CBD’s Role in A Healthy Pain Response

The statements mentioned in this content have not been evaluated by the FDA, and are not intended to prevent, diagnosis, or treat any disease. Always work with your personal healthcare provider.

One of the most common reasons patients seek medical care is due to pain. I know this from personal experience as a large number of patients who visit my clinical practice are in pain.  Approximately 40% of adults in the United States are suffering from chronic pain, with an estimated annual cost of up to $635 billion.¹ Being in pain can significantly damage your quality of life and interfere with both physical and mental activities. You often are unable to do the things you love to do and your work productivity may suffer. Conventional medicine’s answer to pain is often a prescription to opioid drugs. In chapter 2 of this book, I briefly touched upon the dangers of opioid side effects and addiction.

By contrast, phytocannabinoids like CBD are safer and aren’t addictive. The CB₁ receptor is found throughout many areas of the body but its expression is weak in brain stem regions that control respiration. Since cannabinoids work through this receptor, the potentially fatal respiratory depression that occurs with opioid drugs does not occur with cannabinoids.² Cannabinoids like CBD also reduce opioid tolerance and dependence.³

New research indicates that CBD actually allows people to eliminate or reduce their use of opioids. In an eight-week study, researchers investigated 97 patients between 30 and 65 years old who suffered from chronic pain who had been on opioids for at least one year.⁴ More than half of the chronic pain patients (53%) reduced or eliminated opioid use within eight weeks after beginning supplementation with CBD-rich hemp extract. Quality of life improved in nearly all CBD users (94%). The participants taking the CBD-rich hemp extract experienced significantly improved sleep and reduced pain severity. Unlike opioids, CBD is not addictive and is therefore a safer alternative.⁵

CBD and Joint Pain

Osteoarthritis (OA) is a disease that leads to joint degeneration, intermittent inflammation, and peripheral neuropathy (nerve pain). There’s a lot of logical reasons why CBD would be effective for sore, stiff joints. For example, receptors responsive to cannabinoids, including  CB₁, CB₂, GPR55, PPARα, and PPARγ, are located on human joint cartilage from people who have osteoarthritis symptoms.⁶ Cartilage cells from OA-affected joints express a wide range of cannabinoid receptors.⁶ This suggests that cartilage cells can respond to cannabinoids like CBD. What’s more, osteoarthritis leads to a combination of inflammatory, nociceptive, and neuropathic pain.⁷ Most pain is nociceptive pain. It refers to the type of pain that results from injury to body tissues. The endocannabinoid system reduces nociceptive as well as the other two types of OA-related pain.⁷

A number of animal studies have investigated the role of CBD in managing pain from osteoarthritis and rheumatoid arthritis. In one of these studies, researchers investigated whether CBD could relieve osteoarthritis-related pain.⁸ They also studied whether CBD could support a healthy inflammatory response and stop the development of OA-related pain and joint neuropathy. The scientists induced OA in male rats and then observed the effects of injecting CBD into the animals’ joints. In end-stage OA, CBD dose-dependently improved measures of joint health. CBD also reduced transient joint inflammation.  Prophylactic administration of CBD before the disease was at its worst stopped the development of later joint pain and protected nerve health. The researchers concluded, “These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.”

Additional research strongly suggests CBD has a role to play in supporting joint health during rheumatoid arthritis. In an animal model of rheumatoid arthritis, CBD injected at 5 mg/kg per day or 25 mg/kg per day orally led to clinical improvement and protection against severe joint damage.⁹ It also supported healthy levels of inflammatory markers both in cell culture and in mice. According to the scientists, “Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect” in an animal model of rheumatoid arthritis.

CBD and Nerve Pain

Neuropathic pain is a form of chronic pain that occurs due to damage to the central or peripheral nervous systems. This type of pain is caused by physical trauma such as from accidents, surgery, or stroke, diseases like diabetes, cancer, and immune conditions, and certain medications such as cancer chemotherapy drugs. It is a severe, abnormal pain that often is triggered even when there is no stimulus or in the presence of normally harmless stimuli such as a light touch or stroking (like that which occurs when putting on clothing). Mild temperature changes, such as those that occur when you shower, can also trigger a painful response. Neuropathic pain is also linked to accompanying mental disturbances such as depression, anxiety, sleep problems, and less social interactions with family and friends.

Standard pharmaceuticals used for neuropathic pain are not always effective. At least half of people who suffer from this type of pain don’t experience meaningful pain relief after taking these medications.¹ Furthermore, the drugs often produce severe side effects such as dizziness, sedation, depression, and sleep disorders.¹ Consequently, many people find them intolerable.

In many studies of neuropathic pain in rodents, CBD had a beneficial effect. For example, mice were given a chemotherapy agent known to cause neuropathic pain.¹⁰ Cannabidiol injected into the abdomen of the animals before the chemotherapy agent reduced (but didn’t prevent) the chemotherapy-induced neuropathy. After CBD, the mice’s hind paws were less painful after pressure was administered.

In another study, researchers investigated CBD’s effects on neuropathic pain caused by sciatic nerve injury or inflammation in rats.¹¹ Giving the rats CBD orally from day seven to two weeks after onset of the injury or inflammation decreased the increased sensitivity to pain after exposure to heat and touch.

Additionally, other researchers administered moderately high doses of intranasal cannabidiol in one group of mice and injected cannabidiol into the abdominal area of another group mice (intraperitoneal administration).¹² At the same time, the scientists induced type 1 diabetes in the animals. Both the intranasal cannabidiol and intraperitoneal cannabidiol reduced the development of peripheral neuropathic pain. The pain reduction continued even after cannabidiol was discontinued and without any improvement in diabetes in the animals.

THC, the psychoactive component of cannabis, may be more effective at relieving pain compared with CBD.¹ However, CBD can be used in higher doses compared with THC since it does not produce the high that THC does.¹ This gives CBD an advantage over THC.

Most of the clinical research on CBD and neuropathic pain used a combination of both CBD and THC.^13-15 Despite the lack of human studies focusing on CBD-use alone in neuropathic pain, there’s a lot of evidence from preclinical animal studies showing its effectiveness.⁵ What’s more, as mentioned earlier in the chapter, CBD use can help people wean off of opioids and isn’t addictive. This indicates CBD is a preferable option to many pain relievers.

CBD May Soothe Muscle Pain

Approximately 10% of the population suffers from widespread musculoskeletal pain.¹⁶ This group includes the 2% to 4% of the population that has fibromyalgia.¹⁷ People in pain frequently use marijuana or other products containing THC and CBD. The National Pain Report, a survey of 1,300 people, compared three regulatory body-approved pharmaceutical fibromyalgia treatments with cannabis.¹⁸ In regards to effectiveness of the treatments, the survey respondents strongly preferred cannabis over the prescription medicines.

CBD alone without THC may have a role to play in supporting the health of people with muscle and musculoskeletal pain. In a rat study, researchers used intramuscular injections of CBD and the mildly psychoactive cannabinoid cannabinol (CBN), alone and both combined to determine whether they could decrease muscle pain in the animals.¹⁹ CBD or CBN each decreased muscle pain. When used together, there was longer-lasting pain reduction compared to when each was used separately. However, CBN, as a breakdown product of THC, is mildly psychoactive and therefore many people may be reluctant to use it. This study showed that CBD does have a pain-reducing effect on its own and that CBD or CBD combined with CBN “may provide analgesic relief for chronic muscle pain disorders such as temporomandibular disorders and fibromyalgia without central side effects.”

In Chapter 1, I discussed a substance known as palmitoylethanolamide (PEA), which isn’t an endocannabinoid but works on the endocannabinoid system by helping the body make better use of the endocannabinoid AEA. In my patients suffering from pain, I often use both CBD and PEA for the best effects. PEA is able to reduce temporomandibular joint (TMJ) pain.²⁰ It also can increase the effectiveness of standard fibromyalgia treatments.²¹

Visceral Pain and Irritable Bowel Syndrome

CBD may also reduce visceral pain, including pain involved in irritable bowel syndrome (IBS). Visceral pain affects the area surrounding the stomach, rectum, bladder, or uterus. An example is the abdominal pain that happens during IBS. Menstrual cramps and pelvic pain caused by bladder infections are other types of visceral pain.

CBD works through the endocannabinoid system, which regulates pain sensitivity caused by chronic stress.^22,23 Changes to this system may be the reason why there’s a link between chronic stress and irritable bowel disease(IBD)/IBS.^22,23 Research in rodents indicates stress during early life alters the endocannabinoid system, which increases the chances of developing IBS.²⁴

Through its ability to regulate visceral pain, the endocannabinoid system may also be involved in the way in which psychological stress damages GI function. During stress, concentrations of the endocannabinoid anandamide decline while levels of the endocannabinoid 2-AG in the brain increase.²⁵ By relieving stress, CBD may block stress-induced visceral pain. CBD benefits the hypothalamus-pituitary-adrenal (HPA) axis in mice exposed to psychological stress.²⁶  The HPA axis controls the production of the stress hormone cortisol and is involved in the way the body handles stress. In addition, a number of human studies show CBD has a calming effect. I discussed these studies and other evidence of CBD’s stress-reducing properties in Chapter 2 of this book.

Headaches and Other Types of Pain

CBD may be able to reduce a variety of different kinds of pain. For example, there’s evidence it may reduce headaches and migraines.²⁷ While there have been no clinical trials on the use of CBD and endometriosis, the endocannabinoid system is involved in regulating the pain that accompanies this condition.²⁸ This suggests that CBD could play a role in supporting a healthy pain response in this disorder. In addition, cannabinoid-rich hemp oil reduced body pain and other symptoms in girls who reacted adversely to the human papillomavirus (HPV) vaccine.²⁹ Furthermore, in seven kidney transplant patients, a group of patients who often experience pain, researchers gave the study subjects varying doses of CBD from 50 to 150 mg twice a day for three weeks.³⁰ Two patients experienced complete improvement in pain, four experienced a partial improvement in the first 15 days, and one patient had no change.

How Cannabinoids Like CBD Reduce Pain – Mechanism of Action

CBD and cannabigerol (CBG) both have analgesic effects and their pain-relieving abilities may also be due to their ability to support a healthy inflammatory response.³¹

Endocannabinoids produced in the body can also block pain-inducing mechanisms in the gastrointestinal tract, the spine, and other areas of the body.³² This may lead to reducing pain in IBS, as well as from headaches, muscle spasms, and fibromyalgia.³² Deficiencies in endocannabinoids may lead to pain,³² and replenishing levels of these endocannabinoids through supplementation with CBD and other cannabinoids may help.

CBD’s potential ability to reduce pain may involve a type of receptor known as type 1 vanilloid receptor (TRPV₁). Researchers have found the TRPV₁ receptor in neurons that help regulate pain.³³ I went into more detail about TRPV₁ in Chapter one of this book.

CBD works in a way that’s different from substances like non-steroidal anti-inflammatory drugs (NSAIDS).  Unlike those drugs, it doesn’t inhibit the COX-1 enzymes.^34,35 Blocking this enzyme is linked to gastrointestinal ulcers and bleeding. In addition, CBD doesn’t inhibit COX-2.^34,35 Inhibition of this enzyme is associated with heart attacks and strokes.

The bottom line? Clinical experience, preclinical studies in animals, and some human studies show that CBD may support a healthy pain response. It’s non-addictive and isn’t psychoactive like THC. Therefore, I find it to be extremely clinically useful when dealing with my many patients who are suffering from pain.

1. Casey SL, Vaughan CW. Plant-Based Cannabinoids for the Treatment of Chronic Neuropathic Pain. Medicines (Basel). 2018;5(3).
2. Miller RJ, Miller RE. Is cannabis an effective treatment for joint pain? Clin Exp Rheumatol. 2017;35 Suppl 107(5):59-67.
3. McCarberg BH. Cannabinoids:their role in pain and palliation. J Pain Palliat Care Pharmacother. 2007;21(3):19-28.
4. Capano A, Weaver R, Burkman E. Evaluation of the effects of CBD hemp extract on opioid use and quality of life indicators in chronic pain patients: a prospective cohort study. Postgrad Med. 2020;132(1):56-61.
5. VanDolah HJ, Bauer BA, Mauck KF. Clinicians’ Guide to Cannabidiol and Hemp Oils. Mayo Clin Proc. 2019;94(9):1840-1851.
6. Dunn SL, Wilkinson JM, Crawford A, Bunning RAD, Le Maitre CL. Expression of Cannabinoid Receptors in Human Osteoarthritic Cartilage: Implications for Future Therapies. Cannabis Cannabinoid Res. 2016;1(1):3-15.
7. O’Brien M, McDougall JJ. Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids. Curr Opin Pharmacol. 2018;40:104-109.
8. Philpott HT, OʼBrien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. 2017;158(12):2442-2451.
9. Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000;97(17):9561-9566.
10. Harris HM, Sufka KJ, Gul W, ElSohly MA. Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice. Planta Med. 2016;82(13):1169-1172.
11. Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007;556(1-3):75-83.
12. Toth CC, Jedrzejewski NM, Ellis CL, Frey WH, 2nd. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol Pain. 2010;6:16.
13. Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014;47(1):166-173.
14. Hoggart B, Ratcliffe S, Ehler E, et al. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain. J Neurol. 2015;262(1):27-40.
15. Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. 2004;112(3):299-306.
16. Gran JT. The epidemiology of chronic generalized musculoskeletal pain. Best Pract Res Clin Rheumatol. 2003;17(4):547-561.
17. Stensson N, Ghafouri B, Ghafouri N, Gerdle B. High levels of endogenous lipid mediators (N-acylethanolamines) in women with chronic widespread pain during acute tissue trauma. Mol Pain. 2016;12.
18. Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016;1(1):154-165.
19. Wong H, Cairns BE. Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain. Arch Oral Biol. 2019;104:33-39.
20. Hugger A, Schindler HJ, Türp JC, Hugger S. [Pharmacological therapy of temporomandibular joint pain]. Z Evid Fortbild Qual Gesundhwes. 2013;107(4-5):302-308.
21. Del Giorno R, Skaper S, Paladini A, Varrassi G, Coaccioli S. Palmitoylethanolamide in Fibromyalgia: Results from Prospective and Retrospective Observational Studies. Pain Ther. 2015;4(2):169-178.
22. Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010;126(1):21-38.
23. Storr MA, Sharkey KA. The endocannabinoid system and gut-brain signalling. Curr Opin Pharmacol. 2007;7(6):575-582.
24. Marco EM, Echeverry-Alzate V, López-Moreno JA, Giné E, Peñasco S, Viveros MP. Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain. Behav Pharmacol. 2014;25(5-6):547-556.
25. Morena M, Patel S, Bains JS, Hill MN. Neurobiological Interactions Between Stress and the Endocannabinoid System. 2016;41(1):80-102.
26. Viudez-Martínez A, García-Gutiérrez MS, Manzanares J. Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress. J Psychopharmacol. 2018;32(12):1379-1384.
27. Baron EP. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science. 2018;58(7):1139-1186.
28. Sanchez AM, Cioffi R, Viganò P, et al. Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis. Reprod Sci. 2016;23(8):1071-1079.
29. Palmieri B, Laurino C, Vadalà M. Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination. Isr Med Assoc J. 2017;19(2):79-84.
30. Cuñetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplant Proc. 2018;50(2):461-464.
31. Williamson EM, Evans FJ. Cannabinoids in clinical practice. 2000;60(6):1303-1314.
32. Smith SC, Wagner MS. Clinical endocannabinoid deficiency (CECD) revisited: can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2014;35(3):198-201.
33. O’Hearn S, Diaz P, Wan BA, et al. Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies. Ann Palliat Med. 2017;6(Suppl 2):S209-s214.
34. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245-259.
35. Burstein SH, Zurier RB. Cannabinoids, endocannabinoids, and related analogs in inflammation. Aaps j. 2009;11(1):109-119.