Cannabis as a Treatment for Alzheimer’s Disease

Cannabis as a Treatment for Alzheimer’s Disease

July 16, 2017 Medical Research No Comment

Alzheimer’s disease is a chronic neurodegenerative brain disorder characterized by a marked and progressive decline in cognitive function.   According to the Alzheimer’s Association, ten percent of Americans age 65 and older suffer from Alzheimer’s disease and the at-risk population is growing rapidly. With 5.5 million Americans already diagnosed, it is estimated by 2050, the population of Americans living with Alzheimer’s disease could reach 16 million without intervention.

Unfortunately for the millions in the U.S that suffer from it, there is no known cure for Alzheimer’s disease.  However, in recent years, scientists and researchers have conducted many exploratory studies that have revealed a potentially powerful new tool in the treatment of Alzheimer’s disease.

Cannabinoids are Antioxidants and Neuroprotectants

Cannabis and Alzheimer’s disease.  To the average person, the words don’t seem to fit together.  Until that is, they realize that the U.S. government holds a patent on the use of cannabinoids as antioxidants and neuroprotectants.  In layman’s terms, the patent claims that certain elements found in the Cannabis sativa plant are useful in the treatment of Alzheimer’s disease, Parkinson’s, and HIV dementia.

Before we dive into why cannabis is such a promising treatment for Alzheimer’s, we should first discuss what causes Alzheimer’s disease and examine the drugs currently used in the treatment of Alzheimer’s.

What causes Alzheimer’s disease?

While researchers are divided on exactly what causes Alzheimer’s disease, scientists have identified two proteins, Beta-Amyloid and Tau1, that play a significant role in its development.

Beta-Amyloid is a protein peptide that typically forms a plaque in brain tissue as we get older.  For many, the formation of these plaques represents a normal part of the aging process.  But in a brain affected by Alzheimer’s disease, instead of the neurons repairing themselves after an injury or re-growing to delay the aging process, the proteins are broken off into smaller fibrils. Because Beta-Amyloid is insoluble, these fragments will clump together outside the neurons and form thick plaques called senile plaques.

Tau proteins are plentiful in nerve cells.  Their primary function is to help stabilize microtubules, which are essential in many cellular processes.   These microtubules work like tracks that guide molecules and proteins as they move from the body of the neuron to its axon and then back to the body.  With Alzheimer’s disease, chemical changes occur in the Tau proteins which cause them to fill with phosphate and collapse.  Tau proteins combine with other Tau proteins to create twisted fibers known as neurofibrillary tangles, effectively disrupting the cell’s transport system.

All these changes disrupt the functions of the neurons.  The cells’ homeostasis is disrupted; glucose absorption by the neurons is inhibited; inflammation occurs; cytokines accumulate, causing worsening inflammation; injury and degeneration of the neurons take place; and finally, apoptosis (cell death) occurs.

The loss of neurons impairs the brain’s cognitive and motor functions, resulting in the symptoms of dementia. While it’s technically inaccurate to say that these proteins are what causes Alzheimer’s disease initially, it is apparent that the accumulation of these toxic proteins2 is responsible for the progression of the disease.

Current Treatments for Alzheimer’s Disease

As previously mentioned, there is no cure for Alzheimer’s disease.  Current treatments focus primarily on the management of its symptoms.  Drugs currently used in the treatment of Alzheimer’s disease include:

  • Cholinesterase Inhibitors
  • Memantine
  • Antidepressants
  • Anxiolytics
  • Antipsychotics
  • Sleeping pills

Like most medications, drugs used to treat Alzheimer’s disease can cause adverse side effects and complications, including:

  • Allergic reaction which includes hives, itchiness, rashes, redness of the skin, breathing difficulties, chest pain, shortness of breath, etc.
  • Nausea and vomiting.
  • Indigestion, diarrhea, and other gastrointestinal symptoms.
  • Muscle weakness and cramps.
  • Easy fatigability.
  • Headache and dizziness.
  • Decreased appetite.

Long-term side effects and complications of these Alzheimer’s disease treatment medications include reduced heartbeat, hypotension, yellowing of the skin, tingling of the distal extremities, weight gain or loss, increased anxiety, muscle twitching, shivering, convulsions, stroke, heart and liver problems, and kidney complications.

Cannabis: An Alternative Treatment for Alzheimer’s Disease

There is ample evidence to support the efficacy of cannabinoids as a treatment for Alzheimer’s disease. Cannabinoids work at the cellular level, so they have the potential to not only remove the buildup of senile plaques but to also inhibit the inflammatory process that can accelerate the progression3 of Alzheimer’s disease.

Cannabinoids Can Reduce and Remove Beta-Amyloid Plaques

One of the hallmarks of Alzheimer’s disease is the formation of senile plaques caused by Beta-Amyloid proteins.  A study conducted by scientists at the Salk Institute revealed that cannabinoids have the ability to reduce and remove Beta-Amyloid4.  In the study, scientists exposed neurons containing high levels of Beta-Amyloid proteins to THC and found that the THC reduced the level of the toxic proteins, thus allowing the neurons to survive.

Cannabinoids Inhibit the Formation of Neurofibrillary Tangles

Activation of the CB receptors of the endocannabinoid system affects Tau phosphorylation5, according to one study.  The study showed that when the CB1 and CB2 receptors were activated by cannabidiol (CBD), tau protein hyperphosphorylation was reduced, which also effectively reduced the formation of neurofibrillary tangles.

We know that the introduction of cannabidiol (CBD) helps the brain to repair and heal itself.  CBD can also reduce other pathological processes6 associated with neuronal injuries such as neuroinflammation, excitotoxicity (overactivation of the neurons), disruption of the mitochondria’s functions, and oxidative stress (the cell’s inability to rid itself of free radicals and toxins).

Cannabinoids Can Reduce and Inhibit Inflammation

As Beta-Amyloid deposits and amyloid aggregation increase, proteotoxicity (toxicity that is caused by misfolded proteins) occurs.  Increases in proteotoxicity cause the cells to release cytokines and chemokines.  These small proteins attract more cells to the site of the injury. As more cells migrate to the location of the lesion, inflammation worsens, and more and more neurons die, resulting in decreasing cognitive function7.

A study8 on THC showed that it could suppress the immune system by inhibiting the release of cytokines and chemokines as well as enhancing the function of the T-regulatory cells (a part of the immune system that regulates its action to prevent over-activation of the immune response).  When proteotoxicity and inflammation are controlled, toxic plaque formation and progression of Alzheimer’s disease can be reduced9.

Cannabinoids Can Inhibit Acetylcholinesterase

Acetylcholine10 is one of the most important neurotransmitters.  It is heavily involved in the activation of muscle contractions and also plays a part in memory, attention, reasoning, and learning.

Acetylcholinesterase, on the other hand, breaks down acetylcholine.  In Alzheimer’s Disease, acetylcholinesterase is known to accelerate the process of amyloid fiber formation.

Research has shown that THC can inhibit the actions of acetylcholinesterase11.  THC binds with the acetylcholinesterase, specifically its peripheral anionic site which is responsible for the amyloid formation. By inhibiting the peripheral anionic site and inhibiting the formation of amyloid, aggregation is reduced, and acetylcholine levels improve.

Studies on Cannabinoids & Alzheimer’s Disease

Not convinced yet?  Here are some promising studies demonstrating the efficacy of cannabinoids as a treatment for Alzheimer’s disease.

  • One study was done to see if medical cannabis oil12 was safe and effective as a treatment for the symptoms of dementia. Ten patients with Alzheimer’s disease participated in a four-week trial, and the results were very significant.  The patients showed a substantial decrease in issues related to delusions, agitation/aggression, irritability, apathy, sleep, and caregiver distress.  The study concluded that the addition of medical cannabis oil to the patients’ overall treatment protocol was both a safe and effective treatment for Alzheimer’s disease.
  • A study conducted on mice with advanced Alzheimer’s disease showed that THC and CBD working together were effective in decreasing the mice’s memory impairments13.
  • In another study, cells with Beta-Amyloid were incubated with THC, and its levels were checked over time. It showed that a low concentration of THC was able to reduce Beta-Amyloid levels14. THC was also able to decrease hyperphosphorylation and enhance mitochondrial function. The study determined that THC has potential therapeutic benefit for Alzheimer’s disease through multiple functions and pathways.
  • In this study, a group of cells was exposed to Beta-Amyloid. Some of the cells were treated with CBD and others were not.  As expected, exposure to Beta-Amyloid caused damage to the cells. However, cells that were treated with CBD before they were exposed to Beta-Amyloid had a substantially greater cell survival rate15.  The results demonstrated that CBD possesses a mixture of neuroprotective, anti-oxidative, and anti-apoptotic effects against beta-amyloid peptide toxicity.
  • Another study done on mice that were inoculated with Beta-Amyloid protein showed that CBD reduced inflammation and inhibited Beta-Amyloid formation16.

In conclusion, there is very clearly a future for cannabinoids as a part of a regular program of treatment for Alzheimer’s disease. Ongoing research and studies are continuing to show positive results. The main properties of cannabinoids as an anti-inflammatory, anti-oxidative, and neuroprotective agent make it an ideal preventive medication or a part of the treatment for Alzheimer’s disease.

 

References:

1 Dimitri P. Agamanolis, M.D.
Neuropathology, Chapter 9: Degenerative Disease: Alzheimer’s Disease. 
http://neuropathology-web.org/chapter9/chapter9bAD.html

2 Iuvone T., et al. 2009.
The National Center for Biotechnology Information, Cannabidiol: a promising drug for neurodegenerative disorders? 
https://www.ncbi.nlm.nih.gov/pubmed/19228180

3 Meraz-Ríos, et al. August 13, 2013.
The National Center for Biotechnology Information, Inflammatory process in Alzheimer’s Disease. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741576/

4 Salk News. June 27, 2016
Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells. 
http://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/

5 Ester Aso and Isidre Ferrer. March 5, 2014
The National Center for Biotechnology Information, Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

6 Ester Aso and Isidre Ferrer. March 5, 2014
The National Center for Biotechnology Information, Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. 
https://www.ncbi.nlm.nih.gov/pubmed/24634659

7 Lee KS, et al. October 10, 2009.
The National Center for Biotechnology Information, Peripheral cytokines and chemokines in Alzheimer’s disease. 
https://www.ncbi.nlm.nih.gov/pubmed/19828948

8 Prakash Nagarkatti, et al. October 1, 2009
The National Center for Biotechnology Information, Cannabinoids as novel anti-inflammatory drugs. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

9 Antonio Currais, et al. June 23, 2016.
Nature Partner Journals, Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. 
http://www.nature.com/articles/npjamd201612

10 Wikipedia, Acetylcholine.
https://en.wikipedia.org/wiki/Acetylcholine#Cellular_effects

11 Lisa M. Eubanks, et al. March 2006.
The National Center for Biotechnology Information, A Molecular Link Between the Active Component of Marijuana and Alzheimer’s Disease Pathology. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562334/

12 Shelef A, et al. 2016.
The National Center for Biotechnology Information, Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study. 
https://www.ncbi.nlm.nih.gov/pubmed/26757043

13 Aso E, et al. October 4, 2016.
The National Center for Biotechnology Information, Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model. 
https://www.ncbi.nlm.nih.gov/pubmed/27567873

14 Cao, Chuanhai, et al. April 29, 2014.
IOS Press Content Library, Journal of Alzheimer’s Disease, The Potential Therapeutic Effects of THC on Alzheimer’s Disease. 
http://content.iospress.com/articles/journal-of-alzheimers-disease/jad140093

15 Iuvone T., et al. April 2004.
The National Center for Biotechnology Information, Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. 
https://www.ncbi.nlm.nih.gov/pubmed/15030397

16 Esposito G., et al. August 15, 2007.
The National Center for Biotechnology Information, Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. 
https://www.ncbi.nlm.nih.gov/pubmed/17592514

 

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