A single inhalation of vapor from dried toad secretion containing 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life

The primary aim of the present study was to assess the sub-acute and long-term impact of the inhalation of vapor from dried toad secretion containing 5-MeO-DMT from the Bufo alvarius toad on psychological affect and cognition. A total of 42 participants completed (parts of) the test battery at baseline and after the session, while 24 participants completed the test battery 4 weeks after intake. Relative to baseline, ratings on satisfaction with life and convergent thinking significantly increased right after and over 4 subsequent weeks. Likewise, subjective ratings of non-judgment and awareness also increased over time and reached significance at 4 weeks. Ratings of depression, anxiety, and stress as assessed with DASS-21 or BSI-18 questionnaires decreased on the day after the session and reached significance at 4 weeks. Ratings of depression, stress, and convergent thinking on the day after the session were negatively correlated with levels of ego dissolution or oceanic boundlessness that were rated after the session. Scores on satisfaction with life the day after the session were positively correlated with scores on ego dissolution and oceanic boundlessness.

Inhalation of the vapor from dried toad secretion containing 5-MeO-DMT produced sub-acute and long-term improvements in subjective ratings of satisfaction with life, depression, anxiety, and stress. Relative to baseline, ratings of satisfaction with life significantly increased between 7 and 11% immediately after the session as well as 4 weeks after. Reductions in DASS ratings of depression (18%), anxiety (39%), and stress (27%) were evident right after the session and kept decreasing to 68%, 56%, and 48%, respectively, after 4 weeks, at which point the decrements reached statistical significance. BSI-18 ratings of depression, anxiety, and somatization indicated a similar pattern of improvement. Overall, this suggests that a single dose of vapor from dried toad secretion containing 5-MeO-DMT can bring about changes in affect and cognition that last for a prolonged period of time. Similar findings have been reported for 5-MeO-DMT and other related tryptamines. For example, in a recent survey, the use of 5-MeO-DMT in a naturalistic setting was associated with unintended improvement in depression and anxiety (Davis et al. 2019). Additionally, consumers of ayahuasca, a brew containing N,N-dimethyltryptamine (DMT), displayed significant reductions in ratings of depression and stress that persisted for 4 weeks after intake (Uthaug et al. 2018). Likewise, high-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life in cancer patients (Griffiths et al. 2016). The authors reported that at the 6-month follow-up, these changes were maintained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety (Griffiths et al. 2016).

Notably, increased neurogenesis has been suggested as a central mechanism to underlie instant and long-term antidepressant properties of psychedelic compounds such as ketamine (Duman and Aghajanian 2012; Ma et al. 2017) and psilocybin (Catlow et al. 2013; Idell et al. 2017). Neurogenesis and synaptic plasticity may play a crucial role in how neural circuits regulate their excitability and connectivity and may link the neurobiology of depression to the therapeutic effects of glutamatergic drugs such as ketamine (Abdallah et al. 2015). In that respect, it is of interest that changes in glutamate transmission following ayahuasca use have been associated with improvements in a certain aspect of mindfulness as well (Sampedro et al. 2017). Alternatively, it has been proposed that therapeutic improvements in affect following the use of psychedelics might be mediated through sigma-1 receptor (S1R). The endogenous ligands for the S1R include neurosteroids and natural tryptamines, such as DMT and 5-MeO-DMT. Research suggests that both DMT and 5-MeO-DMT modulate innate and adaptive inflammatory responses through the sigma-1 receptor of dendritic cells (Szabo et al. 2014), which in turn might improve the etiology and symptomatology of neuropsychiatric diseases, such as depression.

Inhalation of vapor from dried toad secretion containing 5-MeO-DMT increased convergent thinking as assessed with the Picture Concept Task by 20 and 37% within 24 h and 4 weeks after the session. The PCT has previously been used in two observational ayahuasca studies to show that the brew increases divergent performance during the acute psychedelic state (Kuypers et al. 2016) but improves convergent thinking up until 4 weeks after the psychedelic experience (Uthaug et al., 2018). Likewise, the present data also suggests that the main impact of vapor from dried toad secretion containing 5-MeO-DMT on creativity is to improve convergent thinking following the psychedelic experience. However, in the present study, convergent thinking was also negatively correlated to subjective ratings of ego dissolution and oceanic boundlessness on the day after the session. This suggests that convergent thinking was poor in participants that reported a strong psychedelic experience and that the overall increase in convergent thinking relative to baseline may not be related to inhaling vapor but to another factor. For example, it cannot be overlooked that improvements in convergent thinking performance resulted from practice or learning effects that can arise from the repeated performance of the same task over time. We attempted to minimize learning effects by administrating parallel versions of the PCT at each time point, but the present study lacks a proper control group to evaluate the effectiveness of this precautionary measure. Alternatively, it can also not be overlooked that the overall improvement in convergent thinking after the session relates to improvements in mindfulness capabilities, such as acting with awareness, that contribute to optimization of cognitive functioning (Lebudaa et al. 2015). Long-term increases in convergent thinking may therefore coincide with improvements in mindfulness that were observed in the present sample of people inhaling vapor from dried toad secretion containing 5-MeO-DMT. In fact, inhalation of the vapor induced long-term improvements in two mindfulness parameters (e.g., non-judgment and awareness) as measured by the FFMQ-15. Similar findings have been reported in an observational study that compared aspects of mindfulness before and 24 h after an ayahuasca session using the long version of the FFMQ (Soler et al. 2016).

Moreover, most participants had a strong psychedelic experience as measured by the EDI and 5D-ASC and scored high on ratings of ego dissolution, as well as on the composite factor oceanic boundlessness. This is in line with previous findings about 5-MeO-DMT’s ability to induce strong mystical experiences (Barsuglia et al. 2018). Additionally, close inspection of the frequency distribution of ratings of ego dissolution and oceanic boundlessness demonstrated that 20–30% of the participants of the present study only had a low to medium psychedelic experience. This variability in psychedelic experience may have been caused by differences in doses administered at ceremonies, inhalation techniques, and the actual concentration of 5-MeO-DMT in the secretion from the Bufo alvarius toad used by different facilitators. Analysis of the five samples of dried secretion from the Bufo alvarius toad revealed that about 25–30% of the dried secretion consisted of the primary component 5-MeO-DMT. The samples also presented (very) low amounts of additional tryptamines such as bufotenine (0.08–0.18%), DMT, and N-methylserotonin (0.01–0.03%). Differences in tryptamine concentration observed in the dried toad secretion samples might very well affect the strength of the psychedelic experience, particularly when facilitators offer doses that span a wide range (i.e., 30–120 mg) as during sessions in the present study. Participants that inhaled vapor from a 30 mg dose of dried toad secretion may have received about 7.5–9 mg of 5-MeO-DMT whereas those who received a 120-mg dose of dried toad secretion may have inhaled up to 30–36 mg of 5-MeO-DMT. However, these estimates could also be lower as drug delivery may not have been complete due to individual differences in inhalation techniques, drug metabolism, and compound ratio following heating or when doses were only partially inhaled (Evans and Relling 1999; Hadidi et al. 1999; Shen et al. 2010; Yu et al. 2003). Nevertheless, it has become clear, from the visits to the session(s) where vapor from dried toad secretion containing 5-MeO-DMT was administered, that dose(s) are not standardized and vary between facilitators. This is likely one of the main reasons why the psychedelic experience of ego dissolution and oceanic boundlessness differed between the participants.

It could be argued that the changes in affect and cognition that were observed in the present study are not related to a pharmacological effect from the inhalation of vapor from dried toad secretion containing 5-MeO-DMT, but rather due to uncontrolled confounders such as expectations of participants prior to, and after, the session. It is conceivable that participants were psychologically distressed in anticipation of the session, which would explain why subjective stress as rated with the BSI-18 and DASS-21 was higher at baseline, prior to the session. Though a contributing role of expectation cannot be completely ruled out, there is also good evidence to suggest that changes in affect and cognition observed in the present study were related to the actual psychedelic experience. Correlational analysis demonstrated that ratings of satisfaction with life were positively correlated to levels of ego dissolution and oceanic boundlessness, whereas ratings of stress and depression were negatively correlated to the level of ego dissolution. This indicates that the magnitude of mental health changes that were observed after the session was directly associated with the strength of the actual psychedelic experience caused by inhalation of the vapor from dried toad secretion containing 5-MeO-DMT. This finding is in line with previous studies on psychedelics such as psilocybin and ayahuasca that have shown that stronger psychedelic experiences are associated with larger changes in therapeutic outcome measures (Bogenschutz et al. 2015; Griffiths et al. 2016; Roseman et al. 2017; Ross et al. 2016; Uthaug et al. 2018).

Several limitations of the present study should be taken into account, the main one being the lack of a proper control group. Thus, the present findings can therefore only be taken as a preliminary indication of the impact of inhaling vapor from dried toad secretion containing 5-MeO-DMT on mental health parameters. Placebo-controlled, randomized clinical trials are needed to replicate the current findings and to control for non-pharmacological factors that could explain the current findings as well. A second limitation is that about 40% (N = 33) of the volunteers that gave consent (N = 75) to participate in the current did not complete any measures after the ceremony. Of those that completed the assessments the day after the ceremony (N = 42), 50% did not complete the follow-up assessment at 4 weeks after the session. Their reasons for not completing the assessments are unknown but potentially could be driven by disappointments that emerged over the experience. Most participants listed either “understanding myself” or “solving problems” as their motivation for attending the sessions. Other motivations included self-development, the search for a spiritual experience or spiritual healing and curiosity. It is unknown whether the experience from inhaling vapor from dried toad secretion containing 5-MeO-DMT fulfilled the expectations and motivations of all participants. Mental challenges following a 5-MeO-DMT experience have been reported and can include feelings of grief, anxiety, panic, or paranoia (Barsuglia et al. 2017; Davis et al. 2018). Resurfacing of these experiences can occur even weeks after the experience (Sandoval 2006) and may lead to psychological difficulties, particularly in the absence of counseling (Johnson et al. 2008). The possibility thus exists that participants that did not fill out the follow-up measures did not do so because they experienced negative after-effects. In that case, their lack of responding would strongly bias the current findings. In this light, the fact that facilitators in the field often do not provide professional psychological counseling during and after the sessions is particularly worrisome. Structured counseling sessions during the acute psychedelic experience with additional sessions before and after would potentially increase the ability of users to integrate their experience with the vapor from dried toad secretion containing 5-MeO-DMT, increase our understanding of positive and negative outcomes of exposure to the vapor and reduce the number of volunteers lost to follow-up.

Additionally, as the use of vapor from dried toad secretion containing 5-MeO-DMT through means of inhalation increases, there are several ethical and ecological considerations worth highlighting. The International Union for Conservation of Nature (IUCN) red list of threatened species at present does not classify the Bufo alvarius toads as an endangered species. The classification dates back however to an assessment of the toad population in 2004 (Hammerson and Georgina 2004). The increasing popularity of inhalation of vapor at underground ceremonies and acknowledgement of its therapeutic potential may however affect the stability of the toad population in the long run. The increasing demand for the vapor will disturb the ecological equilibrium of the toads through the invasion of habitat, excessive milking, amphibian trafficking, and black-market dynamics (PsychedelicsToday 2018). Harassment of the Bufo alvarius toad however can be easily prevented by using synthetic 5-MeO-DMT instead of vapor from dried toad secretion containing 5-MeO-DMT. Switching to synthetic 5-MeO-DMT offers the advantage that it does not contain a cocktail of different compounds, can be produced and dosed in a standardized manner, and is therefore much safer to use in naturalistic as well as controlled research settings.

Despite the limitations of this study, the results underscore the effects of 5-MeO-DMT, the main active ingredient in the secretion from the Bufo alvarius toad, on mental health in humans. This study suggests that a single administration of vapor from toad secretion containing 5-MeO-DMT produces rapid and persistent improvements in satisfaction with life, mindfulness and psychopathological symptoms, and that these changes are associated to the strength of the psychedelic experience. These results provide evidence supporting further research examining the potential therapeutic effect of 5-MeO-DMT.