A new study published in Molecular Psychiatry provides preliminary evidence that cannabidiol, a compound derived from cannabis, may reduce cognitive decline and brain pathology in a mouse model of Alzheimer’s disease. Researchers found that chronic administration of cannabidiol improved memory performance and reduced the accumulation of amyloid-beta plaques—one of the hallmarks of Alzheimer’s. These benefits were linked to cannabidiol’s ability to regulate overactive brain cells in a key region involved in memory.

Cannabidiol, or CBD, is one of the main components of cannabis. Unlike tetrahydrocannabinol (THC), it does not produce a high and is generally considered safe. In recent years, researchers have been exploring its potential therapeutic effects on various neurological and psychiatric conditions, including epilepsy, anxiety, and neurodegenerative diseases such as Alzheimer’s. One area of interest is whether CBD can calm excessive brain activity, a problem observed in people and animals with Alzheimer’s disease.

The research team, based in China, conducted a series of experiments to test whether CBD could reduce symptoms of Alzheimer’s in genetically modified mice known as 5×FAD mice. These animals are widely used in research because they develop Alzheimer’s-like symptoms, including memory loss and the buildup of toxic amyloid-beta plaques in the brain. The researchers administered a low daily dose of CBD to these mice for just over a month and then assessed their behavior, brain activity, and the extent of brain pathology.

To evaluate memory function, the mice completed a series of behavioral tests. In a novel object recognition test, CBD-treated mice spent more time exploring new objects, indicating improved recognition memory. In two separate spatial memory tasks—the Morris water maze and the Barnes maze—CBD-treated mice learned the location of a hidden platform more quickly and remembered it better than untreated mice. These improvements in memory occurred without changes in general motor function or anxiety-like behavior, suggesting that CBD had specific effects on cognition.

Beyond behavior, the researchers looked directly at the brains of the mice. They found that CBD treatment led to a reduction in amyloid-beta plaques, particularly in the dentate gyrus, a part of the hippocampus that plays an important role in learning and memory. The reduction was most noticeable in smaller plaques, which are typically newly formed. This suggests that CBD may help slow the formation of new plaques rather than clear out existing ones. Importantly, the extent of plaque reduction in the dentate gyrus was strongly associated with the improvements in memory, highlighting the relevance of this brain region in both pathology and treatment response.

The study also investigated how CBD might achieve these effects at the molecular level. The researchers focused on glycine receptors, which help regulate electrical activity in the brain by dampening excessive neuronal firing. These receptors are particularly abundant in the dentate gyrus. Previous studies have shown that CBD can enhance the activity of glycine receptors by binding to a specific site on the receptor protein.

Using genetic techniques, the researchers disrupted glycine receptor function in some mice to test whether these receptors were necessary for CBD’s effects. In mice where glycine receptors in the dentate gyrus were either knocked down or altered to prevent CBD binding, the beneficial effects of CBD disappeared. These mice showed no improvements in memory and no reduction in amyloid-beta plaques, strongly suggesting that glycine receptors are a key mechanism behind CBD’s therapeutic action.

To explore how this might affect brain function, the researchers used several techniques to measure neuronal activity. In untreated Alzheimer’s model mice, neurons in the dentate gyrus were overly active, firing more rapidly than normal. Chronic CBD treatment reduced this hyperactivity, bringing the cells’ behavior closer to normal levels. This calming effect was not observed in mice with disabled glycine receptors, further reinforcing their central role.

The team also recorded brain activity in living mice by implanting electrodes and using calcium imaging, a technique that tracks real-time cellular activity. They found that after CBD infusion, many neurons in the dentate gyrus showed a marked drop in activity. In contrast, mice with a mutated version of the glycine receptor that could not interact with CBD showed little to no change.

While these findings are promising, there are several limitations to the study. First, the research was conducted in mice, not humans. Although animal models are useful for understanding disease mechanisms and testing treatments, they do not capture all aspects of human Alzheimer’s. Second, the study only used male mice, and future research will need to explore whether the same results hold true in females. Third, while the study identified glycine receptors as an important target for CBD, the compound interacts with many other receptors and systems in the brain. More work is needed to understand how these other pathways may contribute to its effects.

Despite these limitations, the findings add to a growing body of evidence suggesting that CBD has potential as a treatment for Alzheimer’s disease. By reducing abnormal brain activity and slowing the formation of harmful plaques, CBD may help preserve memory and cognitive function. The study also highlights the importance of glycine receptors in regulating brain activity and offers a new avenue for therapeutic intervention.

The study, “Cannabidiol ameliorates cognitive decline in 5×FAD mouse model of Alzheimer’s disease through potentiating the function of extrasynaptic glycine receptors,” was authored by Jin Jin, Chonglei Fu, Jing Xia, Heyi Luo, Xianglian Wang, Si Chen, Huanhuan Mao, Kai Yuan, Lin Lu, Wei Xiong, and Guichang Zou.