An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that can cause hypoxia. Other symptoms include insufficient breathing, small pupils (with the exception of pethidine, where there may be dilated pupils), and unconsciousness, however its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.Opioid overdoses are diagnosed based on symptoms and examination. Risk factors for opioid overdose include high levels of opioid dependence, use of opioids via injection, high dosed opioid usage, having a mental disorder or having a predisposition for one, and use of opioids in combination with other substances, such as alcohol, benzodiazepines, or cocaine. Dependence on prescription opioids can occur from their use to treat chronic pain in individuals. Additionally, if following a period  of detoxification, which allows the tolerance level to fall, the risk of overdose upon return to use is high.Initial treatment of an overdose involves supporting the persons breathing and providing oxygen to reduce the risk of hypoxia. Naloxone is then recommended to those who cannot reverse the opioids effects through breathing. Giving naloxone via nasal administration or as an injection into a muscle has shown to be equally effective.
Three of the major opioid receptors include mu, kappa, delta, and nociception, each playing a role in eliciting the effects associated with opioids. An opioid overdose results from over-activation of these receptors, which can cause permanent brain damage from cerebral hypoxia or neurotoxicity.Mu receptors have an analgesic effect on the brain, and are found in various parts of the nervous system including the cerebral cortex and thalamus. They can be found in the nucleus accumbens, the pleasure centre of the brain, as well as the amygdala. Kappa receptors, in the hypothalamus, produce a similar analgesic effect. They bind with dynorphins to stimulate anti-reward effects —dysphoria— and other negative effects of withdrawal. While mu receptors are the source of addiction, kappa receptors contribute to continued abuse. They generate dysphoria in response to increasing stress levels via corticotropin-releasing factor (CRF). This increases erratic shifts in mood during withdrawal period and can prompt relapse. Delta receptors, found in the basal ganglia of the limbic system, have been shown to reduce anxiety by binding with enkephalins, although this requires further research. The most recent addition to these receptors are nociception opioid receptors. Although they have been determined to be receptors to certain ligands from opioids, their role has not yet fully understood.When opioids are ingested, the ligand binds to these constitutively active receptors to reduce neural activity. This is accomplished by inhibiting adenylyl cyclase and cyclic AMP, which are necessary for communication within the central nervous system.