Administration effects of four psilocybin mushroom extracts on serotonin levels and endothelial nitric oxide synthase activity levels in vivo and in vitro after one hour
Research Square (Research Square) – July 18, 2023
Source: OpenAlex
Summary
Four psilocybin mushroom species, known for their psychedelic properties, temporarily increase blood pressure. This pharmacology investigation, using 5 mg/kg extracts in Wistar rats (in vivo) and heart cells, reveals a key biological mechanism. Extracts boosted serotonin, a vital neurotransmitter, while suppressing endothelial nitric oxide synthase (eNOS) activity. This suppression impacts nitric oxide (NO) pathways, offering a chemistry-based explanation for the temporary blood pressure rise, despite being safe for heart function at this dose. Different mushroom species showed varied effects, highlighting the complexity of these alkaloids and their neurotransmitter receptor influence.
Abstract
Abstract Background Psilocybin-containing mushrooms induce antidepressant and momentary increase in blood pressure (BP) with potential risk to users with cardiovascular diseases. Irregularities in nitric oxide (NO) levels play a key role in endothelial dysfunctions leading to increases in BP. Mushrooms species show large variation in potency which may potentially induce different outcomes and mechanisms of action. Effects of the mushrooms on the endothelial nitric oxide synthase activity is not known. Aim To investigate safety and effects of administration of four psilocybin-containing mushroom species, Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis and Psilocybe cubesis leucistic A + strain , on acute haemodynamic and LV parameters in normal Wistar rat and on serotonin, NO levels and endothelial NO synthase (eNOS) activity in vivo and in vitro on H9C2 cardiomyocytes. Methods Mushrooms were extracted with hot-boiling water and administered (5 mg/kg) through a direct catheterization in anaesthetized rats. Nuzak (0.2 mg/kg) and Nω-Nitro-L-arginine methyl ester hydrochloride (LNAME) were used as positive controls and negative control group given saline. Levels of serotonin, NO and eNOS activities were measured after 1-hour treatment. Results Mushroom treatments incited non-significant increase in LV parameters peaks only after 20 minutes and not immediate like with LNAME. Mushrooms induced a significant increase in serotonin levels and a suppressing effect on the eNOS activity in vivo in rats and in vitro in cardiomyocytes. Conclusion Mushroom treatments were safe on the LV function and induced a significant serotonin level with the concentration investigated. Disturbance in eNOS pathways may be the underlying mechanism involved in the psilocybin-mushroom extracts to inducing temporary BP increase. The four mushrooms exhibited different cardiac effects indicating variations depending on mushroom species.