The purpose of this study is to determine if psilocybin-related tryptamines bind to the 5-HT2A receptor through molecular calcium imaging. We hypothesized that psilocybin-related tryptamines would bind to the 5-HT2A receptor with appreciable affinity.
5HT2A receptors have gained popularity in research due to their suspected role in mental health, such as depression, anxiety, schizophrenia, and bipolar disorders. Common antipsychotic drugs and hallucinogens used for mental health treatment are known to bind to the 5HT2A receptor and activation of this receptor is believed to lead to a downstream improvement of behavioral and emotional symptoms experienced by the patient. Recent research has explored the possibility of using tryptaminergic compounds, such as lysergic acid diethylamide (LSD) and psilocybin, for mental health treatment due to their 5HT2A receptor binding affinity and agonist characteristics.
Tryptamines found in “magic mushrooms” such as psilocybin, baeocystin, norbaeocystin, and aeruginaescin are of interest as possible therapeutics. Utilizing specific 5HT2A receptor-overexpressing cell lines, we examined if our compounds of interest bind to and activate the 5HT-2A receptor. The 5HT2A receptor is a G-protein coupled receptor (GPCR) and agonist binding leads to the activation of intracellular Gq-mediated second messengers which results in an increase in intracellular calcium levels. Gq-dependent calcium flux assays, which measure the flux of intracellular calcium levels with a calcium-sensitive dye (Fluo-4), were used in vitro with 5HT2A overexpressing cells to analyze the binding affinity of each compound relative to 5HT.
Our results showed that our psilocybin-related tryptamines have appreciable binding with the 5HT2A receptor which aligns with previous studies. This indicates their potential efficacy as therapeutic medications. Future studies can be done to examine their binding affinity for other sites on the 5HT2A receptor or for the 5HT2B and 5HT2C receptors.
Author(s): Hunter Wells
Advisor(s): Ryan Rakoczy, Psychology
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