“Compounds derived from the plant Cannabis demonstrate many therapeutic properties suggesting that they could delay the onset and progression of Alzheimer’s disease (AD).

The goal of the present experiment was to observe the effects of chronic cannabidiol (CBD) administration on the behavior and brain pathology of an AD tauopathy mouse model, Tau P301S-Line PS19 mice.MethodsMice were orally given CBD (20 mg/kg) or vehicle, daily, beginning around 3 months of age. At 6 months old, mice were tested on a battery of tasks to assess object recognition, motor function, and spatial learning and memory. The mice were retested at 9 months old on the behavioral tasks and the fear conditioning paradigm was added. Following completion of behavioral testing, the mice were perfused for histological analysis.

Results Chronic CBD treatments did not appear to affect the behavior nor restore the reduced hippocampal volume of Tau P301S mice. However, a deeper assessment of the changes in inflammatory markers showed a treatment effect on a measure of microglia reactivity. Robust sex differences were revealed with Tau P301S males showing more severe pathology relative to females. Finally, daily treatments of CBD did not negatively impact the behavior or brain of any of the experimental groups suggesting that its chronic administration was relatively safe.

Conclusions Taken together, the results suggested that CBD can have beneficial effects on some of the pathology associated with AD, even in an aggressive model of this neurodegenerative disease, but the impacts on impaired behavior were minimal.”

https://pubmed.ncbi.nlm.nih.gov/41736228

“Cannabidiol (CBD) is a safe, readily available, and relatively inexpensive treatment option that has been shown to improve pathologies associated with AD.”

https://journals.sagepub.com/doi/10.1177/13872877261421654

“Background and objective: Neuropsychiatric symptoms (NPS) are highly prevalent in persons with dementia and have been associated with adverse health outcomes. Neuropsychiatric symptoms can impose major physical, psychosocial, and financial burdens on caregivers while contributing to additional pressure on healthcare systems. Although atypical antipsychotics have received regulatory approval for treating specific NPS, such as agitation, their use in older adults has been linked to higher risks of mortality, cardiovascular events, and falls. Cannabinoids have emerged as promising pharmacological treatments for NPS in dementia, including agitation, anxiety, and depressive symptoms, owing to their behavior-modulating effects. The objective of this study was to provide a comprehensive assessment of the efficacy and safety of cannabinoids for NPS in dementia, which may help refine evidence-based guidelines for their use.

Methods: We systematically reviewed studies from MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to August 2025. Search terms relevant to cannabinoids and dementia were used. Randomized controlled trials on the use of cannabinoids for treating NPS in dementia with published results were included. Participant characteristics, including age, sex, and baseline cognition, were collected. Random-effects meta-analyses were conducted to examine standardized mean differences in NPS scores between cannabinoid and placebo groups. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool (RoB 2) for randomized trials. Heterogeneity between studies was analyzed through I² statistics. Additionally, subgroup analyses and meta-regressions were performed for variables of interest. Last, risk ratios for outcomes related to adverse events were calculated to evaluate the safety of cannabinoids in this population.

Results: Of the ten included studies (328 participants), eight assessed total NPS and nine reported on agitation in persons with dementia. Our results indicated that cannabinoids did not decrease total NPS (standardized mean difference [SMD]: – 0.18, 95% confidence interval [CI] – 0.48 to 0.12; p = 0.2) compared to placebo, but reduced agitation (SMD: – 0.52, 95% CI – 1.00 to – 0.05, p = 0.03) with high heterogeneity (I² = 77.2%). However, after removing studies rated as high risk (RoB 2) for a sensitivity analysis, the result was no longer statistically significant (SMD: – 0.35, 95% CI – 0.79 to 0.10, p = 0.1). Subgroup analyses demonstrated that cannabinoids were beneficial with doses higher than 10 mg of tetrahydrocannabinol-equivalent (SMD: – 0.63, 95% CI – 0.98 to – 0.28, p < 0.01), and in patients with severe dementia (SMD: – 0.96, 95% CI – 1.75 to – 0.16, p < 0.01). The risk of overall adverse events did not differ significantly between cannabinoid and placebo treatments, though cannabinoids were associated with an increased risk of sedation (risk ratio = 2.09, 95% CI = 1.22 to 3.57, p < 0.01).

Conclusions: This review provides up-to-date evidence that cannabinoids are efficacious for alleviating dementia-related agitation and are generally well tolerated in this population, though sedation was more commonly reported in the cannabinoid group. However, the data remained scarce for other NPS and requires further research.”

https://pubmed.ncbi.nlm.nih.gov/41748849

https://link.springer.com/article/10.1007/s40263-026-01277-w

“Objective: Cannabis use has increased among older adults, yet the neurocognitive effects in this demographic remain unclear. Prior work has suggested cannabis may increase brain volume in areas rich in cannabinoid (CB1) receptors, though negative effects are often reported in adolescents. This study sought to clarify the relationship between cannabis use and brain health among middle-aged and older adults.

Method: Using data from the UK Biobank, which includes health information from over 500,000 adults, associations between cannabis use, regional brain volume, and cognition in participants aged 40-70 years (mean age = 54.5) were evaluated.

Results: Lifetime cannabis use was positively associated with regional brain volume in CB1-rich regions, including the caudate, putamen, hippocampus, and amygdala. Greater lifetime use was also linked to better performance in learning, processing speed, and short-term memory. Individuals reporting use limited to adolescence also showed larger regional volumes and better cognitive performance than non-users. Sex differences in cannabis effects on brain volume and cognition were also observed.

Conclusions: Results highlight that cannabis may influence brain health differently across the lifespan, potentially offering protective effects in older age while posing risks earlier in development. Protective effects may result from endocannabinoid-mediated modulation of inflammation, immune function, and neurodegeneration. Observed sex differences likely reflect variation in the endocannabinoid system and underscore the importance of considering sex as a biological variable in studies of cannabis and brain health.”

https://pubmed.ncbi.nlm.nih.gov/41379083

https://www.jsad.com/doi/10.15288/jsad.25-00346

“Alzheimer’s disease is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaque deposition and neurofibrillary tangles composed of hyperphosphorylated tau. Dysregulation of glycogen synthase kinase-3β (GSK3β) promotes tau hyperphosphorylation and amplifies Aβ-induced neurotoxicity, driving pathogenesis. Despite extensive research, current therapies targeting these core mechanisms remain largely ineffective at halting disease progression.

Based on prior clinical and preclinical evidence, we hypothesize that cannabidiol (CBD), a non-psychoactive phytocannabinoid, may exert multitarget therapeutic effects in AD by modulating Aβ aggregation, tau hyperphosphorylation, and GSK3β activity.

We investigated CBD’s interactions with Aβ-42/40, tau, and GSK3β using molecular docking, molecular dynamics simulations and ADMET predictions.

Our results show that CBD binds to Aβ with binding free energies of -7.81 kcal/mol, -7.46 kcal/mol, and -7.25 kcal/mol, disrupting aggregation by interacting with key residues (HIS6, HIS13, HIS14, GLU14, GLU22, ASP15, and ASP23). MD simulations confirm that CBD destabilizes Aβ’s β-sheet structure, preventing fibril formation. CBD binds tau with binding free energies of -9.91 kcal/mol, -9.70 kcal/mol, and -9.66 kcal/mol, disrupting tau aggregation and preventing neurofibrillary tangle formation. MD simulations show that CBD induces structural changes in tau, reducing β-sheet packing and inhibiting tau-tau interactions. CBD also binds to GSK3β with binding energies of -8.94 kcal/mol, -8.51 kcal/mol, and -8.41 kcal/mol, competing with ATP to inhibit its kinase activity and reduce tau phosphorylation. ADMET analysis indicates CBD’s favorable oral bioavailability and low toxicity.

These findings support CBD as a promising multitarget therapeutic for AD, warranting further preclinical and clinical investigations.”

https://pubmed.ncbi.nlm.nih.gov/41105605/

https://journals.sagepub.com/doi/10.1177/13872877251386440