The lack of controlled clinical studies on the effectiveness of cannabis to treat medical conditions has been a major concern for the industry. In January 2017, the nonprofit organization Multidisciplinary Association for Psychedelic Studies (MAPS) began a clinical study of the use of smoked whole-plant marijuana to treat symptoms of post-traumatic stress disorder (PTSD) in U.S. veterans. The study, now ongoing at the Scottsdale Research Institute in Phoenix, Arizona, has been approved by the Public Health Service, the Food and Drug Administration, the Drug Enforcement Agency (DEA), and institutional review boards, and is funded by a $2.1 million grant to MAPS from the Colorado Department of Public Health and Environment. Sue Sisley, MD, is the site principal investigator on the study, and Marcel Bonn-Miller, PhD, is the coordinating principal investigator. Sisley spoke to us about the study and the overall environment for medical cannabis research in the United States.
You are now enrolling patients for a clinical trial of smoked marijuana for PTSD in U.S. veterans. First, why did you choose to study smoked marijuana specifically? Would you consider conducting studies that did not use the whole plant?
We chose to study smoked marijuana because of the many veterans and others who already report using smoked marijuana to successfully treat their PTSD symptoms. There is already a great deal of well-funded research into using isolated or synthetic cannabinoids and nonsmoking delivery systems for therapeutic purposes, but ours is the very first clinical trial to look at the safety and effectiveness of the smoked marijuana plant. The marijuana plant cannot be patented, so there has been no private investment or government funding into developing it into a federally legal prescription medicine. That’s why it fell to MAPS, the nonprofit study sponsor, and our team of researchers, to start research into the whole plant.
How did you determine which strains to use in the study?
We’re investigating the safety and efficacy of four types of smoked marijuana to manage chronic, treatment-resistant PTSD symptoms. The doses of marijuana (excluding placebo) in this study were chosen because they contain a range of tetrahydrocannabinol (THC) and cannabidiol (CBD) ratios and potencies generalizable to what many veterans are currently using to manage PTSD symptoms in nonclinical settings in states with legalized medical marijuana. The marijuana that we’re using in the study came from the National Institute on Drug Abuse (NIDA), the sole provider of marijuana for research in the United States. The four potencies we’re using are placebo (<1% CBD/<1% THC), high THC (<1% CBD/12% THC), high CBD (12% CBD/<1% THC), and balanced (9% CBD/9% THC). These different potencies are not “strains,” but rather material that has been processed from several strains to create blended marijuana with precise CBD and THC ratios. Unfortunately, we had to use a lower balanced ratio (9% CBD/9% THC) than what we were originally approved to use (12% CBD/12%THC) because that’s all that NIDA had available.
The restrictions for sourcing cannabis for medical research in the United States have been a significant concern. What do you think the future holds on this issue?
MAPS is currently working with Professor Lyle Craker, PhD, of the University of Massachusetts-Amherst to end the NIDA monopoly on marijuana for research by obtaining a license from the U.S. DEA for a license to grow marijuana for research. The DEA announced its intention to grant licenses to additional marijuana growers for research in August 2016, and it has received at least 25 applications, but neither Craker’s nor any of the other applications have been approved. We’re hoping that Attorney General Jeff Sessions and the Trump administration will soon end the obstructive NIDA monopoly, encourage independent marijuana research, and take action by granting Craker’s license.
In the current legal and political environment, and given the withdrawal of Johns Hopkins from the study, how significant are the barriers to patient enrollment in the study?
The withdrawal of Johns Hopkins from the study didn’t have much impact, if any, on enrollment. We’ve already enrolled nearly one-third of the participants we’ll need at our Scottsdale Research Institute study site in Phoenix. We would like to see faster enrollment, but we’re confident that we’ll be able to enroll all 76 veterans in Phoenix.
Do you think your study will pave the way for more FDA-approved studies of the medical use of cannabis?
As scientists, we don’t know yet what the results will be, so it’s impossible to say whether we’ll have very encouraging results, somewhat encouraging results, or just more questions. Either way, this trial has absolutely been the spearhead of a nationwide effort from researchers and clinicians to finally look at smoked, whole-plant medical marijuana from a scientific perspective. So, I’d have to say that regardless of the results, in that sense this study has already been a success: It will be easier for researchers to study medical marijuana in the United States from now on.
Given the challenges of conducting these studies in the United States, have you considered working with partners in other countries?
Yes, and in fact our friends at Tilray Pharmaceuticals in Canada have just started their own clinical trial of marijuana for symptoms of PTSD. We’ve shared our research protocol with them (and in fact it’s available online at maps.org) and they’re doing almost the same trial, with the exceptions that they’re using vaporized instead of smoked cannabis, and that they are looking at PTSD in anyone who suffers from it, such as police, firefighters, ambulance workers, and rape victims, whereas we are only looking at PTSD in military veterans. We’re excited to compare our results.
Sue Sisley, MD, is an Arizona-based physician practicing Internal Medicine and Psychiatry. Her keynote address at the 2017 Cannabis Science Conference was titled “Researching Medical Cannabis: Navigating Barriers to Efficacy Research.”
This interview was originally published in in the 2017 Cannabis Science Conference Final Program & Exhibitor Guide in partnership with LCGC and Spectroscopy magazines and Joshua Crossney of jCanna. The full program guide is available as an e-book here: http://www.chromatographyonline.com/lcgc-e-books-08-02-2017