Abstract and Introduction
Abstract
Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval −9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.
Introduction
Chronic musculoskeletal pain conditions are a major global burden and rank among the top 11 conditions of 328 diseases,[44] adding to the global burden of pain.[6]
Medical cannabis has been suggested as a modulator of joint pain because of the possible anti-inflammatory and analgesic properties of phytocannabinoids as shown in animal studies.[18,38] Yet, a systematic review of randomised controlled trials conducted in 2020 by the International Association for the Study of Pain (IASP) Presidential Task Force on cannabis and cannabinoid analgesia found sparse evidence of a beneficial effect in the trials performed to date.[19] This lead to the conclusion that cannabinoids, based on the current available evidence, could not be recommended for pain management.[34]
One notable observation by the IASP Task Force was the lack of high-quality trials examining the analgesic properties of cannabidiol (CBD) without the addition of delta-9-Δ-tetrahydrocannabinol (THC).[28]
The mechanisms of action of CBD have not been fully elucidated. Cannabidiol could mediate its effects by acting as an antagonist of the 5-HT1A[20,25,46] receptor, agonist of the transient receptor potential vanilloid family[31] causing desensitization in a similar fashion to capsaicin, and adenosine A2A receptor agonist.[33] Cannabidiol is generally well tolerated in clinical trials[41] and considered nonintoxicating,[27] although sedation can occur at higher doses.[39] However, long-term effects and safety of cannabinoid treatments have not been studied.[21]
In a recent meta-analysis of 17 preclinical trials with different pain models, a small yet significant effect was found for CBD with a standardised mean difference of 1.12 (95% confidence interval [CI] 0.84–1.40)[38] with the greatest effect seen in neuropathic pain models (nerve injury, chemotherapy, and diabetes) and conflicting results in inflammatory pain models (formalin, Freund adjuvant, and carrageenan) and osteoarthritis.[18]
Van de donk et al. performed a randomized controlled crossover trial[15] exploring the effects of a single dose of cannabis medication (18.8 mg CBD, less than 1 mg THC) in patients with fibromyalgia but this combination had no effect on pressure pain threshold or patient-reported pain. Likewise, Bebee et al. performed a randomized controlled trial[2] exploring the effects of a single dose 400 mg CBD in patients admitted to the emergency department for acute low back pain and found no effect on pain intensity 2 hours after administration when compared with a placebo. Despite a paucity of clinical evidence, CBD is currently used for pain conditions as is evident from a web-based survey of CBD users from 2018 which showed that 62% of respondents reported using CBD for medical conditions with chronic pain and arthritis or joint pain as the main reasons.[12]
Thus, at present, CBD is being introduced as medicine worldwide with a lack of evidence for its effect. This necessitates investigation of CBD including dosing regimens and treatment efficacy in different pain conditions in high-quality studies as recently suggested.[21]
The aim of this single-centre randomized double-blind placebo-controlled trial was to investigate the analgesic effect and safety of 12-week administration of synthetic CBD as an add-on treatment to conventional pain management in patients with hand osteoarthritis (Hand-OA) and psoriatic arthritis (PsA).
Pain. 2022;163(6):1206-1214. © 2022 Lippincott Williams & Wilkins
