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Cbd oil effectiveness for pain

Should You Take CBD for Pain?

People looking for a safer pain reliever are turning to cannabis-derived CBD. Michigan Medicine experts weigh in on what’s currently known about the trendy supplement.

Want to learn more on this topic? Listen to this podcast from the Rogel Cancer Center on Medical Marijuana for Cancer Patients.

CBD, short for cannabidiol, is undergoing a surge in popularity as the hot new supplement, with a promise to treat a variety of conditions including pain, anxiety, and insomnia, just to name a few. It’s also available in all manner of forms, from lotions and oils to CBD-infused food and drink. But does it work?

CBD is one of the compounds in the cannabis plant, better known as marijuana. Unlike the famous cannabinoid tetrahydrocannabinol (THC), CBD doesn’t cause the psychological effects typical of being “high”. Both CBD and THC act on the body’s natural endocannabinoid system, which plays a role in many processes including appetite, pain and memory.

The scientific evidence around CBD use is thin, a fact that is mainly due to politics. “Cannabis has been a Schedule 1 drug for a long time, which has limited the type of research needed to figure out how best to use it therapeutically,” says Kevin Boehnke, Ph.D., research investigator in the department of anesthesiology and the Michigan Medicine Chronic Pain and Fatigue Research Center. Under the U.S. Federal Controlled Substances Act, Schedule 1 drugs are defined as having no currently accepted medical use and a high potential for abuse.

Yet marijuana has been used as a medicinal plant for thousands of years, he notes. In fact, one of the first recorded uses of cannabis was for rheumatism, also known as arthritis. Cannabis products were widely used as medicines in the 19th and early 20th centuries, and were listed in the U.S. Pharmacopoeia before the onset of Federal restriction in 1937 under the Marijuana Tax Act.

Much of the research literature around CBD in particular supports its use as a treatment for childhood epilepsy. Indeed, in 2018 the FDA approved the CBD-based drug Epidiolex as a drug for childhood epileptic conditions. In a substantial policy shift, Epidiolex was designated as Schedule V, which is the least restrictive drug schedule and indicates little potential for abuse.

While there aren’t any published clinical trials on CBD in pain, Boehnke notes that ongoing preclinical studies in animals have demonstrated that CBD reduces pain and inflammation, and studies of CBD in humans show that it is well-tolerated and has few negative side effects. “There are also observational studies that ask why people use CBD and if it’s effective, and results tend to be quite positive. People report using CBD for anxiety, pain, sleep — all things that go hand-in-hand with chronic pain,” he says. The passage of the 2018 Farm Bill removed hemp-derived CBD (

So many people are turning to CBD as an alternative pain reliever, especially in light of the opioid crisis, that in a commentary published in Annals of Internal Medicine, Boehnke and Daniel Clauw, M.D., director of the Chronic Pain and Fatigue Research Center, provided advice for clinicians on how to counsel their patients about CBD and cannabis use.

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They also provided guidance for the Arthritis Foundation, who recently surveyed 2,600 people with arthritis and found that 29% currently use CBD to treat arthritis symptoms.

Boehnke and Clauw recommend that people with chronic pain talk to their doctor about adding CBD to their treatment plan, and continue to use their prescribed medication. They offer the following advice for people wanting to try CBD:

Don’t smoke or vape. Bottom line is smoking anything harms the lungs. Vaping has been associated with a recent epidemic of lung disease, according to the Centers for Disease Control & Prevention.

Purchase from reputable sources. Like vitamins and other supplements, CBD products aren’t regulated or FDA approved to treat disease, so buyer beware. Look for products that have been tested by an independent third party lab “so you don’t end up with a product that has THC in it or a product contaminated with heavy metals or pesticides,” says Boehnke.

Route of administration matters. CBD is best taken in pill or capsule form for slow extended release or as an oral tincture (infused oil that contains CBD) for faster effect onset.

Start low, go slow. Take a small amount and slowly increase your dosage until you start to get symptom relief over a matter of weeks. Track your symptoms to get a sense of whether or not CBD is a helpful part of your treatment plan.

Check your state laws. While medical marijuana is legal in many states, it’s still illegal at the Federal level, putting CBD in a legal gray zone in many areas.

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 [1] 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.

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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 [2] 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 [4] 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 [5] Nichols JM, Kaplan BLF. Immune Responses Regulated by Cannabidiol. Cannabis Cannabinoid Res. 2020;5(1):12-31. [6] 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. [7] 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. [8] 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.

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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 [9] 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 [10] 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 [11] 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 [12] 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 [13] 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.

Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic

Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients’ reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r).


This retrospective observational study examined pain, anxiety, depression symptoms, and wellbeing in 279 participants over 18 years old, prescribed with CBD-rich treatment at a network of clinics dedicated to medical cannabis in Quebec, Canada. Data were collected at baseline, 3 (FUP1), and 6 (FUP2) month after treatment initiation. Groups were formed based on symptom severity (mild vs moderate/severe) and based on changes to treatment plan at FUP1 (CBD vs THC:CBD). Two-way mixed ANOVAs were used to assess ESAS-r scores differences between groups and between visits.



This retrospective observational study suggests CBD-rich treatment has a beneficial impact on pain, anxiety, and depression symptoms as well as overall wellbeing only for patients with moderate to severe symptoms; however, no observed effect on mild symptoms. The results of this study contribute to address the myths and misinformation about CBD treatment and demand further investigation.


Cannabidiol (CBD) is one of the primary cannabinoids found in significant but variable concentrations in cannabinoid-based medicines (CBM). While structurally similar to Δ9-tetrahydrocannabinol (THC), CBD does not cause intoxication or euphoria (Russo 2017) and has showed considerable tolerability in humans with a low abuse potential (Chesney et al. 2020). This favorable safety profile has led to the recent mitigation of legal and regulatory barriers surrounding purified CBD products in several countries and recent increased interest in CBD treatments. While recent rulings clarified that CBD is not a drug under the 1961 United Nations as Single Convention on Narcotic Drugs, regulatory status in the USA remains extremely confusing. When derived from cannabis, CBD is a schedule 1 drug but when derived from “industrial hemp” plants it may be lawful federally (Corroon and Kight 2018; Corroon et al. 2020). In Canada, CBD is controlled under the Cannabis Act as are all cannabinoids, cannabis, and cannabis-derived products (Canada Go 2021). This regulatory status imparts restrictions and access obstacles for researchers.

CBD is widely touted as a panacea for a wide range of health problems and has been marketed as a dietary and “wellness” product (Russo 2017; Khalsa et al. 2020; Eisenstein 2019). CBD’s potential effects as an add-on therapy have been studied for social anxiety disorders, schizophrenia, non-motor symptoms in Parkinson’s disease, and substance use disorders (Bergamaschi et al. 2011; Crippa et al. 2019; McGuire et al. 2018; Millar et al. 2019; Prud’homme et al. 2015; Thiele et al. 2019; Leehey et al. 2020). However, the evidence of its effectiveness for indications other than drug-resistant pediatric epilepsy conditions remains very limited (Larsen and Shahinas 2020; Franco et al. 2020) and safety considerations such as drug-drug interactions associated with unsupervised use remain (Chesney et al. 2020; Freeman et al. 2019). Randomized controlled trials (RCTs) are limited in their rigorous design, population sample, and duration of observation making generalization of results and long-term data scarce. Therefore, real-world evidence (RWE) provides valuable insights and supplemental information about the use, safety, and effectiveness of CBD-based treatments (Graham et al. 2020).

RWE from retrospective analyses and patient registries shows that CBMs are used for pain (chronic, neuropathic), mental health conditions, cancer-related symptoms (nausea, fatigue, weakness), HIV/AIDS, and neurological conditions (Bonn-Miller et al. 2014; Gulbransen et al. 2020; Lintzeris et al. 2020; Lucas and Walsh 2017; Sexton et al. 2016; Waissengrin et al. 2015). Symptom control is the primary reason for use of CBM, with most patients looking to address unalleviated symptoms, perceived symptom intensity, and burden on health-related quality of life independently of primary diagnosis (Sexton et al. 2016; Waissengrin et al. 2015; Baron et al. 2018; Purcell et al. 2019; Swift et al. 2005; Webb and Webb 2014). The Edmonton Symptom Assessment Scale-revised version (ESAS-r) is a validated scale to assess symptom burden developed for use in oncology and palliative care (Hui and Bruera 2017), it has relevance to medical cannabis care as patients are often treated for similar symptom management (Good et al. 2019; Pawasarat et al. 2020). Specifically, studies showed self-perceived improvement in ESAS-r emotional symptoms (anxiety and depression) scores following CBM treatment in oncology patients, while pain and wellbeing symptoms showed no improvement (Good et al. 2019; Pawasarat et al. 2020). Yet, RWE on CBD-rich products is scarce (Goodman et al. 2020; Shannon et al. 2019). In addition, although careful titration and treatment adjustment after initiation is critical to symptom improvement and adverse effects care, current literature has failed to address this issue.

In this study, we investigated treatment with CBD-rich products within a dedicated clinical setting in Quebec, Canada, and the effects on a very common clinical symptom expression of pain and comorbid anxiety and depression symptoms, as well as the effect on overall wellbeing. We also examined the relevant clinical effects that were observed when CBD-rich treatments were replaced by THC:CBD-balanced products at subsequent follow-up visits.

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Study population

This study is a retrospective examination of patients who were prescribed CBD-rich products by physicians at a clinic dedicated to CBM treatments operating at four locations across Quebec, Canada. All data are collected as part of standard clinical procedures during the initial visit and during 3 (FUP1) and 6 (FUP2) month follow-up visits and extracted from electronic medical records (EMR) (Prosk et al., 2021). All data were anonymized following extraction from the EMR and no identifiers linking to original data were maintained. A waiver of consent was required and approved by Advarra Ethics Committee, who also approved the study protocol, and by the provincial privacy commission (La commission daccès à linformation du Quebec).

Adult patients, at least 18 years of age, who were initially treated exclusively with CBD-rich products from 1 October 2017 to 31 May 2019 and for whom outcome scores and product information were recorded at FUP1 were included in this study. Patients were generally referred by primary-care physicians and specialists for an assessment on the suitability of medical cannabis to treat refractory symptoms. A complete medical history, including primary and secondary diagnoses, was collected at baseline visit. Medical cannabis treatment decisions are determined at the discretion of a clinic physician according to a standardized clinical procedure, including symptom identification, selection of product format, cannabinoid profile, and dosage based on existing evidence (MacCallum and Russo 2018; Cyr et al. 2018), but also to minimize risk of adverse effects. Patient and physician preference may also indicate initiation with products that have higher CBD and lower THC concentration in order to limit use of THC and its inherent potential adverse events. The follow-up visits serve to assess treatment compliance, safety, and effectiveness.

CBD-rich products in Canada

CBD-rich products are administered in various methods and formats, but most commonly as oral plant-derived extracts or oils and as inhaled dried flowers. In the Canadian medical cannabis program, CBD-rich cannabis oils contain approximately 0.5–1 mg of THC/mL and 20–25 mg of CBD/mL depending on the product manufacturer. Table 1 provides cannabinoid content and THC:CBD ratio for the three most common oil products (over 85% of patients) authorized at the clinic. Furthermore, product details in this study sample are described in Table 3. The clinic procedure dictates that all products with a ratio of CBD (mg) to THC (mg) higher than 10 are considered CBD-rich products.

Table 1 THC and CBD contents and associated THC:CBD ratio for the three most common oil products authorized at the clinic

Treatment adjustments occur at follow-up visits as a result of lack of effectiveness, presentation of adverse effects, or social or economic barriers. Adjustments may include a change of the recommended CBD-rich product, method of administration, dosage, or a change in product formulation such as the introduction of THC:CBD-balanced or THC-rich products. We investigated the change from CBD-rich to THC:CBD products during FUP1 by forming two groups based on their product adjustment at FUP1 (CBD-rich vs THC:CBD). Products at FUP1 reflect those recommended at the visit. Therefore, the adjusted treatment affects only the evaluation at FUP2.


Patients age, sex, and diagnosis were recorded at baseline. Patients completed the ESAS-r (Edmonton Symptom Assessment System-revised version) at each visit. The ESAS-r is a self-administered scale, rating the severity of symptoms from 0 (absence of symptom) to 10 (worst possible severity) at the time of assessment (Hui and Bruera 2017). Symptoms evaluated include six physical- (pain, tiredness, nausea, drowsiness, lack of appetite, and shortness of breath), two emotional- (depression, anxiety), and one overall wellbeing-related symptoms. ESAS scores can be categorized as mild (score 0 to 3) moderate (score 4 to 6) or high (score 7 and above) (Butt et al. 2008) and the threshold for clinically significant improvement is a decrease of 1 point (Hui et al. 2015). Since pain and mental health issues represent the most common symptoms for patients and physicians seeking medical cannabis treatments, we investigated effects on pain, depression, and anxiety symptoms as well as overall wellbeing. For each symptom, two groups of patients were formed: moderate-severe severity group in which a baseline score of 4 or more was recorded and a mild severity group with baseline score of 0 to 3.


Mean scores and standard deviation (SD), as well as percentage, where appropriate are presented for each variable. All analyses were performed on each ESAS-r symptom separately through the data analytics software R v4.0.2. An initial analysis compared the overall ESAS-r scores between each visit no matter the severity of the group, and looked at the role of product group (CBD/THC:CBD vs CBD/CBD group) (between-factor). Tukey HSD post hoc test was used to confirm where the differences occurred between groups.

To determine whether CBD-based treatments have different effectiveness based on the severity of patient symptoms, two-way mixed ANOVAs with severity group as between-factor and visit as a within-factor were conducted to assess the change in ESAS-r scores between visits. Paired t-tests were subsequently performed to assess the difference in mean scores within each severity group between baseline and FUP1. Significant p value was set at 0.05 and all analyses were two-tailed. Partial eta-squared (η 2 p) are reported to indicate magnitude of differences between groups.



A total of 1095 patients were seen at the four clinic sites during the study period. Out of those, 715 were eligible for the study (at least 18 years old and initially treated exclusively with CBD-rich products). A total of 279 patients with ESAS-r scores and product information at FUP1 were analyzed (190 (68%) female, mean age = 61.1, SD = 16.6). The analyzed sample did not differ from the study-eligible group in terms of age, sex, or THC and CBD initial doses (all ps > 0.4). Table 2 outlines patient sample size and demographic information for each symptom and treatment group. Two hundred and ten (75%) patients were prescribed CBD-rich products to treat chronic pain, 19 (7%) for cancer-related symptoms, 21 (7.5%) to treat neurological disorders (Parkinson’s disease, multiple sclerosis, and drug-resistant epilepsy among others), 8 patients for inflammatory disease (arthritis), 10 for gastrointestinal disorders (Chron’s disease, inflammatory bowel syndrome, ulcerative colitis), 2 for anxiety, 1 for depression, 2 for headaches, and 6 unclassified. The chronic pain category included all medical indications for which pain was the main symptom such as but not limited to fibromyalgia, spinal stenosis, and chronic low back pain. Overall, 116 (41.6%) patients adjusted their prescription by adding THC at FUP1 (either to a THC:CBD-balanced combination or a THC-rich treatment). Two hundred and three (73%) patients had moderate/severe ESAS-r scores on at least 2 of the examined symptoms, 57 (20%) on three, and 75 (27%) on all four symptoms. Twenty-nine (10%) patients report no moderate/severe symptoms; these people may use CBD for other ESAS-r symptoms not examined here (shortness of breath, tiredness, nausea, drowsiness, appetite). There was no statistical difference on either age, sex, or THC and CBD initial doses between the patients who completed one FUP versus those who completed two FUP (all ps > 0.1).

CBD-rich products characteristics

The baseline average daily doses for CBD and THC are presented in Table 3. The maximum initial CBD dose recorded (156 mg) was prescribed for the treatment of pain of one patient. The maximum THC dose recorded at FUP1 (90 mg) was prescribed for two patients for the treatment of pain.

Table 3 Details of the THC and CBD component of the CBD-rich, the THC:CBD 1:1, and the THC-rich formulations

Outcome of CBD treatment

Mean ESAS-r scores of pain, anxiety, depression symptoms, and overall wellbeing at baseline, FUP1, and FUP2 are described in Table 4 and Fig. 1.

Table 4 Mean and standard deviation (SD) scores of ESAS-r scales for each severity group (mild or moderate/severe) and for each product group (CBD/CBD or CBD/THC:CBD)

CBD-rich treatment effectiveness on pain, anxiety, depression symptoms, and on overall wellbeing in 279 patients. FUP1, follow-up visit at 3 month; FUP2, follow-up visit at 6 month. Mixed ANOVAs revealed a significant effect of visit on symptom reduction between baseline and FUP1 but not between FUP1 and FUP2

All average ESAS-r scores decreased between baseline and FUP1 and FUP2. This was further demonstrated by ANOVAs which revealed a significant effect of visit on mean ESAS-r scores for each symptom assessed (pain: F(2,634) = 4.9, p < 0.008; anxiety: F(2,624) = 8.36, p < 0.001, depression: F(2,629) = 5.36, p < 0.004; wellbeing: F(2,613) = 8.31, p < 0.001; all η 2 p between 0.008 and 0.02). In all assessed symptoms, no significant main effect of adding THC at FUP1, nor visit-by-product interaction, were observed (all ps > 0.2). Post hoc tests revealed ESAS-r mean scores significantly decreased between baseline and FUP1 (all ps < 0.003) for all symptoms, between baseline and FUP2 for anxiety and wellbeing (both ps < 0.03), but not between FUP1 and FUP2 for any symptoms (all ps >0.5). This suggests statistical improvement recorded at FUP1 is still present at FUP2 in all symptoms independently from treatment adjustment at FUP1.

CBD treatment impact according to symptom severity

From Table 2, moderate or severe scores at baseline were most common for pain (205 patients, 73.5%) and poor wellbeing (202 patients, 72.4%).

Clinical effect (difference of 1.3 to 2.5 points) observed in all symptoms for patients with moderate/severe symptoms between baseline and FUP1; however, there was no clinical effect for patients with mild symptoms (from − 0.3 to − 1.8) (Fig. 2). No clinical effect was observed in any symptoms between FUP1 and FUP2 for patients with moderate/severe symptoms (− 0.4 to 0.5) as well as for patients with mild symptoms (from − 0.7 to 0.4).

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CBD-rich treatment effect according to symptom severity: mild or moderate/severe in 279 patients. FUP1, follow-up visit at 3 month; FUP2, follow-up visit at 6 month. a Mean ESAS-r scores for the pain symptom, b mean ESAS-r scores for the anxiety symptom, c mean ESAS-r scores for the depression symptom, and d mean ESAS-r scores for overall wellbeing. According to mixed ANOVAs, patients with moderate/severe symptoms reported symptom reduction whereas patients with mild symptoms reported symptom deterioration from baseline to FUP1. No effect was statistically significant between FUP1 and FUP2

The ANOVA revealed that all main and interaction effects were significant at the 0.001 level with effect sizes large for severity (η 2 p = 0.29), medium for visit (η 2 p = 0.06), and small for the interaction (η 2 p = 0.03). Post hoc tests revealed a significant score difference between baseline and FUP1 and FUP2 (both ps < 0.05) but not between FUP1 and FUP2 (p = 0.98). Patients with moderate/severe symptoms on pain experienced important improvement at FUP1 (t(194) = 7.61, p < 0.001) whereas ESAS-r scores for patients with mild symptoms actually increased (t(64) = − 2.03, p < 0.05) (Fig. 2a).



The ANOVA showed main effects of visit, severity group (both ps < 0.001 with η 2 p = 0.04 and η 2 p = 0.4, respectively) and a significant group-by-visit interaction (F(2,620) = 34.47, p < 0.001; η 2 p = 0.1). Post hoc tests revealed a significant score difference between baseline and FUP1 and FUP2 (both ps < 0.01) but not between FUP1 and FUP2 (p = 0.85). Specifically, the scores of moderate/severe group decreased notably (t(110) = 9.56, p < 0.001) between baseline and FUP1 but the scores of the group with mild depression symptoms did not (p = 0.07) (Fig. 2c).



This retrospective study explored the use of CBD-rich products in a medical cannabis clinical setting in Canada and associated effectiveness on a common symptom cluster presentation of pain, anxiety, depression, and poor sense of wellbeing, as measured by ESAS-r.

Patients treated with CBD-rich products were mainly women in their sixties, seeking predominantly chronic pain management.

Our findings show that overall effectiveness of CBD treatment is primarily by patients with moderate to severe symptoms. A deficiency in the endocannabinoid system (ECS) may provide a possible explanation for this result (Russo 2016). The ECS could be more deficient in patients with moderate/severe symptoms compared to mild symptoms leading to increased improvement in the first group. The absence of significant improvement for patients with mild symptoms at baseline may be explained by a smaller margin for symptom improvement. In such patients, CBD treatments may have been targeted to other clinical symptoms not assessed in the current study. There is a probable placebo effect; however, there were no differences in initial CBD doses between the severity groups. Furthermore, associated placebo effect would likely be decreased by FUP3M, also considering the significant treatment cost. The distinct beneficial impact of CBD treatment observed for patients with moderate-severe symptoms could elucidate discrepancies found in the literature.

RCTs on CBM and pain symptoms provide inconclusive results; however, several report that treatments of THC and CBD have some benefit for pain management (Häuser et al. 2018; Russo 2008; Prosk et al. 2020). Our results are largely novel as research on the effect of CBD on pain control is very limited (Boyaji et al. 2020). The reduction in reported anxiety may also contribute to the improvement in pain perception.

Discrepancies still exist regarding the anxiolytic effect of CBD. Some RCTs indicate an anxiolytic effect of CBD upon experimentally induced scenarios (Bergamaschi et al. 2011; Zuardi et al. 2017; Bhattacharyya et al. 2010; Skelley et al. 2020); however, these findings are difficult to replicate (Larsen and Shahinas 2020; Hundal et al. 2018; Crippa et al. 2012). This reinforces our findings that CBD may have a differential effect depending on anxiety severity. Regarding the effects of CBD on depression symptoms, further research is required to draw conclusions (Khalsa et al. 2020; Schier et al. 2014; Turna et al. 2017).

The addition of THC to CBD during FUP1 did not produce any effect on ESAS-r scores at FUP2 in this analysis; however, the magnitude of the difference between groups is small. The examination of treatment regimen has been seldom addressed in the literature and further development is required to inform guidelines for prescription and refinement of clinical practice.

Furthermore, a significant discrepancy is observed between the recorded dosages of oral CBD in RCTs and dosages in real-world settings. The average daily CBD dosage authorized at our clinic (11.5 mg) is closer to other observational studies (Gulbransen et al. 2020) compared to what is seen in RCTs (up to 1000 mg for a single dose) (Larsen and Shahinas 2020). The presence of THC and other cannabinoids in CBD-rich products may affect the outcomes in this study. The majority of RCTs investigated single-dose administration of CBD making it difficult to compare observed treatment outcomes with chronic dosing clinical settings. Importantly, medical cannabis products are generally not covered by most insurers and patients rely on out-of-pocket payments. The cost of CBD remains very high globally, approximately $CAD 5–20 per 100 mg (Canada Go 2021; Eisenstein 2019; Canada 2020). Availability of reliable cannabinoid testing in certain international jurisdictions is also limited. The gap between effective doses demonstrated in RCTs and the actual affordable doses demonstrated by RWE mandate the need for a precise pricing and marketing strategy at the initiation of any drug development process.


Limitations are common in real-world data (RWD), especially in retrospective studies. In this study, with no control group, no causality effect can be drawn between CBD-rich treatment and symptom improvement. Most patients treated with CBM present with multiple severe symptoms and the analyses presented here are limited to identify the treatment outcomes for such patients. Further studies can investigate the use of CBD to treat several symptoms simultaneously.

The self-reported subjective assessment used may be biased by the patient’s positive expectation of treatment, which could lead to a possible placebo effect. This perceived effectiveness bias may also be increased by social and economic barriers. The current context of medical cannabis access, including social stigma, high cost, and lack of universal insurance coverage can increase the patient selection bias. Self-selection bias is increased by the significant patient interest in medical cannabis as these patients must be motivated to access the non-traditional medication system. This bias limits the generalizability of results but is common across international medical cannabis regimens and should not discount the observed results. The heterogeneity of the patient population with a variety of diagnoses and the diversity of medical cannabis preparations also affects the external validity of the study. However, clinical findings from within Canada’s controlled regulatory program do provide important models for international consideration. Future research is required in controlled clinical settings to examine these factors in order to provide a more complete account of CBD effectiveness.

Also, there was a large drop of sample size (53% loss) due to missing data. Additionally, there was an important loss to follow-up at the 6-month visit (FUP2) due to missed appointment and cost barriers, limiting the power of the findings. The total treatment cost has significant impact on treatment continuation. Improved patient retention and more robust, harmonized data collection methods will improve future observational studies and allow for long-term assessment. Collection of detailed, accurate product information is a challenge, especially with inhaled products (Corroon et al. 2020). There are opportunities for administration devices and other technology advancements to improve this limitation. Lastly, this study did not include safety data assessment, future studies should investigate safety considerations of CBD (Chesney et al. 2020). Collection of high-quality RWD will require improvements in patient retention, data monitoring, and more robust data collection methods within a controlled clinical setting.


This study on CBD-rich products demonstrates the potential of RWE for the advancement of medical cannabis research and practice guidelines, especially in a world where CBD use is exponentially increasing but scientific data are limited. It revealed that CBD-rich treatments have a beneficial impact on patients with self-reported moderate or severe symptoms of pain, anxiety, or depression and overall wellbeing but not in patients with mild symptoms. Further investigation is clearly required, but as of now the hyped, and often illegal, marketed claims of CBD as a wellness product are unsubstantiated. Our findings have important and novel implications to clinical practice, especially the examination of treatment plan adjustment during the first follow-up after initiation with CBD treatments. Improvements in access regimes, oversight, and clarification from regulatory agencies are also needed to improve the validity of RWE and assessment of the use of CBD-rich products.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.