Cannabis combined with oxycodone for pain relief in fibromyalgia pain: a randomized clinical self-titration trial with focus on adverse events

Abstract

Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.

Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.3% Δ⁹-tetrahydrocannabinol and 8% cannabidiol (max. times inhalation sessions/day), or a combination of both for 6 weeks. The primary endpoint was treatment-related adverse events, assessed using a 10-point composite adverse event (cAE) score; additionally, we recorded daily reported pain relief and daily tablet and cannabis consumption.

Results: In total, 23 patients were treated with oxycodone, 29 with cannabis, and 29 with the oxycodone/cannabis combination. Three patients from the oxycodone group (13%) and 18 patients from the cannabis groups (31%, 9 in each group) withdrew from the trial within 2-3 weeks because of the severity of AEs. There were no differences in treatment-related cAE scores among the three groups that completed the study (p = 0.70). The analgesic responder rate showed a ≥1- point reduction in pain in 50% and a ≥2-point reduction in 20% of patients, while 50% of patients experienced no treatment benefit. The combination treatment reduced oxycodone tablet consumption by 35% (p = 0.02), but it did not affect the number of cannabis inhalation sessions.

Conclusions: Cannabis combined with oxycodone offered no advantage over either treatment alone, except for a reduction in opioid tablet intake; however, the overall drug load was the highest in the combination group. Moreover, cannabis was poorly tolerated and led to treatment discontinuation in one-third of participants treated with cannabis.

Clinical trial registration: The trial was registered at the WHO International Clinical Trials Registry Platform (trialsearch.who.int) on July 26, 2019, identifier NL7902.

Keywords: adverse (side) effects; analgesia; cannabis; oxycodone; self-titration.

Figure 1

Consort flow diagram.

Figure 2

Survival curves: number of patients in the study. Blue line: oxycodone group; orange line: cannabis group; green line: combined cannabis and oxycodone group. In the oxycodone group, 23 patients began treatment, while 3 patients dropped out. In the other two groups, 29 patients started treatment, while 9 patients dropped out.

Figure 3

(A–F) Daily reported composite adverse event score during the 42 days of treatment. (A–C) Intention-to-treat population; (D–F) per-protocol treatment. Circles: median ± interquartile ranges; ×: maximum reported pain scores.

Figure 4

(A–F) Daily reported pain scores during the 42 days of treatment. (A–C) Intention-to-treat population; (D–F) per-protocol treatment. Circles: median ± interquartile ranges; ×: maximum reported pain scores.

Figure 5

Use of oxycodone tablets and cannabis inhalation sessions in the three treatment groups. (A) Median oxycodone tablets (±interquartile ranges) used per day in patients who received oxycodone only. (B) Median number of inhalation sessions per day (±interquartile ranges) in patients who received cannabis only. (C) Median oxycodone tablets (±interquartile ranges) used per day in patients that additionally received cannabis. (D) Median number of inhalation sessions per day (±interquartile ranges) in patients who additionally received oxycodone. The dashed lines depict the maximum allowed oxycodone doses and cannabis inhalation sessions.