04/14/17

An Opioid Shell Game

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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

© Alexi Novikov

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

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© Olena Yakobchuk | 123rf.com

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 23rd. 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

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

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© Yurly Kirsanov | 123rf.com

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

© zerbor | 123rf.com

© zerbor | 123rf.com

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?