In November 2012, Colorado got plenty of buzz as the first state in the nation to pass an amendment legalizing marijuana. The retail sale of recreational marijuana followed in January 2014. Shops peddling the drug soon sprouted across the landscape from street corners to strip malls.
But if marijuana is now a fixture of everyday life in Colorado, questions about it continue. One of the most intriguing is the potential cannabis has to treat a host of ailments, including inflammatory bowel disorder, chronic pain, sleep loss, epilepsy and Parkinson’s disease. With legalization, researchers finally had an opportunity to lead controlled clinical trials to test the anecdotal evidence patients have offered of marijuana’s medical benefits.
There have been many obstacles, however, as Dr. Maureen Leehey, a neurologist at the UCHealth Neurosciences Center and Professor of Neurology with the University of Colorado School of Medicine, can attest. Her experience illustrates the difficulties of conducting evidence-based research into the medical effectiveness of marijuana. Despite its popularity, the drug still must clear significant regulatory hurdles before research yields any solid answers about its benefits to patients.
Can CBD help with Parkinson’s disease symptoms?
Leehey is principal investigator of a randomized, double-blind study of cannabidiol (CBD), one of the most concentrated of the hundreds of compounds in the cannabis plant. The question: can CBD effectively reduce symptoms of motor disorders, such as tremor, in patients with Parkinson’s disease, a progressive neurodegenerative disorder, compared to a placebo?
Grant funding from the Colorado Department of Public Health and Environment (CDPHE) helps to support the study, which launched in 2018 with the goal of having 60 patients complete it. COVID-19 halted patient recruitment the past year, but it’s back underway, with 53 patients enrolled as of early March, said Leehey’s senior professional research assistant, Dr. Ying Liu. Forty have completed the study, Liu added.
The primary outcome measure for the study is the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), which evaluates a host of motor functions. But Leehey and her team also are looking at no fewer than 56 secondary outcome measures – everything from liver function to sleep patterns to depression and cognition.
Managing and analyzing all that data is complex. But the challenges go further.
No easy task to launch CBD and Parkinson’s study
With marijuana legalized, Leehey began hearing from a number of her patients that cannabis, especially products high in CBD, helped them cope with the debilitating symptoms of Parkinson’s disease. CBD made for an attractive study target. Unlike its cannabis cousin THC, CBD doesn’t get its users high – an essential consideration for those persons with Parkinson’s that struggle with thinking, gait and balance problems. In addition, pre-clinical animal studies showed promise for CBD in reducing Parkinson’s symptoms.
Leehey found that getting a study of CBD with human subjects wasn’t easy. The barriers included simply obtaining CBD for a small pilot study and meeting a host of regulatory requirements for administering it. She finally found a flavored oral CBD solution to use in the pilot, which 10 patients completed.
In addition, the pilot study showed the CBD caused side effects, especially diarrhea, dizziness and daytime sleepiness. In some patients taking the CBD solution, there was also concern about liver dysfunction.
The pilot study had helped Leehey settle on a proper dose of CBD for the next study step, a randomized trial in which neither she nor her patients would know whether they were getting the drug or a placebo.
A farm for cannabis research at the University of Mississippi, funded by the National Institute on Drug Abuse (NIDA) ultimately yielded CBD for the randomized study, to be administered twice daily to patients orally in approximately 100-milligram CBD and 3.5-milligram THC doses.
The University of Mississippi product, however, was less an instant solution than a sticky situation. The CBD arrived as a frozen extract Leehey described as “a black goo.” To make the stuff patient-palatable, the study team turned to Jacci Bainbridge, a PharmD and Professor with the Department of Clinical Pharmacology at CU’s Skaggs School of Pharmacy and Pharmaceutical Sciences. Bainbridge devised a process to thaw the goo, add flavorings and sesame seed oil, and stopper the concoction in vials for half the study patients. The other half get a placebo.
But Leehey and her team also needed to monitor patients for side effects while protecting their identities. Bainbridge and a study biostatistician provided lists of patients receiving medication or placebo, with their identities removed.
Obtaining study product remains a question
Study results await. But if the findings justify moving on to a large-scale Phase 3 study, Leehey will again be faced with the problem of securing product, as NIDA considers the current trial only a “proof of concept” and will not be the source.
“We have to find a commercial partner,” Leehey said.
On the surface, that shouldn’t be a problem. The 2018 federal Farm Bill allowed states for the first time to cultivate, transport and sell products derived from hemp – defined as cannabis plants that contain no more than 0.3 percent of THC. That means CBD extracted from hemp is not a controlled substance, so long as the hemp and the products do not exceed the THC limit and meet a set of federal and state standards. Colorado would seem to be well positioned to take advantage: in 2019, Colorado had some 88,000 acres registered for hemp production.
However, there is a catch. States that want to develop industrial hemp production must either create and submit plans for regulating it to the United States Department of Agriculture (USDA), or follow the USDA’s Domestic Hemp Production Program. Colorado put together its proposed state plan last June, but did not get approval from the USDA to move forward. Leehey said the state plans to resubmit the revised proposed plan later this year. If it clears the hurdle, she has a couple of local companies in mind to secure hemp-derived CBD.
Whatever the economics of CBD production and the popular demand for it, the bottom line for Leehey is whether or not the evidence supports that it helps her patients with Parkinson’s disease without burdening them with too many side effects.
“I don’t want patients spending money on CBD if it is not helping them with their symptoms, but if it can help, we want to be able to dose it correctly,” she said.
The experiences of two of her patients suggest that the research will yield more questions and decisions for individual patients living with Parkinson’s disease.
An active response to Parkinson’s diagnosis
Both Dennis Mullen, 71, of Westminster, and Mel Preusser, 78, of Denver, take an active role in managing their Parkinson’s disease. They exercise regularly, watch their diets and educate themselves about their condition through reading, classes and support groups.
Mullen ran his own FedEx Ground business until his 2010 diagnosis forced him to retire because the job required extensive walking. Since then he’s battled tremors, stiffness and muscle freezing that occasionally stymie him during routine activities like trips to the pantry.
He admits that his initial diagnosis of Parkinson’s disease left him depressed. But his wife and kids helped him shed those feelings.
“I said I won’t let this get me down,” Mullen said. “I’m a fighter.”
He said he works to stay abreast of the latest information about Parkinson’s disease.
“I take a bunch of different ideas and try them,” he said. “You have to grasp the things that are out there and try to keep up to date on what is working and not working for people.”
His vigilance alerted him to articles about CBD being used to treat seizures in kids and later its possible help for people with Parkinson’s disease. That led him to Leehey’s study.
“I said, ‘I want to get into that,’” Mullen recalled. He was particularly interested because of a worsening tremor in his left hand that has eroded his manual dexterity – “anything that needs a steady hand,” as he put it.
Preusser, who retired from a career in education as superintendent of Eagle County Schools, got his Parkinson’s disease diagnosis from Leehey four or five years ago after noticing a persistent tremor in his dominant left hand. He said he’d enrolled in trials focusing on diet and dexterity prior to the CBD study, both to seek help for his condition and to extend his knowledge about it.
“I got into the trials as a learner,” Preusser said. “I also want to be a contributor. I’ve read about so many studies being aborted because of a lack of participation. I want to help the process and contribute to the research in any way I can.”
Uncertain responses to CBD
Both men completed the CBD trial. Neither felt any positive effects after taking the drug, although their experiences were different.
Mullen thinks he got the placebo. “I kept wanting to feel something different,” he said, “but I didn’t feel anything.” He is anxious to see the results of the trial and added that he would still be willing to take CBD to treat his Parkinson’s disease symptoms.
Preusser is convinced that he did get the CBD, explaining that after the first administration he felt lightheaded. “Things weren’t quite as concrete and were more ethereal than how I commonly perceive my surroundings,” he said.
The dizziness forced him to go to another room at the clinic to lie down. He said at his second visit, he got half the dose, which seemed to diminish the side effect.
But like Mullen, Preusser said he derived no benefit from whatever he took. “I didn’t notice any diminishment of my tremor or change in my level of cognition,” he said. He remains open, however, to the idea that CBD could help some people with Parkinson’s disease.
“I understand that every patient is different,” he said. “It may work miracles for the next guy. For me, not so, but there may be a point when I might reconsider or something may prompt a different assessment.”
Sticking to the management plan
Regardless of the study’s findings, Mullen and Preusser said they plan to keep doing the things that help them live productively with Parkinson’s disease. For Mullen, that includes stretching, walking, acupuncture, regular pool and gym work, and attention to diet, especially cutting down on sugar.
Preusser said he exercises at least 45 minutes a day and walks regularly, sometimes several miles. His weekly schedule always includes “one adventure, rain or shine, winter or summer,” such as a lengthy hike or skiing – he still hits the slopes at Loveland Basin.
Whatever the outcome of Leehey’s trial, Preusser advised others with Parkinson’s disease to have as many tools as possible to mitigate the symptoms and lead a healthy life.
“Find what works and stick to it,” he said. “I didn’t go into the [CBD] trial with the idea that it’s a magic bullet. If not for me, there is still something for research to gain from the study.”