Using quantitative textual analysis of open-ended reports from first-time ayahuasca users (9 with treatment-resistant depression, 20 healthy controls), the study identified five core experiential clusters—altered states of consciousness, cognitive changes, somatic alterations, auditory experiences and visual perceptual content—and found that participants with depression reported more aversive bodily reactions. These findings align with central axes of the psychedelic experience and may inform therapeutic applications of ayahuasca.
Ayahuasca is a brew with psychoactive properties that has been used as an entheogen for centuries, with more recent studies suggesting it is a promising treatment for some clinical disorders. Although there is an emerging scientific literature on its effects, to the best of our knowledge no study has explored the self-reported experiences of first-time ayahuasca users with quantitative textual analysis tools. Accordingly, the current study aimed to analyze the subjective experience of naive individuals with depression and healthy controls after consuming ayahuasca. For this purpose, responses from a subsample of participants from a previous clinical trial to open-ended questions regarding their experience with ayahuasca underwent textual analysis. Data from nine patients with treatment-resistant depression and 20 healthy individuals were included, and quantitative textual analysis was performed using IRaMuTeQ 0.7 alpha 2 and R 3.1.2. The analysis identified five clusters: alterations in the state of consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Additionally, findings suggest specific features of the experience of people with depression with ayahuasca, such as increased aversive bodily reactions. The results are consistent with previous findings indicating central axes of the psychedelic experience, and may inform therapeutic approaches using ayahuasca.
Cruz and colleagues situate their work in the context of growing clinical interest in ayahuasca, a traditional brew containing N,N-DMT and beta-carboline alkaloids, which has been investigated for potential therapeutic effects in mood and substance-use disorders. Earlier clinical trials have reported reductions in depression severity after ayahuasca dosing, and qualitative studies have described a range of subjective phenomena—visual visions, somatic purging, insights, and spiritual or cultural themes—but no prior study has applied quantitative textual-analysis tools to first-time ayahuasca users to compare clinical and non-clinical groups. The current study therefore aims to quantitatively characterise the self-reported acute experiences of ayahuasca-naïve individuals with treatment-resistant depression and healthy controls. Using transcribed, open-ended reports collected shortly after a single dosing session in a controlled setting, the investigators apply automated textual-analytic methods to identify recurring thematic clusters and to examine associations between those clusters and sociodemographic or clinical variables. The work seeks to illuminate how ‘set’ (pre-existing psychological state) and setting may shape subjective experience, with implications for therapeutic applications of ayahuasca.
Papers cited by this study that are also in Blossom
Santos, R. G., Landeira-Fernandez, J., Strassman, R. J. et al. · Journal of Ethnopharmacology (2007)
O'shaughnessy, D. M., Berlowitz, I., Rodd, R. et al. · Therapeutic Advances in Psychopharmacology (2021)
Bouso, J. C., González, D., Fondevila, S. et al. · PLOS ONE (2012)
Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)
The data derive from a subsample of participants in a previously reported randomised, double-blind, placebo-controlled clinical trial of ayahuasca in adults 18–60 years old with treatment-resistant depression. For the present analysis only participants who received ayahuasca were included: nine patients with treatment-resistant depression and 20 healthy individuals, all naïve to ayahuasca and other classical psychedelics. Exclusion criteria included current medical conditions, pregnancy, neurological disease, bipolar disorder or schizophrenia, history of mania/hypomania, and substance abuse. The extracted text does not clearly report recruitment dates or additional trial-site details beyond affiliation with a university hospital setting. Each participant received a single oral dose of ayahuasca calculated as 1 mL/kg from a single batch whose mean concentrations (± SD) were reported for N,N-DMT (0.36 ± 0.01 mg/mL), harmine (1.86 ± 0.11 mg/mL), harmaline (0.24 ± 0.03 mg/mL), and tetrahydroharmine (1.20 ± 0.05 mg/mL). The placebo was a liquid designed to mimic colour and flavour. During dosing, participants were instructed to remain silent with eyes closed and were provided a predefined music playlist; two researchers were available in an adjacent room for support. Primary and secondary clinical outcomes reported in the parent trial were changes in HAM-D and MADRS scores at specified post-dosing days, but the current paper focuses on open-ended experiential reports collected approximately 4 hours after ingestion, once acute effects had subsided. Interviews began with the prompt “Can you please freely describe your experience?” and lasted on average 13.7 minutes. Reports were audio-recorded, transcribed, proofread, and cleaned of certain punctuation to facilitate automated analysis. The textual corpus was built in Brazilian Portuguese and later translated for reporting. Sociodemographic and clinical variables were coded and dichotomised for association testing; missing values were treated as null. Quantitative textual analysis used IRaMuTeQ 0.7 alpha 2 and R 3.1.2. Methods included Descending Hierarchical Analysis (DHA, Reinert method), Specificities analysis, and Correspondence Factor Analysis (CFA). Texts were segmented (default 40 words per text segment), and DHA partitioned the corpus into clusters based on word frequency and association. Inclusion criteria for words in clusters required frequency above the corpus mean and a chi-square with the cluster greater than 3.84 (p < 0.05, df = 1). The authors analysed active word forms (nouns, verbs, adjectives, adverbs, pronouns, and unrecognised forms). Cramer's V was used to report effect sizes for word–cluster associations and α was set at 0.001 to limit type I error. The text indicates ethical approval and compliance with relevant standards and the Helsinki declaration, but the extraction truncates the full ethics statement.
The textual corpus comprised 869 text segments (TS), 2,968 distinct words occurring 29,029 times (mean occurrences per TS = 33.41). Active word forms numbered 1,829, of which 691 had a frequency ≥ 3. DHA retained 75.03% of the corpus for cluster analysis and produced five thematic clusters. Cluster labels and relative representation (as presented in the paper) were: Cluster 1 "Alterations in the state of consciousness" (~15.2% of TS), Cluster 2 "Cognitive changes" (~14.6% of TS), Cluster 3 "Somatic alterations" (~18.1% of TS), Cluster 4 "Auditory experiences" (~29.4% of TS), and Cluster 5 "Visual perceptual content" (~22.1% of TS). For the five most associated words per cluster, Cramer's V indicated associations ranging from small to medium effect sizes and, in Cluster 2, larger effects; exact Cramer's V values are not provided in the extracted text. Cluster content and notable associations were reported as follows. Cluster 1 included words tied to onset and phenomenology of altered consciousness, with strong co-occurrence of "eye" with "open" and "close", and terms such as "sleep", "slow", "nap", "dream", and temporal words like "hour". Middle-aged participants showed a small association with this cluster. Cluster 2 grouped cognitive-process words—"remember", "question", "look", "understand"—and comparative terms such as "same", alongside perceptual qualifiers like "blurred" and "strange"; small associations were observed with male gender, higher income, and past cannabis use. Cluster 4 was dominated by auditory and music-related vocabulary—"music", "speak", "listen", "sound", "silence", "voice"—and captured both positive and negative reactions to music (for example, "relax" versus "bother"). Female participants and those reporting no religion were more strongly associated with this cluster. Cluster 3 contained somatic and often aversive bodily terms—"vomit", "pain", "bathroom", "hungry", "stomach", "breathe", "dizziness"—and was uniquely associated with a diagnosis of depression, suggesting greater reporting of negative somatic experiences among depressed participants. Cluster 5 encompassed visual content with central words such as "see" linked to "colour" and specific colours, and human-like figures (e.g. "puppet", "woman") with actions like "dance" or "jump"; this cluster showed neutral-to-positive valence (e.g. links between "see" and "beautiful") and was associated with participants without depression, as well as with low income, living alone, and non-tobacco use. Correspondence Factor Analysis indicated that Clusters 1, 2, and 4 were closely related in a common area of the factor space, whereas Clusters 3 and 5 occupied more isolated positions. The Specificities analysis mapped co-occurrence communities among words, but specific numeric indices from that analysis are not reported in the extracted text.
Cruz and colleagues interpret the five clusters as reflecting core axes of the acute ayahuasca experience in naïve users: altered states of consciousness, cognitive processing changes, somatic/purgative responses, auditory/music- and speech-related elements, and visual perceptual content. The prominence of visual phenomena—participants described vivid colours, human-like figures and motion—and the reported ability to modulate visions by opening or closing the eyes are highlighted as central to the altered-state domain. Cognitive-cluster content suggested attempts to compare or reframe perceived reality, while the auditory cluster underscored the importance of music and spoken guidance in shaping experience. A key finding is the differential pattern in participants with depression: somatic, often aversive, bodily sensations (Cluster 3) were more strongly associated with depressed individuals, whereas more neutral-to-positive visual content (Cluster 5) predominated among healthy participants. The authors note that this could reflect greater somatic symptomatology in depression or cognitive biases affecting recall and reporting. Small effect sizes for most sociodemographic associations are emphasised, and the CFA result that cognitive, consciousness-alteration and auditory clusters are closely related is reported as consistent with interlinked dimensions of the psychedelic experience. The discussion positions these results relative to prior qualitative and psychometric work, noting overlap with previously identified thematic domains (visions, corporal experiences) and suggesting parallels with structured measures such as the 5D-ASC (for example, a Vigilance Reduction factor that might correspond to Cluster 1). The authors also observe that this study, unlike some previous reports, identified a distinct auditory cluster and did not retrieve a substantial corpus of emotional or spiritual/transcendental themes; they attribute this partly to the clinical, university-hospital setting used here rather than ritualistic or psychotherapeutic environments. Limitations the authors acknowledge include the small sample size, which limits statistical power and generalisability, and the inability within this dataset to link specific depressive symptom profiles to particular experiential patterns. The authors recommend future research combining subjective verbal reports with physiological measures, exploring psychometric correlates of verbal-report dimensions, and conducting studies in different settings to clarify the influence of contextual factors on subjective experience. The extracted text does not present further conclusions beyond the discussion, and no separate Conclusion section is present in the provided material.
Exploratory and qualitative data analyses were conducted to generate familiarity with the content. Exploratory and qualitative data analyses were conducted to generate familiarity with the content. Interviews were read, one by one, by two co-authors (LC and BB). This was done to familiarize researchers with the context in which terms appeared, helping with the interpretation of the results provided by the automated analysis. IRaMuTeQ 0.7 alpha 2and R 3.1.2.were used to run the quantitative analysis. The analysis was implemented using text-segments (TS). Through TS, texts are divided by the context in which words appear and sized in accordance with the corpus extension. For this study, the default Iramuteq option was used (40 words per text segment, see S1). Reports were analyzed in their original language (Brazilian Portuguese), to avoid any loss of content and context, with the software output being translated into English for the presentation of results in the current article. Descending Hierarchical Analysis (DHA, Reinert Method), Specificities and Correspondence Factor Analysis (CFA) were used. DHA organizes textual content in clusters with specific meanings, separated by the frequency of their vocabularies, similarity, and association. Specificities and CFA is a method that plays the role of associating texts with variables and indicate tendencies, proximities, and oppositions of the text segments (TS) in graphical visualization, locating those elements in a Cartesian graphic with factors based on their classifications and allowing graphic visualization of the co-occurrence between the words and the possible clusters they are part of Loubère. The index of co-occurrence between the words (i.e., the relationship of the words between them and the communities formed by clusters composed of words that are most associated) are indicated by the specificities of the analysis. Specificities analysis highlights the co-occurrence between words and the communities formed by associated words. Words and categories were included in their respective classes by DHA based on the criteria of having a frequency greater than the mean of occurrences in the corpus and chi-square value with the cluster greater than 3.84 (the critical value for p < 0.05 with df = 1). The words of interest (active forms) selected for analysis were adjectives, nouns, pronouns, verbs, adverbs, and forms not recognized by the IRaMuTeQ dictionary. In addition, when words had other associated forms (e.g. look, looking), the most frequent form was included in the graphic representation. Chi-square test was used to indicate the association between words and their clusters. Cramer's V was reported as a measure of effect size for the association. α was set at 0.001 to avoid inflation of type I error.
In this study, we sought to analyze subjective aspects of the experience of people with depression and healthy controls after the consumption of a single dose of ayahuasca. The textual analysis, which congregate words repeated with high frequency during the participants' reports describing the experience, identified five clusters. Broadly speaking these clusters refer to experiencing an altered state of consciousness, encompassing cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Each of these clusters showed specific associations with sociodemographic (e.g. age, gender, income, marital status) or clinical variables (depression diagnosis, substance use), but effect sizes were generally small. Cluster 1 (14.5% of the TS) seems to indicate the onset and experience of an altered state of consciousness. The importance of the visual component at the beginning of the experience is notable, which seems to be the central mediator of consciousness during this adaptive process. A central feature of the ayahuasca experience is that, according to user reports, visual hallucinations can be "switched on" or "off " by closing or opening the eyes. This highlights the crucial role of visual processing in the altered states of consciousness induced by ayahuasca consumption, which is also reflected in the strong association between the word "eye" and "open" and "close" in Cluster 1. It has been suggested that ayahuasca visions are often coupled with insights and topics with high personal relevance, including philosophical, metaphysical and spiritual epiphanies, potentially contributing to the therapeutic effects of the substance. These alterations in consciousness states can also be perceived initially as a decrease in the level of consciousness, which may explain the presence of words like "sleep", "slow" and "nap", in addition to content suggesting dream-like experiences ("dream") and changes in time perception ("hour"). Middle-aged participants showed a significant association with this cluster, with a small effect size, which may suggest more marked consciousness alterations in naïve older participants, but without further data that remains speculative. Cluster 2 (15.1% of the TS) includes a number of cognitive processes, through verbs such as "remember", "question", "look" and "understand". It may indicate a sensory-perceptive integration of experience, with the association between "look" and "reality" or "look" and "understand". The use of psychedelic substances may lead to an intense modification in one's perception of reality, which is reflected in this cluster through words such as "blurred" or "strange". Furthermore, a central word in this cluster word co-occurrence graph was "same", which can mark an attempt to compare the perceived reality with an ordinary state of consciousness. This cluster is closely linked to Cluster 1, with shared characteristics of altered states of consciousness and their perception. Small effect sizes were observed for associations between this cluster with male, high income, and cannabisuser participants, which may reflect possible cognitive biases in these groups (e.g. more rumination in cannabis users, but further research in this area is required to establish more robust conclusions. Auditory characteristics of the experience and setting are highlighted in Cluster 4 (which gathered 29.4% of the TS), with words such as "music", "speak", "listen", "sound", "silence", and "voice". Most words in this cluster are associated with music, emphasizing the essential role of the music setting in shaping the experience. In the word co-occurrence graph, it is possible to see how participants reacted positively or negatively to music (through words like "relax" or "bother", for example). Speech was also an essential component of the experience. Some word associations can help us to understand speech as a process of understanding and dealing with the experience during it, such as links between "speak"-"good"-"better" or "speak"-"think"-"calm". These auditory elements were particularly present in the reports of female participants and those without religion, which suggests these setting features were more salient for these groups. These findings also underscore the potential significance of spoken guidance provided during psychedelic experiences. Cluster 3 (18.1% of the TS) includes words such as "vomit", "pain", "bathroom", "hungry", "stomach", "breathe", and "dizziness", describing somatic aspects of the experience, particularly aversive feelings. That is in line with the purgative characteristic of ayahuasca, with users often going through difficult phases of the experience at its initial stages. Notably, the only category associated with this cluster was a diagnosis of depression. This may indicate a higher occurrence of negative somatic feelings in people with depression, consistent with the idea that depression is not only characterized by ideational, but also somatic symptoms (be, 2006). By contrast, this may represent cognitive biases in people with depression, leading to more negative evaluation, recall, and reporting of experiences. Cluster 5 (22.7% of TS) seems to describe specific visual content. The word "see" is quite central in the co-occurrence graph, being linked to "color", which then connects to specific colors. Human-like figures ("puppet", "woman") and their potential actions ("dance", "jump") are also represented. It is interesting to highlight the presence of neutral and positive biases (for example, the word co-occurrence graph reveals a link between "see" and "beautiful") in this cluster, given that it is associated with people without depression. This may indicate, in contrast with Cluster 3, more benign experiences in healthy participants. This cluster is also associated with low income, living alone, and not using tobacco. Further studies may explore whether this represents a sampling artefact or if these associations are consistent. The current findings are in agreement with those reported by Apud et al., who also recruited a clinical group (SUD). The five clusters indicated in their work show some overlap with the results reported here, for instance the 'visual perception content' and 'somatic alterations' clusters are linked to their 'visions' theme and 'corporal experiences' themes. Similar findings have also been reported by first-time ayahuasca users without clinical conditions. It is possible that these core features of psychedelic experience can be measured by specific questionnaires. For instance, psychometric analysis indicates that the 5D-ASC questionnairehas a factor linked to Vigilance Reduction (VIR), which may capture phenomena described in Cluster 1, containing words such as "sleep", "slow", "nap", and "dream". Similarly, Cluster 4 has words such as "music", "speak", "listen", "sound", "silence", and "voice" that are potentially related to a factor measuring Auditive Alteration (AVE). Future studies should explore the relationship between psychometric scales and verbal reports of experiences, trying to identify to which extent common dimensions of the psychedelic experience are assessed by existing instruments, leading to their refinement and development of new measurements. In contrast to previous research, current findings include a distinct cluster centered on auditory experiences, which encompasses both music and speech-related information, but lack a significant number of reports describing emotional and spiritual/transcendental aspects of the ayahuasca experience. This may be linked to characteristics of setting, with the current study being conducted in a university hospital, as opposed to previous investigations that took place in ritualisticor psychotherapy settings. In addition to potential setting effects, findings from the current study also support the idea that the set, specifically previous emotional state of participants, is linked to a more or less challenging experience. For example, Cluster 3 ('somatic alterations'), describing mainly negative physical experiences, has a stronger association with individuals of depression, while Cluster 5 ('visual perceptual content'), with more neutral and positive content, is more prevalent in reports of individuals without depression. This is in line with previous studies indicating that belonging to a clinical group modulates the experience with ayahuasca, for example with the study by Fernandez et al.suggesting that reports by people with depression focused on topics with higher therapeutic value in comparison to healthy individuals. As indicated, the need of subjective effects of psychedelics for therapeutic efficacy has been debated. Recent research on non-hallucinogenic psychedelic analogs with therapeutic potential has suggested that neural plasticity and neurotrophic factors may be fostered independently of subjective experience. While our study explored subjective states through quantitative analysis self-reports, it did not seek a direct comparison between subjective experience and therapeutic potential. Current results do indicate that the subjective state (depression, in this case) appears to influence how individuals assess and remember their experience. Whether attributed meaning has causal potential or is an epiphenomenon, it is undeniable that human beings live in the context of their symbolic representations, so it is unlikely that future therapeutic perspectives will reach its full potential by ignoring this fundamental dimension of human experience. The current study has some important limitations. The sample investigated was limited in size, which may have reduced statistical power and ability to generalize results. Nevertheless, the number of participants recruited is consistent with that reported in other experimental studies in which psychedelic substances are administered to participants (e.g. Ref.[n = 27]; Ref.[n = 29]; Ref.[n = 17]). Additionally, in the scope of the current work, it was not possible to explore the relationship between specific symptoms and profiles of depression with the subjective experience of consuming ayahuasca. Future studies should investigate this further, given the potential clinical benefits of ayahuasca for people with depression. In summary, this study is the first to employ quantitative methods to analyze the subjective experiences of people with depression and healthy controls after the consumption of ayahuasca in a clinical setting. Findings highlight certain features of the psychedelic experience, such as visual content, effects on cognition, and somatic alterations, as well as specific aspects of how people with depression react to ayahuasca, such as increased aversive bodily reactions. Future studies should try to combine subjective reports with physiological data, aiming to elucidate specific mechanisms of the cognitive changes, including therapeutic effects, caused by ayahuasca. Given the context sensitivity of psychedelic experiences, studies in different settings may also help clarifying the extent to which contextual factors affect the perception of users of their experience.
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