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Alzheimer’s disease is the most common form of dementia, affecting over 4.5 million Americans. Studies have shown cannabis can limit the progression of the disease.
Overview of Alzheimer’s Disease
Alzheimer’s disease is a progressive type of dementia that destroys memory, behavior and thinking. The disease causes brain cells degenerate and die, leading to a steady decline in memory, intellectual and social skills. As brain cells die, the brain shrinks.
Scientists believe Alzheimer’s disease is caused by a combination of genetic, lifestyle and environmental factors1. Age seems to play a role, as risk increases significantly at and beyond the age of 65. The disease affects nearly half of people over the age of 8511.
Hallmarks of the disease include plaques, which are clumps of protein fragments called amyloid-beta, and tangles, which are twisted fibers of the protein tau. Plaques and tangles build up in the brain and interfere with cell communication and nutrient transport, thus contributing to brain cell death.
Alzheimer’s typically begins with mild confusion or forgetfulness, but progresses over time at a rate that varies person to person. Memory loss persists and worsens, causing individuals to repeat statements or questions, forget conversations or appointments, routinely misplace possessions and eventually forget names of family members, friends, and everyday objects. Alzheimer’s will also cause a person to lose their sense of day, have difficulty finding the right words, have problems concentrating and thinking, and to experience depression, anxiety, social withdrawal, mood swings and irritability.
There is no cure for Alzheimer’s disease and medications and other management strategies may only temporarily improve symptoms.
Findings: Effects of Cannabis on Alzheimer’s Disease
Studies have determined that two of the major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), reduce the buildup of plaques and tangles, and therefore show viable potential as treatment options for Alzheimer’s disease. Cannabis’ potential efficacy for Alzheimer’s disease has been linked to its interaction with the endocannabinoid system, which modulates several pathological processes associated with the neurodegenerative disorder, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress3,5. The endocannabinoid system’s CB1 receptors have shown to regulate the neurotransmitters involved in excitotoxic neurodegenerative processes, while its CB2 receptors have shown to reduce the inflammation associated with Alzheimer’s disease4,24.
THC has been shown to be effective at lowering amyloid-beta levels and enhancing mitochondrial function, therefore causing the researchers to conclude “that THC could be a potential therapeutic treatment option for Alzheimer’s through multiple functions and pathways”7,9. An earlier study also found THC to be effective at preventing amyloid beta aggregation, indicating it could impact the progression of the disease10. Another showed THC to reduce nocturnal motor activity and agitation in patients with dementia, suggesting it could be beneficial for treating behavioral and circadian disturbances24.
The brains of Alzheimer’s patients experience an over-activation of microglia (cells that form myelin), which contributes to excessive tau buildup and eventually tangles. However, CBD has been shown to modulate microglial function and control neuroinflammation19. In addition, CBD has been shown to improve the survival rate of cells through a combination of neuroprotective, anti-oxidative, anti-inflammatory and anti-apoptotic effects against the toxicity caused by beta-amyloid, therefore showing potential as a therapeutic option for Alzheimer’s13. One study that found CBD’s neuroprotective effects and its ability to promote the regeneration of brain cells was effective for reversing the cognitive deficits caused by Alzheimer’s8.
A lack of glucose uptake has been linked to a worsening of brain diseases like Alzheimer’s disease, and findings in a 2016 animal trial suggest that cannabis could promote an increased glucose uptake in the brain, suggesting that cannabis could be beneficial for treating Alzheimer’s disease through multiple methods14.
One study found that early deficits in Alzheimer’s could be caused by a blockage or deficiency of cannabinoids, suggesting that supplementing with cannabinoids found in cannabis could reduce the risk of developing the disease20.
Cannabinoids provide a multi-faceted approach in the treatment of Alzheimer’s. In addition to reducing amyloid-beta levels, modulating microglial function and increasing glucose uptake, they protect brain cells from the deleterious effects of amyloid-beta, reduce inflammation, and support the brain’s repair process by enhancing neurogenesis (birth of new cells) and providing neuroprotective effects6,11,16,17,18,21. They’ve shown to improve psychomotor agitation, aggression and communication in those diagnosed with dementia2.
States That Have Approved Medical Marijuana for Alzheimer’s Disease
Currently, 11 states have approved medical marijuana specifically for the treatment of Alzheimer’s disease. These states include Arizona, Arkansas, Delaware, Illinois, Maine, Michigan, New Hampshire, North Dakota, Oregon, Ohio and Rhode Island.
In Washington D.C., any condition can be approved for medical marijuana as long as a DC-licensed physician recommends the treatment.
Four other states will consider allowing medical marijuana to be used for the treatment of Alzheimer’s disease with the recommendation from a physician. These states include: California (any debilitating illness where the medical use of marijuana has been recommended by a physician), Connecticut (other medical conditions may be approved by the Department of Consumer Protection), Massachusetts (other conditions as determined in writing by a qualifying patient’s physician), Nevada (other conditions subject to approval), and Washington (any “terminal or debilitating condition”).
Recent Studies on Cannabis’ Effect on Alzheimer’s Disease
- Alzheimer’s disease. (2014, June 17). Mayo Clinic. Retrieved from http://www.mayoclinic.org/diseases-conditions/alzheimers-disease/basics/definition/con-20023871.
- Amanullah, S., MacDougall, K., Sweeney, N., Coffin, J., and Cole, J. (2013). Synthetic cannabinoids in dementia with agitation: Case studies and literature review. Clinical Neuropsychiatry, 10 (3-4), 142-147. Retrieved from https://pdfs.semanticscholar.org/b8be/e18d22e95dbe90cf6057e9f4648d9b3c5b02.pdf?_ga=1.196675940.916023079.1489098264.
- Aso, E., & Ferrer, I. (2014). Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Frontiers in Pharmacology, 5, 37. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/.
- Aso, E., & Ferrer, I. (2016). CB2 Cannabinoid Receptor As Potential Target against Alzheimer’s Disease. Frontiers in Neuroscience, 10, 243. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885828/?report=classic.
- Bedse, G., Romano, A., Lavecchia, A.M., Cassano, T., and Gaetani, S. (2015). The role of the endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer’s disease. Journal of Alzheimer’s Disease, 43(4), 1115-36. Retrieved from http://content.iospress.com/articles/journal-of-alzheimers-disease/jad141635.
- Campbell, V.A., and Gowran, A. (2007). Alzheimer’s disease; taking the edge off with cannabinoids? British Journal of Pharmacology, 152(5), 655–662. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190031/.
- Cao, C., Li, Y., Liu, H., Bai, G., Mayl, J., Lin, X., Sutherland, K., Nabar, N., and Cai, J. (2014). The potential therapeutic effects of THC on Alzheimer’s disease. Journal of Alzheimer’s Disease, 42(3), 973-84. Retrieved from http://content.iospress.com/articles/journal-of-alzheimers-disease/jad140093.
- Cheng, D., Low, J.K., Logge, W., Garner, B., and Karl, T. (2014, August). Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice. Psychopharmacology, 231(15), 3009-3017. Retrieved from http://link.springer.com/article/10.1007%2Fs00213-014-3478-5.
- Currais, A., Quehenberger, O., Armando, A.M., Daugherty, D., Maher, P., and Schubert, D. (2016, June 23). Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. Aging and Mechanisms of Disease, doi:10.1038/npjamd.2016.12. Retrieved from http://www.nature.com/articles/npjamd201612–.
- Eubanks, L.M., Rogers, C.J., Beuscher, A.E. 4th, Koob, G.F., Olson, A.J., Dickerson, T.J., and Janda, K.D. (2006, November-December). A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Molecular Pharmaceuticals, 3(6), 773-7. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/.
- Fagan, S.G., and Campbell, V.A. (2014, March). The influence of cannabinoids on generic traits of neurodegeneration. British Journal of Pharmacology, 171(6), 1347-1360. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954477/.
- Garcia-Arencibia, M., Garcia, C., and Fernandez-Ruiz, J. (2009, December). Cannabinoids and Parkinson’s disease. CNS & Neurological Disorders Drug Targets, 8(6), 432-9. Retrieved from http://www.eurekaselect.com/93569/article.
- Iuvone, T., Esposito, G., Esposito, R., Santamaria, R., Di Rosa, M., and Izzo, A.A. (2004, April). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. Journal of Neurochemistry, 89(1), 134-41. Retrieved from http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2003.02327.x/full.
- Köfalvi, A., Lemos, C., Martin-Moreno, A.M., Pinheiro, B.S., García-García, L, Poso, M.A., Valerio-Fernandes, A., Beleza, R.O., Agostinho, P., Rodrigues, R.J., Pasquare, S.J., Cunha, R.A., and de Ceballos, M. (2016, March 11). Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease. Neuropharmacology, doi:10.1016/j.neuropharm.2016.03.015. Retrieved from http://www.sciencedirect.com/science/article/pii/S0028390816300879.
- Krishnan, S., Cairns, R., and Howard, R. (2009, April 15). Cannabinoids for the treatment of dementia. Cochrane Library, 2, 10.1002/14651858.CD007204.pub2. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/14651858.CD007204.pub2/full.
- Libro, R., Giacoppo, S., Soundara Rajan, T., Bramanti, P., and Mazzon, E. (2016, April 21). Natural phytochemicals in the treatment and prevention of dementia: An Overview. Molecules, 21(4), 518. Retrieved from http://www.mdpi.com/1420-3049/21/4/518/htm.
- Liu, C.S., Chau, S.A., Ruthirakuhan, M., Lanctôt, K.L., and Herrmann, N. (2015, August). Cannabinoids for the treatment of agitation and aggression in Alzheimer’s disease. CNS Drugs, 29(8), 615-23. Retrieved from http://link.springer.com/article/10.1007%2Fs40263-015-0270-y.
- Manuel, I., Lombardero, L., Laferla, F.M., Giménez-Llort, L., and Rodríguez-Puertas, R. (2016, August 4). Activity of muscarinic, galanin and cannabinoid receptors in the prodromal and advanced stages in the triple transgenic mice model of Alzheimer’s disease. Neuroscience, 329, 284-93. Retrieved from http://www.sciencedirect.com/science/article/pii/S0306452216301610.
- Martín-Moreno, A.M., Reigada, D., Ramírez, B.G., Mechoulam, R., Innamorato, N., Cuadrado, A., & de Ceballos, M.L. (2011). Cannabidiol and Other Cannabinoids Reduce Microglial Activation In Vitro and In Vivo: Relevance to Alzheimer’s Disease. Molecular Pharmacology, 79(6), 964–973. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102548/.
- Orr, A.L., Hanson, J.E., Li, D., Klotz, A., Wright, S., Schenk, D., Seubert, P., Madison, D. V. (2014). Amyloid-beta inhibits E-S Potentiation through suppression of cannabinoid receptor 1-dependent synaptic disinhibition. Neuron, 82(6), 1334–1345. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114400/.
- Ramírez, B.G., Blázquez C., Gómez del Pulgar, T., Guzmán, M., de Ceballos, M.L. (2005, February 23). Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. The Journal of Neuroscience, 25(8), 1904-13. Retrieved from http://www.jneurosci.org/content/25/8/1904.long.
- Shelef, Assaf. Barak, Y., Berger, U., Paleacu, D., Tadger, S., Plopsky, I., and Baruch, Y. (2016, February 27). Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: An-open label, add-on, pilot study. Journal of Alzheimer’s Disease, 51(1), 15-19. Retrieved from http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150915.
- Walther, S., and Halpern. M. (2010, August). Cannabinoids and dementia: A review of clinical and preclinical data. Pharmaceuticals (Basel), 3(8), 2689-2708. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033945/
- Walther, S., Mahlberg, R., Eichmann, U., and Kunz, D. (2006, May). Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology, 185(4), 524-8. Retrieved from http://link.springer.com/article/10.1007%2Fs00213-006-0343-1.
- What Is Alzheimer’s? (n.d.). Alzheimer’s Association. Retrieved from http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp#symptoms.