Alzheimer’s disease (AD) and other forms of dementia involve progressive cognitive decline, memory loss, and behavioral and psychological symptoms (BPSD) such as agitation, anxiety, and aggression. Underlying processes include amyloid-beta (Aβ) plaque accumulation, tau hyperphosphorylation, neuroinflammation, and oxidative stress. Limited disease-modifying treatments have increased interest in non-intoxicating hemp-derived cannabinoids like cannabidiol (CBD) and cannabigerol (CBG). These compounds interact with the endocannabinoid system and other pathways, offering potential neuroprotective, anti-inflammatory, and symptom-relieving effects. https://www.mdpi.com

This post reviews some of the scientific evidence on CBD and CBG for Alzheimer’s and dementia-related conditions, and discusses formulation differences (particularly nano-emulsified versus regular hemp extracts held under the tongue).Evidence remains preliminary; these are not FDA-approved treatments for dementia or Alzheimer’s. Always consult a healthcare provider before use, especially in older adults.

Mechanisms: How CBD and CBG May Support Brain Health

CBD and CBG target multiple pathways relevant to neurodegenerative diseases:

– Neuroprotection and Anti-Inflammatory Action: A 2025 systematic review and meta-analysis of preclinical AD models showed that CBD significantly reduced neuroinflammation markers, including glial fibrillary acidic protein (GFAP) (p < 0.0001), IL-6, and iNOS, with variable effects on TNF-α and IL-1β. These changes could help reduce reactive gliosis and neuronal damage.  https://www.mdpi.com

– Amyloid and Tau Pathology: Preclinical studies suggest CBD may reduce Aβ-induced toxicity, modulate plaque formation or clearance, and influence tau phosphorylation. In cell and animal models, CBD has counteracted Aβ cytotoxicity and supported cognitive function.

– Antioxidant Effects: Both CBD and CBG exhibit antioxidant properties that may protect against oxidative stress, a key contributor to neurodegeneration.

CBG has shown neuroprotective potential in models of cerebral ischemia and inflammation, which can contribute to vascular dementia.

Evidence for Symptom Management: Agitation, Anxiety, and Behavioral Symptoms

BPSD significantly affects quality of life for patients and caregivers. Clinical studies have explored cannabinoids primarily for these symptoms:

– A 2022 randomized, double-blind, placebo-controlled trial found that a broad-spectrum cannabis oil rich in CBD (30% CBD, 1% THC; administered sublingually) significantly reduced agitation compared to placebo in patients with dementia-related behavioral disturbances over 16 weeks.https://www.frontiersin.org

– The phase 2a CANBiS-AD trial (2024), a randomized, double-blind, placebo-controlled study, evaluated oral CBD (up to 600 mg/day) in Alzheimer’s patients with BPSD. It showed numerical improvements in Neuropsychiatric Inventory (NPI) scores for agitation, anxiety, apathy, and caregiver distress, though larger trials are needed for confirmation.https://www.cambridge.org/ 

– An open-label trial of a high-CBD/low-THC sublingual solution over 8 weeks reported reductions in anxiety and agitation in mild-to-moderate Alzheimer’s or MCI patients, with some cognitive improvements noted.https://www.ajgponline.org.

– Ongoing trials include NCT05822362 (effects of CBD on AD biomarkers in at-risk individuals) and NCT04436081 (THC-free CBD oil for agitation in Alzheimer’s). 

– A 2025 randomized trial of low-dose balanced THC-CBD extract also suggested potential benefits for symptoms in AD-related dementia. https://pubmed.ncbi.nlm.nih.gov/

A 2025 meta-analysis indicated borderline significant benefits for behavioral symptoms and agitation with CBD (p=0.05), with generally mild adverse events. Preclinical data further support CBD improving age-related cognitive decline via reduced brain inflammation. https://doi.org/

Clinical evidence focuses more on symptom relief than disease modification and is limited by small samples and short durations.

CBG Research: Studies on Neurodegenerative Models

Research on CBG for dementia and Alzheimer’s is at an earlier stage than for CBD, with most data from preclinical models. Direct studies include:

– In a 2025 mouse study of transient global cerebral ischemia (a model relevant to vascular contributions to dementia), CBG (1–10 mg/kg) attenuated memory impairments, reduced hippocampal neuronal loss and neuroinflammation, and supported markers of neuroplasticity. https://pmc.ncbi.nlm.nih.gov/

– In a rat model of Alzheimer’s disease induced by intracerebroventricular administration of amyloid-beta 42, both CBD and CBG were investigated for effects on cognitive deficits. CBG treatment improved learning and memory performance in behavioral tests, reduced neuroinflammatory cytokines (such as TNF-α and IL-1β), and decreased Aβ plaque expression in the hippocampus and cerebral cortex. https://www.researchgate.net/

Additional cell-based studies suggest minor cannabinoids including CBG can block Aβ accumulation, promote its degradation, and prevent oxidative cell death (oxytosis). Human data specific to dementia remain limited, though acute CBG (20 mg) has shown reductions in anxiety and improvements in verbal memory recall in healthy adults.https://doi.org/, https://pubmed.ncbi.nlm.nih.gov/

Combinations of CBD, CBG, and other minor cannabinoids may offer synergistic (“entourage”) effects by addressing multiple AD hallmarks, such as inflammation and protein aggregation.

Nano-Emulsified vs. Regular Hemp Extract (Sublingual/Oil Under the Tongue)

Most hemp extracts for cannabinoids are lipid-based oils intended for sublingual use—held under the tongue for 30–60 seconds to promote mucosal absorption, which partially bypasses first-pass liver metabolism. Standard sublingual oils typically achieve moderate bioavailability, with effects onset in 15–45 minutes and duration of several hours. Absorption depends on holding time, individual factors, and the oil base.Nano-emulsified formulations reduce cannabinoid particles to nanoscale (<100–200 nm) using emulsifiers, creating micelles or liposomes that enhance water dispersibility and mucosal penetration. When compared for sublingual or oral-mucosal delivery:

– Bioavailability and Absorption: Nano versions often demonstrate significantly higher and faster absorption. Pharmacokinetic studies show nano-emulsions or self-nanoemulsifying systems can increase peak concentration (Cmax) and overall exposure (AUC) by 2–3 times or more compared to standard oil drops, with shorter time to peak (Tmax). This leads to more efficient delivery even via the sublingual route.
pmc.ncbi.nlm.nih.gov

– Blood-Brain Barrier (BBB) Penetration: Both regular and nanoemulsified CBD and CBG are highly lipophilic and cross the BBB primarily through passive diffusion. However, nanoemulsified formulations typically result in greater brain delivery because higher systemic blood levels mean more molecules are available to reach and cross the BBB. Preclinical studies have shown that CBD nanoemulsions can achieve substantially higher brain exposure; for example, one study reported a 3.7-fold increase in brain AUC (area under the curve) with a nanoemulsion compared to another nanoparticle formulation, with rapid brain uptake observed within minutes.
Similar principles apply to CBG, though direct nano-CBG brain delivery data are more limited.

https://www.sciencedirect.com

– Onset and Predictability: Nano formulations may provide quicker onset and more consistent effects, which could be particularly beneficial for managing acute symptoms such as agitation or anxiety in dementia patients.

https://pmc.ncbi.nlm.nih.gov

https://pmc.ncbi.nlm.nih.gov

– Dosing Efficiency: Higher absorption could allow lower nominal doses to achieve similar effects, which may be advantageous for elderly users to minimize load or side effects.

Standard sublingual oils retain the full plant matrix (terpenes, minor cannabinoids) that may support the entourage effect observed in preclinical neuroprotection studies. Nano products can be formulated from isolates or full/broad-spectrum extracts, but processing may slightly alter some minor compounds. Long-term safety data for nano versions in dementia populations are still limited.

For sublingual use in neurodegenerative conditions, nano-emulsified CBD and CBG could offer improved reliability, faster onset, and potentially greater brain exposure compared to regular hemp oils. At the same time, traditional oils emphasize natural synergy. Clinical trials rarely detail exact formulation pharmacokinetics, so individual response, product quality (third-party tested for potency and purity), and medical guidance matter most.

Safety, Considerations, and Limitations

Reviewed trials generally report good tolerability with mild side effects (e.g., dizziness, sedation). Potential drug interactions exist via liver enzymes (CYP450), relevant for polypharmacy in older adults. THC-containing products may introduce additional psychoactivity risks.

Limitations include small sample sizes, variable dosing/formulations, short study durations, and a stronger focus on symptoms than on core pathology or biomarkers. Larger, longer-term randomized controlled trials with standardized preparations are needed.

Future Directions and Conclusion

Ongoing research, including biomarker-driven trials (e.g., NCT05822362) and studies on agitation, will help clarify optimal dosing, formulations, and potential disease-modifying roles. CBD and CBG combinations or multi-cannabinoid extracts may provide broader benefits. Advances in delivery systems, such as nano-emulsification for sublingual use, could enhance therapeutic consistency.

While preclinical and early clinical data are encouraging—particularly for managing agitation, anxiety, and neuroinflammation—CBD and CBG should be considered investigational supportive options alongside standard care, not replacements or cures. Prioritize high-quality, tested products and medical supervision.

*This article is for informational purposes only and does not constitute medical advice.*

 References (All Cited Studies)

– de Morais Cury et al. (2025). A randomized clinical trial of low-dose cannabis extract in Alzheimer’s disease. https://pubmed.ncbi.nlm.nih.gov/

– Velayudhan et al. (2024). Cannabidiol for behavior symptoms in Alzheimer’s disease (CANBiS-AD): a randomized, double-blind, placebo-controlled trial. https://www.cambridge.org/ 

– Hermush et al. (2022). Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial.https://www.frontiersin.org

– Wu et al. (2025). Therapeutic Potential for Cannabidiol on Alzheimer’s Disease-Related Neuroinflammation: A Systematic Review and Meta-Analysis. https://www.mdpi.com.

– Kohara et al. (2025). Cannabigerol Attenuates Memory Impairments, Neuronal Loss, and Neuroinflammation in a Mouse Model of Transient Global Cerebral Ischemia. https://pmc.ncbi.nlm.nih.gov/

– Ahmad et al. (study on CBD and CBG in amyloid-beta 42 rat model of Alzheimer’s). Effects on cognitive deficit.https://www.researchgate.net/

– Ozonsi et al. (2024). Caring for Behavioral Symptoms of Dementia (open-label high-CBD/low-THC sublingual).https://www.ajgponline.org.

– ElSohly et al. (2023) and related PK studies on nano-emulsified vs. oil cannabinoid bioavailability https://pmc.ncbi.nlm.nih.gov

– Coles, M., et al. (2022). Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer’s disease. Frontiers in Neuroscience, 16, 962922. https://doi.org/

-Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain https://www.sciencedirect.com/

– Wu, S., et al. (2025). Therapeutic Potential for Cannabidiol on Alzheimer’s Disease-Related Neuroinflammation: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 26(24), 11963. https://doi.org/

– Landucci, E., et al. (2022). Cannabidiol inhibits microglia activation and mitigates neuronal injury in a model of seizure.https://pubmed.ncbi.nlm.nih.gov/

Hermush et al. (2025) — Enhancing cannabinoid bioavailability: a crossover study comparing a novel self-nanoemulsifying drug delivery system and a commercial oil-based formulation..

https://pmc.ncbi.nlm.nih.gov

Nakano et al. (2019) — Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol

https://pmc.ncbi.nlm.nih.gov

– ClinicalTrials.gov entries: NCT05822362, NCT04436081, NCT04075435.

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