Participants

We recruited our sample from three different countries in Europe (Czech Republic (N = 25), Spain (N = 10), and The Netherlands (N = 7)). In all three locations, the participants inhaled vapor from dried toad secretion containing 5-MeO-DMT. The participants were invited to enter the study on site. Overall, 75 participants agreed to participate in the study at baseline. Of those, 42 participants completed the test battery both before inhalation of the vapor from dried toad secretion containing 5-MeO-DMT (baseline) and within 24 h, while only 24 completed the test battery at the third and final assessment 4 weeks after intake.

Most participants were from Europe (n = 34 [81%]) while the rest of the participants were from Asia (n = 2 [4.8%]), Australia (n = 2 [4.8%]), South America (n = 3 [7.1%]), and North America (n = 1 [2.4%]). Sixty percent of the sample were males and 40% females. The mean age for the entire group was 38 years (SE = 0.80).

Furthermore, their motivation to inhale vapor from dried toad secretion containing 5-MeO-DMT included increasing self-understanding (N = 18 [42.9%]), solving personal problems (N = 5 [11.9%]), the combination of both (N = 1 [4.2%]), and other (N = 18 [42.9%]) reasons. A listing of these “other” motivations or reasons to inhale vapor from dried toad secretion containing 5-MeO-DMT is given in Table 1. In regard to education level, most participants had completed high school (N = 14 [33.3%]), a similar percentage had obtained a bachelor’s degree (N = 13 [31%]), a Master’s degree (N = 11 [26.2%]), and a lower proportion held a Ph.D. (N = 3 [7.1%]). One participant had only completed elementary school (N = 1 [2.4%]). In total, 15 participants reported having had no previous experience with 5-MeO-DMT (whether this was a toad, synthetic, or plant was unspecified), while the majority (92.9%) had experience with other psychedelics (e.g., LSD, psilocybin, etc.). In regard to mental health status as per self-reports, 32 (76.2%) of the participants reported having no mental health disorder, 1 (2.4%) participant reported having depression, 1 (2.4%) participant reported having a personality disorder, and 1 (2.4%) participant reporting having another mental health disorder not included on the administered list. Furthermore, 4 (9.4%) participants reported having anxiety, while 3 (7.1%) participants reported addiction. As per the nature of this observational study, participants who attended the session to inhale vapor from dried toad secretion containing 5-MeO-DMT were included in the study if they met the inclusion criteria (fluent in either Spanish, Czech, Dutch, or English, were over 18 years of age, and gave their written informed consent). The study was approved by the Ethical Review Committee for Psychology and Neuroscience (ERCPN), from Maastricht University, Maastricht, The Netherlands. Participation was voluntary and no incentives, monetary, or otherwise, were offered in exchange for participation.

Table 1 Listings of motivations for participants for inhaling vapor from dried toad secretion containing 5-MeO-DMT Full size table

Setting

The sessions in the Czech Republic and The Netherlands were conducted in the open, e.g., in a garden or in nature at a secluded location, whereas the session in Spain was held inside in a tipi or a rented house (as these sessions took place in winter).

The goal of the sessions was to relieve individuals from psychological and physiological issues, increase their well-being, and facilitate personal insights/personal healing. The facilitator was often assisted by another person, either with a background in coaching (i.e., a person trained in supporting clients in achieving a specific goal through providing training and guidance), or a person with no (clinical) background in psychology or in psychedelic-assisted therapy at all. These individuals (with or without background) had previous experience with 5-MeO-DMT (if this was a toad, synthetic form, or plant was not specified), and got involved at the sessions out of personal interest. Participants on antidepressant medications or suffering from a mental health disorder such as schizophrenia, other psychoses, or cardiovascular illnesses were not allowed to participate in the sessions by the facilitator or the assistants. Yet it is important to highlight that many facilitators and their assistants lacked the clinical expertise to identify and exclude participants with contraindications.

The facilitator or their assistants provided participants with preparatory instructions prior to the session. Dietary preparation included not eating (red) meat and foods containing high levels of salt or sugar. Additional advice was to avoid stress, calm the mind, increase mindful introspection, focus on their intention, and abstain from alcohol and other substances to reduce purging and other adverse events that might arise from combining the use of multiple medications (polypharmacy) with the inhalation of vapor from dried toad secretion containing 5-MeO-DMT. In each session, a facilitator administered the vapor by placing the dried toad secretion in a glass pipe, and then heating it up using a torch lighter. During the administration of the vapor from dried toad secretion containing 5-MeO-DMT, the participant remained either standing or lying down on the ground or floor. The participant was instructed to inhale as much of the vapor as possible and to hold it in for some seconds before exhaling. The assistants remained on site after the session to assist in the integration process of the experience if this was deemed necessary and/or requested by the participant. The facilitator would chant (Cantos de Haaco Camaac, healing shamanic chants), and/or play various musical instruments (rattle, drums, flute) during the experience of the participants.

Study procedure

The nature of the study was essentially observational and involved three consecutive assessments: a baseline assessment prior to inhalation of vapor from dried toad secretion containing 5-MeO-DMT, a second assessment conducted within 24 h post-session, and a follow-up assessment at 4 weeks after. Individuals who were at the location to inhale the vapor from dried toad secretion containing 5-MeO-DMT received a detailed explanation of the research aims and were invited to sign the informed consent in order to participate in the study. They completed a 30-min test battery consisting of questionnaires and a psychometric test prior to the session, which were used as baseline measures. The test battery was administered again on site after the acute effects of the vapor from dried toad secretion containing 5-MeO-DMT had disappeared, or within the following 24-h through an online survey created in Qualtrics. The follow-up assessment at 4 weeks after intake was administered online, also through Qualtrics.

Samples

It is worth noting that none of the session facilitators weighed the dose of dried toad secretion that they administered in the glass pipe, but instead, they relied on visual inspection when preparing the individual dosages. We therefore do not know the actual doses of dried toad secretion that were given during sessions to each participant. Some facilitators reported having administered around 20–30 mg of dried toad secretion, while others reported to administer up to 100–120 mg. We did however obtain five samples of the dried Bufo alvarius toad secretion to identify the compounds that it contained. These samples were analyzed for the presence of the following tryptamines, N-methyltryptamine (NMT), N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-dimethyltryptamine (bufotenin, 5-HO-DMT), N,N-dimethyltryptamine (DET), 5-hydroxy-Nω-methyltryptamine (N-methylserotonin, NMe-5HT); steroid lactones (bufogenin, bufotalidin); and tryptophols (5-methoxytryptophol (5-MeO-tryptophol), 5-hydroxytryptophol (5-HO-tryptophol), and 5-methoxy-3-indoleacetic acid (5-MIAA)). The availability of different compounds in the toad secretion in milligrams (in case of tryptamines calculated to the weight of freebase) per 1 g of dried toad secretion in each of these samples is given in Table 2. For details of the analysis, see supplementary content in Appendix 1.

Table 2 Overview of compound concentrations in milligrams or micrograms per 1 g of secretion) in samples of dried secretion from the Bufo alvarius toad Full size table

Test battery

The test battery consisted of six questionnaires; the Ego Dissolution Inventory (EDI), the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC), the Satisfaction with Life Scale (SWL), the Depression, Anxiety, Stress Scale-21 (DASS-21), the Five Facets Mindfulness Questionnaire (FFMQ-15), and the Brief Symptom Inventory-18 (BSI-18). The BSI instrument overlaps with the DASS-21 but offers the additional sub-measure of somatization, which is why it was selected. In addition, a computerized version of the Picture Concept Test (PCT) was administered. It is worth noting that the EDI and 5D-ASC were administered only once and had to be filled out within 24 h after the session to measure the intensity of the acute effects of the inhalation of vapor from dried toad secretion containing 5-MeO-DMT.

Ego Dissolution Inventory

EDI is an 8-item self-report scale that assesses the participant’s experience of ego dissolution (Nour et al. 2016). The participants answered the scale with making a mark on a line from either “No, not more than usually” (0%) to “Yes I experience this completely/entirely” (100%). The EDI is scored by calculating the mean percentage of all the 8 items. The higher the total score, the stronger the experience of ego dissolution. The internal consistency of the EDI is excellent with a Cronbach’s alpha (α) of 0.93. In this study, the original English version or non-validated, non-formal translations in Czech, Spanish, and Dutch of the EDI were used.

5-Dimensional Altered States of Consciousness Rating Scale

The 5D-ASC is a 94-item self-report scale that assesses the participants’ alterations from normal waking consciousness (Studerus et al. 2010). The participant is asked to make a vertical mark on the 10-cm line below each statement to rate to what extent the statements applied to their experience in retrospect from “No, not more than usually” to “Yes, more than usually.” The 5D-ASC contains the 11 subscales experience of unity, spiritual experience, blissful state, insightfulness, disembodiment, impaired control and cognition, anxiety, complex imagery, elementary imagery, audio-visual synesthesia, and changed meaning of percepts. In addition, we compiled the key dimensions of “oceanic boundlessness” which is one of the five key dimensions of the scale with a Cronbach’s alpha (α) of 0.95 that identifies mystical-type experiences and has been compared with the “heaven” aspect of Huxley’s mescaline account (Dittrich 1998). Information about the four remaining dimensions anxious ego dissociation, visual restructuralization, auditory alterations, and finally reduction of vigilance can be found in the referenced article. In this study, the original English version of the 5D-ASC was used in addition to non-validated, non-formal translation in Czech, Spanish, and Dutch made by our team. Internal consistencies across subscales in the Dutch, Czech and Spanish population were 0.94, 0.83, and 0.94, respectively.

The following questionnaires and computerized test were distributed at baseline, within 24 h, and at the 4-week follow-up.

Satisfaction with Life Scale

SWL is a 5-item self-report scale (Diener et al. 1985). The purpose of the scale is to assess someone’s subjective satisfaction with life. The items are answered on a Likert scale ranging from 1 “Strongly disagree” to 7 “Strongly agree.” The total score is obtained by summarizing the points on each item. Scores can range from 5 to 35 points, indicating greater life satisfaction with higher scores. The scale has good psychometric properties. The original SWL in English has a Cronbach’s alpha (α) of 0.87, and was used in addition to a validated translation in Spanish with a Cronbach’s alpha (α) of 0.88 and a validated translation in Dutch with a Cronbach’s alpha (α) of 0.85 (Beuningen 2012; Vazquez et al. 2013). Finally, a non-validated translation of the questionnaire in Czech was obtained and used by the research team.

Depression, Anxiety, and Stress Scale 21

DASS-21 is the shorter version of the original self-report questionnaire Depression, Anxiety, Stress Scale 42 (Henry and Crawford 2005). The purpose of this scale is to measure the constructs of depression, anxiety, and stress. The participants responded by rating the concordance with each statement from 0 “Did not apply to me at all” to 3 “Applied to me very much, or most of the time.” The sub-scale scores for depression, anxiety, and stress are calculated by summing the scores for the relevant items. The original DASS has 42 questions. To have the comparable scores, the sum of the DASS-21 is multiplied by 2. The total scale of the DASS-21 had a Cronbach’s alpha (α) of 0.93. In this study, the English version of the scale or the validated translations into Spanish, Czech, and Dutch were used. The Cronbach’s alpha (α) of the Spanish, Dutch, and Czech versions are 0.96, 0.95, and 0.87, respectively (Daza et al. 2002; Kučera et al. 2018; Wardenaar et al. 2017).

Five Facets Mindfulness Questionnaire-15

This measure is a short form of the 39-item FFMQ (Baer et al. 2006). The FFMQ-15 is a self-report questionnaire which measures five different factors: (1) observe, noticing experience that are both internal and external such as thoughts and emotions; (2) describe: describing internal experiences; (3) acting with awareness: focus on the present activity; (4) non-judgment: not evaluating or judging the present experience; (5) non-reaction: allowing thoughts and feelings to come without acting or reacting upon them (Gu et al. 2016). The purpose of this scale is to obtain an understanding of an individual’s mindfulness-related capacities. The participants answered the FFMQ-15 by rating the concordance with each statement on a 5-point Likert scale that ranges from 1 “never true” to 5 “very often or always true.” The total FFMQ-15 score is obtained by adding all the sub-scale scores. The original scale has shown good internal consistency, and the Cronbach’s alpha (α) of each sub-scale was non-reaction = 0.77, non-judgment = 0.78, describe = 0.83, observe = 0.69, and awareness = 0.70(Baer et al. 2006). The original English version of the FFMQ-15 was used in addition to non-validated, non-formal translations in Spanish, Dutch, and Czech. Internal consistencies across subscales in the Dutch, Czech, and Spanish population were 0.66, 0.63 and 0.61, respectively.

Brief Symptom Inventory 18

The Brief Symptom Inventory 18 (BSI-18) is a self-report scale which contains subscales on somatization, depression, and anxiety (Derogatis 2001). Participants were asked to rate a list of issues people can experience on a 5-point Likert scale ranging from 0 “None at all” to 4 “Extremely.” The BSI-18 is a reliable instrument for the assessment of psychological distress in both clinical and general populations with strong internal consistency and a Cronbach’s alpha (α) of each sub-scale from the validated English version was as follows: somatization = 0.82, depression = 0.87, anxiety = 0.84 (Franke et al. 2017). In this study, the original English version of the BSI-18 or the non-validated, non-formal translations in Spanish, Dutch, and Czech were used. Internal consistencies across subscales in the Dutch, Czech, and Spanish populations were 0.85, 0.85, and 0.83, respectively.

Picture Concept Task

A creativity task with non-verbal stimuli was used, i.e., the PCT (Kuypers et al. 2016). The PCT was composed of stimuli from the Wechsler Preschool and Primary Scale of Intelligence and the Wechsler Intelligence Scale for Children. Each stimulus contains between 4 and 12 color pictures shown in two or three rows. The participants are instructed to find an association between one of the pictures of each row. They are asked to provide the correct solution as there is only one correct answer. The correct answers are taken as the dependent measure of convergent thinking. To assess divergent thinking, the participants were asked to provide as many alternative associations as possible by sticking to the rule: 1 item per row. This is the regular instruction included in the measures of divergent thinking, and it is used to calculate several parameters, i.e., originality, fluency, and the ratio of both, which reflect quantity and quality of divergent thinking. Fluency is defined as the number of alternative associations. Originality is calculated by evaluating the originality of the alternative association relative to those provided by all other participants in a session. Alternative answers were uniquely reported by a single participant received an originality score of 2. Answers that were shared with a single participant were valued as 1, and answers that were shared by 3 or more participants were rated as zero. Mean originality (creativity) scores and ratio originality scores, weighed for fluency (originality/fluency), were used as measures of divergent thinking. Three parallel versions of the PCT were used at baseline and the two follow-up measures after the session to avoid learning effects. Each parallel version consisting of 17 stimuli were shown, and participants had 30 s per stimulus.