Therapeutic activation of the endocannabinoid system for opioid use disorder, chronic pain, and cancer-related pain: a review of current evidence.

INTRODUCTION

Opioid use disorder (OUD) and chronic pain are major global health challenges. Although opioid therapies provide effective analgesia, long-term use is limited by safety concerns, dependence, and variable efficacy. Modulation of the endocannabinoid system (ECS) has emerged as a potential therapeutic strategy for pain management and opioid-related disorders.

AREAS COVERED: This narrative review summarizes evidence on ECS-targeted interventions for OUD, chronic non-cancer pain, and cancer-related pain. Relevant literature was identified through PubMed using terms related to the ECS, cannabinoid receptors (CB1 and CB2), phytocannabinoids (Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]), synthetic cannabinoids, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors, and opioid-cannabinoid interactions. Emphasis is placed on interactions between ECS and opioid signaling pathways and findings from preclinical and clinical studies evaluating efficacy and safety.

EXPERT OPINION: This narrative review summarizes evidence on ECS-targeted interventions for OUD, chronic non-cancer pain, and cancer-related pain. Relevant literature was identified through PubMed using terms related to the ECS, cannabinoid receptors (CB1 and CB2), phytocannabinoids (Δ⁹-tetrahydrocannabinol [THC] and cannabidiol [CBD]), synthetic cannabinoids, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors, and opioid-cannabinoid interactions. Emphasis is placed on interactions between ECS and opioid signaling pathways and findings from preclinical and clinical studies evaluating efficacy and safety.