A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut?

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 productionwhich 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.

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“…Reduced serotonin receptor expression and the prevalence of altered depressive-related behaviours in HD are consistent with other forms of depression [ 213 , 216 , 217 ]. This shows that reduced serotonergic signalling underpins the genesis of depressive-like traits in HD [ 213 , 216 , 217 ]. It is worth noting that 5-HT production in the gut might alter vasculature (membrane) permeability across the body and the blood-brain barrier (BBB) [ 217 - 220 ].…”

“…Identifying the genesis and pathology of depression seems important for early diagnosis of HD-linked depression and improved clinical diagnosis and outcome. One of these important diagnostic indicators of depression is the disruption of the serotonin (5-HT) signalling system [ 213 , 216 , 217 ]. Additionally, enterochromaffin cells (ECs) in the gut produce nearly 95% of the body's 5-HT, a hormone with autocrine, paracrine, and endocrine effects [ 217 - 219 ].…”

“…One of these important diagnostic indicators of depression is the disruption of the serotonin (5-HT) signalling system [ 213 , 216 , 217 ]. Additionally, enterochromaffin cells (ECs) in the gut produce nearly 95% of the body's 5-HT, a hormone with autocrine, paracrine, and endocrine effects [ 217 - 219 ]. Reduced serotonin receptor expression and the prevalence of altered depressive-related behaviours in HD are consistent with other forms of depression [ 213 , 216 , 217 ].…”

“…Additionally, enterochromaffin cells (ECs) in the gut produce nearly 95% of the body's 5-HT, a hormone with autocrine, paracrine, and endocrine effects [ 217 - 219 ]. Reduced serotonin receptor expression and the prevalence of altered depressive-related behaviours in HD are consistent with other forms of depression [ 213 , 216 , 217 ]. This shows that reduced serotonergic signalling underpins the genesis of depressive-like traits in HD [ 213 , 216 , 217 ].…”

“…This shows that reduced serotonergic signalling underpins the genesis of depressive-like traits in HD [ 213 , 216 , 217 ]. It is worth noting that 5-HT production in the gut might alter vasculature (membrane) permeability across the body and the blood-brain barrier (BBB) [ 217 - 220 ]. Dysbiosis that disrupts 5-HT levels has also been linked to depression, posttraumatic stress disorder (PTSD), autism spectrum disorder (ASD), anxiety, Parkinson's, Alzheimer's diseases, etc .…”