PainRelief.com Interview with:
Donald I. Abrams, MD
Division of Hematology-Oncology
Department of Medicine,
Zuckerberg San Francisco General Hospital
University of California, San Francisco
PainRelief.com: What is the background for this study? What are the main findings?
Response: A number of years ago, Kalpna Gupta, PhD, an investigator then at the University of Minnesota, came and told me about her mice with Hemoglobin SS who experienced pain that responded to laboratory cannabinoids. She was going to apply for a grant from the National Heart, Lung and Blood Institute to continue her studies and sought us out because of our prior clinical trials with cannabis and pain. Dr. Gupta wanted to include a pilot proof of principle human study in her application and asked if we could design one. As cannabidiol (CBD) was just becoming known at that time, we suggested to do a study in patients with sickle cell disease and pain looking at a delta-9-tetrahydrocannabinol (THC)-dominant strain of inhaled cannabis, a CBD-dominant strain, a balanced 1:1 strain and placebo. She said that we would only have funds to do a two-arm study, one of which needed to be placebo. As we had already shown that there was a trend for vaporized cannabis that was predominantly THC to add to the analgesic effect of sustained-release opioids in patients with chronic pain, we chose to investigate a 4.4% THC:4.9% CBD product obtained from the National Institute on Drug Abuse.
We designed a crossover trial so that each participant would spend two 5-day inpatient stays separated by at least a month in our Clinical Research Center at Zuckerberg San Francisco General Hospital. During one stay they would add vaporized cannabis to their stable ongoing analgesic regimen and during the other stay they would inhale placebo cannabis three times a day. We use the Volcano vaporizer device that heats the plant material and not an oil as has become popular in the recent “vaping” craze. Our target was to enroll 35 patients with sickle cell disease and chronic ongoing pain on an opioid-containing regimen. Our primary endpoint was change in pain as measured by way of a visual analog scale and the Brief Pain Inventory as well as safety.
PainRelief.com: What should readers take away from your report?
Response: Over the course of the trial we managed to only have 23 participants complete both arms of the study. We saw no increased short-term adverse effects of the cannabis compared to the placebo. On each of the 5 days evaluated, cannabis produced a greater reduction in pain than placebo; however none of the pain results reached statistical significance. A significant difference in interference with mood was detected. Use of concomitant opioids was similar during both treatment periods.
PainRelief.com: What recommendations do you have for future research as a result of this work?
Response: We know from the small amount of prior published literature that sickle cell patients are increasingly using cannabis as an adjunct to their ongoing analgesic regimens, usually reporting added pain relief. Here we attempted a randomized placebo-controlled crossover trial to confirm the safety and effectiveness of vaporized cannabis with a THC:CBD ratio of ~1:1 in this patient population. Although we did not perceive a statistically significant difference between the cannabis and placebo treatment periods, looking at the tables and figures suggests that a larger, perhaps longer, study may be warranted. The intervention appears to be safe in this population challenged with multiple comorbidities and frequently on an extensive amount of concomitant medications. There is also a possibility that the presence of the CBD in the cannabis product we studied may have negated some of the analgesic effect of the THC just as it appears to dampen some of the psychoactivity.
PainRelief.com: Is there anything else you would like to add?
Response: As mentioned, a larger study would be a good idea, although I must say it was challenging to recruit the small number of patients we did accrue. Part of the issue is that we do all of our trials as inpatient studies. Perhaps an outpatient study with a more “real world” dosing regimen would be easier to enroll and may produce a more definitive result. Also, it would still be optimal to study THC, CBD, THC:CBD and placebo to begin to tease out the contributions of these dominant cannabinoids to the analgesic effect. The risk there being that by time such a study is ready to be launched there may be a new cannabinoid du jour displacing CBD. Whether or not vaporization is the optimal delivery system is also something that is unknown. Perhaps a tincture or an oral preparation may provide longer periods of effectiveness than inhalation. But if we start manipulating the cannabinoid profiles as well as the delivery systems the number of possible study arms becomes daunting.
Disclosures: See JAMA article. No current advisory positions.
Abrams DI, Couey P, Dixit N, et al. Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(7):e2010874. doi:10.1001/jamanetworkopen.2020.10874
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