ORIGINAL RESEARCH published: 05 May 2021 doi: 10.3389/fphar.2021.623923 The Shipibo Ceremonial Use of Ayahuasca to Promote Well-Being: An Observational Study Debora Gonzalez 1,2,3*, Jordi Cantillo 1, Irene Perez 1, Maria Carvalho 4, Adam Aronovich 5, Magi Farre 6,7, Amanda Feilding 3,8, Jordi E. Obiols 9 and José Carlos Bouso 1,5,10 1 International Center for Ethnobotanical Education, Research and Services (ICEERS), Barcelona, Spain, 2PHI Association, Barcelona, Spain, 3Fundación BeckleyMed, Barcelona, Spain, 4Catholic University of Portugal, Barcelona, Spain, 5Medical Anthropology Research Center, Department of Anthropology, Philosophy and Social Work, University of Rovira I Virgili, Tarragona, Spain, 6Clinical Pharmacology Unit, Hospital Universitari Germans Trias I Pujol and Institut de Recerca Germans Trias I Pujol (IGTP), Barcelona, Spain, 7Department of Pharmacology, Therapeutics and Toxicoloy, Universitat Autònoma de Barcelona, Barcelona, Spain, 8The Beckley Foundation, Oxford, United Kingdom, 9Department of Clinical and Health Psychology, Faculty of Edited by: Psychology, Autonomous University of Barcelona, Barcelona, Spain, 10Department of Neurosciences and Behavior, Ribeirão Fernando Mendive, Preto Medical School, University of São Paulo, Brazil Center for the Rehabilitation of Drug Addicts and Research on Traditional Medicines, Peru Promoting well-being is one of the main goals to improve health in the world. We examined Reviewed by: the well-being and quality of life over the course of one year in a sample that participated in Charles D. Nichols, an Indigenous Shipibo healing program where traditional healers work in a series of Louisiana State University, United States ayahuasca ceremonies. We also explored the role of decentering as a mediator of Paulo Cesar Ribeiro Barbosa, psychological well-being. Participants who attended the program responded to an Universidade Estadual de Santa Cruz, Brazil online survey that included a Psychological Well-Being Scale; Oxford Happiness *Correspondence: Questionnaire; The World Health Organization Quality of Life Spirituality, Religiousness, Debora Gonzalez and Personal Beliefs scale; the WHO Quality of Life-BREF scale; and Decentering scale. deboragonzalez@iceers.org Baseline (T0) and postassessment (T1) were completed by 200 individuals. Of these, 101 completed the follow-up assessment at three months (T2), 91 at 6 months (T3), and 94 at Specialty section: This article was submitted to 12 months follow-up (T4) after leaving the center. ANOVA test was performed in a Ethnopharmacology, representative subsample to control the passing of time two months before attending a section of the journal Frontiers in Pharmacology the program (T-1). Pearson’s test was performed to examine the relationship between Received: 30 October 2020 psychological well-being and decentering during the period of T0 and T1. A significant Accepted: 21 April 2021 increase was observed in all the scales at all time points (p ≤ 0.01). The subgroup analysis Published: 05 May 2021 performed in a representative subsample allowed us to infer that the significant differences Citation: in outcomes are due to the effect of their stay at the center and not the passing of time. We Gonzalez D, Cantillo J, Perez I, Carvalho M, Aronovich A, Farre M, found a relationship between decentering and the improvement of psychological well- Feilding A, Obiols JE and Bouso JC being (r  0.57; p < 0.01). Our results suggest that the Indigenous Shipibo healing work (2021) The Shipibo Ceremonial Use of Ayahuasca to Promote Well-Being: An with ayahuasca has value to improve long-term well-being and quality of life for Observational Study. Westerners. Front. Pharmacol. 12:623923. doi: 10.3389/fphar.2021.623923 Keywords: well-being, quality of life, herbal medicine, Shipibo, ayahuasca, traditional medicine Frontiers in Pharmacology | www.frontiersin.org 1 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being INTRODUCTION determination of other inorganic elements have displayed safe administration concentrations in 19 samples made from these In recent years, a growing interest in well-being, both in society in plants collected from the União do Vegetal (Guimarães et al., general as well as in mental health care, developed. This trend is 2020). Safety has been demonstrated by the long history of use, in reflected in the World Health Organization (WHO, 2001) observational studies on long-term users in ceremonial contexts definition of mental health as “a state of complete physical, (Grob et al., 1996; Halpern et al., 2008; Fabregas et al., 2010; mental and social well-being and not merely the absence of Bouso et al., 2012; Bouso et al., 2015; Barbosa et al., 2016; disease or infirmity” (WHO, 2006). Promoting well-being has Jiménez-Garrido et al., 2020), and in the laboratory (Mello become a principal goal for improving health in general among et al., 2019; dos; Santos, 2011; Hamill et al., 2019). Moreover, academics, health-care professionals, and policymakers alike open trials and randomized trials have shown the efficacy of (WHO, 2020a). Although there is no consensus on the ayahuasca as a rapid antidepressant (Osorio et al., 2015; Sanches definition of well-being, clinical research on this concept is et al., 2016; Palhano-Fontes et al., 2019). Observational studies rooted in two complementary schools of thought. The show a higher level of well-being in long-term users of ayahuasca eudaimonic model postulates a psychological well-being that is (Bouso et al., 2012; Lawn et al., 2017; Ona et al., 2019) and lifestyle achieved through the development of the human being’s modifications (Grob et al., 1996). potential. This is determined by the combination of six Today, interest in ayahuasca is a global phenomenon. Outside factors: autonomy, self-acceptance, environmental mastery, its native Amazonian habitat, ayahuasca has a presence in dozens positive relations with others, purpose in life, and personal of countries, including other parts of South America, North growth (Ryff, 1989). Alternatively, the hedonistic model America, Europe, Australia, New Zealand, and some parts of defines well-being as a subjective state based on the pleasure Asia (Tupper, 2008). This expansion has happened through three and enjoyment of life, determined through three factors: life ways: religions that use ayahuasca as a sacrament; the satisfaction, the presence of positive affect, and the absence of psychonautic use of ayahuasca brew by Western people and negative affect (Diener et al., 1999). In other words, hedonic neo-ayahuasqueros; and the cross-cultural vegetalismo or construct deals exclusively with affect, measuring whether people Indigenous-style ayahuasca healing ceremonies conducted in are “feeling good”, but should be complemented with the an often overtly commodified way for non-Indigenous clients eudaimonic construct that deals with personal-value fulfillment both in the Amazon and abroad (Tupper, 2009). In these and meaningfulness, whether people are “doing well” or not traditions, aspiring ayahuasqueros go through an extended and (Michaelson et al., 2009). difficult period of training involving demanding dietary and One of the strategies to promote comprehensive human behavioral restrictions—although real mastery is acknowledged welfare at the international level has been to develop a to take decades or a lifetime (Langdon, 1979). strategic plan 2014–2023 to foster the appropriate integration, However, the absence of international regulation of ayahuasca regulation, and supervision of traditional medicine (TM) (WHO, use poses a number of serious risks, both for Indigenous peoples 2013). Traditional medicine is the sum total of the knowledge, and for the international community in general. On the one hand, skill, and practices based on the theories, beliefs, and experiences Indigenous people see the desecration and cultural appropriation indigenous to different cultures—whether explicable or of their knowledge, symbols, stories, ceremonies, dances, and not—used in the maintenance of health, as well as in the songs (Zuluaga, 2000; Tupper, 2009), and fear that their ancestral prevention, diagnosis, improvement, or treatment of physical heritage will be changed or lost. On the other hand, Westerners and mental illness (WHO, 2020b). Herbal medicines constitute who take ayahuasca have no guarantees about the composition of the main component of traditional medicine, which has been the ayahuasca, unwanted pharmacological interactions, exposure used for thousands of years (WHO, 2010). Quality standards, to unreliable information, and unqualified and unethical safety, and efficacy of the herbal products are needed to be practitioners (Labate and Araujo, 2004; Qui, 2013; Kavenská, considered herbal medicines. However, governments and Simonvá, 2015). consumers are interested in more than herbal medicines and Since these risks underlie all traditional medicines using herbal are now beginning to consider traditional medicine practices and medicines, the World Health Organization has promoted practitioners and whether they should be integrated into health international recognition of traditional medicine by regulating service delivery (WHO, 2020c). the products, practices, and practitioners (Callaway et al., 1999). Ayahuasca is an herbal concoction used for ritual and healing It has included—for the first time—diagnostic criteria based on purposes since pre-Columbian times (McKenna, 1999). It is traditional Chinese medicine in the 11th edition of the usually obtained by boiling the pounded stalks of the vine International Classification of Diseases (ICD-11) (WHO, Banisteriopsis caapi (Spruce ex Griseb.) Morton and the leaves 2018). This effort has a reciprocal impact on the safety of of the bush Psychotria viridis Ruiz & Pav. (Schultes, Hoffman, doctors and patients, both in the countries of origin and in 1992). B. caapi contains ß-carboline alkaloids such as harmine, the countries that import medicinal practices and products. tetrahydroharmine (THH), and harmaline, that are reversible For example, acupuncture is covered by public and private inhibitors of monoamine oxidase A (MAO-A), while P. viridis is insurances in different European countries by accredited rich in the tryptamine hallucinogen dimethyltryptamine (DMT), professionals favoring the exercise of good practices among an agonist of serotonin (5-HT)1A/2A/2C and sigma-1 receptors professionals and patients. Knowledge-based policies are (Riba et al., 2003; Fontanilla et al., 2009). Quantitative crucial for the integration of traditional medicine into national Frontiers in Pharmacology | www.frontiersin.org 2 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being health systems, and research should be prioritized and supported In addition to the icaros, the Shipibo also works with Nicotiana in order to generate knowledge (WHO, 2013). Randomized rustica, commonly known as Mapacho, Aztec, Brazilian, or strong placebo-controlled clinical trials provide a high internal tobacco, as an important plant ally in the ceremony. They validity but low external validity. Therefore, clinical trials in occasionally blow smoke on the participants to transmit the the laboratory have to be combined with observational icaros, cleanse heavy energies, and maintain protections. In research to study how these medical systems are working in addition, several plants and flowers in the form of steam baths the real world. and flower baths are used outside of the ceremonies in order to cleanse the energies that are being pulled out by the icaros. Several Traditional Context perfumes, such as agua florida or pusanga, are also used to help This article presents the results of a longitudinal observational the person “blossom” and attract positivity into their lives. study evaluating various parameters related to the psychological, The present study investigated the long-term effects of subjective, spiritual well-being, and quality of life of Western ayahuasca in the well-being of participants from a holistic people attending retreats at the Temple of the Way of Light in view. The primary outcome of this study was psychological Iquitos, Peru (Temple of the Way of Light, 2016). Ceremonies are well-being. Secondary variables were subjective well-being, run by five male and female Shipibo onanyabo (the plural form of spiritual well-being, quality of life, and decentering. We the Shipibo term for an ayahuasca practitioner), supported by two hypothesized that the psychological well-being would be Western facilitators. Although these ceremonies are rooted in the improved after drinking ayahuasca in this traditional healing traditional Shipibo medical system, they have been adapted to work context still maintained after a one-year follow-up. Second, working with Western participants. According to the Shipibo we hypothesized that subjective well-being, spiritual well-being, onanyabo, their work over the course of the series of ceremonies quality of life, and decentering would also improve after drinking follows a coherent and structured progression, with the first ayahuasca. Given that previous studies have shown that ceremony being a diagnostic session. As the ceremony begins, decentering is a psychological process underlying ayahuasca’s the first icaro that they perform is meant to create a safety effects (Soler et al., 2016; Franquesa et al., 2018; Gonzalez et al., structure around the ceremonial space, with the intention of 2020; Murphy-Beiner, Soar, 2020) and that this psychological protecting the participants from energetic interferences from the process mediates psychological well-being (Park and Park, 2017; outside environment and between participants. Following Carmody et al., 2009), we finally hypothesized that changes in Dobkin de Rios (1984), icaro is the generic name given to the psychological well-being after being at the center will be mediated medicine songs used by the curanderos of the Peruvian Amazon by changes in decentering. Basin (for a deeper review regarding icaros, see Bustos, 2008). During the initial diagnostic session, the onanyabo aims to detect energetic blockages in the participants, “scanning” their bodies MATERIALS AND METHODS with the help of the icaro. The following ceremonies, according to the onanyabo, aim to This study is part of a broader research project that aims to cleanse and clear “dense energies” that participants may carry. prospectively assess the long-term effects of ayahuasca on Although the Shipibo does not necessarily make the same psychopathological symptoms in different subsamples with conceptual connections, Western facilitators often understand depression, anxiety, posttraumatic stress disorder, and grief. Grief these dense energetic knots to correlate with psychosomatic and data have been published in a previous study (Gonzalez et al., 2020). emotional imprints leftover from individual and trans- In the present article, only the data for the subsample that have generational traumas, repressed emotions, or self-sabotaging not been previously diagnosed with a mental disorder and do not unconscious views that are rooted in past difficult life suffer from any of those psychopathological symptoms have been episodes, particularly childhood experiences. However, included and analyzed. The study was approved by the Ethics diagnosis is also a continuous process throughout the Committee on Animal and Human Experimentation of the cleansing and clearing process, reaching into and revealing Autonomous University of Barcelona (UABCEEAH Barcelona, deeper layers of energetic and spiritual ways of being. When Spain) and was conducted in accordance with the Declaration of “heavy energies” are uncovered, the onanyabo claim to use icaros Helsinki. Participants signed an online informed consent and were to disconnect and dispel them within the individual’s body, not financially compensated for their participation. sending the “energies” back into the earth. By clearing dense energies from the past, participants become “unstuck” and often Participants and Procedure significantly transform their relationship with themselves, others, Participant enrollment was carried out between 2015 and 2017. and the world in general. During 2018, the follow-up period of one year was concluded. Once the cleansing and clearing have been done, a culminating Participants were invited to participate in the study through the last ceremony occurs. The onanyabo focuses on sealing in the Web site of the Temple of the Way of Light (Temple of the Way of “spiritual surgery” and aligning the body, mind, and spirit, Light, 2016) after having booked their stay at the center. This together with the perceived energetic structure of each center offered retreats of 9, 12, or 30 days, where participants participant, protecting the energetic and physical body while drank ayahuasca between 1 and 12 times in a ceremonial context illuminating the pathway forward. under the guidance of Shipibo onanyabo. Frontiers in Pharmacology | www.frontiersin.org 3 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being A total of 200 participants were eligible for the analysis. The the participants assess the extent to which they form part of their screening process involved two stages. First, to be accepted by the experiences. It employs a Likert scale (1  I totally disagree, 6  I center, individuals had to be 18 years or older. Moreover, people totally agree). Reliability for this scale was found to be 0.91. with previous clinical disorders (psychosis, depersonalization, and mania), people taking certain medications (i.e., MAOIs or Spiritual Well-Being SSRIs), subjects with a heart condition, those with chronic high WHO Quality of Life Spirituality, Religiousness, and Personal blood pressure, and pregnant women were not accepted (Temple Beliefs (WHOQOL-SRPB BREF) (WHOQOL SRPB Group, of the Way of Light, 2019). Second, participants must respond to 2006) is a 32-item Likert scale (1  not at all, 5  an extreme a short online questionnaire including the following questions: 1) amount), covering quality-of-life aspects related to spirituality, Please indicate the exact date when you will attend to the retreat; religiousness, and personal beliefs. It is divided into eight scales: 2) Please mark “yes,” “uncertain,” or “no” to the following Spiritual Connection, Meaning and Purpose in Life, Experiences questions: Are you currently going through a period of (b.1) of Awe and Wonder, Wholeness and Integration, Spiritual depression, (b.2) anxiety, (b.3) posttraumatic stress, or (b.4) grief Strength, Inner Peace, Hope and Optimism, and Faith. Each related to the death of a loved one; 3) Have been diagnosed with a facet score is derived by averaging the score obtained from the mental disorder in the past?, and 4) Can you understand with ease responses to the four questions comprising that particular facet. everything you read in the English language? The domain score is calculated by adding the scores of the facets. Participants were included in the study if they were not Cronbach’s a for the SRPB facets has been found to be strong, currently experiencing depression, anxiety, posttraumatic ranging from 0.77 (meaning and purpose in life) to 0.95 (faith), stress, and grief symptoms related to the death of a loved one; whereas Cronbach’s a for the complete WHOQOL-SRPB if they have not been diagnosed with certain mental disorders in instrument is excellent (α  0.93). the past; and if they affirmed having adequate knowledge of the English language. Once participants were included in the study, Quality of Life assessments were done 15 days before attending the retreat (T0) WHO Quality of Life-BREF (WHOQOL-BREF) (WHOQOL and 15 days (T1), three months (T2), six months (T3), and Group, 1998) is a shorter version of the original WHOQOL- 12 months (T4) after leaving the center. Only participants who 100 (Power et al., 1999). This questionnaire was designed to assess responded baseline (T0) and postassessment (T1) were finally quality of life in four domains: Physical Health, Psychological included in the analysis. Participants who signed informed Health, Social Relationships, and Environment. It comprised 24 consent more than two months before attending the center items, scored on a 4–20 scale, with higher scores indicating a were invited to respond to an additional assessment two better quality of life. For the purpose of this study, only the first months before entering the center (T-1) in order to control three scales were used. The scale has been shown to have adequate for the effect of time on outcomes in a subgroup. psychometric properties with Cronbach’s coefficient α values All questionnaires were administered online using LimeSurvey ranging from 0.68 to 0.82 (61). (version 1.92.), which allowed for the collection and preservation of the data for confidentiality on a secure server that is accessible Decentering only to the researchers with a secure password. EQ-Decentering (Fresco et al., 2007): this scale assesses decentering, defined as the ability to observe one’s thoughts Measures and feelings in a detached manner. This is an 11-item, self- A series of questionnaires were administered to the subjects. report measure of decentering. Items are rated on a 5-point Likert scale (1  never to 5  always). The original EQ showed a high- Psychological Well-Being reliability coefficient with Cronbach’s α value of 0.90. Psychological Well-Being Scales (PWBS) (Ryff, 1989) is a 42-item Likert-type scale (1  completely disagree, 6  completely agree), Ayahuasca Samples Analyses which measures psychological well-being through scales of Self- Two ayahuasca samples collected during the participants’ Acceptance, Positive Relationships, Autonomy, Environmental enrollment were analyzed (Gonzalez et al., 2020). The Mastery, Personal Growth, and Purpose in Life. Scores in each ayahuasca was prepared by boiling the stems of domain range from 6 to 42 where higher scores indicate greater Banisteriopsis caapi (Spruce ex Griseb.) Morton, rich in levels of well-being. In the current study, the sum of the score harmine, tetrahydroharmine, and harmaline, combined ratings across the six dimensions was added including an overall with the leaves of Psychotria viridis Ruiz & Pav., rich in PWBS measure (α  0.89), with higher scores reflecting DMT. Analyses were carried out by Energy Control higher PWBS. (energycontrol-international.org) using liquid chromatography–mass spectrometry (LC–MS). One Happiness ayahuasca sample contained 2 mg/ml DMT, 2 mg/ml of Oxford Happiness Questionnaire (Hills and Argyle, 2002) harmine, 0.37 mg/ml of harmaline, and 1 mg/ml of measures happiness or subjective well-being (Medvedev and tetrahydroharmine. The other sample contained 2 mg/ml Landhuis, 2018). A series of statements about happiness are DMT, 2 mg/ml of harmine, 0.65 mg/ml of harmaline, and given and the participants indicate their degree of agreement 2 mg/ml of tetrahydroharmine. No other psychoactive with each one. In psychometric terms, it consists of 29 items, and compounds were detected. Frontiers in Pharmacology | www.frontiersin.org 4 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being FIGURE 1 | Participant flow throughout the study. Statistical Analyses were conducted using repeated measures analysis of variance Baseline sample characteristics, setting variables, persistent adverse (ANOVAs) with post hoc Bonferroni correction in order to effects, benefits of ayahuasca over time, and risk’s perception of the examine differences in primary and secondary outcomes ayahuasca use in the participants’ original countries were analyzed between the periods of T-1 to T0 and T1 to T0. Effect sizes descriptively. Changes in primary and secondary outcome variables were calculated using Cohen’s d. between each time point and baseline were tested using Student’s In this study, p values <0.05 were considered statistically paired two-sided T-test or the Wilcoxon-paired test, as appropriate. significant. Statistical analysis was performed using Statistical Bonferroni corrections were applied to correct for multiple Package for the Social Sciences (SPSS for Windows, version 20). comparisons. A 95% CI for the mean of the primary outcome at all-time point assessments was included to further clarify plausible values. Effect sizes were calculated using Cohen’s d. Effect sizes were RESULTS defined as large up to 0.8 (d > 0.8), medium (d > 0.5), and small (d ≤ 0.2) (Cohen, 1992). Pearson’s linear correlation coefficient was used Participants to examine the relationship between Decentering (EQ-Decentering) Out of 437 participants who were assessed for eligibility, 90.8% of and Psychological Well-Being Scale (PWBS). Correlation participants signed the informed consent form. However, 18.4% coefficients between 0.30 and 0.70 were considered moderate. of participants were excluded because baseline assessment (T0) Additional subgroup analysis was performed separately for was not available, 36.7% were excluded because postassessment patients who responded to T-1, T0, and T1 assessments. We used was not available (T1), and 2% expressed a desire to abandon the the chi-square test for categorical variables and Fisher–Snedecor study. Finally, 200 participants were eligible for the analysis, for continuous variables to evaluate homogeneity between the having completed the baseline and postassessment. Overall, the group that completed the follow-up at T1 and a subgroup that rate of participants not responding to the assessment at T2 was completed an additional assessment at T-1. Subgroup analyses 49.5%, at T3 was 54.5%, and 53% at T4 (Figure 1). Frontiers in Pharmacology | www.frontiersin.org 5 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being TABLE 1 | Demographic characteristics of participants. p < 0.01). Calculating effect sizes according to Cohen’s method, Sociodemographic N = 200 we found a high effect size at all assessment points (T1  0.89, characteristics 95% CI  0.72–1.04; T2  0.91, 95% CI  0.67–1.11; T3  1.12, N % 95% CI  0.89–1.35; and T4  0.82, 95% CI  0.56–1.07). Subjective well-being also showed a significant improvement Male 104 52.3 at all-point assessments (T1, T2, T3, and T4: p < 0.01), showing a Age in yearsa 41.84 (11.69) [20; 69] moderate effect size at T1  0.76, 95% CI  0.62–0.90; T2  0.58, Educational level Primary school 4 2.0 95% CI  0.37–0.77; and T4  0.69; 95% CI  0.45–0.90. Secondary/High school 20 10.0 Unexpectedly, the effects size was higher at T3  0.91 95% College/University 169 84.5 CI  0.68–1.12. Other 7 3.5 Similarly, the WHOQOL-SRPB showed a significant Race Caucasian 178 89.0 improvement on the total score for all assessments (T1, T2, Hispanic 9 4.5 T3, and T4: p < 0.01), showing a high effect size at T1  0.96, Asian 6 3.0 95% CI  0.80–1.11; T3  1.05, 95% CI  0.83–1.725; and T4  Others 7 3.5 0.90, 95% CI  0.67–1.11. The effect size at T2 was medium. T2  Country 0.71, 95% CI  0.52–0.90. United States of 57 35.4 America The WHOQOL-BREF questionnaire also showed significant United Kingdom 29 18.0 improvements in physical health, psychological health, and social Australia 16 9.9 relationship scales after the retreat (T1: p < 0.01). The effect size Canada 18 11.2 was larger for the psychological health scale (T1  0.96, 95% CI  Germany 9 5.6 0.81–1.10; T2  0.70, 95% CI  0.49–0.88; T3  0.94, 95% CI  Other 32 19.9 Marital status 0.75–1.13; and T4  0.70, 95% CI  0.51–0.87). Single 93 46.7 Finally, decentering significantly improved after the retreat Married 35 17.6 (T1: p < 0.01) and at all follow-up assessments (T2, T3, and T4: Living as married 30 15.1 p < 0.01). Decentering also showed a high-effect size at all-time Divorced or separated 41 20.6 point assessments (T1  0.97, 95% CI  0.82–1.12; T2  0.87, 95% Employed 146 73.0 Nonreligious 190 95.0 CI  0.66–1.06; T3  0.87, 95% CI  0.63–1.09; and T4  0.87, a 95% CI  0.61–1.10). Data are expressed as mean (SD) [range]. The improvements achieved in the key variables after the retreat remained stable at 12 months, with no significant differences observed between T4 and T1, except in spiritual Baseline Sample Characteristics strength (T4–T1  −0.20 (0.57); p  0.001) (Supplementary The demographic characteristics of participants are summarized Table S1). in Table 1. The motivations for attending the retreat were Persistent benefits and adverse effects derived from the spiritual growth (66.7%) and personal development (32.4%). ayahuasca experiences at the center are shown in Table 3. None of the participants indicated a therapeutic motivation or recreational purpose, such as drug tourism. Of the overall sample, Correlation Analyses 65.5% had never used ayahuasca before. Of the remaining 34% of The significant increase in decentering between T0 and T1 was the sample (n  68), 9.5% drank ayahuasca less than 4 times, 13% found to be associated with the significant increase in the between 4 and 10 times, and 11.5% more than 10 times. Psychological Well-Being Total Scale between T0 and T1 (r  0.53; p < 0.01). Setting Variables Participants attended an average of 14.93 (SD  7.58) days at the Subgroup Analyses center (range 9–31), where they participated in an average of 6.21 Of the 200 participants who completed the baseline and (SD  1.57) ayahuasca ceremonies (range 1–12). Of the 200 postassessment (T0 and T1), a subgroup of 42 participants participants who responded at T0–T1, 54% perceived ayahuasca who completed an additional assessment two months prior to as the most relevant factor in the evolution of their well-being the retreat (T-1) were eligible for the subgroup analysis during their stay at the center, followed by the work of the Shipibo (ANOVA). The homogeneity of the groups was tested by healers (36%), being with other guests (6%), the experience of comparing key variables (baseline characteristics, primary and being in the jungle (2.5%), and having attended other alternative secondary outcome measures). Significant differences were found activities, such as yoga classes (1.5%). only in people with a university degree (control subsample  87.3%; subsample  73.8%; p  0.031). No other significant Main Outcome Analyses differences were found in primary and secondary outcomes The results for outcome variables at all assessment points (T0, T1, measures (p > 0.05). T2, T3, and T4) are presented in Table 2. Psychological Well- The average number of days registered in the subsample Being Scales Total score was significantly increased from baseline between T-1 and T0 was 44.29 (SD  5.42), and between T0 to all point times follow-up assessment (T1, T2, T3, and T4: and T1, it was 46.0 (SD  9.13). Mean values of primary and Frontiers in Pharmacology | www.frontiersin.org 6 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being TABLE 2 | Outcome of repeated measures at baseline (T0) and each time point during follow-up. Values are given as means differences (with standard deviations). Measures T1–T0 T2–T0 T3–T0 T4–T0 a† b† c† Mean (SD) Sig. Mean (SD) Sig. Mean (SD) Sig. Mean (SD) Sig.d† N = 200 N = 101 N = 91 N = 94 PWBS Autonomy 2.83 (4.93)** 3.12 (4.73)** 3.16 (4.06)** 3.05 (4.38)** Environmental mastery 2.39 (3.87)** 2.56 (4.11)** 2.63 (3.55)** 2.43 (4.05)** Personal growth 1.69 (3.97)** 1.53 (3.94)** 1.56 (3.58)** 1.91 (4.07)** Positive relations 2.63 (3.85)** 2.69 (4.35)** 2.62 (4.02)** 2.44 (4.48)** Purpose in life 3.66 (5.39)** 3.21 (5.54)** 4.43 (5.84)** 3.82 (6.29)** Self-acceptance 3.93 (5.06)** 3.91 (5.05)** 4.26 (4.59)** 3.87 (5.91)** Total 16.88 (19.0)** 16.75 (18.49)** 18.73 (16.77)** 16.43 (19.92)** WHOQOL-BREF Physical health 1.39 (1.83)** 1.11 (1.74)** 1.15 (1.68)** 1.22 (1.97)** Psychological health 2.03 (2.11)** 1.63 (2.34)** 1.78 (1.89)** 1.68 (2.39)** Social relationships 2.14 (2.72)** 1.81 (2.85)** 2.31 (2.70)** 2.10 (3.08)** Oxford happiness 0.52 (0.68)** 0.43 (0.75)** 0.54 (0.60)** 0.50 (0.73)** EQ-decentering 5.87 (6.03)** 4.30 (4.94)** 4.48 (5.16)** 4.65 (5.37)** WHOQOL-SRPB Spiritual connection 0.52 (0.97)** 0.42 (1.04)** 0.67 (1.03)** 0.70 (1.04)** Meaning of life 0.45 (0.69)** 0.31 (0.72)** 0.47 (0.66)** 0.45 (0.72)** Experience of awe 0.55 (0.76)** 0.48 (0.71)** 0.71 (0.78)** 0.66 (0.74)** Integrity and integration 0.46 (0.63)** 0.38 (0.60)** 0.47 (0.55)** 0.45 (0.57)** Spiritual strength 0.43 (0.60)** 0.26 (0.64)** 0.29 (0.49)** 0.22 (0.64)** Inner peace 0.50 (0.72)** 0.39 (0.78)** 0.56 (0.67)** 0.49 (0.69)** Hope and optimism 0.68 (0.72)** 0.47 (0.75)** 0.53 (0.67)** 0.53 (0.74)** Faith 0.56 (0.58)** 0.48 (0.62)** 0.48 (0.54)** 0.50 (0.59)** Total 0.52 (0.54)** 0.39 (0.55)** 0.53 (0.50)** 0.49 (0.55)** † Bonferroni correction is performed. a p value calculated by paired sample T-test from T0 to T1 (N  200). b p value calculated by paired sample T-test from T0 to T2 (N  101). c p value calculated by paired sample T-test from T0 to T3 (N  91). d p value calculated by paired sample T-test from T0 to T4 (N  94). Asterisks indicate p values: **p < 0.01 in the paired sample T-tests. PWBS, Psychological Well-Being Scales; WHOQOL-BREF, World Health Organization Quality of Life; WHOQOL-SRPB, World Health Organization Quality of Life Spirituality, Religiousness, and Personal Beliefs. TABLE 3 | Adverse effects and benefits of ayahuasca at each time point during follow-up. T1 T2 T3 T4 N = 200 N = 101 N = 91 N = 94 n % N % n % n % Persistent benefits of ayahuascaa No 6 3.0 11 10.9 3 3.3 6 6.5 Yes 194 97.0 90 89.1 87 96.7 87 93.5 Physical health 95 47.5 43 42.6 33 36.7 36 38.7 Mental health 146 73.0 57 56.4 63 70.0 65 69.9 Personal well-being 175 87.5 70 69.3 76 84.4 77 82.8 Social relationships 126 63.0 58 57.4 51 56.7 46 49.5 Spiritual 164 82.0 78 77.2 77 85.6 76 81.7 Lifestyle 118 59.0 42 41.6 43 47.8 42 45.2 Persistent adverse effects of ayahuascaa No 195 97.5 100 99.0 91 100.0 94 100.0 Yes 5 2.5 1 1.0 0 0.0 0 0.0 Physical health 3 1.5 1 1.0 0 0.0 0 0.0 Mental health 1 0.5 0 0.0 0 0.0 0 0.0 Personal well-being 0 0.0 0 0.0 0 0.0 0 0.0 Social relationships 1 0.5 0 0.0 0 0.0 0 0.0 Spiritual 0 0.0 0 0.0 0 0.0 0 0.0 Lifestyle 1 0.5 0 0.0 0 0.0 0 0.0 a Multiple-choice response. Frontiers in Pharmacology | www.frontiersin.org 7 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being FIGURE 2 | Graphs of the mean values (dots) of primary and secondary outcomes at T-1, preassessment (T0) and postassessment (T1). (A) Psychological Well- Being Scales: Total Scale. (B) WHO Quality of Life Spirituality, Religiousness, and Personal Beliefs (WHOQOL-SRPB): Total Scale. (C) Oxford Happiness Questionnaire. (D) World Health Organization Quality of Life-BREF (WHOQOL-BREF): Psychological Health Scale. (E) World Health Organization Quality of Life-BREF (WHOQOL- BREF): Social Relationship Scale. (F) EQ-Decentering Scale. *p value < 0.05. **p value < 0.01. T-1  Two months before entering the center; T0  15 days before entering the center; T1  15 days after entering the center. PWBS, Psychological Well-Being Scales; WHOQOL-SRPB, World Health Organization Quality of Life Spirituality, Religiousness and Personal Beliefs; WHOQOL-BREF, World Health Organization Quality of Life. secondary outcomes in the subgroup analysis are presented in [1.31 (SD  1.58); p < 0.001] and not between T0 and T1 [0.12 Figure 2. (SD  1.48); p > 0.999], and Social Relationships Scale improved ANOVA revealed a significant main effect of time on the [F (2; 80)  22.00; p < 0.001; d  0.79; 95% CI, 0.44–1.15] only PWBS Total [F (1.6; 58.6)  26.84, p < 0.001]. Post hoc tests between T1 and T0 [1.76 (SD  2.22); p < 0.001] and not between showed a significant improvement only between T1 and T0 T0 and T1 [0.37 (SD  1.80); p  0.574]. [17.49 (SD  18.98); p < 0.001] and not between T0 and T-1 Finally, the significative increase in decentering [F (1.4; 56.6)  [−0.88 (SD  11.62); p > 0.999]. These results indicate that the 29.90; p < 0.001] is observed only between T1 and T0 [6.32 (SD  reduction in the total score of psychological well-being was only 6.68); p < 0.001) and not between T0 and T1 [−0.78 (SD  3.32); observed during participants’ stays at the center. Effect size was p  4.111]. Effect size between T1 and T0 was large (0.95; 95% CI, large (0.92; 95% CI, 0.62–1.22). 0.65–1.26). Similarly, ANOVA revealed a significant main effect of time on secondary variables during participants’ stays at the center (Figure 2). Oxford Happiness Questionnaire [F (2; 82)  26.14; Risk’s Perception of the Ayahuasca Use in p < 0.001] shows an improvement only between T1 and T0 [0.61 the Participants’ Original Countries (SD  0.61); p < 0.001] and not between T0 and T-1 [−0.07 (SD  At T2, 92.5% of the sample wished to continue taking ayahuasca 0.55); p > 0.999]. The effect size between T1 and T0 was large in the future. However, only 14.9% drank ayahuasca between 1 (0.99; 95% CI, 0.66–1.31). and 3 times, 11.7% between 4 and 10 times, and 8.5% more than Total Scale of WHOQOL-SRPB [F (1.4; 57.3)  49.02; <0.001] 10 times at T4. This means that 64.9% of the sample didn’t drink shows the improvement only between T1 and T0 [0.58 (SD  ayahuasca over the 12 following months after leaving the center. 0.45); p < 0.001] and not between T0 and T1 [−0.06 (SD  0.26); Nevertheless, 92% of the sample affirmed to be exposed to p  0.504). The effect size between T1 and T0 was large (1.29; 95% several risks in taking ayahuasca in their country of origin, such as CI, 0.93–1.65). legal charges (71.3%), health problems due to the lack of The subscales of the WHOQOL-BREF show a similar pattern, guarantees regarding the composition of ayahuasca (40.8%), or being Psychological Health Scale improved [F (1.7; 71.3)  18.30; the disability to consult with professional experts in case of p < 0.001; d  0.83; 95% CI, 0.53–1.13], only between T1 and T0 adverse effects (26%). Moreover, 40.3% of the sample affirmed Frontiers in Pharmacology | www.frontiersin.org 8 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being risks related to their personal safety not being able to guarantee medical intervention that is not explicable by our Western, that the person administering ayahuasca follows a professionally materialist worldview, probably because of our epistemological regulated practice and complies with a code of ethics. Finally, and perceptual biases (Turner, 1992; Walsh, 1990). Expanded more than a half of the sample (59.7%) affirmed that ayahuasca science (Lorimer, 2019) is necessary to establish the extent to should be practiced by Amazonian healers or practitioners with which the medical intervention of the healers could be conceived comprehensive traditional training. as performative contextual healing or whether it is a qualified and replicable medical practice rooted in indigenous knowledge and the underlying ontologies. DISCUSSION The effect size is high in all PWBS total assessments, self- acceptance being the subscale which presents a higher In this prospective, observational non-controlled study, we improvement after the retreat and follow-up assessments. Self- examined the long-term impact that ayahuasca, used in a acceptance is defined as a positive attitude toward oneself that ceremonial Shipibo context, can have on the integral well- entails a regulation process of the self-concept, which is one of the being of the individual. Participants who have completed the most significant and powerful regulators of behavior and affect evaluations throughout the year show a significant increase in (Markus and Wurf, 1987). Distortions in the experience of one’s psychological well-being, subjective well-being, spiritual well- “self” are central to the psychedelic experience, such as in the being, and quality of life after the stay in the retreat. These “ego-dissolution experiences” (Nour et al., 2016). However, outcomes are confirmed by the reports of most of the following Gergen (1985), self is also a construct cocreated by participants who affirmed sustained benefits on personal culture, societies, and individuals at a particular time and place, well-being over one year, followed by spiritual benefits. The which is constituted in relationship with others. This implies that subgroup analysis performed in a representative subsample beyond the phenomenological experience with ayahuasca, the allowed us to infer that the significant differences in outcomes reflection process of the experience during the integration are due to the effect of their stay at the center and not the sessions where people are able to share in a collective with passing of time. their own subculture could allow for the organic emergence of Well-being is a relevant worldwide factor directly linked to the new meanings about the self that could be easier to accept. prevention of mental disorders as well as to the promotion of Indeed, several authors describe how ayahuasca ceremonies mental health (Huppert, 2009). In fact, well-being is a highly may enhance interpersonal bonds and social identity (Dobkin complex construct that entails physical, mental, and social well- de Rios, 1984; Winkelman, 2007). being (WHO, 2001). The results presented in this article show a Another ability related to self-regulation is decentering, which significant and sustainable long-term improvement in well-being engenders disidentification from internal experiences and from a holistic view, including the physical and social reduced reactivity to thought content (Bernstein et al., 2019). relationships quality of life in addition to psychological, This is an important mechanism of change that functions as an subjective, and spiritual well-being. These results are in line emotional regulation–mediating process underlying different with several studies that have observed a high level of well- salutary effects (Teasdale et al., 2002). Given the relevance of being in people who take ayahuasca regularly in ritual this mechanism to promote health and well-being, multiple communitarian context (Ona et al., 2019), and in religious clinical intervention programs focus on teaching patients the ceremonies (Bouso et al., 2012; Bouso et al., 2015; Barbosa techniques to develop this ability (Sauer, Baer, 2010; Bieling et al., et al., 2016). Ayahuasca users have shown even higher well- 2012). Our results show a high-effect size in the ability of being than those who had taken classic psychedelics such as LSD decentering at all point assessments as well as a moderate or Psilocybe mushrooms (Lawn et al., 2017; Griffits et al., 2019), correlation between the improvement in decentering and especially in life satisfaction, social relationships, spiritual psychological well-being after the retreat. These results are awareness, and attitudes about self and life (Griffits et al., supported by several studies, which have found a significant 2019). Since LSD or mushrooms are not usually used in a improvement in this ability, 24 h after taking ayahuasca (Soler ritual context, these results lead us to consider the role of the et al., 2016; Dominguez-Clave et al., 2019; Gonzalez et al., 2020; ceremony in the positive and long-term impact on the well-being Murphy-Beiner, Soar, 2020), being maintained over one-year of the Western people (Cooper, 1987). Kaptchuk (2002) argues follow-up (Gonzalez et al., 2020). Given that the development that the alternative medicine used in ritual settings may of this skill has not been formally taught in the ayahuasca administer an especially large dose of “performative efficacy,” ceremonies of those previous studies, these results lead us to which relies on the power of belief, imagination, symbols, hypothesize about the possibility that the development of this meaning, expectation, persuasion, and self-relationship. These ability could be acquired and sustained long-term through an factors could be understood in biomedical science as the placebo experiential learning process (Kolb, 1984) with what is effect or what Miller and Kaptchuk (2008) call “contextual traditionally known as “master plants” (Luna, 1986). healing.” Indeed, in our sample, 36% of the participants Experiential learning is an embodied, complex process often affirmed that the work of the Shipibo healers was the most triggered by an emotionally intense experience in a important factor in the improvement of their well-being, even contextually rich learning environment that becomes more than ayahuasca itself. However, as it has been explained in embodied in memory traces (Morris, 2019). Understanding the introduction, Shipibo healers claim to be performing a specific the benefits of ayahuasca as an experiential learning process Frontiers in Pharmacology | www.frontiersin.org 9 May 2021 | Volume 12 | Article 623923 Gonzalez et al. Ayahuasca to Promote Well-Being opens the door to investigating multiple mechanisms of action DATA AVAILABILITY STATEMENT that have not yet been studied in depth in the field of psychedelics, such as the mediating role of cognitive reappraisal and The original contributions presented in the study are included in contextualized meaning-making (Zepke and Leach, 2002). the article/Supplementary Material, further inquiries can be It is important to consider the limitations of this study. directed to the corresponding author. First, the naturalistic design of the study does not allow us to isolate the effects of ayahuasca from the other diverse variables in the setting, which include the work of the ETHICS STATEMENT Shipibo onanyabo during the ayahuasca ceremony. In fact, the separation of the effects of ayahuasca from the onanyabo’s The studies involving human participants were reviewed and work is not conceived within this traditional medicine system. approved by the Ethics Committee on Animal and Human Moreover, without a placebo control group, it is not possible Experimentation of the Autonomous University of Barcelona to determine the efficacy of ayahuasca as herbal medicine to (UABCEEAH Barcelona, Spain). The patients/participants promote well-being. Second, the sample selected is not provided their written informed consent to participate in this study. representative of the general population as they must have financial resources to attend this center, and all of them wish to drink ayahuasca motivated by personal or spiritual growth AUTHOR CONTRIBUTIONS at baseline. Third, since participation in the study was not mandatory for people who signed up for the retreats, not all DG and JBS conceptualized the study design; IP and AA collected those who attended the center during the two-year period the data; JC analyzed the data; DG, MC, AA, MF, AF, JO, and JBS were recruited for the study. Furthermore, social desirability wrote the manuscript. response bias is associated with the use of self-report questionnaires. Vegetalismo, which includes the use of ayahuasca and many FUNDING other plant medicines, is still the primary operational health- care system in the Peruvian jungle since it is empirically This work was financially supported by the ICEERS and the efficient for the people, deeply rooted in the culture, and Beckley Foundation. financially accessible (Mabit, 1993). At the same time, more and more Western people travel to the Peruvian cities, such as Iquitos, in search of other alternative forms of healing and ACKNOWLEDGMENTS self-transformation they do not find in the Western biomedical system (Fotiou, 2010; Jara, 2014). However, in The authors wish to thank Matthew Watherston for allowing us the absence of international regulation of this medical system, to conduct the study at the Temple of the Way of Light and people are exposed to several risks; these risks were mentioned Aubrey Marcus for his generous philanthropic contribution. by 92% of the sample. Enhancing well-being is the best way to Special thanks to all of the volunteers for their participation promote mental health (Hupper, 2009) and the vision of the and contributions to our understanding in this field. World Health Organization is the attainment of the highest possible level of health by all people (WHO, 2020a). In view of this, we hope that this study can contribute to the further SUPPLEMENTARY MATERIAL recognition of ayahuasca as a herbal medicine used in the traditional medical context. Future studies are needed to The Supplementary Material for this article can be found online at: explore and evaluate vegetalismo as a traditional medicine https://www.frontiersin.org/articles/10.3389/fphar.2021.623923/ system. full#supplementary-material Placebo for Prevention of Depressive Relapse. J. Consulting Clin. Psychol. 80, REFERENCES 365–372. doi:10.1037/a0027483 Bouso, J. C., González, D., Fondevila, S., Cutchet, M., Fernández, X., Ribeiro Barbosa, P. C. R., Strassman, R. J., da Silveira, D. X., Areco, K., Hoy, R., Pommy, J., Barbosa, P. C., et al. (2012). Personality, Psychopathology, Life Attitudes and et al. (2016). Psychological and Neuropsychological Assessment of Regular Neuropsychological Performance Among Ritual Users of Ayahuasca: a Hoasca Users. Compr. 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Netw. 9, 1. doi:10.1111/ Copyright © 2021 Gonzalez, Cantillo, Perez, Carvalho, Aronovich, Farre, Feilding, j.1471-0374.2009.00245x Obiols and Bouso. This is an open-access article distributed under the terms of the Tupper, K. W. (2008). The Globalization of Ayahuasca: Harm Reduction or Benefit Creative Commons Attribution License (CC BY). The use, distribution or Maximization?. Int. J. Drug Pol. 19, 297–303. doi:10.1016/j.drugpo.2006.11.001 reproduction in other forums is permitted, provided the original author(s) and Turner, E. (1992). “Training to See what the Natives See,” in The Shaman’s through the copyright owner(s) are credited and that the original publication in this journal is Time: 500 Years on the Path of Knowledge. Editors J. Narby and F. Huxley cited, in accordance with accepted academic practice. No use, distribution or (London, United Kingdom: Thames & Hudson), 260–262. reproduction is permitted which does not comply with these terms. Frontiers in Pharmacology | www.frontiersin.org 12 May 2021 | Volume 12 | Article 623923