5-Methoxy-N,N-dimethyltryptamine: An ego-dissolving endogenous neurochemical catalyst of creativity

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5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness that is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions (e.g., Advaita Vedānta, Mahāyāna Buddhism, inter alia). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing research; however, empirical evidence indicates that its remarkable psychoactivity is partially mediated via agonism of the 5-HT1A/2A (serotonin) receptor subtypes. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. We propose that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool with the potential to significantly advance our understanding of the psychological and neuronal processes which underpin cognition and creativity (e.g., downregulation of the default mode network, increased global functional connectivity, neuroplasticity, σ1 receptor interactions, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of our conjecture. Specifically, we argue that 5-MeO-DMT has significant neuropsychopharmacological potential due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., “ego death”). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective, and potential scenarios of abuse are addressed, particularly in the context of neuroethics, cybernetic manipulation, and military research on torture.

HTML5 full-text version (integrated AI text-to-speech synthesis):
icon-volume-up https://christopher-germann.de/papers/5-meo-dmt-creativity/index.html

Final version: https://link.springer.com/article/10.1007%2Fs41470-019-00063-y
DOI: https://doi.org/10.1007/s41470-019-00063-y

BioRxiv Preprint: https://www.biorxiv.org/content/10.1101/578435v2

Sherwood, A. M., Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K.. (2020). Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use. ACS Omega , 5(49), 32067–32075.

Plain numerical DOI: 10.1021/acsomega.0c05099
directSciHub download

See also: https://www.researchgate.net/publication/333320523_CLINICAL_CONSIDERATION_OF_5-MeO-DMT

An enigmatic endogenous psychoactive tryptamine with profound psychological effects. Advancing the science of consciousness...
Incilius alvarius
Incilius alvarius
Structural similarities with serotonin

( 5-hydroxytryptamine)


Structural similarities between serotonin (5-HT) and 5-MeO-DMT

The Swiss depth-psychologist Carl Gustav Jung

"There is no coming to consciousness without pain. People will do anything, no matter how absurd, in order to avoid facing their own Soul. One does not become enlightened by imagining figures of light, but by making the darkness conscious."
~ C.G. Jung

The Death of Socrates
William Blake - The doors of perception
Functional connectivity density (LSD vs. control)
Tagliazucchi et al., 2016
Multicriteria decision analysis of relative drug harm
CogNovo, Marie Curie Actions
Breaking Conventions, University of Greenwich, London
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Incilius alvarius
Structural similarities with serotonin
The Swiss depth-psychologist Carl Gustav Jung
The Death of Socrates
William Blake - The doors of perception
C.G. Jung - The Red Book
Functional connectivity density (LSD vs. control)
Tagliazucchi et al., 2016
Multicriteria decision analysis of relative drug harm
CogNovo, Marie Curie Actions
Breaking Conventions, University of Greenwich, London
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5-methoxy-N,N-dimethyltryptamine - An ego-dissolving endogenous neurochemical catalyst of creativity - christopher_b_germann_2019
BioRxiv Preprint

There is no coming to consciousness without pain. People will do anything, no matter how absurd, in order to avoid facing their own Soul. One does not become enlightened by imagining figures of light, but by making the darkness conscious. The latter procedure, however, is disagreeable and therefore not popular.
~ C.G. Jung

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Christopher Germann and Prof. Roger Malina discuss Chris’ current work in the Cognovo PhD program, on quantum cognition which applies the mathematical formalisms of quantum theory to understanding cognitive processes. Chris is currently working on non-commutativity in decision theory, with laboratory experiments in visual decision making. He is also studying the role of the endogenous neurotransmitter DMT (N,N-Dimethyltryptamine) in perception and cognition.

Chris Germann is a Marie-Curie research fellow in the CogNovo doctoral programme at the Cognition Institute of Plymouth University, which is government-funded by the European Commission. Chris has broad interdisciplinary interests and he is momentarily mainly focusing on cognitive psychology and neuroscience. He is particularly interested in irrationality and decision making and the neuronal Serotonin system and its role in perception and cognition (for instance, creativity and neuroplasticity). Furthermore, philosophy of science and mind capture his deepest curiosity.

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Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R.. (2019). 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. American Journal of Drug and Alcohol Abuse

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Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leão, R. N.. (2018). A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus. Frontiers in Molecular Neuroscience

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Lancelotta, R. L., & Davis, A. K.. (2020). Use of Benefit Enhancement Strategies among 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) Users: Associations with Mystical, Challenging, and Enduring Effects. Journal of Psychoactive Drugs

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Sherwood, A. M., Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K.. (2020). Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use. ACS Omega

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Dakic, V., Minardi Nascimento, J., Costa Sartore, R., MacIel, R. D. M., De Araujo, D. B., Ribeiro, S., … Rehen, S. K.. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Scientific Reports

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Ermakova, A. O., Dunbar, F., Rucker, J., & Johnson, M. W.. (2021). A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology

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Riga, M. S., Soria, G., Tudela, R., Artigas, F., & Celada, P.. (2014). The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: Reversal by antipsychotic drugs. International Journal of Neuropsychopharmacology

Plain numerical DOI: 10.1017/S1461145714000261
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Winne, J., Boerner, B. C., Malfatti, T., Brisa, E., Doerl, J., Nogueira, I., … Leão, R. N.. (2020). Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT. Experimental Neurology

Plain numerical DOI: 10.1016/j.expneurol.2020.113175
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Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leão, R. N.. (2019). Corrigendum: A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus (Frontiers in molecular neuroscience, (2018), 11, 10.3389/fnmol.2018.00312). Frontiers in Molecular Neuroscience

Plain numerical DOI: 10.3389/fnmol.2019.00079
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Halberstadt, A. L., Nichols, D. E., & Geyer, M. A.. (2012). Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: Comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor. Psychopharmacology

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Uthaug, M. V., Lancelotta, R., Ortiz Bernal, A. M., Davis, A. K., & Ramaekers, J. G.. (2020). A comparison of reactivation experiences following vaporization and intramuscular injection (IM) of synthetic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting. Journal of Psychedelic Studies

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Germann, C. B.. (2019). 5-Methoxy-N,N-dimethyltryptamine: An Ego-Dissolving Endogenous Neurochemical Catalyst of Creativity. Activitas Nervosa Superior

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Schwelm, H. M., Zimmermann, N., Scholl, T., Penner, J., Autret, A., Auwärter, V., & Neukamm, M. A.. (2021). Qualitative and Quantitative Analysis of Tryptamines in the Poison of Incilius alvarius (Amphibia: Bufonidae) . Journal of Analytical Toxicology

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Halberstadt, A. L.. (2016). Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine. Pharmacology Biochemistry and Behavior

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Riga, M. S., Bortolozzi, A., Campa, L., Artigas, F., & Celada, P.. (2016). The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT1A and 5-HT2A receptors. Neuropharmacology

Plain numerical DOI: 10.1016/j.neuropharm.2015.10.016
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Plain numerical DOI: 10.2174/138920010794233495
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Jiang, X. L., Shen, H. W., & Yu, A. M.. (2016). Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms. Pharmacological Reports

Plain numerical DOI: 10.1016/j.pharep.2016.01.008
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Plain numerical DOI: 10.1016/j.apsb.2016.07.007
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Germann, C. B.. (2019). 5-methoxy-N,N-dimethyltryptamine: An ego-dissolving endogenous neurochemical catalyst of creativity. BioRxiv 578435

Plain numerical DOI: 10.1101/578435
directSciHub downloadURL: https://www.biorxiv.org/content/10.1101/578435v2
Truncated URL: https://t.co/LDkVtS8WqA
PDF: https://www.biorxiv.org/content/biorxiv/early/2019/03/17/578435.full.pdf
DOI: https://doi.org/10.1101/578435
Stats: https://rxivist.org/papers/46248
Google Scholar: https://scholar.google.com/scholar?cluster=8867435362829874238
Europe PMC: https://europepmc.org/abstract/ppr/ppr73330
ResearchGate: https://www.researchgate.net/publication/335329415_5-Methoxy-NN-dimethyltryptamine_An_Ego-Dissolving_Endogenous_Neurochemical_Catalyst_of_Creativity

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