Use of Phyllomedusa bicolour secretion during kambô ritual: observational responses, dosage, and risk of adverse events

Abstract The ‘kambô’ ritual involves application of Phyllomedusa Bicolor poison to superficial burns made on the user’s skin. Existing kambô literature describes case reports of severe harms. The objective of the current study was to better characterize typical observed responses to kambô administration. We performed a retrospective review of a kambô practitioner’s practice. Statistical analysis was descriptive, and characterized the number of kambô points or location of points administered as well as physical responses such as facial swelling, diaphoresis, immediate bowel movement, syncope, and occurrence of emesis. There were 147 unique participants that underwent 241 kambô rituals included. The mean number of points administered was 4.2 ± 2.2, while the median was 3 (range 1–11). Common physical responses included facial swelling (70.5%), diaphoresis (53.3%), bowel movement (45.2%), and syncope (10.4%). Higher number of points administered and receiving kambô at multiple locations appeared to increase facial swelling and diaphoresis. Responses to kambô are likely to be dose-dependent. No severe adverse effects were recorded in the sample, although some responses or components of the kambô ritual may promote risks of harm due to hyponatremia, asphyxiation from emesis, and injury due to syncope.


Background
Poisonous secretions from Phyllomedusa bicolour or the Giant Monkey Frog have been administered as part of a ritual termed kambô. Sometimes referred to as "sapo" which translates "toad" in Spanish, the name kambô comes from the traditional folk tale of the shaman who discovered the medicine, Kampu, whose spirit was said to have merged with all the Phyllomedusa bicolour frogs after his death. The secretion is applied by making superficial dot-like burns on the skin termed 'points' using a hot ember from end of a titica vine (Heteropsis flexuosa) and applying the secretion onto the exposed vasculature, where it is sequentially absorbed into systemic circulation [1] ( Figure 1). Several indigenous tribes of the Amazon basin including those in Brazil, Peru, Ecuador, and Columbia perform the Kambô rituals as part of their traditions [2]. Historically, the indigenous peoples use the secretion for many purposes: to increase stamina and resilience while hunting, treat ailments such as malaria and snake bites, and to clear negative energies or bad luck (panema) [3]. In recent years participants outside of the traditional indigenous regions seek the administration of the kambô frog's secretion through skin burn points for various reasons ranging from spiritual cleansing to the treatment of a number of mental or physical ailments such as depression, anxiety, addiction, pain, chronic infectious, and autoimmune conditions.
The Phyllomedusa bicolor secretion contains hundreds of identified compounds including alkaloids, steroids, bioorganic amines, proteins and peptides [4,5]. The secretion appears to be part of the frog's innate immune defenses, providing protection from microbes, fungal infections, and predators [6]. Many amphibian-derived compounds, including those found in Phyllomedusa bicolor, have been isolated, patented, and studied individually. Some peptides contained in the secretion such as the dermorphins and deltorphins exhibit potent opioid binding activity [7,8]. Others such as phyllokinin, phyllomedusin, sauvagine, and phyllocearulein have observable effect on blood pressure, gastric secretion and contraction, and vascular permeability [6,[9][10][11][12]. Dermaseptin is an anti-cancerous and antimicrobial agent being investigated for its ability to kill a variety of pathogens with low risk of cytotoxicity to the host [13][14][15][16]. Despite there being a some amount of biochemical literature on the peptides derived from kambô, there is little investigation that has attempted to understand the totality of the crude secretion's effect when applied to superficial skin burns such as in traditional application.
There is apparent increasing interest in kambô rituals and related incidence of harms . Google search trends reveal the term 'kambô' reached an all-time high in popularity among US users of the search engine in Oct 2021, with a sharp increase in popularity of the term since 2015 (Google Trends, Jan 1st 2000-Oct 27th 2021) [17]. Many websites that discuss psychedelic substances have published articles relating to kambô and tout it as a powerful way to increase the healing potential of psychedelics [18,19]. In parallel, MedLine was the first to publish an article about kambô indexed in 2014 with increasing reports in recent years (terms kambô or Phyllomedusa bicolour) [20]. Recent medical literature has highlighted case reports describing severe harms such as psychosis, cardiac events, hyponatremia, potential hepatoxicity, and death [21][22][23], yet lacks characterization of typical responses [2][3][4][5][6][7]. Therefore, we aimed to describe demographics of people seeking kambô, motivations for use, use parameters, and observed physical responses to administration.

Program description
A single facilitator who completed a training and certification offered by the International Association of Kambô Practitioners (IAKP) in safe administration practices led the kambô rituals performed on subjects in this sample. Participants complete a screening, receive instructions for preparation, as well as support in the post-use phase. Screening consists of completing an intake form and participation waiver in which potential participants report their age, sex, ethnicity, past medical history, current drug and supplement regimen, as well as their motivations or intended purpose for using kambô. Persons who report advanced cardiovascular conditions (uncontrolled hypertension, myocardial infarction, stroke, aneurysm), use of antihypertensive medication, Addison's disease, pregnancy, epilepsy or seizure disorder, liver or kidney dysfunction, schizophrenia, bipolar disorder or other serious psychiatric conditions, as well as recent use of selected illicit substances are excluded from kambô use [24]. All participants received a follow up email two days after the ritual, encouraging further contact with the facilitator if needing support or wishing to communicate feedback.

Ritual overview
The facilitator procured kambô via the IAKP, who claim the kambô is harvested and purchased from the Matsés peoples of Brazil. The practitioner instructed participants to fast for at least eight hours prior to use of Kambô due to strongly purgative effects and high potential for emesis, although imbibe water per usual. Subjects participated in the ritual either individually or in a group fashion with a maximum of six participants. A protective prayer and intention setting practice initiated the ceremonial container.
Before administration of kambô, the practitioner offered two other plant based Amazonian sacraments. Namely, a tobacco based intranasal snuff from Nicotiana rustica (Rapé) and an ophthalmic drop derived from the Tabernaemontana sananho shrub (Sananga). Anthropologists report that these sacraments are used in conjunction with kambô traditionally [25]. The choice of whether participants used each or both of these prior to kambô use was not recorded, although we estimate based on the facilitator feedback that a large majority of users partook.
Directly prior to kambô administration, each participant drank 1-2 liters of room-temperature water, which aids in comfort of vomiting (prevents dry heaving). Participants were instructed to avoid distilled or alkaline water. They are additionally instructed to sip water during the ritual. If the participant is kambô -naïve, the facilitator administered a test-point which consists of a single point-administration of kambô. The facilitator then observed the participant for 2-5 min to evaluate sensitivity, gauge appropriate additional dosage, and monitor for adverse reactions. Additional points may have then been administered. During the ritual, the facilitator provided emotional support to the participant, assisting them to the bathroom if needed, singing traditional songs, playing musical instruments, and providing energetic purification using incense. The effects of kambô lasted approximately 20-40 min, although the ritual in its entirety lasts between 2-2.5 h.

Participants & study design
We performed a retrospective record review of participants that underwent a Kambô ritual conducted between August 1st 2018 and June 31st 2019. Rituals were conducted within the Southwest region of the United States. There was no specific exclusion criteria for the study, although participants that did not have self-reported records available regarding ethnicity and age, or missing session information were excluded. Demographic variables such as age, sex, ethnicity, and motivation for using kambô were extracted from participant intake forms, while number of points administered, location of the points, and ratings of physical reactions to administration were recorded during their kambô session by the kambô facilitator.
There are no instruments designed to measure the effects of kambô, thus dichotomous scales (presence/ absence), categorical coding (e.g. location of points), or six point Likert scales (e.g. no diaphoresis = 0 to profuse diaphoresis = 6) were used to record the types and degrees of observed physical reactions to kambô. Shivering, syncope, and immediate bowel movements during the ritual were recorded as present/absent while facial swelling and diaphoresis were recorded using likert scales on a scale of 0-5, with 0 indicating absence and 1-5 indicated graded severity. Facial swelling was defined by the presence of symmetric bilateral swelling under the eyes, and around the cheeks and lips. In some participants, data regarding physical responses were incomplete, either due to conditions that precluded the practitioner from recording the data or a decision to start recording certain physical parameters at a later time. No data were knowingly omitted due to adverse harms or atypical responses.

Statistical analysis
We analyzed demographics and data related to physical responses subsequent to kambô administration descriptively. Frequencies, medians, and Inter Quartile Range (IQR) are presented for categorical variables. Primary experimental comparisons investigated associations between kambô exposure and the presence of diaphoresis and facial swelling. We performed an analysis on both the number of points administered as well as location of points administered. We chose these variables for comparison as the number of points may approximate dose, while receiving kambô at more than one location may increase systemic exposure. We use the term 'multi-site application' to denote sessions in which persons received kambô in multiple locations. We used Mann-Whitney U tests for dichotomous variables, and used the Kruskal-Wallis test for analysis when more than two groups were present. An alpha value of = 0.05 was used to determine statistical significance. We coded free text responses regarding motivation for participation into themes; treatment of medical condition, spiritual exploration, cleansing or purification, and personal growth. Participants were not limited to a single theme if their response demonstrated plurality in intention.

Sample demographics
Our data set contained 147 unique participants with a total of 241 kambô sessions. The sample was 68% female (n = 100) with a mean age of 38.9 ± 13.3 years.

Dosing, point location, and physical responses
The dosing in points, locations of points and observed physical response across all sessions are summarized in Table 1. The median number of points administered across the entire sample was 4.0 (IQR = 2.0). Males received a similar number of points to females.
Persons that received kambo at multiple locations (multi-site application, n = 36) experienced greater facial swelling (median rating 2 vs. 3) and diaphoresis (median rating 1 vs. 3) compared to participants that received kambo at a single location (n = 203). We found no statistical association between location of points and occurrence of syncope, a bowel movement, or shivering Participants whom received more points were significantly more likely to experience facial swelling (p = <0.001) and diaphoresis (p = 0.008). Differences between the number of points administered in persons with or without syncope (4.3 ± 2.5 vs 4.2 ± 2.1) or persons that shivered vs. did not shiver (3.4 ± 1.8 vs 4.2 ± 2.4) appeared minimal.

Discussion
To our knowledge, this is the first report of physical observations from numerous participants undergoing a kambô ritual. Our study characterized participant demographics, motivations of use, and explored the number of points (dose) and location of points. The majority of participants were persons that identified as female and Caucasian who sought out kambô for spiritual purposes and physical cleansing.
The analysis of this data set suggests that physical responses to kambô tend to increase with the number of points administered as well as administration of kambô at multiple body locations. These results may be expected given that number of points approximates dose administered and administration of kambô at several locations in the body may increase the overall amount of kambô in systemic circulation as administration is less localized.
While there were no serious sequelae observed in response to kambô administration in the study, physical responses such as facial swelling (70.5%) or syncope (10.4%) may carry risks of severe consequences such as compromised respiration or traumatic injury. In addition, 100% of participants in the kambô ritual drank 1.5-2 L of water and vomited (not recorded due to near certain predictability of emesis as a physical response), which could introduce risk of aspiration if the participant were in the supine position, or other consequences associated with electrolyte dilution and loss. These risks could be mitigated by having adequate personnel to assist persons to the restroom and catch them if syncope occurs, instructing participants to limit fluid intake to 2 L of water prior to use, and keeping participants either sitting upright or in the recovery position.
There have been a number of case reports documenting severe harms in response to administration of kambô including death [21,22,26,27]. Harms documented in existing case reports are somewhat disparate and include hyponatremia (SIADH), psychosis, seizures, hepatotoxicity, and sudden cardiac death. Due to the ritual involving intake of a large volume of water acutely as well as vomiting, it is reasonable to conclude some cases of severe harm may have involved excessive water intake or electrolyte losses that resulted in seizures or arrhythmias. Electrolyte losses may be compounded by use of other strong purgatives such as oral or rectal tobacco as well as the ritual psychedelic sacrament ayahuasca. Kambô is typically not considered to be strongly psychoactive, thus a report of psychosis is more difficult to interpret, although could also relate to use of confounding substances (e.g. ayahuasca) or pre-existing illness.

Limitations
This was a retrospective chart review of the kambô ritual practiced by a single facilitator. The study's methodology precludes any strong conclusions be drawn due to potential for confounding variables or biases. The sample had a high prevalence of females and persons with autoimmune disorders, although these demographics may be more reflective of participant affinity for the facilitator opposed to persons seeking kambô, due to the facilitator being female, having a history of autoimmune disease, and giving lectures on the topic. In the same vein, although severe harms were not observed in the study, it may be a function of the facilitator's conservative style and/or proactive approach to risk mitigation as opposed to inherent safety of kambô, and lack of use in close proximity to other strong purgatives (e.g. ayahuasca, oral or rectal tobacco). While the number of points is thought to approximate dose, the size of the points and variability in the secretion contents from different frogs limits understanding of dose-response effects. Rating scales employed are not standardized or validated instruments for measurement of response to kambô and were subjectively scored by the facilitator. Although no severe adverse outcomes were observed acutely, some participants may have had other adverse outcomes that occurred post-experience that was not captured in the data set or made known in follow-up emails. No biological measures such as blood pressure or samples such as blood draw were collected and no surveys or scales were administered to the participants. These limitations make it difficult to evaluate the frequency of hyponatremic blood levels versus severe observable symptoms of hyponatremia. The facilitator's involvement as a study investigator also contributes to the risk of bias in the data collection process.

Conclusion
Responses to kambô appear affected by both number as well as location of points administered. Observed responses such as facial swelling, emesis, bowel movement, and syncope as well as aspects of kambô use such as imbibing large amounts of water in short periods of time can introduce risks for medical emergency. However, in this sample of kambô administrations, no severe adverse harms were observed, likely due to risk mitigation strategies and close supervision by the administering facilitator. As the kambô ritual grows in popularity, a greater awareness amongst clinicians regarding risks associated with kambô is necessary.
Further study is needed to draw any conclusions about the safety or efficacy of the kambô ritual including but not limited to, physiological metrics, toxicity, acute and long term effects of regular use of kambô, biological effects, psychological effects, drug interactions, and potential contraindications. In addition to simple biological measures such as heart rate, blood pressure, cytokine levels, stress hormone secretion etc., psychometric scales should be administered before and after the kambô ritual in future studies to measure negative or positive psycho-emotional outcomes of kambô participation. Pharmacological studies in animal models using the whole secretion administered in a transdermal manner need to be conducted. More data needs to be collected from practitioners and participants in the forms of surveys, treatment details, and demographic information to better characterize who is seeking kambô, for what reasons, and the incidences of adverse events. With the increasing popularity of those seeking and participating in the kambô ritual, it is crucial to initiate more scientific research to evaluate the potential benefits and harms of kambô.

Disclosure statement
Benjamin Malcolm is a psychopharmacology consultant through Spirit Pharmacist. Caitlin Thompson is founder and senior kambô practitioner at Medicine Frog Kambo and is founder of EntheoZen (nutritional supplement company). John Tegzes declares that he has no conflict of interest.

Funding
The author(s) reported there is no funding associated with the work featured in this article.