“Cannabidiol (CBD) has gained a lot of interest in recent years for its purported medicinal properties. CBD has been investigated for the treatment of anxiety, depression, epilepsy, neuroinflammation, and pain.

Recently there has been an interest in CBD as a possible treatment for age-related disorders such as Alzheimer’s disease and related disorders (ADRD). Here we tested the hypothesis that chronic CBD administration would improve learning and memory in the SAMP8 mouse model of Alzheimer’s disease.

SAMP8 mice aged 11 months (at the start of the study) were administered vehicle or CBD (3 or 30 mg/Kg) daily via oral gavage for 2 months. Vehicle-treated young SAMP8 mice (age 3 months at the start of the study) served as unimpaired controls. After 30 days of treatment (4 and 12 months of age), learning and memory, activity, anxiety, strength and dexterity were assessed.

High dose CBD treatment significantly improved learning and memory of the 12-month-old mice in the T maze. Novel object recognition memory was also improved by CBD in aged CBD treated mice. Aged CBD treated mice also displayed less anxiety in the elevated plus maze test compared to controls. However, activity and strength levels were similar between groups. Biochemical analysis revealed decreased markers of oxidative stress, providing a possible mechanism by which CBD treatment impacts learning, memory, and anxiety.

These results highlight the potential use of CBD as a therapeutic for age related cognitive impairment and dementia.”

https://pubmed.ncbi.nlm.nih.gov/40811673/

“Cannabidiol (CBD) is an abundant phytocannabinoid found in the Cannabis sativa plant.”

“CBD is thought by many to have medicinal properties. Except for a few conditions including two rare forms of epilepsy and multiple-sclerosis-associate spasticity, CBD has not been approved by the FDA”

“Here, we examine the potential use of CBD in treating age- related memory loss, anxiety, strength and dexterity impairment in the Senescence-accelerated mouse -prone 8(SAMP8) mice, a polygenic model of spontaneous onset AD.”

“Our results indicate that CBD can reverse age-related changes in the SAMP8 mice. CBD reversed memory impairment in both the T-maze and NOR with a 24-hour retention interval. These results indicate that CBD is able to reverse memory impairment in both spatial and recognition tasks. Taken together therefore, there appears to be an antioxidant effect of CBD contributing to the improvement in memory in the aged mice. These results show that CBD is an attractive therapeutic warranting further investigation in AD, and other neurodegenerative diseases.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0296586

“Aging is associated with cognitive decline, and currently, there are no approved medications that can prevent these impairments.

Recently, cannabinoids derived from Cannabis sativa have emerged as promising therapeutic compounds with neuroprotective, anti-inflammatory, and cognitive-enhancing properties. Despite their benefits, further research is needed to fully understand their efficacy across various conditions.

This study investigates the effects of cannabidiol (CBD) on memory impairment and brain inflammation in aging mice.

Fourteen-month-old C57 mice were administered CBD orally for 7 months and subsequently evaluated between 19 and 21 months of age using behavioral tasks that are sensitive to dysfunction of the perirhinal cortex, hippocampus, amygdala, and various brain regions that are crucial for motor control and coordination.

The findings of this study indicate that CBD reduces inflammatory response in the brain and improves cognitive decline associated with aging.”

https://pubmed.ncbi.nlm.nih.gov/40416734/

“The findings of this study show that CBD targets inflammatory responses in the brain and can improve cognitive decline associated with aging. It is possible that the effects of CBD treatment can be enhanced if an extract with THC and terpenoids is used.”

https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1567650/full

“Age-related cognitive decline and neurodegenerative diseases, such as Alzheimer’s disease, represent major global health challenges, particularly with an aging population. Mitochondrial dysfunction appears to play a central role in the pathophysiology of these conditions by driving redox dysregulation and impairing cellular energy metabolism. Despite extensive research, effective therapeutic options remain limited.

Cannabinol (CBN), a cannabinoid previously identified as a potent inhibitor of oxytosis/ferroptosis through mitochondrial modulation, has demonstrated promising neuroprotective effects.

In cell culture, CBN targets mitochondria, preserving mitochondrial membrane potential, enhancing antioxidant defenses and regulating bioenergetic processes. However, the in vivo therapeutic potential of CBN, particularly in aging models, has not been thoroughly explored.

To address this gap, this study investigated the effects of CBN on age-associated cognitive decline and metabolic dysfunction using the SAMP8 mouse model of accelerated aging.

Our results show that CBN significantly improves spatial learning and memory, with more pronounced cognitive benefits observed in female mice. These cognitive improvements are accompanied by sex-specific changes in metabolic parameters, such as enhanced oxygen consumption and energy expenditure. Mechanistically, CBN modulates key regulators of mitochondrial dynamics, including mitofusin 2 (MFN2) and dynamin-related protein 1 (DRP1), while upregulating markers of mitochondrial biogenesis including mitochondrial transcription factor A (TFAM) and translocase of outer mitochondrial membrane 20 (TOM20). Additionally, CBN upregulates key synaptic proteins involved in vesicle trafficking and postsynaptic signaling suggesting that it enhances synaptic function and neurotransmission, further reinforcing its neuroprotective effects.

This study provides in vivo evidence supporting CBN’s potential to mitigate age-related cognitive and metabolic dysfunction, with notable sex-specific effects, highlighting its promise for neurodegenerative diseases and cognitive decline.”

https://pubmed.ncbi.nlm.nih.gov/40412024/

“CBN shows promise as a therapeutic agent for age-related cognitive decline and metabolic dysfunction.”

https://www.sciencedirect.com/science/article/pii/S2213231725002058?via%3Dihub

“Alzheimer’s disease (AD) is the most common form of dementia, characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles, leading to neuronal loss and cognitive impairments. Recent studies have reported the dysregulation of RNA splicing in AD pathogenesis.

Our previous transcriptomic study demonstrated the neuroprotective effect of the phytocannabinoid cannabinerol (CBNR) against the cell viability loss induced by Aβ in differentiated SH-SY5Y cells. This study also highlighted the deregulation of genes involved in mRNA splicing after Aβ exposure or CBNR pre-treatment.

Here, we investigated whether CBNR could restore the splicing defects induced by Aβ in an AD in vitro model.

Using the rMATS computational tool for detecting differential alternative splicing events (DASEs) from RNA-Seq data, we obtained 96 DASEs regulated in both conditions and, remarkably, they were all restored by CBNR pre-treatment. The pathway analysis indicated an over-representation of the “Alzheimer’s disease-amyloid secretase pathway”. Additionally, we observed that Aβ exposure increased the frequency of retained introns (RIs) among the shared DASEs, and that this frequency returned to normality by CBNR pre-treatment. Interestingly, most of these RIs contain a premature in-frame stop codon within the RNA sequence. Finally, analyzing the DASE regions for miRNA hybridization, we found 33 potential DASE/miRNA interactions that were relevant in AD pathogenesis.

These findings revealed a novel trans-gene regulation by CBNR, potentially explaining part of its neuroprotective role. This is the first study demonstrating the involvement of a cannabinoid in the regulation of mRNA splicing in an AD model.”

https://pubmed.ncbi.nlm.nih.gov/40243843/

“In conclusion, we documented for the first time that a cannabinoid, CBNR, is able to regulate AS in an in vitro AD model. CBNR pre-treatment restored the splicing defects produced by Aβ exposure, involving genes also highly associated with AD. Moreover, thanks to this mechanism, CBNR probably counteracts the Aβ-induced mis-regulation of genes, due to premature stop codons and miRNA or lncRNA targeting. This work improves our knowledge of the molecular mechanisms that can be potentially useful in treating AD, corroborating the fact that drugs targeting post-transcriptional splicing processes could be considered novel and valid choices in neuroprotection and prevention issues.”

https://www.mdpi.com/1422-0067/26/7/3113