Deadly Adulterants: New Dangers of Illicit Drugs

Mark S. Gold, MD

The “cutting” or “adulteration” of street drugs is common practice in the manufacturing, distribution and selling of illicit drugs, all in the name of increased profit. The term “adulterant” generally refers to addition of substances with some psychoactive effects such as caffeine, ephedra, or even paracetamol, which are cheaper than the main substance, have similar or complimentary effects when added, and thus help conceal the fact that the desired substance has been cut or diluted. Substances without psychoactive properties such as lactose, other sugars, or talc, are added to a drug primarily to increase the bulk or weight of the illicit substance, or for aesthetic purposes in order to fool the user. Some adulterants are simply the result of the particular manufacturing process used to make the drug. For example, illicitly manufactured methamphetamine is frequently contaminated by non-stimulant impurities such as lead or mercury (extremely toxic heavy metals), or from carcinogenic solvents used in the synthesis. These adulterants are highly toxic, causing numerous medical consequences including death.

The proliferation of dangerous adulterated drugs is exploding. Deaths from unintentional overdose are now endemic, grabbing headlines across the nation, and not just in the hood or impoverished communities. Overdose from adulterated heroin, cocaine, prescription opioids or ecstasy is occurring throughout the socioeconomic strata, and is not biased by race, income or area code. In this paper, I will describe the most commonly adulterated drugs and explain the process and risks involved.

Fentanyl
In March 2015, DEA issued a nationwide alert on fentanyl as a threat to health and public safety. Apparently, nobody listened because during the last 3 years the availability of illicitly manufactured fentanyl has caused an unprecedented rise in overdose and deaths. Last year (2016) in Massachusetts, for example, three quarters of the state’s fatalities from unintentional overdose had fentanyl in their system—this is up from 57 percent in 2015. Regrettably, this trend is spreading across our nation. At the same time in San Francisco, two patients at the Contra Costa Regional Medical Center emergency department (ED) were seen for severe nausea, vomiting, central nervous system depression, and respiratory depression, just 30 minutes after ingesting what they believed was Norco, a prescription opioid pain medication that contains hydrocodone and acetaminophen that they bought from a friend. Analysis of the drug and specimens from the patient’s revealed that the pills were in fact counterfeit, containing dangerously high levels of fentanyl and a highly sedating phenothiazine called Promethazine (trade name Phenergan).

Why now?
As the opioid epidemic evolves, and legitimate prescriptions for opioids are increasingly difficult to attain, a cheap, easy to manufacture, non-pharmaceutical fentanyl is being sold as:
1. An ingestible (snorted or smoked) powder sometimes added to, or substituted for cocaine.
2. A small solidified dot on blotter paper for sublingual administration.
3. Tablets that are pressed and colored to look like prescription opioids such as Hydrocodone (Vicodin, Lortab) or Oxycodone (Percocet), which is what actually killed the music legend Prince in 2016.
4. Mixed with cheap heroin to dilute the dose while delivering a dangerously powerful, fast acting high. Over the past few years the headlines have shifted away from doctors simply overprescribing opioids in “pill mills” many of which were in southern Florida, to dealers and addicts forgoing the hassle of attaining prescription medication or manufacturing and imprinting counterfeit pills, to adding homemade fentanyl to cheap heroin. The reason is always market forces and profit margin.

What Exactly is Fentanyl?
Fentanyl is a synthetic opioid analgesic that is chemically similar to morphine but 50 to100 times more potent. Because of its high lipophilicity, fentanyl rapidly crosses the blood brain barrier which partially explains its extreme potency, rapid onset and potential for abuse.

Fentanyl is a schedule II prescription drug that is commonly used during surgery with anesthesia, in carefully titrated amounts, administered by highly trained anesthesiologists. Fentanyl is also administered post surgically to control severe pain. More recently, fentanyl is used to treat patients with severe chronic pain. It can be delivered several ways including injection, transdermal patch, or as a dissolvable, sublingual lozenge. In its prescription form, it is available under the trade names Actiq®, Duragesic®, and Sublimaze®. When properly and appropriately prescribed and managed by an experienced pain physician, fentanyl can be a Godsend for patients with severe chronic pain.

Lethality
Fentanyl is so lethal because it’s so strong and fast acting. How strong? One gram of pure fentanyl can be cut into approximately 7,000 doses for street sale. How fast? When I say fast acting, I mean it can kill you in the time it takes for the drug to pass from the injection site to the brain, I’m talking a few seconds, and unlike other opioids, there is not enough time to administer naloxone to reverse the effects. Even more frightening, fentanyl can kill via passive contact. Thus, exposure to an amount no larger than a few grains of sand is lethal. In fact, law enforcement professionals are being warned not to field test anything that might contain fentanyl due to the risk of passive exposure and death.

Fentanyl and Heroin
According to federal DEA field reports, the Mexican cartels have increased production of a fentanyl analogue known as acetyl fentanyl, which can be easily made in clandestine labs, and cost much less to produce. According to the DEA, acetyl fentanyl may be slightly less potent than fentanyl, but is still quite deadly and difficult to identify, as it is not yet included in most toxicology assays for identifying drugs in urine or blood. Hopefully, this will change soon.

Some experts speculate that the legalization of novel, high potency cannabis products (available as candy, sweetened and “natural” beverages, and popular vaporized products) has driven down the profit margin for Mexican cannabis. As a result, the Mexican cartel is flooding the market with cheap heroin, laced with acetyl-fentanyl to replace revenue lost to legally available cannabis products.

Current street names (which change frequently) for fentanyl and acetyl-fentanyl-laced heroin include: Apache, Goodfella, Murder 8, TNT, and Tango and Cash, to name a few. Acetyl fentanyl is not approved for medical use in the United States and currently a schedule I controlled substance under the Federal Controlled Substances Act. Meaning, it has no legitimate medical use.

Recent DEA surveillance reveals that acetyl fentanyl laced heroin cost a little more on the street than regular heroin, yet it sells because users believe it’s extreme potency produces a higher-high, and thus worth the few extra dollars. Remember, opioid addicts are always looking for the better high and will often risk their lives to get it.

Cathinones
Cathinone is a stimulant found in the khat plant in East Africa and in southern Arab regions. When its leaves are chewed it produces a mild stimulant effect, not unlike the coca leaves in the Andes region of South America.

Synthetic Cathinones, recently known as “bath salts”, are often sold as or added to street stimulants such as methamphetamine, cocaine and MDMA (Ecstasy and Molly). In fact, buyers seek “Molly” because they prefer the effect from cathinone laced Ecstasy, rather than pure MDMA. It may be a moot point because recent surveillance data shows that most street Ecstasy contains high doses of synthetic cathinones. This results in more profit for the dealer and the manufacturer.

Cathinones are popular because like all drugs of abuse, they stimulate the release of dopamine in the striatum. In addition, like Ecstasy (XTC) which was initially dubbed the “love drug”, synthetic cathinones inhibit the reuptake of serotonin, and to a lesser degree, norepinephrine, producing a unique and somewhat “warm” euphoria. Additionally, cathinones are a hydrophobic molecule that easily crosses the blood-brain barrier.

Cathinones also affect the peripheral nervous system (PNS) by blocking adrenergic receptors, thus inhibiting smooth muscle contraction. This can result in blurred vision, increased blood pressure and heart rate to dangerously high levels. Like XTC, some users blunt or prune the serotoninergic nerve endings in their brain causing serious and sometimes intractable depression and significant and possibly permanent cognitive deficits.

Lesser known additives and adulterants include talc, an easily attainable and finely ground powdery substance often added to cocaine or heroin to add bulk and to dilute the purity to increase profits. But, talc can cause serious medical problems due to the combined toxicity with the psychoactive substance, and the route of administration. For instance, injecting or snorting talc can cause granulomas in the lungs or liver. Other common adulterants in street drugs include quinine, which is frequently added to heroin. Quinine can cause serious, unpredictable and life-threatening blood disorders and cardiovascular reactions including low platelet count and hemolytic-uremic syndrome which leads to progressive renal failure and other serious sequelae.

The local anesthetic lidocaine, and an anti-parasitic drug called levamisole are often added to cocaine and other street stimulants. It is understandable why lidocaine is used to cut cocaine-they are both fast acting local anesthetics, but why levamisole? Recent research reveals that levamisole may be partially metabolized into an amphetamine-like compound which could increase dopamine concentration in the reward pathway and thus activate endogenous opioids. In other words, it can mimic the effects of cocaine at a fraction of the cost. The DEA has estimated that 69% of the seized street cocaine contains levamisole which is associated with several types of severe blood disorders including leukopenia, agranulocytosis, multifocal inflammatory leukoencephalopathy and Neutropenia.

Other highly toxic and dangerous adulterants such as strychnine and even ground glass have been found in samples of street drugs, which obviously result in serious medical complications and death. As America’s drug epidemic evolves, technologically savvy, but ethically challenged chemists have figured out that selling adulterated street drugs is a highly lucrative business that shows no sign of recession. It follows that if these amateur pharmacists can make acetyl fentanyl, they will soon learn to make even more potent analogues including carfentanil, of which the toxicity has been compared to that of nerve gas. Why? Carfentanil has a quantitative potency that is approximately 10,000 times stronger than morphine and at least 100 times more potent than fentanyl, with psychoactive response in humans starting at approximately 1 microgram. For this reason, carfentanil is intended for use in large-animals only as its extreme potency makes it too dangerous for use in humans.

To date, most illicit carfentanil is imported from China, but it won’t be long before stronger fentanyl analogues such as carfentanil will be homemade by amateur chemist and sold cheaply in the US.

What can we do?
Education of the public to create awareness and professional education for medical and treatment professionals is a good start. Yet, as in all prevention efforts, parents of young children provide the greatest hope, because no addict’s first drug is heroin or fentanyl. Delaying initiation to all intoxicants is the only proven prevention strategy. In addition, increasing basic scientific research germane to the neurobiology, etiology and pathophysiology of addictive disease is desperately needed if we are to stay ahead of the profit motivated purveyors of these poisons.

Mark S. Gold, MD, Chairman of the RiverMend Health Scientific
Advisory Boards, is an award-winning expert on the effects of opiates,
cocaine, food and addiction on the brain. His work over the past 40
years has led to new treatments for addiction and obesity which are
still in widespread use today. He has authored over 1000 medical
articles, chapters, abstracts, journals, and twelve professional books
on a wide variety of psychiatric research subjects, including psychiatric
comorbidity, detox and addiction treatment practice guidelines