Medical cannabis data remain limited, leaving physicians reluctant to prescribe it

Many physicians are reluctant to prescribe medical cannabis amid its uncertain legal status and preliminary, sometimes contradictory, clinical data.

Jason W. Busse, DC, PhD, the associate director of the Michael D. Degroote Centre for Medical Cannabis Research at McMaster University in Canada, and colleagues recently surveyed Ontario-based family physicians regarding their attitudes toward medical cannabis.

The researchers identified three themes: physicians were reluctant to authorize cannabis use, had concerns regarding the potential harms of cannabis — particularly for neurocognitive development, mental illness and drug interactions in older adults — and lacked practical knowledge on the topic due to both limited evidence and lack of education.

Nonetheless, it is evident that patients continue to use cannabis for medicinal purposes.

Researchers in Washington, where cannabis is recreationally legal, conducted a cross-sectional study using electronic health record data from 185,656 adults who were screened for cannabis use at a primary care visit between Nov. 1, 2017, and Oct. 31, 2018. They reported that 2% of the study population had documented medical cannabis use. Nearly half of these patients had health conditions associated with potential benefits from cannabis use, as outlined by the National Academies of Sciences, Engineering and Medicine’s (NASEM) review. But the researchers also found that about 60% had a condition that is associated with potential risks from cannabis.

Evidence of effectiveness

According to NASEM, oral cannabinoids are an “effective” antiemetic for patients with chemotherapy-induced nausea and vomiting. Adults with chronic pain who were treated with cannabis or cannabinoids also had increased odds for “a clinically significant reduction” in symptoms.

However, the data on cannabis’s effectiveness for other conditions are not definitive. The NASEM review cited “moderate” evidence of improvement in short-term sleep outcomes, and “limited” evidence that suggests it is effective for appetite and weight in patients with HIV or AIDS, and that it improves clinician-measured multiple sclerosis spasticity symptoms, anxiety symptoms and posttraumatic stress disorder symptoms.

Overall, “there are mixed results, with some studies appearing more beneficial than others, but the wide variability in the studies makes them difficult to compare,” Healio Primary Care Peer Perspective Board Member Margot L. Savoy, MD, MPH, FAAFP, an associate professor of family and community medicine at the Lewis Katz School of Medicine, Temple University, said in an interview. “This is one of the limitations of knowing who might benefit from treatment or what dose or formulation would be potentially of help.”

Legality

Other limitations of treating patients with cannabis involve its legal status.

There is a patchwork of qualified legality across the country, with adult and medical use programs in 17 states plus Washington, D.C., and Guam; CBD or low-tetrahydrocannabinol (THC) programs in 12 states; and various forms of medical authorization in 18 states plus Puerto Rico and the U.S. Virgin Islands, according to the National Conference of State Legislatures. However, cannabis is classified as a Schedule I substance, which makes conducting research complicated, Savoy said.

“Even when it’s legalized recreationally at the state level, at the federal level it remains illegal, which makes it a difficult thing to study as a medication,” Megan Lemay, MD, an assistant professor of medicine at Virginia Commonwealth University and an internal and addiction medicine specialist, told Healio Primary Care.

Furthermore, legalities do not always overlap with the existing evidence. For example, although cannabis likely has “limited potential” to treat glaucoma, the NASEM review states that glaucoma is “among the most recognized qualifying ailments” across jurisdictions.

On a state level, the physician’s role in the provision of medical cannabis is to document that a patient has a medical condition that qualifies them for medical cannabis under state law, which protects them from federal repercussions, but there are fewer protections for patients, Jon O. Ebbert, MD, MSc, a faculty member at the Mayo Clinic, and colleagues wrote in the Mayo Clinic Proceedings.

“States have variable statutory approaches for patient legal protections addressing legal arrest, housing, and employment,” Ebbert and colleagues wrote.

Savoy said that some family physicians, particularly those who care for patients impacted by incarceration over drug use, have voiced their support for the decriminalization of THC use.

“While we may not all agree that it is the right treatment of choice, there seems to be agreement that arresting people and the consequences of that arrest and incarceration on their future lives is often devastating and contributes to health disparities and income inequality,” she said.

Cannabis-related enforcement has disproportionately affected Black and Latino communities, according to Steven W. Bender, JD, a professor of law and associate dean for research and faculty development at Seattle University School of Law.

The disparities are “particularly evident in racial profiling and inequities in arrests despite equal usage with whites, and in the deleterious consequences for noncitizens of drug convictions,” Bender wrote. “Additional consequences ... range from those in higher education of student loan denials ... to denials of federally subsidized housing and state-supplied welfare and food stamps to poor users.”

Risks

In addition to legal action, there are other concerns regarding cannabis use.

“I think some of the issues are less about the legalization and more about the vilifying of physicians for trying to manage pain with opiates and anxiety with benzodiazepines in previous years,” Savoy said. “Many were trying to do the best things for their patients and feel very wary of falling for the ‘it’s safe and not addicting’ line we were sold in the past.”

As an addiction specialist, Lemay said that the development of cannabis use disorder is her biggest concern with long-term cannabis use.

“In the lay public, there’s a feeling that cannabis is not an addictive substance, but 10% or more of patients who use cannabis daily or almost daily develop cannabis use disorder, meaning they are using more longer than they intended and may experience negative consequences of their continued use,” she said.

People with a previous substance use disorder are more likely to develop cannabis use disorder, according to Lemay.

“My other big concern is the association of cannabis use with depression, anxiety and psychotic disorders, which I’m especially worried about because these are some of the common reasons patients want to use cannabis medically,” Lemay said.

In addition to these patients, there are other populations that should avoid using cannabis. Savoy said that cannabis could impact development and cause delay in children and adolescents; worsen lung diseases such as asthma or COPD; increase the risk for preterm labor among pregnant women; and transfer THC in breast milk 6 days after the last use.

“People with cardiovascular disease should use caution as well,” Savoy said.

Healio previously reported that cannabinoids can cause cardiomyopathy, myocardial infarction, arrhythmias, sudden death, cerebrovascular accident and potential anti-atherogenic effects.

The NASEM review lists additional, “substantial” risks, including an association between smoking cannabis and respiratory disease, motor vehicle collisions, lower birth weight and schizophrenia or other forms of psychosis.

Clinical implications

Research in the area of medical cannabis is still preliminary. Savoy said she has advised a few patients to consider medical cannabis in the past because their chronic pain was not well-managed with opiates and alternative medications. For these patients, she said escalating opiate doses were subsequently stabilized or reduced.

“I still have concerns that we are trading one addictive substance for another, and I appreciate I’ve been sensitized by the backlash to managing pain with opiates, leading to major addiction issues in the country. That said, we are limited in what truly works to address some of these issues, so I am open to seeing more studies that support the safety and efficacy of use,” Savoy said.

There are multiple areas within cannabis that require further investigation. One is the resolution of contradictory findings. Marcus A. Bachhuber, MD, an assistant professor in the department of medicine at Albert Einstein College of Medicine, and colleagues found that states with medical cannabis programs had lower rates of opioid overdose deaths, but when Chelsea L. Shover, PhD, an assistant professor in residence at the UCLA David Geffen School of Medicine, and colleagues used the same methodology to extend the analysis through 2017, they found the trend reversed: states with medical cannabis programs had more opioid overdose deaths.

In addition, Lemay said one of the most important areas is “more structured research about the potential side effects and harms of the use of medical cannabis.”

“Most of our research on that is just side effects observed in these small studies,” she added.

With additional evidence, some physicians may feel more comfortable recommending medical cannabis to their patients.

“I think if the evidence shakes out and we find that it is truly limited in its harm but able to provide benefits, there will be a chance of more clinicians being willing to prescribe it for their patients,” Savoy said.

References:

Bachhuber MA, et al. JAMA Intern Med. 2014;doi:10.1001/jamainternmed.2014.4005.

Bender SW. UC Davis Law Rev. 2016;https://ssrn.com/abstract=2901528.

Busse JW, et al. CMAJ Open. 2021;doi:10.9778/cmajo.20200187.

Ebbert JO, et al. Mayo Clin Proc. 2018;doi:10.1016/j.mayocp.2018.09.005.

Matson TE, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2021.9375.

McCormick MC, et al. NASEM. 2017;doi:10.17226/24625.

National Conference of State Legislatures. Cannabis Overview. Available at: https://www.ncsl.org/research/civil-and-criminal-justice/marijuana-overview.aspx. Accessed May 18, 2021.

Shover CL, et al. Proc Natl Acad Sci USA. 2019;doi:10.1073/pnas.1903434116.