title: 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.
authors.affiliation: Department of Biotechnology and Molecular Biology, Opole University, 45-040 Opole, Poland. olga_zhuk@uni.opole.pl.
authors.forename: Olga
authors.initials: O
authors.lastname: Zhuk
authors.affiliation: Faculty of Chemistry, Opole University, 45-040 Opole, Poland. izajm@uni.opole.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Jasicka-Misiak
authors.affiliation: Faculty of Chemistry, Opole University, 45-040 Opole, Poland. anna.poliwoda@uni.opole.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Poliwoda
authors.affiliation: Department of General and Clinical Pharmacology, Odessa National Medical University, 65000 Odessa, Ukraine. ignozy@gmail.com.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kazakova
authors.affiliation: Department of General and Clinical Pharmacology, Odessa National Medical University, 65000 Odessa, Ukraine. godovan@mail.ru.
authors.forename: Vladlena V
authors.initials: VV
authors.lastname: Godovan
authors.affiliation: Museum of Natural History, University of Wrocław, 50-335 Wrocław, Poland. marhal@uni.wroc.biol.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Halama
authors.affiliation: Faculty of Chemistry, Opole University, 45-040 Opole, Poland. piotr.wieczorek@uni.opole.pl.
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Wieczorek
mesh_terms: D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D021461:Animals, Outbred Strains; D001522:Behavior, Animal / Q000187:drug effects; D045424:Complex Mixtures / Q000633:toxicity*; D005260:Female; D006213:Hallucinogens / Q000633:toxicity*; D007928:Lethal Dose 50; D000432:Methanol / Q000737:chemistry; D051379:Mice; D011562:Psilocybin / Q000031:analogs & derivatives* / Q000633:toxicity; D012997:Solvents / Q000737:chemistry
chemical_list: D045424:Complex Mixtures; D006213:Hallucinogens; D012997:Solvents; D011562:Psilocybin; C009105:psilocin; D000432:Methanol
references.citation: Br J Pharmacol Chemother. 1963 Feb;20:106-20
references.pmid: 14023050
references.citation: J Ethnopharmacol. 1993 Sep;40(1):21-40
references.pmid: 8246528
references.citation: J Pharm Pharmacol. 1976 Oct;28(10):775-6
references.pmid: 10375
references.citation: J Pharm Sci. 1967 Jan;56(1):146
references.pmid: 6067681
references.citation: Psychopharmacology (Berl). 2010 Apr;209(2):163-74
references.pmid: 20165943
references.citation: Ther Adv Psychopharmacol. 2014 Aug;4(4):156-69
references.pmid: 25083275
references.citation: Med Hypotheses. 2013 Nov;81(5):766-7
references.pmid: 23932733
references.citation: J Chromatogr. 1984 Nov 16;312:467-72
references.pmid: 6543215
references.citation: J Chromatogr. 1987 Nov 6;408:402-8
references.pmid: 3429538
references.citation: Ther Drug Monit. 2013 Aug;35(4):420-42
references.pmid: 23851905
references.citation: Neuropharmacology. 2011 Sep;61(3):364-81
references.pmid: 21256140
references.citation: Pharmacol Res. 1991 Apr;23(3):217-32
references.pmid: 2068047
references.citation: Planta Med. 1985 Oct;51(5):385-7
references.pmid: 17342589
references.citation: J Psychopharmacol. 2011 Nov;25(11):1434-52
references.pmid: 20855349
references.citation: J Psychopharmacol. 2011 Nov;25(11):1548-61
references.pmid: 21148021
references.citation: Neuron. 2007 Feb 1;53(3):439-52
references.pmid: 17270739
references.citation: J Basic Microbiol. 1994;34(1):17-22
references.pmid: 8207663
references.citation: Drug Test Anal. 2012 Jul-Aug;4(7-8):556-76
references.pmid: 22517680
references.citation: Neuropharmacology. 1990 Mar;29(3):193-8
references.pmid: 2139186
references.citation: Biochem Pharmacol. 1991 Aug 8;42(5):1099-105
references.pmid: 1872895
references.citation: Lloydia. 1977 Nov-Dec;40(6):566-78
references.pmid: 600026
references.citation: Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):319-23
references.pmid: 9164589
references.citation: J Med Chem. 2000 Nov 30;43(24):4701-10
references.pmid: 11101361
references.citation: Arch Gen Psychiatry. 2011 Jan;68(1):71-8
references.pmid: 20819978
references.citation: Pharmacol Ther. 2004 Feb;101(2):131-81
references.pmid: 14761703
references.citation: J Chromatogr B Biomed Sci Appl. 1998 May 29;709(2):255-63
references.pmid: 9657222
references.citation: Neuropharmacology. 1983 Aug;22(8):993-1000
references.pmid: 6604885
references.citation: J Psychiatry Neurosci. 2013 Mar;38(2):78-83
references.pmid: 23171696
references.citation: J Neurosci. 1989 Oct;9(10):3482-90
references.pmid: 2795135