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浙江大学教授李晓明团队联合董晓武、张岩团队,在成功解析大麻疗效机制和破解大麻“致毒密码”的基础上,设计出具有显著镇痛作用,又削弱耐药、成瘾等副作用的新型小分子药物,为非阿片类镇痛药和抗焦虑、抑郁等情感障碍药物的研发开辟了全新路径。2026年4月13日,相关研究成果发表于《Cell》。

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浙江大学教授李晓明团队联合董晓武、张岩团队,在成功解析大麻疗效机制和破解大麻“致毒密码”的基础上,设计出具有显著镇痛作用,又削弱耐药、成瘾等副作用的新型小分子药物,为非阿片类镇痛药和抗焦虑、抑郁等情感障碍药物的研发开辟了全新路径。2026年4月13日,相关研究成果发表于《Cell》。

. 不成瘾的大麻素可精准镇痛. 科技导报, 2026 , 44 (8) : 10 -10 .
. Science & Technology Review, 2026 , 44 (8) : 10 -10 .
浙江大学教授李晓明团队联合董晓武、张岩团队,在成功解析大麻疗效机制和破解大麻“致毒密码”的基础上,设计出具有显著镇痛作用,又削弱耐药、成瘾等副作用的新型小分子药物,为非阿片类镇痛药和抗焦虑、抑郁等情感障碍药物的研发开辟了全新路径。2026年4月13日,相关研究成果发表于《Cell》。
大麻素1型受体(CB1)表达降低是导致杏仁核活性异常,进而引起焦虑、抑郁发生的重要原因,外源性大麻素通过激活杏仁核CB1可产生抗抑郁等情绪调控作用。CB1下游存在2条主要信号通路。其中Gi/o信号主要负责镇痛、抗焦虑等治疗效应,β-arrestin(β-阻遏蛋白)信号则与药物耐受、成瘾等副作用密切相关。基于前期研究,团队利用AI辅助,设计出能够“偏向”Gi/o信号通路同时避免触发β-arrestin通路的全新CB1小分子化合物。
研究发现,CB1与β-arrestin偶联时,受体结合口袋内3个芳香氨基酸残基与传统大麻类激动剂产生明显空间位阻,因而必须采取“深埋构象”,导致副作用的发生。基于此,团队针对传统激动剂参与空间位阻的基团进行了理性改造——引入2种不同基团获得新型小分子,从而改变配体与受体结合模式,使其无法进入那个通往副作用的“深埋口袋”。
细胞水平的功能实验与结构验证一致显示。传统大麻类药物无差别地激活了2条通路,而理性设计的小分子能在高效激活Gi信号的同时,选择性削弱β-arrestin信号通路的活化。
进一步药物代谢动力学分析显示,理性设计的小分子具有优异的血脑屏障透过性,在热板测试、炎性痛、神经病理性疼痛等多种急、慢性疼痛模型中,均展现出显著的镇痛效应。在安全性评估中,连续给药7 d未见明显的耐受,条件性位置偏好实验未发现成瘾性,同时对体温和运动能力的影响也显著降低,成功规避了传统大麻素类药物的典型中枢副作用。
研究人员表示,这一研究成果目前已推进至大动物模型,在更复杂生理病理系统中验证了小分子的疗效与安全性,为开发新型有效安全的镇痛、抗抑郁、抗焦虑药物打下了基础。同时,团队正在进一步完善临床前研究,推进临床试验。
(综合:《Cell》、浙江大学官网、浙江在线)

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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