Dickie Sanders was not naturally prone to depression. The 21-year-old BMX rider was known for being sweet spirited and warm -- a hugger not a hand-shaker. The kind of guy who called on holidays. Who helped his father on the family farm. Who spent countless hours perfecting complicated tricks on his bike.
Yet on Nov. 12, 2010, Sanders was found dead on the floor of his childhood bedroom. He had shot himself in the head
with a .22 caliber youth rifle.
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The suicide was the culmination of five days of strange behavior that began shortly after Sanders snorted a powdery substance he bought from a friend. Instead of the brief high he was seeking, he experienced days of insomnia, along with waves of terror and frightening delusions, including an incident where he “saw” 25 police cars outside his parents' kitchen window and then slit his own throat with a butcher knife. That incident landed Sanders in the hospital with stitches. For a few hours, the hallucinations subsided.
“I don't like the way this is making me feel," Sanders told his stepmother, Julie, as the two awaited his release from the hospital. "I promise I won't do anything again. I'm done.”
But the paranoia flared up with a vengeance that night, and back home, Dickie's father lay in bed with his son, arms wrapped around him, until he finally nodded off. It's unclear when Dickie woke up, made his way downstairs to his bedroom and found the rifle he had won in a shooting contest years before. No one heard the gunshot.
An autopsy revealed a powerful stimulant in his system: methylenedioxypyrovalerone, also known as MDPV.
MDPV is a common ingredient in a street drug known as "bath salts." Sanders' death occurred the month after Mark Ryan, director of the Louisiana Poison Center, began to receive the first string of calls from emergency rooms around the state about patients taking the drug. For such a benign name, the symptoms were dangerous and bizarre. People were showing up just like Sanders had -- paranoid, agitated, violent and hallucinating.
“These guys were seeing things like monsters, demons and aliens, and those were consistent terms,” Ryan said. “We didn't ask, ‘Are you seeing monsters and aliens?' They were telling us that.”
We didn't ask, 'Are you seeing monsters and aliens?' They were telling us that.
Soon after Dickie Sanders died, Ryan teamed with Kentucky's poison control center and began to build a database of every bath salts case recorded in the two states. In the report, they listed behaviors brought on by the drugs. One patient high on the substance repeatedly fired guns out of the house at strangers. Another broke all the windows in a house and then wandered barefoot through the broken glass. A third left her 2-year-old daughter in the middle of a highway because she “had demons.”
“Bath salts” are nothing like the epsom salts often added to bathwater; it's just the most common code name given to a specific type of synthetic drugs made in underground labs and marketed as household items. The drugs have been camouflaged as plant food, stain remover, toilet bowl cleaner and hookah cleaner. They've been sold online and in "head shops," businesses that sell drug paraphernalia. The boxes usually contain a foil wrap or plastic bag of powder, though sometimes they take the form of pills or capsules. The color of the powder ranges from white to yellow to brown, the price from $30 to $50. And nearly every box has a label that says “not for human consumption.”
When bath salts first appeared in 2010, the products were crudely packaged -- a label from an ink-jet printer slapped onto a plastic container, Ryan said. But over time, they began to look increasingly more professional and often specifically tailored to the place. Products in Louisiana donned names like Hurricane Charlie, NOLA Diamond, Bayou Ivory Flower. Bath salts had also surfaced in Illinois, Kentucky and Florida, but Louisiana was hit especially hard.
The product that Sanders snorted was called Cloud 9. At the time of his death, he was in a drug program for marijuana abuse, actively attending group meetings and undergoing frequent drug tests. He was told that the drug was legal, a great high and wouldn't show up on a drug test.
Cathleen Clancy is associate medical director at the National Capital Poison Center in Washington D.C., where they catalog the effects of bath salts on the area's emergency room cases. Users are often hyper-agitated, hot and sweating, she said. Their heart rate is dangerously high, their blood pressure is up, and seizures are common.
Often even high doses of common sedatives don't help them. Doctors instead must turn to antipsychotics or other powerful medications.
Early on, doctors began noticing something else that was strange. Compared with other drugs, bath salts didn't follow a normal dose-response pattern. With cocaine or methamphetamine, the drug entered the bloodstream, and, within hours, began to wear off. Not so for bath salts.
“Some patients were in the hospital for 5 days, 10 days, 14 days,” Ryan said. “In some cases, they were under heavy sedation. As you try to taper off the sedation, the paranoia came back and the delusions."
As Ryan was scrambling to grasp the scope of the problem in Louisiana, scientists 1,000 miles away were beginning to tease out the drug's chemistry. What was it about this substance, they wondered, that could make a man cut his own throat or a mother leave her 2-year-old in the middle of a highway?
What few people knew was that the chemical components of the drug long predated the Louisiana outbreak. In the 1970s, a medicinal chemist named Richard A. Glennon was studying what it would take to convert a stimulant drug to a hallucinogen and vice versa in order to determine how these substances work in the brain. He knew that small modifications to a drug's molecular structure could result in major changes in its effects. By introducing an oxygen atom to the side chain of amphetamine, he created something called a beta-keto amphetamine. Beta-keto amphetamine was what we now call cathinone, and at the time, in the U.S., it was a new class of stimulant.
“We didn't expect any type of activity from it, but we found out it was an active stimulant,” Glennon said. “And it was at least as potent, if not more potent, than amphetamine.”
Scientists would soon realize, it behaved like no stimulant anyone had ever seen.
Shortly after, a group from the National Institute for Drug Abuse (NIDA) visited Glennon's lab. One of the scientists informed Glennon that his compound was identical to the active ingredient of a plant called Catha edulis, or khat, a plant native to East Africa and the Arabian Peninsula that produces an amphetamine-like high when chewed or brewed as tea.
“He said, ‘Eureka, this is the active constituent of khat,'” Glennon recalled. “So we found ourselves in possession of a lot of the early pharmacological data on this.
Few things make amphetamine more potent than it already is. But add an extra methyl group - a carbon atom bound to three hydrogen atoms - and you get the more potent methamphetamine. Glennon made the same change to his cathinone, and the already powerful stimulant became suddenly even more powerful. In 1987, he published his results in the journal, Pharmacology, Biochemistry and Behavior. The title of the article was "Methcathinone: A New and Potent Amphetamine-like Agent." It was the first time the term "methcathinone" had been used.
Soon after his paper was published, Glennon received a letter in the mail from a scientist at the Lensoviet Technological Insitute in St. Petersburg, Russia. What Glennon was calling methcathinone, the scientist told him, already existed in the Soviet Union. Methcathinone had sprung up as a major drug of abuse there in the 1970s and had increased tenfold in the eighties. There, they were calling it ephedrone, or "Jeff" on the streets.
Glennon's 1987 article, the Russian scientist wrote, was the only published reference he could find on methcathinone. He went on to write that despite its popularity in the Soviet Union, the widespread drug problem had been kept quiet by Soviet authorities for "political motives."
In the past four decades, Glennon has published more than two dozen papers and book chapters on cathinone, its effects and how it compares to other drugs.
In 1993, cathinone was classified by the federal government as a Schedule I substance, a category that includes heroin and LSD, and is reserved for drugs with a high potential for abuse and "no currently accepted medical use in treatment in the United States."
For decades though, synthetic cathinones were less of a real problem in the U.S. and "more like a theoretical, scientific problem," Glennon said. That is, until 2010.
At the same time Mark Ryan was battling the rapid rise of bath salts in the deep South, the mysterious new drug was brought to Glennon's attention. One common ingredient in bath salts was a stimulant called mephedrone. Glennon, who now runs at lab at Virginia Commonwealth University School of Pharmacy, noticed that mephedrone bore a strong resemblance to compounds he had synthesized years earlier. Mephedrone is a synthetic cathinone.
He set out to learn more. In April 2012, his lab and two others at VCU School of Medicine won a joint five-year grant from NIDA to synthesize the ingredients in bath salts and study the drug's effect on brain transporters embedded in frog cells and in lab rats. They were determined to find out what it did to the brain and how, exactly, it produced such powerful effects.
Meanwhile, in Louisiana, lab tests were showing that, in addition to mephedrone, nearly every single blood and urine sample from bath salts users contained another ingredient, the same ingredient found in Dicki Sanders' blood: MDPV. MDPV is also a synthetic cathinone. But, scientists would soon realize, it behaved like no stimulant anyone had ever seen.
AT THE ROOT OF EVERYTHING: DOPAMINE
It's impossible to talk about bath salts without talking about dopamine -- a natural neurotransmitter involved in the basic experience of pleasure. Chocolate, sex, gambling, nicotine, even the buzz of a smartphone in a pocket, all cause a rush of dopamine in the brain's reward center, the nucleus accumbens. Tiny dopamine molecules surge forth from nerve cells in the brain to send a cascade of signals to other nerve cells, and then they retreat back into the cell in a process called reuptake. It's the constant release and retreat of this chemical that causes feelings of pleasure, exhilaration and a sense of well being.
Dopamine also has profound effects on memory, learning, motivation and motor control. When the dopamine balance gets upset, it can wreak havoc on these parts of the brain. Parkinson's disease is an example of dopamine gone wrong.
Except for one thing: MDPV is as much as 10 times stronger than cocaine.
Methamphetamine, amphetamine and cocaine all produce excessive dopamine in the space between two neurons -- the synapse -- but through different mechanisms. Both amphetamine and methamphetamine primarily work by causing an abnormal amount of dopamine to surge forth from the nerve cells, shifting the brain's reward pathways into overdrive. Cocaine on the other hand is what's called a reuptake inhibitor. That means it acts like a stopper in a kitchen sink, blocking the retreat, or reuptake, of dopamine back into the cell. It's this excessive dopamine, which goes on to stimulate the next neuron, which causes a dizzying rush of energy and a fierce, sometimes euphoric high.
To investigate how bath salts influence this dopamine system, Glennon recruited his colleague, Louis De Felice, who was already well entrenched in research on amphetamine, methamphetamine, ecstasy and cocaine.
Louis De Felice, a neuroscientist at VCU School of Medicine, is beginning to crack the code on bath salts. De Felice is a bearded, jovial man with a fondness for Latin American novels, old voltage batteries and a mechanical interest in how things work. On his office shelves are replicas of an old amplifier, the first-ever microscope and flamingos. Lots of flamingos.
When he was 10, De Felice's family moved from New Jersey to Florida, and he hated it. He couldn't get used to the weather, the slatted windows, and the flamingos. But a friend suggested he might overcome his aversion if he'd stop fighting his new reality and embrace Florida -- if he'd move toward the flamingo, instead of away from it. De Felice heeded the advice, both literally and figuratively. Now, in his office where he researches the science of illicit drugs, he is surrounded by the birds: wooden, stuffed and glass. His surroundings, he says, exemplify his life philosophy: “Go toward the flamingo.”
De Felice credits that philosophy for his unwillingness to give up when a project baffles him. And bath salts were a new challenge. De Felice was fascinated by certain aspects of the symptoms: the seemingly superhuman strength, how people high on the drug had a tendency to tear off their clothes, to attempt even to tear off their body parts. He wanted to nail down the mechanics of how they worked, to bring the strange picture into focus.
De Felice and his research team began to test the basic elements of bath salts -- the same chemicals that had been found in Dickie Sanders' blood. Mephedrone, they found, seemed to act like amphetamine, causing an excessive surge of dopamine from the cell. That was no surprise, since the molecules are structurally similar.
When they turned to MDPV, however, they were startled by what they saw. Even though MDPV was in the same structural family, it seemed to produce a totally different effect. The way it worked was in fact the opposite of mephedrone. It worked, instead, like cocaine. It blocked the reuptake of dopamine back into the cell. The team''s findings have been accepted for publication later this year by the British Journal of Pharmacology.
“We thought, how can things that were so similar structurally act so different functionally,” DeFelice said. “That was a big surprise.”
Taking bath salts, it seemed, was similar to taking amphetamine and cocaine at the same time. Except for one thing: MDPV is as much as 10 times stronger than cocaine.
Imagine the space between the nerve cells as a kitchen sink and the water as dopamine. In the brain's natural state, the faucet, or nerve cell endings, are always leaking some dopamine, and the drain is always slightly open, vacuuming some of the chemical back into the cell. Methamphetamine turns the faucet on high. Cocaine closes the drain. Bath salts, researchers discovered, do both at the same time. With the faucet on and the drain closed, the water overflows. In other words, the drug was flooding the brain.
“In all the areas where dopamine is important, you've got too much of it,” De Felice said. “When you realize the implications of that for drugs people take, you're like, oh my gosh, what an insidious combination this is.”
THE FROG AND THE FISH HOOK
At a far end of De Felice's lab, YooRi Kim, a Ph.D. candidate, squints as she holds a plate of frog eggs up to the light. The eggs are tiny, black seed-like things, about the size of a pencil tip, and they're floating in cloudy water. The plate gives off a sour scent; it smells faintly of dead frogs.
“You see how this one is oozing stuff out,” she said, pointing to one of the eggs. “That's dead.”
Summer is a bad season for frog eggs, she explains. From November to February, the eggs tend to be healthy, but by mid-summer, only the hardiest make it to the microscope. She identifies a healthy egg and delicately plucks it out from the tray with a pipette. Under the scope, she positions the cell with a needle, immobilizes it, and then pierces its membrane with two glass electrodes – one measures voltage; the other injects current.
Magnified, the egg is eerily beautiful – yellow and imperfectly round, like a moon.
"But for hours and hours, you've essentially removed the dopamine transporters."
Across the hall, a room of Chilean frogs float in a murky solution. Ten days earlier, eggs were removed from the ovaries of one of the frogs. In order to use these eggs to study bath salts, Kim needed them to express dopamine transporters. Dopamine transporters are proteins on the cell's membrane that act like a gate, allowing the movement of dopamine into and out of the cell.
First, Kim injected the egg with RNA that encodes for the dopamine transporter. Then she let them incubate for seven days, while the cell sprouted the transporters -- millions of them. She was essentially programming the egg cells to act more like nerve cells.
Now, she's infusing the cells in a solution of bath salts to see how they behave. To the left of the microscope, hanging from a wall, are syringes filled with a selection of highly controlled substances: cocaine, amphetamine, MDMA (the main component of ecstasy) and the core elements of bath salts (MDPV and mephedrone.) When she turns a lever, the drugs travel down tubes and into a solution bathing the cell. To her right is an operating board of knobs and switches that allow her to stabilize the voltage of a cell before shooting it up with drugs. Next to that is a computer.
Kim hits a voltage clamp knob and, after introducing dopamine to be sure the cell is working correctly, turns a lever to inject the cell with amphetamine. At the computer, she studies a line floating across the screen. The line represents the current flowing through the cell's transporter, tiny electrical signals amplified on the screen. At first, the line is fairly flat, but when she adds the stimulant, it dips. Each drug has its own electrochemical fingerprint. The dip represents activity in the transporters as the amphetamine releases dopamine. She removes the drug, washes it out, and the line climbs back up, but it doesn't return to baseline right away.
“Because it's amphetamine, it's not recovering completely,” Kim says.
Amphetamine opens the dopamine transporter, she explains, and even after it's removed, it continues to stay open for a while, which causes the nerve to slowly leak out dopamine like a dripping faucet. Hence the slow recovery.
When she adds cocaine, the opposite happens. The line climbs upward, a sign that the cell is probably becoming hyperpolarized and the transporter being blocked. The cocaine is likely blocking the cell's transporter, preventing dopamine's reuptake back into the cell -- plugging the drain. Like amphetamine, when she removes cocaine, the line eventually returns to the original position.
But when she treats a cell with mephedrone and then turns the lever to add MDPV, something strange and interesting happens. As with cocaine, the line on the computer climbs rapidly upwards, but when she takes it away, the line does not return back to baseline like it did with the cocaine. In fact, as long as the cell stays alive, the line never returns to its original position.
“Forty-five minutes after adding MDPV, it still can't go back to baseline,” Kim says.
What they've found is that there seemed to be a time delay built into the drug, so that mephedrone is acting before MDPV, releasing dopamine from the cell before reuptake is blocked. And once MDPV takes hold, it doesn't seem to let go.
“This is why people who abuse the drug feel the effects the next day,” she says.
Why MDPV causes such a prolonged response is central to this research, and De Felice has a theory. If you look at the chemical structure of MDPV, it has one structural feature that the other molecules don't: a short carbon chain with a methyl group at the end.
“It's got this little arm that sticks out,” he explains. “I think it's kind of like a fish hook. I think it goes in and it doesn't come out. That may be what makes it different than cocaine. It gets stuck in the transporter, and it holds it closed.
This could explain the strange behavior among abusers of these drugs, De Felice said. In fact, he thinks ingesting bath salts is akin to knocking out the dopamine transporters altogether.
"Eventually the body will replace them, presumably," he said. "But for hours and hours, you've essentially removed the dopamine transporters. So you've really messed up the whole balance of neurotransmitters in the brain."
In Glennon's lab, they're in the process of synthesizing a substance that lacks this so-called “fish hook” in an attempt to isolate what it is that makes MDPV so uniquely powerful. The next step is to compare MDPV to this altered substance in cells and lab rats.
HOLIDAY PLANS CANCELED
Christmas morning is usually slow for Louisiana's poison control center, but on Dec. 25, 2010, Mark Ryan got a call about a bath salts case. Then another call, and another. In the six weeks following the death of Dickie Sanders, Ryan had noticed a rise in the use of bath salts, and that morning the calls were coming in rapid-fire succession: 11 in all. So Ryan canceled his vacation plans and started making his own calls.
“Merry Christmas,” he told Louisiana State Health Officer, Jimmy Guidry. “I think you should know, my family's going skiing, and I'm staying here.” Bath salts, Ryan told Guidry, had become such a public health crisis that the center was in a state of emergency. The problem required immediate action.
Guidry remembers the phone call: “He was concerned, and he was definitely getting my attention,” Guidry said. It was an unusual situation, he said, particularly since bath salts were sold legally, and they were not prescription drugs. He assigned his legal team to the job, talked to law enforcement, studied the data, and ultimately determined that the drug fit all the criteria needed to be controlled as a dangerous substance.
“I remember trying to figure out how to approach this,” Guidry said. “I believed [Ryan] and valued his professional opinion, and I knew we had to do something very serious with the backing of law enforcement.”
A week later, Guidry called Ryan back, and said, “We're ready to move. What should we ban?” By Jan. 6, Guidry had used emergency rule -- an extraordinary and rarely used measure -- to ban the five ingredients commonly found in bath salts products: MDPV and mephedrone, along with three others: methylone, methedrone and flephedrone.
And it was a good thing. By then, the Louisiana Poison Center had received more than 110 calls about bath salts in December alone. That's compared to four calls during the entire month of October and 24 calls in November. And the trend was being mirrored in areas throughout the country.
On July 9, 2012, responding to rising cases of bath salts abuse, President Obama signed into law the Synthetic Drug Abuse Prevention Act, which bans MDPV, mephedrone and 29 other bath salts ingredients.
On July 26, the Drug Enforcement Administration announced that it had seized more than five million packets of synthetic drugs and arrested 90 people in a nationwide crackdown called Operation Log Jam. Of the drugs seized, 167,000 packets and ingredients to make an additional 392,000 products were synthetic cathinones. The raid also targeted another class of synthetic drugs known as synthetic cannabinoids or synthetic marijuana, commonly called K2 and Spice.
Of note, 60 percent of synthetic drug cases reported to poison control centers nationwide involved users age 25 or younger, according the the Drug Enforcement Administration.
As soon as the drugs were declared illegal, drugmakers began finding new ways to get around the law ...
In the first half of 2011, the number of bath salts cases reported to U.S. poison control centers climbed almost every month, peaking in June at 743. (Note: the cases reported usually represent the most severe.) But then they began to fall, dropping to 222 by December 2011. This June logged 415 calls. [e]
One explanation is that fewer people are abusing bath salts. But a more likely explanation, Ryan said, is that police and emergency room doctors and are getting more accustomed to seeing them and no longer calling poison control.
Authorities like Ryan have also noticed another trend -- one possibly as dangerous as the drugs themselves: they're changing. In Louisiana for example, after the five common bath salts ingredients were banned, the products didn't disappear, they just evolved. As soon as the drugs were declared illegal, drugmakers began finding new ways to get around the law by making slight tweaks to the formula, creating substances that don't show up on drug tests while skirting the law.
“What [drugmakers] are looking for is the side effects,” Guidry added. “They just have to change the chemistry, and they've got something that's not on the list, and it's not illegal. They continue to make it legal to have these horrible side effects.”
“It's like that arcade game Whac-a-Mole,” Ryan said. “Every time you think you've got a handle on it -- boom -- it pops up in three different places.”
And perhaps even more troubling, the doses vary wildly.
“There's no consistency to what's in the package,” Ryan continued. “We tested packages for how much MDPV was in them. One of them only contained 17 milligrams. One contained 2,000 milligrams.”
It explained why one person might have a mild reaction to the drug, while another would end up in the psych ward or counting imaginary police cars outside their window. “It became extremely confusing to the clinicians and to us because there was no standard,” Ryan said.
It's the inconsistency of synthetic drugs that worries experts the most. Tiny mistakes in drugmakers' laboratories can make huge differences in how the drug reacts when it enters the human body. Simple highs can become debilitating illnesses. In 1982, in Northern California, for example, a synthetic heroin made in an underground lab caused a group of users to permanently develop symptoms nearly identical to advanced Parkinson's Disease.
Also troubling is how little is known about what these drugs do to the brain long term. Understanding how bath salts work, DeFelice said, will not only help to explain the extreme length and potency of a bath salts high, it also will reveal the extent of cell death and damage to the brain. This could help researchers design better tests, treatment, even antidotes.
"MDPV is irreversible, it won't let go," De Felice said. "I don't know of any other drug that has that same feature of not allowing you to escape from it."
Knowing more about bath salts might have lessened the horror that Dickie Sanders battled in his final days. In the two years since, his parents, Julie and Richard Sanders, have tried to raise awareness about bath salts by sharing his story with the public and talking to other families who have lost people to the drug.
“It's so hard to understand how something sold over the counter can result in death,” Julie Sanders said. “I can't grasp it, I just still can't grasp that thought.”
Terry Adams, a pro-BMX rider and one of Dickie's closest friends, often thinks about his friend. “If we're riding in a group of friends,” Adams said, “and someone's doing [bike tricks] that remind me of him, I say, ‘Dickie did that. Dickie could do that really good.'”
Six months ago, Adams drove 35 minutes to the strip-mall parking lot where Sanders used to train, and spent the afternoon riding there by himself. He did the tricks Sanders liked to do. He remembered his friend's signature trick: how he'd pop his BMX bike onto its back wheel and, hands free, uses his full body to pump it in circles. He remembered how people would shout “Dickie! Dickie!” when he rode, and how cars would be forced to stop and wait until he finished a move -- how some would clap when he was finished, how some would get impatient and honk.
At the end of the day, Adams crouched on the asphalt and with a permanent marker, scrawled a note onto the ground: “I stopped by to ride your spot. I miss you Dickie.”
It was Adams' way of honoring a memory that will remain forever, pointlessly, in the past tense: Meeting his friend in that parking lot. Riding with him for hours until the sun goes down, and finally heading home, exhausted, with Dickie still there, in the dark, perfecting a trick. “Riding hard.”
Posted: Sept. 20, 2012