Medical Marijuana and the Opioid Crisis

BETWEEN 1999 AND 2014, the Centers for Disease Control and Prevention (CDC) reported sales of prescription opioids in the United States nearly quadrupled.¹ During this period, 351,630 deaths were attributed to opioid overdoses. In 2016, there was an average of 115 such deaths per day.² And, to date, this figure continues to escalate at an alarming rate.

The Opioid Crisis

According to CDC, prescription opioids are not the cause of the opioid crisis in this country. Instead, it cites illicitly manufactured fentanyl (IMF) — a synthetic opioid — as the main driver behind the crisis. Indeed, from 2012 to 2015, there was a 264 percent increase in synthetic opioid deaths. And, even though prescription opioid rates have fallen, overdoses associated with IMF have risen dramatically, contributing to a sharp spike in synthetic opioid deaths, as IMF is often mixed with heroin, counterfeit pills and cocaine with or without user knowledge.³

The reason opioid prescriptions nearly quadrupled between 1999 and 2014 is twofold. First, it was a response to patients who reported chronic pain to their doctors but were under-prescribed pain medication. Second, millions of Americans experience severe or chronic pain due to myriad health conditions.⁴

According to the Journal of Pain, based on the 2012 National Health Interview Survey, 25.3 million American adults suffered from daily pain; 23.4 million American adults reported a lot of pain; 25.4 million American adults experienced category 3 pain; and 14.4 million American adults experienced the highest level of pain, category 4.⁵

The five most common chronic pain conditions include chronic low back pain, chronic neck pain, fibromyalgia, osteoarthritis and tension headaches. Other highly painful conditions include multiple sclerosis and rheumatoid arthritis.

Marijuana As a Replacement for Opioids

To address the dramatically increasing number of opioid overdoses, researchers, doctors and chronic pain patients have asked if marijuana could be used as an adjunct to or substitute for opioids in the treatment of chronic pain, potentially alleviating the opioid crisis.

In fact, there is growing public and government support to use marijuana to treat chronic pain. A recent Gallup poll showed 64 percent of Americans are in favor of legalizing marijuana6 and, as of June, 31 states plus Guam, Puerto Rico and the District of Columbia have legalized the medical use of cannabis. Fifteen other states have more restrictive laws limiting tetrahydrocannabinol (THC) content, for the purpose of allowing access to products that are rich in cannabidiol (CBD), a nonpsychoactive component of cannabis. As of January, nine states plus the District of Columbia have legalized the recreational use of cannabis, and another 13 states plus the U.S. Virgin Islands are considered to have decriminalized cannabis.⁷

In addition to public support, a growing body of research shows there is sufficient data to indicate marijuana could be beneficial in treating chronic pain, and by extension, potentially alleviate the current opioid crisis. Following are some findings:

• In a population-based, cross-sectional study in May, using the all-capture Medicaid prescription data from 2011 to 2016, medical marijuana laws and adult-use marijuana laws were associated with lower opioid prescribing rates (5.88 percent and 6.38 percent, respectively). The study’s researchers said medical and adult-use marijuana laws have the potential to lower opioid prescribing for Medicaid enrollees, a high-risk population for chronic pain, opioid use disorder and opioid overdose, and marijuana liberalization may serve as a component of a comprehensive package to tackle the opioid epidemic. The researchers also said marijuana is one of the potential non-opioid alternatives that can relieve pain at a relatively lower risk of addiction with virtually no risk of overdose.⁸
• A study titled Health Effects of Cannabis and Cannabinoids: Current State of Evidence and Recommendations for Research conducted by the National Academies of Sciences, Engineering and Medicine in 2017 found there is conclusive or substantial evidence cannabis or cannabinoids are effective for treating chronic pain in adults. In addition, it said there is moderate evidence cannabis or cannabinoids are effective for improving chronic pain.⁹
• A study conducted in 2017 by Bradford and Bradford using quarterly data on all fee-for-service Medicaid prescriptions during 2007 through 2014 tested the association between medical marijuana laws and the average number of prescriptions filled by Medicaid beneficiaries. It found the use of prescription drugs was lower in states with medical marijuana laws than in states without them in five of the nine broad clinical areas studied.¹⁰
• In a study conducted by the University of Michigan in 2016, patients using medical marijuana to control chronic pain reported a 64 percent reduction in their use of more traditional prescription pain medications such as opioids. The 185 patients from a medical marijuana dispensary in Ann Arbor also reported fewer side effects from their medications and a 45 percent improvement in quality of life since using cannabis to manage pain. Researchers said their results suggest, for some people, medical marijuana may be an alternative to more common prescription painkillers.¹¹
• In an April study, results from observational and retrospective studies showed people who use cannabis are more likely than people who do not to also use other drugs. People who take medical cannabis are also more likely to report medical and nonmedical use of opioid analgesics, stimulants and tranquilizers. The researchers surmised given that people who take medical cannabis and those who do not are likely to have different underlying morbidity, it is possible medical cannabis use reduces prescription drug use, yet prescription drug use remains relatively high. They concluded studies comparing people who take medical cannabis with people who do not cannot draw conclusions about the effect of medical cannabis on drug use.¹²
• In a study dated March 7, researchers stated the potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might outweigh their potential harms. According to the researchers, the quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities.¹³
• A study conducted in 2012 by the Centre for Addictions Research of British Columbia in Canada stated there is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates to treat chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side effects) by patients in a clinical setting. Additionally, it found cannabinoids can prevent the development of tolerance to and withdrawal from opiates and can even rekindle opiate analgesia after a prior dosage has become ineffective. According to the researchers, novel research suggests cannabis may be useful in treating problematic substance use.¹⁴ The researchers say these findings suggest increasing safe access to medical cannabis may reduce the personal and social harms associated with addiction, particularly in relation to the growing problematic use of pharmaceutical opiates. Despite a lack of regulatory oversight by federal governments in North America, they said, community-based medical cannabis dispensaries have proved successful at supplying patients with a safe source of cannabis within an environment conducive to healing, and may be reducing the problematic use of pharmaceutical opiates and other potentially harmful substances in their communities.¹⁴
• A systematic review and meta-analysis of cannabinoids for medical use conducted in 2015, which examined a total of 79 trials (6,462 participants) for several indications, including chronic pain, indicated there was moderate-quality evidence to support the use of cannabinoids for treating chronic pain.¹⁵
• In September 2017, the UCLA Cannabis Research Initiative (UCLA-CRI) was created at the UCLA Semel Institute for Neuroscience and Human Behavior. Its initial priorities are the therapeutic potential and health risks of cannabis and to provide education and research to lead public policy and public health decisions regarding cannabis.

The UCLA-CRI’s first planned study is the world’s first placebo randomized controlled clinical trial to evaluate whether cannabis can reduce or eliminate opioid use in chronic pain patients who have been using opioids long-term. Its second study is a prospective observational study of individuals who are opioid-dependent and are initiating cannabis use in an attempt to reduce or eliminate opioid use.

According to Jeff Chen, MD, director at UCLA-CRI, “There is substantial evidence that cannabis is effective for chronic pain, and there is emerging preliminary evidence that cannabis may be opioid-sparing. That is, when used in combination with opioids, cannabis may be able to reduce the amounts of opioids needed to achieve the same level of pain relief. There is also preliminary evidence that CBD possesses anti-addictive properties. And, there is preliminary evidence that cannabinoids may be able to reduce neuroinflammation, which is associated with chronic pain and chronic opioid use. Neuroinflammation is also associated with a host of psychiatric disorders such as depression and anxiety.”

Igor Spigelman, PhD, a neuro-pharmacologist at UCLA-CRI, is conducting translational neurobiology research into disorders such as chronic pain, and he is currently leading the study titled Peripherally Restricted Novel Cannabinoids for the Treatment of Chronic Pain. “Specifically, Dr. Spigelman is working with a novel cannabinoid that has been modified so it does not cross the blood-brain barrier,” said Dr. Chen. “Therefore, it cannot activate the cannabinoid type 1 receptors in the central nervous system, which means no psychoactivity. However, it can activate cannabinoid receptors in the periphery and, thus, reduce pain and inflammation.”

The Future of Marijuana

Although there has never been a documented case of a marijuana overdose, some study results have provided negative and contradictory evidence such as how marijuana can help patients with chronic pain but it can cause adverse health effects,¹⁸ or how marijuana can cure addiction to opioids but it can be addictive itself. Most researchers agree much more research and clinical trials are needed before they can say for certain if marijuana can help treat patients with chronic pain or whether marijuana can help alleviate the current opioid crisis.

Stanford professor and drug policy expert Keith Humphreys described thestudies concerning cannabis legalization and the decrease in opioid-related deaths and hospital admissions as falling victim to a form of logical error known as ecological fallacy: “It’s correlation, not causation, because you cannot use statistical information about entire populations to understand individual behavior.”¹⁶

And, Susan RB Weiss, PhD, director of the division of extramural research at the National Institute on Drug Abuse, who testified on “Researching the Potential Medical Benefits and Risks of Marijuana” before the Subcommittee on Crime and Terrorism on July 13, 2016, said “Promising preclinical findings do not always prove to be clinically relevant, and even fewer lead to new treatments.”¹⁷

According to CDC, “Even though pain management is one of the most common reasons people use medical marijuana in the U.S., there is limited evidence that marijuana works to treat most types of chronic pain. A few studies have found that marijuana can be helpful in treating neuropathic pain. However, more research is needed to know if marijuana is any better or any worse than other options for managing chronic pain.”¹⁸

The Cannabis and Cannabinoid Research (CCR) journal agrees: “More research is needed to better understand the efficacy, dose-response effects, routes of administration and side-effect profiles for cannabis products that are commonly used in the United States.”

Yet, CCR adds, “Results from studies evaluating cannabis pharmacotherapy for pain demonstrate the complex effects of cannabis-related analgesia. There are multiple randomized controlled clinical trials that show cannabis as an effective pharmacotherapy for pain. However, further examination of preclinical studies of cannabis in pain models underscores the nuances of cannabis’s analgesic and antihyperalgesic effects in animal models, and experimental research examining the effects of cannabis on human pain responding has focused either on healthy adults or clinical pain samples.”

Most importantly, CCR says, “Further studies are necessary to further elucidate the role of cannabis as a potentially safer alternative to opioids for pharmacological pain management.” And, it warns, “As cannabis use increases, additional research to support or refute the current evidence base is essential to attempt to answer the questions that so many healthcare professionals and patients are asking.”¹⁹

Unfortunately, conducting more research can be problematic. Since 1970, marijuana has been designated a Schedule I drug under the Controlled Substances Act, which defines drugs under this designation as having high potential for abuse and no currently accepted medical use. 20 This designation results in barriers for researchers to conduct research and clinical trials on the plant because it is infinitely more difficult for them to obtain a research license and funding for a drug that is illegal. Currently, the University of Mississippi is the only federally approved marijuana grower, through its contract with the National Institute on Drug Abuse’s Drug Supply Program, to supply researchers with highly controlled grown marijuana.²¹

Until the required research and clinical trials have been conducted, and the results have been carefully reviewed to show definitively that marijuana can be used as a treatment for chronic pain, and by extension alleviate the opioid crisis, the probability marijuana will remain designated a Schedule I drug is high.