Full Report

Arthritis: Osteoarthritis

The Disease

OA is a degenerative joint disease, characterized by damage to the cartilages in joints, inflammation of the joints, thickening of the bone around the joint, and bone spurs.  These changes result in chronic pain, joint instability, stiffness, and joint space narrowing.  The cartilage between the bones absorbs and dissipates the load of our weight in our lower extremities or the shear force in our joints of our upper extremities when they are abused by repetitive grasping and pushing.  The cartilage in the joints gradually thins and ultimately results in bone sliding against bone.  OA is the most common form of arthritis, a leading cause of impaired mobility among the elderly and the most common cause for total hip and knee replacements.  Aging, joint trauma, obesity, and genetic predisposition are some of the risk factors for developing OA.

Research

With repetitive shear and loading forces to the cartilage, the normally quiet chondrocytes become “active” and start multiplying and producing more matrix.1  This increase in activity is associated with an increase need for energy which is supplied by the mitochondria inside the cell as they use food and oxygen to produce the energy needed.  With age, the mitochondria in the chondrocytes begin to dysfunction causing them to not utilize oxygen fully which results in the accumulation of Reactive Oxygen Species (ROS) inside the cell, called oxidative stress.2,3  This oxidative stress causes the cell to start producing MMPs (see above) which destroy the collage matrix.4  In addition, the chondrocytes start releasing inflammatory mediators which cause inflammation in and around the joint which, in turn, aggravates the chondrocytes more, resulting in a vicious cycle of progressive destruction of the joint.1  When the homeostasis of production and destruction of collagen is upset and destruction exceeds production, this marks the progression from reversible to  irreversible cartilage degradation and, ultimately, total destruction.3,4,5,6  Just when the process becomes irreversible is yet to be determined.  However, when compounds that reverse oxidative stress are added to damaged chondrocytes, the levels of MMPs decrease dramatically.4

Because CBD has well known anti-inflammatory activity, reduces oxidative stress, and has potential pain-relieving capabilities, it is well positioned to be possibly very effective in the treatment of OA.  In a veterinary clinic, dogs with OA treated with oral CBD at a dose of 2mg/kg twice daily showed a significant decrease in pain and a significant increase in activity.7  The only change in blood chemistry was a slight increase in the amount of alkaline phosphatase, which may have been due to remodeling of the bone in the affected joint secondary to improvement of the joint.  Other studies have shown that transdermal CBD (CBD lotion placed on the joint) significantly reduced swelling, spontaneous pain, immune cell infiltration, joint redness, and synovial thickening.8,9  In the one study, animals in endstage OA (thought to have irreversible damage) had significant improvement in their ability to support weight bearing that was dose dependent.9 

Bottom Line

Research has shown that CBD has the capabilities to alleviate the pain, inflammation, and swelling in OA.  In addition, it has the potential to reverse the cycle of cartilage destruction and joint degradation.  Multiple anecdotal reports are available on the internet, some with pictures, that suggest that CBD may be extremely helpful in the treatment of OA.  However, further studies are needed to determine the potential CBD may have.  At this time, the FDA has not approved CBD for the treatment of OA.

 

References:
  1. Houard X, etal. Homeostatic mechanisms in articular cartilage and role of inflammation in osteroarthritis.  Curr Rheumatol Rep 2013;15(11):375
  2. Bolduc JA, etal. Reactive Oxygen Species, Aging and Articular Cartilage Homeostasis. Free Radic Biol Med. 2018; Aug 31. pii: S0891-5849(18)31500-4.
  3. Portal-Nunez S, etal. Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis.  Biochem Pharmacol. 2016;108:1-10.
  4. Reed KN, etal. The role of mitochondrial reactive oxygen species in cartilage matrix destruction.  Mol Cell Biochem. 2014;397(1-2): 195-201.
  5. Collins, Y, etal. Mitochondrial redox signaling at a glance. J Cell Sci 2012;125:801-6.
  6. Minocherhomju S, etal. Mitochondrial regulation of epigenetics and its role in human diseases.  Epigenetics 2012;7(4):326-34.
  7. Gambel L, etal. Pharmacokinetics, safety, and clinical efficacy of cannabidiol treatment in osteoarthritic dogs.  Frontiers Vet Sci 2018;5:165.
  8. Hammell C, etal. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis.  Eur J Pain 2016;20(6):936-48.
  9. Philpott H, etal. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.  Pain 2017;158:2442-2451.

 

 

 

Arthritis: Rheumatoid Arthritis

The Disease

Rheumatoid arthritis is the most common form of chronic inflammatory arthritis affecting about 1% of the world’s population and being 3 times more common in men than in women.  It is an autoimmune disease, in which the immune system attacks the synovial membrane causing it to swell and become hyperplastic (having more cells).  This causes the symptoms of pain, swelling, redness, and stiffness of the joints.  The smaller joints tend to be most affected, especially in the hands and wrists and the disease is bilateral, affecting both sides of the body.  Most people think of RA as involving only the joints, however, RA is a systemic disease and affects the homeostasis of the whole body.  Systemic inflammation and autoimmunity precede the development of the arthritis in RA, sometimes appearing years prior to the onset of symptoms.   RA is affected by genetics (certain HLA gene types are 5 times more likely to develop RA than those without those genes), infections (RA will often develop after an infection in people susceptible to the disease), immune system (Rheumatoid factor, an auto-antibody, is found in 80% of RA patients and people with a different autoimmune disease are 5 times more likely to develop RA), hormones (women 3 times more likely to develop RA than men), stress (stress is higher in RA patients), and microbiome (the gut bacteria are abnormal in patients with RA and tend to normalize with therapy).1,2  In addition, RA patients have multiple comorbidities including: depression, diabetes, heart disease, obesity, insomnia, eye disorders, hearing loss, kidney disease, skin disease, and mouth conditions.  The loss of homeostasis in so many bodily systems and the pain associated with RA makes CBD attractive as a possible therapy for RA because if its ability to restore homeostasis and its pain relief.

 

Research

In RA, inflammation occurs and the synovium becomes thicker and full of cells and is called pannus.  Pannus has unique characteristics, and, like a cancer, it can invade the cartilage and bone.  Over time, this invasion causes the deformation of the joints commonly seen in RA.  The hyperplastic cells in the synovium are called fibroblast-like synoviocytes (FLS) which cause the formation of the synovial pannus and the cancer-like invasiveness seen in the disease.3   The number of vanilloid receptors (TRPV2) on the synoviocytes in RA in increased, and is very high when invasion of the joint by the pannus is present.3  When an agonist (a compound that will stimulate a receptor) binds to TRPV2, the invasiveness of FLS decreases, inflammatory cell inflammation decreases, joint damage is reversed, and the amount of pain decreases.3  Because CBD is a TRPV2 agonist, it is seen to be a prime candidate for treating RA.4   In addition, the inflammation within the joint causes the chondrocytes to release MMPs (enzymes that break down the proteins in collagen) which cause destruction of the collagen matrix and ultimately the collagen itself.   When inflammation decreases the MMP’s decrease and the joint improves.5

Although RA is a systemic disease, most modern therapy is directed to relieving the pain and stiffness in the joints.  On the systemic inflammation and autoimmunity, CBD has the potential to reduce inflammation and its effect on the immune system is well known.6  Therefore, CBD has the potential to improve the pain (see Pain: inflammatory pain), the joint abnormalities, and the systemic features of RA.  In a study of RA patients, Savitex (a drug containing both THC and CBD) was found to significantly improve overall pain, pain on movement, pain at rest, quality of sleep, and disease activity.7

Bottom Line

The basic science and limited human studies along with numerous anecdotal reports of patients with RA suggest the CBD can be very helpful in treating the symptoms and reversing the damage of RA.  However, at this time the FDA has not approved CBD for the treatment of RA.

 

 

References

  1. Arthritis Foundation, Rheumatoid Arthritis, Viewed 9/7/2018, 1355 Peachtree St NE, Suite 600
    Atlanta,GA 30309. < https://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/>.
  2. Zhang X, etal. The oral and gut mmicrobiomes are perturbed in rheumatoid arthritis and partl normalized after treatment. Nature Medicine. 2015;21:895-905.
  3. Laragione T, etal. The cation channel TRPV2 is a new suppressor of arthritis severity, joint damage and synovial fibroblast invasion.  Clin Immunol 2015;158(2):183-92.
  4. Qin N, etal TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 2008;28(24):6231-8.
  5. Reed KN, etal. The role of mitochondrial reactive oxygen species in cartilage matrix destruction.  Mol Cell Biochem. 2014;397(1-2): 195-201.
  6. Rieder S, etal. Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.  Immunobiology 2010;215(8):598-605.
  7. Blake DR, etal. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain cause by rheumatoid arthritis. Rheumatology (Oxford). 2006;45(1):50-2.

Arthritis

The Disease

Arthritis is joint inflammation characterized by swelling, pain, stiffness and decreased range of motion.  In almost all arthridites, the cartilage in the joint ends up being damaged and ultimately destroyed giving rise to the symptoms associated with the disease.  There are over 100 different known causes of arthritis but most research with CBD has been done in 2 of them: osteoarthritis (OA) and rheumatoid arthritis (RA).  Osteoarthritis, also known as degenerative arthritis, is the most common arthridites and associated with aging, injury, and other issues, while rheumatoid arthritis is considered an inflammatory and/or autoimmune disease. 

Research

Although the causes and the cellular changes inside the joints are different in these two diseases, ultimately, in both diseases, the cartilage self-destructs by releasing enzymes (proteases) that degrade the building blocks of cartilage (collagens and proteoglycans).1  Collagen is a matrix of collagens, proteoglycans, and other proteins with some cells living in the matrix that are called chondrocytes.  The chondrocytes control the production of new matrix the cartilage is gradually worn away from movement, etc. and, when the joint is healthy, new matrix is produced at a rate to perfectly compensate for that which is lost.2  This homeostasis is interrupted when the matrix is lost faster than it can be replaced (excessive wear), the chondrocytes slow down their production of matrix secondary to oxidative stress, or the environment becomes hostile (inflammation or autoimmune disease).  In all of these cases, the end stage is the production of enzymes called metalloproteinases (MMPs) which destroy the proteins in the collagen matrix.1  Once the matrix starts being destroyed, it enters a self-sustaining cycle of increasing inflammation and oxidative stress that results in the collagen ultimately destroying itself.

Interesting, the joints of both humans and animals have functional endocannabinoid systems (ECS).  The ECS help maintain the homeostasis of the joint by: 1) maintaining healthy chondrocytes, 2) influencing the production of collagen matrix, and 3) maintaining the health of the other tissues in the joint including the bone, synovium (membrane that lines the joint) and the synovial fluid (the fluid contained in the joint by the synovium).3,4  CBD, through its anti-inflammatory and anti-oxidant effects that work, not like most anti-inflammatory drugs, but by changing the cell signaling events that underlie the self-sustaining cycle of inflammation and oxidative stress has great promise for treating arthritis.  In addition, the anti-nociceptic and anti-inflammatory pain effects of CBD has potential to block the pain associated with arthritis.5  Therefore, not only does CBD has the theoretical potential to alleviate the symptoms of these arthridites, it has the potential to reverse the disease itself if the cartilage is not to severely damaged.6,7  It seems that the public is aware of these potentials of CBD, such that, chronic paint of arthritis is the most common reason for people to take CBD.8,9  In a recent review, the authors concluded that because of the preclinical and human data that do exist, the use of cannabis should be taken seriously as a potential treatment of joint pain.9

Bottom Line

CBD has great potential to alleviate the pain and symptoms of arthritis, in particular osteoarthritis and autoimmune arthritis.  However, at this time the FDA has not approved CBD for the treatment of any type of arthritis.

(Note: See Arthritis: Rheumatoid Arthritis and/or Arthritis: Osteoarthritis for more information on these individual conditions.)

References

  1. Goldring M, Marcu K. Cartilage homeostasis in health and rheumatic diseases.  Arthritis Res Therapy 2009;11:224.
  2. Bolduc JA, etal. Reactive Oxygen Species, Aging and Articular Cartilage Homeostasis. Free Radic Biol Med. 2018; Aug 31. pii: S0891-5849(18)31500-4.
  3. Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritis knees. Arthritis Rheum 2008;58:145–53.
  4. Richardson D, etal. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2008;10:R43.
  5. Booz G. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.  Free Radic Biol Med 2011;5(5):1054-61.
  6. Laragione T, etal. The cation channel TRPV2 is a new suppressor of arthritis severity, joint damage and synovial fibroblast invasion.  Clin Immunol 2015;158(2):183-92.
  7. Reed KN, etal. The role of mitochondrial reactive oxygen species in cartilage matrix destruction.  Mol Cell Biochem. 2014;397(1-2): 195-201.
  8. Corroon J, Phillips J. A cross-sectional study of cannabidiol users.  Cannabis and Canna Res 2018;3(1):152-161.
  9. Miller RJ and Miller RE. Is cannabis an effective treatment for joint pain? Clin Exp Rheumatol.2017 Sep-Oct;35 Suppl 107(5):59-67.

 

Pain: Neuropathic Pain

The Disease

Neuropathic pain is caused by damage or disease of the sensory nervous system.   There are two different types of neuropathic pain, pain caused by direct damage to a nerve and pain that occurs from normally non-painful stimuli, called allodynia.  Nerve damage pain may also be divided into peripheral and central, where central involves damage to the brain and/or spinal cord while peripheral involves damage to nerves outside the brain or spinal cord.  This latter division is sometimes confusing because lots of conditions cause damage to and/or affect both peripheral and spinal cord nerves and/or they may involve both neuropathic and nociceptive pain and they may also include some aspects of allodynia. (Note: Nociceptic pain is pain caused by stimulation of pain receptors on nerve and is discussed in detail under Pain: Nocioceptic Pain.)   Examples of central neuropathic pain include: spinal cord injury, multiple sclerosis, stroke, etc.  Peripheral pain examples include:  herpes zoster, toxins, radiation injury, physical trauma, etc.  Combined central and peripheral neuropathic pain examples include: diabetes, chemotherapy-induced peripheral pain, some immune disorders, etc.  (Note: Chemotherapy-induced pain and Cancer pain are discussed in detail under Pain: Cancer Related Pain.) 

Allodynia can be divided into 3 types, 1) mechanical: triggered by touching or stroking the skin, 2) thermal: can be triggered by hot or cold but is associated with normally mild changes in skin temperature, and 3) movement allodynia: triggered by normal movements of joints or muscles.  The latter division is often associated with nociceptive pain with the brain learning that if a certain movement occurs (or continues to occur) pain will result.  An example is a sprained ankle.  The first time the abnormal movement occurs, the movement does not cause pain but the damage to the ligaments simulate the pain receptors on the “normal” peripheral nerves and the person feels “real” pain from the damage (nocioceptic pain).  The next time that same movement starts to occur, the central nervous system senses the movement and the person experiences “pain” even before the pain receptors are stimulated and damage has occurred.  This happens because the body is trying to protect itself from damage before the damage occurs.  Over time, this learned response may cause even normal movements to cause perceived pain even though no damage or disease is affecting the nerves.

Opiates are often used in neuropathic pain but increasing doses are often required over time to maintain some degree of pain control.  The side effects (mental dysfunction, addiction, etc.), workplace drug testing, and lack of effective pain control limit the effectiveness of narcotic pain treatment for neuropathic pain.  Antidepressants, anti-epileptic drugs, electro-stimulation, and other treatments have been used with varying degrees of success, however, side-effects often result in discontinuation of therapy.

In summary, the neuropathic pain is often associated with other types of pain especially in the beginning of the course of the disease process but ultimately nerve damage, disease, or disfunction occurs.  Neuropathic pain is often very difficult to treat with modern medications and successful outcomes are rare.

Research Findings  

Chronic pain causes changes in the endocannabinoid system in the spinal cord that can result in allodynia.1,2  Some of these changes can be reversed by phytocannabinoids and several reviews of cannabinoid use in neuropathic pain have concluded that cannabinoids are useful in decreasing both pain caused by damage to central and peripheral nerves and in patients with allodynia, especially in those who are not responding to usual medical treatment.3-5 Studies in animals have shown that CBD is effective in reducing neuropathic pain but the pain relief is enhanced when combined with low amounts of THC.6,7 THC is also effective in reducing neuropathic pain, but the amounts required prohibit its use because of side effects.7  Savitex (an FDA approved combination of 50% THC and 50% CBD) and a synthetic cannabinoid (Naloxone) produce some pain relief in neuropathic pain patients but their side effects far outweigh their advantages.8,9  Numerous studies in humans with pain that is refractory to modern medicines have shown that cannabinoids are effective in decreasing pain in these patients.10,11 In patients with allodynia, cannabinoids have been effective in not only lowering pain but in improving other life functions including: sleep and perceived quality of their condition.12  In an animal model, diabetic neuropathic pain is prevented and reversed with CBD, probably due to its effect in preventing the release of inflammation cytokines in the spinal cord.13,14    The mechanisms of action of CBD in relieving neuropathic pain seem to be multiple including: decreasing inflammatory cytokines released by damaged neurons, decreasing the repetitive firing of sensory neurons in the spinal cord, stimulating morphine-like receptors in the CNS, changing one’s perception of pain in the brain, etc. (Note: see Pain for more information). 15,16

 

Bottom Line

THC/CBD treatment seems to decrease pain in many types of neuropathic pain but the amount required often results in adverse THC-induced side effects.  CBD and CBD-enriched hemp oil have the potential to decrease many of the mechanisms associated with neuropathic pain, but no studies using CBD-enriched hemp oil (without high doses of THC) in humans have been done yet.  The FDA has not yet approved CBD or CBD-enriched hemp oil for use in humans for pain.  

 

                References

  1. Sagar D, etal. Dynamic changes to the endocannabinoid system in models of chronic pain. Phil Trans R Soc B 2012; 367;3300-11.
  2. Starowicz K, Przewlacka B. Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system. Phil Trans R Soc B 2012; 367:3286-99.
  3. Langford RM, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.  J Neurol. 2013 Apr;260(4):984-97
  4. Aviram J, Samuelly-Leichtag G. Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician. 2017 Sep;20(6):E755-E796.
  5. Boychuk DG, etal. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14.
  6. Casey SL, etal. Cannabis constituent synergy in a mouse neuropathic pain model. Pain 2017; 158(12):2452-60.
  7. Casey S, Vaughan C. Plant-Based Cannabinoids for the treatment of chronic neuropathic pain. Medicines 2018; 5:67.
  8. Mucke M, etal. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2018 Mar.
  9. Walitt B, et al. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7
  10. Hoggart B, 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 Jan;262(1):27-40.
  11. Kahan M, etal. Prescribing smoked cannabis for chronic noncancer pain. Can Fam Phys 2014; 60:1083-90.
  12. Deshpande A, etal. Efficacy and adverse effects of medical marijuana for the chronic noncancer pain. Can Fam Phys 2015; 61:e372-81.
  13. et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment Eur J Pain. 2014 Aug;18(7):999-1012
  14. Toth C, etal. Cannabinoid-medicated modulation of neuropathic pain and microglial accumulation in a murine type I diabetic peripheral neuropathic pain.  Molecular Pain 2010; 6:16.
  15. Wang D, et al. Activated microglia in the spinal cord underlies diabetic neuropathic pain. Eur J Pharmacol. 2014 Apr 5;728:59-66.
  16. Skaper S, Di Marzo V. Endocannabinoids in nervous system health and disease: the big picture in a nutshell.  Phil Trans R Soc B 2012;367:3193-3200.

 

 

 

Pain

The Disease

Pain is not a disease but a symptom felt by individuals who are experiencing something uncomfortable, either real or perceived.  The uncomfortableness may be due to a multiplicity of factors including:

  1. Stimulation of nerve fibers in the periphery due to injury, i.e., cuts, incisions, tears, etc. (Nocioceptic Pain)
  2. Damage to nerve fibers in the periphery, spinal cord, or brain. (Neuropathic Pain)
  3. Release of chemicals from inflammation that stimulate nerves as pain (Inflammatory Pain)
  4. The brain’s learned response that certain movements, stimulations, or situations lead to pain so one feels pain before damage is done. (A type of Neuropathic Pain called allodynia)
  5. The feeling of pain in an amputated limb. (A type of Neuropathic Pain called Phantom Pain)
  6. Pain caused from emotional, mental, or behavioral factors, i.e., headache, stomach ache, etc. (Psychogenic Pain)
  7. Pain secondary to cancer and or cancer therapy.
  8. Chronic Pain often involves a combination of several of the above.

 

Pain can be classified many ways and the above list should just be considered an example. In all cases of pain, the concept of perception is foremost.  Therefore, the feeling of pain is not just the stimulation of nerves but the brain’s perception of the stimulation.  This is so important because in stressful situations when someone is physically hurt, pain may not be perceived until the stress of the situation is resolved, i.e., injuries in sports or war.  In non-stressful situations, the amount of injury to produce the feeling of pain is often very similar from one individual to another, however, the perception of the intensity of the pain and the person’s ability to function with the pain can vary greatly.  CBD-enriched hemp oil has been shown to effect many of the physiologic and psychologic changes that occur with different types of pain.  With some types of pain in certain individuals, CBD-enriched hemp oil is adequate to control the pain perception and with other types of pain or individuals, it may only be helpful and require other medications to control the perception.  The following research explanations are generalized descriptions.  For more detailed analysis of the research on any particular time of pain, go to the disease list and find that particular subject, i.e, Pain-Neurologic, or Pain-Inflammatory, etc.

 

Research

Pain is a complex experience produced by a unique combination of nerve cells that integrates the cognitive-evaluative, sensory-discriminative, and motivational-affective components that are located in different sections of the brain.1 Clinically, the sensation of pain can be treated by reducing the sensory input as well as by manipulating affective-motivational and cognitive factors as well as blocking the local causes of the pain.1 If the anterior cingulate cortex (ACC), a specific area of the brain associated with pain processing, is disconnected from the rest of the brain, the patient will still be able to localize the pain, but the pain does not bother the patient.1 CBD has been shown in both animals and in humans (via MRI studies) to effectively do the same thing.1  Other studies have found that CBD works in the brain in a manner similar to that of morphine.2,3 In addition, CBD changes the way our brain reacts to expected pain by changing how we remember painful events and reducing the anxiety associated with learned pain.4,5  This data suggests that CBD is useful in pain management by disassociating the perception of pain from the stimulus of pain.

Disassociation is not the only mechanism by which CBD assists with pain management.  CBD blocks nocioceptive pain in rodents but not so much in humans, however, it does change the perception of nocioceptive pain in humans.6  CBD is anti-inflammatory which, as the inflammatory process lessens, the pain lessens.7-9  Diabetic neuropathic pain is prevented and reversed with CBD, probably due to its effect in preventing the release of inflammation cytokines in the spinal cord.10,11  Cannabinoids have been found to significantly reduce neuropathic pain and help with the pain-related morbidities of sleep and quality of their symptoms.12-14  Cannabinoids have been shown to be helpful adjuvants in patients with chronic pain and with cancer-associated pain, especially in those patients who are not controlled on usual pain medications or are having to increase their pain medications repetitively.15-19 However, when using products with significant amounts of THC, their effectiveness in reducing pain is often outweighed by their adverse side effects.16,20,21 

Bottom Line

Cannabinoids, including CBD, are helpful in some types of pain but not so helpful in others.  The side effects of THC limit the effectiveness in pain control of cannabinoids containing significant amounts of this compound.  Most studies of pain have been performed using cannabinoids with significant amounts of THC.  However, the limited studies of CBD and CBD-enriched hemp oil in pain have yielded encouraging results in both pain perception and the elimination of the stimuli of pain.   However, at this time the FDA has not approved CBD or CBD enriched hemp oil for the management of pain.

 

 

References:

  1. Fuchs P, etal. The anterior cingulate cortex and pain processing. Frontiers Integrative Neuroscience 2014; 8:35.
  2. Laun AS, etal. GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol. Acta Pharmacol Sin. 2018 Jun 25.
  3. Ruiz-Medina J, etal. GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception. 2011 Jul-Aug;61(1-2):43-50.
  4. Bitencourt R, Takahashi R. Cannabidiol as a therapeutic alternative for post-traumatic stress disorder: From bench research to confirmation in human trials. Frontiers Neuroscience 2018; 12:502
  5. Jurkus R, etal. Cannabidiol regulation of learned fear: Implication for treating anxiety-related disorders. Frontiers Pharm 2016;7:454.
  6. Lötsch J, etal. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain. 2018 Mar;22(3):471-484.
  7. Brunstein S. Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.01.059
  8. Xiong W, etal. Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha-3 glycine receptors. Exp. Med. Vol. 209 No. 6 1121-1134
  9. Costa B, etal. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol; 2007; 5:556(1-3):75-83
  10. Toth C, etal. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Molecular Pain 2010; 6:16.
  11. Wang D, et al. Activated microglia in the spinal cord underlies diabetic neuropathic pain. Eur J Pharmacol. 2014 Apr 5;728:59-66.
  12. Lynch M, Campbell R. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharm 2011;72(5):735-44.
  13. Meng H, etal. Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis. Anesth Analg. 2017 Nov;125(5):1638-1652.
  14. Serpell M. et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment Eur J Pain. 2014 Aug;18(7):999-1012
  15. Hoggart B, 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 Jan;262(1):27-40.
  16. Kazantzis NP, etal. Opioid and cannabinoid synergy in a mouse neuropathic pain model. Br J Pharmacol 2016;173(16):2521-31.
  17. Darkovska-Serafimovska M, etal. Pharmacotherapeutic considerations for use of cannabinoids to relieve pain in patients with malignant diseases. J Pain Res 2018;11:837-47.
  18. Fallon M, etal. Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo—controlled phase 3 studies. Br. J Pain 2017;11(3):119-33.
  19. Boychuk DG, etal. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache 2015;29(1);7-14.
  20. Casey S, Vaughan C. Plant-based cannabinoids for he treatment of chronic neuropathic pain. Medicines 2018;5;67.
  21. Kahan M, etal. Prescribing smoked cannabis for chronic noncancer pain. Can Fam Physician 2014;60:1083-90.

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