WRITTEN BY ELĒMENT APOTHĒC MEDICAL ADVISORY BOARD MEMBERPain affects around 50 million adults in the United States and is one of the most common reasons that people seek out their healthcare provider (1).
Pain has proven to be a complex condition to manage and often leads to reductions in mobility and daily activity, anxiety and depression, and an overall reduction in quality of life. Commonly used medications such as anti-inflammatories (eg, ibuprofen, naproxen), opioids (eg, OxyContin®, Vicodin®), nerve pain medications (eg, Lyrica®, Neurontin®), and medications for sleep (eg, Valium®, Xanax®)–all come with the risk of unwanted side effects and some, such as opioids and sleep medications, can cause dependance. The risk of dependence and/or unwanted side effects has led both patients and healthcare providers to seek alternatives to prescriptions (2).
Cannabidiol (CBD) is quickly gaining popularity with patients to treat a variety of conditions, including pain. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are two major cannabinoids (active components) found in the Cannabis sativa plant that have demonstrated positive effects in pain and other conditions. Unlike THC, CBD does not contain intoxicating properties (also previously referred to psychoactive) and does not produce a “high” feeling (3). There is growing interest with CBD specifically amongst researchers as they learn more about how CBD works in the body (4). CBD could be a promising candidate for pain management and an alternative to more commonly used medications due to its non-addictive and antioxidant properties, better safety profile, and its ability to play a role in pain, inflammation, and anxiety (4-6).
What Is the Endocannabinoid System?
It is not fully understood how CBD works in the body, but it has been shown to interact both directly and indirectly with the body’s endocannabinoid system (3).
The endocannabinoid system is a complex biological system that regulates many processes in the body (5,7). The main function of the endocannabinoid system is to keep the body in a state of balance, or homeostasis, through communication with other body systems. The endocannabinoid system can regulate food metabolism and behavior, mood and anxiety, pain perception, memory, and the brain reward system (4,8).
The endocannabinoid system includes cannabinoid receptors, with the two most extensively studied being cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). CB1 receptors are predominantly located in the central nervous system (a part of the nervous system found primarily in the brain and spinal cord), while CB2 receptors are primarily found on immune cells and are associated with immune modulation. Cannabinoids such as THC and CBD can mimic the body’s natural endocannabinoids and activate the body’s endocannabinoid system. Modulating this system could potentially lead to benefits not only for pain but a variety of other diseases, including mental health disorders, nerve and movement disorders, autoimmune disease, spinal cord injury, cancer, heart disease, stroke, traumatic brain injury, and osteoporosis (8).
CBD and Different Types of Pain
The beneficial effects of cannabinoids, including CBD, have been demonstrated with different types of pain in animal studies. The effects of CBD on pain reduction in human studies are limited, but promising (8).
Chronic pain is any pain that lasts longer than several months. Researchers conducted an 8 week study in 97 participants with chronic pain in 2020 to assess the impact of full hemp extract (from the flower of the hemp plant which contains the highest concentration of plant cannabinoids and terpenes-including CBD) on opioid medication use and quality of life measures. Over half of the participants (53%) reduced or eliminated their opioid medications within the 8 weeks study period and almost all (94%) reported quality of life improvements, with a significant improvement in pain and sleep. Study researchers concluded that CBD-rich extract could significantly reduce opioid medication use and improve chronic pain and sleep quality in patients with chronic pain who are currently using opioids. More studies are needed to confirm and expand upon these findings (9).
In 2018, researchers tested the efficacy of CBD gel (applied to the skin) on adult participants with knee pain in a 12-week study. Participants used either 250 milligrams or 500 milligrams daily, split into two divided doses or placebo (gel that contains no CBD). Overall, participants’ weekly pain levels didn’t improve much with CBD compared to placebo. However, additional analyses evaluated the average weekly worst pain scores and Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function scores and these analyses showed that participants in the 250 mg CBD daily group experienced significant improvement compared to participants in the placebo group (10).
Peripheral neuropathy is also known as nerve pain. A study conducted by researchers in 2020 using CBD oil (applied to the skin) for 4 weeks in 29 participants with nerve pain of the lower extremities (any area of the body between the hip and toes). This study showed significant reductions in intense pain, sharp pain, and cold and itchy sensations, with a larger reduction in participant ratings of intense pain, sharp pain, and itchy sensations. There was also a greater overall reduction in patient ratings for deep pain. There were no side effects reported in the study by the participants. The study researchers concluded that CBD oil can be effective in this patient population for improving pain and other types of sensations common to peripheral neuropathy and may be an effective alternative therapy (6).
Multiple Sclerosis (MS) is a disease of the central nervous system and can cause a wide variety of symptoms including pain, muscle spasm, fatigue, inflammation, and depression. High rates of dissatisfaction and quality of life have been reported in this patient population and have left many patients with MS searching for alternatives to manage their symptoms. A web-based survey conducted in 2017 by the National Multiple Sclerosis Society indicated that 66% of participants used cannabis to manage MS symptoms (11). Most studies in humans to date have used cannabis products containing CBD and THC in a 1:1 ratio. Sativex® is a prescription only medication approved in some countries to treat muscle stiffness and spasms related to MS. There is a growing body of moderate quality evidence for the safety and efficacy of cannabis treatment using 1:1 CBD/THC mixtures for managing spasms, pain, and bladder dysfunction due to MS (12). Currently, there is very limited data on the efficacy of CBD alone in managing the symptoms of MS, but there is some evidence that CBD may also be beneficial in reducing fatigue, pain, spasticity, and ultimately improve mobility (13). More studies are needed.
Fibromyalgia (FM) is a medical disorder that causes widespread pain in the muscles and bones. Additional symptoms include fatigue, sleep, memory, and mood issues. It is thought that FM is due to abnormal pain perception processing. Currently, there have not been many studies conducted in humans to determine if CBD is effective for FM. Despite very limited research, there is some evidence to support the use of CBD in FM. Given its known immune system regulating and pain perception effects, many patients are trying CBD products as a substitute for conventional pain medications.
A group of researchers conducted a national online survey in 2021 and found that CBD product use is common among patients with FM. Many of the survey participants using CBD in this study reported improvements across numerous FM-related symptoms (14). An additional analysis in this study found that CBD products were used as a substitute for pain medications. Overall, 72% of the 878 participants included in the additional analysis indicated that they had substituted CBD products for pain medications. When participants were subdivided by most commonly used CBD product, the CBD-cannabis subgroup had the highest proportion of participants (79.4%) reporting CBD product substitution for other pain medications, followed by the hemp subgroup (74.7%), and CBD isolate (64.3%). The most common reasons for substituting CBD products for pain medications were fewer adverse side effects and better symptom management. Overall, those who substituted CBD products reported greater symptom improvements that those who did not, with the greatest symptom improvements reported in the CBD-cannabis subgroup (15).
Another study conducted in 2019 examined the effects of cannabis in 20 participants with chronic pain and FM. The treatments in this study were given as a combination of CBD/THC in different concentrations. Study participants were administered treatment through inhalation. Study results indicated that a mixture of CBD and THC may be beneficial for reductions in pain. The study found that a CBD-THC solution (through a single inhalation) was better than placebo (a treatment containing no THC or CBD) and either substance on its own. The most commonly reported adverse events (not related to inhalation) were drug high, dizziness, and nausea (16).
Is CBD Safe?
Research shows that CBD can be safe and well-tolerated in both animals and humans.3 Doses of CBD as high as 1,500 mg/day taken repeatedly appear to be safe and well tolerated without significant side effects (17). As with any treatment, start low, go slow, and stay low–starting at very low doses as low as 5-10mg and slowly increase if needed. The most commonly reported side effects are tiredness, diarrhea, dry mouth, and changes in appetite and weight (18,19).
Use of CBD can cause elevated liver function tests and caution should be used in patients with known liver dysfunction (20). Monitoring for drug interactions is important since patients with chronic pain conditions typically take multiple medications that might be metabolized (broken down in the body) by similar processes as CBD. Cannabinoids, including CBD, may interfere with warfarin (a blood thinner). Warfarin INR levels should be monitored when cannabinoids and warfarin are taken together (21).
Many factors that can affect the safety of CBD include length of use, lack of consistency in CBD products, dose, and route of administration (eg. oral like tinctures, or topical like transdermal patches or lotions). Healthcare providers with medical cannabis expertise are an important resource to determine if CBD may be a suitable alternative for painful conditions and for choosing a high-quality product.
- Centers for Disease Control and Prevention. Managing Chronic Pain. December 18, 2019. Accessed September 12, 2022. https://www.cdc.gov/learnmorefeelbetter/programs/chronic-pain.htm.
- Dahlhamer J, Lucas J, Zelaya, C, et al. Prevalence of chronic pain and high-impact chronic pain among adults — United States, 2016. MMWR Morb Mortal Wkly Rep 2018;67:1001–1006. DOI: http://dx.doi.org/10.15585/mmwr.mm6736a2.
- 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. Published 2020 Nov 23. doi:10.3390/ijms21228870.
- Boyaji S, Merkow J, Elman RNM, Kaye AD, Yong RJ, Urman RD. The role of cannabidiol (CBD) in chronic pain management: an assessment of current evidence. Curr Pain Headache Rep. 2020;24(2):4. Published 2020 Jan 24. doi:10.1007/s11916-020-0835-4.
- Brandly D. CBD and chronic pain. Published March 4, 2018. Accessed October 30, 2021. https://drdavidbrady.com/cbd-chronic-pain/.
- 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. doi:10.2174/1389201020666191202111534.
- Ebbert JO, Scharf EL, Hurt RT. Medical cannabis. Mayo Clin Proc. 2018;93(12):1842-1847. doi:10.1016/j.mayocp.2018.09.005.
- Corroon J, Felice JF. The endocannabinoid system and its modulation by cannabidiol (CBD). Altern Ther Health Med. 2019;25(S2):6-14.
- 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. doi:10.1080/00325481.2019.1685298.
- 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 (supplement1): s26. doi:10.1016/j.joca.2018.02.067.
- Kindred JH, Li K, Ketelhut NB, Proessl F, Fling BW, Honce JM, et al. Cannabis use in people with Parkinson’s disease and multiple sclerosis: a web based investigation. Complement Ther Med (2017) 33:99–104. doi:10.1016/j.ctim. 2017.07.002.
- Longoria V, Parcel H, Toma B, Minhas A, Zeine R. Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination. Biomedicines. 2022 Feb 24;10(3):539. doi: 10.3390/biomedicines10030539. PMID: 35327341; PMCID: PMC8945692.
- Rudroff T, Sosnoff J. Cannabidiol to Improve Mobility in People with Multiple Sclerosis. Front Neurol. 2018 Mar 22;9:183. doi: 10.3389/fneur.2018.00183. PMID: 29623067; PMCID: PMC5874292.
- Boehnke KF, Gagnier JJ, Matallana L, Williams DA. Cannabidiol use for fibromyalgia: prevalence of use and perceptions of effectiveness in a large online survey. J Pain. 2021;22(5):556-566. doi:10.1016/j.jpain.2020.12.001.
- Boehnke KF, Gagnier JJ, Matallana L, Williams DA. Substituting cannabidiol for opioids and pain medications among individuals with fibromyalgia: a large online survey [published online ahead of print, 2021 May 13]. J Pain. 2021;S1526-5900(21)00220-0. doi:10.1016/j.jpain.2021.04.011.
- 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. doi:10.1097/j.pain.0000000000001464.
- Bergamaschi MM Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a cannabis sativa constituent. Curr Drug Saf. 2011;6(4):237-249. doi: 10.2174/157488611798280924.
- Iffland K, Grotenhermen F. An Update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017;2(1):139-154. Published 2017 Jun 1. doi:10.1089/can.2016.0034.
- Corroon J, Phillips JA. A cross-sectional study of cannabidiol users. Cannabis Cannabinoid Res. 2018;3(1):152-161. Published 2018 Jul 1. doi:10.1089/can.2018.0006.
- VanDolah HJ, Bauer BA, Mauck KF. Clinicians' guide to cannabidiol and hemp oils. Mayo Clin Proc. 2019;94(9):1840-1851. doi:10.1016/j.mayocp.2019.01.003
- Damkier P, Lassen D, Christensen MMH, Madsen KG, Hellfritzsch M, Pottegård A. Interaction between warfarin and cannabis. Basic Clin Pharmacol Toxicol. 2019 Jan;124(1):28-31. doi: 10.1111/bcpt.13152. Epub 2018 Nov 6. PMID: 30326170.
SAHAR SWIDAN, PHARMD, ABAAHP, FAARFM, FMNM, FACA
Dr. Sahar Swidan is President and CEO of NeuroPharm and Former CEO of Pharmacy Solutions in Ann Arbor, MI and Adjunct Associate Professor of Clinical Research and Leadership at George Washington University School of Medicine and Health Sciences, and Adjunct Clinical Associate Professor of Pharmacy at Wayne State University. She currently serves on the Element Apothec Medical Advisory Board.
She received her Doctor of Pharmacy degree and completed a 3-year research Fellowship in Bio-Pharmaceutics and Gastroenterology at the University of Michigan. Following her fellowship, she was Director of Pharmacy at Chelsea Community Hospital and the clinical pharmacist for the inpatient head and chronic pain service.
Dr. Swidan is board certified and an advanced fellow in anti-aging and regenerative medicine. She is an internationally renowned speaker in the areas of pain management, headaches, and HRT. She has authored several book chapters, articles, and patient education material in head and general pain management and personalized medicine.
Most recently, Dr. Swidan has contributed in authoring Metabolic Therapies in Orthopedics, Second Edition. This edition provides continued knowledge on how optimizing metabolic pathways can improve the success of regenerative therapies through emerging technologies, integrative approaches, clinical research, and compelling evidence from over 30 experts. Dr. Swidan provides key insight in the areas of drug-related muscular pain and sarcopenia and the effects of hormones on the musculoskeletal system.
Dr. Swidan edited and authored a book with many thought leaders from around the globe titled Advanced Therapeutics in Pain Medicine which aids clinicians in advancing their current toolbox in the treatment of various pain syndromes.