Codeine
Codeine, also known as methylmorphine, is a medication primarily used for pain relief (analgesic), as well as for treating coughs and diarrhea. It is classified as a controlled substance in the United States, where it is available only by prescription, while in other countries, it may be legal without a prescription when combined with other medications in lower doses. Derived from the opium poppy plant, Papaver somniferum, codeine was first isolated by French chemist Pierre-Jean Robiquet in 1832 and has a history of use dating back to the 19th century.
In addition to its pain-relieving properties, codeine affects the nervous system by being metabolized into morphine and other metabolites that can block pain signals and suppress cough reflexes. Despite its medicinal benefits, codeine can lead to side effects such as constipation, dizziness, and sedation, and it carries the risk of addiction and abuse. Though perceived as less potent than stronger opioids like oxycodone and fentanyl, codeine's accessibility has raised concerns about its misuse, especially among younger populations, with its recreational use often involving concoctions like "lean" or "sizzurp." Understanding both its beneficial and potentially harmful effects is essential for safe consumption.
Subject Terms
Codeine
ALSO KNOWN AS: Methylmorphine; morphine methylester; 3-methylmorphine
DEFINITION: Codeine is a drug used primarily as an analgesic, but it also is used in antidiarrheal and antitussive medications.
STATUS: Legal by prescription in the United States (US); legal outside the US without a prescription if combined with other drugs in relatively small dosages
CLASSIFICATION: Controlled substance: Schedule I (derivatives of codeine), II (codeine alone), III (with other analgesics), or V (in cough preparations with other drugs)
SOURCE: Milky fluid of immature seed capsules of the opium poppy plant (Papaver somniferum); also synthesized from morphine
TRANSMISSION ROUTE: Oral, intramuscular, subcutaneous, and intravenous
History of Use
Codeine was isolated from opium by French chemist Pierre-Jean Robiquet in 1832 and was used in the nineteenth century for pain relief and diabetes control. Near the end of the nineteenth century, codeine was used to replace morphine, another substance found in the opium poppy, because of the highly addictive properties of morphine. Codeine has effects similar to, albeit weaker than, morphine and was not thought to be addictive. Codeine was subsequently used in treatment for withdrawal from morphine.
The first detailed report of codeine addiction is thought to be from 1905, and reports by others followed. In the 1930s, concern over the widespread abuse of codeine in Canada was noted. Codeine abuse in the US was evaluated more fully in the 1960s, leading to the inclusion of codeine as a Schedule II controlled substance. Schedule II drugs have a high potential for abuse.
In the late twentieth and early twenty-first century, among substance abusers, prescription cough syrups containing codeine began to be mixed with soft drinks and candy (in a combination known as lean syrup, sizzurp, or purple drank). The combination was popularized by the hip-hop community through music and popular culture remains a substance of concern.
Effects and Potential Risks
Codeine primarily exerts its medicinal effects by being metabolized by liver enzymes to substances that bind to specific receptors in the central and peripheral nervous systems. One of the most potent of these substances is morphine. The codeine metabolites can effectively block the transmission of pain signals to the brain and can inhibit the cough reflex. The metabolites also contribute to the usefulness of codeine in treating diarrhea by affecting, among other things, the contraction of gastrointestinal tract muscles.
Short-term use of codeine provides pain relief and euphoric effects. Some of the more common side effects of codeine ingestion include itching, constipation, dizziness, sedation, flushing, sweating, nausea, vomiting, and hives.
Long-term use of codeine can lead to tolerance, necessitating higher doses to achieve the same euphoric effect. Endorphin (natural painkiller) production may be slowed or stopped, causing increased sensitivity to pain if codeine is not used. More serious side effects include respiratory depression, central nervous system depression, seizures, and cardiac arrest.
Although codeine is relatively mild when compared to popular opiates, such as oxycodone or fentanyl, its abuse and popularity within youth culture remained concerning in the mid-2020s. Its euphoric effects, relatively easy accessibility when compared to other opiates, and inclusion in recreational drinks remained concerning. Codeine abuse continued to be a problem, especially in younger demographics.
Bibliography
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Ware, Orrin D. "Lean/Sizzurp Ingredients, Use, and Coping With Mental Health Symptoms." Substance Abuse: Research and Treatment, vol. 17, 2023, doi.org/10.1177/11782218231195226. Accessed 23 Aug. 2024.
Xie, Junqing, et al. "Association of Tramadol vs Codeine Prescription Dispensation with Mortality and Other Adverse Clinical Outcomes." JAMA, vol. 326, no. 15, 19 Oct. 2021, pp. 1504-1515, DOI: 10.1001/jama.2021.15255. Accessed 22 Nov. 2022.