Vaporized cannabis does not significantly reduce chronic pain and associated symptoms compared with vaporized placebo in patients with sickle cell disease (SCD); however, inhaled cannabis is more effective than placebo in decreasing pain interference on mood, according to results from a randomized clinical trial published in JAMA Network Open.

Investigators of the pilot study, Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease (ClinicalTrials.gov Identifier: NCT01771731), compared the safety and efficacy of inhaled cannabis with inhaled placebo for the relief of chronic pain in adults with SCD.

The crossover design necessitated that participants complete both treatment arms of the study. During 2 separate periods of inpatient stays at the inpatient clinical research center at Zuckerberg San Francisco General Hospital in California, patients inhaled vaporized cannabis with an approximate 1:1 ratio of Δ-9-tetrahydrocannabinol (4.4%) to cannabidiol (4.9%) or placebo cannabis (from which all cannabinoids had been removed) using a vaporizer 3 times daily for 5 days. Inpatient stay periods were separated by at least 30 days. Pain was assessed upon admission and then daily, 2 hours after treatment inhalation, using the visual analog scale during each 5-day period; the Brief Pain Inventory was administered on day 1 and day 5.

Of 27 randomly assigned participants, 23 participants (mean age [SD], 37.6 [11.4] years; 56% women) completed both phases of the study. The majority of participants identified as Black or African American (91.3%).


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Pain rating assessments were compared on the respective days of the 2 admission periods. The mean (SD) difference in pain rating between the cannabis and placebo was -5.3 (8.1) for day 1, -10.9 (7.0) for day 2, -16.5 (9.2) for day 3, -8.9 (6.7) for day 4, and -8.2 (8.1) for day 5. None of these differences were found to be significant.

Comparing day 1 and day 5 pain interference ratings, no significant mean differences were identified between cannabis and placebo for interference in general activities, walking, sleep, or enjoyment; however, a significant decrease in interference with mood was observed (mean [SD], day 1: 0.96 [0.59] vs day 5: -1.4 [0.6]; P =.02).

No difference was observed between treatment periods in the concomitant use of opioids. The order of intervention had no effect on patient response to treatment. There were no significant differences in treatment-related adverse effects.

The primary limitations of this pilot study were the small sample size and short treatment durations, which according to the authors may explain the lack of difference in opioid use between the treatment periods. The investigators also acknowledged that the dosing regimen of 3 times per day may not have been optimal and suggested that ad libitum use of cannabis vapor may result in better pain relief.

“To our knowledge, this is the first randomized, placebo-controlled clinical trial of vaporized cannabis in participants with SCD and chronic pain,” wrote the authors. “[Because] no significant adverse effects were observed, this proof of principle 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.”

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Abrams DI, Couey P, Dixit N, et al. Effect of inhaled cannabis for pain in adults with sickle cell disease. JAMA Netw Open. 2020;3(7):e2010874.