The Use of Cannabis as a Potent Anti-Inflammatory Medication - Part 2
The Use of Cannabis as a Potent Anti-Inflammatory Medication – Part 2
In part 1 of this article, some of the general applications of cannabinoids both synthetic and natural were covered. The power in these mysterious substances, comes at least in part, from their anti-inflammatory effects. In this article, we’ll cover the chronic immune response, where it lurks, the definition of cellular inflammation, and active areas of research where cannabis plays a special role.
Many would argue, myself included, that nearly all disease of affluence are inflammatory. Chronic inflammation is the bane of civilization. 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. It has been shown that cannabis reduces pain and inflammation under these circumstances.
This is one of the main reason why and how medical marijuana came to be legalized in certain states of America.
So what exactly is it that cannabis helps?
Let’s start first with a general definition so that we can all speak the same language. 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.
Arterial plaque (and much more) is a result of the above response. Simply living La Vida Industria is all it takes sometimes. It is real tissue injury. Here I’m referring to atherosclerosis because of its textbook presentation, but we could just as easily be describing other pandemics like metabolic syndrome, neurodegeneration like Alzheimer’s disease, or chronic pain. In total there are three main regions where inflammation prefers to occur: blood vessel, brain and as an excess of visceral fat.
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 (belly fat as it is sometimes called), TNF-alpha, is a known cytokine (immune cell messenger) that activates NF-kB. This odd sounding chemical messenger is at the core of chronic inflammation.
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.[ref]Barry Sears PhD. What is Cellular Inflammation? (http://www.zonediagnostics.com/cellular-inflammation/) 08/06/2013[/ref]
CANCER
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.”[ref]Lancet. 2001 Feb 17;357(9255):539-45.[/ref]
Cellular inflammation is the initiating cause of chronic disease because it disrupts hormonal signaling networks throughout the body.[ref]Barry Sears PhD. What is Cellular Inflammation? (http://www.zonediagnostics.com/cellular-inflammation/) 08/06/2013 p. 1[/ref]
TARGETING CELLULAR INFLAMMATION WITH CANNABIS
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 inflammation (pain) are often left in the lurch. These are the patients I would see who have been through a dozen doctors, taking 20 or more medications, and are no better off.
Wouldn’t it be amazing 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?
While there is a paucity of good anti-inflammatory prescription medications that a doctor can treat you with, current research demonstrates that several classes of cannabinoids can influence many of the inflammatory mechanisms mentioned above.
Let’s look at the classic model of inflammation once again: atherosclerosis.
CB1 BLOCKADE & CB2 STIMULATION DECREASE PLAQUE
It turns out that cannabinoids, acting via both CB1 and CB2 receptor modulation, have an important role in immune system regulation. Because inflammation plays a key role in atherogenesis, cannabinoids can potentially affect atherogenesis via modulation of the immune system[ref]Sandeep Singla MD. Cannabinoids and Atherosclerotic Coronary Heart Disease .Clinical Cardiology
Volume 35, Issue 6 pages 329–335, June 2012 (online: http://onlinelibrary.wiley.com/doi/10.1002/clc.21962/full) 11/23/2014[/ref]. CB1 & CB2 receptors have been identified on many immune cells and endothelial cells. Let’s see what the data shows:
Both CB1 and CB2 are G-protein coupled receptors that modulate second messengers and signalling components such as adenylate cyclase,…and members of the nuclear factor κ B (NF-κB) family. [ref]IBID[/ref]
In one study a synthetic cannabinoid agonist (stimulant) with CB2 selectivity was used. The decrease in extent of atherosclerosis was associated with a decrease in pro-inflammatory cytokine gene expression and attenuated oxidized low-density lipoprotein (ox-LDL)-induced NF-κB activation[ref]IBID[/ref].
In other words a synthetic CB2 stimulant (agonist) decreased plaque formation through a reduction in NF-kB.
What these studies suggest is that we may have a new, powerful, and potentially game-changing syllabus of cannabinoids that may actually “cure” heart disease, and by inference dozens of other chronic inflammatory diseases.
In part three more compelling evidence of the use of cannabis in suppressing inflammation will be provided.
You can read Part 1 of Dr. Christopher Rasmussen’s articles on Cannabis and Inflammation here.
The Use of Cannabis as a Potent Anti-Inflammatory Medication
The Use of Cannabis as a Potent Anti-Inflammatory Medication
Did you know that endothelial inflammation, the source of atherosclerosis (and the cause of heart disease, hypertension and stroke), is the underlying cause or contributor in 50% of all mortalities[ref]Lusis AJ Department of Medicine, Biology Institute, University of California, Los Angeles 90095, USA Atherosclerosis. Nature. 2000 Sep 14;407(6801):233-41[/ref], not just heart disease?
Chronic inflammation is closely associated with cardiovascular disease (CVD), as well as a broad spectrum of neurodegenerative diseases including Alzheimer’s disease (AD)[ref]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[/ref].
In addition, there are inflammatory mechanisms in pain, stroke, diabetes, cancer, obesity, chronic autoimmune processes, and possibly even some psychiatric disorders like depression to name just a few.
That means that we are suffering from unprecedented amounts of inflammation brought about by our modern lifestyle here in the west. Right now, we do not have any medications that effectively suppress this type of inflammation.
In treating pain we reach for Aspirin, Motrin, Acetaminophen, or we obtain a prescription for an opiate. That’s it for our choices but they all have dangerous side effects. Wouldn’t it be great if we had a powerful, safe, anti-inflammatory medicine that could be used by anyone who needed it regardless of how ill they may be?
Well, look no further because exciting new research is providing compelling evidence that the use of cannabis, with its ability to suppress pain and cellular inflammation, may be the Holy Grail of anti-inflammatory medicines.
As you probably already know, marijuana acts on certain special receptors in the brain and the body, the CB1 and CB2 receptors respectively. We also have endogenous (within the body) cannabinoids just like our endogenous opiate system. Agonists stimulate these receptors while antagonists block them.
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.[ref]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.[/ref]
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 (similar in structure) are also very effective against chronic pain of both neuropathic and inflammatory origin[ref](Herzberg et al., 1997; Bridges et al., 2001; Fox et al., 2001; Guindon and Beaulieu, 2006)(Tsou et al., 1996; Richardson et al., 1998a,b,c; Li et al., 1999; Martin et al., 1999b; Guindon et al., 2006)[/ref]. In fact, the endocannabinoid system has been recently implicated in the pain relieving actions of acetaminophen (Tylenol) and the anesthetic induction agent Propofol[ref]IBID p. 22[/ref].
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. 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[ref]IBID p. 22[/ref].
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[ref]IBID p. 24[/ref].
Meanwhile, before we discuss the Sativa plant in greater detail, how many readers can tell me what inflammation really is?
In the next article, we’ll discuss what chronic, cellular inflammation actually is, its many faces, and how marvellous chemicals contained in marijuana affect that system.