CBD for pain relief….is it possible without side effects?
I will preface this post with: We can’t substitute one quick fix with another. You’ve still got to put in the “work” on the whole–movement, mindfulness, breath, nutrition, stress reduction.
Using cannabidiols (CBD) is not a quick fix.
Ok, onward……I am writing this because I like knowing why I am ingesting something….what effects it has and why….even though it’s just one small part of a myriad of nature’s way.
Opioid meds seemed like a great idea at first–access our own natural endogenous opioid system with a synthetic form—hmmm, maybe no so great after-all. Results: many people with decreased pain, but now an epidemic of dependency and an escalating black-market crisis and so many stranded without having knowledge to access their own bodies innate wisdom.
So, I write this asking to take it with a resolve to use the evidence as a support, just as I would hope you will use cannabidiol products as a resource and not a “take-one and-fix-it” solution.
Cannabis sativa has been used medicinally for centuries. The cannabis plant has some 80 known cannabinoids. And we have an endogenous (within our own bodies) source of cannabinoids in each of us–endocannabinoids. Endocannabinoids are made in our cell membranes (the linings of our cells) from phospholipids. Our endocannabinoid system includes the cannabinoid receptors CB1 and CB2 and the endocannabinoid ligands anandamide (Ananda means Bliss in Indian Sanskrit) and sn-2-arachidonylglycerol (2-AG) and their enzymes.
These ligands (by-products of a small family of fatty acids), have an affinity for the CB1 and CB2 receptors. Anandamide exhibits a higher bond for the CB1 receptor than the CB2 receptor. Although the two endocannabinoids are found in the systemic circulation at equal concentrations, the concentration of 2-AG is about 200 times higher than that of anandamide in the brain. Anandamide and 2-AG have different pathways and may be produced under different conditions. ¹
The two cannabinoid receptors mentioned above, have been identified within our bodies. CB1, represented at very high levels in the central nervous system (brain, spinal cord), is also found at lower levels in the peripheral (not in the central nervous system (CNS)) tissues. In fact, CB1 receptors are the most G-protein coupled receptors found in the brain.
They are found in the following areas of the brain (in rank order): substantia nigra (in the basal ganglia, important in reward and movement), globus pallidus (part of the basal ganglia), hippocampus (memory), cerebral cortex (executive function), putamen (part of the basal ganglia), caudate nucleus (part of the basal ganglia), cerebellum (coordination of movement), and amygdala (memory, decision-making and emotional responses).
So you see the aspect of movement being a large central aspect of the CB1 receptor sites.13
CB1 receptors are also found outside of the CNS, such as in adipocytes (fat cells) and hepatocytes (liver cells), and in musculoskeletal tissues. 13
CB2 is found predominantly in the immune system (mast cells, B cells, T4 and T8 cells, microglial cells, macrophages, natural killer cells and to a lesser extent monocytes and polymorphonuclear neutrophils). They occur in the immune system at 10-100 times greater than CB1 receptors. 6
CB1, CB2 and the endocannabinoids have a diverse distribution in peripheral tissues, including primary afferent neurons (those that take the neural messages towards the CNS). CB1 receptors are also densely expressed on peripheral nerve terminals such as C fibers (those that carry messages of danger), large diameter Aß and Aδ fibers, as well as in the dorsal root ganglia.¹
CB1 receptor activation in the CNS has the psychoactive effects that may not be desired if used therapeutically. However, as there are CB1 receptor sites in the peripheral tissues, these could be accessed for non-psychoactive properties.²
While selective activation of CB2 receptors also inhibits experimentally induced inflammatory pain and itch or the persistent pain of neuropathic origin, activation of both CB1 and CB2 receptors appears to have synergistic effects on pain suppression.³
“The endocannabinoid system’s salient homeostatic roles have been summarized as, “relax, eat, sleep, forget, and protect.” It is involved in embryological development, neural plasticity, neuroprotection, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and most importantly from the viewpoint of recent drug development: hunger, feeding, and metabolism.” 13
It has been proposed that migraine, fibromyalgia, irritable bowel syndrome, multiple sclerosis, Huntington’s, Parkinson’s, and other similar processes are due to a “clinical endocannabinoid deficiency syndrome.” 13
So perhaps in those that experience more pain, there is a “deficiency syndrome” occurring, where the body just doesn’t have the resilience of that system built up for a number of reasons.
Cannabinoids & Pain
With the production of synthetic CB2 agonists (those similar ligands that help initiate a physiological response when in contact with a receptor), such as HU308 and AM1241, studies were conducted that demonstrated that anti-nociceptive (nociceptors are receptors that respond to noxious or unpleasant stimuli) and anti-hyperalgesic effects in temporary, as well as persistent pain states by activating what was at the time thought to be essentially a peripheral cannabinoid receptor.
These studies gave promise to these CB2 agonists to become an important treatment option for inflammatory and neuropathic pain states. Most of these studies were done on lab animals, not in clinical trials. However there was a study demonstrating selective activation of CB2 receptors on human sensory neurons which blocked the inflammatory response by inhibiting Ca2+ release (necessary for the cellular channels to open and continue the cascade of nerve.)
Another study showed that endocannabinoid levels in the periaqueductal gray area of the brain (an area dense in opioid receptors)¹, increase in response to peripheral inflammation. Since then several studies have demonstrated that both CB1 and CB2 receptors undergo increased expression (meaning they are more prevalent) during inflammation and after peripheral nerve injury-induced painful neuropathies.4
By contrast, several studies demonstrated that morphine (an opioid) has only limited effectiveness in alleviating peripheral neuropathy symptoms, possibly due to the decreased expression of peripheral opioid receptors. In addition, chronic opioid treatment leads to analgesic tolerance–so the more you take the more you will have to take to get the same effect, as your tolerance builds up.
Opioids are also known for their development of hyperalgesic effects (meaning that after a period of taking opioids, one could actually become more sensitive to certain painful stimuli, which together with the well-known respiratory depressant effects have led to part of the failure of opioid therapy to successfully treat chronic pain populations.4 Not a viable option in the long-term. That, and patients are also often provided with no alternative to help mitigate their pain without medications.
In one study, the anti-hyperalgesic effect of a CB2 agonist, WIN 55,212-2 was time-dependent. Seven days following injury, hyperalgesia was partially reduced and, on day 14, thermal hyperalgesia was further reduced, whereas the mechanical allodynia (pain response from something that is not normally painful) was completely reduced. In contrast to the effects of repeated treatment, a single dose of the cannabinoid did not modify the pain threshold, suggesting that it needs to be in the system over a repeated time. 5
This above mentioned CB2 agonist demonstrated decreased nitric oxide synthase (NOS) and prostaglandins (PGE2), both inflammatory markers. It did this by activating CB2 receptors present on inflammatory cells, such as macrophages, natural killer cells and T lymphocytes; specifically, the cannabinoid could reduce the release of those mediators known to sensitize peripheral nociceptors.5
Cannabinoids & Chemo-Induced Pain
There are a fair amount of studies to demonstrate improved cancer related pain.
“One study has evaluated the possible role of CB2 receptors in suppressing neuropathic nociception produced by treatment with chemotherapeutic (chemo) agents. Unlike neuropathy induced by traumatic nerve injury, neuropathy induced by chemo may occur in the absence of peripheral nerve degeneration. A dysregulation of cellular calcium homeostasis, attributable to atypical mitochondrial function, has been implicated in chemo-evoked neuropathy. Vincristine is a chemo agent commonly employed to treat leukemia, lymphomas and solid tumors.
Treatment with vincristine induces mechanical allodynia under conditions in which responses to thermal stimulation are preserved. CB2 agonist, AM1241 partially reversed vincristine-induced mechanical allodynia in a manner that was blocked by a CB2 (but not a CB1) antagonist. By contrast, the mixed cannabinoid agonist WIN55,212-2 fully reversed vincristine-evoked mechanical allodynia. The anti-allodynic effects of WIN55,212-2 were involved with both CB1 and CB2 receptors. Recent work also suggests that CB2 agonists are effective in suppressing peripheral neuropathy evoked by paclitaxel (taxol) administration in rats.”6
CBD is one of the some 113 active cannabinoids in cannabis. It is a major phytocannabinoid, accounting for about 40% of the plants extract. CBD does not have the psychoactive effects of tetrahydrocannabinol (THC), making it a viable source to stimulate your CB receptors without producing the possibly unwanted effects of THC. 14
In January 2018, the World Health Organization released a report stating that CBD has “no addictive properties, is non-psychoactive, evinces no discernible side effects and shows great potential to serve as a viable form of treatment for a number of maladies.”
We can access CBD via hemp oil that ingested orally or topically, capsules, topical creams, or tinctures. Sometimes it’s hard to know which form to take. It’s going to be individual. You may need some with a bit of THC to help you specifically. Others will do fine with a form that is just CBD without any THC.
You want it to be easily absorbed. You want it to be from a clean source…just like you want your foods and supplements from a clean source. It may take some trial and error. If you live in a state that has full legal access to cannabis products, this process may be a little more feasible. You can go to a facility that carries all sorts of products. And hopefully the person there can help guide you.
You may want to speak to a health care practitioner that is well versed in using these products medicinally. There are emerging MD’s, Psychologists, RN’s, PT’s, Chiropractors and Acupuncturists that are using these products with their patients to help with sleep, anxiety and of course pain.
I have personally found hemp oil it to be beneficial for my headaches. Take it at the immediate onset of a headache and it’s gone or at least downgraded within 5 minutes. I don’t know any medication that I feel good about taking that does that. This hemp oil has no adverse, undesirable side effects.
And in taking it daily, I think of it as assisting with all those processes discussed above, “neural plasticity, neuroprotection, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory.” Why wouldn’t I want to take this?
Some get deterred by the cost of the product. Can you tell me, is it better to spend thousands on prescription medications every month? Is it better to spend countless hours in pain, where you are not able to work or take care of your family? What is it worth to you?– should be a question of what is the value provided on the other side of being “sick?” How valuable is it for you to be a functioning human being, who enjoys life? I say, that’s worth the price of a bottle that lasts me 2 months.
Cannabinoids are found not only in the plant Cannabis sativa, but also within our own bodies–known as our endocannabinoid system.
Our endocannabinoid system is represented in both our central nervous system as well as our peripheral system.
It is known that this system is involved in embryological development, neural plasticity, neuroprotection, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory.
It might be summarized as functioning as the system that helps regulate, “relax, eat, sleep, forget, and protect.”
Possibility exists that some of our pain processes (fibromyalgia, migraine, IBS, MS, etc) are highly connected to a “endocannabinoid deficiency syndrome.”
It has been demonstrated that our endocannabinoid system is involved in reducing both inflammatory and neuropathic pain states.
CB2 receptors are implicated in producing an anti-hyperalgesic response (unlike opioids) and does so in a time-dependent way—having effects 7-14 days out, and effects that improve with increased repeated dosages.
Exogenous CBD Use: It is possible to enhance our own natural systems with exogenous forms of CBD, much like we use phyto-estrogens, or phyto-progesterones, we can use phyto-cannabinodiols. More to come on that in a follow-up post.
So, we can see that there is research/evidence out there to suggest that our endocannabinoid system is involved in both inflammatory, as well as neuropathic pain states. There is value in trying something alternative to opioids or other pain medications out there, and hopefully gives you more information about how CBD helps pain.
If you found this article helpful, please share it. If it left you with more questions, please feel free to contact Tianna to see how we can begin to work together to help you improve your pain by looking at your whole person, one which may include supplementing with CBD to help with your pain.
D., & M. (2004, October 01). Endocannabinoids and exercise. Retrieved March 12, 2018, from http://bjsm.bmj.com/content/38/5/536
Kunos, G., Osei-Hyiaman, D., Bátkai, S., Sharkey, K. A., & Makriyannis, A. (2009). Should peripheral CB1 cannabinoid receptors be selectively targeted for therapeutic gain? Trends in Pharmacological Sciences,30(1), 1-7. doi:10.1016/j.tips.2008.10.001
Seltzman, H. H., Shiner, C., Hirt, E. E., Gilliam, A. F., Thomas, B. F., Maitra, R., … Spigelman, I. (2016). Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain. Journal of Medicinal Chemistry, 59(16), 7525–7543. https://dx.doi.org/10.1021%2Facs.jmedchem.6b00516
Spigelman, I. (2010). Therapeutic Targeting of Peripheral Cannabinoid Receptors in Inflammatory and Neuropathic Pain States. In L. Kruger & A. R. Light (Eds.), . Boca Raton, FL.
Costa, B., Colleoni, M., Conti, S., Trovato, A. E., Bianchi, M., Sotgiu, M. L., & Giagnoni, G. (2004, January). Repeated treatment with the synthetic cannabinoid WIN 55,212-2 reduces both hyperalgesia and production of pronociceptive mediators in a rat model of neuropathic pain. Retrieved March 10, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574173/
Guindon, J., & Hohmann, A. G. (2008). Cannabinoid CB2receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. British Journal of Pharmacology,153(2), 319-334. doi:10.1038/sj.bjp.0707531
Sparling, P. B., Giuffrida, A., Piomelli, D., Rosskopf, L., & Dietrich, A. (2003). Exercise activates the endocannabinoid system. NeuroReport,14(17), 2209-2211. doi:10.1097/00001756-200312020-00015
Hammell, D., Zhang, L., Ma, F., Abshire, S., Mcilwrath, S., Stinchcomb, A., & Westlund, K. (2015). Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. European Journal of Pain,20(6), 936-948. doi:10.1002/ejp.818
Pagano, E., Capasso, R., Piscitelli, F., Romano, B., Parisi, O. A., Finizio, S., . . . Borrelli, F. (2016). An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse. Frontiers in Pharmacology,7. doi:10.3389/fphar.2016.00341
Cannabis and Cannabinoids. (n.d.). Retrieved March 12, 2018, from https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq/
Gutierrez, T., Farthing, J. N., Zvonok, A. M., Makriyannis, A., & Hohmann, A. G. (2007). Activation of peripheral cannabinoid CB1and CB2receptors suppresses the maintenance of inflammatory nociception: a comparative analysis. British Journal of Pharmacology,150(2), 153-163. doi:10.1038/sj.bjp.0706984
Brownjohn, P., & Ashton, J. (2012). Spinal cannabinoid CB2 receptors as a target for neuropathic pain: an investigation using chronic constriction injury. Neuroscience,203, 180-193. doi:10.1016/j.neuroscience.2011.12.028
- Mcpartland, J. M., Guy, G. W., & Marzo, V. D. (2014). Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System. PLoS ONE,9(3). doi:10.1371/journal.pone.0089566
- Cannabidiol. (2018, March 18). Retrieved March 20, 2018, from https://en.wikipedia.org/wiki/Cannabidiol