Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment
In a prospective study of 11 volunteers, inhalation of vaporised synthetic 5‑methoxy‑N,N‑dimethyltryptamine produced immediate increases in salivary cortisol and decreases in IL‑6, alongside improvements in affect and mindful non‑judgment that persisted to one week. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience, suggesting a dissociation between subjective effects and acute neuroendocrine/immune responses.
Authors
- Jordi Riba
- Johannes Ramaekers
- Alan Davis
Published
Abstract
Rationale
5-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.
Objectives
The 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.
Methods
Assessments (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).
Results
5-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.
Conclusion
Inhalation 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.
Research Summary of 'Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment'
Introduction
Uthaug and colleagues frame 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) as a short-acting tryptamine with growing use in naturalistic and ceremonial settings for spiritual exploration and to address mood problems. Earlier research and surveys suggest 5-MeO-DMT produces intense but brief mystical-type effects, has a low addiction liability, and may share therapeutic potential with related serotonergic psychedelics such as DMT-containing ayahuasca or psilocybin. Preclinical and in vitro studies indicate that DMT-like compounds can modulate immune function and neurogenesis, and the immune hypothesis of psychiatric disease motivates assessing links between inflammatory processes and mental health outcomes following psychedelic exposure. The present study set out to prospectively examine acute neuroendocrine and inflammatory responses, and short-term changes in affect and mindfulness-related capacities, after inhalation of vaporised synthetic 5-MeO-DMT in a naturalistic setting. Primary aims were to measure salivary cortisol and inflammatory markers (IL-6, CRP, IL-1β), and secondary aims were to assess changes in depression, anxiety, stress, satisfaction with life, and facets of mindfulness, plus whether subjective psychedelic intensity related to biomarker or mental-health changes. The investigators hypothesised reductions in mood symptoms and exploratory links between psychometric changes and salivary stress/immune markers.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Uthaug, M. V., Lancelotta, R., Szabo, A., Davis, A. K., Riba, J., & Ramaekers, J. G. (2020). Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology, 237(3), 773-785. https://doi.org/10.1007/s00213-019-05414-w
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