Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

Abstract

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Taking Different Roads: l‐Tryptophan as the Origin of Psilocybe Natural Products

“…These data, along with alkaloid production that is triggered in the fungus upon formation of the ephemeral fruiting bodies, [31] suggest that nematodes are not psilocybin's primary target. In addition, toxicity of psilocybin in mammals is near negligible in terms of acute physiological damage, with a LD 50 /ED 50 ratio >1000 in mice [32] . Regarding any potential antiinsect activity, a preprint article describes that only a single individual of Sciaridae sp.…”

“…In addition, toxicity of psilocybin in mammals is near negligible in terms of acute physiological damage, with a LD 50 /ED 50 ratio > 1000 in mice. [32] Regarding any potential antiinsect activity, a preprint article describes that only a single individual of Sciaridae sp. (dark winged fungus gnat) completed the entire developmental cycle (i. e., egg to adult) feeding solely on P. cyanescens.…”

Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis

“…Psychoactive mushrooms have been used as entheogens during transcendental ceremonies by Mexican inhabitants, mainly by shamans, for thousands of years. Mushrooms used for religious and spiritual rituals are called “magic mushrooms.” 1–3 There are many mushroom species that contain high levels of psychotropic tryptamines, including the genera Pluteus , Panaeolus , Inocybe , Gymnopilus , Galerina , Pholiotina , and especially Psilocybe 4–7 . In the 1950s, these magic mushrooms were introduced to Europe thanks to Gordon Wasson, who brought them from Mexico from the shaman Maria Sabina of the Mazatec tribe 8,9 .…”

Norpsilocin: freebase and fumarate salt

“…The clinical effects observed for extracts of 'magic mushrooms' differ from those observed for pure psilocybin (Zhuk, et al 2015). This indicates that the minor components of 'magic mushrooms' have psychoactive properties that are important, or that they work in conjunction with psilocybin as part of an entourage effect (Russo, 2011).…”