Role of Medical Marijuana

From Medscape Education Clinical Briefs
Role of Medical Marijuana: Up in Smoke? CME/CE

News Author: Sue Hughes
CME Author: Charles P. Vega, MD



Marijuana continues to stay in the news cycle, as 23 states plus the District of Columbia have passed laws allowing for medical cannabis and recreational use of marijuana is now permitted in the states of Colorado, Washington, and Oregon. The broader acceptance of medical cannabis has led to higher rates of use among patients unfamiliar with marijuana, and many of these patients may select an edible product for reasons of tolerability.

A research letter by Vandrey and colleagues, which appears in the same issue of JAMA as a systematic review of medical cannabis, notes that 16% to 26% of patients receiving medical cannabis are treated with edible forms of the drug. The authors also evaluated whether product labels in 3 US cities were accurate in reflecting the drug concentrations of these edible products.

The researchers were provided 75 products in total; the cannabis dispensaries were unaware that their products would be tested. Only 17% of edible cannabis products were correctly labeled for their concentration of Δ9-tetrahydrocannabinol (THC); 23% of products underestimated and 60% overestimated their THC levels.

The researchers state that previous studies suggest an ideal ratio of cannabidiol (CBD) to THC of 1:1 to maximize the efficacy of medical cannabis and limit adverse events. However, only 13 edible products listed their concentration of CBD, and a total of 59% of edibles had a detectable level of CBD. The median THC:CBD ratio among products that contained CBD was 36:1.

This report calls into question the quality control of active ingredient among edible forms of medical cannabis. The even bigger issue is whether medical cannabis is effective across multiple disease states. The current systematic review and meta-analysis by Whiting and colleagues evaluates this issue.

Study Synopsis and Perspective

With many US states now having laws in place to facilitate access to medical marijuana for a variety of medical conditions, 2 new reviews have highlighted the lack of evidence to support its use in most indications.

An editorial also raises questions about the legal implications for clinicians prescribing such products. The reviews, published in the June 23/30 issue of JAMA, note that 23 states and the District of Columbia have enacted laws to allow the prescription of medical marijuana for certain medical conditions.

Reviewing the medical literature on medical marijuana, the 2 papers come to similar conclusions: there is some evidence to support the use of marijuana for nausea and vomiting related to chemotherapy, specific pain syndromes, and spasticity from multiple sclerosis. For most other indications, such as hepatitis C, Crohn's disease, Parkinson's disease, or Tourette's syndrome, however, the evidence supporting the use of medical marijuana is of poor quality.

A third paper published in the same issue of JAMA highlights the large variability in specific cannabinoids in various medical marijuana products and found that contents did not conform to what was advertised on the label.

In an accompanying editorial, Deepak Cyril D'Souza, MBBS, MD, and Mohini Ranganathan, MD, both from the Yale University School of Medicine, New Haven; VA Connecticut Healthcare System, West Haven; and Connecticut Mental Health Center, New Haven, Connecticut, note that for most of the conditions that qualify for medical marijuana use, the evidence fails to meet US Food and Drug Administration standards.

They call for government support to conduct high-quality trials, and until such trials are available, they suggest it may be prudent to wait before widely adopting use of medical marijuana. "Perhaps it is time to place the horse back in front of the cart," they conclude.

Legal Implications Unclear

The editorialists point out that for physicians, the legal implications of certifying patients for medical marijuana remain unclear, given the differences between the views of state vs federal government.
They emphasize that the prescription, supply, or sale of marijuana is illegal by federal law and that it is not known to what extent a physician who certifies a patient for medical marijuana may be liable for negative outcomes and whether malpractice insurance will cover any liability.

In one of the review papers, Kevin P. Hill, MD, from McLean Hospital, Belmont, Massachusetts, examined 28 randomized clinical trials of cannabinoids in various indications.He notes that there are 2 cannabinoids (dronabinol and nabilone) that are approved by the US Food and Drug Administration for nausea and appetite stimulation.

Apart from these 2 indications, Dr Hill found that use of marijuana for chronic pain, neuropathic pain, and spasticity resulting from multiple sclerosis is supported by high-quality evidence. Six trials that included 325 patients examined chronic pain, 6 trials that included 396 patients investigated neuropathic pain, and 12 trials that included 1600 patients focused on multiple sclerosis.

Several of these trials had positive results, suggesting marijuana or cannabinoids may be efficacious for these indications.The other review paper, by a team led by Penny F. Whiting, PhD, from University Hospitals Bristol National Health Service Foundation Trust, United Kingdom, evaluated 79 trials of cannabinoids in a total of 6462 participants.

Indications included nausea and vomiting caused by chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity resulting from multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.

There was better evidence of efficacy in nausea and vomiting (with 47% of patients receiving treatment showing a complete response vs 20% with placebo in 3 trials), pain (with 37% of patients receiving treatment reporting a reduction vs 31% receiving placebo in 8 trials), and spasticity (with an average reduction in the Ashworth spasticity scale of −0.36 in 7 trials).

Both reviews report an increased risk for short-term adverse effects including dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, hallucination, addiction, and worsening of psychiatric illnesses such as anxiety and mood disorders.

Inaccurate Labeling

For the research letter on dosing, a team led by Ryan Vandrey, PhD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, report that of 75 products purchased (47 different brands), 17% were accurately labeled, 23% were underlabeled, and 60% were overlabeled with respect to tetrahydrocannabinol content.

"Edible cannabis products from 3 major metropolitan areas, though unregulated, failed to meet basic label accuracy standards for pharmaceuticals," the authors write.

"Because medical cannabis is recommended for specific health conditions, regulation and quality assurance are needed," they conclude.

In their editorial, Dr D'Souza and Dr Ranganathan note that there are inconsistencies in how medical conditions are qualified for medical marijuana use within a state and between states. For example, in Connecticut, psoriasis and sickle cell disease, but not Tourette syndrome, qualify, even though the supporting evidence for all 3 conditions is uniformly of very low quality.
Similarly, posttraumatic stress disorder is approved as a qualifying condition in some, but not all, US states.

The editorialists also point out that marijuana is a complex of more than 400 compounds, including up to 70 cannabinoids, which have individual or interactive effects, and that the composition of cannabis preparations can vary substantially.

The editorialists advise that because of the risk for psychosis with marijuana, there need to be explicit contraindications for use in patients with schizophrenia, bipolar disorder, or substance dependence, as well as measures to minimize their access to it. They suggest that follow-up programs should be introduced to monitor long-term outcomes in patients taking medical marijuana.

Given that cannabinoid exposure during critical periods of brain development is associated with long-lasting changes in behavior and cognition, they add that careful consideration is needed to determine at what age exposure to medical marijuana is justifiable.

JAMA. 2015;313:2431-2432, 2456-2483, 2491-2493.