WHAT DOES A THORN IN THE FOOT, HEART DISEASE, AND A MEERSCHAUM OF MARIJUANA HAVE IN COMMON? PART ONE OF A FOUR PART SERIES. By Chris Rasmussen MD, MS.
Inflammation, the first two generate it and the third, a bowl of cannabis (when smoked or otherwise consumed), reduces it. However, it’s a tad more complex than that. So pull up a chair next to the fire, light your pipe, and let’s talk.
We hear the word inflammation all the time. But what does it really mean? In this series of four articles I will explain to the reader what inflammation is at a cellular level. Why we need to understand it, the current status of prescription anti-inflammatory medication, the exciting role cannabinoids currently play, and the future use of cannabis.
Please note, gentle reader, that inflammation is the single most important concept in all of preventive medicine. If it is not the root cause of our diseases of affluence, it plays a major role in promoting and advancing these ailments. It demonstrates how widely differing diseases share a common origin. In America, and other industrialized countries, we suffer from unprecedented levels of inflammation.
There are different types of inflammation acute and chronic, silent and overt (pain). As far as disease states go silent inflammation is the most predominant in the American population affecting at least 200 million people. It’s the “grey area” between wellness and measurable disease. A good example would be atherosclerosis. It takes 40 years to make plaque and during that time it is painless hence, silent. Any male age 65 or older with a typical American lifestyle has heart disease until proven otherwise. That pretty sobering isn’t it?
A relatively new disease has reared its head like a cyclops with conjunctivitis; it’s an epidemic of blood vessel inflammation which has spawned our nation’s first killers: heart disease, and thrombotic (blood clot) stroke. Inflammatory processes occur in most of the other deadly disorders we commonly encounter too. In fact, the disturbing truth is that endothelial inflammation, the source of atherosclerosis, is the underlying cause or contributor in 50% of all mortalities, not just heart disease.
WHY DO WE NEED TO KNOW THIS?
Our very lives depend on this knowledge. Once you learn what inflammation does to you, how it generates disease, you will realize how important it is to stop it cold if possible. This explains why changing one’s diet and lifestyle often helps to prevent, even cure, many seemingly unrelated diseases. Chronic inflammation is closely associated with cardiovascular disease (CVD), as well as a broad spectrum of neurodegenerative diseases including Alzheimer’s disease (AD). Unfortunately, the modern American lifestyle: the way we eat, drink and be merry is closing in on us. We have become a nation of the sick and inflamed. Currently, there is no pill that your doctor can prescribe that alleviates the type of inflammation we are talking about here.
In perhaps one of the most profound revelations in medicine, it turns out that nearly all first-world diseases have an inflammatory origin or component.
The implications are profound. It means that modern, industrial living is putting us straight on the path toward one of the major killers in this country: heart attack, stroke and many cancers. It also means that if we had a powerful anti-inflammatory medicine that worked at the cellular level it would have broad, sweeping, actions in preventing, or treating these diseases. Cannabis, with its ability to suppress pain and cellular inflammation, may indeed be the holy grail of anti-inflammatory medication.
Here’s an interesting factoid: when treating the root causes, any strategy that decreases inflammation from let’s say the coronary arteries will also help to decrease inflammation in other organ systems like the brain. Therefore, when you set out to “cure” atherosclerosis you also decrease your risks for neurodegeneration, and cancer also. You don’t even have to try-it comes with the turf so to speak because they all share a common origin if you look deep enough. That’s exceptional news because it tells us, at least in theory anyway, that there is one relatively simple path to take which liberates us from the major diseases of western civilization: the so called diseases of affluence. All we have to do is decrease our inflammatory burden.
It runs deep into our culture. There are inflammatory mechanisms in pain, stroke, cardiovascular disease (CVD), diabetes, cancer, obesity, chronic autoimmune processes, and possibly even some psychiatric disorders like depression to name just a few.
In order to do this-i.e., reverse the tide of chronic, degenerative diseases, we need to eliminate the source of inflammation at its origin. Diet and lifestyle changes work if you start early enough, I’m living proof of that. But many in the anguish of far advanced disease need stronger Kung Fu. More potent Kung Fu? How about our standard anti-inflammatory drugs like Motrin or prednisone, how do they stack up? These drugs have their usefulness but they have no indication in treating chronic diseases like atherosclerosis-they simply address the wrong inflammatory components. Is there anything else? Well, maybe. Investigational and currently marketed CB receptor agonists (stimulants), and antagonists are already in use that possess amazing properties including treating inflammation. Here’s just a few uses:
There is widespread potential for therapeutic applications of CB receptor ligands. CB1 receptor agonists, for example, relieve pain, nausea and vomiting, reduce hyperexcitability in epilepsy, and increase food intake of debilitated patients. On the other hand CB1 receptor antagonists may be useful for the modulation of behavior in addiction and for treating obesity. In fact, rimonabant… had been approved for that indication, but has meanwhile been withdrawn from the market due to serious side-effects resulting in an increased suicide rate. Antinociceptive effects, especially in neuropathic and chronic pain, indications of medical need, may be achieved by selective CB2 receptor agonism thus avoiding adverse CB1 effects. Further fields of application for CB2 receptor agonists are inflammatory diseases including multiple sclerosis and arthritis. A few CB receptor agonists have already been licensed for clinical use, including dronabinol (Δ9-THC), nabilon, a synthetic THC analog, and a combination of Δ9-THC with cannabidiol to reduce psychotropic effects. [Emphasis mine]
So far compelling evidence exists for anandamide, THC, cannabidiol, and synthetic cannabinoids in effectively treating animal models of pain from chemical, mechanical, and thermal stimuli. Recent animal studies indicate that anandamide and cannabinoid ligands are also very effective against chronic pain of both neuropathic (Herzberg et al., 1997; Bridges et al., 2001; Fox et al., 2001; Guindon and Beaulieu, 2006) and inflammatory origin (Tsou et al., 1996; Richardson et al., 1998a,b,c; Li et al., 1999; Martin et al., 1999b; Guindon et al., 2006). In fact, the endocannabinoid system has been recently implicated in the pain relieving actions of acetaminophen (Tylenol) and the anesthetic induction agent Propofol.
In addition to the role of CB1 receptors, there is recent evidence implicating CB2 receptors in the antihyperalgesic activity of cannabinoids in models of acute and chronic, neuropathic pain, especially of inflammatory origin [14 citations]. Cannabinoid agonists may also release endogenous opioids, and a functional interplay between the endocannabinoid and opioid systems in modulating analgesic responses has been suggested by numerous studies. [7 citations] [Emphasis mine]
In human studies the data initially were not as clear cut. Recently however, the role of cannabinoids in ameliorating pain and inflammation has been revealed. From The Endocannabinoid System as an Emerging Target of Pharmacotherapy the authors note:
To the extent that pain and inflammation accompany many of the disorders discussed in the rest of this review, cannabinoids would be expected to provide significant benefit due to their analgesic and anti-inflammatory properties.  [Emphasis mine]
Meanwhile, before we discuss our friend the Sativa plant in greater detail, how many of you can tell me what inflammation is? Yes, you there, what is inflammation pray tell?
THE CLASSIC (ACUTE) INFLAMMATORY RESPONSE
Let’s start with the classic inflammatory response which was first described by Aulus Cornelius Celsus (c. 25 B.C.-c. 50) in De Medicina. De Medicina‘s contents came from a vast collection of writings of the school of Hippocrates. In fact, in De Medicina, Celsus (although apparently not a physician himself) references some 80 Greek medical writers, and he has been called both the Roman Hippocrates, and the Cicero of Medicine. His medical philosophy was also influenced by Asclepiades, who established Greek medicine in Rome, and by the famous medical school of Alexandria.
He characterized the five cardinal signs as Dolor (pain), Rubor (redness), Calor (heat), Tumor (swelling) and Functio laesa (loss of function). This classic response is what you see when you puncture your skin with a thorn for example. Another example would be an infected joint where we see a painful, swollen, warm, red joint with decreased function. What we called a “pus knuckle,” from someone punching his opponent in the tooth, was the kind of injury we would see every night on call at LA County hospital. It’s a simple formula: gather two pugilists, add 2 quarts of grain alcohol, and then start punching.
Incidentally, even if the acute response sounds maladaptive it surely isn’t. We need an intact acute response so that we do not bleed to death from a minor wound or become septic from a superficial infection. Normally the response fades and the patient recovers. That’s it, that’s the way it’s supposed to work. Yet, in the above “knuckle” we humans (with joint-loving oral flora) sometimes need help so we open it up and drain it as you would a festering carbuncle. In other cases the response smolders like one of those underground coal fires that’s been burning in West Virginia for 100 years. We call that chronic.
NEW YORK TIMES 2014 NOBEL PRIZE IN MEDICINE AWARDED: POT REVERSES HEART DISEASE!
Did anyone catch that article in the Times? Right, it’s a made up headline but it’s not too farfetched. Here’s the deal. Right now Americans are awash in inflammation with absolutely no recourse. Wouldn’t it be peachy if pot contained super-promising chemical contenders that could slake your inflamed organs like ice water on an asphalt melting day? Many scientists agree that the cannabinoids hold the key. So the race is on to find a new, safer, class of anti-inflammatory drugs. Surely a Nobel Prize waits for the intrepid discoverer. And don’t call me Shirley.
Meanwhile, there are some supplements that work pretty well like curcumin, and Boswellia (frankincense) but they operate through boring, if not well understood, pathways known as the COX and LOX enzyme systems. Aspirin for example, is a nonspecific COX inhibitor. The cannabinoids appear to work through different, novel, and more powerful mechanisms which are turning out to be bountiful areas for research. As of now our anti-inflammatory medicines come with a shopping list of side, and adverse, drug effects. Basically, we are stuck with the non-steroidal anti-inflammatory drugs called NSAID’s, and corticosteroids for the treatment of most non-infectious inflammatory conditions. Yet, these drugs cause as many problems as they help when taken chronically.
Therefore, it comes as no surprise that Big Pharma is elbows deep in finding promising candidates teased from the matrix of Mary Jane.
In part two we’ll discuss what chronic, cellular inflammation actually is, its many faces, and how certain chemicals contained in marijuana affect that system.
 Lusis AJ Department of Medicine, Biology Institute, University of California, Los Angeles 90095, USA Atherosclerosis. Nature. 2000 Sep 14;407(6801):233-41. – See more at: http://inflanation.com/preventive-medicine-2/inflammation-part-8-the-maillard-reaction/#_ftn2
Paula Grammas. Neurovascular dysfunction, inflammation and endothelial activation: Implications for the pathogenesis of Alzheimer’s disease Journal of Neuroinflammation. (http://www.jneuroinflammation.com/content/8/1/26) 12/12/2011
 Alexander Fuchs, et al., The Natural Product Magnolol as a Lead Structure for the Development of Potent Cannabinoid Receptor Agonists. PLoS One. 2013; 8(10): e77739.
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