Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of <7 and >7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis <7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols >7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.

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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.

Background: Lifestyle factors are associated with musculoskeletal pain and metabolic chronic diseases. To date, intensive lifestyle medicine programs have predominantly targeted metabolic rather than musculoskeletal conditions. Objective: To assess the feasibility of an intensive interprofessional lifestyle medicine program for patients with musculoskeletal conditions. Design: Prospective observational feasibility study. Setting: Tertiary academic medical center. Patients: Adults diagnosed with musculoskeletal condition(s) and lifestylerelated chronic disease(s) who previously completed standard-of-care musculoskeletal treatments, enrolled from 2018 to 2020. Interventions: Patients enrolled in an intensive interprofessional lifestyle medicine program led by a physiatrist, with options to interface with an acupuncturist, dietician, massage therapist, psychologist, physical therapist, and smoking cessation specialist. The physiatrist engaged in shared decision making with patients to establish program goals related to function, overall health, and required lifestyle changes. Bimonthly interprofessional team conferences facilitated communication between treatment team and patients. Main Outcome Measures: Feasibility was measured by patient participation and goal attainment. Secondary outcomes included changes from program enrollment to discharge in patient anthropometric, metabolic lab, sleep apnea risk, and Patient-Reported Outcomes Measurement Information System (PROMIS) function, pain, and behavioral health measures. Results: Twenty-six patients enrolled in the program (18 [69%] female, mean age 59 [SD 14.5] years, baseline hemoglobin A1c 6.0% [0.8%], high-sensitivity C-reactive protein 7.7 [12.1] mg/dL, 25-hydroxy vitamin D 32.0 [14.2] ng/mL). Of 21 (81%) patients who completed the program, 13/21 (62%) met their goal. On average, program completers presented for 26.2 (10.6) total visits over 191 (88) days. By discharge, program completers achieved clinically meaningful improvement in PROMIS Anxiety (mean difference À3.5 points, 95% confidence interval [À6.5 to 0.5], p = .035), whereas noncompleters did not (p > .05). Conclusions: An intensive interprofessional lifestyle medicine program for patients with musculoskeletal conditions is feasible. With training in lifestyle intervention, physiatrists are well suited to lead interprofessional teams aimed at assisting patients in making lifestyle changes to achieve personalized function-and health-related goals.

Introduction: There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored. Objectives: The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain. Methods: In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level. Results: Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief. Conclusion: These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.