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

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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.

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Most cited references 27

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The role of inflammation in depression: from evolutionary imperative to modern treatment target.

Andrew Miller, Charles L. Raison (2016)

Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

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Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

R R Griffiths, W A Richards, U McCann … (2006)

Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.

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Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

PCR Barbosa, Michael P Bogenschutz, Alyssa Forcehimes … (2015)

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.

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Author and article information

Contributors

Malin V Uthaug:

ORCID: http://orcid.org/0000-0001-7903-1325

malin.uthaug@maastrichtuniversity.nl

Johannes G Ramaekers: j.ramaekers@maastrichtuniversity.nl

Journal

Journal ID (nlm-ta): Psychopharmacology (Berl)

Journal ID (iso-abbrev): Psychopharmacology (Berl.)

Title: Psychopharmacology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0033-3158

ISSN (Electronic): 1432-2072

Publication date (Electronic): 10 December 2019

Publication date PMC-release: 10 December 2019

Publication date (Print): 2020

Volume: 237

Issue: 3

Pages: 773-785

Affiliations

[1 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, , Maastricht University, ; Universiteitssingel 40, Maastricht, 6229 ER The Netherlands

[2 ]Innate Path, Lakewood, CO USA

[3 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; Division of Mental Health and Addiction, , Oslo University Hospital, ; Oslo, Norway

[4 ]GRID grid.261331.4, ISNI 0000 0001 2285 7943, College of Social Work, , The Ohio State University, ; Columbus, OH 43210 USA

[5 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, , Johns Hopkins University, ; Baltimore, MD 21224 USA

Author information

Malin V Uthaug http://orcid.org/0000-0001-7903-1325

Article

Publisher ID: 5414

DOI: 10.1007/s00213-019-05414-w

PMC ID: 7036074

PubMed ID: 31822925

SO-VID: 28317cbb-14cb-484e-8c95-7b1501172f52

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 15 July 2019

Date accepted : 25 November 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: #T32DA07209

Award Recipient : Alan K Davis

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: 5-methoxy-n,n-dimethyltryptamine,field study,affect,immunology,mindfulness

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: 5-methoxy-n,n-dimethyltryptamine, field study, affect, immunology, mindfulness

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

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Most cited references 27

The role of inflammation in depression: from evolutionary imperative to modern treatment target.

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

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