which cbd oil to use for chronic pain

Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients’ Perspectives and Attitudes

Cannabis products have become easily available and accessible after decriminalization of cannabis for recreational and medicinal use in many states. Cannabidiol (CBD) has been of increasing interest to patients and is being used to self-medicate a variety of ailments. However, very limited information is available to patients and providers to form an educated opinion regarding its indicated use to treat the many conditions this substance has been implied to be helpful for. The aim of this survey was to learn about participants’ attitudes and views towards cannabis-based medicine (CBM) with a focus on perception of “CBD” and its potential role for pain management.

Materials and Methods

We recruited survey participants from seven pain management clinics in Southern California to learn about their knowledge, beliefs, and personal experience with CBD products. After Institutional Review Board (IRB) review, an internet survey platform was utilized to administer the survey online.

Results

A total of 253 participants answered the survey. Participants were 45.4 ± 13.8 (Mean ± SD) years of age, the majority identified as white (56.1%), had an annual household income of less than $20,000, and were primarily insured by Medicare (22.5%) or Medicaid (43.9%). Among participants, 62.0% reported trying a CBD product [including products containing delta-9-tetrahydrocannabinol (THC)]. The majority responded that these products have helped their pain (59.0%) and allowed them to reduce their pain medications (67.6%), including opioids (53.7%). They reported believing that CBD was a good treatment option (71.1%), not harmful (74.9%), and not addictive (65.3%). About half of participants (51.9%) report that they would be more comfortable with their physician prescribing CBD products. The overall attitude and experience of participants regarding CBD is reported as positive, while 91.9% of people expressed a desire to learn more about it.

Summary

In summary, most participants expressed a positive attitude about CBD products as a treatment option, reported positive outcomes when used for multiple different conditions, and would prefer to obtain information about and prescription for CBD from their physicians.

Introduction

Public demand for the legalization of cannabis resulted in legalization of medical cannabis in the United States first in California in 1996. 1 As of December 2020, thirty-six states and 4 territories have legalized the use of marijuana for medical purposes, creating a new treatment option for patients seeking alternative therapies. Perceived health benefits have been reported in mainstream and social media like eg, pinterest. 2 Unfortunately, this growing body of information around cannabis-based medications, specifically CBD and related health benefit claims, is not based on sound scientific research in the vast majority of cases. To further complicate the picture, cannabis-based medications including CBD products are poorly regulated in terms of their production and testing, vary in purity and consistency, and are often mislabeled. 3 As a result, the consumer of cannabis-based medications including CBD often cannot be sure about the actual quality and content of the products they consume.

Fortunately, the scientific interest in cannabinoid research has increased in recent years. 4 In particular, there has been a focus on the phytocannabinoid cannabidiol (CBD). 5 , 6 However, the evidence available is inconclusive at best, and this emphasizes the need for scientifically valid information about this compound. 7

A PubMed search revealed that the number of published research studies investigating the effects of CBD has more than doubled since the year 2016. CBD has been investigated as a treatment for childhood epilepsy, 8 , 9 reviewed as a potential treatment for chronic pain, 10–13 and some studies suggest usefulness to treat anxiety disorders. 14–16 There is ongoing research about whether the legalization of cannabis products affects opioid use and abuse. Recent studies have discovered a negative correlation between opioid use and cannabis laws 17 and have suggested that cannabis products might decrease use of opioid medications and the associated risks. 17–22

Taken together, the consumer of CBD products faces a landscape in which there is budding scientific evidence of beneficial effects for several conditions against a background of unproven claims and questionable products on the market. This currently ambiguous situation and somewhat unclear messaging around cannabis-based medications to the public poses the important questions around the current knowledge and believes about these products. Surveyed populations to date include a primary care setting, 23 young adults 24 and social media posts. 2

Given that one leading cause mentioned for CBD consumption is pain, the aim of this study was to assess the knowledge base, beliefs, and personal experience with CBM and CBD products by surveying patients seen at a series of pain management clinics. These results can help to address the gap of patients believes and supported scientific findings around CBD and aid health care providers in navigating conversations with their patients around these compounds.

Materials and Methods

Material and Methods are reported according to the checklist for reporting Results of Internet E-surveys (CHERRIES). 25

Design

Participants were recruited voluntarily (convenience sample, no incentive) from seven pain clinics in Southern California. Surveys were administered between December 4th 2018 and February 4th 2019.

IRB (Institutional Review Board) Approval and Informed Consent

The research protocol was reviewed by the Western Institutional Review Board (WIRB) and was determined to be exempt from the requirement of IRB approval meeting the criteria under 45 CFR §46.101(b)(2), including waiver of informed consent. In the specific case of our data collection, the exemption was granted since our research was a voluntary survey, no direct identifiers were collected, and the results will not be submitted to the Food and Drug Administration (FDA) for marketing approval.

Development and Pre-Testing

The survey ( Supplemental Material 1 ) was designed (JMS, TMB, CGH) and underwent multiple rounds of internal review and editing by VitaMed Research, LLC. study staff. Our demographic questions were written similar to those being asked in the Census. For our questions about CBD we utilized Yes/No answers, answers on the Likert scale (3-point, 5-point), and some questions with guided answer choices including an “other” option. Following this we entered, reviewed, and tested the questions in the SurveyMonkey environment with several test-runs to eliminate spelling and formatting errors. After this a QR code was created in the software and posters and index cards were distributed in the clinics. This survey is a new survey and has not been utilized prior. The goal of this survey was to collect broad attitudes towards and perception of CBD products to help and guide the generation of new hypothesis.

Recruitment Process and Description of the Sample Having Access to the Questionnaire

The survey information/link was posted openly in the form of posters, flyers, and business cards containing QR-codes at seven pain clinic locations in Southern California including the University of California, San Diego, Department of Anesthesia Division of Pain Management. Three were locations of Desert Clinic Pain Institute in Riverside County. Three were locations of Summit Institute, two in Riverside County and one in San Bernardino County. Both Desert Clinic Pain Institute and Summit Institute are complex pain management clinics who primarily serve Medicare and Medicaid populations. The survey was open to be answered by all patients and staff within our clinics. Additionally, Clinic patients were recruited by clinic staff by direct invitation or by providing business cards during their appointment ( Supplemental Materials 2 and 3 ).

Survey Administration

The survey was accessed using a QR code linked to the electronic format. The survey consisted of 32 questions that are presented including their answer choices in Tables 1 and ​ and2 2 and Supplemental Tables 1 and 2 . The survey included questions about the participants demographics ( Supplemental Table 1 ; 12 questions; zip-code data not shown), awareness and efficacy ( Table 2 ; 6 questions), personal experience ( Table 3 ; 7 questions; open-ended item responses were reported verbatim in Supplemental Table 3 ), and knowledge and beliefs about CBD ( Table 3 ; 7 questions). All questions required an answer before proceeding to the next question, but each question had the option of a neutral answer or “Decline to answer”. Since flyers and index cards were publicly available in the clinics, it cannot be excluded that in addition to patients, their family members, friends, or clinic staff participated in the survey. Additionally, theoretically the possibility exists that a responder could have answered the survey more than once. This is prevented by a function of the survey platform that does not allow multiple answers of the survey from the same IP address. However, IP addresses were not collected by us to avoid registering any sort of identifiers. Because of these limitations we cautiously describe our cohort as participants in a pain clinic environment and not as patients.

Table 1

Have you tried a CBD product?, N (%), N = 247
 Yes 152 (62.0)
 No 87 (35.5)
Do you believe the CBD product has helped your condition?, N (%), N = 151
 Not at all 1 (0.7)
 Not really 13 (8.6)
 A little bit 48 (31.8)
 A lot 59 (39.1)
 Completely 30 (19.9)
If a CBD product has helped your condition, what type of condition did it help? Check all that apply. N (%), N = 150
 Back pain 101 (67.3)
 Neck pain 67 (44.7)
 Limb pain 35 (23.3)
 Nerve pain 70 (46.7)
 Fibromyalgia 31 (20.7)
 Migraines 50 (33.3)
 Other (please specify) 58 (38.7)
What types of products have you tried? Check all that apply. N (%), N = 151
 Oral tincture 79 (52.3)
 Edible 82 (54.3)
 Capsule/Pills 34 (22.5
 Spray 26 (17.2)
 Cream 75 (49.7)
 Ointment/oil 75 (49.7)
 Inhaled/smoked 95 (62.9)
 Other (please specify) 11 (7.3)
Did any of the CBD products you used contain THC (the chemical that gets you “high”)?, N (%), N = 151
 Yes 85 (56.3)
 No 51 (33.8)
 I do not know 13 (8.6)
 Decline to answer 2 (1.3)
Please choose the answer that best applies to this statement: I was able to reduce the amount of pain medication I take by using CBD products. N (%), N = 151
 Strongly disagree 6 (4.0)
 Disagree 7 (4.6)
 Neither agree nor disagree 36 (23.8)
 Agree 56 (37.1)
 Strongly agree 46 (30.5)
Please choose the answer that best applies to this statement: I was able to reduce the amount of opioid medication I take by using CBD products. (eg, Percocet, Norco, Morphine, Oxycodone), N (%), N = 151
 Strongly disagree 9 (6.0)
 Disagree 6 (4.0)
 Neither agree nor disagree 55 (36.4)
 Agree 40 (26.5)
 Strongly agree 41 (27.2)

Notes: A majority of participants has tried a CBD product in several different formulations and for several different conditions and believe it has helped. Most participants additionally have used CBD products containing THC. More than 50% of participants believe they were able to reduce their pain medication (including opioids) by using CBD products. Descriptive data are presented as N and percent replies per question (%).

Table 2

Comparison Between Products Containing CBD and CBD/THC

Did any product you used contain THC?
Yes No
Total N = 136 N = 85 N = 51
N % within ‘contain THC’ % within ‘reduce med’ N % within ‘contain THC’ % within ‘reduce med’ Χ 2
Able to reduce pain medication? 0.31
 Strongly disagree 1 1.2 20.0 4 7.8 80.0
 Disagree 3 3.5 50.0 3 5.9 50.0
 Neither agree nor disagree 21 24.7 61.8 13 25.5 38.2
 Agree 33 38.8 67.3 16 31.4 32.7
 Strongly agree 27 31.8 64.3 15 29.4 35.7
Able to reduce opioid medication? 0.56
 Strongly disagree 4 4.7 44.4 5 9.8 55.6
 Disagree 3 3.5 60.0 2 3.9 40.0
 Neither agree nor disagree 28 32.9 57.1 21 41.2 42.9
 Agree 24 28.2 68.6 11 21.6 31.4
 Strongly agree 26 30.6 68.4 12 23.5 31.6

Notes: Explorative analysis was performed to compare perceived medication reduction between products containing CBD and CBD/THC. No significant difference was found for either pain medication or opioid medication reduction between groups. “Yes” and “No” answers were analyzed by Pearson’s Chi-Square test. Descriptive data are presented as N and percent replies per question (%) either as % within “contain THC” or % within “reduce med”.

Table 3

Knowledge, Opinions, and Interest

Do you know if there is a difference between medical marijuana and CBD?, N (%), N = 241
 No, there is no difference 6 (2.5)
 I do not know 82 (34.0)
 Yes, there is a difference 153 (63.5)
If you have used CBD products in the past, are you familiar with how much CBD is in the product you have used?, N (%), N = 241
 Extremely familiar 34 (14.1)
 Very familiar 42 (17.4)
 Somewhat familiar 43 (17.8)
 Not so familiar 33 (13.7)
 Not at all familiar 15 (6.2)
 I have not used CBD products 74 (30.7)
I believe CBD is a good treatment option. N (%), N = 239
 Strongly disagree 8 (3.3)
 Disagree 3 (1.3)
 Neither agree nor disagree 58 (24.3)
 Agree 50 (20.9)
 Strongly agree 120 (50.2)
I believe CBD is harmful. N (%), N = 239
 Strongly disagree 131 (54.8)
 Disagree 48 (20.1)
 Neither agree nor disagree 51 (21.3)
 Agree 4 (1.7)
 Strongly agree 5 (2.1)
I believe CBD can be addicting. N (%), N = 239
 Strongly disagree 115 (48.1)
 Disagree 41 (17.2)
 Neither agree nor disagree 76 (31.8)
 Agree 3 (1.3)
 Strongly agree 4 (1.7)
If I were to consider using CBD, I would feel more comfortable if it was prescribed by a doctor. N (%), N = 237
 Strongly disagree 25 (10.5)
 Disagree 13 (5.5)
 Neither agree nor disagree 76 (32.1)
 Agree 60 (25.3)
 Strongly agree 63 (26.6)
I would prefer to buy CBD products from my doctor over other sources (smoke shops, dispensaries, internet). N (%), N = 237
 Strongly disagree 23 (9.7)
 Disagree 20 (8.4)
 Neither agree nor disagree 79 (33.3)
 Agree 65 (27.4)
 Strongly agree 50 (21.1)

Notes: About a third of Participants do not know if there is a difference between medical marijuana and CBD and a wide variety of responses exists regarding familiarity with CBD. At the same time, participants believed that CBD was a good treatment option, not harmful, and not addictive. About half of participants report that they would be more comfortable with their physician prescribing CBD products. Descriptive data are presented as N and percent replies per question (%).

Data Analysis

Data was analyzed utilizing IBM SPSS Statistics Subscription software (Build 1.0.0.1298 64-bit edition, IBM, Armonk, NY). Demographics and the results to our questions are presented as descriptive statistics. Pearson’s Chi-Square test was utilized for exploratory data analysis in Table 3 . The total N and missing answers are shown in each table and the percentage of total (%) was calculated as percentage of answered questions, unless “Missing” was specified as an answer result. In the Results section, we present the results as the “majority” of answers. The majority was defined as the sum of percent answer choices in one direction excluding the neutral answer choice on the Likert scale. For guided answer choices that included “other”, we presented some examples of the most frequently chosen answers. For Yes/No answer choices we presented the answer choice with the most frequent replies. The complete answer choices are listed in the data tables ( Tables 1 and ​ and2, 2 , Supplemental Tables 1 – 3 ).

Results

A total of 253 participants started the survey and we received between 237 and 253 responses per question with the overall number of responses decreasing towards the end of the survey. Of the 152 participants that answered “yes” to having tried a CBD product, 151 answered the follow-up questions.

Analysis of demographic data ( Supplemental Table 1 , N = 253) shows that participants were 45.4±13.8 (Mean±SD) years old, the majority identified as white (56.1%), non-Hispanic (51.8%), had an annual household income of less/equal than $20,000 (56.1%), and received healthcare coverage through Medicare (22.5%) or Medicaid (43.9%). Additionally, 36.4% were unable to work due to disability and 5.1% of the cohort reported to have served on active duty in the United States armed forces.

Next, we asked the participants questions regarding awareness of CBD ( Supplemental Table 2 , N = 247). The majority reported knowing someone (family, friend, neighbor) who has used a CBD product (80.6%). Additionally, 80.6% report that somebody they know has previously suggested them to use a CBD product for their pain, while 29.6% report that their treating providers suggested use of a CBD product for their pain condition. When asked about the perceived efficacy of CBD products, 78.1% responded that they know somebody who has benefited from using a CBD product for their condition and 7.3% of participants report that someone they know developed side effects while using a CBD product. When asked if they were interested in learning more about the use of CBD to treat medical conditions, 91.9% replied with “yes”.

When asked if they have tried a CBD product, ( Table 1 , N = 151–247), 152 (62.0%) participants replied that they have tried a CBD product, and 56.3% report that the CBD product they have used contained tetrahydrocannabinol (THC). When asked if the CBD product helped their condition, participants responded “A lot” (39.1%), or “Completely” (19.9%). When asked about what conditions the CBD products have helped with the most frequently reported conditions were back pain (67.3%), nerve pain (46.7%), and neck pain (44.7%). When asked what type of products they have used, the most frequent responses were inhaled/smoked (62.9%), edibles (54.3%), and oral tinctures (52.3%). All other conditions and products reported can be viewed in detail in Table 1 and verbatim responses are listed in Supplemental Table 3 . When asked if using a CBD product was able to reduce the amount of pain medication in general, the majority agreed (37.1%) or strongly agreed (30.5%). Additionally, participants reported that the CBD product helped to reduce the amount of opioid medication specifically [“Agree” (26.5%), “Strongly Agree” (27.2%)]. When this data was analyzed by Pearson’s Chi-Square test ( Table 2 ) for perceived differences in pain and more specific opioid medication reduction between products containing either CBD or CBD/THC, we found no difference between groups [Χ 2 = 0.31 for “Able to reduce pain medication”; Χ 2 = 0.56 for “Able to reduce opioid medication”].

To gain further insights regarding knowledge, opinions, and interest we next asked a set of questions to all participants focusing on these topics ( Table 3 , N = 237–241). We were interested to know whether participants distinguish between medical marijuana and CBD with 63.5% answering “Yes, there is a difference”. We then asked the participants about their knowledge of CBD quantity in the product that they have used. Very similar percentages across possible answers were received pointing towards an overall unfamiliarity regarding knowledge of CBD content in used products. Overall, participants report that CBD is a good treatment option [“Agree” (20.9%), “Strongly Agree” (50.2%)], and disagree that CBD is harmful [“Disagree” (20.1%), “Strongly disagree” (54.8%)], or can be addicting [“Disagree” (17.2%), “Strongly disagree” (48.1%)]. Additionally, participants report being more comfortable if CBD products would be prescribed and or dispensed by a doctor [prescribed: “Strongly Agree“ (26.6%), “Agree” (25.3%), “Neither agree nor disagree“ (32.1%), “Disagree“ (5.5%), “Strongly disagree“ (10.5%)] [dispensed: “Strongly Agree” (21.1%), “Agree“ (27.4%), “Neither agree nor disagree“ (33.3%), “Disagree“ (8.4%), “Strongly disagree“ (9.7%)].

See also  cbd oil strength for reducing tumors

Discussion

Discussion of Data

Taken together, participants report some perceived beneficial effects using CBM and CBD products including the reduction of pain medication. While the familiarity with dosing was mixed and participants used a wide variety of products including products containing THC, they report that these products have helped them with many different pain-involving and neurological conditions. This finding is in alignment with similar reports describing CBD effects ranging from placebo-equivalent to highly effective. 13 The effects of CBM and CBD on painful conditions seem to be context specific, with no effect on pain shown in patients with Crohn’s disease, 26 and pain-relieving effects reported for pain associated with Multiple Sclerosis, spinal cord injury, brachial plexus injury, limp amputation, 27 peripheral neuropathy 28 and fibromyalgia. 29 This cohort also reported that products both with and without THC have helped them to reduce overall pain medication and more specifically opioid medication. The ability of CBD to significantly reduce opioid use and improve chronic pain has also been reported in an 8-week prospective cohort study in chronic pain patients published by Capano et al. 30 In general, participants report a preference for obtaining products prescribed or recommended by their physician and to have the ability to access them in the doctor’s office rather than from other sources.

Overall, our study describes the attitudes and experiences of the participants with CBM and CBD-containing products (medical cannabis) in a pain management clinic environment with a large Medicare and Medicaid patient population. The majority of participants are residents of Riverside County, with a smaller amount from neighboring San Bernardino and San Diego Counties. The demographic representation of our cohort is in alignment with an anonymous survey distributed via social media that reported their sample of CBD users to be primarily white with a yearly household income of less than $25,000. 24 The data asking about participants awareness of CBD as a treatment option and efficacy ( Supplemental Table 2 ) show that the majority of participants have had interactions with their peers, and to a lesser degree their providers talking about CBD. A similar response was observed in a survey among primary care patients, where only 18% describes their medical providers as being a good source for information regarding cannabis derived medications. 31 When asked about their personal experience, 35.5% of participants have never tried a CBD product while those who have report trying several different products for multiple conditions. A majority described some positive effects of CBD products on their conditions and reduction of pain medication. It is important to mention that 36.5% of participants did not know or think that there is no difference between medical marijuana and CBD, further manifesting the criticism that we cannot say for certain which types of products were consumed. The survey question regarding the knowledge of CBD dosing showed that almost all answer choices were represented as similar percentages, suggesting that there is a high variability of familiarity with CBD content in CBD products. In a publication looking at the CBD concentration in a variety of products, one study shows inaccurate labeling of products in the majority of cases. 3 The combination of variable familiarity and CBD concentration in available products puts patients in a difficult position when they are in search for a standardized CBD product to try as a therapeutic option. In addition, it is unknown if there was any THC present in the consumed products. Here, requirements for quality control and labeling for all hemp-based products being marketed would take the guesswork out of exact dosing and allow for better understanding of the products that patients may be accessing. This is particularly needed as there are no quality studies evaluating CBD dosing ranges for pain. Additionally, there is a need to evaluate differences between efficacy of CBD isolate products and whole plant extracts (limited to <0.3% THC content – 84 FR 58522). Patients have a need to know the exact THC content of a product, as unregulated whole plant extracts may result in a positive drug test result.

Discussion of Current Literature

Current Evidence for CBD and Pain

When looking at the current literature, it is evident, that well-controlled studies investigating the effects of CBD on pain are currently not available. 7 However, some literature is starting to investigate its effects. For example, a well-controlled study of purified CBD has demonstrated that CBD has low abuse potential, even within sensitive populations. 32 In a preclinical study, CBD use has also been attributed to reducing drug-seeking behavior in mice. 33 These positive results have brought up discussions about the role of CBD in combating the world’s opioid epidemic. While studies have investigated the combined use of fentanyl with CBD, the results were inconclusive and currently the impact of CBD on opioids is not known. 7 , 34 Another recent study was investigating the role that CBD plays on craving behavior in abstinent individuals with heroin use disorder. 35 This study shows that CBD doses (Epidiolex) of 400 mg and 800 mg were able reduce craving and anxiety induced by heroin’s cues compared to placebo. However, while the CBD doses of 400 mg and 800 mg are relevant from a pharmacologic and therapeutic perspective, these doses vastly exceed the regularly commercially available hemp-CBD products which may present cost challenges as Epidiolex therapy is around $16,000/year. 34 Several manuscripts review the current state of knowledge and point out important questions. Specifically, could CBD have a role in addressing the national opioid crisis? 10 , 11 Conversely, the data supporting THC as an analgesic and for opioid-sparing effects is more robust, specifically for neuropathic pain. 36–39 The known benefit of THC for pain raises the question of whether the small THC component in some products was responsible for perceived analgesic effects and reduction of pain medications in our cohort, further highlighting the uncertainty of product content/potency consumed by respondents.

Patients Perceptions

Multiple surveys focusing on patients perspectives have been published. 18 , 19 , 40–42 In the patient-focused surveys by Boehnke et al, improved quality of life, better side effect profile, improved pain and health, and decreased opioid use were reported among medical cannabis users. 19 , 41 , 42 Both the reported improved pain and decreased opioid use show similarities with our reported findings for “CBD products”, but these results need to be interpreted in the context of uncertainty regarding the CBD/THC content of the products consumed by respondents of this survey. Additionally, participants in this cohort reported being able to reduce overall use of pain medication. A different survey reported that consumers are using CBD as a specific therapy for multiple different conditions including pain, anxiety, depression, and sleep disorders. 40 In general, survey data emphasizes the need for controlled research investigating the potential use of CBD for a variety of conditions.

Study Limitations

This study has several limitations that need to be discussed. Regarding the demographics, the survey participants in this cohort are predominantly insured by Medicare or Medicaid and a limitation could be that this is not reflective of the general pain patient population and general population that is exposed to available CBD preparations. Additionally, terms like “CBD product”, “Hemp”, “Cannabis”, “Medical Cannabis”, “Medical Marijuana” that have been added to this manuscript and explained in the glossary were not well defined for the survey participants. One question in Table 1 (“Did any of the CBD products you used contain THC (the chemical that gets you “high”?”) additionally needs clarification. With this question, we intended to ask participants if they distinguish between products that are sold as “CBD only” products and products that contain THC in higher percentages than 0.3%. Since the verbiage does not clearly state this intent, the results of this question therefore need to be interpreted with caution. This survey was distributed in a pain clinic environment and was not limited to patients. We cannot exclude that family members or clinic staff participated in the survey. Also, the relatively small sample size (n=253) is associated with bias (eg, a voluntary response bias) and may not be generalizable, particularly since only 70% have used a product. There are general limitations in a survey design, including non-sampling biases. 43 Additionally, there is the potential for recall bias, the representativeness of the sample, and the inherent uncertainty about what constitutes a “CBD product”. Medical cannabis and cannabinoid products have been associated with a prominent placebo effect particularly important to keep in mind with self-reported benefits. 44 Given these limitations, this is a well-described cohort demographically, and the data can be interpreted in this particular context. Voluntary surveys such as this one can help to identify areas for future more controlled research.

Conclusion

Taken together, the opinions, beliefs, and experiences about and with CBM and CBD were predominantly positive in this cohort. Participants reported to be able to reduce overall pain and specifically opioid medication and would be more comfortable receiving CBD through prescription or purchase from their healthcare provider. It is now our responsibility as medical and scientific communities, working with the FDA, to produce well-designed studies that can either support or disprove the anecdotes about cannabis and hemp by providing a stronger evidence-base for effectiveness in treating pain and other conditions, and continue to press for quality control of any product being consumed by patients.

Acknowledgments

We would like to thank our clinic personnel in the Center of Excellence clinics of Desert Clinic Pain Institute and Summit Institute for their help and efforts in completing this study.

Glossary

Cannabidiol (CBD) product – Any product that has a high CBD, and “low or no” (< 0.3%) THC content. This nomenclature was used in our survey.

Cannabinoid  Any substance that acts on the cannabinoid receptor system, both plant-derived and synthetic

Cannabis – A genus of plants with several species

CBD – Cannabidiol, a naturally occurring compound found in the Cannabis plant

CBM – Cannabis-based medicine

Hemp – The CBD-rich cannabis species containing less than 0.3% THC

Medical Cannabis/Marijuana – herbal drug derived from plants of the genus Cannabis containing >0.3% of THC

Disclosure

Vitamed Research, LLC. was supported by an unrestricted grant from Verséa™ Pharmaceuticals.

Dr Moeller-Bertram is Co-Founder and Chief Medical Officer for Verséa™ Pharmaceuticals. He also was supported by grants from Versea Holdings, LLC, during the conduct of the study.

Dr Backonja is a medical advisor as Medical Director for Verséa™ Pharmaceuticals.

Dr Wallace is a medical advisor for Verséa™ Pharmaceuticals.

Dr Michelle Sexton is a medical advisor for Verséa™ Pharmaceuticals and reports personal fees from Verséa™ Pharmaceuticals, outside the submitted work.

Dr Jan M Schilling reports grants from Verséa™ Pharmaceuticals, during the conduct of the study.

Younger Individuals Are More Likely to Use CBD to Treat Chronic Pain

Individuals aged 18 to 34 years who experience chronic pain are more likely to use cannabidiol (CBD) or cannabis for pain, results of a new survey conducted by the Harris Poll on behalf of the Samueli Foundation show.

“The prevalence of persistent pain among young adults is alarming, and their use of cannabis or CBD oil indicates they are seeking more ways to manage their pain through self-care,” Wayne Jonas, MD, executive director of Integrative Health Programs at Samueli Foundation, said in a statement.

“We know cannabis and CBD can be effective in treating pain that stems from various conditions, such as cancer,” he said. “But there’s insufficient evidence to support the effectiveness of CBD and cannabis in treating common chronic pain conditions.”

The survey shows that individuals aged 18 to 34 years are more likely to experience chronic pain, at 65%, than older individuals aged 35 and older, at 52%, with 73% of younger individuals saying they experience pain every day.

Among younger individuals who experience chronic pain, 22% say that they use cannabis and/or CBD for pain and are twice as likely to do so compared with those aged 45 years or older.

Young individuals commonly experience back (32%), knee (22%), and neck (20%) pain, according to the survey results.

Approximately 29% said that they talked to their doctors about their pain since the beginning of the pandemic compared with 15% of those aged 45 years and older who spoke to their physicians.

However, nearly 75% do not know which type of health care provider can help manage the pain best.

“This should be a wake-up call to physicians that their patients are looking for more information from them about managing their chronic pain, especially for non-drug approaches,” Jonas said. “It’s up to providers across the health care system to engage in regular conversations with patients to uncover the best ways to manage their pain on a daily basis.”

Approximately 78% of individuals use non-drug treatments to manage their pain, while approximately 70% use pharmacological treatments. The most common approaches are OTC pain relievers (53%), exercise (43%), heat or ice (34%), healthy eating (26%), and cannabis or CBD (16%).

Since the beginning of the pandemic, 66% of individuals said that they changed their pain management approach. Approximately 80% said that they are interested in healthy eating, 71% are interested in exercise, and 68% are interested in massage therapy.

About 83% of individuals reported that their quality of life would greatly improve if they could manage their pain better.

Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline

The panel found that this difference was not important for most patients, because the intervention effects were negligible and/or very imprecise, for example confidence intervals that include both important benefit and harm

Events per 1000 people

Reduction in pain

Based on data from 3939 patients in 27 studies

Use of medical cannabis or cannabinoids probably results in a small increase in the proportion of patients experiencing an important reduction in pain

The “minimally important difference” for patients was defined as an improvement of 1 cm on a 10 cm visual analogue scale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Improved physical function

Based on data from 2425 patients in 15 studies

Use of medical cannabis or cannabinoids results in a very small increase in the proportion of patients experiencing an important improvement in physical functioning

The “minimally important difference” for patients was defined as an improvement of 10 points on a 0-100 point SF-36 physical functioning subscale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Improved emotional function

No important difference

Based on data from 2115 patients in 10 studies

Use of medical cannabis or cannabinoids does not improve emotional functioning

The “minimally important difference” for patients was defined as an improvement of 10 points on a 0-100 point SF-36 emotional functioning subscale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Events per 1000 people

Improved role function

No important difference

Based on data from 1128 patients in 7 studies

Use of medical cannabis or cannabinoids does not improve role functioning

The “minimally important difference” for patients was defined as an improvement of 10 points on a 0-100 point SF-36 physical role functioning subscale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Improved social function

No important difference

Based on data from 1405 patients in 8 studies

Use of medical cannabis or cannabinoids does not improve social functioning

The “minimally important difference” for patients was defined as an improvement of 10 points on a 0-100 point SF-36 social role functioning subscale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

1.3 to 3.5 months

Events per 1000 people

Improved sleep quality

Based on data from 2652 patients in 9 studies

Use of medical cannabis or cannabinoids results in a small increase in the proportion of patients experiencing improved sleep quality

The “minimally important difference” for patients was defined as an improvement of 1 cm on a 10 cm visual analogue scale

No serious concerns

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Potential short term harms

1.3 to 3.5 months

Events per 1000 people

Based on data from 1033 patients in 5 studies

Use of medical cannabis or cannabinoids probably results in a small increase in the proportion of patients experiencing cognitive impairment

No serious concerns

No serious concerns

See also  do you need a prescription for cbd oil in illinois

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Events per 1000 people

Based on data from 2505 patients in 15 studies

Use of medical cannabis or cannabinoids probably results in a small increase in the proportion of patients experiencing drowsiness

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

Events per 1000 people

Based on data from 895 patients in 7 studies

Use of medical cannabis or cannabinoids probably results in a small increase in the proportion of patients experiencing impaired attention

No serious concerns

No serious concerns

No serious concerns

No serious concerns

GRADE certainty ratings

The authors have a lot of

confidence that the true

effect is similar to the

The authors believe that

the true effect is probably

The true effect might be

markedly different from

the estimated effect

The true effect is

different from the

See all outcomes

Patient decision aids

Key practical issues

The weak recommendation reflects a high value placed on small to very small

improvements in self reported pain intensity, physical functioning, and sleep quality, and

willingness to accept a small to modest risk of mostly self limited and transient harms

Values and preferences

Therapeutic trials should start with low dose, non-inhaled cannabidiol products,

gradually increasing the dose and tetrahydrocannabinol level depending on

clinical response and tolerability

Prior cannabis experience should be considered, and adverse events should be

For younger or adolescent patients, cannabidiol-predominant preparations

should be preferred, because of uncertain effects of tetrahydrocannabinol on

Patients should avoid driving or operating machinery while starting or changing

dose of medical cannabis

Women contemplating pregnancy, pregnant women, or women who are breast

feeding should be encouraged to discontinue use of medical cannabis in favour

of alternative therapy

No additional practical issues

©BMJ Publishing Group Limited.

Disclaimer: This infographic is not a validated clinical decision aid. This information is provided without any representations, conditions or warranties that it is accurate or up to date. BMJ and its licensors assume no responsibility for any aspect of treatment administered with the aid of this information. Any reliance placed on this information is strictly at the user’s own risk. For the full disclaimer wording see BMJ’s terms and conditions: https://www.bmj.com/company/legal-information/

Find recommendations, evidence summaries and consultation decision aids for use in your practice

Linked Research

Medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised clinical trials

Linked Editorial

Medical cannabis for chronic pain

  1. Jason W Busse , chiropractor, methods co-chair, associate professor 1234,
  2. Patrick Vankrunkelsven , general practitioner, clinical chair 56,
  3. Linan Zeng , methodologist 27,
  4. Anja Fog Heen , medical resident 8,
  5. Arnaud Merglen , paediatrician 9,
  6. Fiona Campbell , anaesthesiologist, professor 10,
  7. Lars-Petter Granan , physiatrist, associate professor 11,
  8. Bert Aertgeerts , general practitioner, professor 1213,
  9. Rachelle Buchbinder , rheumatologist, professor 1415,
  10. Matteo Coen , general internist 1617,
  11. David Juurlink , general internist, professor 1819,
  12. Caroline Samer , pharmacologist, assistant professor 2021,
  13. Reed A C Siemieniuk , general internist, methodologist 2,
  14. Nimisha Kumar , medical student, patient representative 22,
  15. Lynn Cooper , patient representative 23,
  16. John Brown , patient representative 4,
  17. Lyubov Lytvyn , patient liaison expert 2,
  18. Dena Zeraatkar , methodologist 224,
  19. Li Wang , assistant professor 23,
  20. Gordon H Guyatt , general internist, distinguished professor 2,
  21. Per O Vandvik , general internist, associate professor 8,
  22. Thomas Agoritsas , general internist, methods co-chair, assistant professor 225
    1 Michael G DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, ON, Canada 2 Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada 3 Department of Anesthesia, McMaster University, Hamilton, ON, Canada 4 Chronic Pain Centre of Excellence for Canadian Veterans, Hamilton, ON, Canada 5 Belgian Centre for Evidence Based Medicine (CEBAM), Leuven, Belgium 6 Department of Public Health and Primary Care, Katholieke Universiteiti Leuven, Leuven, Belgium 7 Pharmacy Department/Evidence-based Pharmacy Centre, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China 8 Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway 9 Division of General Pediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland 10 Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada 11 Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway 12 Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven 13 CEBAM, Belgian Centre for Evidence-Based Medicine, Cochrane Belgium 14 Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia 15 Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia 16 Division of General Internal Medicine, Department of Medicine, Geneva University Hospital, Geneva, Switzerland 17 Unit of Development and Research in Medical Education, Faculty of Medicine, University of Geneva, Geneva, Switzerland 18 Division of Clinical Pharmacology and Toxicology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada 19 Departments of Medicine and Pediatrics, University of Toronto, Toronto, ON, Canada 20 Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals 21 Faculty of Medicine, University of Geneva, Switzerland 22 Indiana University School of Medicine, Indianapolis, IN, USA 23 Canadian Injured Workers’ Alliance, Thunder Bay, ON, Canada 24 Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA 25 Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211, Geneva, Switzerland
  1. Correspondence to: J W Busse bussejwmcmaster.ca

Abstract

Clinical question What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes?

Current practice Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries.

Recommendation The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain.

How this guideline was created An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective.

The evidence This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain.

Understanding the recommendation The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms. Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation.

The increasing legalisation of medical cannabis globally, escalating use by patients, lack of training in the use of medical cannabis or cannabinoids during formal medical education, and inconsistent guidance from professional associations and federal agencies have led to confusion regarding the role of medical cannabis in the management of chronic pain.

In this guideline we have sought to address this confusion by asking what is the optimal, evidence based use of medical cannabis or cannabinoids for chronic pain (box 1).

Overview of chronic pain and medical cannabis or cannabinoids

What is chronic pain and who is affected?

Pain that persists or recurs for three months or more is defined as chronic.1 Approximately 20% of the population in North America,2 Australia,3 and Europe4 report chronic pain; 10-14% report moderate to severe pain in the UK.5 Chronic pain is more common among women,6 elderly people,7 veterans,8 indigenous populations,9 and the socioeconomically disadvantaged.10 The prevalence of chronic pain of any type among middle and low income countries reaches 33%.10

What effect does medical cannabis or cannabinoids have on chronic pain?

Cannabinoids are thought to affect pain through various pathways, including the endocannabinoid system, which has receptors in the central nervous system, periphery, immune and hematologic systems. Cannabis contains over 100 cannabinoids; the 2 most studied of which are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC inhibits glutamate and 5-hydroxytryptamine release and increases dopamine secretion. CBD enhances adenosine receptor signalling, and decreases reactive oxygen species, tumour necrosis factor, and T cell proliferation, without the psychoactive effects of THC.11 The multifaceted analgesic and anti-inflammatory properties of cannabinoids may positively influence the perception of pain across different conditions.

What about opioids?

Opioids are prescribed for 1 in 3 people living with chronic pain12; but increasing recognition of the harms associated with long term opioid use13 and greater appreciation for their, at best, modest benefits14 have generated enthusiasm for alternatives, including medical cannabis.15

In the US, 36 of 50 states and the District of Columbia have legalised cannabis for medical use,1617 and some US states have passed laws encouraging cannabis as a substitute for opioids when managing chronic pain.18

The guideline panel developed this recommendation based on a series of linked systematic reviews19202122 and use of the GRADE approach and standards for trustworthy guidelines. Box 2 includes all of the articles linked in this BMJ Rapid Recommendation package. The infographic provides the recommendation together with an overview of the absolute benefits and harms of medical cannabis or cannabinoids for chronic pain in the standard GRADE format. Clinicians and their patients can find consultation decision aids to facilitate shared decision making in MAGICapp.

Linked articles in this BMJ Rapid Recommendation cluster

Busse JW, Vankrunkelsven P, Zeng L, et al. Medical cannabis or cannabinoids for chronic pain: a clinical practice guideline. BMJ 2021;374:n2040

Summary of the results from the Rapid Recommendation process

Wang L, Hong PJ, May C, et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. BMJ 2021;374:n1034. doi:10.1136/bmj.n1034

Review of randomised trials that assessed medical cannabis or cannabinoids for chronic pain

Zeraatkar D, Cooper MA, Agarwal A, et al. Long-term and serious harms of medical cannabis or cannabinoids for chronic pain: a systematic review of non-randomised studies. medRxiv 2021 doi:10.1101/2021.05.27.21257921

Review of observational studies exploring long term harms associated with use of medical cannabis or cannabinoids for chronic pain

Zeng L, Lytvyn L, Wang X, et al. Values and preferences towards medical cannabis or cannabinoids among patients with chronic pain: a mixed methods systematic review. BMJ Open 2021;0:e050831. doi:10.1136/bmjopen-2021-050831

Review of studies exploring patients’ values and preferences regarding use of medical cannabis or cannabinoids for chronic pain.

Noori A, Miroshnychenko A, Shergill Y, et al. Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies. BMJ Open 2021;11:e047717. doi:10.1136/bmjopen-2020-047717

Review of evidence assessing the impact of medical cannabis or cannabinoids when added to opioids among patients living with chronic pain.

Expanded version of the results with a multilayered recommendation, evidence summaries, and decision aids for use on all electronic devices

Current practice

Although increasingly prescribed or authorised, medicinal cannabis or cannabinoids for chronic pain remains contentious for many physicians because of the suspected or known dangers associated with cannabis use.2324 Some have criticised the substitution of one addictive substance (opioids) for another with uncertain benefit (cannabis).25 In 2018, the vice-president of medical professionalism for the Canadian Medical Association advised that medicinal cannabis should be phased out of practice altogether26; however, surveys show that physicians want more education and guidance around use of medical cannabis or cannabinoids as a potential pain management therapeutic.2728

Clinical practice guidelines have emerged to address this knowledge gap, but with inconsistent recommendations (table 1). The most recent guideline, from the National Institute for Health Care and Excellence (NICE), made strong recommendations against the use of medical cannabis for chronic pain outside of clinical trials.32 Legal action has subsequently been approved against NICE over concerns that their recommendations are overly restrictive and will prevent reasonable access to medical cannabis.33 Current guidelines have important limitations, including limited or absent involvement of patients, failure to consider patient values and preferences to inform recommendations, inadequate consideration and management of financial and intellectual conflicts of interest in panels, selected review of the evidence, and excessive use of strong recommendations in the face of low certainty or absent evidence.34

Current guidance for medical cannabis or cannabinoids and chronic pain

Individuals using cannabis without authorisation from a physician typically consume inhaled forms (that is, smoked or vapourised) with high concentrations of the psychotropic cannabinoid delta-9-tetrahydrocannabinol (THC) and endorse both therapeutic and recreational use. In a Canadian cohort study of 709 community adult users of cannabis in 2018, 80% of those reporting medical use also acknowledged recreational use.35 The use of a recreational substance for therapeutic benefit has raised concerns both regarding the underlying motives of patients seeking medical cannabis and the potential for diversion.36

How this recommendation was created

Our international panel included general practitioners, a physical medicine and rehabilitation physician, internists, a paediatrician, a paediatric anaesthesiologist, pharmacists, physicians specialising in pain management, clinical pharmacologists, a chiropractor, a rheumatologist, methodologists, and people living with chronic pain (including a veteran). The panel decided the scope of the recommendation and the outcomes that are most important to patients. Parallel teams conducted systematic reviews on the benefits and harms of medical cannabis or cannabinoids, long term harms of medical cannabis or cannabinoids, the impact of providing medical cannabis or cannabinoids on opioid substitution, and a systematic search for evidence about patients’ values and preferences (box 2; appendix 1 on bmj.com). The panel met virtually to discuss this evidence and formulate a recommendation. No panel member had financial conflicts of interest; intellectual and professional conflicts were minimised and managed (see appendix 2 on bmj.com). These considerations may be particularly important regarding medical cannabis, as a recent investigation uncovered links between commercial organisations and patient groups and individuals lobbying for increased access to cannabis for medical use.112113

The panel followed the BMJ Rapid Recommendations procedures for creating trustworthy recommendations,114 including using the GRADE approach to critically appraise the evidence and create recommendations (appendix 3 on bmj.com).115 The panel considered the balance of benefits, harms, and burdens of medical cannabis, the certainty of the evidence for each outcome, typical and expected variations in patient values and preferences, and acceptability.116

The evidence

The linked systematic review reports the effects of medical cannabis or cannabinoids, typically when added to standard care, in people living with chronic pain resulting from cancer or non-cancer causes.19 Table 2 gives an overview of the number and types of patients included, the formulations of cannabis and cannabinoids administered, the method of administration, and study funding among randomised trials exploring the benefits and harms of medical cannabis or cannabinoids for management of chronic pain.

Characteristics of 32 eligible randomised clinical trials included in systematic review of medical cannabis for chronic pain

Guided by current surveys and guidance on outcome assessment,6869 the panel identified eight patient-important outcomes needed to inform their recommendation: (1) pain relief, (2) physical functioning, (3) emotional functioning, (4) role functioning, (5) social functioning, (6) sleep quality, (7) opioid substitution, and (8) adverse events.

When considering the adverse events reported among eligible trials, the panel prioritised (in order of importance): cognitive impairment, vomiting, impaired attention, drowsiness, dizziness, nausea, and diarrhoea.

Regarding long term harms, the panel was provided with evidence regarding the risk of cannabis dependence, motor vehicle accident causing injury, falls, suicidal ideation, and suicide associated with medical cannabis or cannabinoid use for chronic pain.

Understanding the recommendation

The panel made a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient to manage pain symptoms), for people living with chronic cancer or non-cancer pain. Strong recommendations indicate that all or almost all fully informed patients would choose the recommended course of action. Weak recommendations reflect the uncertainty in typical patients’ preferences, as well as the likely wide variability in preferences between patients.7071

Who does it apply to?

The recommendation applies to adults and children living with moderate to severe chronic pain regardless of pain mechanism—neuropathic pain (resulting from injury to the somatosensory nervous system, such as diabetic neuropathy); nociceptive pain (injury to non-neural tissues producing noxious stimulus, such as osteoarthritis); and nociplastic pain (pain arising from altered nociception despite no clear evidence of tissue damage, such as fibromyalgia)72—as well as cancer related chronic pain. The panel is confident that the recommendation applies to people with different subtypes of pain as the linked systematic review contained adequate representation from such groups and settings, and, after applying optimal methodology,73 we found no evidence of credible subgroup effects across clinical subtypes of chronic pain. Chronic pain may result from a specific lesion, but in some cases the cause is unspecified.74 Moreover, many people living with chronic pain present with mixed pain—a combination of nociceptive, neuropathic, and/or nociplastic features.7576

No trial eligible for our systematic review explored the effect of inhaled forms of medical cannabis or enrolled patients in palliative care. Our recommendation does not apply to smoked or vapourised forms of cannabis, cannabis provided for recreational purposes, or patients receiving end-of-life care. Moreover, inhaling cannabis is associated with adverse pulmonary events77 that oral and topical administrations avoid.

Trials eligible for our reviews largely excluded chronic pain patients with concurrent mental illness, or those receiving disability benefits or involved in litigation, and did not report the representation of veterans; the generalisability of our recommendation to these populations is therefore uncertain. The median of the mean age among eligible randomised trials we reviewed was 53; a separate review has concluded that, in general, cannabinoid based medicines are safe and acceptable in older adults.78

Patients recruited among eligible trials were adults. However, the panel (which included a general paediatrician and a paediatric anaesthesiologist) could see no reason why the expected benefits would be systematically different among adolescents and emerging adults. Regarding potential harms, the panel noted the evidence for an association between use of cannabis and adverse neurocognitive effects,79 including acute psychotic episodes.80 However, the literature reporting this association has solely focused on recreational use of cannabis, in particular on high doses of inhaled THC,7381 which would not be administered for therapeutic purposes. Neither our review of randomised trials19 nor observational studies20 identified evidence for an association between medical cannabis or cannabinoids and early onset psychosis, but these studies were restricted to adult patients.

Indirect evidence from paediatric populations with epilepsy managed with medical cannabis offers some safety information. A 2020 systematic review of medical cannabis and cannabinoids for paediatric epilepsy found four randomised and 31 non-randomised studies that explored benefits and harms.82 All the randomised trials were considered low risk of bias, whereas the observational studies were at high risk of bias, primarily due to lack of a control group and unblinded outcome assessment. Most studies administered cannabidiol (CBD), often at very high doses (up to 50 mg/kg per day), and three studies provided combination products (CBD and THC). Treatment duration ranged from 10 days to 146 weeks, and no randomised trial followed patients for more than 14 weeks. Two studies that captured emergency department visits found no association between such visits and use of medical cannabis (very low certainty evidence).

In light of current direct and indirect evidence, and because our recommendation applies solely to medical non-inhaled cannabis or cannabinoids, the panel felt the suggestion to consider a trial of medical cannabis or cannabinoids for chronic pain could also apply to younger patients. However, while there is some evidence supporting the safety of CBD in children,82 the safety profile of THC is less certain and the potential for adverse neurocognitive effects should be considered when deciding whether to trial medical cannabis products containing THC.

The evidence suggested the possibility of a subgroup effect, with medical cannabis or cannabinoids showing larger benefits for chronic non-cancer pain and little or no benefit for chronic cancer pain; however, there were few trials informing this subgroup analysis, the analysis of effect was between rather than within trials, and tests of interaction were non-significant (suggesting that chance was a likely explanation).19 As such, the subgroup effect was deemed of very low credibility83 and thus did not affect our recommendation.

Absolute benefits and harms

The infographic explains our recommendation and provides an overview of the absolute benefits and harms of medical cannabis or cannabinoids for chronic pain (GRADE Summary of Findings). Estimates of baseline risk for effects come from the control arms of trials eligible for review.

The panel was confident that non-inhaled medical cannabis or cannabinoids:

Result in a small increase in the proportion of people living with chronic pain experiencing an important improvement in pain and sleep quality (high and moderate certainty evidence, respectively)

Result in a very small increase in the proportion of people living with chronic pain experiencing an important improvement in physical function (high certainty evidence)

Do not improve emotional functioning, role functioning, or social functioning (high certainty evidence)

Result in a small to very small increase in the proportion of people living with chronic pain experiencing cognitive impairment, vomiting, drowsiness, impaired attention, and nausea, and a moderate increase in the proportion of individuals experiencing dizziness that increased with longer follow-up (GRADE moderate to high certainty evidence).

It is unlikely that new information will change interpretation for outcomes that are high to moderate certainty of evidence.

The panel was less confident about:

Whether use of medical cannabis or cannabinoids resulted in reduced use of opioids (GRADE very low certainty evidence)

Whether the use of medical cannabis or cannabinoids was associated with increased risk of cannabis dependence, road traffic accident causing injury, falls, suicidal ideation or suicide, and other potential serious harms (GRADE very low certainty evidence).

Values and preferences

The systematic search for empirical data on patients’ values and preferences related to medical cannabis or cannabinoids for chronic pain identified 15 studies of adults with both cancer and non-cancer chronic pain (appendix 1 on bmj.com).

We found moderate to high certainty evidence that:

People living with chronic pain have greater preference for medical cannabis products with a balanced ratio of THC:CBD or high CBD products, and not for high THC products

Use of medical cannabis or cannabinoids is influenced by both positive (such as support from friends and family) and negative social consequences (such as stigma surrounding cannabis use, disapproval from healthcare providers)

Concerns about medical cannabis or cannabinoids included adverse drug effects, addiction, tolerance, losing control or unusual behaviour, and these are related to unwillingness to use cannabis

Some patients feel that the cost of medical cannabis or cannabinoids is too high, while some report that legalisation has improved access and positively influenced their decision to pursue medical cannabis for symptom relief.

We found low to very-low certainty evidence that:

Patients had varying levels of willingness to use medical cannabis or cannabinoids and most patients who used medical cannabis products reported positive attitudes towards its use

Patients with a history of substance use preferred medical cannabis or cannabinoids over prescription opioids

Patients were motivated to use medical cannabis or cannabinoids to reduce use of prescription medication and felt that it was safer than opioids.

Our weak recommendation in favour of a trial of medical cannabis or cannabinoids reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and a willingness to accept a very small to modest risk of mostly self limited and transient harms. All panel members agreed on the strength of the recommendation (weak); all but two panel members (20 of 22) agreed with the direction of the recommendation.

The panel, including patient partners, believes that there is great variability in how much reduction in pain severity, improvement in physical functioning, or sleep quality each patient would consider important. Patients who place a high value in improving these symptoms by any amount (for example, patients with lower tolerance to pain or those with severe symptoms) are more likely to pursue a trial of medical cannabis or cannabinoids. For example, a 1 in 10 chance of experiencing important pain relief may be insufficient to justify a trial of medical cannabis if patients are achieving reasonable results with their current management and if the unlikely, but possible, development of cognitive impairment or impaired attention would preclude their ability to function at work or at home. Alternately, patients experiencing problematic pain despite optimisation of non-cannabis management, which is a prevalent condition, or who wish to explore the potential for opioid substitution may be willing to consider a trial of medical cannabis or cannabinoids.

Practical issues and other considerations

Box 3 outlines the key practical issues for patients and clinicians discussing a trial of medical cannabis or cannabinoids for chronic pain, which are also accessible along with the evidence as decision aids to support shared decision making in MAGICapp.71

Key practical issues

Medication routine

Therapeutic trials should start with low dose, non-inhaled cannabidiol (CBD) products, gradually increasing the dose and THC level depending on clinical response and tolerability (such as starting at a dose of 5 mg CBD twice daily and increasing by 10 mg every 2-3 days to a maximum daily dose of 40 mg). If response is unsatisfactory, clinicians may consider adding 1-2.5mg THC per day and titrating 1-2.5 mg every 2-7 days to a maximum of 40 mg/day.

Prior cannabis experience should be considered, and adverse event monitoring should be carefully conducted.

For younger or adolescent patients, CBD-predominant preparations should be preferred because of uncertain effects of THC on neurocognitive development.

Administration

Our evidence synthesis was largely informed by oral preparations of medical cannabis or cannabinoids, including sprays, tablets, and oil drops administered sublingually. Our recommendation does not apply to inhaled forms of cannabis, which entails pulmonary exposure to particulate matter and toxins.

Adverse effects

Serious adverse events are unlikely with medical cannabis or cannabinoids, and patients cannot fatally overdose. Dizziness is the most common non-serious adverse event with medical cannabis treatment.

Pregnancy and nursing

Evidence regarding adverse effects of medical cannabis or cannabinoids use during pregnancy or breastfeeding is inconclusive: pregnant women or women contemplating pregnancy should be encouraged to discontinue use of medical cannabis in favour of alternative therapy. Cannabis use during breastfeeding should be discouraged.

Travel and driving

Avoid driving or operating machinery while starting or changing doses of medical cannabis or cannabinoids.

Medical cannabis or cannabinoids are legally available in: Argentina,84 Australia,85 Barbados,86 Bermuda,87 Brazil,85 Canada,88 Chile,88 Colombia,88 Croatia,89 Czech Republic,89 Denmark,89 Ecuador,90 Estonia (with a permit),89 Finland,89 Germany,89 Ghana (only for products with <0.3% THC),91 Israel,88 Italy,88 Jamaica,88 Lebanon,92 Lesotho,91 Malta,89 Mexico,93 the Netherlands,88 New Zealand,94 Peru,95 the Philippines,96 Saint Vincent and the Grenadines,97 San Marino,98 South Africa,91 South Korea,99 Sri Lanka,100 Switzerland,88 Thailand,88 the United Kingdom,88 United States (not at the federal level, but in 36 states and the District of Columbia),17101 Uruguay,88 Vanuatu,102 Zambia and Zimbabwe.91 As of 2018, nabiximols (a cannabis extract consisting of THC and CBD) have been available in all European Union member states except for Bulgaria, Cyprus, Greece, Hungary, Latvia, Romania, and Slovakia. For example, nabiximols are available in Austria, Belgium, France, Ireland, Lithuania, Luxembourg, Malta, Poland, Portugal, Slovenia, and Spain.89 Nabiximols are also available in Turkey.103

Once a trial of medical cannabis has been initiated, unexperienced cannabis users should be reviewed at least every month until a stable dose is achieved; experienced users can be reviewed after three months. If benefits are non-sufficient or problematic adverse events are reported, clinicians may elect to return to a previously tolerated dose, increase CBD or reduce THC dose, or change the route of administration. Cannabis should be discontinued if, despite these strategies, patients continue to experience problematic side effects, a maximum dose is achieved without important benefits, or patients are diverting cannabis or develop a cannabis use disorder. If management with medical cannabis is successful, patients should be followed up (for example, every 3-6 months) after a stable dose is achieved.104105

In the absence of approved products and monographs, efforts are under way to offer pragmatic dosing and administration guidance to clinicians who wish to initiate trials of medical cannabis or cannabinoids with their patients. Following preliminary guidance,105 an industry-led international consensus panel has promoted dosing strategies that involve starting with low doses of oral products (oils, soft gels) that are CBD-predominant and then gradually increasing dose and THC level depending on clinical response and tolerability (for example, starting at a dose of 5 mg CBD twice daily and increasing by 10 mg every 2-3 days to a maximum daily dose of 40 mg).104 If response is unsatisfactory, clinicians may consider adding 1-2.5 mg THC per day and titrating 1-2.5 mg every 2-7 days to a maximum of 40 mg/day.106 Prior cannabis experience should be considered, and adverse event monitoring should be carefully conducted. CBD-predominant preparations should be preferred for younger or adolescent patients because of uncertain effects of THC on neurocognitive development.

Dosing should be individualised and informed by titration, after starting at the lowest plausible therapeutic dose. For example, daily oral doses range from 2.5 mg to 40 mg for dronabinol, from 0.2 mg to 6 mg/day for nabilone, from 1 to 16 oral sprays for nabiximols (dronabinol/cannabidiol), and from 5 to 20 mg/kg/day for Epidiolex (an oil based extract of cannabis containing 98% CBD). Upper limits of dosages may vary between countries. Topical preparations theoretically require lower doses and stay local, therefore reducing harms associated with ingested forms of cannabis; however, commercial products typically lack pharmacokinetic data establishing their ability to cross the aqueous layer and remain localised.107108

The opioid sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.22 Clinicians may, however, consider medical cannabis as part of an approach to help facilitate opioid tapering among consenting patients. Importantly, forced opioid tapering is ineffective and may cause harm.109110

Advertised content of medical cannabis products may not be accurate. One US analysis of 84 products found that 26% contained less CBD than labelled, which could negate any potential clinical effect.111 Furthermore, with the exception of Epidiolex and Sativex, non-synthetic cannabinoids lack a drug identification number and cannot be prescribed by physicians, only authorised.

The bioavailability of oral preparations of medical cannabis or cannabinoids ranges from 13% to 19% and can take up to four hours to reach peak concentrations.107 Dronabinol, THC, and CBD are metabolised in the liver, via cytochromes P450 (CYP) 2C9 and CYP3A, and about a third of the molecules and metabolites are eliminated in the urine (remaining metabolites are eliminated in the faeces). Several metabolites of THC are considered psychoactive. The elimination half-life of dronabinol ranges from 25 to 36 hours, and its main metabolite (11-hydroxy-delta-9-tetrahydrocannabinol) is 44-59 hours; the half-life of CBD is 56-61 hours. The effects of medical cannabis or cannabinoids may be enhanced in patients with renal or liver impairment.

Costs and resources

The panel focused on the perspectives of people living with chronic pain rather than those of society or payers when formulating their recommendation. As identified in our review of patient values and preferences, both legal availability of medical cannabis or cannabinoids and costs are likely to influence decision making.

Uncertainties for future research

Key research questions to inform decision makers and future guidelines include:

Are there systematic differences in treatment effects of medical cannabis or cannabinoids for chronic cancer pain versus chronic non-cancer pain and for nociceptive versus neuropathic versus nociplastic pain?

Are there systematic differences in treatment effects of different formulations and types of medical cannabis or cannabinoids, including CBD, CBD:THC, THC, and PEA?

Does medical cannabis or cannabinoids reduce opioid use for chronic pain?

Are the effects of medical cannabis or cannabinoids consistent among adolescents and young adults with chronic pain?

What is the optimal dose, formulation, and method of administration of medical cannabis or cannabinoids for chronic pain?

What are the benefits and harms of inhaled medical cannabis?

What are the benefits and harms of prolonged medical cannabis or cannabinoid use?

How patients were involved in the creation of this article:

Three people with lived and living experience of chronic pain were members of the guideline panel. These members were involved throughout the process of guideline development, particularly with respect to identifying important outcomes and informing the discussion on values and preferences. Our patient partners agreed that while small reductions in pain severity and small to very small improvements in physical functioning and sleep quality were important to them, these values may not be shared by all patients; they expected moderate to great variability in how much importance other patients would place on small reductions in pain. These panel members participated in teleconferences and email discussions and met all authorship criteria.

Education in practice

How do you currently approach giving pain management advice for patients living with chronic pain? Do you consider offering a trial of medical cannabis or cannabinoids?

The recommendation for medical cannabis or cannabinoids is weak, and patient’s preferences are likely to vary as to whether they wish to pursue a trial of therapy. What information could you share with your patients to help them reach a decision?

Chronic pain is common in many clinical settings. How might you share this guideline recommendation with colleagues to facilitate their learning about current best evidence?

Having read the article, can you think of one thing you have learned which might alter how you consult with patients living with chronic pain?

How often do you practice shared decision making for such preference-sensitive decisions?

Acknowledgments

We thank Will Stahl-Timmins and colleagues at The BMJ for design of the infographics.

Footnotes

This BMJ Rapid Recommendation article is one of a series that provides clinicians with trustworthy recommendations for potentially practice changing evidence. BMJ Rapid Recommendations represent a collaborative effort between the MAGIC group (http://magicproject.org/) and The BMJ. A summary is offered here and the full version including decision aids is on the MAGICapp (https://app.magicapp.org), in multilayered formats for all devices. Those reading and using these recommendations should consider individual patient circumstances, and their values and preferences and may want to use consultation decision aids in MAGICapp to facilitate shared decision making with patients. We encourage adaptation and contextualisation of our recommendations to local or other contexts. Those considering use or adaptation of content may go to MAGICapp to link or extract its content or contact The BMJ for permission to reuse content in this article.

Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 2. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Personal, professional, and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions.

Funding: The Michael G DeGroote Centre for Medicinal Cannabis Research funded the MAGIC Evidence Ecosystem Foundation to support the creation of this Rapid Recommendation. The central operating funding for the Michael G DeGroote Centre for Medicinal Cannabis Research is from a philanthropic gift to the Michael G DeGroote Initiative for Innovation in Healthcare. The centre receives no funding from industry.

Transparency: JWB affirms that the manuscript is an honest, accurate, and transparent account of the recommendation being reported; that no important aspects of the recommendation have been omitted; and that any discrepancies from the recommendation as planned (and, if relevant, registered) have been explained.

See also  cbd oil for stroke recovery