Opioids should not be first line therapy for chronic non-cancer pain .

A large review of 96 randomized trials shows opioids offer only small improvements in chronic noncancer pain: modest reductions in pain, minimal gains in physical function and sleep, and no meaningful benefit in emotional or social outcomes. Benefits often fall below established minimal important differences. Compared with active treatments such as NSAIDs, low-dose TCAs, or synthetic THC, opioids perform similarly. Harms—including nausea, constipation, dizziness, and sedation—are consistently increased, alongside well-documented risks of misuse and overdose. While opioids should not be first-line therapy, a minority of patients may achieve clinically meaningful relief, making opioid trials a preference-sensitive decision after optimizing non-opioid options.