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Medical News & Perspectives
November 28, 2018

States Move to Substitute Opioids With Medical Marijuana to Quell Epidemic

JAMA. Published online November 28, 2018. doi:10.1001/jama.2018.17329

As state governments grapple with ways to curb the opioid epidemic in their own backyard, New York and Illinois took a relatively new approach last summer by modifying existing medical marijuana laws to allow certain patients to substitute their opioids with medicinal cannabis.

In each state, patients with an opioid prescription or a condition for which an opioid is indicated can instead buy cannabis at a registered dispensary with a physician’s written certification.

After he okayed new regulations, New York State Department of Health Commissioner Howard Zucker, MD, JD, said in a statement that the action “offers providers another treatment option, which is a critical step in combatting the deadly opioid epidemic affecting people across the state.” In Illinois, Gov Bruce Rauner said the law he signed into effect in August is “creating an alternative to opioid addiction.”

Why Allow Substitutions?

Some experts say these laws may be in response to several studies that indicated opioid overdose death rates were lower in states that permit medical marijuana, and that opioid prescribing was lower in Medicaid and Medicare Part D programs in states with legalized medical marijuana. But the studies show an association, not a cause-and-effect relationship, said Ajay Wasan, MD, MSc, vice president of scientific affairs for the American Academy of Pain Medicine. “A lot of those states had other … initiatives to decrease opioid prescribing at the same time,” he noted.

What’s more, the epidemic goes far beyond prescribed opioids. Illicitly manufactured fentanyl has driven much of the increase in opioid overdose deaths since 2013, the Centers for Disease Control and Prevention (CDC) has reported. So laws that allow prescribed opioids to be substituted with medical marijuana overlook a major drug supply that’s fueling the epidemic.

When states adjust their statutes, lawmakers “should be careful about what kind of overdoses they’re talking about,” said Karmen Hanson, MA, a health policy analyst with the Denver-based National Conference of State Legislatures.

“Are they from illicit substances, are they from prescription-looking pills, were those legitimate pills, or were those contraband pills getting crafted in some other country or somebody’s basement? It’s really hard to make generalizations on this topic without knowing exactly what the study or the statistic you’re referencing really reflects,” Hanson said. Opioids—prescription and illicit—were involved in about two-thirds of drug overdose deaths in 2016, the CDC has reported.

Despite those caveats, Hanson noted that other states are looking into substitution laws. “It’s of growing interest to policy makers that are hoping to potentially reduce the opioid epidemic, but the science is just now starting to look at this specific issue,” she said.

It Makes Sense, but …

In its 2017 report on cannabis and cannabinoids, the National Academies of Sciences, Engineering, and Medicine concluded that evidence supports using medical marijuana or cannabinoids to relieve pain. But is it an effective substitute for an opioid?

Given the opioid epidemic’s toll, “it makes sense” to try substitutions, said Chinazo Cunningham, MD, MS, professor of medicine and director of the Montefiore Buprenorphine Treatment Network at the Albert Einstein College of Medicine and Montefiore Medical Center in New York City. “[W]e know that cannabis reduces pain,” she added. In addition, opioid prescribing rates also have dropped since 2012, so some patients will have to consider other options. Enacting substitution laws “is one way where people see that they can address their pain,” Cunningham said.

Wasan said data on the efficacy of substituting prescribed opioids with medical marijuana are scant. “But most people agree that it’s a reasonable thing to try,” he added. “If you’re going to certify someone for medical marijuana, you should use it to wean the opioids down.”

Case reports have shown that medical marijuana helped some patients with pain to reduce their opioid use by 60% to 100%. In a survey examining medical marijuana’s safety in older adults, about two-thirds of 2736 patients past age 65 years used medical marijuana for cancer or nonspecific pain. Among 791 patients who answered questions about their medication changes, 18% stopped using opioids or reduced their dose after 6 months. However, another study of 1514 patients in Australia who used opioids for chronic noncancer pain showed that medical marijuana didn’t improve their outcomes or reduce their opioid use.

At the University of Pittsburgh Medical Center, where Wasan is vice chair for pain medicine in the Department of Anesthesiology, many of the patients with chronic pain do well with prescribed opioids. Yet some are interested in trying medical marijuana to see if it will help them reduce or stop opioids. Many are women in their 70s.

“[They’ve] never used a single controlled substance in their life,” he said. “They want to take the weakest thing possible, [but] they don’t want to do any vaping.” Options include pills, creams, oils, lozenges, transdermal patches, cookies, and brownies.

Cunningham said many of the patients who ask about medical marijuana at Montefiore simply don’t want to use opioids. “They’re sort of afraid of opioids or they want to come off of opioids,” she said.

Since February, when Pennsylvania’s medical marijuana law went into effect, and while previously practicing in Massachusetts, where medical marijuana is legal, Wasan has seen benefits from using it to wean patients from opioids. “[I] would say about two-thirds are successful,” he noted.

However, laws that allow medical marijuana as a substitute for opioids for treating pain should specify the clinical scenarios in which it is allowed, Wasan explained. “We need to have careful patient selection and evaluation and follow-up,” he said.

For example, he noted, neuropathic pain tends to respond better to medical marijuana than does nonneuropathic pain. One of the main cannabinoid receptors, CB1, is abundant in the central and peripheral nervous systems. Small studies have shown that medical marijuana reduced diabetic peripheral neuropathy pain in patients with treatment-refractory pain, and it helped alleviate HIV-associated neuropathic pain.

However, a recent Cochrane review of 16 studies that included 1750 participants concluded that potential benefits of cannabis-based medications in relieving chronic neuropathic pain may be outweighed by adverse events including somnolence, confusion, and psychosis. Nevertheless, the authors noted that studies in the review were small in size, which could lead to bias, and none produced high-quality evidence to support using medical marijuana for neuropathic pain.

… We Need More Research

Small studies and poor-quality evidence often lead experts to the same conclusion: more research is needed. “This is a really big issue,” Cunningham said. “As states are moving forward with their cannabis policies, the federal government is not keeping up and is, in fact, hampering the scientific discovery.”

Medical marijuana is legal in 31 states, the District of Columbia, Guam, and Puerto Rico even though federal law deems any marijuana use illegal. The US Drug Enforcement Administration (DEA) classifies marijuana as a Schedule I drug with high potential for abuse and severe psychological and/or physical dependence.

The only US source of marijuana that researchers can legally tap is from a federally overseen farm at the University of Mississippi. But marijuana from the farm “is a very different product … than is used by everybody else,” Cunningham said. Some reports indicate that commercially sold marijuana could have levels of tetrahydrocannabinol—the psychoactive component—that are 2 or 3 times higher than what comes from the farm. Thus, investigators who want to study marijuana face extensive regulatory and supply barriers.

“We advocate strongly for more research,” said Jeffrey Selzer, MD, chair of the public policy committee for the American Society of Addiction Medicine. He noted that some animal studies indicate that cannabidiol—a nonpsychoactive component of marijuana—has potential for treating opioid use disorder. Similar studies should be allowed to go forward in humans in well-designed clinical studies with appropriate institutional review board approval and patient protections, Selzer added.

“[W]e need to be able to do the research to help figure out what the best policies should be and what critical care should look like,” Cunningham said.

Medication Instead of Marijuana

New York’s substitution law added opioid use disorder to its list of qualifying conditions for medical marijuana. So along with recommending marijuana as a stand-in for opioids, the law permits marijuana as treatment for opioid use disorder—a somewhat controversial move when the CDC and other experts recommend approved medications. Although Illinois didn’t go the same route, Pennsylvania included opioid use disorder as a qualifying condition under its medical marijuana laws, and Hanson said New Jersey is considering it.

Methadone, buprenorphine, and naltrexone are approved by the US Food and Drug Administration (FDA) for opioid use disorder along with counseling and psychosocial support. Evidence supporting their use “is just so compelling,” said Selzer.

The drugs “successfully treat addiction due to opioids, they prevent overdose, they result in much fewer complications related to opioid use disorder’s assorted health consequences—things like HIV seroconversion—and there’s really no evidence that medical marijuana would do the same,” Selzer added.

Both the FDA and the Substance Abuse and Mental Health Services Administration have tried to dispel the long-held notion that medication treatment essentially substitutes 1 drug for another, even if someone takes the medication for a lifetime. The National Institute on Drug Abuse also explains that the approved medications don’t produce an almost immediate high followed by a quick comedown, and they reduce cravings for and the euphoric effects of opioids.

But the medications are vastly underused. The FDA has advocated for wider availability by suggesting broader insurance coverage and offering the treatment in criminal justice systems. A study published earlier this year showed that among nearly 18 000 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014, only about one-third received medication treatment within a year afterward. The data also showed that methadone or buprenorphine use was associated with lower rates of all-cause or opioid-related mortality.

“[T]he area to really focus on the most is getting effective treatment to people who need it,” Cunningham said.

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