Inhalation of vaporized cannabis did not significantly reduce self-reported pain levels or disease-related symptoms in adults with sickle cell disease (SCD) compared with placebo, yet patients who received cannabis did report greater improvements in mood, according to research published in JAMA Network Open. These findings, while limited to a small patient sample, mean that researchers will have to look elsewhere for a safe and effective alternative to currently available pharmaceutical agents for patients with SCD and chronic pain.
“Our findings were a little underwhelming in that there was no statistically significant difference between cannabis and placebo for pain,” lead study author Donald Abrams, MD, a recently retired integrative oncologist and professor at the University of California-San Francisco, told ASH Clinical News, “but we know from observational studies that patients with SCD are using cannabis mainly for pain relief.”
In this pilot randomized clinical trial, Dr. Abrams and colleagues enrolled adult patients with SCD and chronic pain who were electively admitted for 5 days to a single inpatient clinical research center. Prior to enrollment, all participants were using a stable pain medication for at least 2 weeks. Patients also were required to have prior experience smoking cannabis, so they would know how to inhale and what neuropsychological effects to expect, and current users were required to discontinue use for 1 week before admission.
Investigators randomized patients to one of two treatment arms:
- vaporized cannabis containing 4.4% tetrahydrocannabinol (THC) and 4.9% cannabidiol (CBD)
- vaporized placebo cannabis from which CBD had been extracted
The participants inhaled the vapor 3 times daily (8 a.m., 2 p.m., and 8 p.m.). This vaporization process, which should not be confused with “vaping”, was chosen because it results in plasma THC levels similar to that of smoked cannabis without significant exposure to carbon monoxide and other combustion products, the authors noted.
All patients continued their outpatient pain medication regimen with additional as-needed inpatient analgesics. The crossover design of the study meant that each participant was exposed to both cannabis and placebo: During the first 5 day elective hospitalization, they received either the vaporized cannabis or vaporized placebo, which was followed by a month-long washout and a subsequent second 5-day period of exposure to the opposite treatment.
To assess pain and its interference on daily life, participants completed the Brief Pain Inventory and a visual analogue scale to score their pain during each 5-day period.
A total of 23 patients completed both treatment arms. “Our target was to have 35 patients enrolled, but quickly we found that patients with SCD have many challenges that prevent them from taking 10 days out of their life to be hospitalized for something that’s not medically necessary,” Dr. Abrams commented.
The mean age of the enrolled study population was 37.6 years. There were no significant differences between the cannabis and placebo groups in terms of the mean difference in pain rating assessments or pain interference ratings during the hospital stays. However, the investigators observed a significant mean difference in the decrease in interference with mood on days 1 and 5, which favored cannabis (p=0.02).
There were no differences between the two groups in terms of treatment-related adverse effects, and the researchers reported that vaporized cannabis was well tolerated. Sedation was the most common side effect. In general, patients were using at least one opioid analgesic at study entry, which was maintained during their admission. “Since no significant adverse effects were observed, this study has the potential to encourage and guide future larger and longer investigations into the potential use of cannabis-based interventions in chronic pain that could help to attenuate the ongoing public health crisis related to opioid use.”
Limitations of this study included the small sample size, as well as the relatively short treatment duration, which the investigators suggested “may have contributed to the inability to demonstrate decreased opioid use among participants receiving the active drug compared with the placebo.”
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:e2010874.