Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease

Abstract

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.

The Effects of Cannabinoids on Sleep

“… 63 , 64 Cannabis products have potential analgesic properties for those with a chronic pain manifestation of their RLS symptoms; additional mechanisms may relate to the anxiolytic and/or sedative hypnotic effects of these products but are generally unknown at this time. 65 , 66 There is a lack of objective efficacy measures with the use of cannabis for RLS in the literature. Therefore, caution is recommended with use of cannabis products in RLS, given the limited evidence base and potential for abuse and psychoactive effects.…”

Opioid Use in Adults With Sickle Cell Disease Hospitalized During Vaso-Occlusive Crisis: A Systematic Review

“…In a qualitative study that examined the management of chronic pain in adults with SCD in the current opioid epidemic, the authors reported that participants offered marijuana as the most common non-opioid pharmacological method used successfully for pain relief [ 42 ]. Identifying the optimal mode of administration of marijuana for effective, evidence-based, pain relief must be prioritized, as a recent randomized trial indicated insignificant differences between inhaled marijuana and placebo [ 46 ]. Participants in the qualitative study also offered non-pharmacological methods such as warm compresses, praying, music, and acupuncture as pain relief measures to combat SCD pain [ 42 ].…”

Opioids and Sickle Cell Disease: From Opium to the Opioid Epidemic

“…Alternatives to opioids for sickle cell pain are not available yet. The status of cannabinoids is unsettled and Kratom failed as replacements to opioids [ 75 , 76 ]. The systemic side effects of NSAIDs in adults such as renal failure, cardiovascular compromise and gastrointestinal bleeding are worse than the systemic side effects of opioids [ 17 ].…”