Medical marijuana and Alzheimer's disease
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Alzheimer’s is a complex neurodegenerative disease that affects roughly 1 in 10 people aged over 65. It is the leading cause of dementia and can be fatal, with progression from early symptoms to death usually taking 8-10 years.
As more research goes into cannabis as a medicine, there is a growing body of evidence suggesting that cannabis may play an important role in mediating the neurodegeneration caused by diseases like Alzheimer’s. Could cannabis be the future of Alzheimer’s prevention?
UNDERSTANDING ALZHEIMER’S DISEASE
Alzheimer’s is a chronic neurodegenerative disease. It usually has a progressive and slow onset, meaning symptoms get worse over time. There is currently no cure for this disease.
The main causes of Alzheimer’s are still unknown. However, in roughly 1 to 5% of cases clear genetic differences have been identified as the main cause of the disease.
Alzheimer’s is characterized by a build up of 2 abnormal protein fragments in the brain known as plaques and tangles. Plaques and tangles usually begin forming in the hippocampus, a part of the brain where memories are formed. Over time, these plaques and tangles accumulate in the hippocampus and begin to kill brain cells, making it harder to form new memories.
Eventually more plaques and tangles spread throughout different regions of the brain. They continue to kill off brain cells which further affects the normal cognitive and physical function of a patient. From the hippocampus, the disease generally moves on to the part of the brain that controls language, making it harder for patients to remember words and their meanings.
Next, the disease tends to target the front of the brain, which is responsible for managing logical thought. This makes it harder for patients to make plans, remain organized, or solve problems and understand concepts.
After this, the disease will move on to target the brain’s emotional centre. This often leaves patients unable to control their moods and feelings. Next, the disease will attack the part of the brain responsible for processing information obtained via our 5 basic senses. This can lead to hallucinations and delusions, making it harder for a patient to see, feel, and respond to what is happening around them.
Alzheimer's then tends to attack the back of the brain responsible for storing important memories long-term memories. Soon enough, patients will find it hard to recall important parts of their lives such as when they got married or had children.
Finally, the disease begins destroying a person’s ability to function, affecting their ability to balance, move, and even breath. This eventually leads to the death of the patient.
STAGES AND SYMPTOMS OF ALZHEIMER’S DISEASE
Alzheimer’s disease is usually experienced in 3 different stages characterized by varying levels of cognitive and functional impairment.
The first stage of the disease is known as Mild Alzheimer’s. In the early stages of the disease most patients remain relatively functional and retain the ability to perform tasks such as driving, working, or partaking in social activities.
However, most patients will begin experiencing simple memory lapses. These can include:
- Forgetting newly learned facts or information like names.
- Misplacing or losing objects.
- Difficulties planning or organizing.
- Difficulties concentrating or focusing.
Unfortunately many people pass off these symptoms as a normal part of aging, which often means that patient’s are not diagnosed with Alzheimer’s until the disease has progressed further.
The second stage of the disease is known as Moderate Alzheimer’s. By this stage, patients are experiencing greater cognitive and functional impairment and consequently rely on greater levels of care.
Memory impairment continues throughout this stage and is often accompanied by mood changes like getting angry or frustrated or seeming noticeably irritable. Some patients may also begin acting strangely, such as refusing to bathe or participate in social gatherings or other events that may be mentally or socially challenging.
By this stage, damage to the brain will make it noticeably more difficult for patients to remember words, express thoughts, or perform basic daily tasks.
Moderate Alzheimer’s is the longest stage of the disease, with many patients experiencing it for multiple years. Noticeable symptoms at this stage include:
- Forgetting memorable events or parts of one’s own history.
- Withdrawing from socially or mentally challenging events.
- Difficulty recalling important details like one’s own address or phone number.
- Confusion about what day it is.
- Needing help choosing appropriate clothing.
- Issues controlling one’s bladder or bowels.
- Changes to sleep patterns.
- Wandering or becoming lost.
- Strong personality or behavioural changes like delusions or weird suspicions.
The final stage of Alzheimer’s is characterized by strong functional and cognitive impairment. By this stage, patients will begin losing the ability to respond to their environment, keep up conversation, and control movement. They may also struggle to speak and communicate, and tend to experience significant personality changes and begin to rely extensively on care.
In the final stage of Alzheimer's symptoms generally include:
- Inability to complete basic daily tasks without help.
- Losing awareness of recent events or current situations.
- Problems walking, bathing, sitting, chewing, and even swallowing.
- Extreme difficulties communicating.
- Increased vulnerability to infections.
CANNABIS AND ALZHEIMER’S
The discussion around cannabis as possibly playing a role in managing and preventing Alzheimer’s and other neurodegenerative diseases focuses on two parts;
- the ability of cannabis compounds to rid the brain of specific proteins, and
- the ability of cannabis compounds to act as neuroprotectants.
CANNABINOIDS AND AMYLOID BETA
Amyloid beta is a toxic protein believed to be one of the main culprits responsible for the formation of the plaques that attack the brain during Alzheimer's disease.
These plaques are essentially just build ups of amyloid beta, which is formed as a sort of by-product by the reaction of two enzymes with a particular type protein (known as amyloid precursor proteins).
Amyloid beta molecules have been noted to clump together in the brain and build up to form the plaques responsible for the neurodegenerative effects of Alzheimer’s. Research shows that the buildup of amyloid beta molecules (called oligomers) are also capable of weakening communications at specific synapses in the brain, possibly leading to the a patient’s inability to form or retrieve memories.
A 2016 study conducted by researchers at the Salk Institute in San Diego used a synthetic neuron model to show that high concentrations of amyloid beta leads to a specific type of inflammation of a cell, ultimately leading to cell death. This is caused by the introduction of pro-inflammatory genes into the brain.
Using THC, the main psychoactive component found in cannabis, the researchers were able to remove amyloid beta molecules from the brain, block the inflammatory response caused by these compounds, and ultimately help protect brain cells.
These effects were caused by the activation of specific cannabinoid receptors in the brain which form part of the body’s natural endocannabinoid system. While the study isn’t conclusive, it is one of the first to demonstrate that cannabinoids affect both the accumulation of amyloid beta in nerve cells as well as the subsequent inflammation caused by this build up.
CANNABINOIDS AS NEUROPROTECTANTS
Prior to the study by the Salk Institute, research had already begun uncovering the unique neuroprotective properties of certain cannabinoids.
To be clear, it is important not to mistake cannabis as a substance that promotes neurogenesis. In fact, some evidence even suggests that cannabis use may enhance cognitive problems associated with memory.
However, research does show that the endocannabinoid system (the system that mediates the effects of compounds found in cannabis) plays an important role in adult neurogenesis, probably through activation of both CB1 and CB2 receptors.
Due to a spark in interest in the unique role of the endocannabinoid systems, a growing body of literature has examined how the activation of CB1 and CB2 receptors may relate to neurogenesis in the brain, especially in the hippocampus which, as we saw earlier, is the considered one of the first targets of Alzheimer’s disease.
In 2015, Irish researchers reviewed this growing body of literature. Their review found that there is a growing body of evidence that shows that cannabinoids may play pivotal roles in at least some of the phases of neurogenesis. The researchers also noted that the effect of these cannabinoids on the proliferation and survival phases of neurogenesis were of particular interest.
While the body of research into the cannabinoids, the endocannabinoid system, and neurogenesis is growing, the existing evidence still doesn't make a clear case for cannabis.
Instead, it opens up the discussion of how cannabinoids (both endogenous, synthetic, and plant-derived) are involved in the complex process of neurogenesis and whether, in the future, we may be able to manipulate these compounds in a way that could be beneficial in preventing neurodegenerative disease like Alzheimer’s.