<!-- Definition and use -->
Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, including pain relief.
The terms "opioid" and "opiate" are sometimes used interchangeably, but the term "opioid" is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum.
Medically they are primarily used for pain relief, including anesthesia. Extremely potent opioids such as carfentanil are approved only for veterinary use. Opioids are also frequently used recreationally for their euphoric effects or to prevent withdrawal. Opioids can be fatal, and have been used, alone and in combination, in a small number of executions in the United States.<!-- Side effects -->
Side effects of opioids may include itchiness, sedation, nausea, respiratory depression, constipation, and euphoria. Long-term use can cause tolerance, meaning that increased doses are required to achieve the same effect, and physical dependence, meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms. The euphoria attracts recreational use; frequent, escalating recreational use of opioids typically results in addiction. An overdose or concurrent use with other depressant drugs like benzodiazepines can result in death from respiratory depression.
<!-- Mechanism -->
Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Partial agonists, like the anti-diarrhea drug loperamide and antagonists, like naloxegol for opioid-induced constipation, do not cross the blood–brain barrier, but can displace other opioids from binding to those receptors in the myenteric plexus.
<!-- History, society and culture -->
Because opioids are addictive and may result in fatal overdose, most are controlled substances. In 2013, between 28 and 38 million people used opioids illicitly (0.6% to 0.8% of the global population between the ages of 15 and 65). By 2021, that number rose to 60 million. In 2011, an estimated 4 million people in the United States used opioids recreationally or were dependent on them. As of 2015, increased rates of recreational use and addiction are attributed to over-prescription of opioid medications and inexpensive illicit heroin. Conversely, fears about overprescribing, exaggerated side effects, and addiction from opioids are similarly blamed for under-treatment of pain.
thumb|upright=1.3|Educational video on opioid dependence.
Terminology
thumb|600px|class=skin-invert-image|alt=Opiates v. opioids with chemical structures indicated. Many classical opiates are also referred to as opioids in modern nomenclature.|[[Opiates and opioids with chemical structures indicated. Many classical opiates are also referred to as opioids in modern nomenclature.]]
Opioids include opiates, an older term that refers to such drugs derived from opium, including morphine itself. Opiate is properly limited to the natural alkaloids found in the resin of the opium poppy although some include semi-synthetic derivatives. Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone, and fentanyl; antagonist drugs such as naloxone; and endogenous peptides such as endorphins. The terms opiate and narcotic are sometimes encountered as synonyms for opioid. Narcotic, derived from words meaning 'numbness' or 'sleep', originally referred to any psychoactive compound with numbing or paralyzing properties. As an American legal term, narcotic refers to cocaine and opioids, and their source materials; it is also loosely applied to any illegal or controlled psychoactive drug. In some jurisdictions all controlled drugs are legally classified as narcotics. The term can have pejorative connotations and its use is generally discouraged where that is the case.
Medical uses
Pain
The weak opioid codeine, in low doses and combined with one or more other drugs, is commonly available in prescription medicines and without a prescription to treat mild pain. Other opioids are usually reserved for the relief of moderate to severe pain.
Acute pain
Opioids are effective for the treatment of acute pain (such as pain following surgery). For immediate relief of moderate to severe acute pain, opioids are frequently the treatment of choice due to their rapid onset, efficacy and reduced risk of dependence. However, a 2018 report showed a clear risk of prolonged opioid use when opioid analgesics are initiated for an acute pain management following surgery or trauma. They have also been found to be important in palliative care to help with the severe, chronic, disabling pain that may occur in some terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis. In many cases opioids are a successful long-term care strategy for those with chronic cancer pain.
Just over half of all states in the U.S. have enacted laws to restrict prescribing or dispensing opioids for acute pain.
Chronic non-cancer pain
Guidelines have suggested that the risks of opioids are likely greater than their benefits when used for most non-cancer chronic conditions including headaches, back pain, and fibromyalgia. Thus they should be used cautiously in chronic non-cancer pain. If used, the benefits and harm should be reassessed at least every three months.
For treating chronic pain, opioids are an option after other less risky pain relievers have been considered, including paracetamol or NSAIDs like ibuprofen or naproxen. Some types of chronic pain, including the pain caused by fibromyalgia or migraine, are preferentially treated with non-opioid drugs. The efficacy of using opioids to lessen chronic neuropathic pain is uncertain.
Opioids are contraindicated as a first-line treatment for headache because they impair alertness, bring risk of dependence, and increase the risk that episodic headaches will become chronic. Opioids can also cause heightened sensitivity to headache pain. This practice has led to a new and growing problem with addiction and misuse of opioids. Because of negative effects, the use of opioids for long-term management of chronic pain is not indicated unless other less risky pain relievers have been found ineffective. Chronic pain which occurs only periodically, such as that from nerve pain, migraines, and fibromyalgia, is better treated with non-opioid medications. They are frequently used combined with opioids, such as paracetamol combined with oxycodone (Percocet) and ibuprofen combined with hydrocodone (Vicoprofen), which boosts the pain relief but is also intended to deter recreational use.
Other
Cough
Codeine was once viewed as the "gold standard" in cough suppressants, but this position has since been questioned. Some recent placebo-controlled trials have found that it may be no better than a placebo for some causes including acute cough in children. Additionally, there is no evidence that hydrocodone is useful in children. Similarly, a 2012 Dutch guideline regarding the treatment of acute cough does not recommend its use. (The opioid analogue dextromethorphan, long claimed to be as effective a cough suppressant as codeine, has similarly demonstrated little benefit in several recent studies.)
Low dose morphine may help chronic cough but its use is limited by side effects.
Diarrhea
In cases of diarrhea-predominate irritable bowel syndrome, opioids may be used to suppress diarrhea. Loperamide is a peripherally selective opioid available without a prescription used to suppress diarrhea.
The ability to suppress diarrhea also produces constipation when opioids are used beyond several weeks.
Shortness of breath
Opioids may help with shortness of breath particularly in advanced diseases such as cancer and COPD. However, findings from two recent systematic reviews of the literature found that opioids were not necessarily more effective in treating shortness of breath in patients who have advanced cancer.
Restless legs syndrome
Though not typically a first line of treatment, opioids such as oxycodone and methadone are sometimes used in the treatment of severe and refractory restless legs syndrome.
Hyperalgesia
Opioid-induced hyperalgesia (OIH) has been evident in patients after chronic opioid exposure.