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.
Bibliografisk noteFunding Information:
This study was financially supported by grants from Regionernes Medicinpulje (grant no. EMN 2017‐00901) and the Danish Ministry of Health (Forsøgsordning med medicinsk cannabis grant no. 1610893). Research Nurse Elma Budalica thanked for technical assistance and Research Secretary Tine Kjær for secretarial assistance.
KZ, SHS, AH, CSH, TPE, LV and TSJ has nothing to declare. Outside the submitted work, NBF has received consultancy fees from Merck, Almirall, NeuroPN, Vertex and Novartis Pharma, has undertaken consultancy work for Aarhus University with remunerated work for Biogen, Merz and Confo Therapeutics, and has received grants from IMI2PainCare, an EU IMI 2 (Innovative medicines initiative) public–private consortium and the companies involved are: Grunenthal, Bayer, Eli Lilly, Esteve and Teva. TPA holds stocks in Novo Nordisk A/S. Outside the submitted work, JH has received consultancy fee from UCB and MP do consultancy work for Institute Horsted.