Rise of Marijuana Cries Out for Research, Regulation, Physicians Say

What are the consequences of making marijuana available? Doctors from the University of Colorado share this account from the emergency department (ED):

A decade ago, they write in the Annals of Internal Medicine,¹ a child with marijuana exposure was a rare event. After the federal government minimized enforcement of the state’s medical marijuana law in 2009, children began showing up in the ED at the state’s largest pediatric hospital, mostly after consuming products containing marijuana, or cannabis. Eight children were hospitalized in 14 months. There had been no hospitalizations in the previous 4 years.

“These hospitalizations are almost always due to unintentional, unsupervised ingestion of an edible product containing cannabis, such as candy or baked goods,” the Colorado doctors write in a special commentary section of Annals on marijuana’s rising availability, published today. “We still see several each month.”

The opioid crisis has left patients and physicians looking for alternatives to treat pain, reduce anxiety, and improve sleep. Today, 34 states allow medical marijuana and 10 permit recreational use, but gaps in evidence put physicians and insurers in a bind. When should marijuana be prescribed? What doses are appropriate? And will marijuana ever be covered by insurance?

Research and regulatory gaps will only grow unless the scientific community and policy leaders fill the void, according to the commentary series in Annals, the official journal of the American College of Physicians, which represents both primary care physicians and specialists.

Authors from the Center for Preventive Cardiology at the Oregon Health and Sciences University (OHSU) highlight the urgency for policy makers: They cite data that show a 455% increase in marijuana use from 2002 to 2014 among adults aged 55 to 64 years and a 333% increase among those 64 years or older—the population eligible for Medicare or close to it. “Health providers often do not ask for a history of marijuana use, and—depending on state laws—patients may not always be forthcoming in disclosing it,” they write. Thus, it’s important for doctors to ask about marijuana use in a nonjudgmental way.²

Editors of Annals received more than 100 manuscripts from readers about aspects of prescribing or recommending marijuana, and the 6 commentaries selected address both medical and recreational use:

• A paper from the University of Pittsburgh Medical Center (UPMC) Health Plan outlines the “conundrum” surrounding marijuana: There is great interest among physicians, insurers, and patients in using cannabis products instead of opioids for pain relief, but “much of [the] evidence is observational or anecdotal,” instead of the gold standard of a clinical trial.³
• Like the UPMC Health Plan authors, Jan K. Carney, MD, MPH, of the University of Vermont, writes about the lack of standardization of the product. She notes supplies in federally sanctioned research projects “may be less potent than state products, creating an environment where research findings—even if experiments are rigorously conducted—may not mirror real-world outcomes.”⁴
• Kevin P. Boehnke, PhD, and Daniel J. Clauw, MD, of the University of Michigan Medical School, describe dosing with cannabidiol, the component of cannabis that is not intoxicating. They say this should be used alone before adding tetrahydrocannabinol, commonly known as THC. Neither, however, is a first-line treatment before opioids, the authors say.⁵
• When it comes to what forms of marijuana are best for medical use, various papers recommended drops or edibles, or vaping instead of smoking. In June 2018, the FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with 2 rare and severe forms of epilepsy. It was the first FDA-approved drug that contained a purified drug substance derived from marijuana.
• While the papers saw potential for medical marijuana, both Carney and the OHSU authors discussed the potential harms of recreational use. Carney cited survey data to show that 30% of the public now believes marijuana prevents health problems, while the OHSU authors highlighted a 1988 study in the New England Journal of Medicine that found that smoking marijuana restricted oxygen flow through body at 5 times the rate of tobacco.
• As marijuana goes mainstream, more women are smoking it during pregnancy and while breastfeeding, despite the lack of evidence this is safe for the baby. Absent clinical trials, marijuana and its components should be avoided by pregnant women and nursing mothers, writes Eli Y. Adashi, MD, MS.⁶

Special Challenges for Payers

A program in Pennsylvania has convened stakeholders to promote clinical research, according to the authors from the UPMC Health Plan. At the same time, these authors say, the federal law that treats marijuana as a Schedule I drug with “no currently accepted medical use” remains a roadblock to research and to insurance coverage.

In an email to The American Journal of Managed Care^® (AJMC^®), Chester B. Good, MD, MPH, of the Center for Value-Based Pharmacy Initiatives and lead author on the UPMC Health Plan commentary, said health insurers already weigh “real-world evidence” to support coverage decisions, but they do so in combination with evidence from clinical trials, evidence-based guidelines, and FDA approvals. In the case of medical marijuana, consideration of nontraditional traditional data is especially difficult, he said, “because dispensaries are not under the purview of health plans and insurers typically do not know what specific product has been dispensed.”

When products have varying concentrations of active ingredients, different forms of administration and dosing, “the challenge of using ‘real world’ data is considerable, even within the context of [medical marijuana] patient registries,” Good said.

“With these caveats,” he said, “it is my personal belief that insurers will need to consider nontraditional data, and eventually (assuming removal of legal constraints) can use these data for coverage decisions.”

AJMC^® asked Good if lack of coverage for medical marijuana creates inequities for low-income patients with cancer. He said this question assumes medical marijuana is safe and effective, and right now the evidence is not adequate; however, the question “raises an important ethical question.”

As evidence increases, Good said insurers may consider targeted coverage after “thoughtful analysis” in state-level medical marijuana programs. But as long as medical marijuana is a Schedule I drug, and the evidence gap persists, inequities will likely remain, which he said, “may or may not be clinically significant.”

Indeed, payers who spoke with Evidence-Based Oncology™ in October 2018 said the legal barriers and the lack of an FDA-approved product have left them no choice but to deny coverage. The article addressed medical marijuana within the context of cancer care; a study had found that 80% of oncologists had discussed medical marijuana with patients but only 30% felt they had adequate information on the subject. Meanwhile, none of the major professional oncology organizations had guidelines on marijuana, except that the American Cancer Society has called for more research.

Today, rules for prescribing medical marijuana vary by state, but frequently this requires a special license; oncologists often refer cancer patients to prescribers who also treat patients with chronic pain or other conditions.

Developing clinical trials for marijuana while investors are getting commercial marijuana markets off the ground can create conflicts. The Pittsburgh Post-Gazette reported last month that the Pennsylvania Department of Health rejected all 8 applicants to the research initiative—including the University of Pittsburgh School of Medicine—after opposition arose from the existing dispensaries. A second application process is planned.

“It is imperative that clinicians who are licensed to recommend medical marijuana, insurers, and academic institutions participate in this program to create mechanisms to comprehensively assess outcomes,” Good and his co-authors wrote. “These partnerships will be critical for the development of real-world evidence that can inform future use of these products and may form the basis to allow for insurance coverage.”

References

1. Heard K, Monte AA, Hoyte CO. Consequences of marijuana: observations from the emergency department [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-3280.

2. Kaufman TM, Fazio S, Shapiro MD. Marijuana and cardiovascular disease—what should we tell patients? [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-3009.

3. Good CB, Parekh N, Fischer K, Schuster J, Manolis C, Shrank W. Treating pain—the cannabis conundrum [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-3237.

4. Carney JK. Advocating for blunt policy [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-3167.

5. Boehnke KF, Clauw DJ. Cannabinoid dosing for chronic pain management [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-2972.

6. Adashi EY. Marijuana use during gestation and lactation—harmful until proved safe [published online January 7, 2019]. Ann Intern Med. doi: 10.7326/M18-3175.