. Ayahuasca is a remarkable ethnopharmacologic combination in which the presence of the MAO-inhibiting β-carbolines prevents the gastrointestinal degradation of DMT, allowing its access to systemic circulation and the CNS. Ayahuasca is receiving increased attention from the general public and biomedical researchers for its therapeutic potential. Acute administration induces an introspective dream-like experience characterized by visions and autobiographic and emotional memories. Studies of long-term users have suggested that ayahuasca may have beneficial effects for individuals with substance use disorders. Reports of decreased consumption of alcohol, cocaine, and other addictive drugs are common in regular ayahuasca users. Ayahuasca may also have potential to treat other psychiatric conditions. In a recent pilot study conducted in patients with treatmentresistant depression, the authors reported a rapid-onset antidepressant effect that was maintained weeks after administration of the single dose. These results have been replicated using a larger patient sample. Despite these initial reports of beneficial psychological effects and of amelioration of some forms of psychopathology, little is know with regard to the psychological mechanisms that may underlie these effects. Several aspects of the ayahuasca-induced subjective experience are analogous to the experience of mindfulness practice as understood by contemporary Western psychological conceptualizations. Although mindfulness is a complex construct difficult to define, from a secular perspective, being Bmindful^entails a particular quality of awareness, that is present-centered, non-reactive, characterized by openness, acceptance, and by a non-judgmental stance towards the experience (Kabat-Zinn 1990;. Another construct, closely related to mindfulness is the notion of Bdecentering^. Decentering or Bdefusion^is the ability to take a detached view of one's own thoughts and emotions considering them as impermanent events of the mind). The analogy is based on the following: First, studies on the phenomenology of the ayahuasca experience emphasize the detached view of one's own thoughts and emotions that the substance elicits. Increasing this capacity is the goal of mindfulness interventions. The recollection of highly emotional events simultaneous with a detached view of these events, as induced by ayahuasca, may help the reprocessing of emotional experiences. Second, both ayahuasca and mindfulness practice seem to induce similar effects on other domains including increased awareness, changes in selfperspective, decreased hopelessness, and positive impact on general well-being). Based on the common aspects of the ayahuasca experience and mindfulness practice, the present study aimed to further understand the psychological experience induced by ayahuasca and to explore if an enhancement of mindfulness-related capabilities could be achieved through ayahuasca use. To this end, we assessed the effects of the intake of a single dose of ayahuasca on several mindfulness-related measures.
EXPERIMENTAL PROCEDURES
Participants and study procedure The investigators contacted circles of individuals involved in ayahuasca use and explained to them the goals and methods of the study. Contacts were asked to pass the information to their acquaintances and a sample of 25 individuals (14 females) was recruited. Exclusion criteria included current psychiatric disorder and alcohol or other substance use disorders and evidence of current significant medical illness. Their mean±SD age was 43.6±12 years, and were relatively well-educated, with an average 15±4 years of education. They all have an interest in psychoactive drugs for personal experimentation. Twenty-three had prior experience with ayahuasca, having taken it on average 79 times (range 1-500). The other two took it for the first time in the course of the study. All participants had abstained from ayahuasca for at least 15 days before assessment and neither consumed alcohol, medications, or any other drugs in the day prior to ayahuasca intake nor in the 24 h thereafter. Ayahuasca was taken in a non-religious setting, and participants were not affiliated to any ayahuasca religion. The main motivation of the participants was to use ayahuasca as a tool for self-knowledge and introspection. Ayahuasca was taken in a dimly lit room, with participants sitting or lying down on mattresses. Recorded music was played throughout the session, and participants could freely leave the room to go to the bathroom or to a room next door if they wished to stay on their own for some time. Experimenters were present before, during, and after the ayahuasca session and directly administered the questionnaires to the participants. The study was conducted in accordance with the Declaration of Helsinki and subsequent amendments concerning research in humans and was approved by the Sant Pau Hospital Ethics Committee. All volunteers gave their written informed consent to participate. Participants were requested to first respond to the questionnaires described below during the 24 h prior to the ayahuasca session they had planned to attend. They were instructed to respond to the pre-intake questions indicating how they normally felt and acted in the absence of any psychoactive substance. Following the ayahuasca session, they were again asked to respond to the questions indicating how they have felt and acted in the 24 h thereafter. Participants recorded the total volume of ayahuasca ingested by each individual during the session and facilitated samples for analysis. Alkaloid concentrations were determined using a previously described method implementing liquid cromatography-electrospray ionization-tandem mass spectrometry). Based on the analysis, participants ingested on average 43.6-mg DMT (range 28.82-69.81), a moderate dose as compared to the dosages used in a laboratory by our group.
MEASURES
Mindfulness facets were assessed using the following psychometric instruments: The Five Facet Mindfulness Questionnaire. The FFMQ measures five different factors: (1) Observe: noticing external and internal experiences, e.g., body sensations, thoughts, or emotions; (2) Describe: putting words to, or labeling the internal experience; (3) Acting with awareness: focusing on the present activity instead of behaving mechanically; (4) Non-judging the inner experience: taking a nonevaluative stance towards the present experience, thoughts, or emotions; and (5) Non-reacting to the inner experience: allowing thoughts and feelings to come, without getting caught up in, or carried away, by them. Sample items for each sub-scale include the following: Observe BWhen I take a shower or bath, I stay alert to the sensations of water on my body^; Describe BI'm good at finding words to describe my feelings^; Acting with awareness BI am easily distracted^; Non-judging BI tell myself I should not be feeling the way I am feeling^; and Non-reacting BI watch my feelings without getting lost in them^. Participants were asked to rate the degree of concordance with each statement on a 5-point Likert scale that ranges from 1 (never or very rarely, true) to 5 (very often or always, true). The FFMQ has shown adequate psychometric properties in both non-clinical and clinical samples. Cronbach's α for the Spanish version of FFMQ range from 0.8 to 0.91, and the internal consistency of the scale in our sample was of 0.83 and 0.86 (pre-and post-intake, respectively). The Experiences Questionnaire or EQ). This instrument comprises 11 items and measures Bdecentering^, defined as the capacity to observe one's thoughts and emotions as temporary events of the mind. The EQ items are scored in a 5-point-Likert-type scale, ranging from never to all the time, with higher scores indicating more decentering. Sample items include the following: BI can observe unpleasant feelings without being drawn into themô r BI can separate myself from my thoughts and feelings^. The Spanish version of the EQ has demonstrated good psychometric properties, including internal consistency in clinical and non-clinical samples. Internal consistency in our sample was 0.88 at pre-intake and 0.94 at post-intake). To explore if the changes induced by ayahuasca could be comparable to those induced by meditation practice, the MINDSENS Composite Index was also calculated). This index includes those FFMQ and EQ items that have proven to be the most sensitive to meditation practice and to discriminate accurately between meditators and no-meditators).
DATA ANALYSIS
Scores on the composite MINDSENS index, the five FFMQ subscales, and the EQ questionnaire were analyzed using repeated-measures analyses of variance (ANOVAs) with ayahuasca session (before vs. after) as factor. Additionally, in view of the high variability in the degree of previous experience with ayahuasca (from 0 to 500 times), a second analysis was conducted introducing this value as a covariate in the repeated-measures ANOVA. Given the exploratory nature of the present study, no formal correction for multiple comparisons was carried out. Results were considered significant for p values <0.05.
RESULTS
Figureshows the scores obtained for the study variables before and 24 h after the ayahuasca session. The MINDSENS composite index showed a statistically significant increase following the ayahuasca session (F(1,24)=6.78, p=0.016). The analysis of the individual questionnaires showed a significant effect of ayahuasca session on the EQ score (F(1,24)=8.55, p=0.007). Two of the five subscales of the FFMQ also showed significant increases in the 24 h following ayahuasca: Non-Judge (F(1,24)=7.86, p=0.010) and Non-React (F(1,24)=5.06, p=0.034). The introduction of the prior experience with ayahuasca as a covariate in the analysis did not greatly modify the results for the MINDSENS composite index (F(1,23) =5.26, p=0.031). However, it decreased significance of changes on the EQ questionnaire score (F(1,23)=6.45, p=0.018) and increased significance of the pre-vs. post-comparison of scores on the FFMQ Non-Judge (F(1,24)=8.39, p=0.008) and Non-React (F(1,24)=5.06, p=0.009) subscales. Despite the changes in F and p values, the overall pattern of results remained unchanged.
DISCUSSION
By exploring the effects of ayahuasca intake on mindfulness capacities, the present study aimed to better understand the psychological mechanisms underlying the therapeutic potential of ayahuasca. Our findings indicate that ayahuasca intake leads to a rapid increase in several mindfulness-related parameters. Two FFMQ facets changed after ayahuasca, suggesting a decrease in the judgmental processing of personal experiences, along with a reduction in inner reactivity. Additionally, decentering ability was also increased after ayahuasca intake. These combined modifications provide an explanatory mechanism that could contribute to the beneficial effects reported for ayahuasca in the treatment of addiction and depression. It is worth mentioning that prior studies showing benefits associated with long-term ayahuasca use have the confounding factor of participants being members of a religious group. The present results obtained in a lay setting support the notion that ayahuasca may have therapeutic potential per se in the absence of the religion confound. The scores in some mindfulness capacities observed after ayahuasca are analogous to those of experienced meditators). Thus, Soler and colleagues report the following average scores in their experienced meditator sample: BNon-react^, 24.84; BNon-judge^, 30.61; EQ, 41.07; and MINDSENS, 3.70. These values are very close and in some cases lower than those obtained here in the post-ayahuasca assessment: BNon-react^, 25.56; BNon-judge^, 33.16; EQ, 41.41; MINDSENS, 3.66. The similar values obtained in the MINDSENS are a relevant finding. The MINDSENS index was created with those FFMQ and EQ items that were more sensitive to meditation practice. This index is sensitive to several aspects of meditation practice, i.e., to the overall years of practice and to the frequency and length of meditative sessions). Our study indicates that improvements in mindfulness capacities are not exclusive of mindfulness meditation practice, as they can also be obtained by a pharmacological intervention. Our results showed that not all mindfulness facets are equally affected by ayahuasca. Analogously, previous studies comparing meditators vs. non-meditators suggested that not all mindfulness facets are equally modified by practice. For example, in a study comparing a large sample of meditators (n=384) to individuals without meditative experience (n = 286), the first group scored significantly higher in all FFMQ facets and decentering. However, certain facets such as BObserve^, BNon-react^, and BDecenteringâ ppear to be more sensitive than the others to formal meditation practice. Increased ability to BObserve^has been pointed out as essential capacity of meditating individuals. Out of the five facets of the FFMQ, significant changes were observed in the BNon-judge^and BNon-react^facets. Mindfulness is considered a two-factor construct comprising both attentional and attitudinal elements). The BNon-judge^and BNon-react^subscales are considered to measure acceptance). Thus, ayahuasca would particularly foster acceptance of the thoughts and feelings experienced by the individual. This increased self-acceptance could contribute to the therapeutic effects of ayahuasca, as suggested by Thomas. Indeed, a state of increased self-acceptance would be clinically useful, since the attitudinal component of mindfulness, rather than the attentional, appears to be particularly impaired in patients with psychopathology. The ayahuasca experience may induce an introspective exposure to emotional memories, similar to that used in emotional reprocessing interventions. As intended in such interventions, the use of ayahuasca may promote a detached relationship with one's own emotions. This detached manner of approaching the inner experience has been defined as Bdecentering^or Bdefusion^, understood as the metacognitive ability to take a detached view of one's own thoughts and emotions. It allows patients to consider thoughts and emotions as objective temporary events of the mind, rather than statements that are necessarily true. Deficits in decentering have been postulated as a transdiagnostic index of psychopathology. Compared to healthy controls, it is diminished in individuals with cocaine use disorders, eating disorders, major depression, and borderline personality disorder. Increases in decentering have been observed after cognitive behavioral therapy for depression and also after mindfulness-based interventions. Similar to a study in which increases in decentering were reported in a group of patients responding to antidepressant treatment, our data show that psychotropic substances, in our case ayahuasca, can also enhance this ability. Increases in this capacity would explain findings suggesting that ayahuasca has therapeutic effects in depression, a disorder in which the decentering capacity is impaired. Our results are in line with the recent research exploring the therapeutic potential of other psychedelic 5-HT 2A agonists, substances which in recent years are receiving renewed attention in psychiatry. For instance, psilocybin was safely administered to advanced-stage cancer patients and proved effective in reducing anxiety and depressive symptoms related to illness. Promising results have also been reported for lysergic acid diethylamide (LSD), another classic psychedelic. From a mechanistic perspective, these drugs show modulatory activity on the amygdala and the anterior cingulate cortex following acute administration). These areas are key structures of the emotional brain and their function is deregulated in affective disorders. Regular use of psychedelics has also been associated with differences in brain structure relative to non-users. In a study assessing long-term ayahuasca users, the authors found thinning in the posterior cingulate cortex (PCC), a key hub of the default mode network. Thinning in the PCC inversely correlated with prior use of ayahuasca and with scores on self-transcendence. This personality trait, which comprises religiousness, spirituality, and transpersonal feelings, was higher in ayahuasca-using subjects. No differences were found with controls with regard to neuropsychological functioning or indicators of psychopathology. This finding suggested that regular ayahuasca use may lead to default mode network deactivation, which is overactive in depression. Analogously, conventional mindfulness practice also has an impact on the default mode network, indicating further commonalities between the ayahuasca experience and mindfulness training. Although to our knowledge, studies with other psychedelics have not specifically examined modifications in mindfulness capacities, it is possible that psilocybin and LSD also show these facilitating effects. Future studies with these substances should explore this possibility. The current findings should be taken as preliminary, as the study was intended as exploratory and has some limitations that need to be considered. First, the characteristics of the participant sample and its relatively limited size could be biasing our results. Prior exposure to ayahuasca may have led to a ceiling effect, as suggested by the increases in significance obtained in the repeated measures ANCOVA for BNon-Judge^and BNon-react^subscales. On the other hand, it can be argued that the fact that a single ayahuasca dose increases mindfulness capacities in experienced users who were already more Bmindful^than the general population (as shown for instance by the EQ pre-administration values), underscores the power of ayahuasca to enhance these abilities even when the baseline level is high. Although participants manifested being free of any current psychiatric or medical condition, no rigorous criteria were applied to exclude subjects with past diagnoses of mental disorders. The absence of a control group also limits the generalization of the present findings. However, FFMQ facets and decentering appear to be stable over time). This makes it unlikely that our results are due to natural fluctuations of these variables, rather than the consequence of ayahuasca intake. Lastly, only one dose of ayahuasca was ingested, although the subjective effects of ayahuasca are dose-dependent. Future studies should explore the impact of different doses and be conducted using randomized controlled designs. In summary, the present study provides evidence supporting the claim that ayahuasca has therapeutic potential. The present findings additionally suggest that this is due to increases in mindfulness-related capacities. Further research is warranted to corroborate these results, to test whether the benefits induced by ayahuasca on mindfulness capacities are maintained over time. Positive results would argue strongly in favor of conducting studies involving psychiatric populations.
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Study Details
- Study Typeindividual
- Populationhumans
- Characteristicsobservational
- Journal
- Compound
- Author