Kamsrijai Utcharaporn, Charoensup Rawiwan, Jaidee Wuttichai, Hawiset Thaneeya, Thaweethee-Sukjai Benjamard, Praman Siwaporn
School of Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai, 57100, Thailand; School of Integrative Medicine, Major of Applied Thai Traditional Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
J Ethnopharmacol. 2025 Feb 10;338(Pt 3):119113. doi: 10.1016/j.jep.2024.119113. Epub 2024 Nov 15.
Hemp (Cannabis sativa L.) is increasingly being recognized for its medicinal properties beside utilizing it for food, oil, and textile fibers. The high level of cannabidiol (CBD) content in hemp's flowers shows promising neuroprotective properties without causing psychotomimetic or addictive effects. Recently, products containing CBD and its precursor, cannabidiolic acid (CBDA), have been used to treat stress-related cognitive impairment. However, the therapeutic potential of hemp extract remains inadequately explored.
To investigate the effect of CBD/CBDA-rich hemp extract on learning and memory, neuroendocrine alterations, and hippocampal neuropathological changes in the chronic restraint stress model.
Chronic restraint stress (CRS) was induced in male Wistar rats by immobilizing them in a restrainer for 6 h per day for 21 consecutive days. CBD/CBDA-rich hemp extract (10 and 30 mg/kg, intraperitoneal injection) was administered daily, 1 h before restraint. After the last day of CRS, behavioral tests for cognition were conducted using the Y-maze and object recognition tests. Serum corticosterone (CORT) levels were measured by ELISA. Histopathological changes, neuronal density, and the activation of microglia and astrocytes were visualized using cresyl violet and immunohistochemical staining.
A high dose of CBD/CBDA-rich hemp extract effectively ameliorated CRS-induced cognitive impairment and reversed HPA axis hyperactivity in CRS rats by reducing CORT levels and adrenal gland weight. Additionally, CBD/CBDA-rich hemp extract protected CRS-induced damage to hippocampal neurons. Further analysis showed that CBD/CBDA-rich hemp extract reduced specific markers of microglial activation (ionized calcium-binding adaptor molecule-1, Iba-1) and astrocytic structural protein (glial fibrillary acidic protein, GFAP) in CRS rats.
CBD/CBDA-rich hemp extracts remarkably reversed the stress-induced behavioral perturbations and hippocampal damage, suggesting its ameliorative effect on stress response.
大麻（Cannabis sativa L.）除了用于食品、油和纺织纤维外，其药用特性也越来越受到认可。大麻花中高水平的大麻二酚（CBD）含量显示出有前景的神经保护特性，且不会引起拟精神病或成瘾作用。最近，含有CBD及其前体大麻二酚酸（CBDA）的产品已被用于治疗与压力相关的认知障碍。然而，大麻提取物的治疗潜力仍未得到充分探索。
研究富含CBD/CBDA的大麻提取物对慢性束缚应激模型中学习记忆、神经内分泌改变及海马神经病理变化的影响。
通过将雄性Wistar大鼠每天固定在束缚器中6小时，连续21天，诱导其产生慢性束缚应激（CRS）。每天在束缚前1小时腹腔注射富含CBD/CBDA的大麻提取物（10和30mg/kg）。在CRS的最后一天后，使用Y迷宫和物体识别测试进行认知行为测试。通过酶联免疫吸附测定法（ELISA）测量血清皮质酮（CORT）水平。使用甲酚紫和免疫组织化学染色观察组织病理学变化、神经元密度以及小胶质细胞和星形胶质细胞的激活情况。
高剂量的富含CBD/CBDA的大麻提取物有效改善了CRS诱导的认知障碍，并通过降低CORT水平和肾上腺重量，逆转了CRS大鼠的下丘脑-垂体-肾上腺（HPA）轴功能亢进。此外，富含CBD/CBDA的大麻提取物保护了CRS诱导的海马神经元损伤。进一步分析表明，富含CBD/CBDA的大麻提取物降低了CRS大鼠中小胶质细胞激活的特异性标志物（离子钙结合衔接分子-1，Iba-1）和星形胶质细胞结构蛋白（胶质纤维酸性蛋白，GFAP）。
富含CBD/CBDA的大麻提取物显著逆转了应激诱导性的行为紊乱和海马损伤，表明其对应激反应具有改善作用。
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