What is Alzheimer’s?

Alzheimer’s disease is a complex and progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and changes in thinking and behavior. It is the most common cause of dementia in older people, accounting for approximately 60-80% of dementia cases worldwide. This disease mainly affects brain regions responsible for memory, learning, and cognitive functions, such as the cerebral cortex and hippocampus.

Genetic, environmental, and lifestyle factors have been associated with an increased risk of Alzheimer’s disease. Established risk factors include lack of physical activity, obesity, hypertension, diabetes, depression, and smoking.

The exact mechanisms underlying Alzheimer’s disease pathogenesis are not fully understood. However, research suggests that the accumulation of amyloid-beta and tau proteins triggers a cascade of events, including neuroinflammation, oxidative stress, and impaired neurotransmission, leading to synaptic dysfunction and neuronal degeneration.

How is the diagnosis made?

Diagnosing Alzheimer’s disease involves clinical evaluations, cognitive tests, and brain imaging to detect amyloid-beta and tau deposits. The main symptoms include cognitive impairment (e.g., memory loss, repetitive questions, getting lost), apathy, mood swings, behavioral changes, insomnia, restlessness, agitation, aggression, and wandering behavior.

Currently, no cure exists for Alzheimer’s disease, and available treatments focus on managing symptoms and slowing disease progression.

Cannabis and Alzheimer’s Disease

The relationship between cannabis and Alzheimer’s disease has been investigated through 210 studies, with 75% showing positive clinical results and 94% demonstrating overall positive outcomes. Of these studies, 90 are primary research:

• 1 Clinical Meta-analysis
• 2 Double-blind Human Trials
• 1 Clinical Human Trial
• 30 Pre-clinical Meta-analyses/Reviews
• 37 Animal Studies
• 19 Laboratory Studies

Recent findings suggest that cannabinoid-based therapies, such as CBD and THC, may have therapeutic effects on Alzheimer’s disease by interacting with specific receptors in the brain or modulating endocannabinoids and their enzymes. These effects include modifying abnormal protein processing, reducing neuroinflammation, excitotoxicity, oxidative stress, and mitochondrial dysfunction. Animal studies also indicate potential protection against cognitive damage caused by neuroinflammation, thus restoring memory and cognitive function.

Furthermore, cannabinoid-based therapies appear to support the brain’s natural repair mechanisms by increasing the expression of neurotrophins and promoting neurogenesis.

A 2022 systematic review explored the correlation between circadian rhythms, the endocannabinoid system, and Alzheimer’s disease, suggesting that the endocannabinoid system could be a therapeutic target for the disease. According to this research, the expression of the CB2 receptor may improve cognitive deficits by reducing tauopathy and microglial activation, potentially slowing down Alzheimer’s disease.

Clinical trials in humans have shown improvements in symptoms such as agitation, insomnia, loss of appetite, and cognitive function. Patients, families, and caregivers have reported significant improvements in their quality of life.

It is important to note that no study has reported that cannabinoid-based therapies worsen Alzheimer’s disease. Most studies indicate potential therapeutic benefits, although some meta-analyses of clinical trials have yielded mixed or inconclusive results due to variations in cannabis chemotypes and compositions.

Overall, cannabis-based therapies show promise in Alzheimer’s disease treatment. Further research, including ongoing randomized, double-blind clinical trials, aims to uncover the nuances of dosage and chemotypes to validate their effectiveness.

References:

• Abate, G., Uberti, D., & Tambaro, S. (2021). Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy. Biology (Basel), 10(6), 542. https://doi.org/10.3390/biology10060542
• Amir, K. M., Hibatullah, R. M., Razif, A., Sharmili, V., Taufik, H. B. M., Luqman, N. M., Vishnumukkala, T., Sreenivasulu, S., Kabul, W., Huda, M. N. N., Amsyar, A. M., Abdullah, A. M., & Aris, M. M. M. (2023). Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1053680
• Kim, SH., Yang, JW., Kim, KH., Kim, JU., & Yook, TH. (2019). A Review on Studies of Marijuana for Alzheimer’s Disease – Focusing on CBD, THC. Journal of Pharmacopuncture, 22(4), 225-230. https://doi.org/10.3831/KPI.2019.22.030
• Kumar, D., Sharma, A., Taliyan, R., Urmera, M. T., Herrera-Calderon, O., Heinbockel, T., Rahman, S., & Goyal, R. (2022). Orchestration of the circadian clock and its association with Alzheimer’s disease: Role of endocannabinoid signaling. Ageing Research Reviews, 73, 101533. https://doi.org/10.1016/j.arr.2021.101533
• Palmieri, B., & Vadalà, M. (2023). Oral THC: CBD cannabis extract in main symptoms of Alzheimer’s disease: agitation and weight loss. Clin Ter, 174(1), 53-60. https://doi.org/10.7417/CT.2023.2497
• Zhang, Y., Li, H., Jin, S., Lu, Y., Peng, Y., Zhao, L., & Wang, X. (2022). Cannabidiol protects against Alzheimer’s disease in C. elegans via ROS scavenging activity of its phenolic hydroxyl groups. European Journal of Pharmacology, 919, 174829. https://doi.org/10.1016/j.ejphar.2022.174829