The Losing Battle For Perpetual Reward

Or why you can't stay high forever.

The amphetamine high, like the cocaine high, is a marvel of biochemical efficiency. Stimulants work primarily by blocking the reuptake of dopamine molecules in the synaptic gap between nerve cells. Dopamine remains stalled in the gap, stimulating the receptors, resulting in higher dopamine concentrations and greater sensitivity to dopamine in general. Since dopamine is involved in moods and activities such as pleasure, alertness and movement, the primary results of using cocaine or speed—euphoria, a sense of well being, physical alertness, and increased energy—are easily understood. Even a layperson can tell when lab rats have been on a meth binge. The rapid movements, sniffing, and sudden rearing at minor stimuli are not that much different in principle from the outward signs of meth intoxication among higher primates.

Chemically, cocaine and amphetamine are very different compounds. Psychoactively, however, they are very much alike. Of all the addictive drugs, smoked cocaine and speed have the most direct and most devastatingly euphoric effect on the dopamine systems of the brain. Cocaine and amphetamine produce rapid classical conditioning in addicts, demonstrated by the intense cravings touched off by such stimuli as the sight of a building where the user used to buy or sell. Environmental impacts of this nature can produce marked blood flow increases to key limbic structures in abstinent addicts.

In clinical settings, cocaine users have a hard time distinguishing between equal doses of cocaine and Dexedrine, administered intravenously. As we know, it is the shape of the molecule that counts. The amphetamines are shaped like dopamine and norepinephrine, two of the three reward chemicals. Speed, then, is well suited to the task of artificially stimulating the limbic reward pathway. Molecules of amphetamine displace dopamine and norepinephrine in the storage vesicles, squeezing those two neurotransmitters into the synaptic gap and keeping them there. By mechanisms less well identified, cocaine accomplishes the same feat. Both drugs also interfere with the return of dopamine, norepinephrine, and serotonin molecules to their storage sacs, a procedure known as reuptake blocking. Cocaine works its effects primarily by blocking the reuptake of dopamine.

Amphetamine was once one of the most widely prescribed drugs in the pharmacological cornucopia. It exists in large part now as a recreational drug of choice, abuse, and addiction. The same is true of cocaine. It was replaced as a dental anesthetic long ago, in favor of non-addictive variants like Novocain. The same tragic list of statistical side effects that apply to abusers of alcohol, heroin and nicotine also apply to stimulant abusers: Increased risk of car accidents, homicides, heart attack, and strokes.

In the late 1990s, scientists at Johns Hopkins and NIDA showed that opiate receptors play a role in cocaine addiction as well. PET scans demonstrated that cocaine addicts showed increased binding activity at mu opiate receptors sites in the brain during active cocaine addiction. Take away the cocaine, and the brain must cope with too many empty dopamine and endorphin receptors. It is also easy to understand the typical symptoms of cocaine and amphetamine withdrawal: lethargy, depression, anger, and a heightened perception of pain. Both the cocaine high and the amphetamine high are easily augmented with cigarettes or heroin. These combinations result in “nucleus accumbens dopamine overflow,” a state of neurochemical super saturation similar to the results obtained with the notorious “speedball”—heroin plus cocaine.

With the arrival of smokable forms of cocaine and amphetamine, the race to pin down the biology of stimulation became even more urgent. Stimulants in smokable form—crack and ice—are even more rapidly addictive for addiction-prone users. “The reason has to do with the hydraulics of the blood supply,” a researcher at the University of Minnesota explained to me. “High concentrations are achieved with each inhalation, and sent right upstairs to the brain—but not all of the brain simultaneously. The target of the flow of blood is the limbic system, whereas the remainder of the brain is exposed to much milder concentrations.”

This extraordinarily concentrated jolt to the reward center is the reason why smokable cocaine and speed are able to pack such a wallop. The entire range of stimulative effects hits the ventral tegmental area and associated reward regions of the brain in seconds, and the focused nature of the impact yields an astonishingly pleasurable high.

But the long-term result is exactly the opposite. It may sound dour and religious, but the scientific fact of the matter is that continuous chemical pleasure extracts its fee in the end: The body’s natural stock of these neurotransmitters starts to fall as the brain, striving to compensate for the artificial flooding of the reward center, orders a general cutback in production. At the same time, the receptors for these neurotransmitters become excessively sensitive due to the frequent, often unremitting nature of the stimulation.

“It’s clear that cocaine causes depletion of dopamine, norepinephrine, serotonin—it is a general neurotransmitter depleter,” said my research source. “That may account for many of the effects we see after someone has stopped using cocaine. They’re tired, they’re lethargic, they sleep; they may be depressed, moody, and so on.” Continued abuse of stimulant drugs only makes the problem worse. One reason why cocaine and amphetamine addicts will continue to use, even in the face of rapidly diminishing returns, is simply to avoid the crushing onset of withdrawal. Even though the drugs may no longer be working as well as they once did, the alternative—the psychological cost of withdrawal—is even worse. In the jargon used by Alcoholics Anonymous, addicts generally have to get worse before they can get better.

When addicts talk about “chasing a high,” the metaphor can be extended to the losing battle of neurotransmitter levels.

[First published September 28, 2011]

Graphics Credit: http://www.keepcalm-o-matic.co.uk

Strokes in Young People

Drug use as a risk factor.

(First published 12-09-12)

When a stroke happens to anyone under the age of 55, a major suspect is drugs, specifically the stimulants—methamphetamine and cocaine. In the journal Stroke, researcher Brett Kissela and his associates provided additional evidence to support that unpleasant truth.

“We know that even with vascular risk factors that are prevalent—smoking, high blood pressure—most people still don’t have a stroke until they’re older,” Kissela said in a Reuters article. “When a young person has a stroke, it is probably much more likely that the cause of their stroke is something other than traditional risk factors.”

The modest study involved residents of Cincinnati and Northern Kentucky who had suffered a stroke before turning 55. The researchers found that the rate of substance abuse among the stroke group was higher than in control populations. This doesn’t prove that drug or alcohol addiction lead directly to strokes, since drug users often have additional risk factors for stroke and heart disease, particularly if they are also cigarette smokers.

But the suspected link between strokes and young drug abusers is by no means a new one. In 2007, scientists at the University of Texas Southwestern Medical Center in Dallas published a massive survey of more than 3 million records of Texas hospital patients from 2000 through 2003 in the Archives of General Psychiatry. This gigantic database gave the researchers access to the records of virtually every stroke patient in the state of Texas. The researchers found that strokes associated with amphetamine use among young people 18 to 44 years of age represented a rapidly growing category. In fact, the Texas group found that “the rate of strokes among amphetamine abusers was increasing faster than the rate of strokes among abusers of any other drug.”

Curiously, amphetamine and cocaine are responsible for different kinds of strokes. An ischemic stroke, the classic blood clot, is caused by a blockage of blood vessels to the brain. Hemorrhagic strokes result from bleeding caused by the rupture of a weakened blood vessel. In general, hemorrhagic strokes are more severe and more likely to cause death. And what the researchers found was more bad news for speed freaks: “Amphetamine abuse was strongly associated with hemorrhagic stroke, but not with ischemic stroke.” Cocaine abuse was more robustly linked to ischemic strokes. So, it’s not surprising that when it comes to drug and fatal strokes, the clear winner was amphetamine. It’s not entirely clear what causes the difference, but the investigators pointed out that meth injections in lab animals can cause microhemorrhaging, heart attacks, fragmentation of capillary beds, and something called “poor vascular filling.” For cocaine, the culprits are vasoconstriction and disrupted regulation of blood pressure.

More than 14 percent of strokes in hospitals “were accounted for by abuse of drugs,” the researchers wrote. The data showed that for patients with hemorrhagic strokes, “only amphetamine abuse, coagulation defects, and hypertension were strong independent predictors of in-hospital death.”

So what can we conclude? Either the number of speed users in these communities is increasing, or the existing speed communities are using the drug more intensely. Since the rate of increase of speed use was relatively modest during the study years, the researchers concluded that “increased rate in our hospital population is because of the increased intensity of methamphetamine use.” Meaning higher dosages, stronger meth, and more needles.

Sadly, much of this has been known since it least 1990. In that year, research published in the Annals of Internal Medicine, based on a study of stroke victims at San Francisco General Hospital, concluded that “the possibility of serious and sometimes fatal cerebrovascular accidents in people taking potent stimulants and using the intravenous route of administration is not as widely known as it needs to be.”

About 800,000 people in the U.S. suffer a stroke each year, according to figures from the U.S. Centers for Disease Control and Prevention. Strokes are considered America’s leading cause of serious long-term disability.

de los Rios F., Kleindorfer D.O., Khoury J., Broderick J.P., Moomaw C.J., Adeoye O., Flaherty M.L., Khatri P., Woo D. & Alwell K.;  (2012). Trends in Substance Abuse Preceding Stroke Among Young Adults: A Population-Based Study, Stroke, 43 (12) 3179-3183. DOI: 10.1161/STROKEAHA.112.667808

Methamphetamine: An Excerpt

There’s more than one kind of monster.

Type and I pass the pipe.  The overhead light flickers and the wind picks up even more. It’s coming from the north because with each exhale, the smoke slips past my face, back toward the Twin Cities and my dead parents.
 
But for a brief moment, I’m not thinking about all that. I’m feeling the closest thing I can think of to God and he’s playing the samba inside of my body, his fingers gentle, as they press on the backs of my retinas, my spine, the tendons along my hip flexors. I’m thinking that I love drugs more than anything. That they are the one and only constant in my life. Yeah, they demand a lot of attention and effort, but their love is legendary, their compassion endless. I hold each hit for hours, exhale for decades. The determination that comes with the onset of a high rushes back and I’m all about conquering the world and making money and finding happiness in the form of a loving woman who knows when it’s time to brush the backs of her nails across my cheek and then I’m thinking about this being the same thing as what God is doing to me now.

I love it when my heart rattles against my uvula.

I love it when my vision is a camera shutter.

I love it when I know that someday, I will do great things.

I love it when methamphetamines make things okay.

But I don’t love it when I start to hallucinate because the line between knowing it’s only the drugs and knowing your psyche is about to snap the fuck apart like a high wire is oh so delicate....

—From Fiend, a novel by Peter Stenson

Popular “Bath Salt” Hooks Lab Rats

Mephedrone shows addictive properties in animal models.

Cathinones, like methedrine and other stimulants, are primarily dopamine-active drugs. Though they are now illegal in the U.S., they were formerly of primary interest only to pharmaceutical researchers. The best-known cathinone sold in the form of bath salts and plant food—mephedrone—has both dopamine and serotonin effects. It broke big in the UK a few years ago as a “legal” party drug alternative to MDMA. The idea was to get high without testing dirty, as the saying goes.

Behavioral clues about mephedrone have been teased out of rat studies. The Taffe Laboratory at Scripps Research Institute has been focusing on the cognitive, thermoregulatory, and potentially addictive effects of the cathinones, and mephedrone in particular. Scripps researchers have carried the investigation forward with a recent study in the journal Drug and Alcohol Dependence.

Now comes additional evidence, also from the Taffe Lab at Scripps, that mephedrone, or 4-MMC, looks like an addictive drug. In a paper accepted for publication by Addiction Biology, which Addiction Inbox was allowed to review in advance, Dr. Michael Taffe, along with lead author S.M. Aarde and coworkers, demonstrated in an animal study that lab rats will intravenously self-administer mephedrone under normal lab conditions—roughly analogous to shooting speed.

Without suitable strains of test animals, most genetic and neurobiological research would take centuries, and would involve ethical questions about human testing far stickier than the questions raised by work with animals. Animal models are one of the primary pathways of discovery available to neurobiologists and other researchers.

But it’s tricky. Establishing traditional rodent laboratory conditions is a Goldilocks endeavor: The environment must be not too hot, but not too cold, because this can effect rodent behavior. And the drug must be given at rates that are not too frequent and not too rare.

The curious thing about mephedrone is that it appears to combine the effects of prototypical stimulants like cocaine and methamphetamine, with the trippy, “entactogen” effects of MDMA, aka Ecstasy, in the bargain. The drug rapidly crosses the blood-brain barrier, reaching peak levels two minutes after injection, and full effects last about an hour. In one study, 76% of people who had snorted both cocaine and mephedrone reported that the quality of the mephedrone high was “similar to or better than” cocaine. But the paper also states that “human recreational users report 4-MMC to be subjectively similar to MDMA.”

The investigators ran a series of tests with various groups of rats, and found that 80-100% of the rats would happily reward-press a lever for an infusion of mephedrone. “Under these conditions,” writes Taffe, “methamphetamine and 4-MMC have about equal effect on rat self-administration although the 4-MMC is considerably less potent, requiring about 10 times the per-infusion dose for effect.” Although it wasn’t demonstrated directly in this paper, Ecstasy “is at best unevenly self-administered by rats,” and “despite an MDMA-like serotonin/dopamine neuropharmacological effect, mephedrone has a liability for repetitive intake more similar to the classical amphetamine-type stimulants such as methamphetamine.”

It’s a weaker type of stimulant, mephedrone, but it does the trick. It is highly reinforcing. Mephedrone chemically resembles speed, but also has Ecstasy-like effects. "Furthermore, neurochemical data suggest MDMA-like patterns of relatively greater serotonin versus dopamine accumulation in nucleus accumbens.” Even with its added Ecstasy-like effects, the scientists conclude that “the potential for compulsive use of mephedrone in humans is likely quite high, particularly in comparison with MDMA.”

Photo Credit: Creative Commons

Synthetic Drugs: Collected Posts

Catching up with bath salts and spice.


The Low Down on the New Highs: Not all bath salts are alike.

“You’re 16 hours into your 24-hour shift on the medic unit, and you find yourself responding to an “unknown problem” call.... Walking up to the patient, you note a slender male sitting wide-eyed on the sidewalk. His skin is noticeably flushed and diaphoretic, and he appears extremely tense. You notice slight tremors in his upper body, a clenched jaw and a vacant look in his eyes.... As you begin to apply the blood pressure cuff, the patient begins violently resisting and thrashing about on the sidewalk—still handcuffed. Nothing seems to calm him, and he simultaneously bangs his head on the sidewalk and tries to kick you...” [Go here]


The New Highs: Are Bath Salts Addictive? What we know and don’t know about synthetic speed.

Call bath salts a new trend, if you insist. Do they cause psychosis? Are they “super-LSD?” The truth is, they are a continuation of a 70-year old trend: speed. Lately, we’ve been fretting about the Adderall Generation, but every population cohort has had its own confrontation with the pleasures and perils of speed: Ritalin, ice, Methedrine, crystal meth, IV meth, amphetamine, Dexedrine, Benzedrine… and so it goes. For addicts: Speed kills. Those two words were found all over posters in the Haight Ashbury district of San Francisco, a few years too late to do the residents much good…. [Go here]


“Bath Salts” and Ecstasy Implicated in Kidney Injuries: “A potentially life-threatening situation.”

Earlier this month, state officials became alarmed by a cluster of puzzling health problems that had suddenly popped up in Casper, Wyoming, population 55,000. Three young people had been hospitalized with kidney injuries, and dozens of others were allegedly suffering from vomiting and back pain after smoking or snorting an herbal product sold as “blueberry spice.” The Poison Review reported that the outbreak was presently under investigation by state medical officials.  “At this point we are viewing use of this drug as a potentially life-threatening situation,” said Tracy Murphy, Wyoming state epidemiologist…. [Go here]


The Triumph of Synthetics: Designer stimulants surpass heroin and cocaine.

A troubling report by the United Nations Office on Drugs and Crime (UNODC) shows that amphetamine-type stimulants (ATS) have, for the first time, become more popular around the world than heroin and cocaine. Marijuana remains the most popular illegal drug in the world, and the use of amphetamines has fallen sharply in the U.S., but the world trend represents the worldwide triumph of synthetic drug design over the plant-based “hard drugs” of the past…. [Go here]

Marijuana: The New Generation: What’s in that “Spice” packet?

They first turned up in Europe and the U.K.; those neon-colored foil packets labeled “Spice,” sold in small stores and novelty shops, next to the 2 oz. power drinks and the caffeine pills. Unlike the stimulants known as mephedrone or M-Cat, or the several variations on the formula for MDMA—both of which have also been marketed as Spice and “bath salts”—the bulk of the new products in the Spice line were synthetic versions of cannabis…. [Go here]


An Interview with Pharmacologist David Kroll: On synthetic marijuana, organic medicines, and drugs of the future.

Herewith, a 5-question interview with pharmacologist David Kroll, Ph.D., Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, and a well-known blogger in the online science community. A cancer pharmacologist whose field is natural products—he’s currently involved in a project to explore the potential anticancer action of chemicals found in milk thistle and various sorts of fungi—Dr. Kroll received his Ph.D. from the University of Florida, and completed his postdoctoral fellowship in Medical Oncology and Molecular Endocrinology at the University of Colorado School of Medicine. He went on to spend the first nine years of his independent research and teaching career at the University of Colorado School of Pharmacy, where he taught all aspects of pharmacology, from central nervous system-active drugs, to anticancer and antiviral medications…. [Go here]


Mephedrone, the New Drug in Town: Bull market for quasi-legal designer highs.

Most people in the United States have never heard of it. Very few have ever tried it. But if Europe is any kind of leading indicator for synthetic drugs (and it is), then America will shortly have a chance to get acquainted with mephedrone, a.k.a. Drone, MCAT, 4-methylmethcathinone (4-MMC), and Meow Meow--the latter nickname presumably in honor of its membership in the cathinone family, making it chemically similar in some ways to amphetamine and ephedrine. But its users often refer to effects more commonly associated with Ecstasy (MDMA), both the good (euphoria, empathy, talkativeness) and the bad (blood pressure spikes, delusions, drastic changes in body temperature)…. [Go here]


Tracking Synthetic Highs: UN office monitors designer drug trade.

Produced by the United Nations Office on Drugs and Crime (UNODC), the Global SMART Update  (PDF) for October provides interim reports of emerging trends in synthetic drug use. The report does not concern itself with cocaine, heroin, marijuana, alcohol, or tobacco. “Unlike plant-based drugs,” says the report, “synthetic drugs are quickly evolving with new designer drugs appearing on the market each year.” The update deals primarily with amphetamine-type stimulants, but also includes newer designer drugs such as mephedrone, atypical synthetics like ketamine, synthetic opioids like fentanyl, and old standbys like LSD…. [Go here]


The New Cannabinoids: Army fears influx of synthetic marijuana.

It’s a common rumor: Spice, as the new synthetic cannabis-like products are usually called, will get you high--but will allow you to pass a drug urinalysis. And for this reason, rumor has it, Spice is becoming very popular in exactly the places it might be least welcomed: Police stations, fire departments—and army bases. What the hell is this stuff? [Go here]

Photo credit: http://gizmodo.com/

photo credit 2: http://www.clemson.edu/

The Triumph of Synthetics

Designer stimulants surpass heroin and cocaine.

A troubling report by the United Nations Office on Drugs and Crime (UNODC) shows that amphetamine-type stimulants (ATS) have, for the first time, become more popular around the world than heroin and cocaine. Marijuana remains the most popular illegal drug in the world, and the use of amphetamines has fallen sharply in the U.S., but the world trend represents the worldwide triumph of synthetic drug design over the plant-based “hard drugs” of the past.

The 2011 Global ATS Assessment estimates that in 2009, some 14 to 57 million people aged 15-64 took an amphetamine-type substance during the year.  The category includes methamphetamine, synthetic stimulants known as bath salts, and Ecstasy. For ecstasy, which is grouped with the ATS family because of its speed-like qualities, “global annual prevalence” stood at only 11-28 million past-year users in 2009, basically unchanged.  Not so for the use of the new synthetic methamphetamines—compounds such as mephedrone, 4-methylmethcathinone (4-MMC) and MDPV, which first took off in the UK, Canada, and New Zealand. In fact, bath salts in the form of mephedrone are competing with ecstasy as the club drug of the moment. (Ecstasy seizures are currently at a 5-year high in the United States, so the window for alternatives is currently wide open.) Meanwhile, recorded worldwide use of heroin, cocaine, and marijuana remained essentially steady from 2005 to 2009.

So what’s behind the global surge in production of amphetamine-type drugs? What advantages do these stimulants hold over time-tested drugs like heroin and coke?  And why is it happening now?

                                                      Emerging Markets

The seismic changes in worldwide drug production begin with geography. Amphetamine-type stimulants are spreading to new regions, and are now being manufactured in places previously off the radar—Iran, Malaysia, and West Africa, for starters. The UNODC report notes that synthetic stimulants “offer criminals a new entry into unexploited and fresh markets.” The locus of activity is no longer the opium fields of Afghanistan, or the coca plantations of Columbia. In absolute numbers, the report claims, “most ATS users live in Southeast Asia, the most populous subregion the world.”

The growing number of methamphetamine pills seized in Southeast Asia is staggering: “The 93.3 million methamphetamine pills seized in 2009 in China, Lao People’s Democratic Republic, Myanmar and Thailand represent a three-fold increase in comparison with 2008 figures,” the UN report alleges. “In 2010, total seizures surpassed 133 million pills.” Not since the Japanese amphetamine scourge of the post-World War II years has East Asia seen anything like this.

 The UN report singles out two new countries—Lao People’s Democratic Republic, and Malaysia—as nations reporting, for the first time, “the injecting use of crystalline methamphetamine in 2008 and 2009.” And a massive increase in production has been documented in northern Burma. Voice of America News reports that amphetamine-type drug seizures in Burma went from one million pills in 2008 to a mind-blowing 23 million pills a year later.

A regional representative for the UNODC in East Asia said that the seizures “reflect a dramatic increase in production in the Shan State” in Northern Burma. The production of methamphetamine is a primary source of income for the Shan, whose territory is near the borders of China and Thailand. “What we are worried about,” said the UNODC rep, “is the nexus of drugs, of weapons, of money that is moving around that region at a time when elections are pending and the political situation is quite fragile.” At the same time, Burma remains a major supplier of opiates, though competition with Afghanistan may have helped encourage the production of illegal stimulants. UNODC Executive Director Yury Fedotove explained that the market for synthetic stimulants “has evolved from a cottage-type industry typified by small-scale manufacturing operations to more of a cocaine or heroin-type market with a higher level of integration and organized crime groups involved throughout the production and supply chain.“

                                                    Homegrown vs. Manmade

Amphetamines, in all their synthetic forms, have several production advantages over plant-based addictive drugs like heroin and cocaine. In recent years, the U.S. and other countries have cracked down on amphetamine precursor drugs like ephedrine and pseudoephedrine. Once these tried and true compounds for amphetamine manufacture—found in cold and allergy medications—were registered and controlled, traffickers made the switch to different chemical approaches. New building blocks like phelylacetic acid and l-phenylacetylcarbinol (l-PAC) have been found in labs from Canada to Mexico. Growers of opium and coca have no such alternatives available to them. Pharmacologist David Kroll, Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, who has been following the new synthetic drug products on his blog, Terra Sigillata, said that ome of the latest precursors have a problematic history. “Phenylacetate and phelylacetic acid have been investigated in clinical trials for cancer and in the treatment of sickle cell disease,” said Dr. Kroll. “But they didn’t fare well in large clinical trails because they required such high doses, and patients had side effects.”

While this is definitely not a reliable class of compounds from which to fashion new recreational stimulants, Dr. Kroll noted that rendering synthetic drugs illegal can sometimes play havoc with efforts to develop the same drugs for therapeutic purposes. “If these precursors become more strictly regulated, there might be an untoward effect on the prices of other drugs” that use the same compound as a building block, he said.

                                                               New Players

Drug lab seizures in Jordan, Syria, and the United Arab Emirates have also reached new highs—particularly the clandestine manufacture of a form of amphetamine called phenethylline, marketed under the brand name Captagon. Very little in the way of equipment or startup capital is required, which facilitates new players in this market. Captagon, said Dr. Kroll, “makes pretty good sense. The body can metabolize it to amphetamine itself—it’s an amphetamine pro-drug. The other metabolite of the drug is theophylline, the old asthma drug that also acts as a mild stimulant. But it’s potentially as dangerous as amphetamine, depending on how efficient one’s metabolism is.” This is, of course, a huge problem: One bath salts user might have an acceptable drug experience, while another might find that a few whiffs of the same synthetic stimulant will land him or her in the emergency room, with a dangerously elevated heart rate or other complications.

What drug designers, drug manufacturers, and drug suppliers have come to realize is that methamphetamine and other ATS drugs appear to fill the lifestyle void left by the uncertain supply and pricing situation associated with cocaine. Everywhere they land, synthetic stimulants—from biker crank to mephedrone—wreak instant havoc. They simply are not predictable compounds. One bath salts user compared the experience to “a shot of methamphetamine with a PCP chaser." From any kind of rational sociocultural point of view, these are not safe drugs. And it hardly needs repeating that they are highly addictive for many people. The legalization of amphetamine is not a cause likely to gain much momentum any time soon.

Even though the United States has a long history of dealing with amphetamine, this is manifestly not true of every country in the world. And now these untapped markets are fair game for cheaper, longer lasting amphetamine-type stimulants, which “seem to appeal to the needs of today’s societies and have become part of what is perceived to be a modern and dynamic lifestyle,” according to the UNODC report.

We don’t know with complete certainty that the drug data coming out of several key areas—Southeast Asia, Africa, and the Middle East in particular—is accurate. Authorities have captured and dismantled ATS labs in Central and South America as well. In all likelihood, drug production and use in all these regions is underreported. The UNODC document laments that “household and other surveys are lacking or are outdated in some countries in several of the most affected regions.” This is a particular problem in China and India, where no serious national survey of amphetamine-type stimulants has ever been undertaken.

We have a long way to go before we know the outcome of the current craze for synthetic stimulants. The historical wreckage caused by injected methedrine in the 60s and 70s, and smokable ice in the 90s and the aughts, is a grisly matter of public record. Now we are confronted with a baffling cornucopia of designer concoctions whose track record for safe recreation is, thus far, not so good. Amphetamine drugs have sent thousands to their deaths, and countless others to the emergency rooms. And now this deadly deck of stimulants has many more cards in it than it did just a few years ago. Pick a card, any card. First one’s free.

Photo Credit: http://teens.drugabuse.gov/

Bath Salts, Graphically

What you need to know about mephedrone.

The Pat Moore Foundation has put together this nifty chart as a primer on mephedrone, the amphetamine-type stimulant marketed as "bath salts." Thanks PMF! 

 Created by Pat Moore Foundation

Khat to the Chase

Of mephedrone, bath salts, and impaired driving.

 Automobile accidents are the ninth leading cause of death worlwide, according to the World Health Organization (WHO). More than a million people are killed on roads annually, and that number could rise to 2.5 million by 2020. WHO estimates that traffic accidents cost developing countries an astonishing 1-2 % of their gross domestic product (GDP).

For years now, police and public health officials have puzzled over the alarming number of traffic accidents in East Africa. In terms of sheer numbers, Asian countries have the highest total traffic fatalities, according to figures compiled by the Global Road Safety Partnership (GRSP), a consortium including the World Bank, the Red Cross and other aid agencies (PDF HERE). That is not surprising, since these nations contain the majority of the world’s drivers.

However, beyond the picture of traffic fatalities in terms of sheer numbers, or on a per population basis, there is another revealing measure—traffic deaths per motor vehicle. And when the GRSP measured nations by that yardstick, the four worst countries in the world for traffic deaths—judging by the number of fatalities per 10,000 licensed vehicles—were Ethiopia, Tanzania, Lesotho, and Kenya—all East African nations.

Moreover, these are all African countries in which the use of khat--an amphetamine-like plant drug that is the natural precursor of the designer drug known as mephedrone--is legal and common. The major khat-using countries in Africa are commonly listed as: Somalia, Kenya, Yemen, Ethiopa, Tanzania, Lesotho. Note the overlap. Khat, as one online article put it, is “the legal high of east Africa.”

On the tiny island nation of Mauritius, just off the southeast African coast, Touria Prayag writes at allAfrica.com that drivers “zoom past you, zigzag on the roads, nervously changing to the left lane to swiftly veer back on your side without any warning…. brazenly flouting the Highway Code in every imaginable dangerous manner…. And the carnage continues….”

In Ethiopia, annual road crash fatalities account for 114 deaths per 10,000 vehicles, compared to one death per 10,000 vehicles in Great Britain, and an average of 60 deaths per 10,000 vehicles across 39 sub-Saharan African countries. A report in the Bulletin of the World Health Organization (PDF HERE)  notes that Ethiopian truck drivers “are regarded as so dangerous that their trucks are commonly referred to across Ethiopia as ‘al Qaeda.’” Anecdotally, Ethiopians told WHO officials that khat “increased driver confidence and vehicle speed while also making drivers irritable and impairing concentration,” and that high levels of khat could lead to hallucinations.

A Kenya forum on TripAdvisor asks: Are matatus [local taxes piloted by khat-chewing Kenyans] safe?” 

Since khat is legally available in most of East Africa, and comprises a significant part of the social fabric of local cultures, the use of khat is similar to the use of alcohol in higher-income nations. But does khat present the same threat of driving impairment as alcohol? Bolivia is now arguing its right to allow citizens to chew coca leaves in the traditional manner. Is it safe to drive and chew coca leaves? In all of these cases, the challenge is to determine what constitutes a “safe” dose of the drug; a dose that does not endanger people on or near the highway. There is not enough research on khat to answer that question. Nor is there a way to administer roadside tests for khat. The best evidence, African police officers say, is green teeth.

The active ingredients in khat—cathine and cathinone—are similar in structure to amphetamines, and chemically similar to the ingredients used in the manufacture of mephedrone powder. Mephedrone is sold as 4-MMC, Meow Meow, M-Cat, and other nicknames. Cathine and cathinone ramp up dopamine, serotonin and noradrenaline levels in a manner very similar to amphetamine, with many of the same positive effects (mild euphoria, reduced hunger, increased energy) and the same negative effects (depression, fatigue, lack of appetite, drug craving). It is thought that chronic use of khat results in dopamine D2 depletion in areas of the brain involved in goal-directed action.

The current fervor over mephedrone being disguised as bath salts or plant food for black market sales purposes in the U.S and U.K. demonstrates that this question is not academic for developed western nations. Sold as Ivory Wave, or Bliss, or White Lightning, mephedrone and other products containing cathinone are increasingly available across the U.S. states. In 2008, police seized 600 pounds of fresh khat—in Fargo, North Dakota.

A recent paper published in Frontiers in Psychology, authored by a group of Dutch and Spanish psychologists, appears to show that khat users exhibit a specific cognitive deficit: On stop-signal tasks, stop signal reaction time (SSRT) was significantly slower for the khat users. Such tests typically involve rapidly pressing a green “go” button upon seeing an arrow in certain positions, or abruptly aborting the response when the arrow turns red. The test measures “individual ability to stop a planned or ongoing motor response in a voluntary fashion.” For example, someone with Parkinson’s disease would score at the very high end of the SSRT scale.

The study itself involved 20 regular khat users recruited from the immigrant populations of Leiden and The Hague, and matched against 20 khat-free controls. All of the khat users met four or more of the 7 DSM-IV criteria for addiction, and did not consume alcohol the night before the test. The investigators speculate that this reduced level of inhibitory control “may even be involved in the emergence of addiction: the more a drug is used, the less able users are to prevent themselves from using it.”

The parallels to traffic signals and stop signs are obvious, and apt. The authors state that the findings of their study are “rather worrying because, first, many real-life situations require active inhibition of prepotent actions, as in the case of traffic lights turning red, or of criminal actions.” The obvious conclusion is that the chronic chewing of khat leaves “may indeed lead to a marked deterioration of cognitive functions (as inhibitory control) implicated in driving behavior.” Studies by NIDA director Nora Volkow and others have show that cocaine users suffer similar reductions in dopamine D2 receptors and “need significantly more time to inhibit responses to stop signals than non-users.” In general, stimulant drugs taken regularly at high doses appear to disrupt response inhibition due to alterations in dopamine functioning. (Although some studies have shown a facilitation of inhibitory control at lower doses).

The usual caveats apply: It is impossible to rule out pre-existing propensities for impulsivity, disinhibition, and the like. Some health researchers do not agree that the case for driving impairment on khat has yet been made. In the Bulletin of the World Health Organization, Anita Feigin of the Centre for Population Health in Australia writes that, so far, much of the information is anecdotal, “and, as yet, there is no clear evidence of a causal relationship between the use of khat and traffic accidents.” African taxi drivers who immigrate to Australia use khat “to stay awake and alert.” However, Feigin notes that the use of khat has deeply divided the members of east African migrant communities.

It is an interesting conundrum. The developed West has its entrenched tradition of alcohol as a legal high, despite its side-effects, which frequently result in mayhem on the highways. On the other hand, the drinking nations must now contend with demands from other cultures for the decriminalization of khat and coca leaf, which, along with coffee and tea, make up a category we might call the “soft” stimulants.

Because of the connection with mephedrone and other amphetamine-like designer drugs, these questions will not be going away until more research provides some solid answers. Such research may not be long in coming: The NIH-funded Khat Research Program (KRP) at the University of Minnesota, for example, brings American researchers together with a broad group of scientists from Yemenese and German universities to study the effects of a common plant drug most Americans have never heard of—but a drug they may be dealing with in synthetic form sooner rather than later.

Colzato, L., Ruiz, M., van den Wildenberg, W., Bajo, M., & Hommel, B. (2011). Long-Term Effects of Chronic Khat Use: Impaired Inhibitory Control Frontiers in Psychology, 1 DOI: 10.3389/fpsyg.2010.00219


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