Risk Assessment Ayahuasca In a Religious Context: Adverse Effects

The Brazilian Journal of Psychiatry has just released a study that's both a risk assessment and a self reporting of side effects by users of this ceremonial drink. The results were rather positive in gaining much needed information about the type of medications being used with the religious practice – as well as diagnostics of people who partake in it as well as how those factor into adverse events in the use of it. Interestingly, psychiatric drugs being used by patients didn't cause issues that were noteworthy.

Regardless of how Ayahuasca's main ingredients are used, N,N‐dimethyltryptamine and certain monoamine oxidase inhibitor β-carbolines, The importance of gaining scientific data in this manner is imperative as laws loosen to allow for the use of certain psychedelics for multitudes of health issues – and as consumers begin to experiment even more this type of researcher is beyond helpful as both a guide and a foundation for even more.

In this cross sectional study the users were from a known religious institution. They answered a series of questions about the use of the ceremonial psychedelic, adverse effects, safety measures, and in regards to various risks factors including psychiatric diagnostics and pharmaceutical medications used.

Results The most frequent adverse effects among the 614 participants were transient gastrointestinal effects (nausea and vomiting). Fifty participants self-reported a psychiatric diagnosis (depression and anxiety were the most prevalent), and these participants experienced adverse effects more frequently. Psychiatric medication use was reported by 31 participants. No indication of increased adverse effects due to drug-drug interactions was found.

Participants with a reported psychiatric diagnosis experienced adverse effects more frequently than those without one – those with multiple diagnostics were in the 48% category that were taking a drug their doctor gave them for depression. Alarmingly, almost reports of adverse effects came from this sub population that did not report any type of drug interaction – this finding is beyond important as further research into metabolic contraindications with prescription drugs generally leans heavily on this type of clinical data.

As well, those that are educated in this arena and advocates for the use of these therapies and practices can gain knowledge from this clinical trial that may give insight to the combined use of the religious practice with other substances. Many will forego medications when cleansing with this ritual, and this may be a factor that requires further study.

Braz. J. Psychiatry, ahead of print  E-pub Oct 30, 2020

https://doi.org/10.1590/1516-4446-2020-0913

ORIGINAL ARTICLE

Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects

Caro Durante, Rafael G. dos Santos, José C. Bouso, Jaime E. Hallak

Faculdade de Medicina, Universidade Federal da Fronteira Sul (UFFS), Passo Fundo, RS, Brazil

Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil

Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Ribeirão Preto, SP, Brazil

International Center for Ethnobotanical Education, Research and Services (ICEERS), Barcelona, Spain

INTRODUCTION

Ayahuasca is a psychoactive brew traditionally used by indigenous Amazonian cultures for ritual and medical purposes. More recently, it became a ceremonial sacrament for Brazilian syncretistic religions, such as Santo Daime, Barquinha, and União do Vegetal (UDV).1,2 This study was conducted with members of UDV, in which ayahuasca is also called Hoasca and Vegetal, and is consumed ritualistically to promote a non-ordinary state of consciousness that can be described as “mental concentration,” around which the religious practices revolve.2 UDV members can attend regular bimonthly sessions at the existing centers, as well as extra sessions on special occasions. The distribution of ayahuasca during the sessions is supervised by an experienced member, the Mestre, who guides the religious ceremony.2 Currently, UDV is present in 11 countries, with more than 21,000 associated members.3 The brew used by UDV members is prepared with a typical combination of Banisteriopsis caapi and Psychotria viridis, also known as Mariri and Chacrona, respectively.4 By the decoction of these Amazonian plants, their active substances are extracted.1,4 The main component of ayahuasca is the alkaloid N,N‐dimethyltryptamine (DMT), a tryptamine present in the leaves of Psychotria viridis.5 This tryptamine acts predominantly as a 5-HT2A receptor agonist,6 with effects comparable to those of lysergic acid diethylamide, psilocybin, or mescaline.7

DMT is not orally active on its own, since it is metabolized by peripheral monoamine oxidase enzymes (MAO), especially the MAO-A subtype.6 These enzymes occur across several tissue types, and by catalyzing the oxidation of amines8 they have an important role in degrading neurotransmitters. Ayahuasca also includes alkaloids that act as MAO inhibitors (MAOI), namely harmaline, harmine, and tetrahydroharmine. These substances, extracted from Banisteriopsis caapi, belong to a group of β-carbolines known as harmala alkaloids.1,9 The presence of these MAOIs in ayahuasca prevents the degradation of DMT, enabling its absorption into systemic circulation and the central nervous system.1,9

Several conventional drugs exhibit some degree of MAO inhibition, and this effect was exploited by the first antidepressants.10 Inhibition of this enzyme results in an accumulation of the substances it usually degrades, including endogenous neurotransmitters.11 If the inhibition is too intense or sustained, the increased concentration of monoamines can cause systemic manifestations. When combined with monoaminergic substances, some MAOIs can cause deleterious reactions.12,13 One particularly worrisome outcome of inhibiting MAO enzymes, especially in combination with serotonergic agents, is the accumulation of serotonin to toxic levels, a condition known as “serotonin syndrome,” which, although rare, can be fatal.13

The influence of the MAO inhibition through ayahuasca’s β-carbolines is still poorly understood. Concern about the interaction of these MAOIs with other substances is due to research on conventional MAOIs, especially older antidepressants.14 Thus, the risk factors and contraindications generally proposed for ayahuasca are based on the effects and interactions observed from the combination of these medications with monoaminergic drugs, such as selective serotonin reuptake inhibitors, and foods rich in amines, such as aged cheeses and red wine, due to their tyramine content.11,14,15 The β-carbolines in ayahuasca act as selective (mainly on MAO-A) and reversible MAOIs, which could render these alkaloids safer than unspecific and irreversible MAOIs.9,15 Regardless of the mechanisms of action of each harmala alkaloid, their MAO-inhibiting properties and the indispensability of this condition for the psychotropic effects of ayahuasca are well-grounded.9

The subjective effects of ayahuasca are dose-dependent and closely related to serum DMT concentrations.16 These effects usually become noticeable 30-60 minutes after administration, peaking between 60-120 minutes, with an overall duration of 240 minutes.16 Effects on perception, such as characteristic visual imagery (“visions”), are consistently reported by most users. The perceptual alterations are accompanied by changes in cognition, affect, and volition.16 Many of these effects can attain spiritual importance in a religious context.

Common acute physical effects include nausea, vomiting, and diarrhea, which could be a result of increased levels of serotonin in the gastrointestinal tract.17 Cardiac effects such as increased blood pressure and heart rate may also occur and could be attributed to decreased degradation (and, thus, accumulation) of catecholamines, such as norepinephrine.17

Studies on ayahuasca and its safety were performed during the 1990s with UDV members in what came to be known as Hoasca Project. This project provided ayahuasca research some of its seminal works, with preliminary observations about short- and long-term effects. These investigations found no evidence of physical/psychological dependence or permanent sequelae due to long-term ayahuasca use in a religious context.1,17

In 1998, Callaway & Grob14 described the case of a benign serotonin syndrome, possibly induced by the interaction between ayahuasca and a selective serotonin reuptake inhibitor. This is the only case of such a reaction identified in the literature. Indeed, concomitant use of ayahuasca with other drugs and medications is not advised. Studies to establish the safety of ayahuasca in such situations are still required, especially due to the increasing number of users. These studies should investigate whether the previously recognized risk factors of conventional MAOIs apply to ayahuasca and to what degree, as well as whether the institution’s safety measures can prevent serious adverse reactions.

The main objective of this study was to assess the risk profile of ayahuasca use in a religious context. After reviewing the literature to identify important concerns and common adverse effects that could be self-reported, an instrument was developed that inquired about the frequency of the following effects: anxiety, diaphoresis, diarrhea, disorientation, distress, dizziness, drowsiness, dry mouth, headache, irritability, nausea, restlessness, shivers, tachycardia, tinnitus, tremor, and vomiting. Psychiatric diagnoses and psychiatric medication use were also considered risk factors due to their possible interactions with the MAOIs in ayahuasca. The existence and implementation of safety measures were also investigated. The collected data were analyzed to test the hypothesis that users with risk factors experience adverse effects more frequently, which could indicate that drug interactions elevate the concentration of monoamines to toxic levels, or have a negative influence on subjacent psychiatric conditions.

METHODS

This cross-sectional study was conducted with members of UDV centers in the states of Paraná, Rio Grande do Sul, and Santa Catarina. According to the organization’s internal records, these centers have a total of 1,547 associated members (UDV internal data; information granted March 2019), in addition to an undetermined number of non-associated attendees. The only exclusion criteria were age less than 18 years and never having used ayahuasca.

A questionnaire was developed on the use of MAOIs and psychedelics/hallucinogens in a religious context based on needs identified in the literature.8,14–16 The questionnaire was designed to gather basic sociodemographic data and describe relevant aspects of ayahuasca use, especially the general safety of MAOIs, characteristics suggestive of an increased risk of severe reactions, and adverse effects common to serotonin toxicity. Therefore, questions were designed to explore the frequency of ayahuasca use, medication use (mainly psychiatric), history of psychiatric disorders, and perceived adverse effects and their persistence, in addition to satisfaction regarding UDV safety measures.14–17,18,19

The development of the questionnaire carefully considered how incisively the questions could be interpreted and how they might precipitate judgment. Most opinion questions were designed as five-point Likert scales, and the participants were prompted to report a psychiatric diagnosis only if it had been confirmed by a licensed professional. The digital, self-applied questionnaire was shared and answered through an online link, ensuring a broad reach and easy availability. The digital form employed conditional logic to guide respondents through sections of questions, covering a broad range of topics while avoiding an excessive burden. Since the collected data may not thoroughly address some important topics, further investigation is required.

The questionnaire was distributed with the collaboration of volunteers from the UDV medical and scientific department, which represents UDV in the scientific community. Each center had a designated volunteer responsible for promoting the survey and sharing its link through regular UDV communication channels. Thus, the questionnaire was distributed mainly through social network groups. Through the online link, interested members were led to an informed consent form explaining the nature of the study and, after completing it, they proceeded to the questionnaire.

The participants were not necessarily invited directly, but were exposed to information about the survey in group meetings and online spaces commonly frequented by UDV members. Considering that ayahuasca users are a hard-to-reach population, this self-selection method was the only viable approach. Alternative sampling would have required disclosure of known UDV members, violating their right to privacy. The questionnaire remained open and accepted responses for a period of 7 weeks between February and March 2019, with periodic reinforcement of outreach efforts.

The collected responses were imported into LibreOffice Calc for data homogenization and preparation. GNU PSPP was then used to calculate the relative and absolute frequency distributions of the variables. Pearson's chi-square test of independence and Fisher's exact test were used to analyze variables of interest and identify differences between groups.

Because the β-carbolines present in ayahuasca may affect the degradation of monoamines, the concomitant use of serotonergic agents could result in symptoms of serotonin toxicity. Our hypothesis was that concomitant use of antidepressant medication, due to its monoaminergic action, could increase the frequency of reported adverse effects. This would suggest a possible interaction between antidepressants and the MAOIs present in ayahuasca. In addition, the frequency of adverse effects reported by participants with and without a psychiatric diagnosis was also compared. Finally, risk reduction measures were evaluated retrospectively. P-values < 0.05 were considered statistically significant.

Ethics statement

All participants provided electronic informed consent prior to accessing the questionnaire. This study was approved by the Universidade Federal da Fronteira Sul research ethics committee (CAAE: 02039218.5.0000.5564).

RESULTS

The sample consisted of 614 participants who agreed to answer the questionnaire after providing electronic informed consent. A total of 606 participants (99.7% of the sample) reported being members of one of the UDV centers in the three states investigated in the study, thus, the sample corresponds to 39.17% of the total population of UDV’s associate members in these states at that time. The remaining members may have declined to participate or were not reached during efforts to promote the survey. All 15 centers in the three-state area were represented, as well as one authorized distribution center.

The basic sociodemographic profile of the participants was similar to previous findings for Brazilian UDV members, suggesting nationwide homogeneity in this population.4 The participants had a mean age of 40.64 years (SD = 12.77), 52.28% were male, 63.68% were married or cohabiting, and most were highly educated (59.94% had bachelor’s degree or higher). Sociodemographic details are shown in Table 1.

Please visit the Brazilian Journal of Psychiatry to view the Study

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