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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

Sanah Malomile Nkadimeng, L. Hay, Christiaan Ml Steinmann, J.n. Eloff

Research Square (Research Square) July 18, 2023 preprint DOI: 10.21203/rs.3.rs-3088850/v1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vivo and in vitro experimental study
Population Normal Wistar rats and H9C2 cardiomyocytes
Dose 5 mg/kg
Duration 1-hour treatment
Topics Serotonin Psilocybin
Keywords Enos Pharmacology Nitric oxide synthase In vivo
Citations 1
Key findings Psilocybin-containing mushroom extracts suppressed eNOS activity and increased serotonin levels, with non-significant effects on left ventricular function, suggesting eNOS pathway disruption as a mechanism for temporary blood pressure increase.

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.

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