Fentanyl (also spelled fentanil) is an opioid used as a pain medication and together with other medications for anesthesia. Fentanyl is also made illegally and used as a recreational drug, often mixed with heroin or cocaine. It has a rapid onset and effects generally last less than an hour or two. Medically, fentanyl is used by injection, as a patch on the skin, as a nasal spray, or in the mouth.Common side effects include vomiting, constipation, sedation, confusion, hallucinations, and injuries related to poor coordination. Serious side effects may include decreased breathing (respiratory depression), serotonin syndrome, low blood pressure, addiction, or coma. In 2016, more than 20,000 deaths occurred in the United States due to overdoses of fentanyl and fentanyl analogues, half of all reported opioid-related deaths. Fentanyl works primarily by activating μ-opioid receptors. It is around 100 times stronger than morphine, and some analogues such as carfentanil are around 10,000 times stronger.Fentanyl was first made by Paul Janssen in 1960 and approved for medical use in the United States in 1968. In 2015, 1,600 kilograms (3,500 lb) were used in healthcare globally. As of 2017, fentanyl was the most widely used synthetic opioid in medicine. Fentanyl patches for cancer pain are on the WHO List of Essential Medicines, the most effective and safe medicines needed in a health system. For a 100 microgram vial, the average wholesale cost in the developing world is US$0.66 (2015) while in the USA the price is US$0.49 (2017) for that amount.