ALZHEIMER’S & BRAIN AWARENESS
Written by Faith Long, PharmD
Edited by Markita Wilburn, PharmD
June Is Alzheimer’s & Brain Awareness Month
Alzheimer’s Disease (AD) was discovered almost 120 years ago and has remained the leading cause of dementia since 1976. Currently estimated to account for 60-80% of the 55 million dementia cases worldwide — and still, expected to increase. Despite over three decades of research efforts, a cure for AD has yet to be determined. While pharmacological agents for AD are being utilized along the way, they only address symptoms, and their efficacy is moderate at best (1-3). With increasing prevalence, devastating symptoms, and a significant emotional and economic burden, Alzheimer’s Awareness is essential to addressing this public health concern. AD is the only leading cause of death that exists without preventative treatment, disease-modifying agent, or cure — the urgency to develop promising therapeutic options is higher than ever before.
Could Marijuana Be The Answer We’ve Been Waiting Almost 40 Years For?
Marijuana has been used medicinally for more than 5,000 years. It became widely used in the United States following its addition to the U.S. Pharmacopeia (USP) in 1850 for the treatment of a diverse list of conditions. Nearly 100 years later, marijuana became federally prohibited and subsequently removed from the USP. Marijuana was then later reclassified as a Schedule I substance (meaning it has high abuse potential but lacks accepted medical use) under the Controlled Substances Act of 1970, which also significantly limited the use of cannabis for research purposes (4,5).
Federal restrictions were a major barrier to cannabis research until 2015, when the requirement for privately funded researchers to complete the Public Health Service review was eliminated, making approval much easier. With more research and growing evidence of marijuana's therapeutic uses, the Medical Marijuana and Cannabidiol Research Expansion Act of 2022 further increased research opportunities (6).
MMJ and AD
Alzheimer’s Disease (AD) is a neurodegenerative disorder marked initially by cognitive decline, memory loss, and spatial disorientation. As it progresses, patients often experience insomnia, depression, weight loss due to poor appetite, and behavioral issues like agitation and paranoia (2,4,7). After years of unsuccessful symptom management, it was discovered that marijuana greatly improved patients' sleep, restored their appetite, and reduced agitation (3,4). Managing AD symptoms, with the potential use of marijuana, improves the quality of life for both patients, proposing a significant step forward. However, we must first understand the disease’s underlying cause, especially in relation to the endocannabinoid system (ECS) to consider marijuana as a suitable alternative option.
The Endocannabinoid System (ECS)
The ECS maintains homeostasis by modulating physiological processes throughout our entire body. When there is a disruption or imbalance in these physiologic processes, signals are sent to activate the ECS which then corrects the imbalance and restores homeostasis. In the brain specifically, the ECS regulates neurotransmission, stress response, neuroprotection, and synaptic plasticity.
The progression of AD involves the interaction between inflammatory cytokines and neuroprotective cells, such as microglia and astrocytes. These cytokines disrupt microglia and astrocytes, resulting in neuronal dysfunction and neuroinflammation and ultimately accelerating cell death.
While the progression of AD disrupts neuroprotective mechanisms and leads to neurodegeneration, it does not completely block the production or function of endocannabinoids. This demonstrates the role of marijuana in the management and prevention of AD (3,4,5,8).
Potential Benefits of MMJ for AD
CB1 receptors are present throughout the brain and play a role in regulating neurotransmission by modulating inhibitory and excitatory signals, as well as promoting neurogenesis. Using THC, a cannabinoid found in marijuana, to target CB1 receptors helps to manage AD by reducing excitotoxicity and improving cognitive function through neurogenesis.
CB2 receptors regulate inflammation and immune responses by controlling the release of proinflammatory cytokines. AD causes increased expression of the CB2 receptors, and upon activation, CB2 receptors facilitate the removal of Aß plaques. The consumption of CBD, a cannabinoid found in marijuana, exacerbates this process.
Both THC and CBD have therapeutic potential for managing AD. They have the ability to bind to the CB1 and CB2 receptors and are known to have anti-inflammatory effects which are critical elements for slowing progression of AD and addressing the symptoms associated with neurodegeneration. Marijuana offers an incredibly unique approach to AD, providing options for symptom management and potentially slowing disease progression.
References
Alzheimer's Association. Alzheimer's Disease Research: Milestones. Alzheimer's Association. https://www.alz.org/alzheimers-dementia/research_progress/milestones.
Li X, Feng X, Sun X, Hou N, Han F, Liu Y. Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2019. Front Aging Neurosci. 2022;14:937486. Published 2022 Oct 10. doi:10.3389/fnagi.2022.937486
Rebassa JB, Capó T, Lillo J, Raïch I, Reyes-Resina I, Navarro G. Cannabinoid and Orexigenic Systems Interplay as a New Focus of Research in Alzheimer’s Disease. International Journal of Molecular Sciences. 2024; 25(10):5378. https://doi.org/10.3390/ijms25105378
Backes, Michael, et al. Cannabis Pharmacy : The Practical Guide to Medical Marijuana. New York, Black Dog & Leventhal; 2014.
Bridgeman MB, Abazia DT. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188.
ProCon.org. Historical Timeline. Medical Marijuana. https://medicalmarijuana.procon.org/historical-timeline/#2900-bc-1599-ad.
Shakkottai VG, Lomen-Hoerth C. Nervous System Disorders. In: Hammer GD, McPhee SJ. eds. Pathophysiology of Disease: An Introduction to Clinical Medicine, 8e. McGraw-Hill Education; 2019.
Cassano T, Villani R, Pace L, et al. From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases. Front Pharmacol. 2020;11:124. Published 2020 Mar 6. doi:10.3389/fphar.2020.00124