背景:中枢神经系统(CNS)疾病可以是多种多样的,通常伴有合并症,就像抑郁和焦虑一样。尽管像Psilocybe蘑菇这样的替代品可以用于心理健康,但没有基础研究来证明其中枢神经系统的益处。
目的:评估抗焦虑和抗抑郁样作用,以及平菇的急性毒性。
方法:首先,经食管(p.o.)和腹膜内(i.p.)给药后,测定了P.cubensis(2000mg/kg)的急性毒性(LD50)。包括旋转棒测试和脑电图(EEG)以评估自由移动小鼠的CNS毒性。在野外分析了抗焦虑(走动或探索和养育行为)和抗抑郁行为反应,加迷宫,强迫游泳测试,分别,服用1000mg/kg后,p.o.,完整的平菇或极性水溶液(AQ)或甲醇(MeOH)提取物(1、10和/或100mg/kg,i.p.)与参考药物丁螺环酮(4mg/kg,i.p.),氟西汀和/或丙咪嗪(10mg/kg,s.c.和i.p.,分别)。进行AQ和MeOH提取的化学分析以通过使用UHPLC检测裸盖素和/或裸盖素。
结果:在旋转棒试验或脑电图活动中评估的小鼠中,高剂量给药的库贝蘑菇的神经毒性作用不存在。通过口服或腹膜内给药计算LD50>2000mg/kg。虽然整个库贝蘑菇产生了显著的和/或剂量反应的抗抑郁药样作用,p.o.,以及在肠胃外施用AQ或MeOH提取物后,类似于参考药物的作用。如迷宫测试所证实的,行为反应与开放视野中的抗焦虑样作用有关。在AQ提取中主要表征了psilocybin和psilocin的存在。
结论:我们的结果提供了临床前证据,证明了平菇的抗焦虑和抗抑郁样作用,而在肠内或肠胃外给药后不产生神经毒性,其中psilocybin和psilocin主要是在AQ提取后鉴定的。这项研究加强了P.cubensis蘑菇在心理健康和治疗焦虑和抑郁方面的益处。
BACKGROUND: Central nervous system (CNS) diseases can be diverse and usually present with comorbidity, as in the case of depression and anxiety. Despite alternatives like
Psilocybe mushrooms for mental health there is no basic research to evidence their CNS benefits.
OBJECTIVE: To evaluate the anxiolytic- and antidepressant-like effects, as well as the acute toxicity of P. cubensis mushroom.
METHODS: First, the acute toxicity (LD50) of P. cubensis (2000 mg/kg) was determined after the esophageal (p.o.) and intraperitoneal (i.p.) route of administration. The rota-rod test and electroencephalogram (EEG) were included to assess CNS toxicity in free moving mice. Anxiolytic (ambulatory or exploratory and rearing behaviors) and antidepressant behavioral responses were assayed in the open-field, plus-maze, and forced swimming test, respectively, after administration of 1000 mg/kg, p.o., of the whole P. cubensis mushroom or the polar aqueous (AQ) or methanolic (MeOH) extractions (1, 10, and/or 100 mg/kg, i.p.) in comparison to the reference drugs buspirone (4 mg/kg, i.p.), fluoxetine and/or imipramine (10 mg/kg, s.c. and i.p., respectively). A chemical analysis of the AQ and MeOH extractions was performed to detect psilocybin and/or psilocin by using UHPLC.
RESULTS: Neurotoxic effects of P. cubensis mushroom administered at high doses were absent in mice assessed in the rota-rod test or for EEG activity. A LD50 > 2000 mg/kg was calculated by p.o. or i.p. administration. While significant and/or dose-response antidepressant-like effects were produced with the whole P. cubensis mushroom, p.o., and after parenteral administration of the AQ or MeOH extractions resembling the effects of the reference drugs. Behavioral responses were associated with an anxiolytic-like effect in the open-field as corroborated in the plus-maze tests. The presence of psilocybin and psilocin was mainly characterized in the AQ extraction.
CONCLUSIONS: Our results provide preclinical evidence of the anxiolytic- and antidepressant-like effects of the P. cubensis mushroom without producing neurotoxicity after enteral or parenteral administration, where psilocybin and psilocin were identified mainly after AQ extraction. This study reinforces the benefits of the P. cubensis mushroom in mental health and therapy for anxiety and depression.