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Neurodegeneration is a general term used to describe the pathology of dozens of neurologic diseases that have drastically increased in the developed world in the last 40 years. The most notable are what I like to call the ‘gang of three’ neurodegenerative diseases: Alzheimer’s Disease, Parkinson’s Disease, and ALS, also known as Lou Gehrig’s disease.
A fourth member of this ‘gang’ would be autism which has exploded geometrically since the late 1980s, now affecting 1 in 45 boys born in the UK. To give you an idea of what we are up against as far as autism is concerned, consider this: seventy years ago the incidence of autism was 1 in 10,000, some experts claim that it was even more rare — 1 case in 15,000.
The cause or causes for these neurodegenerative diseases are unknown. What we do know is that many substances are associated with them such as pesticides, aluminum and mercury exposure, and many others like certain viruses and even prions (tiny misshapen proteins that can cause Mad Cow disease and its equivalent in humans). There are many other neurodegenerative diseases but these are the most prevalent. They also get most of the media attention too.
Although these diseases are markedly different from each other they all share common features since they are all degenerative in nature. The unique pathophysiology of neurodegeneration lies in the observation that special cells within the brain or spinal column, special immune cells called microglia, become ‘activated’ or switched on. This is a normal, vital function that the brain relies on when for example, it encounters and infection or is exposed to a neurotoxic agent such as mercury or aluminum.
In a normal setting when the brain functions correctly, this immune response happens acutely and subsides just as quickly — after let’s say an acute infection. It’s called the acute inflammatory response.
However, when diseased, this inflammatory response keeps going unabated leading to persistent, chronic immune stimulation which we refer to as chronic brain inflammation, or more technically immunoexcitotoxicity.
Be aware of our ‘fifth’ gang member which we refer to as cognitive decline (CD). CD is so common nowadays as to be considered part of normal aging. It is the slow deterioration of mental faculties which may or may not lead to other more serious diseases.
But the underlying pathology, chronic brain inflammation, appears to be present in all of these diseases. It is the process scientists are desperately trying to understand and to find treatments that lead to clinical improvements or possibly curing the condition.
So far all attempts have been disappointing using drugs that are currently available.
Several recent studies have shown some promise using the cannabinoids as possible drug interventions. The reasoning is simple: THC and other cannabinoids are powerful anti-inflammatory compounds that can markedly decrease the inflammatory response through either direct effects on brain cells themselves or indirectly through stimulation of the endocannabinoid system.
We’ll discuss several exciting studies that support this role.
The first study hails from Israel, ground zero for cannabis research. The research team led by Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine, says that THC has neuroprotective qualities as well as many other beneficial effects.
Using several brain damage models in mice, he has found that extremely low doses of THC — around 1,000 to 10,000 times lower than the level generally reached from an inhaled marijuana cigarette, can have an astonishingly powerful protective effect on the sensitive brain cells that have been injured.
They have demonstrated that the psychoactive component of marijuana, THC, protects the (mouse) brain from hypoxia (low brain oxygen levels), toxic chemicals and seizures. Researchers found that administering THC before or after lab-induced brain injury, led to significant improvements in cognitive (brain) function. Dr. Sarne had this to say:
"The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers conclude. One explanation for this effect is pre- and post-conditioning, whereby the drug causes minute damage to the brain to build resistance and trigger protective measures in the face of much more severe injury. The low dosage of THC is crucial to initiating this process without causing too much initial damage."
Dr. Sarne remarked that there are many applications for this process that could lead to drastic improvements in patient care. For example: injecting low dose THC during cardiac surgery prior to initiating cardiopulmonary bypass which can sometimes damage the brain; or maintaining low dose THC therapy in patients who suffer from chronic seizure disorders to prevent brain injury due to hypoxia from prolonged seizure activity.
This process applies to anyone who is at risk for brain injury either because of their working conditions or because of a disease they may have. Consider all the press we’ve been exposed to lately on high-impact sports which often leads to concussions. It’s the repeated action of concussion on the brain which can lead to pre-senile dementia in athletes. Imagine the possible application of THC here in tiny doses before and after any high-risk sporting event such as (American) football, rugby, boxing, MMA and the like.
Since cannabinoid receptors are located throughout the peripheral and central nervous system, in addition to many other structures such as the heart, the applications appear to be limitless.
In fact, Dr. Sarne is currently working with Dr. Edith Hochhauser of the Rabin Medical Center investigating the effects of low dose THC on experimentally induced heart injury.
One wonders if the ultra-low blood levels of THC found in chronic marijuana smokers — even when not getting high — confers a similar cardio and brain protective umbrella.
In other words, perhaps it’s a very good idea to routinely consume cannabis in order to maintain a certain low minimum of THC in the body at all times. Should one then succumb to an insult such as closed head trauma or a massive stroke or heart attack, this low serum level of THC will help prevent the most devastating consequences: what the medical profession refers to as reperfusion injury.
It’s a fascinating and worthwhile topic which may induce other researchers to investigate. It may lead, someday, to a transdermal patch of low-dose THC designed to prevent neuronal or cardiac injury.
Meanwhile another study dove tails nicely with the above publication. The second study, published in Philosophical Transactions of the Royal Society, was conducted by Dr. Andras Bilkei-Gorzo at the Institute of Molecular Psychiatry at the University of Bonn in Germany. The title of the study is: The endocannabinoid system in normal and pathological brain ageing.
Based on his years of research, Dr. Bilkei-Gorzo has suggested that marijuana acts either directly, or indirectly through the activation of the brain’s cannabinoid system, to trigger the release of powerful antioxidants from brain cells, which act as a cleansing mechanism.
This process is known to stop free radical buildup, remove damaged cells and improve the efficiency of mitochondria.
The mitochondria are the energy source for biological processes. ATP is the currency that cells use for energy which is made within the mitochondria. The brain is one of the most energy intensive organs. Should its mitochondria lose their efficiency, the effects are often horrific. The results (in combination with other degenerative processes) are seen everywhere in diseases such as Alzheimer’s Disease or autism.
Earlier I briefly mentioned the process of chronic (brain) inflammation, or more precisely immunoexcitotoxicity. It involves microglial activation, and subsequent overstimulation: the over-excitation of special brain cells (microglia, glial cells and astrocytes) leading to a massive buildup of free radicals. Once this occurs toxic byproducts of this cascade can cause severe damage to the brain.
This same process also affects the brain’s mitochondria. It leads to mitochondrial dysfunction and lowered brain energy levels. When this occurs the brain becomes much more sensitive to excitotoxicity from any cause. This, in effect, produces an endless loop of excitation, free radical buildup, and further excitation.
Therefore, anything that can arrest free radical generation and help restore mitochondrial function within the brain will have a powerful restorative effect. It may even arrest the damage or at least help prevent further destruction.
Neuroinflammation is at the heart of neurodegeneration, and as we now know, neurodegeneration is a leading cause of death and disability worldwide. There are dozens of ways this condition manifests:
Neuroinflammation refers to the activation of immune cells [immunoexcitotoxicity] in the central nervous system (CNS) in response to a wide variety of stimuli, including infectious diseases, autoimmune or neurodegenerative disorders, peripheral nerve damage, or stress.
Incredibly, only one class of compounds have been shown to exert a potent ability to inhibit this destructive process: the cannabinoids.
Professor Wenk at Ohio State University, conducts similar work and has been cited by Dr. Bilkei-Gorzo. Dr. Wenk’s opinion, based on years of clinical and biological research, is summed up here:
"I’ve been trying to find a drug that will reduce brain inflammation and restore cognitive function in rats for over 25 years; cannabinoids are the first and only class of drugs that have ever been effective. I think that the perception about this drug is changing and in the future people will be less fearful."
Incidentally, chronic inflammation is one of the leading theories of aging. It revolves around the slow deterioration of mitochondrial function and free radical buildup over time leading to a slow, progressive corrosion of cellular function.
If cannabinoids are shown to help restore mitochondrial function in all the body’s mitochondria, not just in the brain’s mitochondria, this may prove to be a significant medical advancement in the treatment of all age-related diseases; which of course include all of the chronic, degenerative illnesses we see everywhere including heart disease, cancers, autoimmune diseases and autism.
From a separate paper authored by Dr. Bilkei-Gorzo which can be found on his website, he mentions the importance of these findings:
Activity of the endocannabinoid system influences brain ageing
"Our group focuses on the potential role of the endocannabinoid system in brain aging, because the cannabinoid system regulates neuronal plasticity [the ability to adapt to change], is involved in the regulation of neuroinflammatory responses and influences cellular stress responses.
We hypothesize that modulation of the cannabinoid system influences the aging process. We already showed that reduced endocannabinoid signaling in mice lacking cannabinoid 1 (CB1) receptors leads to an intensified age-related neuronal loss and to an early onset of learning and memory deficits in ageing" (Bilkei-Gorzo et al, 2005).
It’s interesting to note that mice bred without the CB1 receptor system did not suffer accelerated aging overall, instead the effect was largely swift aging of the brain leading to cognitive dysfunction and enhanced skin aging.
Cognitive dysfunction often is the first sign of neurodegeneration in diseases such as Parkinson’s Disease and Alzheimer’s Disease.
These processes are not restricted to those who are diagnosed with the ‘gang of three’, or any other degenerative disease; we also see this process on a smaller scale with ‘normal’ aging in healthy patients.
As part of their efforts to understand the mechanism by which reduced CB1 signaling (in the CNS) accelerates brain ageing, they currently are investigating the role of endocannabinoid signaling within the brain’s microglia and in the development of age-related neuroinflammatory changes.
If caught early enough, these changes could be stopped before one develops a full-blown disorder for which no effective treatment exists.
Dr. Bilkei-Gorzo and his research team are painstakingly searching for clues regarding the role the CB1 receptor plays in cognitive decline. To quote Dr. Bilkei-Gorzo:
"The intracellular level of metabolic end products, oxidized and misfolded macromolecules increases in ageing, which leads to enhanced cellular stress and severely impairs the function of neurons. We suppose [propose] that the early brain aging observed in CB1 receptor knockout mice [mice bred without CB1 receptors] could also be the result of an alleviated [poor] defense against cellular stress."
Translated, they suspect that an active and healthy cannabinoid system with fully functioning CB1 receptors and ligands (phytocannabinoids from marijuana and/or endocannabinoids from within the brain) is mandatory for brain health. The CB1 ‘system’ (when healthy) functions as a powerful free radical mop cleaning up the synapse of toxic metabolic by-products before they can accumulate and promote cognitive decline.
Based on their preliminary findings they feel that the CB1 receptor is at least in part responsible for some of the signs of neurodegeneration and cognitive decline when the system becomes dysfunctional.
Should this simple observation be proven true we may have an easy, cheap, and potent way to maintain brain function and avoid senility as one ages. Simply use small amounts of cannabis frequently.