08/6/19

Whistling in the Wind Against Insys

John Kapoor, the founder and former CEO of Insys was found guilty in May of 2019 of federal racketeering conspiracy charges for his role in Insys’s kickback scheme to boost sales of Subsys, its fentanyl spray, which is 100 times more powerful than morphine. His four co-defendants, former Insys executives and sales managers Michael Gurry, Richard Simon, Sunrise Lee and Joseph Rowan, were found guilty of federal racketeering conspiracy charges as well. Reuters, FiercePharma and NPR reported Kapoor was found guilty of running a nationwide scheme to pay doctors to prescribe Subsys by retaining them as speakers for what were sham events at strip clubs and expensive restaurants.

The FDA approved Subsys in 2012, but only to treat severe cancer pain. Prosecutors said Kapoor directed efforts to defraud insurers who were resistant to paying for Subsys, which could cost tens of thousands of dollars a month. Insys allegedly set up a call center where employees pretended to be from doctor’s offices. “Jurors heard phone calls in which Insys employees made up diagnoses to ensure that insurance companies covered Subsys.” Alec Burlakoff, the former director of the paid speaker program was seen in an internal promotional video (dressed as a dancing bottle of Subsys) where he and other sales managers were rapping about wooing physicians and capitalizing on opioid titration, boosting dosages of patients who develop a tolerance to the drug.

To be great, it takes a decision to be better than the competition. . . . Get a speaker you can meet with over supper. We can come to your office. We can go and bring some lunch in. While your staff is getting fed we can start discussing Subsys.

Burlakoff reached a plea deal in November and went on to testify against Kapoor. In early April he pleaded guilty and turned state’s evidence in Arizona, implicating Insys executives in a parallel lawsuit. He was forced to forfeit $9.5 million to the state.

Former Insys sales representative Holly Brown testified that Sunrise Lee gave a doctor a lap dance at a Chicago club in 2012. Brown said she saw Lee sitting on the doctor’s lap, “kind of bouncing around. . . . He had his hands sort of inappropriately all over her chest.” Lee is a former stripper turned regional sales manager for Insys. She was hired as a regional sales manager despite having no experience with pharmaceuticals. The Washington Post reported that her only previous managerial experience included running an escort service.

The doctor was Paul Madison who ran a notorious, “shady pill mill.” Madison’s “speaker” events were held at a Chicago restaurant owned by Kapoor and were attended by his friends instead of clinicians. “The idea was these weren’t really meant to be educational programs but were meant to be rewards to physicians.” Insys paid Madison over $70,800. He was convicted in November on unrelated fraud charges for billing insurance companies for chiropractic manipulations that were never performed.

Kapoor, Lee and the other co-defendants denied any wrongdoing. Lee’s attorney specifically denied the lap dance allegation in court and accused prosecutors of “objectifying her in the same way … Dr. Madison did.” The heart of Kapoor’s defense argument was he was unaware of the illegal schemes, blaming Burlakoff and other former employees who pled guilty and then testified for the prosecution.

NPR said Kapoor is among the highest-ranking pharmaceutical executives to face trial for actions taking place in the midst of the opioid epidemic. It was the first successful prosecution of top pharmaceutical executives for crimes related to illegally prescribing and marketing opioids. U.S. Attorney Andrew Lelling said: “”This is a landmark prosecution that vindicated the public’s interest in staunching the flow of opioids into our homes and streets.” The guilty verdict could influence the cases against other pharmaceutical executives, as with Purdue Pharmaceuticals. See “The Tale of the OxyContin Lie” and “Giving an Opioid Devil Its Due” for more on the Sacklers and Purdue Pharmaceuticals.

Last year Insys agreed to pay $150 million over five years to end a Justice Department investigation into the bribery and kickback scheme. Since 2015, Insys shares have fallen 90 percent in value. On June 5, 2019, Insys Therapeutics agreed to settle the government’s separate criminal and civil investigations for $225 million. As part of the criminal resolution Insys will plead guilty to five counts of mail fraud, and pay $195 million to settle allegations that it violated the False Claims Act. Insys has been named in approximately 1,000 lawsuits over Subsys.

According to the charging document, from August 2012 to June 2015, Insys began using “speaker programs” purportedly to increase brand awareness of Subsys through peer-to-peer educational lunches and dinners. However, the programs were actually used as a vehicle to pay bribes and kickbacks to targeted practitioners in exchange for increased Subsys prescriptions to patients and for increased dosage of those prescriptions.

Then on June 10^th, the Wall Street Journal reported Insys filed for chapter 11 bankruptcy. This means the U.S. Justice Department will have to share available money with other unsecured creditors, suggesting it almost certainly will not collect its settlement in full. More than 90% of the company’s revenue came from opioid sales, but it wasn’t enough to cover the costs of lawsuits and investigations. How much the government collects depends on how much Insys can raise by selling its assets and the competition from other creditors. These other creditors include the U.S. Attorneys Office in Massachusetts, and the law firms who defended Insys and its former executives, including Kapoor. Insys spent more on legal costs in the first quarter than it did on research and development, sales, and marketing combined.

The company’s chapter 11 filing on Monday marks the first corporate bankruptcy directly linked to the nation’s opioid crisis, but more are possible as corporations struggle to dig out from under liabilities stemming from accusations that they profited from addiction.

Leo Beletsky, a professor of law and health sciences at Northeastern University, told NPR the trial against Kapoor and Insys overlooked broader issues, such as drug companies legally spending billions of dollars to maximize the use of their medications. “We need to think much more deeply about how we regulate the pharmaceutical industry and how we prevent these kinds of practices from occurring in the first place.” Yet there are no major legislative efforts to regulate the pharmaceutical industry. Hopefully Beletsky’s suggestion will be acted on and not become another example of whistling in the wind against attempts to hold pharmaceutical companies like Insys accountable for their actions.

For more on Insys and fentanyl, see “Fentanyl: Fraud and Fatality” and “A Time of Reckoning Is Coming.”

06/29/18

Through the Fentanyl Looking Glass

Tenniel sketch from “Alice through the looking glass” 1871; in the public domain

A May 1, 2018 research letter in JAMA, “Changes in Synthetic Opioid Involvement in Drug Overdose Deaths,” found that the involvement of synthetic opioids in overdose deaths increased from 14.3% of opioid-related deaths in 2010 to 45.9% in 2016. “Among synthetic opioid-related overdoes deaths in 2016, 79.7% involved another drug or alcohol.” The most common substances were another opioid (47.9%), heroin (29.8%), cocaine (21.6%), prescription opioids (20.9%), benzodiazepines (17.0%), alcohol (11.1%), psychostimulants (5.4%) and antidepressants (5.2%). “Lack of awareness about synthetic opioid potency, variability, availability, and increasing adulteration of the illicit drug supply poses substantial risks to individual and public health.”

Widespread public health messaging is needed, and clinicians, first responders, and lay persons likely to respond to an overdose should be trained on synthetic opioid risks and equipped with multiple doses of naloxone. These efforts should be part of a comprehensive strategy to reduce the illicit supply of opioids and expand access to medication-assisted treatment for opioid addiction.

This was the first time synthetic opioids surpassed prescription opioids and heroin as the primary cause of opioid overdose-related deaths. The analysis was limited because 15% to 25% of the death certificates failed to specify which type of drug(s) were involved in the overdose. In “Synthetics now killing more people than prescription opioids, report says,” CNN quoted the lead author of the JAMA report as saying, “So the actual numbers are likely higher.” He added that the findings track closely to the increased availability of illicit synthetic opioids coming into the US.

A senior staff attorney for the nonprofit Drug Policy Alliance commented how synthetic opioids are easier to manufacture than heroin. She also said China was the primary source for illicit fentanyl. “ Illicitly manufactured fentanyl is almost exclusively made in China. . . . It’s then shipped, broadly speaking, to Mexico, where it’s added to the heroin supply before it enters the United States as a cost-saving measure.”

An added concern is while initially synthetic opioids were mixed with heroin, now it’s “mixed with cocaine, methamphetamines and other substances of abuse.” There are also counterfeit tablets containing fentanyl that are made to look like prescription drugs, such as Xanax—made with pill presses shipped from China. See “Buyer Beware Drugs” for more information on this.

In November of 2017 STAT News reported a Chinese official disputed the claim made by President Trump that most of the fentanyl coming to the US was produced in China. He said: “the evidence isn’t sufficient to say that the majority of fentanyl or other new psychoactive substances come from China.” However, both the DEA and the White House Office of National Drug Control Policy previously pointed to China as North America’s main source for fentanyl, related drugs and the precursor chemicals used to make them. Bejing previously regulated fentanyl and 18 related compounds, including carfentanil, furanly fentanyl, acryl fentanyl and valeryl fentanyl.

Then Reuters reported in January of 2018 how a congressional report of a year-long probe by a Senate subcommittee found it was easy for buyers in the US to purchase fentanyl, often in large quantities, from China through the internet. Staff of the committee focused on six “very responsive” providers in China—out of hundreds of pages of website offering fentanyl for sale. The Chinese sellers preferred to ship the fentanyl using Express Mail Service, which operates worldwide through each country’s postal service, including the U.S. Postal Service. “Surcharges are applied, the investigators said, for customers demanding shipment through private delivery services, such as FedEx, DHL and United Parcel Service, because of the greater likelihood the goods would be seized.”

A Chinese foreign ministry spokesperson said she was unaware of the specifics, but that anti-drug coordination was one of the highlights of China-US law enforcement cooperation. “We stand ready to work with the US to enhance our coordination in this field.” The investigators found that the US Postal Service only received the electronic data of just over one-third of all international packages, “making more than 300 million packages in 2017 much harder to screen.” A spokesperson said the Postal Service continues to work to address this issue. Implementing the use of electronic data was slowed by the need to negotiate with international partners.

The Canadian province of Prince Edward Island is slightly larger than the state of Delaware and the only subnational jurisdiction in North America with no mainland territory. Farming is the heart of the province’s economy, which produces 25% of Canada’s potatoes. It consists of the main island (Prince Edward Island) and 231 minor islands. With only around 143,000 residents, it would seem to be one of the last places in North America to be impacted by the fentanyl crisis. But that’s not true any more. In the beginning of May in 2018, the province’s Department of Health reported fentanyl was found in cocaine seized by police in Charlottetown, the capital city of the province.

About the same time Vox reported on the sharp increase of cocaine and fentanyl overdose deaths in the US. Using data from the CDC, Vox found the number of overdose deaths from cocaine and synthetic opioids to be 4,184, 17 times greater than the 245 deaths reported in 2013. Keith Humphreys, from Stanford University, said no one knows for sure what’s going on. “I can tell you my guesses, but I’m pretty sure no one really, honestly knows what’s going on.” Mixing cocaine and fentanyl in a speedball is possible, but the presence of both drugs in a post mortem toxicology report does not mean they were used at the same time. This is the simplest and most plausible explanation, but it wouldn’t apply to the Charlottetown seizure on Prince Edward Island.

A dealer accidentally mixing cocaine and fentanyl, while possible, is even more unlikely. It would have to be a drug operation that buys and sells both cocaine and opioids. Then the individuals cutting the product would have to neglect to clean the space used for cutting the drugs before switching from one drug to the other. But the picture of dumb and dumber drug dealers who just don’t realize what they are doing doesn’t “cut” it.

A third possibility is that dealers or the traffickers above them are purposely mixing cocaine and fentanyl. “With or without the buyer’s knowledge, drug sellers or someone up the chain may be mixing cocaine and fentanyl before the product hits the street.” Two possible reasons would be to give a supposed cocaine product an extra kick; or to get cocaine users hooked on opioids. Experts are skeptical this practice is widespread. Cocaine and fentanyl have opposite drug effects, “which can be unpleasant to someone who wants a pure upper or downer experience.” One expert said the dealer was already making money off the person. “Why would you want to kill them or piss them off?” Yet while this explanation is unlikely and highly speculative, it seems the best explanation for the Charlottetown seizure.

Although what follows is purely speculative, I’d suggest someone intentionally mixed cocaine and fentanyl as an experiment to see if the newer, “edgier” cocaine had a market; it didn’t. Reluctant to waste the drug batch, the trafficker sold it down the supply chain to dealers in Prince Edward Island. If the price was low enough, it may have been that the local dealers didn’t ask too many questions.

Whatever the true explanation is, individuals using illicit drugs today have stepped through the looking glass into a brave new world where what you get may not be what you thought it was.

11/10/17

Here’s Some Gray Death

The fact-checking website Snopes looked into a report from Indiana claiming there is a new and dangerous drug called “Gray Death.” The report claimed Gray Death could cause the overdose or death of a drug user if it was accidentally inhaled after it became airborne or if it was absorbed through the skin after contact. Their investigation found the report was true. A local Indiana TV station, WDRB, was the source for the Snopes investigation, saying the Indiana Department of Homeland Security announced Gray Death was found in the Hoosier state beginning in May of 2017. But it seems Indiana was late to the Gray Death party.

Gray Death is a drug cocktail of heroin, fentanyl, carfentanl, and often U-47700 known on the street as “Pink” or “U4.” Heroin is two to three times as powerful as morphine. Fentanyl is about 50 to 100 times more powerful than heroin. Carfentil is about 100 times more powerful than fentanyl. U4 is the weakest drug in the mix after heroin, at only 7. 5 times the strength of morphine. The drug cocktail looks like concrete mix, thus the nickname of gray death.

Russ Baer of the DEA told NBC News on May 5, 2017 that Gray Death was initially limited to the Gulf Coast and states like Georgia and the mid-West state of Ohio. But it’s also been spotted in places like Chicago, San Diego, and Lexington. A “Pink”-free precursor to Gray Death was spotted in the Atlanta area back in 2012. “We are more routinely seeing deadly cocktails of heroin, fentanyl, various fentanyl-class substances, along with combinations of other controlled substances of varying potencies including cocaine, methamphetamine, and THC. . . . No one should underestimate the deadly nature associated with these cocktails.”

CNN noted that not only do the ingredients of Gray Death vary from sample to sample, some are present in such low concentrations (because of their strength) they may not show up on tests. Donna Ula, director of forensic chemistry at a biochemical company working with state and federal officials to identify unknown street drugs, said “It’s going to constantly vary, and it’s going to keep the chemists and the medical examiners on their toes.” She said Gray Death is “a fast-track route to the morgue.” A forensic chemist with the Georgia Bureau of investigation said even its gray color is a mysterious. “Nothing in and of itself should be that color.”

There have been several overdoses and overdose-related deaths in Georgia and Alabama linked to Gray Death. The Georgia Bureau of Investigation issued a public safety alert on May 4, 2017 about illegal synthetic opioids (Gray Death). The GBI Crime Lab has received about 50 cases of suspected Gray Death this year. Many contain three or four different opioids. One Metro-Atlanta law enforcement agency seized around 8 kilograms of a substance that when field-tested, didn’t identify what the mixture was. Further analysis at the GBI Lab found furanyl fentanyl and U-47700, two of the opioids regularly found in the Georgia Gray Death cocktail.

On May 10, 2017 The Morning Call reported there is Gray Death in the Lehigh Valley of Pennsylvania. After making two undercover drug buys at a woman’s home in Bethlehem PA, investigators had the drug packets tested because of their off-white color. They suspected they might contain fentanyl. But the preliminary results showed the packets contained a mixture of heroin, fentanyl and U4—Gray Death. After the preliminary identification, a search warrant was quickly issued: “We wanted to get it off the street as fast as possible.”

The woman’s three children, between the ages of 3 and 9, were living in the home with their mother. Police found some of the drug in a cup sitting on the shelf of a kitchen cabinet” within east reach of the children. The woman was arrested and charged with endangering the welfare of children, drug possession and possession of drug paraphernalia. She was freed after posting $5,000 bail. No word was reported on the children, but they were likely not in their mother’s custody given her charges.

According to Healthline News, the combination of synthetic opioids and/or heroin making up Gray Death varies widely. Given that the drugs or their precursors are created in unregulated labs, domestic drug dealers don’t always know how strong a batch is. “The potency can change from one batch to the next.” Dr. Seonaid Nolan, a clinical scientist in addiction medication at the University of British Columbia said: “Because it’s so potent, a small misstep in the preparation of the drug can lead to lethal consequences.”

This high potency also means it’s more difficult for customs and law enforcement to make searches and seizures, as it allows the drug syndicates to ship less physical product across the border. Sometimes the drugs are even shipped directly through the postal system. “Drug traffickers can move a high quantity or high volume of the product in a fairly small package.”

Traditional opiates like heroin are derived from the poppy plant, meaning the poppy plants have to be grown, harvested and then processed before heroin can be manufactured. “However, synthetic opioids can be produced entirely from chemical precursors.” This makes their production much simpler than heroin, since the entire manufacturing process can be done in a lab.

Fentanyl and its analogues have a high lipid solubility, meaning they readily pass through fatty tissues in the body. So fentanyl is used in transdermal patches and even lollipops, allowing it to enter the blood stream without having to be digested in the stomach. Since it doesn’t get metabolized, you need smaller amounts of fentanyl because it can go directly to the brain through the blood system. This also explains its danger if it becomes airborne or comes in contact with exposed skin. Edward Bilsky, a professor of Biomedical Sciences at Pacific Northwest University said:

[These drugs] are very fast acting and produce profound depression of respiration and other central nervous system functions leading to many deaths. . . . First responders and others around the victim need to be careful due to secondary exposure.

According to the DEA, fentanyl analogs, like acetyl fentanyl and furanyl fentanyl are manufactured in China by clandestine labs, and then smuggled into the U.S. through established drug smuggling routes in Mexico. Mexican drug traffickers also manufacture their own analogs of fentanyl. In the past, the Chinese government denied they were the source of illicit fentanyl being smuggled into the U.S. But DEA officials and others met with Chinese officials in 2016, which prompted China to regulate four fentanyl-related substances in an effort to help stem the flow of these opioids into the U.S. in action that went into effect in March of 2017.

Carfentanil was one of these substances. Because of its off-the-charts strength, it was receiving a lot of press coverage in 2016. See “Fentanyl: Fraud and Fatality” and “The Devil in Ohio.” But unless you followed news on the death of Prince, you may not have heard of “Pink” (U-47700 or U4) before. In addition to fentanyl and Percocet (oxycodone-acetaminophen), Pink was found in his system. In November of 2016, the DEA temporarily classified U-47700 as a Schedule I controlled substance, due to its “immanent threat to public health and safety.” The DEA received at least 46 confirmed reports of deaths associated with U-47700—31 in the state of New York and 10 in North Carolina. “This scheduling action will last for 24 months, with a possible 12-month extension if DEA needs more data to determine whether it should be permanently scheduled.”

In addition to Georgia, Pennsylvania and Ohio, drug busts in multiple states are reporting they have seized quantities of Grey Death. Traffic stops in Greenville County South Carolina found 17 pounds of heroin and one pound of Grey Death. There have been two reported seizures of Grey Death in Virginia. Grey Death has been reported in Florida since November of 2016. It’s been found in Alabama. In a video from WCPO in Cincinnati, Ohio, Detective Jim Larkin of the Lorain County Sheriff’s Department wondered why anyone would try something called Grey Death. “Here’s some Grey Death. Now what do think is going to happen to you? Why do you think it’s called Grey Death?”

09/22/17

Be Careful Out There

Recently, around 6 a.m. on a Wednesday, several law enforcement agencies executed federal search warrants at three locations in the West End area of Pittsburgh. In one home, when the SWAT team members entered, one of the suspects was trying to escape through a back window. Another one of the suspects knocked over a table where they had been bagging drugs, “causing the powder narcotics to become airborne” and exposing the SWAT officers to the airborne drug. Eighteen of them were taken to the hospital suffering from various symptoms.

According to Brenda Waters of KDKA, the CBS Pittsburgh affiliate, all eighteen were medically cleared. “None of the … law enforcement officers taking part in the early morning raid were adversely affected by the drugs.” The agencies participating in the raid included Pittsburgh Police, Pittsburgh SWAT, U.S. Immigration and Customs, state police and Homeland Security. In addition to the airborne substance, they found more than 1,000 stamp bags, 250 grams of unpackaged drugs and a “significant quantity of white powder” on a plate in the kitchen. The airborne substance was probably fentanyl; maybe carfentanil.

Dr. Tureurro, the chief of Emergency Services at UPMC Mercy Hospital, where the officers were treated, said they were fortunate to get out of the situation quickly, thus minimizing their symptoms. They had burning sensations in their throats; some became lightheaded; others were nauseous. “The big thing that we did for them is we basically decreased the chance that they could be exposed to anything that was laying on their bodies or on their clothes.” By removing their clothes, then showering and decontaminating themselves, the officers decreased their chances of exposure to any of the substance. The Justice Department press release said:

Fentanyl exposure is an all too real risk to law enforcement as we learned this morning. Quick and professional action by first responders helped avert a potential catastrophe.

The Pittsburgh Post-Gazette reported that the raid originated from a May investigation by Customs and Border Protection when agents intercepted a fentanyl package marked as “plastic fittings” that was shipped from Hong Kong. The accused leader of the drug operation had a history of repeated arrests for felony drug convictions and disregarding bond conditions in his repeated arrests for drug related charges. He had been initially arrested for possession and distribution on June 1^st in relation to the intercepted package of fentanyl from Hong Kong. He was rearrested on July 20^th, discarding a brick of fentanyl on the floor of a police car taking him to jail, and then again on August 2^nd. Each time he was released on bond he resumed his criminal activities. This time he did not receive bail.

This is not an isolated or freak occurrence. In September of 2016, The Washington Post reported on a raid in Harford Connecticut when 11 SWAT officers were exposed to airborne fentanyl and heroin. The powder may have blown into the air after the tactical team tossed a flash-bang grenade, or the suspects could have swept the table where they were packaging the drugs. The officers moved through a “cloud of dust in the air.” Several officers were lightheaded, nauseous; they had sore throats and headaches. As a precaution, the entire team went to a local hospital for treatment.

Jim Pasco, executive director of the National Fraternal Order of Police, said this has been an inherent risk for law enforcement for decades, beginning with “The granddaddy of all problems—being exposed to meth labs.” A DEA spokesperson said law enforcement officers are concerned with protecting themselves and the public.

Law enforcement officers do carry a bigger burden than ever — we are fighting to protect the American public from poisons that bring death and destruction to our communities — but we are also faced with challenges of educating the public as to the deadly risks of these substances and about the inextricable links between misuse of prescription opioids to heroin and fentanyl use and addiction.

Kelly Burch reported for The Fix that in May of 2017 when an East Liverpool Ohio police officer helped in the arrest of drug suspects, they tore open bags of the drugs in an attempt to destroy evidence. Back at the station, the officer noticed a white powder on his uniform and tried to brush it away. “I had placed my thumb, and index finger in it and tried to brush it off. I don’t know if it went through my skin or if it became airborne when I wiped it off, or a combination of both.” Within a few minutes, he didn’t feel like himself. The last thing he remembered was falling backwards into the door.

He received a dose of Narcan at the station and a few more at the hospital. “Never in a million years did I think I would be in the hospital for something that serious, for overdosing.” He knew the job was dangerous and might encounter guns and knives. But “you’re not thinking that a particle of dust or drug killing you.” The experience made him even more determined to keep these powerful drugs off the streets: “I am not letting drug dealers win, you may have almost killed me, but you’re not going to win, you’re not going to come to this city and bring that poison.”

Another Ohio encounter with fentanyl took place in early August of 2017 in Massillion, about 50 miles south of Cleveland. Three nurses at the Affinity Medical Center in Massilon lost consciousness while they were cleaning a room where an overdose victim had been treated. All three were treated with naloxone and are said to have recovered. The nurses union at the hospital wanted to meet with hospital officials to discuss protocols for environmental contamination, but the hospital declined, saying it already has effective policies. Hmmm … with three nurses becoming unconscious, it seems a review of the policies woudn’t hurt.

CTV Vancouver reported in October of 2016 that the CBSA, Canada’s Border Services Agency advised its officers to avoid contact with a package they suspect contains fentanyl. The president of Canada’s Customs and Immigration Union said: “What we’re telling our officers at this time, from a health and safety point of view, is that if there’s a package and they think there could fentanyl, they shouldn’t touch it. They shouldn’t approach it.” If an agent believes a package contains the drug, they are advised to give it to supervisors. “We need to approach this so our officers have the right tools, right training and the right equipment.”

In a June 2016 press release, the DEA announced they had released a short Roll Call Video to all law enforcement agencies about the dangers of improperly handling fentanyl. You can watch the video here. The press release said the DEA was concerned about law enforcement coming in contact with fentanyl on the streets in the course of enforcement activities, such as buy-walk or buy-bust operations. “Officers should be aware that while unadulterated fentanyl may resemble cocaine or heroin powder, it can be mixed with other substances which can alter its appearance.” The report noted the current outbreak involved not just fentanyl, but fentanyl compounds (like carfentanil) as well.

Universal precautions must be applied when conducting field-testing on drugs that are not suspected of containing fentanyl. Despite color and appearance, you can never be certain what you are testing. In general, field-testing of drugs should be conducted as appropriate, in a well ventilated area according to commercial test kit instructions and training received. Sampling of evidence should be performed very carefully to avoid spillage and release of powder into the air. At a minimum, gloves should be worn and the use of masks is recommended. After conducting the test, hands should be washed with copious amounts of soap and water. Never attempt to identify a substance by taste or odor.

The DEA published “A Briefing Guide for First Responders” on fentanyl. It contained a history of fentanyl, a description of illicit forms of fentanyl and fentanyl-related substances, the risks of exposure and treatment, as well as decontamination recommendations.

Fentanyl was first synthesized in 1959 by a Belgian chemist. Other forms of pharmaceutical fentanyl were developed for pain management, including a transdermal patch, a nasal spray, a sublingual tab and a flavored lollipop—yes a fentanyl lollipop. While pharmaceutical fentanyl is diverted on a small scale, the current problem is due to transnational criminal organizations competing for the U.S. market.

China and Mexico appear to be the main source countries for illicit fentanyl smuggled into the United States for domestic‐based processing and distribution. Seizures indicate that China supplies lower volumes of high‐purity fentanyl, whereas fentanyl seizures from Mexico are higher volume but lower in purity. Fentanyl is also routed and smuggled through Canada. China‐based trafficking organizations have also been known to use the internet to distribute fentanyl, fentanyl‐related substances, and synthetic opioids globally.

Among the current fentanyl-related substances on the illicit market are: 4‐fluoroisobutyryl fentanyl, furanyl‐fentanyl, acryl‐fentanyl, acetyl‐fentanyl, carfentanil, and 3‐methylfentanyl, and other synthetic opioids such as U‐47700. I’ve written previously on this website about the fentanyl-related substance, carfentanil (“The Devil in Ohio”). Recently I received an unsolicited email from a “company” in Shanghi offering to send me a free sample of carfentanil. The DEA “Briefing Guide for First Responders” warned that some organizations are distributing pure fentanyl.

During the first quarter of 2017 the DEA indentified 230 instances of fentanyl, fentanyl-related substances and other synthetic opioids in seized drug evidence. The following graphic illustrates the results of their analysis. Fentanyl accounted for about 58% of the identifications. Of those 134 fentanyl identifications, 61% of the samples were combined with heroin; 28% were fentanyl alone. Carfentanil was found in six identifications. U-47700, alprazolam (Xanax) and cocaine’s were found in others.

Because of their hazardous nature, fentanyl and fentanyl-related substances are a serious threat to the health and safety of law enforcement officers and other first responders, such as EMTs. As little as 2-3 milligrams of fentanyl could bring on respiratory depression and possibly death. “When visually compared 2 to 3 milligrams of fentanyl is about the same as five to seven individual grains of table salt.” See the above photo of a penny.

The “Briefing Guide for First Responders” went on to describe treatment for any exposure to fentanyl, repeating some of the actions taken in the above situations:

seek immediate medical attention.
remove the person from the contaminated environment, preferably where there is fresh air.
If a suspected fentanyl-related substance has been inhaled, move the person to fresh air.
If there are overdose symptoms, immediately administer naloxone, which can quickly reverse an opioid overdose.
Multiple doses may be necessary, depending upon the drug’s purity and potency. Continue to administer a dose of naloxone every 2-3 minutes until the individual is breathing on their own for at least 15 minutes or until EMS arrives.
Someone who entered a badly contaminated area or was otherwise exposed to a suspected fentanyl-related laboratory or milling operation without wearing the proper protective clothing should undress and shower with soap and water as soon as possible.
If a suspected fentanyl-related substance was ingested through the mouth or eyes and the person is conscious, rinse their eyes and mouth with cool water.
When there has been any skin contact, wash the exposed area immediately with soap and water.
Do NOT use hand sanitizer, as it may contain alcohol, which is a skin penetrant. This may increase the absorption of fentanyl through the skin.

So if you are a first responder or law enforcement officer—or if for some reason you find yourself exposed to fentanyl—remember the above advice. And first responders and law enforcement officers, remember the safety call given by Michael Conrad, who played the role of Sergeant Phil Esterhaus in Hill Street Blues: “Let’s be careful out there.”

04/14/17

An Opioid Shell Game

Heroin sales and overdoses get a significant mount of attention, but we need to also remember that since 2002, the number of deaths related to controlled prescription drugs (CPD) have outpaced those for cocaine and heroin COMBINED. And the number of individuals who report current use of CPDs is more than those reporting use of cocaine, heroin, methamphetamine, MDMD and PCP (phencyclidine) combined. Each day, 129 individuals die from a drug overdose in the U.S. And yes, five of the seven most prescribed CPDs are opioids. The other two are amphetamine (i.e., Adderall) and methylphenidate (i.e., Ritalin and Concerta).

This information was taken from a yearly statistical summary published by the DEA called the National Drug Threat Assessment (NDTA). The 2016 NDTA Summary covers a wide range of data and classes of drugs. There’s even information on the various drug cartels operating in the U.S. This article will focus on CPDs.

The first figure (Figure 26) gives a comparison of the drug poisoning deaths for prescription drugs, cocaine and heroin from 2007 to 2014. Then Figure 29 shows the top five CPDs distributed nationwide in the BILLIONS of dosage units. Far and away from all the other CPDs, hydrocodone and oxycodone are the most prescribed drugs in the U.S. Both of these figures were taken from the 2016 NDTA Summary.

Not surprisingly, the number of admissions to publically funded treatment facilities for non-heroin opiate/synthetic abuse was 24% higher in 2013 than in 2008. The number of admissions has declined since 2011, but that has been offset by an increase in heroin use between 2011 and 2013.

Recently there has been an increase in the abuse of stimulant medications, specifically amphetamine. Between 2006 and 2011 the nonmedical use of Adderall increased by 67%. Emergency department visits related to Adderall almost tripled between 2005 and 2010. Misuse of ADHD medications as a class resulted in a 76% increase in poison control interventions from 2005 to 2010.

Young adults 18-25 years old represent the majority of the increase in Emergency Department visits, despite children comprising the largest subset of ADHD diagnoses. Many high school and college age students display limited knowledge of either the side effects or the addictive nature of Adderall. This coincides with the popular reputation of the drug on college campuses as a study-aid to improve concentration, and not something harmful or addictive. This contributes to the increased rate of non-medical use among adults.

Looking at concerns with prescription drug use and misuse from another perspective, a report by Quest Diagnostics suggested many Americans are misusing their prescription drugs. In their 2016 Prescription Drug Monitoring Report, Quest Diagnostics found that 54% of patient specimens showed signs of prescription drug misuse. For the purposes of their analysis, a consistent result was when a patient was taking a prescribed drug appropriately. An inconsistent result meant the patient was either not taking their prescribed drug, was taking drugs in addition to those that were prescribed, or was taking drugs that hadn’t been prescribed to them. These three combined causes of “inconsistent test results” indicated potential drug misuse in the Quest report.

About 45% of the inconsistent specimens showed evidence of patients taking drugs in addition to what was prescribed to them, “suggesting the potential for dangerous drug combinations in a sizeable number of patients.” This 2015 finding was considerably higher than other years. STAT News quoted Quest’s medical affairs director as saying, ““The discovery that a growing percentage of people are combining drugs without their physician’s knowledge is deeply troubling, given the dangers.” Of particular concern is the combination of opioids and sedatives, which can lead to respiratory depression, coma and death. The following graphic was taken from the Quest Diagnostics report.

Quest also examined the drug groups associated with the highest number of inconsistencies, by age groups. Unfortunately, given their composite sense of “inconsistent test results,” it is not clear what caused the top inconsistent drug classes. For example, we can speculate that in the under age 10 category, the top two drug inconsistent classes (amphetamine and methylphenidate) were likely due to no drug found, meaning those children were prescribed, but not taking their ADHD medications. The same can be said for the various places that “marijuana metabolite” appeared. However, the inconsistent classes for benzodiazepines, opiates and oxycodone are not distinguished by cause. So while benzodiazepines are noted as the top inconsistent drug class for every age group over 25, it is not clear if that meant they were taken in addition to what was prescribed or not.

One exception to this was with heroin and benzodiazepines. Quest found 1.56% of their tests were positive for heroin. Among adults who tested positive for heroin, 28.6% were also positive for benzodiazepines. Among those who combined these two drugs, 92.3% of the benzodiazepines were not prescribed.

The Fix, an addiction and recovery website, enlisted Peter Grinspoon, the author of Free Refills: A Doctor Confronts His Addiction, to look at the study. Dr. Grinspoon observed that Quest Diagnostics is in the business of doing urine drug testing, so they are interested in promoting drug testing. He went on to say:

Drug tests simply aren’t that accurate. They’re subject to human and lab error, and are rife with both false positives and false negatives. Savvy drug users can outsmart these tests. Any drug testing needs to be interpreted in the context of who is using the drug and why they are using it.

It is true that Quest Diagnostics makes money by increasing the amount of urine testing it does; that it is interested in promoting and highlighting drug-testing. But this was the fifth Prescription Drug Monitoring Report done by Quest. Additionally, Quest provides testing services to about half of all physicians and hospitals in the U.S. So the claim in the report, that it is “well positioned to identify trends in prescription drug monitoring and misuse” is legitimate.

Further, Dr. Grinspoon’s comments on the inaccuracy of urine testing seem overstated. Yes, there are false positives and negatives; and labs can make mistakes. But he gave the impression these errors happen so often that drug testing was a questionable, unreliable procedure. The FDA, among other sources, considers laboratory testing of urine samples to be the most reliable way to confirm drugs of abuse.

He also seems to assume the testing in the Quest report included drug users given urines as part of their treatment within drug treatment programs, which is not the case. Quest specifically stated that drug rehabilitation clinics and addiction specialists were excluded from the analysis “given the higher rates of testing and potentially higher rates of inconsistency.” There is no reason for a drug user to want to outsmart a urine test done in conjunction with their ongoing medical treatment that I can imagine.

The bottom line is that I think the Quest Prescription Drug Monitoring Report still provides helpful and valuable information on the dangerous practice of combining prescription medications. But prescription drug misuse is just one third of a kind if opioid shell game. Along with heroin and fentanyl, it keeps us trying to guess where the next opioid crisis will be.

03/14/17

Fentanyl: Fraud and Fatality

In December of 2016, several former pharmaceutical executives and managers of Insys Therapeutics were arrested on charges they participated in a nationwide conspiracy to bribe medical practitioners to prescribe one of the company’s fentanyl products, Subsys. The medication is approved for treating cancer patients suffering intense episodes of breakthrough pain. “In exchange for bribes and kickbacks, the practitioners wrote large numbers of prescriptions for the patients, most of whom were not diagnosed with cancer.” The indictment also alleges that these same former Insys executives conspired to “mislead and defraud” health insurance companies who were reluctant to approve payment for Subsys when it was prescribed for non-cancer patients.

The Special Agent in Charge of the Boston Field Division of the FBI said top executive of Insys Therapeutics, Inc. allegedly paid kickbacks and committed fraud in selling the highly addictive opioid. “The indictment also alleges that the conspiracy to bribe practioners and to defraud insurers generated substantial profits for the defendants, their company, and for the co-conspirator practioners.” The investigative team included multiple federal agencies, including: FBI, FDA Office of Criminal Investigations; Health and Human Services (HHS), U.S. Postal Service, the Department of Labor, and the Department of Veterans Affairs.

Reporting for STAT News on the indictments, David Armstrong said a Florida doctor was invited to Insys headquarters near Phoenix, where sales officials took him out for a night on the town. In a text message to a sales rep, one of the company’s regional sales managers said: “He had to have had one of the best nights of his life.” The next week the doctor wrote 17 prescriptions for Subsys, when he usually wrote three. “He also received $260,050 in payments over three years for participating in the Insys speaking program — something federal officials allege was nothing more than a mechanism for bribing doctors.”

Subsys was launched in March 2012 into a crowded field of competitors, which included other brand-name medications and several generics. The drug was approved only for cancer patients with intense flares of pain — a narrow market — and only about 2,000 doctors in the country prescribed fentanyl products. The drug is also expensive, costing thousands of dollars a month.

Prosecutors allege the company overcame these challenges with a speaker program, where “educating” doctors on the use of the drug was actually a way to bride them. A former chief executive of Insys wrote to sales managers that they needed to make it clear to sales reps how having one of their top targets as a speaker “can pay big dividends for them.” Doctors didn’t need to be good speakers; they just needed to “write a lot of” Subsys prescriptions. The indictment did not identify any of the parishioners by name who allegedly received and kickbacks.

To sweeten the pot, the Insys employees allegedly scheduled speaking events at establishments owned by doctors, or their families and friends. The events allegedly had little do with education: They were often held at high-priced restaurants and attendees were frequently just friends of the doctor hired as the speaker, the indictment alleges. Fake names were used on sign-in sheets, and some events had no attendees at all, according to prosecutors.

The cancer market for Subsys was considered to be “small potatoes” by one of the indicted former Insys executives. While the alleged bribes led doctors to prescribe more prescriptions for Subsys, insurance companies were reluctant to pay when the drug was prescribed for non-cancer patients. So a system was created to deceive insurers into paying for off-label uses of the drug, which is incidentally, quite expensive. A call center was created at Insys to handle insurance reimbursement approvals for doctors prescribing Subsys.

Employees in this unit are alleged to have contacted insurers, giving the appearance they were calling from the doctor’s office. Along with the supposedly deceptive medical information given to the insurers, they reportedly said patients had difficulty swallowing, which meant Subsys, as a nasal spray, had a distinct advantage over similar products that were in pill form. “Employees of the unit were rewarded with lucrative financial bonuses if the entire unit met a weekly target of reimbursement approvals.”

The Subsys fiasco is not the only fentanyl-related contribution to the opioid problem in the U.S. Two years ago the DEA issued a nationwide alert on fentanyl as a threat to health and public safety. State and local labs reported 3,344 fentanyl submissions in 2014, an increase from 942 in 2013. “In addition, the DEA has identified 15 other fentanyl-related compounds.” Warnings were issued to law enforcement about guarding against fentanyl absorption through the skin or accidental inhalation of airborne powder, as it is 30 to 50 times more potent than heroin. Ingesting as small as .20 mg to 2mg of fentanyl can be lethal. The following image, taken from the 2016 National Drug Threat Assessment (NDTA), illustrates the size of 2mg of fentanyl compared to a penny.

Globally, fentanyl abuse has increased in Russia, Ukraine, Sweden and Denmark. Mexican authorities have seized fentanyl labs run by the drug cartels. Intelligence indicated the precursor chemicals for fentanyl have come from companies in Mexico, Germany, Japan and China.

According to the 2016 NDTA, licit fentanyl is only diverted on a small scale. Illicit fentanyl, typically manufactured in China or possibly Mexico, is smuggled into the U.S. across the border with Mexico. Traffickers usually obtain fentanyl and mix it with heroin on their own. This happens at a variety of locations, including homes and even hotel rooms.

In August 2015, the DEA Manchester, New Hampshire DO, along with the Salem, New Hampshire Police Department, conducted an enforcement operation at a fentanyl mill in a hotel in New Hampshire. The traffickers used a hotel room kitchenette for mixing heroin and fentanyl together. Upon entry by law enforcement officers, the traffickers attempted to dispose of the drugs down the sink, spilling the highly lethal drugs all over the room.

Traffickers in the U.S. are also using fentanyl powder and a pill press to create counterfeit pills of oxycodone and other drugs. Officials in New Jersey and Tennessee seized pills that appeared to be oxycodone. But laboratory analysis indicated they were fentanyl or acetyl fentanyl. In May of 2015, Orange County Police Officers in California seized what appeared to be black tar heroin. “Upon laboratory analysis, the substance was revealed to be fentanyl and showed no traces of heroin or any other drug.”

In another article for STAT News, David Armstrong described the China connection with fentanyl. Raw fentanyl and the machinery necessary for assembly-line production of the drug are coming from Chinese suppliers. “The fentanyl pills are often disguised as other painkillers because those drugs fetch a higher price on the street, even though they are less potent, according to police.” A Southern California fentanyl lab had a dozen different packages shipped to mail centers and residences. A box labeled as a “Hole Puncher” was in fact a quarter-ton pill press. “The Southern California lab was just one of four dismantled by law enforcement in the United States and Canada in March [of 2016].”

In British Columbia, police raided a lab at a custom car business that was allegedly shipping 100,000 fentanyl pills a month to Calgary, Alberta. Federal agents shut down a Seattle lab set up in the bedroom of a home in a residential neighborhood. Police near Syracuse New York raided a similar residential lab, where they were warned by the people there not to touch the fentanyl without gloves because of its potency. “The emergence of decentralized drug labs using materials obtained from China — and often ordered over the Internet — makes it more difficult to combat the illicit use of the drug.” See “Buyer Beware Drugs” for more on this topic.

In January of 2017 the acting administrator of the DEA met with Chinese officials to address the synthetic drug crisis in the U.S. He said: “These meetings underscore our improving relationship and cooperative efforts as we work to stem the flow of dangerous synthetic opioids and related chemicals. I appreciate the good work they are doing in China to help us address our opioid epidemic.” The DEA maintains an office in Beijing and hopes to expand its presence in China. Hopefully, if the China connection with fentanyl is turned off, the future outlook from the 2016 NDTA will not be as bleak.

Fentanyl will remain an extremely dangerous public safety threat while the current production of non-pharmaceutical fentanyl continues. Fentanyl poses not only a threat to users, but also to law enforcement personnel and postal service employees as minute amounts of the drug are lethal and can be inadvertently inhaled or absorbed through the skin. Although many drug users avoid fentanyl, still others actively seek it out for its strong and intense high. In 2015 traffickers expanded the historical fentanyl markets as evidenced by a massive surge in the production of counterfeit tablets containing the drug, and manipulating it to appear as black tar heroin. The fentanyl market will continue to expand in the future as new fentanyl products attract additional users.

In February 2017, Time reported that China announced that carfentanyl (carfentanil) and three related synthetic opioids would be added to its list of controlled substances effective March 1, 2017. The DEA called China’s action a potential “game changer.” Russell Baer, a DEA special agent said: “It’s a substantial step in the fight against opioids here in the United States. . . We’re persuaded it will have a definite impact.” In October, the Associated Press identified 12 Chinese companies the offered carfentanyl for export. That same month China began evaluating whether to add it and three other fentanyls to its list of controlled substances. “Usually, the process can take nine months. This time, it took just four.”

08/30/16

The Devil in Ohio

Around the beginning of July 2016, there were a series of overdoses and deaths in Akron Ohio. The ABC News affiliate in Cleveland reported there had been 173 overdoses in Akron by July 22; 16 of which were fatal. Some of the first people to overdose had not shot up—they were snorting what they thought was heroin. “As soon as I sniffed it, I knew something was up because it got me feeling super intense,” he said. When I woke up, I was on a stretcher. I was freaking out because I didn’t know what happened. I was tied down.”

The overdoses are being attributed to a street mixture of heroin and carfentanil, an opioid considered to be 4,000 times as potent as heroin. There were some misleading news reports at the time suggesting that heroin users themselves were mixing heroin and carfentanil (carfentanyl). Reporting for Cincinnati.com, Terry DeMio said that the Hamilton County Heroin Coalition warned carfentanil had been found in the local heroin of Cincinnati, Akron and Columbus. Dr. Marc Fishman said: “Carfentanil is one of the most potent opioids known, as an anesthetic agent by veterinarians for large animals, not used for humans.” Veterinarians who are licensed to use it cover up hands, arms and faces when they use it … and they keep naloxone handy.

Then the overdoses started happening again in the Cincinnati area. The Washington Post reported there were 78 overdoses and at least three deaths during a 48-hour period. By the end of the week, the overdose total has reached 174. Some of the overdose victims required multiple doses of naloxone to reverse the effects. Although they are still awaiting the lab results, the police believe this is another batch of heroin mixed with carfentanil. So far law enforcement has not been able to identify the source of the mixture. Newtown Police Chief Tom Synan said:

These people are intentionally putting in drugs they know can kill someone. . . . The benefit for them is if the user survives, it is such a powerful high for them, they tend to come back. … If one or two people die, they could care less. They know the supply is so big right now that if you lose some customers, in their eyes, there’s always more in line.

WKRC in Cincinnati reported thirty overdoses in the course of just one day—Tuesday August 23^rd. One man overdosed while driving through an intersection. Another man overdosed at a gas station; with his child in the car. Three other people overdosed in the same house. “It was too early to tell if the spike in overdoses Tuesday night, August 23, had anything to do with carfentanil. But, it was found in several places throughout the city of Cincinnati in early August 2016.”

carfentanil molecule

So what exactly is carfentanil? According to PubChem, carfentanil is an analog drug of fentanyl that was first synthesized in 1974 by a team of chemists working for Janssen Pharmaceuticals. It’s marketed under the trade name of Wildnil as a general anesthetic for large animals, like elephants and rhinoceros. Its extreme potency makes it an inappropriate agent for human use, unless you happen to be a Walter White-type of entrepreneur with heroin. It is classified as a Schedule II controlled substance.

A 2012 study found evidence that the Russian military used an aerosol form of carfentanil and remifentil in the 2002 Moscow theatre incident to subdue Chechen hostage takers. The Washington Post reported the death toll was 170 people; only 40 of the dead were attackers. Because of the lack of information provided to emergency workers, they didn’t bring enough naloxone or naltrexone to prevent the complications experienced by the gassed victims “from both respiratory failure and aerosol inhalation during the incident.” A 10 mg dose of carfentanil could sedate or kill a 15,000-pound elephant or take down a musk ox, bull moose or full grown buffalo. The same amount could kill 500 human beings.

Heroin cut with carfentanil offers a harder-hitting, longer-lasting high and allows dealers a shortcut to increase their supplies. But users often don’t know what they’re getting. In recent months, authorities have linked carfentanil to a spike in overdoses in several states, and have warned that it could spread to others.

On August 9, 2016 Canadian border officials reported they had intercepted a one-kilogram package of carfentanil heading to Calgary from China. The package was shipped to a 24 year-old man at his home address and labeled as “printer accessories.” A kilogram of carfentanil is equivalent to four metric tons of pure heroin. The package could have produced 50 million doses. Roslyn MacVicar of the Canadian Border Services Agency said: “It is hard to imagine what the impact could have been if even the smallest amounts of this drug were to have made its way to the street.”

In a DEA report Donald Cooper presciently thought that analogs of fentanyl would become a future drug of abuse He indicated that the already published synthesis schemes for fentanyl compounds allow for a variety of precursor chemicals to be used in synthesizing the drugs. The DEA became aware of this potentiality from the confiscated notes from an anonymous clandestine laboratory. Two formulas for synthesizing carfentanil have been extracted from separate volumes of the Journal of Organic Chemistry and made available for any enterprising chemist in “Synthesis of Carfentanil” on Erowid. The DEA indicated that over 12 different analogues of fentanyl have been clandestinely produced and identified in the U.S. drug traffic.

Interviewed by CBS News, Kevin McCutheon of Akron Ohio is a long-time addict. He believes when he overdosed he ingested carfentanil. He said he had used fentanyl and has been “doin’ dope,” but this wasn’t the same. The interviewer commented that he had tears in his eyes. He said it was because he was here and knew he shouldn’t be. “It’s the devil.”

06/7/16

Buyer Beware Drugs

At the end of March in 2016, detectives with the Onondaga County Sheriff’s Office executed a search warrant at a split level home in quiet suburban neighborhood about 8 miles north of Syracuse, New York. They discovered a fentanyl processing operation where six people were mixing and packaging fentanyl for street-level sales. Detectives found an estimated 5,866 doses of fentanyl, 2 ounces of A-PVP (flakka), a loaded 12-gauge shotgun, a replica sub machine gun, drug paraphernalia and $3,571. The total street value of the drugs was $60,000.

The individuals arrested were considerate enough to warn the arresting officers not to touch the fentanyl without gloves. The drug is potent enough to be absorbed through the skin if you touch it without gloves. I guess they were concerned about a possible felony murder charge on top of the drug charges. Although the source of the drug was not known at the time of the drug bust, it typically comes from international sources in Mexico and increasingly from China.

A similar arrest took place near Los Angeles, where four men were operating a pill lab in Baldwin Park. Police found several pill presses and large quantities of variously colored powders, among them acetyl-fentanyl and methamphetamine. DEA Agent David Dowling said: “Fentanyl and its analogues pose a serious public health risk. Even small doses absorbed through the skin or accidentally inhaled can be fatal.” They were getting their drug supply from China. The Southern California lab was just one of four by law enforcement in the U.S. and Canada in March of 2016.

David Armstrong reported for STAT News on both of the above incidents as well as a lab in a custom car business in British Columbia that was shipping 100,000 fentanyl pills monthly to nearby Calgary, Alberta. Police reported that the equipment used to press the pills had come from China. Recently a quarter-ton pill press was intercepted before it was transported to a suburban Los Angeles drug lab. It had been labeled as a “Hole Puncher.”

In an affidavit, DEA agent Lindsey Bellomy said that based on wire transfers and other evidence, she “strongly believes” the Southern California group acquired its fentanyl from China. The affidavit lists a dozen deliveries from China to members of the group in January and February.

The China connection is allowing local drug dealers in North America to mass produce fentanyl in pill form, in some cases producing tablets that look identical to an oft-abused version of the prescription painkiller OxyContin. It also has been added to Xanax pills.

The emergence of decentralized drug labs, using materials obtained from China, makes it difficult to police fentanyl sold as a street drug. A report from the Department of State’s Bureau for International Narcotics and Law Enforcement Affairs indicated China is still a major producer and exporter of fentanyl and other drugs for illicit international markets. Lax regulation, low production costs, and government corruption, mixed in with the country’s large chemical and pharmaceutical industries, makes China a perfect supply source for the materials needed for the illicit drug labs.

Fentanyl pills masquerading as hydrocodone were recently blamed for a wave of overdoses and 11 deaths in the Sacramento California area. The Sacramento Bee reported on April 13, 2016 there had been 51 fentanyl-linked overdoses since late Mach of 2016. By April 27th, the death toll was up to 14. The pills were exact replicas of a medium-strength opioid painkiller, Norco. The CDC discussed this outbreak in detail in one of their Morbidity and Mortality Weekly Reports (MMWR).

Analysis of the fake Norco pulls showed they contained fentanyl, promethazine, acetaminophen and trace amounts of cocaine. Normally used to treat nausea vomiting and motion sickness, promethazine is used here to boost the high of the opioid. Reporting for the Digital Journal, Karn Graham said the pills were exact replicas for the real ones. It was only pure luck that health officials were able to get one of the fake pills from an overdose patient in order to analyze its ingredients. Keri Blakinger, writing for The Fix, said in Canada, British Columbia has declared a public health emergency from the increase of fentanyl overdose deaths in the province.

Lookalike oxycodone pills containing fentanyl have also appeared in Tennessee and Ohio. In testimony before the Committee on Homeland Security and Government Affairs in the U.S. Senate, Carole Rendon, the Acting U.S. Attorney for Northeastern Ohio said the overdose deaths from heroin and fentanyl had risen until they began to see an average of two overdose deaths per day in March of 2016. She said: “Opioid addiction knows no boundaries. It is an equal opportunity killer of old and young, men and women, urban, suburban, and rural, rich and poor, black, white, and Hispanic. We are all at risk.”

In February, Tennessee officials warned about the availability of counterfeit drugs, specifically pills being sold as Percocet that actually contained fentanyl. David Reagan, the Chief Medical Officer of the Tennessee Department of Health said: “When people sell fake pills appearing to be oxycodone but actually containing the more powerful pain medicine fentanyl, lives are at risk.” During a traffic stop in May of 2015 a police officer discovered several 30 mg pills of what appeared to be oxycodone, with its signature A/215 stamp characteristic. Lab analysis showed they were fentanyl. In January of 2016, 300 pills stamped with the characteristic markings for Percocet were found to be fentanyl.

Even worse, counterfeit Xanax pills that contain fentanyl are appearing. In October of 2015 at least three people died from ingesting the combination drug in San Franciso. Saint Petersburg Florida reported that nine people died in Pinellas County from what was being sold as Xanax on the street. The pills were actually a combination of fentanyl and Xanax. The Daily Mail said the combination is sold as “Super Pill” on the street for as little as $5 a pill.

Last, and probably worst, there is another synthetic opioid coming onto the illicit drug market, W-18. It is 100 times more powerful than fentanyl; 10,000 times more powerful than morphine. And again, the likely source for the drug is China. Alan Hudson, an associate professor with the department of pharmacology at the University of Alberta, said W-18 is one of the most dangerous drugs in the whole spectrum of analogs. A tiny speck can cause respiratory failure and kill you.

Global News reported that the drug comes from a “W-series” of opioid compounds first discovered at the University of Alberta in Canada in 1982. Of the 32 compounds, W-1 to W-32, W-18 was the most toxic. As little as four kilograms of the drug is enough to produce millions of tablets. An Edmonton-area drug bust in December 2015 netted four kilograms of W-18.

Because of its potency, W-18 exponentially raises the stakes for potential overdoses. “It’s just too potent to even consider using.” It was never listed as a controlled substance; never tested on humans. So it is technically legal and for sale online—typically from China. “Obviously somebody in China has picked up on the fact that W-18 is quite easy to make in large quantities and they’re trying to sell it to the North American market.”

If you are having trouble understanding why the practices above persist, think about basic branding, marketing and salesmanship. Established brands in the drug market include “heroin” and various pills like: “OxyContin”, “Percocet”, “Xanax”, and even “MDMA.” A significant segment of the drug market has a negative view of heroin, so they prefer to use pharmaceutical versions of opiates/opioids. So they seek out “OxyContin”, “Percocet”, and others. There is also a higher production cost for pills due to their stricter regulation. Pharmaceuticals are legally produced; heroin is not.

Over the past 100 years or so, the government has developed a regulatory process to give consumers some assurance that when they buy pharmaceuticals, they are getting what they paid for. Even with all the problems in the existing regulatory procedures, the modern pharmaceutical consumer is better protected today than they were during the time of patent medicines. THERE IS NO REGULATORY PROCESS FOR ILLICITLY PRODUCED DRUGS.

So if drug dealers and manufacturers want to increase their profits, they produce knockoffs of the more popular drug brands (like Percocet or heroin) by substituting cheaper products for the known brands. Since there is no regulatory process, they can and do sell knockoffs to their customers as the real thing with relative impunity. Illicit drugs today are truly a “buyer beware” market. The consumer/user is risking their health and their life as they seek out the newest, best high.

08/24/15

Fake Heroin and Homemade Opioids

Okay, now there is a “fake” heroin on the market. What’s going on in the drug trade? There seems to be wanna-be “Walter White” biochemists trying to tweak opioid molecules for a bigger-and-better high. On July 17, 2015, the DEA issued a final order to temporarily schedule acetyl fentanyl into Schedule 1. This was said to be “necessary to avoid an imminent hazard to the public safety.” Before the action by the DEA, the drug was illicit, but still technically legal as long as it had a label that read “Not for human consumption.”

Paul Gaia, writing for The Fix, said acetyl fentanyl was first identified in 2013. A small amount can produce a euphoria like heroin or oxycodone. Because of the similar euphoria, acetyl fentanyl can be sold as heroin or mixed with heroin or oxycodone to produce a stronger high. Regularly buyers are unaware of the mixture or the added danger it brings. Acetyl fentanyl is said to be 5 to 15 times more potent than heroin. It has resulted in a series of ER visits and at least 39 overdose deaths.

Reporting for Vice News, Tessa Stuart said a Montreal supplier of acetyl fentanyl was busted with three kilograms. “Given that a typical dose of acetyl fentanyl is in the microgram range, a three-kilogram quantity could potentially produce millions of dosage units.” Because of its strength, it requires a larger dose of naloxone, perhaps double, to counteract overdoses. Its greater potency also means the difference between a recreational dose and a lethal dose of acetyl fentanyl is much smaller, leading to the increase in overdoses among individuals who are unaware they are not shooting pure heroin.

An editorial published in 2014, “The Potential Threat of Acetyl Fentanyl,” said that because it is an analogue of fentanyl, before the DEA action, drug distribution networks faced less severe legal penalties from cutting or replacing drugs like heroin or oxycodone with acetyl fentanyl. This legal grey area meant that as long as it was unregulated, there was a clear motivation for distribution networks to replace or mix heroin with it. Pressed into a pill form, acetyl fentanyl can be peddled as oxycodone. The author recommended the elimination of the loophole for products containing an analogue of a controlled substance when it is labeled “not for human consumption.”

Analogues regulated in this way present a challenge for law enforcement and prosecutors because products that are clearly intended for recreational use sidestep regulations of their marketed purpose is something else.

Fentanyl-laced heroin is not new. The CDC warned in a “Morbidity and Mortality Weekly Report” that 10 overdose deaths in Rhode Island in March-May of 2013 were from acetyl fentanyl. On June 27, 2013, the State of Pennsylvania Department of Drug and Alcohol Programs published a bulletin, “News for Immediate Release,” which noted that there were at least 50 confirmed fatalities and five non-fatal overdoses that year from fentanyl or acetyl fentanyl. The “Theraflu” overdose epidemic in the Pittsburgh area in January of 2014 seems to have been acetyl fentanyl-laced heroin.

Fentanyl-related deaths are also going global. Both The Fix and Vice News reported a 25% rise in overdose deaths attributed to fentanyl in British Columbia (BC) over the past three years. A Vice reference to a pill form known as “fake oxy” suggests that what is being sold is acetyl fentanyl. A survey by the BC Center for Disease Control found that 29% of drug users in the province had fentanyl in their system.

And the problem isn’t limited to BC, with a growing number of similar deaths happening across the country. In 2014, fentanyl was a factor in the deaths of 120 people in Alberta, and there have been 50 such deaths already this year. In Ontario, the drug is killing twice as many people as heroin. Across North American, fentanyl is rapidly becoming a drug of choice for many users.

Reporting for The Fix, Paul Gaia said that fentanyl has been a problem in countries such as Russia, the Ukraine and Sweden. Manufacturing labs have been seized in Mexico, Germany, Japan and China. A gas used in the 2002 assault on a Moscow theatre was based on fentanyl. A report from the European Monitoring Centre for Drugs and Drug Addiction, “Fentanyl in Europe” indicated there were an estimated 650 deaths in Estonia due to fentanyl between 2005 and 2011. Almost all the cases were IV drug users of illicitly produced fentanyl.

Not only is there fake heroin, there is the potential to produce a variety of different opiates from yeast. Lexi Pandell, reported for Wired how Stanford researchers have developed a method for replicating the poppy’s opiate-producing chemical pathways by genetically modifying yeast. John Duber, a bioengineer at UC Berkley said that you would need a background in synthetic biology and genetics to produce the right kind of yeast, so it’s not an imminent threat. “But if a strain made for licit purposes got out, then all that would be required is knowledge of brewing beer to ferment it into morphine.” Here is a link to the abstract of their article published in Science.

Dueber said that at this point, “the illicit danger is concrete.” But he also thinks the potential benefits are immense. He suggested that scientists and policymakers start now to consider the possibilities before the science gets ahead of the regulations—like what happened with acetyl fentanyl. Kenneth Oye, an MIT professor, suggested that developers could make yeast less appealing for illegal use by generating yeast strains that produce less-addictive drugs. Or they could make finicky strains that are hard to maintain outside of a lab. Oye also said regulators could require the yeast DNA be “watermarked,” so it could be traced back to specific labs.

In a May 2015 commentary published in Nature, Oye also said:

The synthetic-biology community, in tandem with regulators, needs to be proactive in evaluating the costs and benefits of such dual-use technologies. Here we lay out the priorities for discussions that are crucial to public health and safety, and to the progress of synthetic biology more broadly. These include restricting engineered yeast strains to licensed facilities and authorized researchers and technicians; reducing the attractiveness of engineered yeast strains in the illicit marketplace; and implementing a regulatory approach that is flexible and responsive to changes in understanding and capabilities.

Oye downplayed the high received from hydrocordone in a New York Times article, rightly earning the wrath of the addiction blogger, Guinevere, at Guinevere Gets Sober. She said she’d like to send him some of the mail she’s received over the years by individuals who have spent tens of thousands of dollars buying Vicodin (hydrocodone) through the internet and on the street. “I’d like to see Stanford, MIT, and other schools spend the money on researching effective treatment standards and educating medical students about how to recognize and treat this illness.”

Fake heroin is spreading globally. Hydrocordone and other opiates can be manufactured from yeast. And the FDA is getting ready to approve an antidepressant containing buprenorphine (See “The Coming Depression Apocalypse”). And then there are the heroin and prescription pain killer problems. What does the future hold for opioid addiction?

Faith Seeking Understanding

Charles Sigler, D.Phil.

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