Medical cannabis: Promising uses supported by medical data

Over the past several years, legalization of medical marijuana has caught on like wildfire across the United States. The latest three states to approve medical use—Michigan, Missouri, and Utah—were added to the list as of the 2018 mid-term elections. That makes 34 states that have legalized cannabis for medicinal use through February 2019.

Despite the quick uptick of legislative and public approval, scientific evidence backed by large randomized, controlled trials is lacking. In addition, there are no straight forward data to help clinicians determine which formulation of cannabis to use, what route of administration is most appropriate, how often it should be dosed and for how long, and what is the appropriate ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD)—the two most prominent ligands used for therapeutic purposes.

While public adoption of medical cannabis seems to be progressing faster than researchers can prepare the trials, it is useful to see what data are available and for what conditions medical marijuana may have a promising future.

Autism spectrum disorder (ASD): Earlier this year, researchers from Israel, published an observational study in Nature Scientific Reports, with prospectively collected data, on medical cannabis use in children with ASD.

Interestingly, these authors noted that the impetus for this study came from learning that parents of severely autistic children started turning to medical marijuana for relief “…after seeing the results of cannabis treatment on symptoms like anxiety, aggression, panic, tantrums and self-injurious behavior in children with epilepsy.”

The study focused on the safety and efficacy of medical cannabis in 188 young subjects (median age: 13; 82% male) between 2015 ad 2017. Most patients were treated sublingually with cannabis oil containing 30% CBD and 1.5% THC. After 6 months of treatment, investigators reported that 30% of patients had a significant improvement in their condition, 54% had a moderate change, 6% had a slight change, and 9% had no change. The most common side effect was restlessness (7%).

Chronic disease:  In mid-February 2019, researchers from Italy published retrospective, observational, singe-cohort data on the safety and efficacy of a natural preparation of cannabis, which contains THC but not CBD, and is administered sublingually.

Twenty patients (age range: 18-80 years; mean age: 40 years; 12 women/8 men) were enrolled through a compassionate use program in Italy. Each participant had chronic and severe symptoms of one of the following conditions: neurologic diseases, cancer, fibromyalgia, multiple sclerosis, dystrophy syndrome, insomnia, chronic obstructive pulmonary disease, and hernia.

For 3 months, they took sublingual doses of the galenical oil twice daily, starting at a low dose of 0.5 mL/d, and gradually titrating up to the highest recommended dose of 1 mL/d.

Monthly questionnaires revealed a significant decrease in pain, improved social functioning and general health, and restored physical function. Researchers also observed significant reductions in insomnia and significant improvements in mood and concentration. No adverse events were reported.

Chronic pain and sleep measures: Experts in anesthesia and pain management, led by Ivan Urits, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, published a review article on available data of cannabis pharmaceutical derivatives in chronic, difficult-to-treat conditions.

The derivative with the most data in humans that they reviewed was nabiximols, an oromucosal cannabinoid spray that predominantly contains a mix of THC and CBD. The spray is approved in Canada and many European countries as add-on treatment in patients with multiple sclerosis to reduce spasticity.

The review included the following results with nabiximols reported from various studies:

• Reduced patient-reported MS-related spasticity and improved sleep
• Reduced MS-related pain after 4 weeks, with additional reductions at 14 weeks
• Improved sleep in patients with chronic, cancer-related pain
• Reduced peripheral neuropathic pain and improved sleep and allodynia
• Reduced pain and improved quality of sleep in patients with rheumatoid arthritis

Inflammatory bowel disease (IBD): In October 2018, Jami Kinnucan, MD, assistant professor of medicine at the University of Michigan, Ann Arbor, MI, published a Q&A article in Gastroenterology & Hepatology on the use of medial cannabis in IBD.

Dr. Kinnucan detailed some of the findings that have been reported, including:

• A survey-based study demonstrating improved abdominal pain, appetite, nausea, and diarrhea
• A prospective pilot study that showed a reduction in pain and symptoms and improved general health perception, social functioning, and the ability to work
• The first randomized, controlled trial of medical marijuana in Crohn’s disease, which showed that, in 21 patients who smoked two cannabis cigarettes/day for 8 weeks, Crohn’s Disease Activity Index scores significantly improved vs placebo; nearly half of patients experienced clinical remission, and a quarter were able to discontinue corticosteroids

On the horizon

Time and time again, authors who have published preliminary results have ultimately concluded by emphasizing the need for larger, prospective, randomized, controlled trials. The problem in conducting these larger more rigorous trials in the United States revolves around the illegality of cannabis under current federal legislature.

Nonetheless, the National Institutes of Health (NIH) have made a strong commitment to support cannabis research in the US. The latest data available from the NIH report nearly $140 million dedicated to 330 medical cannabis projects as of fiscal year 2017. This funding applies to bench, animal, and human preclinical and clinical studies that “examine the chemical, physiological, and therapeutic properties of cannabinoids and the physiological systems they affect,” according to the NIH website.

NIH is also funding studies that analyze regional health and social factors related to the changing laws on cannabis use.

Just as some of the preliminary data (and patient anecdotal accounts) indicate a promising future for the use of medical cannabis, so does the dedication of millions of dollars from the NIH to further research. Perhaps, soon, our scientific understanding of medical marijuana will catch up with public support.