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, mindfulness-related capacities, and a decrement of psychopathological symptoms

M. V. Uthaug, R. Lancelotta, K. van Oorsouw, K. P. C. Kuypers, N. Mason, J. Rak, A. Šuláková, R. Jurok, M. Maryška, M. Kuchař, T. Páleníček, J. Riba, J. G. Ramaekers

Psychopharmacology, 2019

https://doi.org/10.1007/s00213-019-05236-w

Abstract

Background : 5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited. Aims The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience.

Methods : Assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations.

Results : Relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.

Conclusion : A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeODMT.

Keywords : Bufo alvarius, Field study, Cognition, Affect, Altered states of consciousness, Satisfaction with life, Psychedelic, 5-MeO-DMT

Introduction

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent, fast-acting, psychedelic substance, which acts as a serotonin 5-HT-1-A/5-HT-2A/C receptor agonist (Krebs- Thomson et al. 2006; Ray 2010; Shen et al. 2010). The psychedelic substance 5-MeO-DMT was initially isolated from the bark of the plant Dictyoloma incanescens (Pachter et al. 1959) and has also been found in the milky-white secretion produced in the skin and the parotoid glands of the Bufo alvarius toad, also known by the scientific name BIncilius alvarius^ and more commonly referred to as the BColorado river toad^ or BSonoran desert toad.^ Besides 5-MeO-DMT, the secretion of Bufo alvarius also contains 5-hydroxy-N,N dimethyl-tryptamine, the closely related O-dimethylated analog of 5-MeO-DMT, commonly known as bufotenine. Moreover, the toad secretion also contains several cardioactive agents like bufagins, various catecholamines such as epinephrine and norepinephrine, and noncardioactive sterols such as cholesterol, provitamin D, gamma sitosteral and ergosterol (Chen and Kovaříková 1967). Since a toad yields about 0.25–0.50 g of dried secretion from a Bmilking session,^ with a 5-MeO-DMT content of up to 15% (Erspamer et al. 1967), a single toad may generate 75 mg of 5-MeO-DMT in its secretion that, when smoked, is already psychoactive in humans at doses as low as 3–5 mg (Weil and Davis 1994). Users have reported that the psychedelic effects of 5-MeO-DMT are more potent and more intense as compared with other psychedelics (Barsuglia et al. 2017, 2018; Davis et al. 2018). A single inhalation of vaporized dried toad secretion produces a psychedelic experience within 15 s (Weil and Davis 1994) and may last up to 20–40 min (Ott 2001).

Some reports suggest that the secretion of the Bufo alvarius toad may have been used historically by indigenous peoples in the southwestern territory of the USA and northern Mexico (Weil and Davis 1994). However, the purpose of these ancient practices has not been fully clarified, and evidence of use as a medicine is scarce. Therefore, it cannot be ruled out that the present use of toad secretion is of more recent origin.

A recent survey among users of 5-MeO-DMT (toad, synthetic, or plant derived) indicated that most respondents used 5-MeO-DMT for spiritual exploration and reported mysticaltype experiences of moderate-to-high intensity (Davis et al. 2018). Interestingly, those respondents who reported a psychiatric disorder mentioned that 5-MeO-DMT had helped them reduce their symptoms of anxiety, depression, and posttraumatic stress, or effectively deal with alcoholism and drug abuse (Davis et al. 2018; Davis et al. 2019). The potential mental health benefits of 5-MeO-DMT have not been studied
in humans but might be similar with those that have been reported for ayahuasca, an Amazonian plant preparation that contains the closely related psychedelic compound, N,N-dimethyltryptamine (DMT). The potential of ayahuasca to rapidly and persistently reduce symptoms of depression has been
shown in a range of open-label studies (De Lima et al. 2011; Sanches et al. 2016), and was recently confirmed in a randomized placebo-controlled clinical trial in patients suffering from treatment-resistant depression (Palhano-Fontes et al. 2018). Moreover, in vitro studies have recently provided evidence
of anti-inflammatory, neuroregenerative, and anti-addictive effects induced by 5-MeO-DMT (Dakic et al. 2017; Szabo et al. 2014). Overall, these findings support a potential role for 5-MeO-DMT as a therapeutic tool.

The present study was conducted to obtain initial data on the effects of 5-MeO-DMT on mental health–related functions such as affect and cognition. We visited several locations in three European countries, where people would inhale vapor from dried toad secretion containing 5-MeO-DMT. Our primary objective was to assess whether inhaling the vapor produces any sub-acute and/or longlasting improvements in measures of affect and cognition. We expected that symptoms of affect, such as depression, anxiety, stress, and somatization reported by participants at baseline would be ameliorated by the use of the vapor from dried toad secretion containing 5-MeO-DMT through the means of inhalation, and that measures of cognition, such as creative thinking- and mindfulnessrelated capacities, would improve. We also expected that such changes would persist over time and would still be
measurable at 4 weeks after intake. As a secondary objective, we aimed to determine whether the sub-acute and long-term effects of inhaling the vapor from the 5-MeODMT- rich toad secretion mental health measures were related to certain aspects of the acute psychedelic state, such as ego dissolution and other subjective experiences that characterize the altered state of consciousness. The rationale for studying these associations is based on the results reported in other studies that have demonstrated a direct
association between the beneficial effects of psychedelic tryptamines such as psilocybin (Garcia-Romeu et al. 2014; Roseman et al. 2017), the DMT-containing brew ayahuasca (Uthaug et al. 2018), and the ability of these drugs to induce mystical experiences and ego dissolution during the acute psychedelic phase.

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