This diversification leads to opioids being modified at varying rates, which can cause the drug to remain in the bloodstream for either a longer or shorter period of time. Therefore, these polymorphisms control opioid tolerance and facilitate overdose. Mental health
Evidence suggests that mental health can be a significant facilitator for opioid abuse. Given that opioids are prescribed for pain management, mental health disorders, such as depression, have been shown to increase use of opioids when treating conditions associated with chronic pain. Evidence has shown that individuals with mood and anxiety disorders have an increased likelihood of being prescribed opioids and continuing usage for lengthy periods of time, consequently increasing likelihood for dependence. As such, affected individuals have almost double the risk of using opioids for pain relief in the long-term. Additionally, mental health challenges associated with trauma, economic depression, social environments conducive to substance abuse and risk-taking behaviours have been shown to increase opioid misuse. Furthermore, mental health challenges associated with cardiovascular disease, sleep disorders, and HIV can cause opioid dependence and subsequent overdose. Notably, cyclic behaviours can be observed between mental illness and opioid abuse where individuals with mental health diagnoses engage in opioid use which further perpetuates mental health challenges and increased drug usage. Mechanism
Opioids bind with neurological opioid receptors to provoke analgesic, sedative, and euphoric effects. Opioids function by stimulating specific G-protein coupled receptors distributed throughout the body—including the brain, skin and spinal cord.
Because of their effect on the part of the brain that regulates breathing, opioids can cause very slow or stopped breathing, during overdoses, leading to hypoxia  or death if left untreated. Hypoxia is typically caused by respiratory depression. The brain uses oxygen to regulate the homeostasis of the body. In animal studies, it was found that opioids act on specific regions of the central nervous system associated with respiratory regulation, including the medulla and pons. During cerebral hypoxia, there is a lack of sufficient oxygen supply to the brain. Prolonged lack of oxygenation from respiratory depression can lead to detrimental damage to the brain and spinal cord and can leave the person unable to walk or function normally, even if treatment with naloxone is given.Alcohol also causes respiratory depression and therefore when taken with opioids can increase the risk of respiratory depression and death.In young children, opioid overdose may not be apparent right away. This is due to absorption, distribution, and metabolism differences between young children and adults, and the higher amount of opioid ingestion per kilogram of body weight. Causes
Risk factors for opioid overdose include opioid dependence, injecting opioids, using high doses of opioids, and use together with alcohol, benzodiazepines, or cocaine. The risk is particularly high following detoxification. Dependence on prescription opioids can occur from their use to treat chronic pain. In young children an overdose is usually due to opioids that are intended for their parents, older siblings, or grandparents.