An Initiative To Legalize Marijuana In California To Appear On Nov. Ballot


In part one I introduced you to a world of hurt. No I didn’t punch anyone. Rather, it’s the world of inflammation, the acute inflammatory response, and several examples of the role of the phytocannabnoids in treating inflammatory diseases. If you thought the acute response was bad think again. The meat and potatoes of degenerative disease are all about going chronic. Today we’ll cover the chronic immune response, where it lurks, the definition of cellular inflammation, and active areas of research where cannabis may play a special role.

Chronic inflammation is a different animal altogether, the bane of civilization. From now on when I refer to inflammation I am referring to the chronic type. This is the response that we are trying desperately to decrease or eliminate among those that suffer from its torpor. The biggest problem is that, with few exceptions, it doesn’t respond well to our pharmaceuticals either. As a result we have an enormous number of people suffering from chronic, degenerative diseases for which there is no cure.

Chronic inflammation is an unchecked biological reaction to tissue injury producing a smoldering, cascade of immuno-vascular responses in an attempt to heal, leading to a pathologic change in the cell population of the affected tissue. It is characterized by repeated healing and injury.

Whoa say what? Yes, my pixilated paramour, chronic inflammation is a never ending immune response-often enough-to our bad lifestyle and eating habits. Simply living La Vida Industria is all it takes sometimes. It is real tissue injury. Here we are referring to atherosclerosis but we could just as easily be describing other pandemics like metabolic syndrome, neurodegeneration or chronic pain.


There are as many different types of silent or chronic inflammation as there are organs in the body. I have classified the three most important types clinically: I call them The Three Amigos of Inflammation. They are endothelial (blood vessel), microglial (brain cell), and adipocytal (fat cell) inflammation. All of these are exponentially increasing in the US.

The type of inflammation occurring in the brain typically involves specialized immune cells called microglia. Their role is similar to the macrophage in peripheral tissues. Although an atheroma (plaque) does not develop as you would see in atherosclerosis, there is free radical formation, and immune cell activation when the microglia become “primed” or switched on during for example, a viral infection. This stimulation produces chemicals that kill invading organisms but in the chronic response it doesn’t let up which eventually kills the surrounding brain cells in a process called the “bystander effect.” This response can occur from eating highly processed foods, exposure to inflammatory metals such as aluminum and mercury, infection, or vaccination to name a few routes. AIDS related dementia from HSV is caused by this very phenomenon. Ultimately, this can contribute to the three main neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD) and ALS. Autism, the fourth skyrocketing neurodegenerative disease, may also get its jump wings from microglial activation. All four diseases are set to overtake the first world. Whatever is causing unprecedented levels of blood vessel inflammation is also contributing to brain inflammation.

The last Amigo is from the overproduction of visceral fat (VF). VF is a cytokine/adipokine factory secreting oodles of inflammatory chemicals and hormones. It’s a very active type of fat cell that is “stored” on (or in) your abdominal organs in much the same way you would encounter a metastatic cancer. Metabolic syndrome, a disease now affecting over 80 million Americans, is characterized by this abnormal accumulation of fat in what I affectionately call the “grain belly,” or beer belly, a more common term. You may have heard it called by the inaccurate term “belly fat.”


In part one we discussed acute inflammation and the dismal state of our prescription anti-inflammatory drug resume. Now that we understand that chronic inflammation is responsible for much of the human misery we see daily, let’s explore what this really means. That way when trapped in the kitchen by some ill-starred biochemist at your next cocktail party, you can actually impress her with your new knowledge on cellular inflammation. And, ignoring her buck teeth, perhaps land a date.

Let me saturate you in acronyms for a moment as we devil into the details. One of the 30 or so maligned products of visceral fat cells, TNF-alpha, is a known cytokine (immune cell messenger) that activates NF-kB.

The definition of cellular inflammation is increased activity of the gene transcription factor known as Nuclear Factor-kappaB (NF-kB). This is the gene transcription factor found in every cell, and it activates the inflammatory response of the innate immune system.[1] [Emphasis mine]

As I explained previously there is classic inflammation with redness, pain, swelling and warmth. This response can be seen when you accidentally staple your hand to that tardy financial report you were tasked with a week earlier. You injure yourself: you feel it right? The pain and swelling are all part of the innate immune system’s response to injury.

Then there is a more subtle, chronic, form which is often called silent inflammation until it blossoms into a real, definable disease often with a painful component. Both forms have their genesis with NF-kB. This immune response can be triggered by anything that stimulates the activity of NF-kB. It also paves the way for the third biggest killer in the western world-cancer.

The role of inflammation in evolution of certain types of cancer has been strongly suggested, linking the inflammatory response to 15–20% of all deaths from cancer worldwide….If genetic damage is the “match that lights the fire” of cancer, some types of inflammation may provide the “fuel that feeds the flames.[2] [Emphasis mine]


It turns out that several classes of cannabinoids can influence many of the below listed mechanisms.

Cellular inflammation is the initiating cause of chronic disease because it disrupts hormonal signaling networks throughout the body.[3]

Several pathways that activate NF-kB are revealed below:

  • TNF-alpha forged in our visceral fat factories-recognized by the omni present grain belly of metabolic syndrome. These tiny fat cells secrete inflammatory cytokines and adipokines (another class of immune cell messengers, the term comes from adipose tissue). The more visceral fat that you carry, the worse the silent inflammation.
  • Another way is by infection from any organism.
  • The generation of reactive oxygen species (ROS) is yet a third pathway. Limiting excessive ROS is fundamental to wellness.

Oxidative stress is closely related to inflammatory response by activating the nuclear factor-kappaB (NF-κB) signaling pathway that controls the transcription of pro-inflammatory genes such as IL-1 beta, IL-8, and tumor necrosis factor-alpha (TNF-alpha).[4] [Emphasis mine]

Much of our first-world diseases stem from bad habits which stimulate ROS formation. Excessive sugar intake, or the diabetic state, are examples. This helps explain why diabetics age faster than non-diabetics. Hyperglycemia is one of the most destructive because it generates ROS, and numerous other dangerous by-products:

Numerous epidemiological studies have identified diabetes mellitus as a major risk factor for atherosclerotic cardiovascular diseases such as stroke and coronary heart disease. Hyperglycemia triggers the activation of numerous key mechanisms/pathways, such as reactive oxygen species and reactive nitrogen species,…advanced glycation end products, eventually leading to endothelial dysfunction in diabetic blood vessels underlying the development of various diabetic complications.

Superoxide production plays a significant role in the pathogenesis of the diabetes-associated endothelial dysfunction. The cellular sources of superoxide anion are multiple…Among these pathways, mitochondrial generation of superoxide appears to play the most crucial role in diabetic complications. Superoxide can also be converted to hydrogen peroxide (H2O2) by superoxide dismutase (SOD), and previous studies have suggested that H2O2 plays a central role in NF-κB activation in coronary artery endothelial cells.[5] [Emphasis mine]

Hyperglycemia-induced superoxide generation might also favor increased expression of iNOSs through the activation of NF-κB, which increases the generation of nitric oxide. Superoxide anion interacts with nitric oxide, forming the potent cytotoxin peroxynitrite, which attacks various biomolecules in the vascular endothelium, vascular smooth muscle, and myocardium, leading to cardiovascular dysfunction via multiple mechanisms [2 citations: Pacher P, Beckman JS, Liaudet L. Physiol Rev. 2007 Jan; 87(1):315-424; Pacher P, Szabó C. Curr Opin Pharmacol. 2006 Apr; 6(2):136-41 The pathogenetic role of nitrosative stress and peroxynitrite and downstream mechanisms is not limited to the diabetes-induced cardiovascular dysfunction but also contributes to the development and progression of diabetic nephropathy, retinopathy, and neuropathy in both experimental animals and humans [Pacher P, Beckman JS, Liaudet L Physiol Rev. 2007 Jan; 87(1):315-424; Pacher P, Szabó C Curr Opin P   harmacol. 2006 Apr; 6(2):136-41] [6]

  • The creation of disproportionate amounts of arachidonic acid (AA) and their downstream inflammatory eicosanoids (certain prostaglandins for example), which can be moderated through diet,[7] is another big source for cellular inflammation. The major source for arachidonic acid comes from excessive consumption of omega 6 PUFA (seed oils), and much less so by eating AA rich foods like egg yolks and red meat.
  • Not surprisingly, AA activates NF-kB on its own.
  • Free fatty acid (FFA) accumulation in the liver (for example with metabolic syndrome) leads to increased activation of nuclear factor-κB (NF-κB) pathway and increased expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-1β).[8]
  • FFA also stimulates skeletal muscle NF-kB leading to insulin resistance.[9]

Patients with metabolic syndrome, all 80 million of them for example, ooze inflammation as evidenced by very high serum hsCRP levels (a standard inflammation marker). While modern medicine uses a small syllabus of pharmaceuticals to treat these patients, they can only suppress the symptoms of their inflamed habitus, such as reducing hypertension or lowering high fasting blood sugars. But for many patients it will be too little too late because the inflammatory response (the high hsCRP and other markers) is still there albeit more hidden. You look better on paper with normal vital signs but you smolder within. Over time many become diabetic and most develop cardiovascular disease.

Unfortunately, for many with chronic, degenerative diseases in advanced stages we need bigger guns which we do not have. Patients with high levels of silent or overt (pain) inflammation are often left in the lurch. These are the patients I would see who have been through a dozen doctors, taking 20 medications, and are still no better-except for the pot they are smoking which seems to help them. Wouldn’t it be groovy if we had drugs that operated on the cellular level to help these patients? A drug or supplement that might suppress NF-kB? Well, we already have some, but most are not commercially available yet. Can you say cannabinoids?

In the next section, part three, I will discuss the medical applications of cannabis in treating chronic, inflammatory diseases. I’ll use atherosclerosis as the model for discussion because it is the textbook example of silent inflammation. Please remember however, that anything that treats or reduces plaque will also tend to reduce inflammation throughout the entire body thus decreasing the risks for cancers and neurodegeneration. And folks, that’s precisely what we need.


[1] Barry Sears PhD. What is Cellular Inflammation? (http://www.zonediagnostics.com/cellular-inflammation/) 08/06/2013

[2] Lancet. 2001 Feb 17;357(9255):539-45.

[3] Barry Sears PhD. What is Cellular Inflammation? (http://www.zonediagnostics.com/cellular-inflammation/) 08/06/2013 p. 1

[4] Materials 2010, 3, 4842-4859; doi:10.3390/ma3104842. p. 4852

[5] Mohanraj Rajesh, et al. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am J Physiol Heart Circ Physiol. Jul 2007; 293(1): H610–H619.

[6] IBID

[7]Lancet. 2001 Feb 17;357(9255):539-45 p. 1

[8] Diabetes December 2005 vol. 54 no. 12 3458-3465 doi: 10.2337/diabetes.54.12.3458

[9] Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease Volume 1792, Issue 3, March 2009, Pages 190–200

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Category: Inflammation, Medical Marijuana, PREVENTIVE MEDICINE

About the Author ()

Dr. Christopher Rasmussen (aka Reality Renegade) is the author of his upcoming book, "InflaNATION: Industrial Diners & A Doc In The Box." By deliberately avoiding harmful industrial foods and the Commercial Sick Care System with its Pills and Procedures paradigm, Dr Rasmussen cured himself of a deadly disease-which became the reason for writing this book. In the book, he provides the facts you must know and the solutions to regain your health, maintain wellness, and outlive your parents' generation in an extraordinarily toxic world.

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