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15 Articles in Volume 15, Issue #7
Advances in the Diagnosis and Treatment of Chronic Pelvic Pain
Call for Standardization and Quality Assurance for Medical Marijuana Products
Chronic Pain and Falls
Is There a Role for NSAIDs in Patients With Cardiovascular Disease?
Legal Considerations of Medical Marijuana
Letters to the Editor: Antibiotics and Microbiome, Hormone Panel
Marijuana: Does it Cause Cognitive Impairment During Driving?
Medical Marijuana Dispensed by Pharmacists in Connecticut
My Policy on Marijuana
NSAID Sensitivity
Pharmacogenetics and Pain Management
Recommending Medical Marijuana for Pain Conditions
The Inhumane and Dangerous Game of Forced Opioid Reduction
Traditional Chinese Medicine & Acupuncture
Untreated Pelvic Pain Common Among Young Women

Call for Standardization and Quality Assurance for Medical Marijuana Products

Marijuana edible products often are mislabeled, leading to calls to reschedule marijuana and install better oversight of this burgeoning industry.

Practical Pain Management interviewed Gregory T. Carter, MD, MS; Marghie Giuliano, RPh, CAE; Amanda Reiman, PhD, MSW;  Michael M. Miller, MD; and Ryan Vandrey, PhD, for this article.

New research has added fuel to the ongoing debate about medical marijuana. In a proof-of-concept study, researchers found that many edible medical marijuana products sold in a sample of dispensaries in 3 major metropolitan areas had higher or lower amounts of active ingredients than was indicated on the product labels, placing patients at risk for not achieving the desired medical outcome or experiencing adverse effects, as reported in a recent issue of JAMA.1

“If this study is representative of the medical cannabis market, we may have hundreds of thousands of patients buying cannabis products that are mislabeled,” said lead author Ryan Vandrey, PhD, Associate Professor of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine, in Baltimore.

Calling for better regulation and oversight of marijuana edibles, Dr. Vandrey and his colleagues noted that patients who consume products that contain more delta-9-tetrahydrocannabinol (THC) than is stated on the label could experience side effects, including anxiety and psychotic reactions. Patients purchasing products that are overlabeled may be undertreated, the authors noted.

Less Than 20% of Products Accurately Labeled

The study assessed the levels of THC and cannabidiol (CBD) in 75 edible cannabis products, including baked goods, beverages, and candy/chocolates. The products were manufactured by 47 different brands and were legally purchased from 3 medical marijuana dispensaries in Seattle, San Francisco, and Los Angeles.

With respect to THC content of the 75 products, 17% were accurately labeled (ie, within 10% of the labeled value), 23% were underlabeled, and 60% were overlabeled. The analysis of CBD content showed that 54 products (59%) had detectable levels of CBD, but only 13 products listed CBD on the label. Of these 13 products, 4 were overlabeled and 9 were underlabeled.

In addition, the median THC:CBD ratio of products with detectable CBD was 36:1; 7 had ratios of less than 10:1; and only 1 had a 1:1 ratio. This finding indicates that most products contained high levels of THC and low relative concentrations of minor cannabinoids, “raising questions about whether there is much difference in therapeutic effect or tolerability of these products compared with dronabinol [Marinol], an FDA-approved medicine containing pure synthesized THC in capsules intended for oral ingestion and manufactured following strict pharmaceutical standards,” Dr. Vandrey said.

“The testing methods utilized in this study have been validated to be accurate in testing cannabis-infused brownies,” Dr. Vandrey continued. “However, it was not possible for the study team to manufacture the variety of food products obtained in the study to confirm the analytical methods are reliable in all food products. This highlights the need to develop standards for analytical testing, in addition to product manufacturing, and also highlights the fact that the plethora of edible products currently available can create difficulties for developing and implementing quality assurance methods,” he said.

No other medicine is “available in such an assortment of preparations … that add unnecessary complexity to manufacturing and testing methods,” said Dr. Vandrey. “There is no reason that cannabis medicine needs to be available in the form of popcorn, soda, chocolate, and lollipops,” which increase the risk that marijuana “will be unintentionally ingested,” he said.

Need to Standardize Medical Marijuana Products

The study illustrates the need to standarize dosing and laboratory testing of medical marijuana products, as is done with pharmacologic agents, experts suggest.

“We are stuck in a catch 22 situation,” said Gregory T. Carter, MD, MS, a physiatrist who specializes in neuromuscular medicine and practices in Spokane, WA. “Standardized products would be easily developed if it were not for federal regulatory and funding limitations. These limitations also have hampered research and led to clinical trials that are generally small and of short duration, particularly when compared to industry-sponsored trials.”

However, Dr. Carter said that the argument that the lack of standardization makes it difficult to dose cannabis can be countered by applying the “principle of beginning therapy with low doses and gradually increasing the dose as tolerated” to maximize benefit and minimize adverse events. Data show that most patients achieve analgesia with average doses of less than 5 grams of marijuana per day, he said. “However, some patients may require a larger amount to obtain relief,” said Dr. Carter, who recommends medical marijuana to selected patients with chronic pain (see Recommending Medical Marijuana for Pain Conditions).

“We have come leaps and bounds in terms of standardization, packaging, labeling, and testing of cannabis products,” noted Amanda Reiman, PhD, MSW, Manager of Marijuana Law and Policy at the Drug Policy Alliance, in Berkeley, CA. “States like California have been self-regulating for the past 20 years, and the evolution that we have seen from a brownie wrapped in cellophane to a brownie that is in a sealed opaque package with the ingredients listed and that has been tested shows how far we have come,” Dr. Reiman said.

“One piece that is still missing … is that there is no third-party verification system in place for laboratories. Dispensaries may have an amazing staff that knows how to work the equipment, but that is not necessarily something that is fluid throughout the industry … in states that are still trying to put their regulations together. Thus, we do still have far to go, and this means that it is really up to us to educate consumers and explain how to titrate the dose, read labels, and think about consumption,” Dr. Reiman said.

“I believe that the standardization will catch up. We’re looking at a practice and behavior that is 5,000 years old and we are just now starting to institute the same type of standardization and technologies of a modern-day industry. [The improvement] is going to be piecemeal, but I think we are definitely headed in the right direction,” Dr. Reiman said.

Ways to Improve Standardization

The expanding use of medical marijuana has created an ”urgent need for regulation and quality control,” according to Dr. Vandrey. “Regulations should be consistent across states where medical cannabis is allowed, and, most importantly, they should be monitored and enforced.”

Typically, food and drugs are regulated by the FDA, but “medicinal cannabis is not recognized by the FDA,” he said. In the absence of federal regulation, he suggested that “states with medical marijuana laws need to account for the quality and testing of medical marijuana products sold to their residents.”

Unfortunately, “Individual states do not have the experience or the resources the FDA has to regulate medicinal cannabis products, medical cannabis regulations vary greatly between states, and there are no incentives for states to work together to create a single agreeable program for regulation and oversight. Thus, the best solution at this point is for changes to be made at the federal level to allow oversight of medical cannabis across states,” Dr. Vandrey said.

One state that is ahead of the curve is Connecticut, where medical marijuana products are analyzed by independent testing facilities that are certified by the Connecticut Department of Consumer Protection before the products reach dispensaries. The products must meet state-mandated safety requirements that include low tolerance limits for specified bacteria, fungi, heavy metals, and pesticides. Connecticut also is the first state to mandate that pharmacists dispense medical marijuana products and run dispensaries (see Medical Marijuana Dispensed by Pharmacists in Connecticut).

Reclassifying Marijuana

Another proposed strategy for improving standardization and research on medical marijuana is to reclassify marijuana as a Schedule II substance. Marijuana is classified as a Schedule I substance under the U.S. Controlled Substances Act, which means that it has a high potential for abuse, no currently accepted medical value, and lack of accepted safety for use under medical supervision. Yet 23 states and the District of Columbia permit the sale and/or use of medical marijuana, and 4 states and the District of Columbia permit the sale and use of marijuana for recreational purposes.

The Compassionate Access, Research Expansion, and Respect States (CARERS) Act of 2015 aims to reclassify marijuana as a Schedule II substance (see Legal Considerations of Medical Marijuana), which experts say may foster research on use of medical marijuana.2

However, not all stakeholders are in support of this legislation. For example, the American Academy of Pediatrics recently reaffirmed its position against the legalization of marijuana in an updated policy statement, citing potential harms to children and adolescents.3 The Academy recognizes that some exceptions should be made for compassionate use in children with debilitating or life-limiting diseases.

“We know marijuana can be very harmful to adolescent health and development,” said coauthor of the policy statement Seth D. Ammerman, MD, FAAP, a member of the AAP Committee on Substance Abuse, in a statement to the press.4 “Making it more available to adults—even if restrictions are in place—will increase the access for teens. Just the campaigns to legalize marijuana can have the effect of persuading adolescents that marijuana is not dangerous, which can have a devastating impact on their lifelong health and development.”

“While cannabinoids may have potential as a therapy for a number of medical conditions, dispensing marijuana raises concerns regarding purity, dosing, and formulation, all of which are of heightened importance in children,” said William P. Adelman, MD, FAAP, a member of the AAP Committee on Adolescence and a coauthor of the policy statement.4 “We need further research to determine the efficacy and correct dosing for cannabinoids, and we need to formulate cannabinoids safely as [we would] … any other medication,” Dr. Adelman said in a statement to the press.4

In a joint letter to the bill’s chief Senate sponsors Rand Paul and Kirsten Gillibrand, the AAP along with the American Academy of Child and Adolescent Psychiatry, American Psychiatric Association, American Society of Addiction Medicine (ASAM), and Smart Approaches to Marijuana state that they do not support several provisions in the current version of the CARERS Act.5 The organizations expressed concern that legalizing marijuana will increase use and addiction rates among youth, placing them at risk for physical and mental health consequences.5

In addition, the organizations cited the need to include the following provisions to help advance research on medical marijuana but not put children and adolescents at risk:

  • Establishing coordinated, interagency mechanisms to monitor and measure health and safety consequences of state statutes that legalize the cultivation, distribution, and possession of marijuana for medicinal or recreational use
  • Permitting more sources of marijuana for research purposes
  • Improving the timeliness of Department of Justice review of FDA-approved research projects.5

“ASAM believes that federal legislation should focus on promoting medical research related to marijuana’s potentially beneficial compounds rather than provide financial services protections for marijuana-related businesses,” said Michael M. Miller, MD, former President of ASAM and Medical Director of the Herrington Recovery Center at Rogers Memorial Hospital, in Oconomowoc, Wisconsin. “ASAM supports research on various cannabinoid compounds found in marijuana but does not believe that smoking is a healthy or supportable route of medication delivery to the body, and prefers research that will lead to more FDA-approved medications where safety, efficacy, purity, and dosage can be specified,” Dr. Miller told Practical Pain Management.

“There is widespread public support for the compassionate use of products that can be helpful to reduce human suffering, and it is this approach that has contributed to the support of use of marijuana for medical conditions,” Dr. Miller said. “Research may well show the benefits of various cannabinoids in specific dosages for a number of conditions, but the public seems to support [the idea] that marijuana plants (and edibles such as cookies that contain marijuana) should become new ‘drugs’ available for ‘therapeutic use’ and that the FDA’s new drug approval processes should be bypassed for making marijuana available for such use. There are but a few examples (eg, Montana) of any actions that seem to counter this tide of public opinion,” Dr. Miller said.

“Most physicians are compassionate, but this should not mean that physicians support the use of smoking as an appropriate way to deliver a potentially helpful substance to the bloodstream,” Dr. Miller added. “ASAM supports reducing criminal penalties for all adults for possession or use of marijuana but not the expansion of legalization, which would authorize the commercial manufacture, distribution, marketing, and sale of marijuana plants and marijuana products,” he said.

What Does the Future Hold For Medical Marijuana?

“I think the future is very bright, especially if cannabis can be rescheduled out of Schedule I by the Drug Enforcement Agency,” Dr. Carter said. He pointed to strategies to separate the therapeutic effects of cannabinoid (CB) receptor agonists from the unwanted consequences of CB1 receptor activation, as well as approaches to develop selective agonists and antagonists for CB1 and CB2 receptors to maximize therapeutic potential. Another area of development is “strains of cannabis that provide optimal beneficial effects while minimizing any untoward effects,” Dr. Carter said.

“I’ve been working in this field for almost 15 years and if you had told me that the ‘what about the children?’ argument was really going to engage people on this issue, I would have thought you were nuts because we’ve spent so much of our time trying to convince folks that changing drug laws will not put drugs in the hands of children,” Dr. Reiman said. “Now, with medical marijuana, we are starting to see families show up in legislative sessions to ask for access, and I think that has been a huge turning point in destigmatizing the idea of using cannabis as a medicine,” Dr. Reiman said.

Dr. Reiman predicted that medical marijuana would be further destigmatized “in light of rising rate of prescription drug overdose and death. We are seeing the rates of opiate use sky rocket while chronic pain issues continue to persist, and I think people are asking, ‘Why not cannabis?’ In addition, I think we will see recognition at the federal level that cannabis does have medicinal properties, and my hope is that this recognition will help states feel more comfortable passing comprehensive laws that will be most effective for people in need where they live,” Dr. Reiman concluded.

“In the future, I think clinical trials and research of medical marijuana should occur with independently tested products that are held to the same standards, including tolerance limits for specified bacteria, fungi, heavy metals, and pesticides,” said Marghie Giuliano, RPh, CAE, Executive Vice President of the Connecticut Pharmacists Association. “In addition, I would hope that there is less of a stigma for patients who are using medical marijuana. Hopefully, more physicians will consider medical marijuana to be an acceptable alternative for treatment of patients who are not well managed on first-line agents.”

Last updated on: September 21, 2015
Continue Reading:
Recommending Medical Marijuana for Pain Conditions

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