Early results of a long-awaited study on marijuana as a treatment for post-traumatic stress disorder show that veterans who smoked two components of cannabis -- tetrahydrocannabinol, or THC, and cannabidiol, or CBD -- saw decreases in their symptoms.
But those who received a placebo during the study did just as well, according to data published Wednesday in the journal PLOS One.
The research, sponsored by the Multidisciplinary Association for Psychedelic Studies, or MAPS, in Santa Cruz, California, aimed to determine whether inhaled cannabis or its components were safe and effective for treating PTSD.
For the study, 80 participants were divided into four groups: those who received cannabis containing high levels of THC, those who received hemp with high levels of CBD, those who received cannabis containing an even mix of THC and CBD, and those who got a placebo.
The participants, who did not know what treatment they'd been given, used the cannabis or placebo for three weeks. They then rested for two weeks and were given one of the four options for three more weeks.
According to the results, all four treatment groups, including those who received the placebo, achieved "significant reductions" in their PTSD assessment scores at the end. Specifically, participants who received marijuana with high levels of THC in the first phase saw a mean reduction in PTSD assessment scores of 15.2 points. Those who received a placebo reported a reduction of 13.1 points, and those who got a treatment containing high levels of CBD or the mix saw reductions of 8.4 points and 8.5 points, respectively.
In patients' personal assessments of their PTSD symptoms, there were no significant differences in scores between treatment groups through Stage 1. But after Stage 2, those who received the mix containing an even amount of THC and CBD reported larger reductions in their PTSD symptoms than those who used CBD only.
"Even though it was not as robust a response that we had hoped to achieve, we learned a lot that will shape future studies," lead researcher Dr. Sue Sisley told Military.com.
Among the lessons learned: Cannabis use was well tolerated by patients in the study. The most common adverse effects reported were cough, sore throat and anxiety. Thirteen participants dropped out after experiencing adverse medical issues related or unrelated to the study.
The research, which has been in the works since 2010, is the first in the U.S. to study whole plant marijuana as a PTSD treatment. Berra Yazar-Klosinski, chief scientific officer at MAPS, described the study as a success because it laid the groundwork for larger studies, demonstrating that marijuana doesn't pose a risk to human subjects and exposing methodological flaws that will be addressed.
"The main issue with the study was that it was not really intended to get a statistically significant difference. ... While it seems like a large study, because we didn't exactly know what types of cannabis would work best for this population, we had like 19 people in each group," Yazar-Klosinski said.
The road to the early results was anything but easy for those who spent years getting the research approved, including Sisley, a former professor at the University of Arizona who fought to get federal approval for the study, which revolved around a controlled substance.
After winning approval in early 2014 from the Health and Human Services Department, the study was set to get underway at the University of Arizona and other locations when Sisley's contract with the school was terminated.
Then, the Department of Veterans Affairs slow-rolled her efforts to recruit veteran patients. When she finally received a grant in 2016 for the research, she sought to recruit at least 76 military veterans and enrolled her first in early 2017.
At that point, the federally supplied cannabis Sisley was required to use for the research was found to be of low quality and moldy. She sued the Drug Enforcement Agency to reconsider the Schedule I status of marijuana. MAPS also has sued to compel the DEA to process marijuana producer and manufacturer licenses for researchers who want to cultivate medical-grade cannabis.
Although the research did not show a large "effect size," the researchers have submitted plans to the Food and Drug Administration for a larger, more comprehensive study to demonstrate whether cannabis can be used as an effective treatment for PTSD. They plan to have more participants, a longer study period and high-quality cannabis sourced from the U.S., if licenses are issued, or Canada, according to Sisley.
Among the issues with the research, Yazar-Klosinski said, was that participants got only three weeks of dosing, which may not have been enough time for those who received THC or CBD to reach a "steady state" similar to what is achieved when a patient takes prescribed medication for a mental condition.
She added that the PTSD assessment, which asks patients to describe their feelings in the past 30 days, may reflect disease fluctuations or natural decline in symptoms over time.
"We have a lot of really rich information that came out of this trial that is going to inform the design of the new study," Yazar-Klosinki said.
The researchers included Sisley; Marcel Bonn-Miller with the Perelman School of Medicine at the University of Pennsylvania; and Paula Riggs, with the University of Colorado School of Medicine.
Sean Kiernan, president of the Weed for Warriors Project, an advocacy group that raises awareness of cannabis in the veteran community, said MAPS and Sisley "deserve a medal for the absolute intentional dysfunction they overcame to complete this study and publish its findings."
"The positive that came from this study is cannabis is safe. The negative is the anti-science prohibitionist mindset is still blockading beneficial research into cannabis," Kiernan said.
If the new research is approved, the researchers will establish a webpage to recruit volunteers, Yazar-Klosinski said.