Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment

Malin V Uthaug,Attila Szabo,Johannes G Ramaekers,Alan K Davis,Jordi Riba,Rafael Lancelotta

doi:10.1007/s00213-019-05414-w

Abstract

Rationale5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce.ObjectivesThe first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1β), as well as the acute psychedelic experience.MethodsAssessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA).Results5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment.ConclusionInhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,N-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.

Highlights

Tryptamine psychedelics such as psilocybin are known to alter perception, mood, and a host of cognitive processes (Nichols2004) and have been indicated for the treatment of mood disorders (Carhart-Harris et al 2018; Griffiths et al 2006; Viol et al 2019)
A similar potential might exist for the short-acting tryptamine 5methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
5-MeO-DMT was first synthesized in 1936 (Hoshino and Shimodaira 1936), but can be found naturally in plants such as the Dictyoloma incanescens (Pachter et al 1959), or in the milky-white secretion, known as bufotoxin, which is produced in the skin and the parotid glands of the Incilius alvarius toad, known as Bufo alvarius (Weil and Davis 1994)

Summary

Introduction

Tryptamine psychedelics such as psilocybin are known to alter perception, mood, and a host of cognitive processes (Nichols2004) and have been indicated for the treatment of mood disorders (Carhart-Harris et al 2018; Griffiths et al 2006; Viol et al 2019). A recent lab analysis revealed that about 25–30% of the bufotoxin, used in a naturalistic setting, consisted of the primary component 5-MeO-DMT, as well as (very) low amounts of additional tryptamines such as bufotenine (0.08– 0.18%), DMT, and N-methylserotonin (0.01–0.03%) (Uthaug et al 2019). Low doses of 5-MeO-DMT (bufotoxin source 50 mg, estimated 5MeO-DMT content 5–7 mg) appear to occasion mystical experiences of similar intensity to high-dose psilocybin (Barsuglia et al 2018), but with a much shorter duration of action. From a recent survey among users in the general population, it appears that 5-MeO-DMT has an acceptable physiological safety profile in naturalistic settings (Davis et al 2018; Davis et al 2019), as well as a low addiction liability (Davis et al 2018). Resurfacing of these experiences can occur even weeks after the experience and may lead to psychological difficulties, in the absence of counseling (Johnson et al 2019)

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Results