IMR Press / JIN / Volume 21 / Issue 5 / DOI: 10.31083/j.jin2105148
Open Access Review
A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut?
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1 National University of Public Services, H-1083 Budapest, Hungary
2 Psychosomatic Outpatient Clinics, H-1037 Budapest, Hungary
3 Center for Neuropsychiatric Research of Traumatic Stress, Department of Psychiatry & UHSL, First Faculty of Medicine, and Department of Psychiatry, Faculty of Medicine Pilsen, Charles University, CZ-12108 Prague, Czechia
4 Neuroscience and Consciousness Research Department, Vision Research Institute, Lowell, MA 01854 USA
*Correspondence: (István Bókkon)
Academic Editor: Parisa Gazerani
J. Integr. Neurosci. 2022, 21(5), 148;
Submitted: 22 June 2022 | Revised: 15 July 2022 | Accepted: 1 August 2022 | Published: 31 August 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Here we present a complex hypothesis about the psychosomatic mechanism of serotonergic psychedelics. Serotonergic psychedelics affect gut microbes that produce a temporary increase of 5-HT by their host enterochromaffin cells (ECs). This increased 5-HT production—which is taken up and distributed by platelets—may work as a hormone-like regulatory signal that could influence membrane permeability in the host organs and tissues and in the brain. Increased plasma 5-HT levels could enhance permeability of the blood-brain barrier (BBB). Transiently increased permeability of the BBB allows for plasma 5-HT to enter the central nervous system (CNS) and be distributed by the volume transmission. Next, this gut-derived 5-HT could modulate excitatory and inhibitory neurotransmission and produce special network disintegration in the CNS. This transient perturbation of the normal neural hierarchy allows patients access to suppressed fear information and perform an emotional reset, in which the amygdale may have a key role.

classic psychedelics
gut-brain axis
membrane permeability
volume transmission
Fig. 1.
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