International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management

Abstract

The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.

Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

“…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 addon treatment to conventional pain management in patients with hand osteoarthritis (Hand-OA) and psoriatic arthritis (PsA).…”

“…This necessitates investigation of CBD including dosing regimens and treatment efficacy in different pain conditions in high-quality studies as recently suggested. 21…”

“…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.…”

Cannabis use disorder in patients with chronic pain: overestimation and underestimation in a cross-sectional observational study in 3 German pain management centres

“…The results of this study lead to a number of additional considerations: Future clinical trials of CbMs for chronic pain should adhere to current protocol guidelines for comprehensive assessment of harms, with explicit reporting of serious adverse events, and quantitative reporting of adverse events using validated methods. 12 More accurate information regarding harms is needed as current epidemiological studies indicate that adults with chronic pain are particularly at risk for adverse cannabis outcomes, mostly, CUD. 13 Although this concerning data on CUD in patients with chronic pain 10 could compromise patient care, some selected patients who may benefit from CbMs and MC should be allowed access with appropriate medical oversight.…”

Methodology considerations for ‘Safety and effectiveness of cannabinoids to Danish patients with treatment‐refractory chronic pain’ by Horsted et al.

“…The author's conclusion is in direct contrast to the conclusion and recommendations from the International Associations for the Study of Pain (IASP) Cannabis Task Force. Based on a thorough evaluation of current evidence, Rice et al (2021) concluded ‘That the available clinical evidence neither supports nor refutes claims of analgesic efficacy or safety for cannabinoids, cannabis, or cannabis‐based medicines’ and suggested future studies and recommendations should follow rigid rules of conclusive randomized, placebo‐controlled randomized controlled trials (RCTs) to provide evidence (Haroutounian et al, 2021).…”