A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut?
Noémi Császár-nagy, Petr Bob, István Bókkon
Journal of Integrative Neuroscience August 31, 2022 DOI: 10.31083/j.jin2105148 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Serotonin |
| Keywords | Enterochromaffin cell Neurotransmission Inhibitory postsynaptic potential Excitatory postsynaptic potential Blood–brain barrier Central nervous system Cell biology Endocrinology |
| Citations | 9 |
| Key points | Proposes that serotonergic psychedelics may work through a gut-brain axis mechanism involving increased 5-HT production by enterochromaffin cells, leading to transient blood-brain barrier permeability and neural network disintegration that facilitates emotional reset. |
Abstract
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.
Comparable studies
Other theoretical and historical papers on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics as Medicines: An Emerging New Paradigm General population | 2016 | Theoretical or philosophical paper | |
| Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate | 2018 | Theoretical or philosophical paper | |
| A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics | 2020 | Theoretical or philosophical paper | |
| Dreams, Hallucinogenic Drug States, and Schizophrenia: A Psychological and Biological Comparison | 1983 | Theoretical or philosophical paper | |
| Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract. | 2022 | Theoretical or philosophical paper |
Citations in the library
Cited by 3
- Potential Serotonin 5-HT2A Receptor Agonist of Psychoactive Components of Silene undulata Aiton: LC-MS/MS, ADMET, and Molecular Docking Studies. Current Pharmaceutical Biotechnology 2025
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
- Exploring the In Vitro Effect of Psilocybin on the Composition and Metabolic Activity of Gut Microbiota in Individuals with Severe Anxiety Drugs and Drug Candidates August 12, 2026
Cites 51
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- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
and 46 more in the library