Chapter 11: Cannabis & Pain Management

The chapter explains how these molecules interact with the Endocannabinoid System (ECS), a critical biological regulatory network found in most vertebrates that utilizes lipid-based neurotransmitters like anandamide and 2-arachidonoylglycerol (2-AG) to maintain homeostasis. The two main receptors, CB1 (located primarily in the central nervous system) and CB2 (found mainly in the peripheral nervous system and immune cells), are detailed, noting that THC acts as a partial agonist at both, while CBD acts as an antagonist, especially at CB1 in the presence of THC. Clinically, evidence supports the efficacy of cannabinoids for treating chronic pain in adults, spasticity related to multiple sclerosis (MS), and chemotherapy-induced nausea and vomiting (CINV). Despite widespread state-level medical legalization, the chapter emphasizes that federal law, specifically the Controlled Substances Act (CSA), still classifies marijuana (containing over 0.3% THC) as a Schedule I drug, although the 2018 Farm Bill legalized hemp (containing less than 0.3% THC). The core agents approved by the FDA are reviewed, including Dronabinol and Nabilone (synthetic THC derivatives for CINV and appetite stimulation), and Epidiolex (a plant-derived CBD solution approved for Lennox-Gastaut and Dravet syndromes). Practitioners are advised to adhere to the principle of "start low, go slow" when initiating therapy, counsel patients on potential drug-drug interactions (especially regarding CYP enzyme systems), and warn them against the quality and safety variability of unregulated over-the-counter CBD products. Additionally, the role of terpenes in conferring plant fragrance and their potential therapeutic significance via the entourage effect—a synergistic interaction with THC and CBD—is explored.