Since ayahuasca use is expanding both internationally and locally in the Spanish context, the aim of this study was to observe the effects of ayahuasca on psychological and health variables in naïve ayahuasca users. This will help medical practitioners to understand possible adverse effects as well as potential therapeutic uses.

We performed two sub-studies. Regarding sub-study 1, 40 ayahuasca-naïve subjects were assessed before using ayahuasca for the first time, and they were followed up with at 1 and 6 months after. Following the usual pattern of participants in complementary and alternative medicines30, the majority of the sample consisted of women with higher education.

The Mini-International Neuropsychiatric Interview (MINI) interview showed that 45% of the sample met the diagnostic criteria for a psychiatric disorder. This finding is in line with the main reasons reported by participants for attending ayahuasca ceremonies, which include the treatment of mental health problems and to achieve psychological well-being27,31,32. Remarkably, at the 1-month follow-up, 61% of participants who initially met the diagnostic criteria no longer met the criteria for any psychiatric disorder. Additionally, 22.2% of participants showed a decrease in the number of psychiatric disorders for which they met the diagnostic criteria, reducing the high prevalence of comorbidity at baseline (50%) to 0% at the 1-month follow-up. Overall, 83.2% of participants reported a clinical improvement. This improvement lasted until the 6-months follow-up. This finding is surprising, considering that this clinical improvement reported in the psychiatric interviews was not fully identified by the questionnaires used. A reduction in psychiatric diagnoses based on clinical interviews after the initiation of ayahuasca use is consistent across studies6,33. These results are also consistent with a recent study published by our group where it was found that half of a large sample (n = 380) of long-term ayahuasca users reduced or eliminated their prescription drugs after they began to regularly use ayahuasca9.

Only one subject met some criteria for a new psychiatric diagnostic, specifically for GAD, after using ayahuasca for the first time. That subject met the criteria for this disorder at 6-months follow-up. There are several reports regarding adverse effects of ayahuasca, leading some of them to psychiatric diagnoses29. In order to obtain more information, the questionnaire scores for this case were checked, and it was noted that the scores on every psychopathology scale from the SCL-90-R decreased notably at 1-month follow-up. At 6-months follow-up, half of the scales of the SCL-90-R increased again, following the general trend of the whole sample. In the clinical interview conducted using the MINI, this subject mentioned that the ayahuasca experience went well, and the traumatic termination of a partnership that they were experiencing was a more probable cause of the anxious state.

Regarding changes in psychological and psychopathological variables, there were improvements in the HAM-D at the 6-months assessment, in anxiety and hostility from the SCL-90-R at the 1-month assessment, and in the role-emotional scale from the SF-36 (see Fig. 2). The only variable that showed consistent change in the 6-month study period was depression as measured by HAM-D, which improved at every assessment. Although differences between baseline and the 1-month follow-up did not reach statistical significance, the scores decreased by half. This improvement was more evident at the 6-months follow-up, where differences between measures reached statistical significance. This finding is in line with previous research in which ayahuasca showed antidepressant effects at 7 and 21 days after its controlled administration in a clinical setting14,15,16. Our sample was not clinical, but 45% of subjects met the criteria for a psychiatric disorder. The same pattern of improvement was observed in the role-emotional scale from the SF-36. A similar study with a sample similar to ours also found long-term improvements in the role-emotional and social function scales from the SF-36 questionnaire25.

Figure 2 Confidence Intervals showing significant differences through different assessments in sub-study 1. HAM-D = Hamilton Depression Rating Scale; SCL-90-R = Symptom Check-List-90-Revised; SF-36 = The Medical Outcomes Study 36-item Short-Form. Full size image

Psychopathology scales of anxiety and hostility from the SCL-90-R only improved at 1-month, but not at the 6-months assessment. This tendency was observed for many scales, despite not being statistically significant. A general trend of improvement at 1-month follow-up was observed, while this improvement progressively decreased up until the 6-months follow-up. This can be clearly seen in Table 3. This pattern suggests that the potential therapeutic benefits of ayahuasca are temporary and do not persist in time, excepting for the case of depression. Several studies comparing ritual long-term ayahuasca users with non-users or with normative data have found better SCL-90-R scores and better scores for other psychopathological and psychological measures in users12,13,33,34. This may suggest that the long-term benefits of ayahuasca use depend on maintaining regular use.

The size of the sample decreased at both follow-ups. Therefore, we wanted to understand any potential limitations in that regard, so we conducted comparisons between drop-out subjects and those who remained in the study. Despite not obtaining significant results, subjects who scored lower on depression symptoms frequency (CAPE), and depression and hostility (SCL-90-R) at baseline tended to remain as study participants at least until the first follow-up. There were no significant differences nor notable tendencies between subjects who quit and those who remained until the last follow-up regarding any variable. This finding suggests that people with a high degree of distress may feel better after ayahuasca use and, subsequently, be more motivated to collaborate with researchers.

When only participants who met diagnostic criteria for a psychiatric disorder were analyzed, all the confidence intervals (CI) of variables overlapped between assessments. However, they indicated remarkable decrease over time in HAM-D scores, in the psychopathology scores measured by SCL-90-R at the 1-month follow-up, decrease in AAQ-II scores at each assessment, and increase of the WHOQOL-Bref score in the same manner. This also suggests an improvement in psychopathological status as it was also found using the MINI, but the sample may have been too small to observe significant differences using CIs. Despite reporting a clear tendency on the questionnaires used, this was not enough so that the CIs did not overlap.

In order to better understand if the eventual differences found between assessments in sub-study 1 were attributable to the use of ayahuasca or to extrapharmacological variables, including the passing of time, or if there are any pre-conditions that may lead a person to get involved in ayahuasca use, we performed sub-study 2. Only the measure of depression, assessed with the HAM-D, showed significant differences between non-users and long-term users, where the latter scored better than the former, a finding consistent with the long-term antidepressant effects of ayahuasca14,15,16. In previous studies, the acute administration of ayahuasca reduced the functional connectivity (FC) of the default mode network (DMN)21, which could be related to the improvements made on a depressed condition35. Moreover, it has been observed that the acute administration of the psychedelic tryptamine psilocybin also reduced the FC in the DMN in patients with MDD36 and resulted in a decrease in depression scores that lasted for at least 6 months37. Therefore, both the lower scores found at months 1 and 6 in naïve users and the lower scores for depression found in our long-term users, as compared with the baseline scores of subjects from sub-study 1, may reflect an actual mid-term antidepressant effect of ayahuasca. Due to the complex effects of ayahuasca, both pharmacological and psychological, employing an integrated approach involving different disciplines would be necessary to explain its efficacy. It has been observed, for example, that ayahuasca acutely enhances mindfulness-related capacities, such as decentering or acceptance38,39, and psychological process variables such as personal values could also be involved in therapeutic outcomes34. These capacities seem to be maintained during the after-glow period and also have persistent effects over the long-term40. Long-term effects may also be associated with the integration of the experience into normal life (e.g. by reconciling unexpressed/unresolved emotional energy), and thus with improvements in psychotherapeutic outcomes41. Furthermore, some authors suggest that the psychedelic experience42 or the mystical-type experiences43 that psychedelic drugs induce can also explain their therapeutic effects. Finally, as ayahuasca is generally taken in ceremonies for which small or large groups of people gather44, its communal use can also be viewed as exerting potential benefits, since feeling part of a community can have an important therapeutic impact10.

The other measure where experienced users scored higher than naïve users was self-transcendence (ST). There are multiple studies that have shown that psychedelics can induce long-term personality changes45. In sub-study 1, subjects did not change their scores in ST between assessments, but in sub-study 2 long-term users scored significantly higher than non-users in ST, a result that has been consistently found in previous studies as well11,12,24. It has been suggested that ayahuasca users’ higher ST scores could be partially explained by their participation in religious practices such as Santo Daime. However, in the study by Bouso et al.12 the samples (ayahuasca users and non-users) were matched for religion, age, and gender, so the difference in that study could be attributed to the ritualistic use of ayahuasca. In the present study, the number of atheists was lower in the group of long-term ayahuasca users, but only 13% of participants were Santo Daime members. Taking all these data into account, it is reasonable to think that higher scores in ST may be a direct consequence of ayahuasca use. A previous study found differences in cortical thickness in several brain areas to exist between long-term users and non-users of ayahuasca, suggesting a physical brain modification after regular ayahuasca exposure without any apparent neuropsychiatric consequences (there were no differences between groups in their performance on psychiatric and neuropsychological tasks)13. In that study, researchers found a correlation between ST and cortical thickness in the posterior cingulate cortex13. Psychedelic drugs may therefore offer an interesting tool for investigating the stability of personality traits and their brain correlates.

Regarding the differences between naïve ayahuasca users’ and experienced users’ baseline scores for quality of life as assessed by the WHOQOL-Bref, they are also consistent between sub-studies. Although in sub-study 1 there were no significant differences between assessments, there was an actual clinical improvement between them (see Table 3). This is consistent with previous research where regular ayahuasca use was associated with a better mental health status or with improvement on psychopathology scales, as was also observed in sub-study 1.

When comparing long-term ayahuasca users with the sub-study 1 subsample of psychiatric diagnosis (n = 18), the number of variables in which significant differences are found increases. This is reasonable in light of the much smaller number of long-term ayahuasca users who met the diagnostic criteria for at least one psychiatric disorder (9%). Ayahuasca-naïve users who met the criteria for a psychiatric diagnosis scored poorly for depression (HAM-D), positive symptoms frequency (CAPE), depression symptoms distress (CAPE), negative symptoms distress, in AAQ-II questionnaire, self-transcendence scale (TCI-R-67), role-emotional (SF-36), and WHOQOL-Bref. Despite not finding statistically significant differences between assessments among the subgroup of naïve users with psychiatric disorders, remarkable improvements were observed for several scales measuring psychopathology and quality of life. This lends support to previous research that found that ayahuasca users gained therapeutic benefits or experienced an enhanced ability to solve personal problems25,33,46.

The main limitation of this study is that there was no control group with which to make comparisons to determine the impact of the intervention. In order to minimize that limitation, we designed sub-study 2. Coherent results were found both between sub-studies and with previously published research. However, further studies using larger samples should consider potential differences between the type and setting of the ceremony.

This study assessed naïve users of ayahuasca in order to collect data regarding its overall effects on psychiatric condition and psychological status. Since ayahuasca use has become globally popular as a self-help practice, it is important to better understand its potential risks and benefits. General mid-term adverse effects were not observed in this study, although some secondary acute reactions were observed in some individual cases (e.g. anxiety) and will be reported in a separate paper. Additionally, from a clinical point of view, there was a substantial decrease in psychiatric symptomatology after the first use of ayahuasca, which persisted until the 6-months follow-up. The most evident improvements were found with regards to depression. These improvements in depression found after performing clinical interviews were also demonstrated by the psychiatric rating scales. Better scores for depression were also observed among long-term users when compared with ayahuasca-naïve users at baseline. The results obtained in this study help to inform us about the effects of the ritualistic use of ayahuasca on mental health. These results suggest that the use of ayahuasca in controlled settings may offer therapeutic benefits. Future studies with larger samples are warranted in order to better understand 1) the more specific effects of ayahuasca use on public health and 2) the reasons why those initiated in ayahuasca use continue to use it or not.