INFORMATIONCBD And Medical Conditions

CBD And Medical Conditions

CBD and Pain Syndromes – A Literature Review

As stated, there a few mechanisms of action postulated for the positive analgesic effect of CBD including 1) proper regulation of a deficient endocannabinoid system, 2) Prominent anti-nociceptive 3) anti-inflammatory and 4) antioxidant effects. These properties have made CBD an ideal research candidate for many chronic pain syndromes. This includes, but is not limited to, rheumatoid arthritis, and various neuropathic pain syndromes such as chronic regional pain syndrome (CRPS), trigeminal neuralgia and post-herpetic neuralgia.  In the most recent review of CRPS in 2017, researchers have identified in neuropathic pain models that the CB-2 receptor shows a high level of expression.  CBD is considered a source of regulation of this overexpression and subsequent reduction of the neuropathic and inflammatory pain[1].

CBD and Low Back Pain/Spine Pain

The prevalence of low back pain is estimated to be around 70% of the population.  This is an enormous drain on quality of life including overall function, work status, and the secondary effects on sleep and mood.  Our general feeling is that low back pain can range from relatively simple (muscle spasm) to a complex issue depending on the pathology of the low back (spinal stenosis, failed back syndrome, degenerative disc disease).  We generally espouse a comprehensive mindset for managing low back pain. This includes physical therapy modalities, possible pharmacologic treatments, interventional therapies, chiropractic care, naturopathic medicine treatment, and behavioral help as well.

In consideration of pharmacologic options, the last decade has seen the ripple effects of the opioid crisis.  Previously proposed as a low-risk endeavor (chronic opioid therapy for non-cancer pain), now has millions of people exposed to opioids, with dependency, physiologic tolerance, and addiction at epidemic levels.

Furthermore, we are seeing more current data showing the risk and abuse of some of our more common atypical opioids (tramadol[2] and buprenorphine[3]) and non-opioid treatments including gabapentin[4] and carisoprodol (Soma ®)[5].  Suffice it to say, the pharmacologic options for chronic low back pain is a risky endeavor.  We feel that judicious use of CBD is a reasonable, low-risk alternative that may produce analgesic benefit, and without the harmful consequences seen with other pharmacologic options being used over the years.

CBD and Fibromyalgia

Fibromyalgia is a diffuse musculoskeletal and nerve pain syndrome that can be difficult to diagnose.  The American College of Rheumatology has recently changed the diagnostic criteria for fibromyalgia. The numbers of patients diagnosed with fibromyalgia over the last 1-2 decades continue to increase.

Current FDA approved medications for fibromyalgia include duloxetine, milnacipran, and pregabalin.  Off label use of standard medications to treat fibromyalgia includes amitriptyline and gabapentin.  Unfortunately for the large group of fibromyalgia patients that suffer daily, chronic pain, many of the above medications either do not produce appropriate pain relief or the side effects are too profound.  Dizziness, headaches, vision changes, slurred speech, cognitive dysfunction, weight gain, and swelling are some of the various side effects.  Initial studies have shown benefits of the endocannabinoid system and specifically CBD as promising and lacking the profound side effects of the more traditional medications.  More recent studies have characterized fibromyalgia as a central pain state (central nervous system hyper-reactivity) and CBD improving symptoms related this[6]. Fibromyalgia is an exceedingly diffuse musculoskeletal and nerve pain syndrome that can be difficult to diagnose. The

CBD and Arthritis

Joint pain from osteoarthritis is an exceedingly common yet potentially complex disease state to treat. It often combines both nociceptive and neuropathic components. The pathophysiology of osteoarthritis relates primarily to the articular cartilage degeneration. Repetitive motion injury, trauma, genetics, and certain medical diseases can predispose and accelerate the joint damage and subsequent debilitating pain in the affected joints. Traditional treatment paradigms typically have included anti-inflammatory medications, both steroidal and nonsteroidal, physical therapy, as well as activity modification. From a pharmacologic perspective, we know long-term, continuous use of corticosteroids can lead to osteoporosis, avascular necrosis, and irreversibly alter the adrenocortical system. Data in the last 10 to 15 years has also shown a heightened risk of nonsteroidal anti-inflammatory medications (NSAIDS) above and beyond gastritis. These include renal damage, elevated cardiovascular (myocardial infarction) risk and elevated stroke risk. As with opioids, long-term use of steroids and NSAIDs carry certain risks for patients. Recently, there has been exciting and promising data regarding the endocannabinoid system and its benefit regarding arthritic degeneration[7]. In murine collagen-induced arthritis, which is a well-vetted experimental protocol for clinical arthritis, CBD has shown to decrease interleukin-1, TNF-a, and interferon-g which are all therapeutic targets for degenerative arthritis[8]

CBD and Neuroprotective Effects

Neuroprotective properties have been shown for CBD in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s, stroke, glutamate toxicity, multiple sclerosis, Parkinson’s disease, and neurodegeneration caused by alcohol abuse.  Ongoing research is underway for many of these neurodegenerative issues.  Most recently a study has shown that CBD enhances quality-of-life scores in patients with Parkinson’s disease[9].

CBD and Seizure Activity

There have been many animal studies[10], anecdotal reports, case studies[11] and human trials[12] for CBD and its limiting effect on seizure activity.  Unfortunately, some of the recent CBD human clinical trials are poorly powered with study design flaws.  There continues to be much optimism in this space, however, and initial and ongoing trials are currently underway for adult and pediatric epilepsy syndromes[13]  Recently, the FDA has approved the first ever branded cannabidiol product for Dravet Syndrome (a specific subset of pediatric seizures), further solidifying cannabidiol as a viable medicine for complex medical issues.

CBD and Diabetes

Diabetes and its debilitating secondary consequences can result in multiple complications including diabetic neuropathy, nephropathy, retinopathy, as well as cardiac and GI manifestations.  Oxidative stress and inflammation play crucial roles in the development of these complications.  In the pathology of Diabetes Type 1 (autoimmune induced), both THC and CBD showed great promise in initial studies. However, THC was limited because of its psychoactive effects.  CBD again showed reductions in pro-inflammatory cytokines (interferon-γ and TNF-α)[14]

Diabetic neuropathy, in addition to many other types of neuropathies (chemotherapy-induced, multiple sclerosis, HIV associated neuropathy, and direct nerve injury) were studied and in an analysis of a grouping of the studies, the endocannabinoid system (CBD in particular)  showed benefit for severe neuropathic pain/numbness sensations[15]

Another example of one of the specific secondary consequences of diabetes, diabetic retinopathy (damage to vision) was studied to assess for benefits with CBD for this condition.  The pathophysiology of diabetic retinopathy is a breakdown of the retinal blood barrier.  Neurodegeneration of the retina is suspected to be the primary insult.  Recent studies have shown the neuroprotective effect of CBD in a rat model for retinal neurotoxicity[16]

CBD and Headache

Due to the complex nature of headaches (migraine, cluster, tension, cervicogenic, etc.) and likely interplay of multiple co-existing causes for complex headaches, studies have been lacking in this realm.  We are limited to anecdotal and case reports mainly.  There has been one retrospective study with 121 patients showing a promising reduction in migraine occurrences from 40% demonstrating a beneficial effect and higher than 10% having their headaches aborted[17]  Many researchers feel that it is significant enough promise to warrant future clinical trials given the limited but positive data that is available.

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[8] Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, Feldmann M. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 2000;97:9561–9566
[9]Chagas et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol. 28(11):1088-98. (2014).
[10] Consroe P and Wolkin A. Cannabidiol–antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. J Pharmacol Exp Ther. 1977 Apr;201(1):26-32.
[11] Press et al. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy & Behavior 45 (2015) 49–52.
[12] Porter BE and Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior 29 (2013) 574–577.
[13] Hussain et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015 Apr 29. pii: S1525-5050(15)00157-2.
[14] Am J Pathol. Horvath et al. 2012 Feb; 180(2): 432–442.
[15] Neurotherapeutics. E J Rahn. 2009 Oct; 6(4): 713–737
[16] El-Remessy AB, Khalil IE, Matragoon S, Abou-Mohamed G, Tsai NJ, Roon P, Caldwell RB, Caldwell RW, Green K, Liou GI. Neuroprotective effect of (−)delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol. 2003;163:1997–2008
[17] Cannabis Cannabinoid Res. 2017; 2(1): 61–71

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