Chronic inflammation and pain represents an emerging public health issue of massive proportions, particularly in view of aging populations. Responses to an ABC News poll in the USA indicated that 19% of adults (38 million) have chronic pain and inflammation.(1) Often, in the case of chronic inflammation, the culprit is an autoimmune disease, which exhibits a wide range of manifestations.
Inflammation is an essential response by the body's immune system to protect an injured area, or draw bacteria and virus away from healthy tissue, so that a normal healing process can take place. However, the system's inflammation response can be called upon unnecessarily when an autoimmune disease or arthritis is in play within the tissues, causing them to act infected or abnormal when they are in fact normal. In these cases, the body can actually damage its own tissue. This condition is termed "chronic inflammation" when the body is unable to shut off the inflammatory response.
This category of inflammation encompasses the following disorders:
Chronic inflammation is not only painful, but unchecked it can lead to serious medical conditions such as heart attacks, stroke, and swollen airways.(2) Even short term inflammation can cause compromises in quality of life.
Over-the-counter treatments commonly used include aspirin, naproxen sodium (Aleve) and ibuprofen. A newer generation of NSAIDS known as Cox-2 inhibitors showed good results for pain relief but were removed from the market because they cause heart attack, stroke, and other cardiovascular events. Milder inflammation is often treated with acetaminophen (Tylenol), but this can cause liver damage.
In the worst cases, doctors will prescribe opioids. Side effects of opioids have been well documented, and include sedation, nausea, vomiting, constipation, and respiratory depression. The biggest problem is the physical dependence on opioids, because they are such a strong class of drug.
The result of these less-than-ideal treatments is that this chronic condition is often either left unchecked causing a great deal of ongoing pain, or the results can be sporadic with some good days and some bad days. Those suffering are searching for better and more consistent treatment options.
Cannabidiol (CBD) is a plant-derived compound that is building a reputation as an effective and safe treatment alternative in the battle against chronic inflammation. Medical studies are showing that CBD is of particular interest in the treatment of chronic inflammation, a major unmet medical need in society today, particularly evident in aging populations.(3)
Cannabinoids act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDS).(4) In 1988, the first cannabinoid receptor was identified, and named CB1. In 1993, CB2 was described. Both are 7-domain G-protein coupled receptors affecting the areas of the central nervous system and spinal cord, where synergy of activity between peripheral and central cannabinoid receptor function has been demonstrated.(5)
CB2, while commonly reported as confined to lymphoid and immune tissues, is emerging as an important mediator for suppressing both pain and inflammatory processes.(6) Studies show that the cannabinoid receptors, coupled with the related endogenous ligands ("endocannabinoids") and metabolizing enzymes comprise the overall endocannabinoid system (ECS).
CBD's unique chemical compounds are able to act universally and consistently in the ECS system to provide relief for those experiencing chronic or sporadic inflammation.
The endocannabinoid system (ECS) function has been prosaically described as "relax, eat, sleep, forget and protect."(7) The endocannabinoid system parallels and interacts at many points with the other major endogenous pain control systems: endorphin/encephalin, vanilloid/transient receptor potential (TRPV), and inflammatory. Interestingly, primary knowledge of each of these pain systems derived from the investigation of natural origin analgesic plants like CBD, poppy (morphine, codeine), chili peppers (capsicum), and willow bark (Aspirin, salicylic acid).(8)
A clinical endocannabinoid deficiency is postulated to be operative in certain treatment-resistant conditions.(9) In trials, pain was reduced in subject samples that included migraine sufferers, with a significant subset of fibromyalgia sufferers reporting significant decrease in pain following administration of CBD. Additionally, a study found the active role of the ECS in intestinal pain and inflammation associated with irritable bowel syndrome could also be addressed with CBD treatments.(10)
The ECS is tonically active in control of pain and inflammation. The CB1 antagonist in particular has proven to be 10-fold more potent than morphine in a wide dynamic range neurons mediating pain. The ECS also mediates central stress-induced analgesia, and in simultaneously active in nociceptive spinal areas.(11)
It was demonstrated that cannabinoid agonists suppress the maintenance of vincristine-induced allodynia through activation of CB1 and CB2 receptors in the spinal cord. (12) Once these receptors are activated, a more consistent system of relief and function is in play since the spinal cord itself is the target.
In addition to the ECS, CBD also acts on cytokines, which are critical components in the management of inflammation. Cytokines are the signaling proteins synthesized and secreted by immune cells upon stimulation. They are the modulating factors that balance initiation and resolution of inflammation.(13)
Science is beginning to indicate that one of the possible mechanisms of immune control by cannabinoids during inflammation is the dys-regulation of cytokine production by immune cells and disruptions of the well-regulated immune response. CBD works to regulate the delicate balance in the right amount of cytokines so that inflammation can be well-managed.
An important effect of cytokines in chronic inflammation is in their ability to decrease or prevent tissue injury when in proper balance. One animal study showed that CBD prevented joint tissue injury in animal models presenting with adjuvant arthritis.(14) In human studies, researchers observed value in CBD treatment of joint inflammation in patients with systemic lupus, rheumatoid arthritis and osteoarthritis.(15)
Endocannabinoids have been reported to affect the cytokine biology of various cell systems. Because of this broad effect, CBD can have a wide range of benefits in keeping these cell systems in their proper balance, thereby curtailing the likelihood for inflammation and tissue damage.
Colitis is an example of internal inflammation that does not involve the joints, but nonetheless is painful and afflicts a large number of people. Colitis is a good representative example of internal inflammation and its effect on general well-being, so it deserves closer analysis.
During the inflammation associated with colitis, several different cellular pathways are activated in the intestinal tract, leading to a pathological state. The number of CB1-expressing cells was found to be significantly increased during episodes of inflammation. A protective role for CB1 receptors in episode of colitis-related inflammation can reduce not only inflammation itself, but the neurological sensitivity to pain receptors.(16)
Additionally, administration of CBD smoothed out the colon membrane, giving further support to the notion that the endogenous cannabinoid system is protective against inflammatory changes. This data indicated that the activation of CB1 and the endogenous cannabinoid system is an early and important physiological step in the self-protection of the colon against inflammation.(17)
In addition to being a natural compound, so as to eliminate the risk of pharmaceuticals, there are other benefits to using CBD for the treatment of chronic inflammation. The mechanisms of use are still not fully understood and being further researched, but CBD had effects beyond an analgesic. CBD is frequently used by individuals with multiple sclerosis for muscle spasm and pain. Low doses of CBD alleviate tremors and are useful for patients with a number of disorders that produce spasms or unstable muscle function.
CBD goes beyond analgesic and anti-inflammatory effects; however, to also address the associated depression and anxiety often present with auto-immune diseases.(18) This mood-leveling benefit also comes into play with chemo-related neuropathy, migraine, Tourette's syndrome, and other disorders that can be linked to inflammation.
With such a wide range of disorders that can cause chronic inflammation, an effective treatment can improve the quality of life for many. CBD attacks inflammation on multiple fronts, through the spinal cord and central nervous system, internal inflammation, joint damage, and even the unwanted side effects of anxiety and depression. For those suffering with the long-term effects of inflammation, whether from auto-immune disease or from another cause, CBD may hold the key for relief.
1 - "Broad Experience with Pain Sparks Search for Relief," ABC News, Stanford Medical Center Poll, abcnews.go.com (2005).
2 - Fimaini, Liberty, Aquirre, Amin, Ali, Stafano, "Opiate, cannabinoid, and eicosandoid Signaling Converges on Common Intracellular Pathways," ScienceDirect.com (January 1999).
3 - Zurier, Burstein, "Cannabiniods, inflammation, and fibrosis" NCBI Resources, (July, 2016).
4 - Zurier, Burstein, "Cannabiniods, inflammation, and fibrosis" NCBI Resources, (July, 2016).
5 - Russo, Ethan, "Cannabinoids in the Management of Difficult To Treat Pain," NCBI Resources (Feb 2008).
6 - Mackie, K, "Cannabinoid Receptors as Therapeutic Targets," PubMed (2006).
7 - Mackie, K, "Cannabinoid Receptors as Therapeutic Targets," PubMed (2006).
8 - Russo, Ethan, "Cannabinoids in the Management of Difficult To Treat Pain," NCBI Resources (Feb 2008).
9 - Russo EB, "Clinical Encocannabiniod Deficiency: Can this concept explain therapeutic benefits of CBD in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?" PubMed (2004).
10 - Massa F, Monory K, "Endocannabiniods and the gastrointestinal tract," PubMed (2006).
11 - Hohmann AG, Suplita RL, Bolton NM, et al. "An endocannabinoid mechanism for stress-induced analgesia," PubMed (2005).
12 - Rahn EJ, Makriyannis A, Hohmann AG, "Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception," PubMed (2007).
13 - Nagarkatti P, Pandey R, Reider S et al, "Cannabinoids as novel anti-inflammatory drugs," PubMed (2009).
14 - Nagarkatti P, et al, "Cannabinoids as novel anti-inflammatory drugs," PubMed (2009).
15 - Nagarkatti P, et al, "Cannabinoids as novel anti-inflammatory drugs," PubMed (2009).
16 - Massa F, Marsicano G, Hermann H, et al, "The endogenous cannabinoid system protects against chronic inflammation," PubMed (2004)
17 - 13 - Nagarkatti P, Pandey R, Reider S et al, "Cannabinoids as novel anti-inflammatory drugs," PubMed (2009).
18 - Williamson EM, and Evans, FJ, "Cannabinoids in clinical practice," PubMed (2000).
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