Huang Joyce, Pham Michelle, Panenka William J, Honer William G, Barr Alasdair M
Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Front Psychiatry. 2022 May 18;13:891512. doi: 10.3389/fpsyt.2022.891512. eCollection 2022.
There are currently relatively few effective pharmacological treatments for obesity, and existing ones may be associated with limiting side-effects. In the search for novel anti-obesity agents, drugs that modify central serotonergic systems have historically proven to be effective in promoting weight loss. Psilocin, which is rapidly metabolized from psilocybin, is an agonist at multiple serotonin receptors. In the present study we assessed the effects of psilocybin and a positive control (metformin) on changes in body weight in a rat model of obesity.
Five groups of adult male rats were pre-conditioned with a cafeteria diet until obese (>600 g) and then treated with either psilocybin (0.1, 1, or 5 mg/kg, i.p.), metformin (300 mg/kg, p.o.) or vehicle control. Treatments were for 27 consecutive weekdays, and body weights and high calorie food intake were recorded daily. Fasting glucose levels were recorded after 11 days of treatment. At the end of treatment rats completed a glucose tolerance test, and multiple fat pads were dissected out to assess adiposity.
The medium dose psilocybin group had to be terminated from the study prematurely. Both the low and high dose psilocybin groups caused a significant decrease in changes in body weight compared to controls. The metformin group produced a greater decrease in change in body weight than either psilocybin groups or controls. Both high dose psilocybin and metformin decreased consumption of the high calorie diet, and exhibited decreased central adiposity.
Psilocybin demonstrated modest but significant effects on weight gain. Further study is recommended.
目前针对肥胖的有效药物治疗相对较少，且现有药物可能伴有局限性副作用。在寻找新型抗肥胖药物的过程中，历史证明，调节中枢5-羟色胺能系统的药物在促进体重减轻方面是有效的。从裸盖菇素快速代谢而来的脱磷酸裸盖菇素是多种5-羟色胺受体的激动剂。在本研究中，我们评估了裸盖菇素和阳性对照（二甲双胍）对肥胖大鼠模型体重变化的影响。
将五组成年雄性大鼠用自助餐式饮食进行预处理，直至肥胖（体重>600克），然后分别用裸盖菇素（0.1、1或5毫克/千克，腹腔注射）、二甲双胍（300毫克/千克，口服）或赋形剂对照进行治疗。连续27个工作日进行治疗，每天记录体重和高热量食物摄入量。治疗11天后记录空腹血糖水平。治疗结束时，大鼠完成葡萄糖耐量试验，并解剖多个脂肪垫以评估肥胖程度。
中剂量裸盖菇素组不得不提前退出研究。与对照组相比，低剂量和高剂量裸盖菇素组均导致体重变化显著降低。二甲双胍组体重变化的降低幅度大于裸盖菇素组或对照组。高剂量裸盖菇素和二甲双胍均减少了高热量饮食的摄入量，并表现出中心性肥胖程度降低。
裸盖菇素对体重增加显示出适度但显著的影响。建议进一步研究。
