Oral capsules of tetra‐hydro‐cannabinol (<scp>THC</scp>), cannabidiol (<scp>CBD</scp>) and their combination in peripheral neuropathic pain treatment
Kanita Zubcevic, Merete Petersen, Flemming W. Bach, Aksel Heinesen, Thomas P. Enggaard, Thomas Almdal, Jakob Vormstrup Holbech, Lene Vase, Troels Stahelin Jensen, Christian Stevns Hansen, Nanna Brix Finnerup, Søren H. Sindrup
Abstract
BACKGROUND: Cannabinoids are often prescribed for neuropathic pain, but the evidence-based recommendation is 'weak against'. OBJECTIVES: The aim was to examine the effect of two cannabinoids and their combination in peripheral neuropathic pain. METHODS: This was a randomized, double-blind, trial with treatment arms for cannabidiol (CBD), tetra-hydro-cannabinol (THC), CBD and THC combination (CBD/THC), and placebo in a 1:1:1:1 ratio and flexible drug doses (CBD 5-50 mg, THC 2.5-25 mg, and CBD/THC 5 mg/2.5 mg-50 mg/25 mg). Treatment periods of 8-week duration were proceeded by 1 week for baseline observations. Patients with painful polyneuropathy, post-herpetic neuralgia and peripheral nerve injury (traumatic or surgical) failing at least one previous evidence-based pharmacological treatment were eligible for inclusion. The primary outcome was the change in weekly average of daily pain measured with a numeric rating scale (NRS). Trail Making Test (TMT) was used as one of the tests of mental functioning. RESULTS: In all, 145 patients were included in the study of which 118 were randomized and 115 included in the intention-to-treat analysis. None of the treatments reduced pain compared to placebo (p = 0.04-0.60). Effect sizes as estimated in week 8 (positive values worse and negative better than placebo) were CBD mean 1.14 NRS points (95% CI 0.11-2.19), THC 0.38 (CI -0.65 to 1.4) and CBD/THC -0.12 (-1.13 to 0.89). CONCLUSIONS: CBD, THC and their combination did not relieve peripheral neuropathic pain in patients failing at least one previous evidence-based treatment for neuropathic pain.