Opioid-sparing effect of a cannabinoid formulation in treating acute radicular pain: a randomized controlled trial

Abstract Background Effective strategies are sought for reducing opioid consumption in the management of acute pain. This randomized clinical trial evaluated the effect of a single sublingual dose of a cannabinoid formulation, containing Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD) and terpenes, on intravenous morphine consumption and pain intensity in patients with acute radicular pain. Methods A single-center, randomized, parallel-group, placebo-controlled clinical trial, conducted at Hadassah Hebrew University Medical Center (Jerusalem, Israel). Adult patients presenting to the emergency department with acute radicular pain (visual analogue scale [VAS] ≥ 6), confirmed by CT or MRI, were consecutively screened. Of 246 eligible individuals, 69 consented and were enrolled. Participants were randomly assigned to receive a single sublingual dose of a high-dose cannabinoid formulation (19.8 mg THC, 19.8 mg CBD, and terpenes; n = 26), a low-dose cannabinoid formulation (9.9 mg THC, 9.9 mg CBD, and terpenes; n = 21), or placebo ( n = 22). The primary outcomes were (1) total intravenous morphine consumption during the 24 h post-treatment, administered via patient-controlled analgesia (PCA), and (2) mean pain intensity at rest and during movement, assessed by VAS. Results Total morphine consumption was significantly lower in the high-dose cannabinoid group compared with the placebo group (mean ± SD: 17.4 ± 14.2 mg vs. 33.2 ± 24.6 mg; p = 0.03; 95% CI [–30.2, –1.4]). Pain intensity scores did not differ significantly among groups (mean ± SD VAS: placebo 5.1 ± 2.1; low-dose 5.5 ± 2.1; high-dose 5.4 ± 2.3; p = 0.78; 95% CI [–13.84, 18.39]). Hallucinations occurred in one participant in the high-dose group and in two in the low-dose group; all episodes were transient (< 1 h) and resolved without intervention. No participant withdrew due to adverse effects. Conclusions A single sublingual high dose of a cannabinoid formulation containing THC, CBD, and terpenes significantly reduced opioid consumption in patients with acute radicular pain, without increasing pain intensity or causing serious adverse effects. These findings support the potential role of cannabinoid formulations as adjuncts in acute pain management. Trial registration Registered with ClinicalTrials.gov, identification ID: NCT04816994.