research

The Efficacy of Medical Cannabis

Removing the stigma, doing no harm

BY Stephen Dahmer, MD

Cannabis is the most widely used psychoactive substance in the western world and has been used medicinally for at least 5,000 years. Phytotherapies (plant medicines), from common birch to willow bark, while materia medica for many of our modern pharmaceuticals, are also incredibly complex and difficult to research in their natural form. Nonetheless, current evidence supports exploring medical cannabis for patients that might benefit.

Regardless of our personal opinions, our patients and peers are already making decisions about cannabis, potentially from questionable resources like doctor Google. Support for allowing medical cannabis is strong: 76% of doctors, 93% of Americans, and 83% of veterans support its legal medical use. At the time of writing this, 36 states have effective medical cannabis laws, 13 states have laws pertaining to low-THC, high-CBD cannabis and no states have repealed effective medical cannabis laws. In some form, 49 states acknowledge the medical benefits of cannabis. 

States acknowledge the medical benefits of cannabis.

Statutes establishing the medical cannabis program in Minnesota were enacted in 2014.  Minnesota licensed physicians, advanced practice registered nurses and physician assistants can certify a patient’s qualifying medical condition. They must be enrolled in the Medical Cannabis Registry before certifying a patient’s qualifying condition. Of the 24,643 physicians with active Minnesota licenses, there are 3,739 practitioners that have registered for the medical cannabis program. Estimates as low as 1.4% of all those Minnesotans dealing with chronic pain had linkage to care or saw a provider that certified patients for medical cannabis.

Deceptive statistics

Unfortunately, most research to date has been funded by NIDA (National Institute on Drug Abuse) and has focused on the harms associated with the plant, further supporting a long history of stigma. Nearly half of the 30 journals that have published the largest number of cannabis studies contain harm-associated words in their titles, such as “abuse,” “addictive/addiction,” “dependence” and “forensic.” How might our opinion of any other medication might change if such resources were mobilized to study its potential for harm?

In addition, research funds for products our patients are using are limited, and there is a daunting thicket of regulations to be negotiated at the federal level—those of the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA)—and at the state level. Designation as a Schedule I substance in the Controlled Substance Act only adds even more complexity and expense to any clinical evaluation. Frustration with these barriers to research, enough to make even the head of NIDA reluctant to conduct studies on Schedule I drugs like marijuana because of the “cumbersome” rules that scientists face when investigating them, has even led me to accept a policy position with the U.S. Cannabis Council (USCC).

In the United States prescribing medications is regulated the FDA, which most of us accept as an important system overdue for an overhaul. Of critical concern to the FDA and all of us is that the products we prescribe are safe. Naturally, we also assume they will present therapeutic value; however, here the bar can be surprisingly low. When Prozac went through its initial clinical trials, the patients reporting the best results were from the control group taking the placebo. We all know that not all patients respond the same to all medications. This is where the art of medicine comes in. When a patient first presents with hypertension, it usually takes some experimentation to find what will work best, and it oftentimes will require three different medications to achieve the best outcomes. Based on thousands of years of use, anecdotal reports and extensive research, we know that cannabis is a remarkably safe medication when used in the medical context. There is no known case of a lethal overdose, and we have been monitoring patients closely in Minnesota since the inception of the program.

Sometimes there are no results. For the many patients who report positive outcomes, medications with far greater risk and downstream complications oftentimes are replaced. It is important to be aware of and open to this option. 

Additional research

Additional research holds the promise of better informing us of both benefits and risks of cannabis, but it isn’t so simple. The issue with cannabis is not a lack of research, but rather the complexity of plant medicines which offer a challenge to the well-designed, randomized controlled trials of single-constituent pharmaceuticals to which we are accustomed.

The cannabis plant can produce many therapeutic benefits and creates multiple research challenges when analyzed by the “One-Molecule, One-Target Paradigm” reductionist approach which has served us well in acute care medicine. Further research is paramount to optimizing the complex pharmacognosy of the plant as a form of personalized medicine while minimizing harm.

Emerging research around the endocannabinoid system, a biological system in which endogenous lipid-based retrograde neurotransmitters bind to the proteins in the cannabis plant and are expressed throughout the vertebrate central nervous system and peripheral nervous system, supports a wide range of therapeutic benefits and are well worth further study.

Supporting the patient

Much of what we do in clinical practice is not crystal clear. To approach health and disease in the absence of absolute clinical evidence is no new challenge. Unfortunately, many of us may feel, when dealing with cannabis, that we prefer to turn our backs to the matter—despite solid evidence that this plant might offer a unique and versatile tool for some of our most difficult to treat patients. As clinicians, including with cannabis, we need to weigh the needs of individual patients against broader social issues and make best decisions based on nuanced individual data points specific to the patient.

Patients who are currently suffering from complicated and intractable conditions, who are unrelieved by currently available drugs and might find relief with cannabis, are those we see often at Cannabis Patient Centers (CPCs). These patients find little comfort in a promise of a better drug 10 years from now, and many have already tried FDA-approved synthetics without the same subjective, yet positive, clinical response. As with other therapies we offer, our assessment of the scientific data on the medical value is but one component of complex clinical decision-making.  

Neuropathic pain is a very difficult problem with no easy solution.

Don’t be fooled by the mainstream mantra that the evidence is not there. In 2017, over 10,000 studies were reviewed by the National Academies of Sciences, Engineering and Medicine, which led them to opine: conclusive or substantial evidence that cannabis or cannabinoids are effective in the treatment of chronic pain, chemotherapy-induced nausea and vomiting and multiple sclerosis spasticity symptoms. There is no link between smoking cannabis and lung cancer, and there is no gateway effect.

Cannabis is already a mainstream medicine. It is estimated there are currently over 5.4 million state-legal medical cannabis patients in the U.S. Illicit market users (a solid harm-reduction argument for clear cannabis policy) further eclipse these numbers. Cannabis is readily available. Being readily available, like other medications, researchers should determine the “five rights” as soon as possible and be proactive in minimizing harm.

One specific area of focus has been the impact of medical cannabis on opioid use. Research has shown a 64% decrease in opioid use among chronic pain patients in Michigan who used medical cannabis. 48% of patients in another study reduced opioid use after three months of medical cannabis treatment. In a 2016 survey, 78% of patients either reduced or stopped opioid use altogether. For patients participating in Medicare Part D, when medical cannabis was an option, 1,826 fewer doses of painkillers were prescribed on average per year, per state. Chronic pain has consistently been the most common patient-reported qualifying condition, making up over 60% of the patients we see.

Current studies

As Vireo-Health is a physician-founded and led company, we are adding to the evidence base for you to have more confidence in this tool and offer it as a form of personalized medicine for your patients. Current projects include a partnership with Dr. Julia Arnsten and her team of opioid research experts at the Albert Einstein College of Medicine and Montefiore Health System. This work involves playing an active role in study development for a unique National Institute of Health R01 $3.8 million grant for medical cannabis research. Listed on www.clinicaltrials.gov, the MEMO-Medical Marijuana and Opioids Study is ongoing, but has already produced a number of peer-reviewed publications. In the January 2022 issue of “NEJM Catalyst,” an overview of the Montefiore Medical Cannabis Program (MMCP), describes the future of medical cannabis based on its five years’ experience of certifying more than 1,600 patients at an academic medical center.

We are currently recruiting for a randomized double-blind placebo-controlled trial of vouchers for discounted medical cannabis soft-gel capsules. In this 4-arm study, “Do Discounted Vouchers for Medical Cannabis Reduce Opioid Use in Adults with Pain (ReLeaf-V) ReLeaf Trial,” participants must suffer from chronic pain, be over 18 years old and have utilized prescription opioids in the last 90 days. The trial lasts 14 weeks, and patients are randomized to a discounted voucher for one of the three soft-gel capsule medical cannabis products (THC-dominant, balanced THC and CBD, and CBD-dominant) or the placebo soft-gel capsule product. 

In Minnesota, Vireo Health is working with Monica Luciana, Angela Birnbaum and others at the University of Minnesota actively recruiting for a pre-post assessment of 90 adults, ages 35 to 55, who are prescribed medical cannabis to treat intractable pain. In the “Neurobehavioral Impacts of Medical Cannabis in Adults with Chronic Pain” study, outcome variables will include:

• Neural structure measured using T1-weighted and T2-weighted MRI scans as well as function measured using functional resting state and task-based MRI.
• Cognition (with an emphasis on learning, memory and executive functions).
• Mental health, including symptoms of anxiety and depression.

Pain relief, use of concomitant medications including prescribed opioids and quality of life indices will also be examined as secondary outcomes.

Participants are actively recruited from CPCs in Minnesota and will be asked to complete four hours of measures prior to ingesting the first prescribed medical cannabis dose. This exciting and unique trial will further examine the neurobehavioral impacts of medical cannabis on adults using cannabis for chronic pain. 

Despite widespread and increasing use of both medical and recreational cannabis, many physicians are unwilling to learn about and therefore unprepared to discuss or recommend these numerous benefits of medical cannabis to their patients. In efforts to address this, a two-day symposium for medical professionals interested in learning more about medical cannabis was hosted in Minnesota. The Spring into Cannabis Symposium was one of the first medical cannabis-focused events to also offer a Continuing Medical Education track to health care practitioners. At the symposium, physicians and researchers from around the country presented on key topics, including cannabis as an alternative to opioids, medical cannabis in neurology and mental health, pediatric uses of medical cannabis and more. Access to the same education from this event, along with other resources, is now available online at “https://visitgreengoods.com/cannabinology/” Yes, we need more research: well-designed condition, product and patient specific research. What is also needed is more physician involvement. To date, there have been no negative legal outcomes for providers supporting medical patients. I encourage you to peruse the existing evidence base as well as the numerous ongoing studies related to the cannabis plant and its constituents. Don’t hesitate to reach out to us, if only to be better informed. We are at an exciting and pivotal moment which promises marked potential for both help and harm to our patients. The plant is not going away, and the sooner we acknowledge this, the more positive impact we can make. Through understanding cannabis better and improving personalized medical research of complex interventions in the future, it is still my hope we can support our patients in exploring the beneficial aspects of the plant while minimizing potential for harm.  

Stephen M. Dahmer, MD, is a family physician and since 2015 has served as chief medical officer of Vireo Health. He is also assistant clinical professor of family medicine and community health at the Icahn School of Medicine at Mount Sinai and director of holistic primary care in Scarsdale, New York.