Pharmacology/Drug Development

While against recommendations, long-term opioid therapy (LTOT) for chronic pain is common. This study aimed to describe the prevalence of opioid prescriptions and to study the association of patient characteristics (demographics, pain characteristics, anxiety, depressive symptoms and pain coping) with future LTOT. The sample included = 1334 chronic musculoskeletal pain patients, aged 18-65, who were assessed for Interdisciplinary Multimodal Pain Rehabilitation (IMMR) in Swedish specialist rehabilitation. Prescriptions were tracked across a two-year target period after assessment. In total, 9100 opioid prescriptions were prescribed to 55% of the sample (M = 6, IQR = 14). Prediction of LTOT was analyzed separately for those who did (24%) and did not (76%) receive IMMR. The odds of receiving opioids was similar for these subsamples, after controlling for differences in baseline characteristics. In both samples, there were significant associations between patient characteristics and future opioid prescriptions. Dysfunctional pain coping was a unique predictor of LTOT in those who received IMMR while pain intensity and depressive symptoms were unique predictors in those who did not receive IMMR. The results underscore that opioid treatment is common among patients in chronic pain rehabilitation and relates to pain and psychological factors. Understanding in detail why these factors relate to opioid prescription patterns is an important future study area as it is a prerequisite for better management and fundamental for preventing overuse.

Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans.

Difelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small-peptidic structure limits CNS entry, minimizing potential CNS-mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single-center, randomized, double-blind, placebo-controlled, 3-way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg intravenously [IV]) or placebo on sequential days with an intervening 24 (±2) hour washout period. The primary endpoints included incidence of increased end-tidal carbon dioxide (ETCO ) ≥10 mm Hg versus baseline or a level >50 mm Hg sustained ≥30 seconds, and incidence of reduction in saturation of peripheral oxygen (SpO ) to <92% sustained ≥30 seconds. Secondary endpoints included incidence of reduced respiratory rate and other safety assessments. Fifteen subjects were randomized and completed the study. No subject on placebo or difelikefalin met the increased ETCO or reduced SpO primary endpoint criteria for respiratory depression. All respiratory measures in each group remained near baseline values during 4-hour postdose observations. No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO , SpO , or respiratory rate. The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms. All TEAEs were mild and resolved without intervention. Difelikefalin 1.0 and 5.0 mcg/kg IV did not produce respiratory depression.

People report substituting cannabis for pain medications, but whether cannabidiol (CBD) is used similarly remains unknown. CBD products can be CBD alone (isolate), hemp extract (containing <0.3% Δ-9-tetrahydrocannabinol [THC], other cannabinoids, and terpenes), or CBD-cannabis (containing >0.3% THC). In a secondary analysis from a cross-sectional survey, we examined substitution patterns among n = 878 individuals with fibromyalgia who currently used CBD. We sub-grouped participants by most commonly used CBD product (CBD isolate, hemp, CBD-cannabis, no preference) and whether they substituted CBD for medications. We investigated rationale for substituting, substitution-driven medication changes, CBD use patterns, and changes in pain-related symptoms (e.g., sleep, anxiety). The study population was 93.6% female and 91.5% Caucasian, with an average age of 55.5 years. The majority (n = 632, 72.0%) reported substituting CBD products for medications, most commonly NSAIDs (59.0%), opioids (53.3%), gabapentanoids (35.0%), and benzodiazepines (23.1%). Most substituting participants reported decreasing or stopping use of these pain medications. The most common reasons for substitution were fewer side effects and better symptom management. Age, hemp products, past-year use of marijuana, and higher somatic burden were all associated with substituting (p's ≤ 0.05). Those who substituted reported larger improvements in health and pain than those who did not. Participants using CBD-cannabis reported significantly more substitutions than any other group (p's ≤ 0.001) and larger improvements in health, pain, memory, and sleep than other subgroups. This widespread naturalistic substitution for pain medications suggests the need for more rigorous study designs to examine this effect. Perspective: This article shows that people with fibromyalgia are deliberately substituting CBD products for conventional pain medications despite the dearth of evidence suggesting CBD products may be helpful for fibromyalgia. CBD's medication-sparing and therapeutic potential should be examined in more rigorous study designs.