Comment · Mon, November 21, 2022 · ND Owner
Where We're Going, We Don't Need Roads
What they were answering
Dontelmyalterimreal · 23 points
I keep meaning to ask… what are the potential benefits of tickling 5-HT2A? I always had the impression that increased activation/density of 5-HT2A was associated with some negative effects (e.g. depression, sexual dysfunction etc) aside from the psychedelic effects. Are the positive effects mediated via downregulation of this receptor?
u/MisterYouAreSoDumb · ND Owner
The interactions with 5-HT2A and mood/cognition are pretty complex, and are very dose-dependent. We are still learning a lot about how activation of 5-HT2A can affect downstream systems.
https://biblio.vub.ac.be/vubirfiles/84273988/Pedzich2022_NPP_PREPRINT.docx_1_.pdf
It also is very dependent on the specific brain region you are talking about. Increased/decreased expression in the frontal cortex will have a different effect than in the striatum, amygdala, hippocampus, etc.
The present review reported that, in the amygdala and hippocampal region, 5-HT2ARs are located on both excitatory and inhibitory neurons. Thus, this receptor, modulating the activity of amygdalar and hippocampal microcircuits, could be critically involved in the regulation of emotional processes and cognitive functions. Moreover, 5-HT2A receptor signaling may be a critical link in the pathogenesis of anxiety and cognitive impairment seen in different disorders. The evidence reviewed here suggests that genetic influences on serotonergic systems and 5-HT2ARs might contribute to individual differences in the emotional memory process. Given that the association between serotonin and anxiety such as panic disorders and PTSD has been strongly demonstrated in the literature and is considered to have a heritable foundation, 5-HT2A hypofunction could represent a neurochemical trait that predisposes individuals to anxiety and impaired regulation of emotional memory, typical features of affective disorders.
So you can't just lump all 5-HT2A activity into the same category. It's more complex than that. Also, the other main mechanism for our new bacopa is the muscarinic acetylcholine receptors.
Muscarinic acetylcholine receptors act in synergy to facilitate learning and memory
So our bacopa is targeting both the 5-HT2A and muscarinic acetylcholine receptors, with the goal of promoting mood and memory. In addition, there is new research that both BDNF and reelin come into play with bacopa's effects. This activation of reelin causes an activation of the NMDA receptor as well, along with controlling the expression of both the 5-HT2A and D3 receptor. Almost nobody is talking about reelin.
https://www.frontiersin.org/articles/10.3389/fncel.2020.00285/full
https://sci-hub.se/10.1016/j.neuroscience.2015.01.031
So it is very complex, and the 5-HT2A activation is only part of the story. There are multiple systems at play in multiple brain regions. This bacopa we have developed is pretty damn cool, and I hope people like it as much as I do!