[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Views 6,864
    Citations 0
    Original Investigation
    July 17, 2020

    Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial

    Author Affiliations
    • 1Division of Hematology-Oncology, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco
    • 2Vascular Biology Center, Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis
    • 3UCSF Benioff Children’s Hospital Oakland, Oakland, California
    • 4School of Public Health, University of Minnesota, Minneapolis
    • 5Hemtology/Oncology Division, Department of Medicine, University of California, Irvine
    JAMA Netw Open. 2020;3(7):e2010874. doi:10.1001/jamanetworkopen.2020.10874
    Key Points español 中文 (chinese)

    Question  Is inhaled cannabis with an approximately 1:1 ratio of Δ-9-tetrahydrocannabinol to cannabidiol a safe and effective adjunct to opioids in adults with sickle cell disease–related pain?

    Findings  This randomized clinical trial including 23 participants found that inhaled cannabis was safe. Inhaled cannabis was more effective than inhaled placebo in interference in mood, but there was no statistically significant difference in pain rating between cannabis and placebo.

    Meaning  These findings suggest that cannabis should be investigated further in larger and longer clinical trials in adults with sickle cell disease with chronic pain as an adjunct or alternative to opioids.


    Importance  Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown.

    Objective  To determine whether inhaled cannabis is more effective than inhaled placebo in relieving chronic pain in adults with SCD.

    Design, Setting, and Participants  This pilot randomized clinical trial included participants with SCD with chronic pain admitted to a single inpatient clinical research center for 2 separate 5-day stays from August 2014 to April 2017. Participants inhaled either vaporized cannabis (4.4% Δ-9-tetrahydrocannabinol to 4.9% cannabidiol) 3 times daily or vaporized placebo cannabis. Pain and pain interference ratings using the Brief Pain Inventory were assessed throughout each 5-day period. Participants with SCD and chronic pain on stable analgesics were eligible to enroll. A total of 90 participants were assessed for eligibility; 56 participants were deemed ineligible, and 34 participants were enrolled. Of these, 7 participants dropped out before randomization. Of 27 randomized participants, 23 completed both treatment arms of the crossover study and were included in the final per protocol analysis. Data analysis was completed in June 2019, with the sensitivity analysis conducted in April 2020.

    Interventions  Inhalation of vaporized cannabis plant (4.4% Δ-9-tetrahydrocannbinol to 4.9% cannabidiol) or placebo cannabis plant using a vaporizer 3 times daily for 5 days.

    Main Outcomes and Measures  Daily pain assessed with visual analog scale and Brief Pain Inventory.

    Results  A total of 23 participants (mean [SD] age, 37.6 [11.4] years; 13 [56%] women) completed the trial. The mean (SD) difference in pain rating assessment between the cannabis and placebo groups 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; however, none of these differences were statistically significant. There was no statistically significant mean (SD) difference in pain interference ratings between cannabis and placebo between days 1 and 5 for interference in general activities (day 1: 0.27 [0.35]; day 5: −1.0 [0.5]), walking (day 1: 0.14 [0.73]; day 5: −0.87 [0.63]), sleep (day 1: 0.59 [0.74]; day 5: −1.3 [0.8]), or enjoyment (day 1: 0.23 [0.69]; day 5: −0.91 [0.48]), but there was a statistically significant mean (SD) difference in decrease in interference with mood (day 1: 0.96 [0.59]; day 5: −1.4 [0.6]; P = .02). No differences in treatment-related adverse effects were observed. Use of concomitant opioids was similar during both treatment periods.

    Conclusions and Relevance  This randomized clinical trial found that, compared with vaporized placebo, vaporized cannabis did not statistically significantly reduce pain and associated symptoms, except interference in mood, in patients with SCD with chronic pain.

    Trial Registration  ClinicalTrials.gov Identifier: NCT01771731