Amid the search for solutions to the opioid epidemic, which kills an estimated 130 Americans every day, some argue that increased access to cannabis could reduce this devastating toll. Part of their reasoning? A 2014 paper published in JAMA Internal Medicine reported lower opioid overdose death rates in states with medical marijuana laws.

A study published Monday in PNAS contradicts that widely cited paper, raising new questions about whether and how medical marijuana can affect the opioid crisis.

The 2014 study found that between 1999 and 2010, states with medical cannabis laws had a nearly 25% lower average rate of opioid overdose deaths than states without such laws. Much has changed since 2010 — 34 states have now legalized medical marijuana and the number of opioid overdose deaths was six times higher in 2017 than it was in 1999 — so Stanford University researchers decided to replicate the original study and expand its analysis to include seven more years of data.

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When they limited their analyses to the same time period as the original study, they saw the same trend. But when they expanded the time frame through 2017, the association between medical marijuana laws and opioid overdose deaths reversed: States with medical marijuana laws had average rates of opioid overdose deaths that were nearly 23% higher than those without these laws.

Lead author Chelsea Shover, a postdoctoral research fellow in psychiatry at Stanford, said this apparent reversal is cause for concern. The 2014 study has been cited in more than 350 scientific articles and drew significant public and media attention. Advocates, industry representatives, and policymakers point to the 2014 findings to argue that marijuana liberalization could help address the opioid epidemic.

“It’s become such a pervasive idea,” said Shover. “It would be amazing if it was this simple, but the evidence is telling us now that it’s not.”

It’s unlikely that the change in findings means that medical marijuana laws were once helpful and are now harmful, Shover said. Instead, as she and her colleagues wrote, the findings suggest that the relationship between medical marijuana laws and opioid overdose deaths “is spurious.”

“This isn’t to say that cannabis was saving lives 10 years ago and it’s killing people today,” said Shover. “We’re saying these two things are probably not causally related.”

Since the Stanford study used the same methods as the original, Shover said it should garner just as much attention. Advocates and policymakers that pointed to data from the 2014 should be interested to know that a longer time frame led to a very different result.

Wayne Hall, a professor at the University of Queensland Centre for Youth Substance Abuse Research in Australia, said the 2014 study made an impact outside the United States. “It’s been cited in my own country as compelling evidence that medical cannabis reduces opioid overdose deaths,” he said. “It will be interesting to see what the response is to the new findings.”

Dr. Sharon Levy, director of the adolescent substance use and addition program at Boston Children’s Hospital and associate professor of pediatrics at Harvard Medical School, has previously expressed concerns about marijuana liberalization as a method to address the opioid epidemic. The relationship between marijuana use and opioid use is extremely complex, Levy said, and poorly understood.

“My life’s work is devoted to helping people with addiction,” said Levy. “But this is the wrong approach.”

Like opioids, medical marijuana is often sought out to manage pain. In fact, according to a 2018 report by New York’s medical marijuana program, the majority of people registering for the program listed severe or chronic pain as their primary condition. If medical marijuana is available as an option for dealing with pain, some people might use it instead of opioids — at least that’s the hypothesis. Several states have even added opioid dependency or “all conditions for which opioids could be prescribed” into their list of qualifying conditions for medical marijuana.

It’s a plausible idea, Shover noted, but these studies should not be considered evidence that it would work. Both the 2014 study and her research were ecological studies. These examine exposures and outcomes at the population level, but cannot capture what is happening at the individual level. In this case, these studies can’t demonstrate that individuals decided to replace opioids with cannabis but only show the number of overdose deaths after states passed medical marijuana laws. Any number of other changes in the state could be factors.

There’s another important limitation. “These large population studies don’t show causality,” said Yasmin Hurd, a neuroscientist and director of the Addiction Institute at Mount Sinai in New York. “There is really no evidence that the changes in medical cannabis laws correlate directly to opioid overdose mortality.”

To get a better idea about how these two factors relate, Hurd said large-scale clinical trials could better reveal how individuals use marijuana and respond to it, and whether cannabis availability could actually reduce the use of opioids. One of Hurd’s recent studies, for example, found that cannabidiol (CBD) could decrease craving and anxiety. But, she said, more studies and larger clinical trials are needed to confirm this finding.

“In a time of an epidemic, we have to think differently,” said Hurd. “We have to be more bold in pushing forward clinical trials on a much faster timeline than we have in the past.”

“This isn’t to say that cannabis was saving lives 10 years ago and it’s killing people today. We’re saying these two things are probably not causally related.”

Stanford's Chelsea Shover, the paper's lead author

The issue of one study contradicting another is not unique to marijuana liberalization and the opioid crisis. Reproducibility is an important and often overlooked aspect of scientific research. Preliminary studies with new and exciting findings understandably garner attention, but it often takes some time before they can be replicated.

The hype surrounding new studies can be especially problematic when they are used to shape public opinion and influence policy decisions. In this case, if the 2014 study is being used to make decisions about how to address the opioid crisis, it’s important to verify its findings.

Hurd agreed. “Is cannabis less of a mortality risk than opioids? Absolutely. Hands down,” she said. “But there’s really no research that says cannabis use per se decreases opioid overdose. You can’t make your medical cannabis laws based on that [hypothesis].”

Medical marijuana does have other therapeutic uses, Shover said, and there are plenty of other, well-supported reasons to consider medical and recreational marijuana laws. “It just doesn’t seem like reducing opioid overdose mortality is one of those benefits,” she said.

There are several strategies for preventing opioid overdose that have more evidence behind them, including increased access to known treatments like methadone and overdose reversals like naloxone. If medical marijuana laws don’t actually affect the number of opioid overdose deaths, then passing them could give policymakers and the public a false sense of addressing the issue.

“The risk is distracting attention away from much more effective interventions that should be implemented to reduce overdose deaths,” said Hall.

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