Cannabidiol Alleviates Aβ1–42-Induced Cognitive Deficits and Neuronal Injury Associated with Modulation of the AEA–FAAH–CB1R Axis and BDNF/TrkB Signaling
- 1Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China
- 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
Abstract
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuronal injury. Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa L., has neuroprotective potential, but its underlying mechanisms remain unclear. Purpose: This study investigated the effects of CBD on Aβ1–42-induced cognitive impairment and hippocampal injury, focusing on endocannabinoid and BDNF/TrkB signaling. Methods: Cognitive function was assessed by Morris water maze and novel object recognition tests; hippocampal pathology and molecular changes were evaluated by H&E staining, immunofluorescence, LC–MS, ELISA, and Western blotting; and CB1R involvement was further examined in Aβ1–42-treated PC12 cells using AM251. Results: CBD improved cognitive performance, attenuated hippocampal histopathological alterations, reduced tau hyperphosphorylation, and partially restored synaptophysin levels. CBD also increased hippocampal AEA levels, reduced FAAH levels, and restored CB1R and BDNF/TrkB-associated signaling. In Aβ1–42-treated PC12 cells, CBD improved cell viability and increased synaptophysin, CB1R, BDNF, and p-TrkB/TrkB levels, whereas AM251 attenuated several CBD-associated effects. Conclusions: These findings suggest that modulation of the AEA–FAAH–CB1R axis and BDNF/TrkB signaling may contribute to the neuroprotective effects of CBD against Aβ1–42-induced cognitive impairment and neuronal injury.
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BibTeX
@article{kong2026cannabidiol,
title = {{Cannabidiol Alleviates Aβ1–42-Induced Cognitive Deficits and Neuronal Injury Associated with Modulation of the AEA–FAAH–CB1R Axis and BDNF/TrkB Signaling}},
author = {Yan Kong and Juan Peng and Jian Sun and Yinglan Nie},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101473},
url = {https://www.mdpi.com/2218-273X/16/10/1473},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cannabidiol Alleviates Aβ1–42-Induced Cognitive Deficits and Neuronal Injury Associated with Modulation of the AEA–FAAH–CB1R Axis and BDNF/TrkB Signaling
AU - Yan Kong
AU - Juan Peng
AU - Jian Sun
AU - Yinglan Nie
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101473
UR - https://www.mdpi.com/2218-273X/16/10/1473
AB - Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuronal injury. Cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa L., has neuroprotective potential, but its underlying mechanisms remain unclear. Purpose: This study investigated the effects of CBD on Aβ1–42-induced cognitive impairment and hippocampal injury, focusing on endocannabinoid and BDNF/TrkB signaling. Methods: Cognitive function was assessed by Morris water maze and novel object recognition tests; hippocampal pathology and molecular changes were evaluated by H&E staining, immunofluorescence, LC–MS, ELISA, and Western blotting; and CB1R involvement was further examined in Aβ1–42-treated PC12 cells using AM251. Results: CBD improved cognitive performance, attenuated hippocampal histopathological alterations, reduced tau hyperphosphorylation, and partially restored synaptophysin levels. CBD also increased hippocampal AEA levels, reduced FAAH levels, and restored CB1R and BDNF/TrkB-associated signaling. In Aβ1–42-treated PC12 cells, CBD improved cell viability and increased synaptophysin, CB1R, BDNF, and p-TrkB/TrkB levels, whereas AM251 attenuated several CBD-associated effects. Conclusions: These findings suggest that modulation of the AEA–FAAH–CB1R axis and BDNF/TrkB signaling may contribute to the neuroprotective effects of CBD against Aβ1–42-induced cognitive impairment and neuronal injury.
SN - 2218-273X
ER -