Novel Synthetic Opioids: An Opioid Epidemic Within an Opioid Epidemic.

North America is currently facing an opioid epidemic. Opioid overdose deaths have increased 200% since 2000, and in 2014, 28,647 drug-poisoning deaths were attributed to some type of opioid. Multiple sources of opioids contribute to this growing problem and include prescription opioids (including natural and semisynthetic opioids, eg, oxycodone, hydrocodone), methadone, and other synthetic opioids (eg, fentanyl, tramadol); heroin; and other illicit opioids produced in clandestine laboratories. These illicitly produced opioids include nonpharmaceutical fentanyl, fentanyl analogs (eg, acetylfentanyl), and novel synthetic opioids, such as U-47700. The increased incidence of toxicity related to synthetic opioids is highlighted by the case report in this issue by Armenian et al, who describe a case of opioid toxicity related to fentanyl and U-47700 in a patient who believed she was receiving “Norco.” To understand the concerns about nonpharmaceutical fentanyl requires some background about the opioid epidemic. Prescriptions for opioid analgesics paralleled an increase in opioid abuse and fatalities between 2002 and 2010, leveling off from 2011 to 2013. However, drug overdose deaths involving natural and semisynthetic opioids, including the most commonly prescribed opioid pain relievers, oxycodone and hydrocodone, increased by 9% between 2013 and 2014. Increased prescriber education and public awareness of the true harms of opioid overprescribing has likely contributed to improvements in prescribing practices. Additionally, local and regional interventions have led to decreased prescribing and subsequent diversion of prescription opioids. However, as the availability of prescription opioids has decreased, the use and availability of other opioids has increased. This is clearly demonstrated by the significant increase in heroin use in several regions of the United States between 2010 and