Category:Opioids: Difference between revisions

[[Opium]] was also a major article of international trade. Most consequential was the nineteenth-century commerce between British India and China; Chinese attempts to halt the inflow of [[opium]], and the British use of force in response, led to the conflicts known as the Opium Wars.<ref name="newsweek"/> The trade was not solely British — prominent American merchants, including John Jacob Astor and Boston trading firms, also participated in the nineteenth-century [[opium]] commerce with China.<ref name="frontline">Opium throughout history. FRONTLINE, ''The Opium Kings.'' PBS; 1998.</ref>

A turning point came between 1803 and 1804, when the young German pharmacist Friedrich Wilhelm Sertürner isolated a crystalline substance from [[opium]]. He named it after Morpheus, the Greek god of dreams — ''morphium'', later [[morphine]].<ref name="serturner">Schmitz R. Friedrich Wilhelm Sertürner and the discovery of morphine. ''Pharm Hist.'' 1985;27(2):61–74. PMID 11611724.</ref> It is generally regarded as the first alkaloid isolated from a plant, and it allowed, for the first time, pain treatment with a defined compound in measured doses. The firm E. Merck began commercial production in 1827.

[[Morphine]]'s use expanded enormously after the mid-nineteenth-century adoption of the hypodermic syringe, which allowed direct injection. Widespread medical and battlefield use — including during the American Civil War — was followed by recognition of how readily [[morphine]] produced dependence.<ref name="chemviews"/>

The pattern then repeated. In 1874 the English chemist C. R. Alder Wright first synthesized [[diacetylmorphine]] from [[morphine]], though the compound attracted little attention at the time. In the 1890s chemists at the Bayer company in Germany developed it further, and Bayer brought it to market in 1898 under the trade name [[Heroin]].<ref name="chemviews"/> It was promoted as a cough remedy and as a non-addictive substitute for [[morphine]] — a claim that proved badly wrong, as [[heroin]] is, if anything, more rapidly habit-forming. [[Heroin]] was withdrawn from ordinary medical use and made illegal in many countries in the early twentieth century.

Through the nineteenth century, [[opium]] and its derivatives were largely unregulated in the United States and were widely sold in patent medicines. A series of early-twentieth-century laws changed this. The Pure Food and Drug Act of 1906 required medicines to disclose ingredients such as opiates on their labels; this measure alone is reported to have reduced opiate sales substantially.<ref name="psmag">One hundred years ago, prohibition began in earnest. ''Pacific Standard.'' 2015.</ref> The Smoking Opium Exclusion Act of 1909 banned the importation of [[opium]] prepared for smoking. The Harrison Narcotics Act of 1914 required those who produced, imported, or distributed opiates — including prescribing physicians — to register and pay a tax; it was subsequently interpreted by courts and enforcement officials to prohibit the prescribing of opioids to maintain people who were addicted, which moved much opioid use outside legal medicine.<ref name="psmag"/>

The '''third wave''', from around 2013, has been driven by illicitly manufactured synthetic opioids — above all [[fentanyl]], which is far more potent by weight than [[morphine]] and is frequently mixed into other illicit drugs, often without the user's knowledge.<ref name="cdc"/> Some analysts describe a '''fourth wave''' marked by combined use of [[fentanyl]] with stimulants such as [[methamphetamine]] or [[cocaine]].<ref name="feinberg">Northwestern University Feinberg School of Medicine, Institute for Public Health and Medicine. What is the opioid epidemic? A public health explainer.</ref>

The progression from [[opium]] to [[heroin]] to [[fentanyl]] — each successive material more potent by weight than the last — has been linked not only to medical and market factors but also to drug prohibition itself. The "iron law of prohibition", a term coined by Richard Cowan in 1986 and summarized as "the harder the enforcement, the harder the drugs", holds that when a substance is prohibited, the illicit market tends to favour more concentrated and potent forms, because these are more efficient to conceal, store, and transport for a given value.<ref name="ironlaw">Thornton M. The potency of illegal drugs. ''J Drug Issues.'' 1998;28(3):725–740. DOI 10.1177/002204269802800309. See also Cowan R. How the narcs created crack. ''National Review.'' 1986; and "Iron law of prohibition", Wikipedia.</ref> The economist Mark Thornton has published research describing this effect for illegal drugs, and an analogous shift is commonly noted during alcohol prohibition in the United States, when consumption moved from beer toward more concentrated spirits. Commentators have invoked the same reasoning to explain why, in the 2010s, [[heroin]] was increasingly displaced by [[fentanyl]] and other still more potent synthetic opioids. Those who emphasize this argument present it as a case against prohibition; it remains one explanation among several for the rising potency of the illicit opioid supply.<ref name="ironlaw"/>

Opioids bind opioid receptors — especially the µ-opioid receptor, with additional activity at the κ and δ receptors — found in the nervous system and elsewhere in the body. Binding at the µ-opioid receptor is associated with the analgesic effects of opioids, with their euphoric effects, and with respiratory depression, the mechanism by which opioid overdose causes death.<ref name="chemviews"/> As with medicines generally, that opioids bind these receptors is well established; the fuller relationship between receptor binding and the range of clinical effects — including the development of tolerance and of dependence — is more complex and remains a subject of research, and should not be regarded as a closed question.

The opioids include compounds of natural origin such as [[morphine]] and [[codeine]]; semi-synthetic compounds such as [[heroin]] ([[diacetylmorphine]]), [[oxycodone]], [[hydrocodone]], and [[buprenorphine]]; and synthetic compounds such as [[fentanyl]], [[methadone]], and [[tramadol]]. [[Naloxone]] and [[naltrexone]] are opioid antagonists — they block opioid receptors rather than activating them. The list is not exhaustive.

The central acute danger of opioids is respiratory depression: at sufficient dose, opioids slow and can stop breathing, and this is the mechanism of fatal overdose. Risk is substantially increased when opioids are combined with other central nervous system depressants, including alcohol and benzodiazepines, and when potency is unknown — the particular hazard of illicitly manufactured [[fentanyl]]. Repeated use is associated with tolerance and with physical dependence, and a withdrawal syndrome on stopping. Figures for these risks in the literature are population estimates that vary between studies, and individual response varies considerably between people.