The United States (U.S.) is experiencing an opioid epidemic, with 3–4% of adults receiving long-term opioid treatment – a level that is nearly four-fold higher per capita than Europe [1]. An estimated 25.3 million adult Americans, constituting approximately 11.2 % of the population, experience chronic pain, and opioids have not demonstrated evidence-based role in its long-term management [[2], [3], [4]]. In a recent meta-analysis involving over 26,000 patients with chronic noncancer pain, opioid analgesics were found to be associated with statistically significant yet small enhancements in both pain relief and physical functioning compared to placebo and these improvements were generally comparable to those observed with the use of non-opioid analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs), antidepressants, and anticonvulsant medications [5]. Opioid dependence is the leading global cause of disability, contributing to 9.2 million disability adjusted life years (DALYs) [6]. Due to rising risk for serious and permanent harms without sufficient evidence for benefits, current guidelines discourage management of chronic pain with long term opioids [3,7,8]. Many patients on long-term opioid therapy (LTOT) claim opioids provide therapeutic efficacy in managing their pain and improving their daily function, despite simultaneously reporting high pain intensity scores and impaired function. However, in literature, there is increasing evidence that no differences in pain and function have been observed between long term opioid and non-opioid users with chronic pain conditions [3,9,10]. One crucial problem in such patients is that they might not interpret the continued pain despite opioid use as a failure of the opioids; rather, they may perceive it as a failure of any potential for pain relief and they continue to request opioid treatment [3,11,12]. There is still a lack of randomized controlled trials have yet evaluated long-term benefits of opioid therapy compared to placebo for pain control, function, or quality of life yet [13].

Clinician-patient conversations on opioid use are typically centered around well-known and established serious side effects of opioids, including addiction, misuse and abuse, neonatal withdrawal, and respiratory depression. Recently, however, other significant but less well-known side effects of long-term opioid use have emerged. This scoping review aims to enhance clinical awareness of these side effects by compiling information on side effects across all body systems into a single paper. This compilation enables providers and patients to accurately assess the risks and benefits of long-term opioid use for pain relief. Additionally, it aims to identify probable side effects on humans that need to be assessed, considering previous animal studies.