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.

Figure 1

The probability (P) of the lethal effect in the population of the tested mice after a single intraperitoneal administration of the mushroom extracts (I—Ph. cyanopus, II—P. semilanceata) at dose 200–450 and psilocin (III) in the doses from 180–420 mg/kg (ln d).

Figure 2

Effect of studied hallucinogenic agents on the head-twitch response in mice, after the administration of the dose. I and II—dried residues of methanolic extracts of Ph. cyanopus and P. semilanceata, respectively; III—pure psilocin. Data are presented as group means ± S.E.M. using in statistics one-way ANOVA tests with the post hoc tests (Bonferroni procedure).

Figure 3

The head-twitch response in mice treated with investigated hallucinogenic stimulants at a dose of 1 mg/kg followed by a single intraperitoneal dose of 200 mg/kg 5-hydroxytryptophan (5-HTP). I—extract of Ph. cyanopus; II—extract of P. semilanceata; III—pure psilocin. Observation period: 10 and 20 min. Control group was administrated only with isotonic solution of Tween-80. Data are presented as group means ± S.E.M. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to the control group using in statistics one-way ANOVA tests with the post hoc test (Bonferroni procedure).