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Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

Zhuk O, Jasicka-Misiak I, Poliwoda A, Kazakova A, Godovan VV, Halama M, Wieczorek PP - Toxins (Basel) (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Molecular Biology, Opole University, 45-040 Opole, Poland. olga_zhuk@uni.opole.pl.

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.

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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).
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toxins-07-01018-f003: 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).

Mentions: Figure 3 shows the results of experiments in which tested mushroom extracts and pure psilocin (at dose 1 mg/kg) were injected 15 min before 5-HTP was injected intraperitoneally. The observation period was 10 and 20 min. In control groups of ten mice, only isotonic solution of Tween-80 (1%) was administrated. Tween-80 (a non-toxic and non-ionic additive) was used in order to increase the solubility of dry residues of methanolic mushroom extracts in water. The obtained data indicated that in mice, the tryptamine derivatives (psilocin and active components of applied fungal extracts) produced head-twitches via agonist binding at serotonin 5-HT2A receptors. The used hallucinogenic factors had only partial efficacy at the receptor relative to a full agonist (5-HTP) even at maximal receptor occupancy. The application of pure psilocin gave significantly lower head-twitch response (about 60% lower) compared to the effect of full agonist (5-HTP) at dose 200 mg/kg. When a mixture of hallucinogenic substances of fungal extracts was used, the HTR effect (compared to the full agonist activity) was reduced by about 45% (extract of Ph. cyanopus) and 30% (extract of P. semilanceata). At this point, it should be underlined that the concentration of psilocin in investigated extracts was at much lower level, according to the dose used in experiments with pure psilocin. Furthermore, the observed interactions between the 5-HT2A receptors and hallucinogens of mushroom extracts were also very effective. It seems, that the presence of the other indoleamine hallucinogenic compounds in the used extracts giving the synergistic effect influenced the serotonergic system.


Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

Zhuk O, Jasicka-Misiak I, Poliwoda A, Kazakova A, Godovan VV, Halama M, Wieczorek PP - Toxins (Basel) (2015)

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).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417952&req=5

toxins-07-01018-f003: 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).
Mentions: Figure 3 shows the results of experiments in which tested mushroom extracts and pure psilocin (at dose 1 mg/kg) were injected 15 min before 5-HTP was injected intraperitoneally. The observation period was 10 and 20 min. In control groups of ten mice, only isotonic solution of Tween-80 (1%) was administrated. Tween-80 (a non-toxic and non-ionic additive) was used in order to increase the solubility of dry residues of methanolic mushroom extracts in water. The obtained data indicated that in mice, the tryptamine derivatives (psilocin and active components of applied fungal extracts) produced head-twitches via agonist binding at serotonin 5-HT2A receptors. The used hallucinogenic factors had only partial efficacy at the receptor relative to a full agonist (5-HTP) even at maximal receptor occupancy. The application of pure psilocin gave significantly lower head-twitch response (about 60% lower) compared to the effect of full agonist (5-HTP) at dose 200 mg/kg. When a mixture of hallucinogenic substances of fungal extracts was used, the HTR effect (compared to the full agonist activity) was reduced by about 45% (extract of Ph. cyanopus) and 30% (extract of P. semilanceata). At this point, it should be underlined that the concentration of psilocin in investigated extracts was at much lower level, according to the dose used in experiments with pure psilocin. Furthermore, the observed interactions between the 5-HT2A receptors and hallucinogens of mushroom extracts were also very effective. It seems, that the presence of the other indoleamine hallucinogenic compounds in the used extracts giving the synergistic effect influenced the serotonergic system.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology and Molecular Biology, Opole University, 45-040 Opole, Poland. olga_zhuk@uni.opole.pl.

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.

Show MeSH
Related in: MedlinePlus