Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center

This methodological paper (2021) describes a study protocol designed for the purpose of investigating ayahuasca-assisted treatment for substance use disorders via various types of longitudinal measures that are sensitive to contextual factors to evaluate the therapeutic outcomes of an established intervention within a naturalistic setting.


Introduction: The present study describes the protocol for the Ayahuasca Treatment Outcome Project (ATOP) with a special focus on the evaluation of addiction treatment services provided through Takiwasi Center, the first ATOP study site. The goal of the project is to assess treatment outcomes and understand the therapeutic mechanisms of an Ayahuasca-assisted, integrative treatment model for addiction rehabilitation in the Peruvian Amazon.

Methods: The proposed intervention protocol highlights the significance of treatment setting in the design, delivery, and efficacy of an addiction rehabilitation program that involves the potent psychedelic tea known as Ayahuasca. After describing the context of the study, we put forth details about our mixed-methods approach to data collection and analysis, with which we seek to gain an understanding of why, how, and for whom this specific ayahuasca-assisted treatment program is effective across a range of outcomes.

Results: The ATOP protocol employs qualitative research methods as a means to determine which aspects of the setting are meaningful to clients and practitioners, and how this may correlate with outcome measures.

Discussion: This paper delineates the core principles, methods, and measures of the overall ATOP umbrella, then discusses the role of ATOP in the context of the literature on long-term residential programs. To conclude, we discuss the strengths and limitations of the protocol and the intended future of the project.”

Authors: Brian Rush, Olivia Marcus, Sara García, Anja Loizaga-Velder, Gabriel Loewinger, Ariane Spitalier & Fernando Mendive



International research remains focused on finding effective interventions for substance use and other mental disorders, and there is growing interest in interventions based on traditional and complementary medicine. A study in the Peruvian Amazon is assessing the outcomes and understanding the therapeutic mechanisms of ayahuasca-assisted treatment.

Ayahuasca is a psychoactive plant beverage that originated in the Amazon region of several South American countries. It was used as a religious sacrament by syncretic Christian churches in the 20th Century, and has since spread to Europe, Australia, and North America.

Ayahuasca is of growing interest to the international research community for its putative therapeutic effects and its implications for global mental health, local and international drug policy, cross-cultural psychiatry, neuroscience, intellectual property law, indigenous rights, and intangible cultural heritage.

Ayahuasca and Treatment for Substance Use Disorders

Ayahuasca may be effective for addressing problematic substance use, including substance use disorders. Observational studies among frequent ayahuasca users have consistently shown either complete remission in some cases or considerably reduced substance use in other cases. Researchers report positive outcomes on addiction-related measures in a follow-up assessment of members of an indigenous community participating in a structured ayahuasca retreat in Canada, and in qualitative interviews with people engaged with rural or urban-based ayahuasca-assisted treatment for substance use disorders.

While more research is needed, the evidence suggests that occasional or long-term use of ayahuasca within well-structured ritual contexts carries little health risk and no addictive potential.

Explanatory Mechanisms: Set and Setting Beyond Neuropharmacology

The underlying mechanisms through which ayahuasca-assisted treatment may exert its therapeutic effects are complex and multi-factorial. These mechanisms include the general effects of tryptamines and harmala alkaloids on both dopaminergic and serotonergic systems.

Brierley and Davidson (2012) reviewed the neurobiological mechanisms underlying harmine pharmacology, and found that harmine can regulate aberrant dopamine reuptake rates, which may be relevant for treatment of substance use disorders. A systematic review of clinical trials published in the last 25 years on the antidepressive, anxiolytic and anti-addictive therapeutic benefits of ayahuasca, psilocybin, and LSD found that several potential mechanisms were involved, including agonism of the serotonin 5-HT1A/2A/2C receptors, modulation of glutaminergic neurotransmission, and anti-inflammatory action.

Neuroimaging studies suggest that the default mode network (DMN) is involved in the entropic brain hypothesis, and that the interoceptive system is also involved in drug use disorders, as it processes information about body state and external stimulation, makes a prediction about risk and benefit, and then launches a behavioral response.

A complex interplay between the dose and quality of the substance ingested, the individual characteristic of the person (set), and the therapeutic context of the experience itself (setting) is proposed to be the key underlying mechanism.

Ayahuasca has historically been used in the treatment of substance use disorders. It has been shown to enhance self-acceptance and the ability to take a detached view of one’s own thoughts and emotions.

DMT-induced experiences of ego dissolution and near-death experiences are known to confer long-term positive changes in well-being. Psychosocial integration of the ayahuasca experience is also noted to be particularly important for positive outcomes.

Ayahuasca users emphasize the importance of the transcendental, or “peak”, mystical experience as a strong mediating factor in treatment outcome. Mystical experiences have also been found to have an important therapeutic value in research on the use of psychedelics for alleviating depression and anxiety in terminally ill cancer patients. Ayahuasca users report more positive mystical experiences, with more enduring impact on life satisfaction, social relationships, spiritual awareness in everyday life, and attitudes about life and self compared to those using other psychedelics.

The importance of the therapeutic setting is highlighted by several studies, including Griffiths et al. (2019), Talin and Sanabria (2017), and LaFrance et al. (2017). These studies highlight the importance of the therapeutic environment for successful substance use treatment outcomes.

Some organizations in Brazil, Colombia, Ecuador and elsewhere offer ayahuasca-assisted treatment for substance use disorders, and ayahuasca tourism engenders certain perceptions, expectations, and a particularly curated kind of esthetic and relational experience with ayahuasca shamanism.

The Ayahuasca Treatment Outcome Project

ATOP is a multi-site research project with subprojects and teams in different countries. The success of ATOP depends on the decisions made by a central team on the core features of the ATOP umbrella, and the commitment of the sub-projects to follow the core principles and protocols.

At a workshop held in October 2013, participants from different treatment centers, scientific disciplines, and therapeutic orientations identified key principles and elements of a common protocol to allow for synthesis of the research across multiple sites.

Core Inclusion Criteria

The ATOP umbrella was defined to evaluate ayahuasca-assisted services for addiction-related challenges, including co-occurring mental health challenges and physical health challenges. It was also decided to include tobacco use disorders within project scope but to exclude “process addictions” such as sex addiction, gambling or video gaming.

Core Methods and Measures

The study used contextual descriptions, interviews, observational design with mixed methods, and scheduled semi-structured interviews with study participants for qualitative analysis.

The ATOP-Takiwasi study was initiated in January 2016 and is the first and only active ATOP study site. It is now poized to report on the first cohort of patients followed for a full 12 months after discharge.

Justification for the Study

The Takiwasi Center is unique among ayahuasca-assisted healing centers because it is an integrative rehabilitation clinic that incorporates rigorous and frequent medical and psychological pre-treatment assessment, ongoing monitoring, and supervision. Takiwasi provides a stable environment for the conduct of a scientifically sound study of treatment outcome, given its longevity and organizational maturity, and its complex protocol of traditional plant medicine, rituals, psychotherapeutic and self-help approaches. Since its inception, Takiwasi has supported more than 70 research studies, mostly master’s and doctoral theses, across several disciplines. These studies have investigated the inpatient population, seminar participants, and a mix of inpatients, seminar participants, and outpatient diet-retreat participants.

Treatment for Substance Use Disorders and Long-Term Residential Programs

The Takiwasi Center offers ayahuasca-assisted healing and long-term residential treatment. This treatment model can be viewed as part of a stepped-care model, whereby one might need to “step up” to this option after less intensive options have been explored. Outcomes are highly variable with respect to therapeutic communities specifically, with the most positive outcomes reported by reviews focused on recovery-oriented outcomes such as legal and employment status and psychosocial functioning. However, treatment completion rates are very low, with 51.8% non-completion rates measured. Positive treatment outcomes appear to be associated with the duration of long-term residential treatment, up to about 18 months, but the cost-effectiveness of such treatment is diminished.

Long-term residential treatment can be an effective treatment option in well-circumscribed, individual circumstances, and within a stepped-care continuum of services and supports. More research is needed to identify alternative and innovative treatment models.


There is considerable anecdotal, retrospective and prospective quantitative evidence about the therapeutic effectiveness of ayahuasca-assisted treatment for problematic substance use, including substance use disorders, as well as mood and anxiety disorders. More research is needed with more diverse samples and cultural/therapeutic contexts.

Takiwasi Center is an alternative treatment option for those seeking ayahuasca-assisted treatment for substance-related challenges, including severe substance use disorders. It offers a unique opportunity to further our understanding of both the therapeutic value and the active ingredients of an integrative therapeutic model.

Contribute to the understanding of ayahuasca-assisted treatment for substance use disorders, inform other potential ayahuasca-assisted modalities for treatment of substance use disorders, and identify strengths, challenges and limitations within the current Takiwasi treatment model.

Research Methods Research Setting

The Takiwasi Center, located in the Upper Amazonian region of Peru, uses ayahuasca in combination with traditional Amazonian medicine, psychotherapy, and community living.

The Center offers a variety of programs and services, including a long-term residential treatment program for substance use-related rehabilitation, modeled in large part after a therapeutic community (TC) model. The treatment philosophy puts a strong emphasis on spirituality, particularly in the framework of traditional Amazonian medicine. Takiwasi is not a religious institution, but has a notable Catholic influence and presence. The main building contains iconography from other spiritual traditions as well, such as Buddhism and yoga.

The model of addiction is embedded in a spiritual framework, where problematic substance use is conceived as a misguided spiritual ‘self-initiation’ that turns into harmful behaviors. At Takiwasi, the philosophy acknowledges that the contextual and ritualized use of sacred medicines can be highly beneficial for the individual.

The Takiwasi treatment regime is highly structured, and consists of a nine-month internment divided into three “trimesters” or treatment phases. The first eight days are dedicated to detoxification, followed by a regime of restricted diet, herbal saunas and baths, and drinking depurative plants. The Center offers individual psychotherapy sessions, group therapy activities, ergotherapy, a variety of workshops, and plant formulas for daily intake. Patients participate in weekly rituals with purgative plants, three to four eight-day isolation plant retreats, and ayahuasca ceremonies two times a month.

Study Design

The study design is grounded on the premise that the treatment protocol at Takiwasi is a complex intervention, delivered within a unique organization with multiple mechanisms of action. The study takes into account the interaction between set and setting, and uses a mixed-methods approach to measure individual health and wellbeing.

A mixed-methods approach is consistent with trends in the literature on recovery from substance use disorders that advocate going beyond assessment of abstinence to incorporate a broad range of metrics for positive treatment outcome.

Our research design was influenced by several practical considerations, including the lack of a realistic opportunity to randomly assign patients to alternative treatment conditions, and the anticipated high treatment drop-out rates.

A research design was formulated that is appropriate and feasible within the Takiwasi context, and a set of core quantitative measures were implemented at baseline, discharge, 3, 6, 12, 18-months and 24-months follow-ups. The baseline assessment includes a research-based, psychiatric interview to define status regarding substance use and other mental disorders by international standards, followed by administration of several measures to assess severity of substance use disorder, quantity and frequency of substance use, motivation for treatment, and quality of life. Although initially conducted via telephone on Internet, the follow-up quantitative data collection was converted to an on-line platform for purposes of cost-efficiency and with personal support available as needed by the respondent.

The qualitative component of the mixed methods design included patient semi-structured interviews, staff, therapists and healers interviews, as well as a contextual description of the Takiwasi treatment center based on existing literature.


Baseline information is gathered at baseline including duration of substance use problems, previous formal and informal treatment experiences, and motivations and expectations.

The Takiwasi treatment process uses ayahuasca in a manner that draws heavily upon Peruvian practices. The specific questions in the interviews reflect these practices.

A framework was developed to explore the subjective experience with ayahuasca and its therapeutic context. The interviews explore various elements of the overall ceremonial/therapeutic process, including elements of the ceremonial experience, activities aimed at integration, psychotherapy or other therapeutic assistance, group sharing, and therapeutic use of other plants.

Study Recruitment and Measuring Treatment Exposure

A significant proportion of clients who initiated services at Takiwasi during the study period left the program before any use of ayahuasca, and therefore, are not eligible for study inclusion. This presents a challenge for any observational study with a follow-up component in substance use treatment services.

The level of treatment exposure for those formally accepted into the study cohort after the initial ayahuasca experience is important to account for in the study design and analysis. Two approaches are used to measure treatment exposure: by calculating the number of weeks of treatment participation and by calculating the program participation index.

To investigate response bias in our study sample due to early or subsequent treatment drop-out, clients who left prematurely will be contacted and a questionnaire will be mounted for on-line completion.

Interviews with Managers, Staff and Healers

In addition to interviews with program participants, managers, staff, therapists, and healers were interviewed. The interviews explored the participants’ personal religious and spiritual practices, their use of alcohol or other drugs, and their beliefs about alcohol and other drugs.

Contextual Description of Takiwasi Center

The contextual description of an ATOP program includes the physical and organizational infrastructure, staff/personnel, prevailing beliefs and mores about addiction, interventions provided, strategies for safety, integration, follow-up and/or continuing care, and cultural and community context.

Analysis Plan

The analysis plan for the mixed methods project is guided by specific predetermined research questions and undertaken by two analytic teams working independently but meeting bi-weekly as a unified project team.

The research questions guiding the analysis were developed by the overall team and included both quantitative and qualitative analyses.

Takiwasi treatment outcomes are associated with the individual’s previous experience with substance use treatment, baseline physical and mental health challenges, and the significance attached to the overall Takiwasi treatment experience.

At 12 months post-discharge, patients report reduced substance use and overall addiction severity, improved symptoms of anxiety and depression, and improved overall quality of life.

The quantitative analysis team will prepare a unified, person-level Excel data file and analyze the data through six steps.

The study analyzes the characteristics of the study sample, treatment participation and perceived importance of Takiwasi treatment activities, and visualizes trends over time across a range of outcome measures. A team-based, measures minimization process is used to reduce the number of predictor and outcome variables. 6) Prepare DAGs to conceptually model the hypothesized relationship between predictor and moderating variables and outcome. These DAGs serve as the basis for multivariate regression modeling.

Post-discharge outcomes will be analyzed with a generalized linear mixed effects model including random intercepts and random slopes, and potentially time-varying baseline and within-treatment covariates.

Qualitative analytics will be conducted with patients in Takiwasi by a team of four researchers using a cloud-based qualitative data analysis program. The team will focus on several themes including recovery capital, expectations and perceptions of treatment, spirituality, religiosity, and social influences.

Integrative quantitative and qualitative analytics will be performed on patients based on their overall treatment outcome and then cross-referenced within each of the three groups to identify important predictive or moderating factors.

Qualitative analytics will be used to analyze manager, staff, therapist and healer interviews. The research questions concern the homogeneity of the therapeutic culture at Takiwasi.

Takiwasi therapists’ main theoretical training, non-psychotherapeutic skills, views on religion, perceptions of care, psychology/psychotherapy, and practice, and the prevailing views and subjective understanding of addiction and related challenges are explored, as well as the match between practitioners and the treatment provided at Takiwasi.

The qualitative analysis team will employ a grounded theory approach and will modify the original guiding research questions according to significant themes that emerge.


Research on ayahuasca has pointed to its therapeutic value for substance use disorders, as well as other mental health challenges, including depression and anxiety. Ayahuasca is also poised to be situated on the bridge between ancestral medical traditions and the modern, westernized medical application of psychedelics.

Ayahuasca-assisted treatment for substance use disorders at Takiwasi Center was evaluated using a comprehensive evaluation protocol. The protocol was designed to investigate the role of context in the determination of treatment outcomes.

The current protocol for a study on ayahuasca-assisted treatment for substance use disorders will contribute to the understanding of ayahuasca-assisted treatment for substance use disorders by using multiple validated measures of predictors, potential moderators, and outcomes, as well as multiple measures of program participation and satisfaction with services.

This study aims to inform other potential ayahuasca-assisted treatment modalities for substance use disorders, as well as psychedelic-assisted therapy more generally, by identifying the role of non-pharmacological elements of the treatment context.

It will be important to explore how the treatment model under investigation might translate to more readily accessible outpatient services using ayahuasca- or other psychedelic-assisted interventions, and for whom they are most appropriate. Using our study as an illustrative case-in-point, the research focuses on evaluating outcomes of an integral treatment program as a whole, where different practices take place (e.g., singing, application of perfumes, and intake of other psychoactive medicinal plant preparations like tobacco juice) during the same session.

To facilitate cross-study comparisons, the ATOP study used a comprehensive set of measures that map well onto the recommended outcome domains for evaluating substance use treatment. The study used a mixed methods design and provided all measurement tools as easily accessible Supplementary Material.

The ATOP measurement model did not include measures of the immediate psychedelic or “mystical/peak” experience, as the purpose of the study was not to assess specific effects of ayahuasca as a dose-response mechanism, nor aim to systematically disentangle pharmacological vs. non-pharmacological factors.

The third study goal is to advance the body of knowledge on treatment of substance use disorders and factors associated with positive treatment outcome in long-term residential therapeutic community treatment alternatives. What role does spirituality play in substance use treatment? Takiwasi’s spiritual model of addiction may provide insight into how the TC model, and other treatment models, can be enhanced within a broad bio-psychosocial-spiritual framework.

The project team will conduct a research protocol to identify strengths, challenges and limitations within the current Takiwasi treatment model in order to contribute to ongoing efforts toward quality improvement.

Limitations and Conclusion

The limitations of the study protocol preclude strong statements of causality, and the study design may identify particular aspects of treatment context that could potentially be manipulated in an experimental design.

We note that a high rate of program not-completion is common to Takiwasi Center and that this is a source of potential bias. A sub-project has been initiated to follow-up with all Takiwasi study patients who have left the program prematurely.

This protocol describes a comprehensive approach to evaluating outcomes associated with a context-dependent ayahuasca-assisted treatment intervention for substance use disorders. It may also provide a framework for conducting studies with psychedelic-assisted therapy more generally.


The authors designed the study, wrote the manuscript, and collected data. SG, AS, GL, FM, and AL-V contributed conceptual support to the manuscript.


The authors would like to thank the participants and financial contributors to the ATOP workshop, Celina De Leon and Simon Green, as well as the managers, staff, therapists and healers at the Takiwasi Center for supporting this work.

Study details

Compounds studied

Topics studied

Study characteristics
Longitudinal Theory Building

PDF of Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center