Role of endogenous hallucinogens in heart failure comorbid with depression

doi:10.12092/j.issn.1009-2501.2026.02.015

Abstract

Abstract:

With the growing global aging population, the incidence of heart failure complicated with depression is increasing, which causes a heavy health and economic burden. In recent years, endogenous hallucinogens, a class of compounds that can produce hallucinogenic effects in the body, have garnered widespread attention in the academic community, as previous studies have confirmed their effects on nervous system diseases, coronary heart disease, pulmonary fibrosis, and anti-tumor activity. However, the mechanisms of action of endogenous hallucinogens in the context of heart failure with depression remain unclear. This review introduces the potential mechanisms from four aspects: regulating the neuro-endocrine network, altering neuroplasticity, modulating the immune-inflammatory system, and reducing oxidative stress and apoptosis. These insights aim to provide therapeutic targets and basic research directions for patients with heart failure complicated with depression, ultimately improving the prognosis and quality of life of these patients.

Key words: hallucinogens, heart failure, depression, endocannabinoids, N,N-dimethyltryptamine

CLC Number:

Qianyuan SHI, Kai HUANG, Yi ZHANG, Jiahao DUAN, Chun YANG, Ling YANG. Role of endogenous hallucinogens in heart failure comorbid with depression[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(2): 272-280.

Figures/Tables 1

References 88

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分类	调节神经内分泌网络	调节神经可塑性	调节免疫炎症系统	减少氧化应激与细胞凋亡
色胺衍生物	能与5-HT受体、DA受体、NE受体、TAARs、 5-HT转运体、单胺氧化酶及Sig-1R结合；在体内急性转化为儿茶酚胺类物质；促进5-HT释放，抑制 5-HT与DA再摄取。	作为成人NSC活性的关键调节因子，调节SGZ干细胞群的增殖与分化；使小鼠新生神经元树突结构更复杂；刺激5-HT2受体，增强BDNF的表达。	NFAT和NF-kB通路激活，下调toll样受体和G蛋白偶联受体的表达；作为IDO的非竞争性抑制剂，显著抑制炎性细胞因子分泌；抑制CD4+T辅助细胞向炎性Th1和Th17极化；上调抗炎因子IL-10的mRNA和蛋白表达；作为内源性调节因子。	降低APAF1的mRNA表达；降低IL-1β、IL-6与TNF-α水平；提高抗炎因子IL-10浓度；减轻人皮质神经元及moMACs和moDCs的氧化应激；脂质过氧化标志物TBARS下降，SOD活性升高。
内源性大麻素	抑制钙通道、促进钾通道开放，减少Ach、NE、谷氨酸释放；在VTA区解除GABA对DA神经元的抑制；在NAc区抑制皮层谷氨酸对CINs影响；调节DRN中GABA能神经元；激活膜相关GR。	局部诱导LTP、远端诱导LTD，促进周围突触的LTP形成；依赖Ca²⁺浓度增加介导DSI和DSE；介导海马体与NAc中TRPV受体诱导LTD。	降低血清TNF-α；减少心肌炎症标志物；减少血管炎症标志物；减少CD45+白细胞数量。	上调抗氧化酶血红素加氧酶- 1 mRNA；提升肌球蛋白重链比率；增强CCL2 mRNA表达；减少ROS、MDA和MPO生成；促进SOD合成。

分类	调节神经内分泌网络	调节神经可塑性	调节免疫炎症系统	减少氧化应激与细胞凋亡
色胺衍生物	能与5-HT受体、DA受体、NE受体、TAARs、 5-HT转运体、单胺氧化酶及Sig-1R结合；在体内急性转化为儿茶酚胺类物质；促进5-HT释放，抑制 5-HT与DA再摄取。	作为成人NSC活性的关键调节因子，调节SGZ干细胞群的增殖与分化；使小鼠新生神经元树突结构更复杂；刺激5-HT2受体，增强BDNF的表达。	NFAT和NF-kB通路激活，下调toll样受体和G蛋白偶联受体的表达；作为IDO的非竞争性抑制剂，显著抑制炎性细胞因子分泌；抑制CD4+T辅助细胞向炎性Th1和Th17极化；上调抗炎因子IL-10的mRNA和蛋白表达；作为内源性调节因子。	降低APAF1的mRNA表达；降低IL-1β、IL-6与TNF-α水平；提高抗炎因子IL-10浓度；减轻人皮质神经元及moMACs和moDCs的氧化应激；脂质过氧化标志物TBARS下降，SOD活性升高。
内源性大麻素	抑制钙通道、促进钾通道开放，减少Ach、NE、谷氨酸释放；在VTA区解除GABA对DA神经元的抑制；在NAc区抑制皮层谷氨酸对CINs影响；调节DRN中GABA能神经元；激活膜相关GR。	局部诱导LTP、远端诱导LTD，促进周围突触的LTP形成；依赖Ca²⁺浓度增加介导DSI和DSE；介导海马体与NAc中TRPV受体诱导LTD。	降低血清TNF-α；减少心肌炎症标志物；减少血管炎症标志物；减少CD45+白细胞数量。	上调抗氧化酶血红素加氧酶- 1 mRNA；提升肌球蛋白重链比率；增强CCL2 mRNA表达；减少ROS、MDA和MPO生成；促进SOD合成。

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