Cannabinoids, Pain, and Opioid Use Reduction : The Importance of Distilling and Disseminating Existing Data, Kent E. Hutchison et al., 2019

Cannabinoids, Pain, and Opioid Use Reduction : The Importance of Distilling and Disseminating Existing Data

Kent E. HUTCHISON, Sarah L. HAGERTY, Jeffrey GALINKIN, Angela D. BRYAN, L. Cinnamon BIDWELL

Cannabis and Cannabinoid Research, 2019, 4, (3), 158-164.

Doi : 10.1089/can.2018.0052



The high prevalence of chronic pain conditions combined with an over-reliance on opioid prescriptions has resulted in an opioid epidemic and a desperate need for solutions. There is some debate about whether cannabis might play a role in addressing chronic pain conditions as well as the opioid epidemic. Recent surveys suggest that a large number of people are using cannabis as a treatment for pain and to reduce use of opioids, and cannabis-derived products demonstrate at least modest efficacy in the treatment of pain in randomized controlled trials. In addition, surveillance studies from countries that have approved the use of Sativex, which is a cannabis-based product, have demonstrated that a combination of D9-tetrahydrocannabinol and cannabidiol has low potential for harm, is well tolerated, and is helpful to patients. Given the number of people in the United States who are already using cannabis to manage pain and opioid use in state-regulated markets, it is imperative to conduct additional research in these areas, and to disseminate information on how to minimize harm and maximize any benefits of using cannabinoids to mitigate pain and reduce opioid use. The purpose of this article is to call attention to the fact that cannabis is being used in the management of chronic pain. Thus, this article also provides a set of guidelines on how to approach using cannabis to treat pain.

Keywords : cannabis; pain; opioids


As the nation continues to grapple with the interconnected problems of chronic pain and the opioid epidemic, practical, and effective solutions that can be deployed quickly remain elusive. Some reviews have suggested that cannabinoids may play an important role in both pain control1 and the opioid problem,2 while others have dismissed this possibility.3 A flaw among some of the more negative reviews is that they often ignore evidence from other parts of the world, indicating that a cannabis-derived medication (e.g., Sativex) is both effective at managing chronic pain and has very low potential for harm. Despite this evidence, there are currently no published guidelines on how to minimize harms and maximize benefits when using cannabis products. The intention of the present communication
is to (1) call attention to the fact that many people are currently using cannabis to treat chronic pain and reduce opioid use; (2) advocate for research at the intersection of cannabis, pain, and opioids; and (3) provide preliminary evidence-based guidelines for using cannabis in light of the fact that many people are already choosing to do in the absence of such direction. To that end, we provide a brief synopsis
of the twin problems of chronic pain and opioid dependence, followed by reviews of studies that have
examined the effect of cannabis products on pain, and of those that have examined the effect of cannabis
on opioid use. In addition, we summarize existing evidence on the safety and tolerability of different oral formulations of cannabis, and suggest evidence-based guidelines regarding the use of cannabis products in the management of pain and reduction of opioid use.

Chronic Pain and the Opioid Epidemic

The opioid epidemic is linked to the use of prescription opioids to manage pain, and recent estimates suggest that 25.3 million U.S. adults suffer from daily chronic pain.4While there are a number of nonopioid-approved treatments for both neuropathic and somatic pain (e.g., nonsteroidal anti-inflammatory drugs (NSAIDS), tricyclic antidepressants, gabapentin, pregabalin), many of these treatments have demonstrated low efficacy, undesirable side effects, and poor tolerability.5,6 Further,
adjunct therapies such as physical therapy, cognitivebehavioral treatments, and acupuncture, which are
accepted as effective for chronic pain,7,8 are not always reimbursed by insurance companies.9

Over the past two decades, opioid prescriptions have risen dramatically. Between 1999 and 2010, there was a fourfold increase in opioid prescriptions,10 while the rate of opioid drug overdose deaths increased 200% since the year 2000.11 Opioid-related overdose deaths continue to increase as those who were initially prescribed opioid medications have turned to street forms of opioids, including heroin and dangerously strong synthetics (i.e., fentanyl and fentanyl derivatives12). Although there are likely multifactorial reasons why this transition occurs, results from qualitative studies suggest that people who previously used prescription opioids transitioned to illegal forms of opioids due to cost and ease of access after becoming physically and emotionally addicted to prescription opioid pills.13 Some estimates suggest that among heroin injectors, 39% report being ‘‘hooked on’’ prescription type opioids before transitioning to heroin.14

In addition to the high risk of overdose, there are a number of other concerns associated with long-term
opioid use. For example, there is a distinct lack of evidence for the usefulness and safety of using opioids in the treatment of chronic pain conditions.15 Of the estimated 91.8 million U.S. adults who use prescription opioids for pain, 12.5% report misuse.16 The high rate of misuse could be explained, at least in part, by tolerance that develops with continued opioid use. Continued opioid use is associated with two key processes: opioid tolerance and opioid-induced pain sensitivity (hyperalgesia). In concert, these phenomena can reduce the efficacy of opioids for treating chronic pain and contribute to opioid misuse.17 Other studies suggest that opioid-induced central immune signaling underlies opioid tolerance and hyperalgesia.18 Relatedly, prolonged opioid use has been associated with neuroinflammation and damage to the brain and immune system.19 Finally, recent evidence suggests that opioid treatment for chronic pain is no more effective than nonopioid medication at facilitating better pain-related function.20 Therefore, in many cases, the adverse consequences associated with opioid use outweigh any
benefit to the patient.

Taken together, the use of opioids as a long-term treatment for chronic pain is associated with notable
drawbacks and distinct danger froma public health perspective. As a result, in 2016 the CDC published new guidelines regarding the prescription of opioids, including a set of 12 recommendations.21 While changes prompted by these guidelines represent important controls, they could compound the problem, as individuals who are dependent and/or rely on opioids to control pain might turn in increasing numbers to opioids purchased illegally, leading to more overdose deaths in the short term.22,23 In conclusion, while opioids are effective short-term analgesics, they have a negative long-termimpact on the individual and on society. The United States needs new, effective approaches that address both pain management and opioid dependence.

Pain Management and Cannabinoids

Patient preferences and behavior In recent years, a number of epidemiological studies and randomized controlled clinical trials have suggested that people are trying cannabis to treat pain conditions. For example, studies indicate that relief from chronic pain is by far the most common motivation
among individuals who use medical cannabis, with 87–94% of medical cannabis users reporting that they use cannabis for relief of a pain condition.24,25 Existing data further suggest that people find cannabis to be an effective strategy for pain management. For example, in a recent study of 2897 medical cannabis patients in the United States, >80% reported that cannabis was more effective than opioid medications for pain management. 26 In another study, the authors surveyed 501 perioperative patients at Mt. Sinai Hospital, and found that >80% believed that cannabis would help with pain management.27 Other studies ranging from survey studies among large community samples to open-label studies of medicinal cannabis have also suggested that many chronic pain patients effectively use cannabis to control pain.28–31 Thus, even in the absence of a consensus in the medical community that cannabinoids are effective at controlling pain, patients believe that cannabis helps control pain and are using cannabis to control pain.

The conclusions drawn from the above studies should be interpreted in the context of the relevant limitations. Specifically, it should be acknowledged that many of the studies supporting the idea that cannabis is associated with decreased opioid use include survey/ self-report data and time-series data at the state level. Randomized trials that test the question of whether cannabis use decreases opioid use are lacking. Therefore, additional research that more rigorously extends upon the existing literature needs to be done before concluding that a causal relationship exists between cannabis use and opioid use.