A Balanced Approach for Cannabidiol Use in Chronic Pain
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Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life. CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations. In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.
Cannabis and its components are being widely used for chronic pain, especially given the multifaceted and persistent nature of chronic pain in many conditions (Kalant, 2001). Cannabidiol (CBD), one of the major phytocannabinoids, has gained significant attraction because it is devoid of the psychoactive effects associated with tetrahydrocannabinol (THC), another major constituent of cannabis (Leweke et al., 2012). With the recent rescheduling (Schedule V) of CBD as Epidiolex for the treatment of Dravet and Lennox-Gastaut syndromes there has been a major shift in the view of these ancient molecules for their medicinal potential (Laux et al., 2019). Preclinical and clinical studies have indicated a potential benefit of CBD use in chronic pain associated with multiple conditions (Wade et al., 2003). However, increasing access to cannabis derived products especially CBD partly because of their approval for recreational and medicinal use in the United States poses risks with inadvertant side-effects from overuse, contamination with adulterants in preparation or harsh chemicals in the plant cultivation, and its teratogenicity in the offspring of users (Bonn-Miller et al., 2017; Young-Wolff et al., 2017; Rubin, 2019). In this mini-review we will evaluate literature discussing CBD use in treating intractable pain and the potential hazards of its overuse and/or misuse (see Figure 1 ).
Pros and cons of cannabidiol use in chronic pain.
Chronic Pain In The United States
Chronic pain affects between 50 and 116 million American adults, a staggering number that surpasses those affected by heart disease, cancer, and diabetes combined (Committee on Advancing Pain Research Care and Education, 2011; Nahin, 2015; NIH, 2020). In addition, these reports conclude that chronic pain costs between $560 and $635 billion annually in both medical expenses and lost productivity. Although there have been some recent therapeutic advances, many patients with chronic pain develop tolerance to conventional medical treatments or suffer adverse effects from widely used prescription medications, such as non-steroidal anti-inflammatory agents or opiates, that have high addictive potential (Labianca et al., 2012). As early as 2003, formulations containing CBD have been used in the clinic to study its efficacy in reducing pain when traditional treatment options have failed.
Reliability and Safety of Cannabidiol Labeled Products
Human use of Cannabis sativa L. for rituals and medicine dates back millennia, and it has made recent advances in treatment of varied conditions (Kalant, 2001; Whiting et al., 2015; Aviram and Samuelly-Leichtag, 2017; Ren et al., 2019). CBD is the major non-psychoactive constituent of cannabis and is also found in hemp, a subspecies of Cannabis sativa that does not produce psychoactive compounds in significant amounts (Pertwee, 2006; Hilderbrand, 2018). With the exception of Epidiolex, a Schedule V preparation, which is a pharmaceutical CBD extract from the plant, cannabis-derived CBD still remains a Schedule I substance according to the United States (US) Drug Enforcement Administration (Drug Enforcement Administration, 2018). However, the US Hemp Farming Act of 2018 legalized the cultivation and refinement of hemp and its constituents, thus beginning a trend of mass marketing for CBD products both legal and illegal (Hemp Production and the 2018 Farm Bill, 2019; Mead, 2019). In states where cannabis has been approved for recreational and/or medical use, there are efforts to equip dispensary staff with scientific knowledge to make evidence-based recommendations, but these efforts are limited and often overshadowed by anecdotal understanding of CBD and other cannabinoids (Haug et al., 2016; Piermarini and Viswanath, 2019). Of major concern, CBD-labeled products have flooded the markets, including, but not limited to, inhalants, bath salts, cookies, ointments, and liquids, for human use. Many forms tout medicinal value for claims that have not been scientifically evaluated. Reports indicate that the cannabinoid content in products purchased online were only accurate in 26 of the 84 products tested (Bonn-Miller et al., 2017). In a more recent report, safety of using unregulated CBD products has been questioned because, of 20 popular CBD products tested by CannaSafe, a cannabis-testing company in California, only 3 contained the contents claimed on the labels (Rubin, 2019). Of these, 2 products had no CBD, and about half of the CBD products had less than 20% of the CBD content claimed. Additionally, toxic gases and solvents were reported in some of these CBD products. Thus, these unregulated products labeled CBD may be a serious health hazard. An urgent need is to regulate CBD products after reliable testing to prevent the inadvertent harmful effects of unidentified constituents of products labeled CBD.
Clinical Outcomes for Cannabidiol in Intractable Chronic Pain
Since the early 2000s, clinical trials involving CBD for the treatment of chronic pain have shown effects ranging from placebo-equivalent to highly effective; many of these studies have been well-designed randomized, double-blinded, and placebo-controlled. In a mixed cohort of patients suffering from intractable pain due to multiple sclerosis, spinal cord injury, brachial plexus injury, and limb amputation, CBD treatment significantly reduced pain on a visual analog scale (Wade et al., 2003). However, these studies were often limited by small cohorts, and the varied disease states indicated that the beneficial effects of CBD are context dependent, which was illustrated in a study where treatment did not improve outcomes in patients suffering from Crohn’s disease (Naftali et al., 2014). CBD was also seemingly effective in treatment of chronic pain associated with kidney transplantation and when given topically to patients suffering from peripheral neuropathy of their lower extremities (Cuñetti et al., 2018; Xu et al., 2019). As well, in patients with fibromyalgia, CBD treatment decreased pain by more than 30% in significantly more patients than placebo (Van De Donk et al., 2019). In studies of generalized chronic pain, CBD treatment did not significantly reduce measures of pain, however there was consistent improvement in patient-reported quality of life and quality of sleep (Notcutt et al., 2004; Capano et al., 2020). A New Zealand study on the safety of CBD treatment in 400 non-cancer chronic pain patients indicated its safety for prolonged use, which was accompanied by self-reported improvements in pain and quality of life (Gulbransen et al., 2020).
The majority of clinical studies for the treatment of intractable chronic pain with CBD typically utilized a combination of 1:1 CBD : THC, which was often in the form of the well-tolerated oromucosal spray Sativex (Nabiximols in the US) (Johnson et al., 2013; Sellers et al., 2013). Combination of the two often improved upon the deleterious and psychoactive effects of THC-only administration (Ueberall et al., 2019). The CBD : THC formulations were effective at reducing mean pain scores in chronic pain patients with multiple sclerosis, improved neurophysical measurements in response to noxious stimuli, reduced intractable chronic pain in advanced cancer, and improved refractory/neuropathic pain following failed spinal cord surgery (Rog et al., 2005; Conte et al., 2009; Johnson et al., 2010; Portenoy et al., 2012; Mondello et al., 2018). There is contradictory evidence that CBD : THC treatment does not always relieve chronic pain in patients with brachial plexus avulsion or advanced-cancer, as evidenced by studies in two-independent cohorts, thus indicating the heterogeneity in disease contexts for which cannabinoids may be effective; of note, although pain was not significantly improved, patients in these studies indicated an improved quality of life (Berman et al., 2004; Fallon et al., 2017; Lichtman et al., 2018). There is a demonstrated need to further understand the mode of action of CBD, and these results are promising, but efficacy of treatment must also be evaluated in other disease states that produce chronic pain such as diabetic neuropathy, rheumatic diseases, and sickle cell disease (Fitzcharles et al., 2016).
Mechanistic Insights For Cannabidiol Treatment Of Chronic Pain
Few preclinical studies have been performed to evaluate the mechanism of analgesia for CBD treatment of chronic pain. Currently available studies rely on rodent and in vitro models but suggest molecular pathways that may be used to enhance CBD use in the clinic, or offer alternative approaches for higher efficacy. Evidence strongly supports that prolonged treatment (i.e. > 7 days) with CBD alleviates chronic pain caused by chronic constriction injury of the sciatic nerve in rats and mice in a cannabinoid receptor-independent manner, and treatment is coincident with decreased hepatic cytochrome p450 and intestinal P-glycoprotein that may increase bioavailable circulating CBD (Costa et al., 2007; Comelli et al., 2008; Casey et al., 2017; Abraham et al., 2019). In vitro studies using human embryonic kidney cells reveal that at high doses CBD interacts with and selectively activates α1– and α1ß-glycine receptors, but these results have yet to be confirmed in vivo (Ahrens et al., 2009; Foadi et al., 2010). Alternatively, there is preliminary evidence that CBD may interact with α3-glycine receptors to reduce inflammation and hyperalgesia following simulated neuropathic pain by ligation of the L5 spinal nerve in adult Sprague-Dawley rats (Xiong et al., 2012). CBD also attenuates hyperalgesia in a mouse model of diabetic neuropathy with data suggesting that treatment reduced inflammatory milieu (Toth et al., 2010). Mouse models of pain associated with chemotherapy were simulated by Paclitaxel treatment, in which CBD produced an analgesic and anti-inflammatory effect via interactions with spinal cord 5-HT(1A) receptors (Ward et al., 2014; King et al., 2017). CBD also exerts analgesia in a 5-HT(1A)-dependent manner in streptozotocin-induced diabetic neuropathy in rats (Jesus et al., 2019). Similar to human studies, CBD did not produce complete analgesia in all models of chronic pain; in a cisplatin-induced mouse model of neuropathy, CBD attenuated but did not prevent hyperalgesia (Harris et al., 2016). Mechanical hyperalgesia was improved by CBD treatment following traumatic brain injury in mice, myofascial pain in rats, and 6-hydroxydopamine-induced mouse model of Parkinson’s disease, however these studies require follow-up to inspect potential mechanisms of action (Belardo et al., 2019; Wong and Cairns, 2019; Crivelaro Do Nascimento et al., 2020). The preclinical work being done to disentangle the mechanisms of CBD in providing analgesic support in chronic pain is flourishing, but much remains in the wake of chronic disease and enhancing our understanding of the mechanisms at play.
Public Health Hazards And Teratogenicity Of Cannabis Products
Rising legalization and use of medical and recreational cannabis and CBD products raises significant health concerns with regards to both unregulated sources of these products discussed above as well as the health effects of prolonged usage. A recent multistate outbreak of coagulopathy from synthetic cannabinoids has been traced to the presence of long-acting anticoagulant rodenticides in “fake weed” (Arepally and Ortel, 2019). Furthermore, the US Centers for Disease Control and Prevention has increased awareness of the risks of severe pulmonary disease associated with use of electronic cigarette devices to “vape” tobacco and cannabis (Centers for Disease Control and Prevention, August 23, 2019). The effects of long-term cannabinoid use are especially unclear in pregnant women, in whom potential teratogenic effects could have implications on future generations. Cannabis and CBD use are rising amongst pregnant women. An estimated 4% of pregnant women use cannabis, and in California, which recently legalized cannabis, about 20% in a cohort of 18- to 24-year-old pregnant women reported using cannabis products in retrospective studies (Young-Wolff et al., 2017). These numbers are likely to rise as legalization continues throughout the US, and pharmaceutical strength preparations become available for several conditions, and because of the availability of CBD through stores and online sources (Millar et al., 2019). While several studies have focused on THC during pregnancy, investigation focused on the effects of CBD usage by pregnant women before, during, and/or after pregnancy are rare. Thus, there is an unmet need to examine the potential effects of CBD on embryonic and fetal development and the postnatal health of children exposed to CBD before birth. We will summarize here conclusions from both animal and human studies on some possible effects of CBD prenatally, perinatally, and postnatally.
CBD use during early gestation could pose a risk to critical pre-pregnancy and early pregnancy events. Successful pregnancy depends on reciprocal interactions between a competent embryo and a receptive endometrium in the mother. In early gestation CBD, THC, and cannabinol are thought to inhibit embryo implantation and placenta development by altering endometrial receptivity (Neradugomma et al., 2019). However, this effect has yet to be seen outside transformed human endometrial cell models. Exposure to CBD in chick embryos decreases the viability of the embryo by 50% to 80% dependent on CBD concentration and can delay embryonic development (Gustafsson and Jacobsson, 2019). Similar delays in embryonic development have been reported in zebrafish embryos exposed to CBD albeit without the decrease in viability (Valim Brigante et al., 2018). Teratogenicity of CBD has been reported in mice where prenatal exposure leads to an increase in craniofacial malformations and eye defects (Fish et al., 2019). Interestingly, these teratogenic effects are similar though milder than those observed for alcohol, THC, and the synthetic cannabinoids HU-210 and CP55,940 countering the popular perception that CBD is an unequivocally safe alternative to THC and other cannabis constituents (Fish et al., 2019). In humans, retrospective meta-analysis has determined that in utero exposure to cannabis is associated with a decrease in birth weight and increased need for neonatal intensive care in infants (Gunn et al., 2016). This effect is likely due in part to the effects of CBD as low birth weights in mice offspring have been reported in response to prenatal CBD exposure exclusively (Fish et al., 2019). The observed teratogenic effects of CBD exposure may be due to the compound itself and/or due to CBD working synergistically with other teratogenic compounds perhaps by enhancing permeability of xenobiotics through the human placental barrier thereby increasing fetal exposure (Feinshtein et al., 2013).
Effects on hormonal and reproductive function following maternal exposure to CBD have been reported in male mice. CBD exposed mice had lower testicular weights and lower overall levels of testosterone (Dalterio et al., 1984). These effects are in line with reports of hormonal and reproductive effects due to postnatal exposure to CBD or cannabis in rats and monkeys. Chronic doses of THC or CBD in rat suppress hepatic testosterone oxidation by selective inhibition of male-specific cytochrome p450 in the adult male rat (Narimatsu et al., 1988). Chronic doses of CBD in rat also cause a significant reduction in testosterone formation and a decrease in testicular enzyme activity (List et al., 1977). In both rhesus monkeys and rats, gonadal function is altered due to exposure to THC or CBD which leads to hormonal imbalance including a decrease in testosterone in male rats and an increase in follicle-stimulating hormone in male monkeys (Rosenkrantz and Esber, 1980). Together, these data suggest that CBD may influence spermatogenesis and libido in males.
Maternal exposure to CBD is also likely to cause neurochemical changes in the brain of the offspring. The α1-adrenergic and D2-dopaminergic receptors in the cerebral cortex and striatum of rats exposed prenatally to either CBD or THC exhibited smaller binding affinities for their respective ligands and hypothalamic dopamine levels in mice have been observed to be greatly depleted in CBD-exposed males as well (Dalterio et al., 1984; Walters and Carr, 1988). Overall, these studies suggest that prenatal exposure to CBD is likely to alter the production of testosterone, the function of the male gonads, and the receptor ligand interactions in the brain of offsprings.
Rising prevalence of the non-psychoactive cannabinoid CBD presents an opportunity for the treatment of intractable chronic pain for which primary treatments are insufficient or not possible. As depicted by the studies reviewed herein, the use of CBD is context-specific, and it should not be used indiscriminately (see Table 1 ). Preliminary mechanistic studies indicate conservation of function via modulation of hepatic cytochrome p450 leading to increased bioavailability of endogenous mediators of pain (i.e. serotonin) and exogenous analgesics (i.e. THC). Therefore, it is important to continue studies into the conditions for which CBD may be effective as a treatment via novel actionable targets. Simultaneously, the growing access to unregulated CBD products, which may be adulterated with potentially toxic compounds, requires regulation and education about CBD for its potential benefits and/or adverse effects in health and disease. This is especially the case in pregnant women, which raises the highest possible risk for the developing fetus and future offsprings. Unfortunately, efforts to discuss the dangers of CBD use have been severely lacking and require immediate attention to prevent the irreparable harm to the masses from the tsunami of CBD products.
Consequence of Cannabidiol treatment in preclinical and clinical settings.
( 1 Sigma)
|HEK cells||Activation of α1 and α1ß -glycine receptors||Ahrens et al., 2009 1 ; Foadi et al., 2010 1|
( 1 Enecta Group;
2 Cayman; 3 NIH; 4 NS)
|Mice||↓inflammation; ↓hyperalgesia||Belardo et al., 2019 1 ; 4 ,Crivelaro Do Nascimento et al., 2020; (Toth et al., 2010) 2 ; (Ward et al., 2014; King et al., 2017); 3 (Harris et al., 2016);|
( 1 NIH; 2 THC Pharm; 3 GW Pharma; 4 Cayman; 5 NS)
↓ hepatic cytochrome p450
|(Costa et al., 2007; Comelli et al., 2008; Casey et al., 2017; Abraham et al., 2019) 3 ; (Xiong et al., 2012) 1 ; (Jesus et al., 2019) 5 ; Wong and Cairns, 2019 4|
( 1 Stanley Brothers; 2 Bedrocan International; 3 Ananda Professional; 4 Tilray; 5 NS)
|Humans||Patient-reported: ↓ chronic pain;
↑ quality of life; ↑ quality of sleep
|(Wade et al., 2003) 5 ; (Cuñetti et al., 2018; Xu et al., 2019); (Van De Donk et al., 2019) 2 ; (Notcutt et al., 2004; Capano et al., 2020) 5 ; (Gulbransen et al., 2020) 4|
CBD : THC
|Humans||improved refractory/neuropathic pain;
Patient-reported ↓ chronic pain; ↑ quality of life;
Improved responses to noxious stimuli
|Johnson et al., 2013; Sellers et al., 2013; Ueberall et al., 2019; (Rog et al., 2005; Conte et al., 2009; Johnson et al., 2010; Portenoy et al., 2012; Mondello et al., 2018) (Berman et al., 2004; Fallon et al., 2017; Lichtman et al., 2018); > NCT01424566; > NCT01361607; > NCT01262651; > NCT01606189; > NCT01337089|
|HES model cells||Adversely impact embryo implantation; Delay placenta development||Neradugomma et al., 2019|
(The Hebrew University)
|MCF7/P-gp, BeWo and Jar cells||↑ placental xenobiotic permeability||Feinshtein et al., 2013|
|Zebrafish embryos||Delay in embryo development;
↑ embryo activity
|Valim Brigante et al., 2018|
|Chick embryos||50–80% ↓ in embryo viability;
Delay in embryo development
|Gustafsson and Jacobsson, 2019|
|Mice offspring||↑ Eye defects; ↓ birth weight;
Abnormal craniofacies; ↓ testicular weight;
↓ testicular testosterone levels
↓ hypothalamic dopamine levels
|Dalterio et al., 1984; Fish et al., 2019|
( 1 NIH; 2 Kyushu University)
|Rat offspring||↓ hepatic cytochrome p450
↓ testicular testosterone levels
↓ binding affinities for α1-adrenergic and D2-dopaminergic receptors
|List et al., 1977 1 ; Rosenkrantz and Esber, 1980 1 ; Narimatsu et al., 1988 2 ; Walters and Carr, 1988 1|
|Rhesus monkeys||↑ follicle-stimulating hormone;
|Rosenkrantz and Esber, 1980|
|Humans||↓ birth weight
↑ need for neonatal intensive care
|Gunn et al., 2016|
CBD, cannabidiol; THC, tetrahydrocannabinol; HEK cells, human embryonic kidney cells; HES cells, human endometrial stroma cells; JAr cells, human choriocarcinoma cells; BeWo cells, human placental cell line from choriocarcinoma; MCF7/P-gp cells, MCF-7 breast carcinoma cells expressing P-glycoprotein; NIH, National Institutes of Health National Institute on Drug Abuse; NS, not specified. The superscripted numbers corresponds with the vendor in the source and the cited article within that row. The symbols “↓” and “↑” indicate worsening and improvement of outcomes, respectively.
DA wrote the manuscript and prepared it for communication. CV co-wrote the manuscript and prepared the table. SK reviewed the contents and prepared the figure. VS contributed to the structure and edited the manuscript. KG defined the content, searched the literature, supervised the writing, and edited the manuscript.
We gratefully acknowledge funding from NIH grants U18 EB029354 and HL147562 to KG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of Interest
KG reports grants from Grifols, Cyclerion, and 1910 Genetics, and honorarium from Novartis, Tautona Group, and CSL Behring, outside the submitted work.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We acknowledge creative commons for their licensing of images used in the figure. All images are freely available through pixabay.com under creative commons license.
How To Use CBD To Help Manage Pain
Dr. Bindiya Gandhi is an integrative medicine physician with expertise in functional and holistic medicine based in Atlanta, Georgia.
Commissions we earn from partner links on this page do not affect our opinions or evaluations. Our editorial content is based on thorough research and guidance from the Forbes Health Advisory Board.
Table of Contents
- CBD for Pain Relief
- CBD for Chronic Pain
- CBD for Arthritis and Joint Pain
- CBD for Neuropathic Pain
Without the intoxicating properties of its cousin delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) can provide the human body with a handful of health benefits. Cannabinoids like CBD interact with receptors in the endocannabinoid system, which plays a role in signaling bodily functions, from emotional responses to motor control to energy balance  Mouslech Z, Valla V. Endocannabinoid system: An overview of its potential in current medical practice. Neuro Endocrinol Lett. 2009;30(2):153-179. .
Over the last two decades, scientists have tested CBD’s efficacy as an analgesic, or painkiller, specifically—and with promising results. While research is ongoing, here’s what we know so far about how we can use CBD oil for pain relief.
Natural Flavor CBD
FAB CBD’s products are made from organically grown, lab tested, Colorado hemp. Their range of products include CBD oils, gummies, topical CBD cream, a vape pen and more.
CBD for Pain Relief
For now, no CBD-based medications are approved as painkillers in the U.S. Epidiolex, which is used for rare forms of epilepsy, is the only CBD treatment approved by the Food and Drug Administration (FDA).
Meanwhile, several countries have approved CBD to treat certain conditions. For instance, the U.K. approved it for multiple sclerosis, and Canada approved it for cancer pain. Ongoing research suggests CBD oil for pain can aid medical conditions, including arthritis and fibromyalgia, at varying doses. Some pain may not be treatable by CBD alone, but it can help when paired with THC or Western medication applications.
Interestingly, 60% of U.S. adults who use CBD products do so for its potential pain-relieving effects, according to a recent Forbes Health survey of 2,000 U.S. adults conducted by OnePoll.
What’s more, 60% of U.S. adults have tried CBD and believe it has medicinal benefits.
CBD for Chronic Pain
Chronic pain is defined as any pain lasting longer than several months. Studies have found CBD, often alongside THC, to be an effective pain reliever for various chronic conditions.
In clinical trials, Sativex, a spray with equal parts CBD and THC, proved significantly successful as an analgesic for cancer-related pain  Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245-259. . The spray, also used for multiple sclerosis-related pain, is approved in Canada to treat cancer pain and is currently undergoing trials for approval and use in the U.S.
A 2019 study found Sativex to be an “effective and well-tolerated add-on treatment” for patients with severe chronic pain stemming from various ailments. The study identified three types of pain: nociceptive (affecting body tissue), neuropathic (affecting nerves) and mixed pain. Sativex helped treat all three kinds but proved especially effective against neuropathic pain.
An earlier study also found CBD to be effective in chronic pain relief for conditions like multiple sclerosis and spinal cord injury, although across a much smaller sample size  Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21-29. .
CBD for Arthritis and Joint Pain
Arthritis is a broad term that encompasses hundreds of joint-related conditions and pains. Common symptoms include swelling, pain and stiffness in the joints and may progress over time.
Already a proven analgesic for other conditions, CBD shows promise as an anti-inflammatory substance in both animal and preclinical trials, which bodes well for arthritis treatment  Nichols JM, Kaplan BLF. Immune Responses Regulated by Cannabidiol. Cannabis Cannabinoid Res. 2020;5(1):12-31.  Mlost J, Bryk M, Starowicz K. Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. Int J Mol Sci. 2020;21(22):8870.  Kosgodage US, Mould R, Henley AB, et al. Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer. Front Pharmacol. 2018;9:889.  Lowin T, Tingting R, Zurmahr J, Classen T, Schneider M, Pongratz G. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 2020;11(8):714. . However, clinical research dedicated to CBD administration for arthritis is less robust and ongoing.
The first controlled trial conducted in 2006 focused on patients with rheumatoid arthritis, an autoimmune disease that causes inflammation in the joints and other affected areas  Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford). 2006;45(1):50-52. . Researchers found that, compared to a placebo, Sativex significantly improved participants’ pain during movement, pain at rest and quality of sleep. Any adverse reactions to the treatment were mild or moderate, and there were no complications with withdrawal.
In 2018 researchers tested the efficacy of topical CBD gel on participants with osteoarthritis-related knee pain over the course of 12 weeks  Hunter D, Oldfield G, Tich N, Messenheimer J, Sebree T. Synthetic transdermal cannabidiol for the treatment of knee pain due to osteoarthritis. Osteoarthritis and Cartilage. 2018;26:S26. . Participants used either 250 milligrams or 500 milligrams, split into two applications, daily. Overall, participants’ weekly pain levels didn’t improve much with CBD compared to placebo. However, when researchers evaluated the average weekly worst pain scores and Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function scores, participants who applied 250 milligrams of CBD daily experienced significant improvement over placebo participants.
Meanwhile, a small 2019 trial suggests a mix of CBD and THC may prove beneficial for people with fibromyalgia, a type of arthritis that results in whole-body pain and fatigue  van de Donk T, Niesters M, Kowal MA, Olofsen E, Dahan A, van Velzen M. An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain. 2019;160(4):860-869. . The study found that, via a single inhalation, a CBD-THC solution performed better than a placebo and either substance on its own.
CBD for Neuropathic Pain
Various conditions and injuries that damage nerves or the nervous system can result in neuropathic pain. This kind of pain manifests as tingling, numbness, muscle weakness and a sharp, shooting, burning or stabbing pain.
Multiple sclerosis (MS) is a common cause of neuropathic pain. The disease wears down myelin, a mixture of proteins and phospholipids that coats nerve cells. Sativex is already approved as an MS treatment around the world due to its success in clinical trials. As a spray, Sativex is absorbed in the mouth. Studies support a median dose of eight sprays a day for patients with MS, which provides about 20 milligrams of CBD and 21.6 milligrams of THC  Sativex Oromucosal Spray – Summary of Product Characteristics (SmPC). Datapharm. Accessed 7/9/2021. . However, doses vary between patients, and each person needs to find their optimal dose.
A 2020 study also tested topically administered CBD oil as a treatment for patients with peripheral neuropathy, or damage to the peripheral nervous system, which sends information throughout your body from the central nervous system  Xu DH, Cullen BD, Tang M, Fang Y. The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities. Curr Pharm Biotechnol. 2020;21(5):390-402. . When compared to placebo, the topical CBD significantly reduced patients’ intense pain and sharp pain, as well as cold and itchy sensations.