William S. Jacobs, MD Chief of Addiction Medicine Medical College of Georgia Medical Director Bluff Plantation Heroin and Synthetic Opioids Thursday, April 6, 2017 9:15 am – 9:40 am Disclosure Information William S. Jacobs, MD No disclosures The 2006 fentanyl crisis in the United States was the result of fentanyl being mixed into heroin and distributed to unsuspecting heroin users. The 2006 fentanyl crisis was fueled by a single clandestine laboratory in Toluca, Mexico, and once the laboratory was seized, the seizures of fentanyl and overdose deaths in the United States suddenly tapered off. During the current fentanyl crisis (2013-present), traffickers have not only used similar historical production and distribution techniques, but have also expanded the fentanyl market by producing wholesale quantities of counterfeit prescription medications containing various fentanyls. The current fentanyl crisis is fueled by China-sourced fentanyls and fentanyl precursor chemicals that are being sold to various individuals and organizations responsible for fentanyl processing and distribution operations; this scenario includes individuals linked to Mexican cartels and other criminal organizations that are not affiliated with Mexican cartels. The seizures of fentanyl-laced pills and clandestine pill press operations all across North America indicate that this is becoming a trend, not a series of isolated incidents. Source: Wikipedia https://ndews.umd.edu/sites/ndews. umd.edu/files/u1486/dea_emerging _threat_report_2016_quarter_4.pdf https://www.dea.gov/docs/Counterfeit%20Prescription%20Pills.pdf May 2015 - Chinese Customs officials seized 46 kilograms of fentanyl and 26 kilograms of acetyl fentanyl hidden in a cargo container destined for Mexico. Six customs officials became ill and one fell into a coma as a result of handling the fentanyls. The fentanyls had been transferred through five different freight forwarders before arriving Figure 11: Synthetic Drug Factory in China. at customs. An unrelated synthetic opioid first made at Upjohn in the 1970s called U-47,700 was placed on Schedule I earlier this month. U-47,700 was found together with fentanyl in the blood of the musician, Prince Rogers Nelson, when he was found dead at his Minnesota home and studio. Buried within a 1978 patent, U-47,700 exemplifies the extent to which recreational drug users will scour the peer-reviewed and patent literature for research chemicals with opioid effects but which were not, at the time, illegal. https://www.forbes.com/sites/davidkroll/2016/11/30/furanyl-fentanyl-joins-u-47700-as-the-second-illicit-opioid- dea-banned-in-november/#2a258eb09ba3 http://www.mdedge.com/emed-journal/article/130514/pain/new- opioid-epidemic-prescriptions-synthetics-and-street-drugs May require up to 10mg naloxone for reversal follwed by naloxone infusion to prevent renarcotization DEA Temporarily Bans Synthetic Opioid U-47700 ("Pink"), Linked to Nearly 50 Deaths Posted on November 15, 2016 The U.S. Drug Enforcement Administration (DEA) has temporarily classified U-47700, nicknamed "Pink," a schedule I drug, which means it has a high potential for abuse and no approved medical use. Since last year, this dangerous synthetic opioid has been linked with at least 46 confirmed deaths—31 in New York and 10 in North Carolina. Law enforcement agencies have seized the drug in powder form and as counterfeit tablets that mimic pharmaceutical opioids. Earlier this year, law enforcement in Ohio seized 500 pills resembling a manufacturer's oxycodone immediate-release tablets. However, laboratory analysis confirmed that they contained Pink. Pink belongs to a family of deadly synthetic opioids far more potent than morphine. It is usually imported to the United States, mainly from illicit labs in China. The drug can be toxic—even in small doses. It is typically taken by itself or combined with other drugs such as heroin and fentanyl. Pink's name comes from the pinkish hue of the powder. It has been available for purchase over the internet and is misleadingly marketed as a "research chemical." Labels that state "not for human consumption" or "for research purposes only" are likely used in an effort to avoid legal restriction. AH-7921 was originally created in the 1970s by Allen and Hanburys Ltd. in an attempt to develop an analgesic medicine, however, further production ceased due to its apparent addictive qualities. This compound has never been sold commercially or reputably as a medicine, nor as a substance with pharmaceutical, medicinal, or industrial applications, as reported by an article on AH-7921, originally published by Forensic Toxicology, and backed up by WHO However, as this source continues, at the time of publication (February 2015), this chemical was legitimately sold for research, as an “analytical reference standard.” https://www.drugtimes.org/designer- drugs/fentanyl-and-its-analogues.html Two simple modifications—the addition of one methyl group and one hydroxyl group (blue circles)— makes the molecule 6.3 times more potent than carfentanyl, 126-times more so than fentanyl, and 6,300 times more than morphine. This is just nuts. Doing the math (5), the estimated lethal dose of ohmefentanyl is 0.16 micrograms, which means that one poppy seed's worth (300 micrograms) of ohmefentanyl is enough to kill 1900 people. Another way of looking at it is even scarier: One ounce of the stuff (28 grams, 28,000,000 micrograms) would be enough to kill 175 million people—half the population of the United States (7). Emerging Synthetic Fentanyl Analogs Author(s): Schueler Harold E. Citation: Acad Forensic Pathol. 2017 Mar; 7(1):36-40. Abstract:Hundreds of synthetic substances have been introduced into the illicit drug market over the last ten years, but none of these drugs has had as poisonous a consequence as the emergence of the synthetic fentanyl analogs. Initially, pharmaceutical grade or illicit fentanyl was mixed with heroin, allegedly to boost the potency of the heroin. Then, the amounts of fentanyl spiked gradually increased until the proportion of fentanyl was greater than the proportion of heroin. Ultimately, many overdose cases began consisting of only fentanyl. The emergence of numerous synthetic fentanyl analogs, including acetylfentanyl, butyrylfentanyl, acrylfentanyl, furanylfentanyl and β-hydroxythiofentanyl, which are manufactured in China, were made available to the illicit drug traffickers over the Internet. [continued next slide] https://doi.org/10.23907/2017.004 Abstract, continued: In July of 2016, the most potent commercially available opioid, carfentanil, started appearing in illicit drug submissions and medical examiner death investigation cases in Northeast Ohio. Postmortem femoral blood carfentanil concentrations are in the picogram per milliliter (pg/mL) range, which is extremely low, and tests the limits of detection for most analytical forensic toxicology laboratories. The interpretation of these low carfentanil blood concentrations in antemortem and postmortem specimens is made difficult due to the overlap in the concentrations between these specimen types. The presence of these powerful synthetic fentanyl analogs presents a challenge to forensic toxicology laboratories preparing to analyze for these substances. https://doi.org/10.23907/2017.004 Street fentanyl can be taken orally, smoked, snorted, or injected Street fentanyl has been sold as: Pills Blotters Patches – cut up and sold as “chicklets” Powder Other forms may resemble ‘popcorn’ or ‘nerds’ candy All have the potential to be lethal! Fentanyl is often added to other drugs without the user’s knowledge. Traces have been found in other drugs including cocaine, Xanax, MDMA, methamphetamine & possibly marijuana. Fentanyl is sometimes sold as heroin, often leading to overdoses. Organized crime groups press the powder form into fake OxyContin tablets (“greenies”). Real Xanax Fake Xanax Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street “Norco” in Central California: A Case Report Alexander Olson, MS, Andres Anaya, MD, Alicia Kurtz, MD, Rawnica Ruegner, MD, Roy R. Gerona, PhD DOI: http://dx.doi.org/10.1016/j.annemergmed.2016.06.014 | In 2013 and 2014, more than 700 deaths were attributed to fentanyl and fentanyl analogues in the United States. Of recent concern is the cluster of unintentional fentanyl overdoses because of tablets thought to be “Norco” purchased on the street in Northern California. U-47700 (trans-3,4-dichloro-N- [2-(dimethyl-amino)cyclohexyl]-N-methylbenz-amide) is a nonfentanyl-based synthetic opioid with 7.5 times the binding affinity of morphine to μ-opioid. We report a case of fentanyl and U-47700 intoxication from what was thought to be illicitly purchased Norco. [continued next slide] A 41-year-old woman presented to the emergency department (ED) for altered mental status shortly after ingesting 3 beige Norco pills bearing a Watson imprint. She had pinpoint pupils and respiratory depression, which reversed after 0.4 mg naloxone administration intravenously. She had complete recovery and was discharged from the ED after a 4-hour observation period. Serum testing with liquid chromatography–quadrupole time-of-flight mass spectrometry (LC 1260 QTOF/MS 6550; Agilent, Santa Clara, CA) confirmed the presence of the medications the patient reported receiving, and additionally fentanyl (15.2 ng/mL) and U-47700 (7.6 ng/mL). In this case report, street Norco purchased in Central California resulted in altered mental status requiring naloxone reversal because