After traveling a long road with tight regulatory curves, researchers at the University of Colorado School of Medicine have opened enrollment in a clinical trial that will study the pain-relieving power of cannabis.
The study, funded by a three-year, $743,000 grant from the Colorado Department of Public Health and Environment, targets patients with a frequent ailment: chronic back and neck pain. It will compare the effectiveness of vaporized cannabis in alleviating short-term pain to the opioid painkiller oxycodone and a placebo, respectively.
Squaring off cannabis and oxycodone as pain relievers heightens the timeliness of the study. The increasing use and abuse of opioids in the United States has earned national headlines the past year or more, with President Trump declaring it a crisis and a national emergency in August. The CDPHE reported 259 deaths in Colorado in 2015 from overdoses of prescription oxycodone and other opioids – more than the statewide number of homicides.
But the roots of the current study run deeper than the topsoil of today’s headlines, said Emily Lindley, PhD, assistant professor with the School of Medicine’s Orthopedic Spine Division. As far back as 2011 and 2012, spine physicians and researchers at UCHealth University of Colorado Hospital began hearing more than occasionally from patients who had medical marijuana cards that they had turned to cannabis to ease their pain.
“These patients were self-reporting that ‘marijuana seems to work for me,’” Lindley said.
In a 2012 survey of 184 spine patients, roughly one in five reported that they used cannabis to relieve their pain. Of those, 85 percent said cannabis gave them at least moderate pain relief, and 77 percent said the relief was equal to or better than what they got from opioids.
“The numbers were higher than what we expected,” Lindley said.
Digging for drug data
Recreational legalization of marijuana in 2014 opened the door to grant funding from the CDPHE, which wants to gain a better understanding of both the risks and potential benefits of marijuana use. The current study began recruiting patients this July after meeting a host of governmental and research review requirements for obtaining, storing and protecting the cannabis and ensuring the safety of patients who consume it.
Prospective study participants, including those with chronic neck and back pain and healthy controls, will be screened for eligibility. Those who will be excluded include individuals with a host of medical conditions and those with substance use disorders. Participants will make three study visits, receiving in random order: vaporized cannabis and a placebo pill; an active oxycodone pill and placebo cannabis; and two placebos disguised respectively as vaporized cannabis and an oxycodone pill. They will not know what they have ingested. The sessions will be at least five days apart, Lindley said.
The visits will take place in the Clinical and Translational Research Center Clinic on the third floor of the UCH’s Leprino Building. During each roughly three-hour session, researchers will monitor participants’ vital signs and conduct a battery of tests of their neurocognition, fine motor skills and field sobriety. As for pain, the key is a device Lindley and CU Chief of Orthopedic Spine Surgery Vikas Patel, MD, developed with engineers at CU-Boulder’s Advanced Medical Technologies Laboratory, led by Mark Rentschler, PhD. The custom tool delivers computer-controlled pressure to the participants’ muscles and records their responses to the pain, which researchers compare to a baseline measurement.
The device is an important advance in studying pain treatment, which traditionally has had to rely on patients’ subjective descriptions of it, said Patel, who is assisting with the study and as a physician with Drug Enforcement Agency clearance to receive cannabis to be used in it.
“It’s a way for us to stimulate pain in a controlled way,” he said.
Probing the roots of pain
The study, which aims to enroll 100 people through June of 2019, “only scratches the surface” or cannabis research, Patel added. Even if it demonstrates that vapor-delivered THC is effective in relieving pain to many in this select group of patients, follow-up studies will be needed to determine proper dosing levels, the most effective methods of use, which varieties of the drug work best for whom, potential side effects, and so on.
“These are all unanswered questions that will require further studies down the road,” Patel said.
The easy availability of cannabis products in Colorado poses a dilemma for a spine surgeon like Patel, whose patients endure acute and chronic pain from compressed nerves, herniated disks, surgical incisions, broken bones and other sources. He makes no judgments when his patients tell him, as many do, that they favor cannabis for pain relief as an alternative to opioids, with their side effects – such as constipation, suppression of testosterone and depression – and their addiction risk.
“I say if it works well with fewer side effects, that’s great,” Patel said.
But he worries about the lack of available data to evaluate the drug, which still resides in a twilight world – legal in Colorado and a handful of other states but still considered a Schedule 1 controlled substance by the federal government: a drug with a high potential for abuse and no accepted medical use. For that reason, Patel said, giving a patient cannabis for post-operative pain relief would be impossible in the hospital, which receives Centers for Medicare and Medicaid Services funding and is therefore subject to federal rules and regulations.
Patients are also potentially at risk because of cannabis’s ambiguous medical status. The products they buy have not gone through the rigorous testing for dosing, safety and efficacy that the FDA demands of other medications. How many THC vapor hits, and at what dose, are most effective to relieve chronic neck pain? No one knows or can even make an educated guess, at least yet.
“Patients are in an odd predicament,” Lindley said. “Providers have limited information about marijuana for pain management, so patients are instead getting their advice from ‘budtenders’ about the form of marijuana to take, and the dose. Providers need research-based evidence to guide their medical recommendations, and we hope to start the first steps.”
Both Lindley and Patel caution that their study is not designed as an attack on opioids, which are proven and effective as pain relievers. “We may find in the study that many people respond better to opioids,” Patel said. “Some people may prefer not to take anything for their pain because they are afraid of the potential for addiction.”
The overall goal for providers and researchers, Lindley said, is to find ways to broaden choices for patients seeking pain relief.
“A lot more patients are aware of the risks of addiction to opioids and are looking for alternatives,” she said. “That’s good. We don’t want them popping pills, but we also don’t want to see them in pain. We want to see if cannabis might have an appropriate place in pain management.”
For more information about the study, email [email protected].