Cannabinoids, Alzheimer's Disease, and Yoga

by Ram

There�s some good news for people with Alzheimer�s disease (AD) and for those who are potential carriers of this disease! Researchers from the Salk Institute discovered that marijuana harbors several potent active compounds that clear the toxic amyloid protein that accumulates in AD brains and which is believed to elicit toxicity resulting in memory loss. Although previous other studies have offered similar evidence that cannabinoids (the chemical compounds present in marijuana) might be neuroprotective and reverse symptoms of Alzheimer�s, this particular study got a lot of media attention since the study also demonstrated the anti-inflammatory properties of cannabinoids. Inflammation is an underlying hallmark of AD and with its dual function of clearing toxic amyloid protein and blocking inflammation, gives marijuana a very unique and important role in allowing people with memory loss due to AD to function normally. But does this mean that we all turn to being potheads just to reap the benefits from this neuroprotective weed? Before we seek out alternative routes, let us look a bit deeper into this psychoactive plant and its natural properties. 

Cannabis, the botanical name for weed or marijuana, has three subspecies: sativa, indica, and ruderalis. Hemp, cannabis, and marijuana all belong to the same plant species: cannabis sativa. This plant is known to synthesize a wide range of psychoactive compounds. One specific class of psychoactive compounds is the cannabinoids that affect many important body-mind functions, including an individual�s movement, feelings, and reactions. Interestingly, cannabinoids are produced naturally in the body by humans and animals (endocannabinoids), plants (phytocannabinoids-in cannabis and some other plants), and synthesized artificially (synthetic cannabinoids). Tetrahydrocannabinol (THC), the most important plant cannabinoid, is also the most widely researched compound, although it is just one of more than 400 known psychoactive compounds. A myriad of physiological effects are attributed to THC including: euphoria, stimulant, muscle relaxant, anti-epileptic, anti-emetic, anti-inflammatory, appetite stimulating, bronchio-dilating, hypotensive, anti-depressant, and analgesic effects. 

Interestingly, one of the main endocannabinoids produced by the human body is termed Anandamide (from the Sanskrit and yogic term Ananda=Joy, bliss, delightful). Anandamide has manifold functions, both physically and physiologically, including eating and sleep patterns, pain relief, rewards, motivation, and pleasure. Studies are underway to boost its levels in the body to treat anxiety and depression. 

Remember the term �runner�s high?� It�s a short-term contentment, bliss, elation, and well-being experienced by people involved in all kinds of physical exercises, including but not limited to athletics, long distance running, and swimming. Yoga practitioners also experience similar feelings and we call it being in the zone (Positive Psychology vs. Yoga Philosophy). Recent studies have attributed these euphoric feelings to the release of various �feel good endogenous chemicals� that produce this response and one such compound is Anandamide. 

So how do THC, Anandamide, and other cannabinoids elicit their neuropsychotic function in the mind-body system? Located in the brain are numerous receptor proteins that specifically bind to cannabinoids. Just as a specific key opens a specific lock, so is the relationship between the cannabinoids and its receptors. When a cannabinoid (endo, plant, or synthetic) engages a specific receptor, it regulates numerous endogenous neurotransmitters and thus elicits physiological and behavioral responses including appetite, pain-sensation, mood, and memory. However, when a person takes the cannabinoid from outside, the combination of the external and the body�s own natural cannabinoid completely overwhelms the receptor system throughout the brain and body. This then disrupts the normal neural communication and throws the entire physiological system off balance. 

I have already written about Alzheimer's disease (AD) on this blog before (Memory Loss�Meditation to the Rescue). AD is a progressive disease of the brain and the predominant form of dementia, and is characterized by loss of memory and reduced cognitive abilities. As the disease progresses, the individual is unable to perform activities of daily living or recognize loved ones. AD is also the sixth leading cause of death in the U.S. and the total number of those affected by the disease is expected to double by 2050. At the moment, there is no drug to cure or treat this disease. The disease is characterized by an accumulation and build-up of toxic amyloid protein that: a) affects normal nerve-nerve communication, b) damages the areas of the brain involved in memory, and c) promotes neuronal cell death by triggering neuroinflammation.

In this new study Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids by researchers at the Salk Institute, tetrahydrocannabinol (THC), the active compound in marijuana, not only appeared to remove the toxic amyloid beta protein in the brain, it also reduced inflammation in the cells thus revealing a dual neuroprotective function. The researchers have cautioned that the study was done in laboratory cell models outside of a human setting, and the findings are preliminary that need to be tested in humans in a clinical trial. What this means is that at this moment there�s no solid evidence to recommend marijuana for people with AD. What then is the alternative? 

Remember, I mentioned endogeneous cannbinoids and Anandamide in particular above. Well, as it turns out, meditation and deep diaphragmatic breathing (pranayama) triggers the production of endogeneous Anandamide and other similar compounds that not only trigger the feel-good response but also block anxiety and the sensation of pain (see High: Insights on Marijuana (The Endocannabinoid system and other Neuroscience) Sebastian Marincolo). While I did not find any scientific study of the effects of yoga asanas on the endocannabinoids system, from my personal experience, I can say that a daily practice of yoga will definitely stimulate the endocannabinoid pathways. When you are engaged in a posture where the asana challenge matches your skill, you have an undivided focus and get totally involved, forgetting everything else but the pose. You are in a state of �flow,� or as Desikachar puts it, �in the zone.� This state requires a whole lot of initial effort to make it accessible (Positive Psychology vs. Yoga Philosophy), but it offers unlimited opportunity to explore and control all mental aspects, including attitudes, emotions, concentration, intent, and faith. Notice how the experience builds contentment and brings a sense of accomplishment. It�s a great positive spiral, and it results in improved health and happiness. My belief is that this emotional state is due to the surge of endogeneous Anandamide and other feel-good chemicals. Thus, instead of smoking pot, one can derive the same benefits of the cannabinoid system through a combination of yoga, meditation and pranayama�I call that �yoga high�!

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Infection: Possible Cause of Alzheimer's Disease?

by Ram

Roads and Fences by Marie Lossky

Alzheimer�s disease was first described in 1906 by a German physician Alois Alzheimer and the disease that got its name from this physician continues to baffle neuroscientists to date about the exact cause, cure, or treatment. Alzheimer�s disease (AD) is a progressive brain disorder that damages specific cells in the region of the brain called hippocampus. Death of neurons in the hippocampal area of the brain triggers short-term memory failure, and often the person's ability to do familiar tasks begins to decline as well. Alzheimer's disease also attacks other areas of the brain responsible for functions such as language and reasoning, resulting in the loss of language skills and judgment. As the disease progresses, patients often exhibit personality changes, emotional outbursts, and disturbing behavior, such as wandering and agitation. People with AD eventually require comprehensive care, thus the disease presents a considerable problem in patient management as well. It may sound strange that despite a century having elapsed since the disease was first described, there is still no cure or proper treatment for this disease.

According to recent statistical data, an estimated 5.4 million Americans of all ages have Alzheimer's disease. By 2050, the number of people with Alzheimer's disease may nearly triple, to a projected 13.8 million. In the last 10 years of the 244 compounds that went to clinical trials only one was approved. And that one approved drug works with limited efficacy only when given to patients during the early stage of the disease. Finding drugs for AD is especially difficult because: 

1. The exact cause of AD is not yet known.
2. The brain is relatively inaccessible, and harder to test and deliver compounds to.
3. No proper animal models exist that recapitulate? exactly the disease in humans.
4. Less is known about the biology of the condition.

 While the exact cause of the disease is still unclear, most of the attention has been driven towards a protein called beta amyloid, which forms toxic aggregates or plaques in the brain of AD patients. When not properly cleared, the toxic beta amyloid blocked transport of essential nutrients and disrupted communication between neurons that ultimately resulted in death of nerve cells, cognitive decline, and memory loss. Evidence suggests that amyloid is deposited early during the course of the disease, even before clinical symptoms appear. Thus, this protein became a major drug target in the search for a cure to Alzheimer�s, with pharmaceutical companies spending billions of dollars designing drugs that bind to and trigger clearance of the toxic beta amyloid. In all these trials, not only were these drugs ineffective in reversing the AD symptoms, in several cases, patients exhibited severe side effects very early on and the trials had to be abandoned prematurely. So targeting beta amyloid in patients with AD may not be the correct approach to stop the disease, and several researchers continued to debate passionately about the amyloid hypothesis while looking into other theories. 

Now a team of researchers is proposing a very different story. In a study published last week, the collaborative team from Harvard and MIT report that beta amyloid may actually have a critical neuroprotective role in the brain: protecting the brain from infections (bacterial or viral). The neuroscientists suggest that beta amyloid acts as a foot soldier by trapping potentially invading harmful bugs and alerting the other defense teams in the brain to their presence. By forming a mesh like structure, beta amyloid traps the microbes and prevents them from traveling deeper into the brain. The researchers also pointed out that animals that overproduced beta amyloid were more resistant to infections and had longer survival rates compared to animals that did not produce the protein. The higher the expression of beta amyloid, the greater was the protective effect from the infection, suggesting that beta amyloid acted as a natural antibiotic. This meant that getting rid of amyloid, as most drug trials tried in the past, could actually be dangerous, especially when the patient contracted any infection. 

So if beta amyloid is actually a protective protein, what eventually triggers Alzheimer�s disease? According to the researchers, the disease could be inadvertently triggered by an infection that causes the formation of excessive beta amyloid. As people get older and their immune system becomes increasingly compromised, it paves the way for microbes to sneak into the brain, resulting in an overabundance of the beta amyloid protein that exceeds the normal protective threshold. An excessive buildup of the protein may trigger the body�s own defense system to go awry that which we know as inflammation (see Chronic Inflammation and Yoga: Combating the Fiery Killer). Thus, what may be a neuroprotector, over time changes its face into a neurotoxic molecule. It is like the soldiers who stage a coup instead of defending their country. 

So what does this mean for pharmaceutical companies? Well, instead of attempting to completely eliminate the beta amyloid protein from the brain, drugs need to be engineered such that they dampen the beta amyloid levels to a stage where they continue to elicit the protective anti-infective properties. And what does it mean for people who have early stages of the disease? Or what does it mean for people who do not have the disease yet but who have a family history of AD? For now, some of us maybe able to avoid the chronic mind-ravaging effects of AD by making healthy changes to our lifestyle, remaining active, achieving ideal weight, reducing stress, and in some cases, taking vitamins, herbs and/or nutraceuticals that are recommended by a physician or licensed practitioner. The brain, like muscles in the body, requires exercise to remain functionally strong and resist infections. Stimulation of the brain increases the branching of brain cells that provide resilience to the brain and also support cognitive function. Thus, it is important to pursue intellectually challenging activity throughout life (see The Power of Mental Exercise, Part 1). 

Maintaining mental agility and learning new tasks as we age will also contribute to our own well-being and independence (see What is Healthy Aging, Anyway) Additionally, brain changes associated with meditation and stress reduction play an important role in slowing the progression of age-related cognitive disorders including AD. Furthermore, maintaining good sleep and sleep habits helps to clear out harmful toxins, a process that may reduce the risk of AD (see Sleep, Alzheimer's Disease and Yoga). If you�re having trouble sleeping, yoga�s stress management techniques can help quiet your nervous system so you fall asleep more quickly and more soundly (see Five Tips for Better Sleep). And if you'd like to add any additional practices to encourage brain health, start meditating on a regular basis (see Memory Loss�Meditation to the Rescue) and keep practicing your yoga asanas (see More on Yoga and Brain Strength: Neuroprotection). It�s not too late to start all these techniques and practices to keep a healthy brain and a strong mind, so better start today! 

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