Million plus in Europe’s 60s generation of ageing drug addicts, report finds

122,000 heroin and crack users aged 35-64 in Britain

More older people than ever are experiencing problems with drug addiction. Photograph: Lester Lefkowitz/Corbis

Keith Richards and Ozzy Osbourne may now be clean, but there are a hidden generation of ageing heroin users in their 50s and 60s who have not been able to kick the habit.

The European drugs agency say there are more than a million problem drug users aged over 40 across the EU, including 122,000 in Britain, who dent the widely held perception that drug use is a youth phenomenon.

„In reality, more older people than ever are reporting experience with drugs at some point in their lives and drug problems have no age limits,“ said the annual report of the European monitoring centre for drugs and drug addiction, published today.

The agency says about a million people across Europe aged 45 to 64 have used cannabis alone in the last year. While they have not „matured out“ of drug use, this is far below levels in the US where nearly 10% of the 50 to 59 age group — the 60s generation — regularly use cannabis.

There is a further group of nearly a million older problem drug users, including 122,000 in Britain aged between 35 and 64 who use heroin and crack, who first became dependent in the 1980s and 1990s. Many have tried detox and methadone substitution but have not managed to stop.

Wolfgang Götz, director of the agency, said that while the Rolling Stone, Keith Richards, says he is clean, many older drug users face a life of repeated overdoses with chronic health implications. They are prematurely experiencing the health problems faced by people 20 years older. Denmark and Germany are among countries developing specialist nursing or retirement homes for older drug users .

source: http://www.guardian.co.uk/society/2010/nov/10/europe-heroin-users-ageing

How Juárez became the world’s deadliest city

In April 2007 Ciudad Juárez—the sprawling Mexican border city girding El Paso, Texas—won a Foreign Direct Investment magazine award for “North American large cities of the future.” With an automotive workforce rivaling Detroit’s and hundreds of export-processing plants, businesses in Juárez employed 250,000 factory workers, and were responsible for nearly one-fifth of the value of U.S.-Mexican trade. The trans-border region of 2.4 million people had one of the hemisphere’s highest growth rates.

Just three years later, as many as 125,000 factory jobs and 400,000 residents have vanished. More than ten thousand small businesses have closed, and vast stretches of residential and commercial areas are abandoned. It is no surprise that the Great Recession temporarily shuttered factories and forced layoffs in a city intimately tied to American consumers. Mexico’s economy contracted by 5.6 percent in 2009, far worse than the United States’s “negative growth” of about 2 percent.

But Juárez has suffered from much more than recession. Its murder rate now makes it the deadliest city in the world, including cities in countries at war with foreign enemies. On average, there are more than seven homicides each day, many in broad daylight. Some 10,000 combat-ready federal forces are now stationed in Juárez; their armored vehicles roll up and down the same arteries as semis tightly packed with HDTVs bound for the United States. Factory managers wake up in El Paso—one of the safest U.S. cities—and go to work in the plants of a city bathed in blood.

To Americans the most notable killing was the March assassination of a U.S. consular employee and her husband on their way home from a child’s birthday party. Witnesses say their car was chased down a boulevard that once symbolized peace between the United States and Mexico and mutual prosperity. It rammed a curb within yards of the bridge to El Paso. Though the killing took place practically under the noses of armed forces stationed in the highly sensitive area, just a few bullet casings were recovered from the scene, indicating that the executioners took their time to clean up and cover their tracks.

Three weeks later the army arrested the alleged killer—a member of a gang aligned with the Juárez Cartel—but almost no one believes this crime will ever be “solved.” And with good reason. In recent years less than 2 percent of Mexican homicide cases have concluded with the sentencing of the perpetrator. In Juárez alone, there are some 200 unidentified corpses dating back to January 2008. As of June 2010 Juárez is in its 30th month of open warfare.

Can Juárez be saved? Will the factories reopen, as they have after past economic downturns, or is the city too dangerous for the business of making legal consumer goods? The economic questions are, perhaps, beside the point. For even if legal manufacturing returns, salvation may remain a distant goal. The economic model—low-wage export-oriented assembly—that investors celebrated also helped Juárez become the illegal narcotics capital of the Western hemisphere, perhaps indelibly.

A tale of two cities
I first got to know Juárez during the 1990s, when I lived and worked there as a graduate student in anthropology. It was exciting then: Juárez was at the heart of debate over the North American Free Trade Agreement (NAFTA). Coming fast on the heels of the Soviet collapse in 1989, NAFTA launched the current era of globalization. In Juárez I had a front-row seat for the unfolding of free trade.

It was a place of head-spinning extremes—gleaming high-tech industrial parks ringed by worker slums. One of the world’s most profitable Walmarts sat within view of settlements without decent water, sewers, or paved roads. Amid the inequalities, however, ordinary, middle-class Juarenses were enthusiastic about their city’s future.
I recently returned to Juárez and was unprepared for the city’s shocking transformation. Friends cautioned against crossing the border. Some had closed their businesses there, or had moved their families north. A few warily ventured into Juárez, but they always hurried back to the United States before dark. For the first time, I heard the once-optimistic Juarenses lament their city.

The economic model that investors celebrated helped Juárez to become the illegal narcotics capital of the Western Hemisphere.
Some see the roots of Juárez’s violence in its recovery from the Mexican Revolution, which ravaged what was in the 1910s and ’20s a frontier town. Certainly part of the city’s personality—and maybe its pathology—can be traced to that period.

Like its booming neighbor to the north, it needed schools, libraries, and hospitals. Instead it got bars and whorehouses. Because of Prohibition, El Pasoans had to find their entertainment across the border, in the richly appointed American-owned casinos and nightclubs. Juárez of the 1920s was like Las Vegas of the 1950s: elegant, exotic, uninhibited.
Older Juarenses speak of the post-Revolution city as if it were two: by day Juárez was a quiet Mexican town modeling itself on the progress it saw in the United States. At night it morphed into a world of exported vice and carnal pleasure. The growth of Fort Bliss during World War II and El Paso’s lingering blue laws reinforced that split personality.

In the late 1960s an experiment in export-oriented manufacturing seemed to give Juárez-by-day the upper hand. Under an agreement between the U.S. and Mexican governments, American firms set up shop across the border and imported materials duty-free from the United States. The companies employed Mexican labor to transform those materials into finished goods for export back, also duty-free. The firms, called maquilas by the locals, found favorable conditions: third-world wages, a government that promoted unionization in name only, and no oversight of the treatment of manufacturing byproducts. Moreover, maquila managers could work “overseas” during the day, and return home at night, thereby avoiding Mexican poverty, environmental problems, and crime. Success begets competition. The trickle of U.S. firms that abandoned their costly Midwestern labor forces became a torrent in the 1980s.

But while Juárez-by-day had triumphed for the time being, Juárez-by-night had not been tamed completely. Factory managers loved their assignments: they enjoyed the comfort and security of their El Paso homes, and, when they wanted, the thrill of Juárez nightlife, including the venues that everyone suspected were fronts for drug money.

Global change comes home
In the summer of 1992, during my first visit to Juárez, a change was snaking its way through the city’s impoverished working-class settlements. Deteriorating rural economic conditions, together with relatively high maquila wages (typically $5-7 a day) prompted a huge immigration to Juárez. The steady stream of potential workers—more than a hundred new residents arrived each day in the 1990s—kept wages down and the costs of housing and services up. Despite their improved conditions, then, workers could enjoy few benefits from their labor. They struggled to meet basic needs, including fees for schooling that would qualify their children for factory work once they were old enough to earn a living.

All the families I met relied on at least one factory salary. But there were plenty of unemployed, too. Mostly young men, these idlers were the right age to be working or in school, but instead they hung around wearing baggy Dickie pants, hair nets, and other insignia of cholo (gang) affiliation. My research assistant, a former Catholic catechist, taught me to recognize and steer clear of the real cholos, who were dangerous, and to salute and acknowledge the others, who were just posing.

The settlements blanketing the steep ravines of the mountains surrounding the city’s center had no infrastructure to speak of, but they did have corners. And boys hung out on those corners day and night. They huddled on their haunches in winter and they lolled in whatever shade they could find in summer. They were guarding turf; they menaced the school kids and factory workers forced to cross their paths, sometimes beating them bloody.

Some idlers were getting high, though not from illegal narcotics. Rather, they mined stolen factory materials—paint thinner, acetone, and buckets of solvent-soaked rags used to wipe down finished televisions. They would distribute “sniffs” to their neighborhood buddies.

But in the mid-1990s life for these young men began to take on another character. A friend who worked in drug treatment told me that she and her co-workers were scrambling to identify new addictions, as banned drugs supplanted the inhalants.

On a 1996 tour of settlements, my friend showed me some of the places where dealers had set up shop. They were not selling injectable narcotics—a syringe was an extravagance in these desperately poor communities—but drugs that could be consumed directly. She spoke of pills, though their identification was elusive. These small retail outlets laid the groundwork for the harder stuff that would soon follow. Over time I realized what the idle kids were up to. They were working, perhaps earning only pennies, for the new dealers.

My observations in Juárez reflected a shift in global drug markets that began far from the city. As globalization of manufacturing ramped up in the 1980s, it did so in parallel with dramatic changes in the production, distribution, and consumption of illegal narcotics. In the early ’90s the global pressures that disrupted the trade routes for cocaine that ran from Andean jungles to U.S. consumer markets converged on Juárez.

This was not obvious then. The local change that seemed most consequential for Mexico’s future was the 1992 election of an opposition party member as mayor of Juárez. Francisco Villarreal Torres, owner of a small chain of house-ware stores and a political outsider, campaigned on promises of good governance and clean conduct. His election proved the viability of the National Action Party (PAN), which went on to win the 2000 presidential election, thereby ending 70 years of one-party rule.

Villarreal’s true rival once he took office was not his political opponent, but Amado Carrillo Fuentes, the subordinate, rival, and successor of famed rural drug lord Pablo Acosta, who died in a 1987 shoot-out with Mexican and U.S. forces. Carillo Fuentes moved operations from the sparsely populated Big Bend region of Texas to Juárez, a relocation that mirrored and exploited the globalization-driven economic success of Juárez.

Acosta’s business had focused on smuggling Mexican pot and heroin across the border to U.S. buyers. Distribution was in the hands of informal dealer networks, from which, reportedly, Acosta only infrequently took a direct cut. With two significant changes to Acosta’s business model, Carrillo Fuentes would turn cocaine into the cornerstone of a multinational, vertically integrated enterprise with diversified products stretching from the Andes (and other source sites) to United States (and other) markets.

In the past, Colombians had used Mexican marijuana smugglers to transport only a small portion of their merchandise; the main trafficking routes wound through the Caribbean. By some estimates, cocaine importation and money laundering accounted for a third of Miami’s economic activity in the 1980s. But the 1993 killing of Pablo Escobar decapitated the Medellín Cartel, and, beginning in 1991, the Cali Cartel was weakened by seizures and arrests (though its leaders remained at large until 1995). When the U.S. Department of Justice began to seize Miami bank assets and prosecute the Colombian traffickers’ lawyers, the Mexican cocaine trade picked up pace and volume.

Trafficking drugs is effectively a licensed affair, the exclusive and protected rights to which are controlled by the military and the police.
Seeing his opening, Carrillo Fuentes shifted from bagman to distributor—the first of his two innovations. He also took advantage of another vacuum: in the years prior to his rise, the prosecutorial assault on crack-cocaine in the United States had jailed and killed thousands of street-level dealers and their bosses. Carrillo Fuentes filled that void with his own retail agents in U.S. cities.

Like any vendor, Carrillo Fuentes looked for new markets and new products. And like transnational firms that sprawled across the city, he saw a business opportunity in the booming factory-worker population of Juárez. His second innovation—perhaps the single action most responsible for the rise in violence—was to call an end to drug traffickers’ long-standing voluntary prohibition against local sales.

Local-market development began modestly enough. Sometime in 1990 or 1991—before the Colombian cartels had ceded their supremacy—residents in a handful of Juárez’s scrappy, tar-paper-and-adobe settlements found their first samples of a narcotic previously limited to export markets: cocaine. It was neither pure nor of high quality—cut several times with talc and baking powder—but it was coke, for the first time, for the Mexican masses.

Gustavo de la Rosa Hickerson, long-time human rights attorney and director of the city’s prison from 1995 until 1998, described to me the explosion of tienditas, retail drug outlets. According to de la Rosa, in 1990 there were fewer than 50 neighborhood dealers. By 1995 the number had climbed to 300. The current estimate exceeds 1,000. Some of these tienditas are distribution centers, employing as many as 50 roving peddlers. And the city is now saturated with dealer-addicts, the “fivers” who sell just enough (about five hits) to cover the costs of their own high. Charles Bowden, in his new book Murder City, estimates that as many as 25,000 Juarenses may be involved in petty drug sales. At the height of the Great Recession, that meant one drug dealer for every four or five employed factory workers.

But this explosion of corner dealers was not responsible for the city’s dramatic transformation. That change came with the system of dealer protection. Each corner dealer works not only under an officer in the cartel, but in tandem with a beat cop. The cop protects the dealer and his gang against encroachments by other neighborhood gangs. The tiendita system is thus a logical extension of the rules of the Mexican drug “plaza,” the long-established formal arrangement between traffickers and security forces.

When foreigners talk about the Mexican drug business and the drug war, they talk about cartels carving up territory among each other and then going after each other’s turf. Mexicans, by contrast, begin with the plaza, a government concession sold to a preferred bidder. Trafficking drugs is effectively a licensed affair, the exclusive and protected rights to which are controlled by the military and the police.

In the tiendita system, it is not only locally “licensed” dealers who send their earnings up the chain of command. Beat cops, too, pay their supervisors and commanders. Hence the Juárez name for what the Drug Enforcement Administration (DEA) calls the “Juárez Cartel”: la línea—“police line.”

Chronically underpaid Mexican police traditionally have made their living livable with bribes—the famous mordita (“bite”). But historically they did not defend violently their right to bite. Street drugs changed that. De la Rosa told me that in the mid-1990s, only two of the city’s then-estimated 500 gangs were known to be armed. Now, 80 percent of them are.

The violence intensifies
This local retail model was highly successful, and it quickly became the industry standard. By 1997 it was dispersed widely across the industrial north. Carrillo Fuentes had risen in seven years to become Mexico’s wealthiest and most powerful drug trafficker, with a fortune estimated at $25 billion. His “assets” included General José de Jesús Gutiérrez Rebollo, the Mexican drug czar. In February 1997, just weeks after his appointment to the job, an investigation revealed that he had been on the Cartel’s payroll. Carrillo Fuentes also bought shares in a Mexican bank, a move that helped simplify his money laundering efforts.

When Carrillo Fuentes died while undergoing plastic surgery that summer, a violent power struggle predictably followed. But by today’s standards it was mild: a mere 72 deaths over eight months. Now, about a hundred are killed every two weeks in Juárez.

The narcoguerra following Carrillo Fuentes’s death introduced Juárez to “message killings”: bodies tortured, dismembered, and stuffed into boxes, car trunks, and barrels. Also new and shocking were the open-air executions: gangland-style killings at jam-packed restaurants. At the time, such crimes were rare enough that the media could follow them up and report on their continued lack of resolution.

The battle for succession remained mostly isolated to the top command in both the Cartel and the police (the probable first victim of that narcoguerra was a high-ranking federal police officer, killed by commandos just four days after Carrillo Fuentes’s botched surgery). With the confirmation of new leadership—Amado Carrillo Fuentes’s younger brother Vicente, according to conventional wisdom—the killing abated. But it never went away. And it never went back underground. Restaurants and bars became safe again, but killings continued in the neighborhoods where tienditas had taken root. There, factory workers lived tensely with the growing groups of tough, largely unemployed men and boys who moved constantly in and out of alliance with the more organized gangs.
There are 6,600 gun shops in the four U.S. border states. Of the 11,000 guns turned over to the ATF in 2009, almost 90 percent were traced to U.S. gun shops.

Meanwhile the city continued to gorge on the profits of local and international narcotics sales. Though few admitted it, everyone knew how the gaudy houses that popped up in the old moneyed enclaves were financed. Ditto the origins of the flashy princesses who began to grace the newspapers’ society pages. City elites chose to overlook the excesses of the trafficking business. “We tolerated the narco,” an upper–middle class friend recently told me. “That was our mistake.” I asked her why conventional, conservative-Catholic Juárez put up with the traffickers. “Look at all those businesses up and down the Avenida de las Americas,” she said, “it’s all money laundering. But it gave us restaurants to enjoy and boutiques to shop in.”

The price of permissiveness grew increasingly steep. In 1993 a no-nonsense retired accountant named Esther Chavez Cano noticed routine newspaper stories on the discovery of female corpses. The details were gruesome: some were found tortured and raped, almost all were tossed to the side of a road, as if they were litter. Chavez Cano began a newspaper column in which she demanded action and accountability. Her writing campaign soon launched a social movement that garnered international attention for the same city that was then proudly boasting of its manufacturing triumphs. She and those she inspired tallied 427 women dead or disappeared between 1993 and 2007, an undeniable symptom of the city’s violent alter ego.

But these horrific killings of young women eclipsed a more prosaic body count: that of the men who turned up dead all over the city with increasing regularity. It is easy enough to see how the murdered girls and women focused the world’s attention on Juárez’s perverse, misogynistic, and violent appetites. Nonetheless, for every publicized female corpse there are ten overlooked male counterparts, according to government data. Whatever the explanation for the high numbers of women killed, the one incontestable fact is that the killing of both women and men began in earnest the very year that the DEA says cocaine trafficking shifted from Miami to Juárez. This was not a coincidence.

The world’s deadliest city
I moved away from the border in 1999 but returned to visit in 2001. I caught up with two friends, also academics, who had been raised in the city’s toughest neighborhoods. We met at a cute bar on the corner of Avenida de las Americas and Avenida Lincoln. It was the kind of place then multiplying around town: refrigerated air, an impressive sound system, and swanky drinks. It shared a parking lot with a California-style sushi bar that in 1997 had been the site of the dinnertime execution of a businessman with suspected drug ties.

We talked about cholos. “Today’s cholo is different,” one of my friends remarked. “Yesterday’s cholo used to compete with merely his attitude, his fashion, and his posture. If the cholos really needed to fight, they fought with what they had available: rocks, stones. And then they got knives. But now some of them have guns.” Today, “some” would be “nearly all,” but as recently as 2001, guns were rare.

That summer I took pictures of a sixteen-year-old boy. He sported a bandana and an oversized tee shirt depicting the Virgin of Guadalupe and his initials in Gothic letters. He smiled so sweetly and eagerly that he hardly looked tough in his portrait. He and his mother beamed when I brought them copies. She surprised me with the pride she took in her son’s apparent cholo ambitions. I had never met such a parent.

That summer I was also surprised by what seemed to me an astronomical increase in the number of kids just hanging out, guarding turf on corners. Neighborhood toughs were now everywhere. And they belonged to a bewildering array of ranked groups, mysteriously nested within hierarchies that most of the teenagers I talked to only vaguely understood.

In 2001 I could see that what was once isolated in the bars and nightclubs and conducted its affairs after hours, had woken up to business in the daytime and set up shop close to home. The gap between Juárez-by-day and Juárez-by-night was narrowing to a sliver.

Today, the sliver has vanished. The Juárez Cartel and its rival, the Sinaloa Cartel, fight each other in the streets, and Mexican federal forces allegedly fight the traffickers. Rumor has it that a third trafficking organization, the Zetas, may have entered the market.

In any case, the violence escalates. There were many milestones along the way: 1993, the year that femicide was first recorded, the year when Amado Carrillo Fuentes reportedly assumed sole leadership of the Juárez Cartel; 1997, the escalation of violence after his death; 2000, when, with considerable fanfare, the FBI announced its mission to Juárez to locate the rumored remains of as many as a hundred victims buried in narcofosas, “drug graves” (only four bodies were found). Also crucial was 2004. That year, the United States lifted its ban on assault weapons, making it that much easier for traffickers to obtain their arms of choice. There are 6,600 gun shops in the four U.S. border states. Of the 11,000 guns turned over to the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF) by Mexican forces in 2009, almost 90 percent were traced to U.S. gun shops.
Homicides in Juárez nearly doubled from 123 to 234 between 1993 and 1994. The rate stabilized for the next dozen plus years, dipping in some, ranging from a low of 176 in 1999 to a high of 294 in 1995. The 2007 spike to 316 murders generated much year-end hand-wringing, but within a month 2007 appeared to be the calm before the storm. Violence exploded in January of 2008, with 46 killings. The total for February was 49. And in March, when President Felipe Calderón deployed thousands of troops to secure the city, the murder count doubled to 117. Now it rarely dips below those levels. One hundred deaths in a month would be considered a respite. May 2010 saw 253.

Mexicans, schooled in the reality of the drug business, find it hard to believe that security forces can fight traffickers. The two groups are indistinguishable.

The familiar explanation for the spasm of violence that has seized Juárez since January 2008 starts with Calderón’s vow upon taking office two years earlier to rid Mexico of all traffickers and his rapid deployment of troops to cartel hot spots. But almost from the start, skeptical observers have suggested that Calderón’s forces appear to be routing all traffickers but one: the powerful Sinaloa Cartel, headed by Joaquín Guzmán Loera, a.k.a. El Chapo (“shorty”). For Mexicans, schooled in the reality of the plaza, it is hard to believe that security forces can fight traffickers; they are, as one journalist put it to me recently in an email, indistinguishable from each other.

Consider the evidence that Mexicans never forget or overlook: shortly after President Carlos Salinas left office in 1994, his older brother’s wife was caught using a fake passport to withdraw more than $80,000,000 from a Swiss bank, part of the fortune her husband somehow managed to amass while working as a government bureaucrat. The disgraced ex-president fled into self-imposed exile in Ireland, a country that has no extradition treaty with Mexico.

His successor, Ernesto Zedillo, declared a U.S.-style war on drugs and then appointed Gutiérrez Rebollo as his drug czar, only to find that Carrillo Fuentes was paying Gutiérrez Rebollo his monthly rent for a national concession.

Even the first opposition president in Mexico’s modern history is not free of suspicion. Shortly after Vicente Fox’s election in 2000, he spent a weekend at the private Cancun retreat of Roberto Hernández Ramírez, CEO of Banamex (Mexico’s second-largest bank) and alleged drug trafficker.
None of this explains the extent of Juárez’s homicidal violence. One major difference between 1997 and 2008, as Gustavo de la Rosa Hickerson pointed out, is that the current war is being fought at every level of the trade, down to the street-level vendor and his protection and tribute network. As Charles Bowden puts it, this is not a war against drugs, it is a war for drugs. One related theory put forward by veteran observer Bill Conroy of Narco News is that the army moved into Juárez to take the concessionaire role away from the police.

The story of the two cities of Juárez thus applies to the entire country: what started in Juárez has become Mexico. The attempt to cripple the drug business in Juárez has meant crippling the city; doing the same in Mexico at large may mean crippling the nation.

Innocent victims
President Calderón has sought to make his drug war palatable by asserting that the country’s war dead—estimated at 23,000 since January 2006 for the country as a whole—deserved to die: their deaths implicate them in illegal activities.

When he first learned about what Juarenses have come to call the “massacre at Villas de Salvarcar,” Calderón hinted that the thirteen teenagers who died at the hands of professional executioners were common criminals and city low life. He could not have been more wrong. In fact they were honor students and athletes who had gathered to celebrate a friend’s seventeenth birthday. They had the misfortune of belonging to a football club whose initials, “AA,” were mistaken for the initials of the Sinaloa cartel’s local enforcers, the Artistic Assassins. And so, in the middle of the night, while the teens danced in a room cleared of furniture, they were gunned down. Seven hours later, when the first daylight photos were taken, the concrete floor where they died still glistened with their clotting blood.

The escalating war over the Juárez plaza coincided with a particularly unpleasant moment in the global market system—in the midst of massive factory layoffs prompted by the economic downtown beginning in 2007. Locals easily grasp that little of the current day-to-day violence in Juárez has much, directly, to do with any cartel. Look at who dies with grim regularity: a gang of teenage car thieves, a group of former cholos who opened a funeral home, a guy pilfering doors from an abandoned neighboring house. Not all victims are entirely innocent—the city is filled with scrappy, hard-working men and women, some of whom have turned to Juárez-by-night for survival now that Juárez-by-day has so little to offer them—but they are not drug dealers or corrupt police, either.
Accommodating the drug business has become a shockingly ordinary part of life. Working-class parents ask few questions when their studious daughters and sons lose factory jobs while their wayward siblings provide the household’s only income.

In February I spent a day with the director of a nonprofit day-care organization as she visited centers her group helped to launch. The owner of one home-based establishment related with good cheer being confronted by a nicely dressed middle-aged couple and their armed bodyguard. They advised her to start paying a $1,000-per-month protection fee. She and her family went into hiding for a few weeks before they reopened—quietly, and with great trepidation. The director laughed when I asked which cartel the extortionists work for. “People like that don’t work for anybody,” she replied. “They extort for a living because no one stops them!” The couple had shaken down the entire block of small family-owned businesses. Little matter that across the street stretched the vast army encampment, home to troops sent to end the city’s lawlessness.

Later my guide told me that Juarenses even have their own terms to distinguish between organized crime and opportunistic crime. The most common form of the latter is the secuestro express: a kidnapping that lasts no more than a few hours, just long enough to pressure a family to cough up an “affordable” ransom, but not long or expensive enough to attract the interests of enterprises that might want a cut.

Night falls
For decades, the maquilas’ critics longed for border businesses to be in control, rather than simply in service, of multinational capital. This is the irony of Carrillo Fuentes’s innovation: he became the Mexican-border trade baron who accomplished all that and more. His generation of traffickers adapted the maquila model to their own use by taking advantage of its infrastructure to move and market their products. No wonder Forbes recognized their achievements by including El Chapo Guzman in its 2010 list of global billionaires.

And what of the maquilas? The signs are not promising: in mid-January university researchers calculated industrial park vacancies at 14 percent—a historic high, up from an already-alarming 10 percent the year before. That month a Siemens customs manager was gunned down on his way to work. In October his subordinate had met her end after U.S. officials found drugs smuggled in a shipment. Mid-level staff are frequent targets, prompting some companies to consider extending their security measures beyond plant executives. It is probably just a matter of time before manufacturing firms move on.

What will be left of Juárez then? In El Paso, there are nightclubs, boutiques, fancy restaurants, and thriving industries. That city is growing in ways that seemed unimaginable even a decade ago. Even the mayor of Juárez has fled north of the border, and that was before he received a threat to his life in February—a severed pig’s head marked with his name.
Those who haven’t abandoned Juárez may be watching the death of it, both day and night.

source: http://bostonreview.net/BR35.4/hill.php

Western roots feed Afghan poppy scourge

For years, there has been much discussion about the best strategy to rid Afghanistan of its poppies. Eradication, said the George W Bush administration. Interdiction and alternative livelihoods, retorted the Barack Obama administration. Licensing and production for medicinal purposes, suggests the influential Senlis Council.

The issues have been fiercely debated: Would there be enough demand for Afghanistan’s legal morphine? Is the government too corrupt to implement this or that scheme? To what extent will eradication alienate farmers? Which crops should we substitute for poppies?

These questions are not unimportant, but fundamentally, they do not address the primary source of Afghan drug production: the
West’s (and Russia’s) insatiable demand for drugs.

Afghanistan accounts for about 90% of global illicit opium production. Western Europe and Russia are its two largest markets in terms of quantities consumed and market value (the United States is not an important market for Afghan opiates, importing the drugs from Latin America instead). Western Europe (26%) and Russia (21%) together consume almost half (47%) the heroin produced in the world, with four countries accounting for 60% of the European market: the United Kingdom, Italy, France and Germany.

In economic terms, the world’s opiates market is valued at $65 billion, of which heroin accounts for $55 billion. Nearly half of the overall opiate market value is accounted for by Europe (some $20 billion) and Russia ($13 billion). Iran is also a large consumer of opium, with smaller amounts of heroin. The situation is similar for cocaine, for which the US and Europe are the two dominant markets (virtually all coca cultivation takes place in Colombia, Peru and Bolivia).

In short, it is the West that has a drug problem, not producer countries like Afghanistan (or Colombia): demand is king and drives the global industry.

How should we reduce opiate consumption and its negative consequences in the West and Russia? Drug policy research has typically offered four methods. There is a wide consensus among researchers that such methods should be ranked as follows, from most to least effective: 1) treatment of addicts, 2) prevention, 3) enforcement, and 4) overseas operations in producer countries. For example, 12 established analysts reached the following conclusions, published a few months ago:

Efforts by wealthy countries to curtail cultivation of drug-producing plants in poor countries have not reduced aggregate drug supply or use in downstream markets, and probably never will … it will fail even if current efforts are multiplied many times over.

A substantial expansion of [treatment] services, particularly for people dependent on opiates, is likely to produce the broadest range of benefits … yet, most societies invest in these services at a low level.

Also, a widely cited 1994 RAND study concluded that targeting “source countries” is 23 times less cost effective than “treatment” for addicts domestically, the most effective method; “interdiction” was estimated to be 11 times less cost effective and “domestic enforcement” seven times. The problem is that the West’s drug policy strategy has for years emphasized enforcement, combined to overseas adventures, to the detriment of treatment and prevention. Also, Russia has been complaining about the suspension of eradication in Afghanistan, but it has a very poor record of offering treatment to its own addicts, rejecting widely accepted scientific evidence. Moscow has chosen a strategy that “serves the end of social control and enforcement,” just like the US: criminalization is emphasized and the largest share of public resources is directed to arrest, prosecute and incarcerate drug users, instead of offering them treatment. This worsens Russia’s HIV epidemic, the fastest growing in the world – with nearly one million HIV infections, some 80% of which related to the sharing of drug needles – while syringe availability remains very limited. For instance, methadone and buprenorphine remain prohibited by law in Russia, even if they are effective in reducing the drug problem by shifting addicts from illegal opiates to safer, legal alternatives. Accordingly, a just released New York University report states that “Nothing that happens in Afghanistan, for good or ill, would affect the Russian drug problem nearly as much as the adoption of methadone” in Russia – which would also help Afghanistan reduce poppy cultivation. Obama announced last year that the US would have access to seven military bases in Colombia under the pretext of fighting a war on terror and a war on drugs. Likewise, Russia recently announced that it would set up a second military base in Kyrgyzstan, to combat drug trafficking. Victor Ivanov, the Director of the Russian Federal Drug Control Service, explained how he was inspired by US drug war tactics in Latin America:

The United States‘ experience is certainly quite effective. The powerful flow of cocaine from Colombia into the United States prompted Washington to set up seven military bases in the Latin American nation in question. The US then used aircraft to destroy some 230,000 hectares of coca plantations … Russia suggests building its military base in Kyrgyzstan since it is the republic’s Osh region that is a center of sorts whence drugs are channeled throughout Central Asia.

Europe’s record on drug policy has improved over the last two decades, important advances having been made to bring harm reduction into the mainstream of drug policy, and rates of drug usage for each category of drugs are lower in the European Union (EU) than in states with a far more criminalized drug policy, such as the US, Canada and Australia. But there is still room for improvement. For example, although opioid substitution treatment and needle and syringe exchange programs now reach more addicts, “important differences between [European] countries continue to exist in scale and coverage”, a recent review of harm reduction policies in Europe concludes. In particular, “Overall provision of substitution treatment in the Baltic States and the central and south-east European regions, except in Slovenia, remains low despite some recent increases. An estimate from Estonia suggests that only 5% of heroin users in the four major urban centers are covered by substitution programs, and that this rate is as low as 1% at national level.“ Lack of funds is no excuse, as there is plenty of money available, for instance, out of the $300 billion Europeans spend every year on their militaries, to maintain among other things their more than 30,000 troops in Afghanistan. The UK was put in charge of counter-narcotics in Afghanistan. However, domestically, leading specialists Peter Reuter and Alex Stevens report that “Despite rhetorical commitments to the rebalancing of drug policy spending towards treatment… the bulk of public expenditure continues to be devoted to criminal justice measures… this emphasis on enforcement in drug control expenditures also holds for the most explicitly harm reduction-oriented country, the Netherlands.“ In the UK, over 1994-2005, “the number of prison cell years handed out in annual sentences has tripled“ (although significant increases have also been made towards treatment). “The prison population has increased rapidly in the past decade [and] the use of imprisonment has increased even more rapidly for drug offenders than other offenders… These increases have contributed significantly to the current prison overcrowding crisis.“ British enforcement costs taxpayers dearly, but the government does not regularly or publicly calculate those costs. Through a Freedom of Information request a document was released that “calculated the annual cost of enforcing drug laws – including police, probation, prison and court costs – at approximately ฃ2.19 billion, of which about ฃ581 million was spent on imprisoning drug offenders.“ All this said, there is one way in which Afghanistan does have a drug problem, namely, its increasing number of addicts. A recent report from the United Nations Office on Drugs and Crime (UNODC) estimated that drug use had increased dramatically over the last few years and that around one million Afghans now suffer from drug addiction, or 8% of the population – twice the global average. Since 2005, the number of regular opium users in Afghanistan has grown from 150,000 to 230,000 (a 53% increase) and for heroin, from 50,000 to 120,000 (a 140% increase). This spreads HIV/AIDS because most injecting drug users share needles. But treatment resources are very deficient. Only about 10% of addicts have ever received treatment, meaning that about 700,000 are left without it, which prompted UNODC chief Antonio Maria Costa to call for much greater resources for drug prevention and treatment in the country. The problem is that the Obama and Bush administrations could not care less: since 2005, the US has allocated less than $18 million to “demand reduction” activities in Afghanistan – less than 1% of the $2 billion they spent on eradication and interdiction. Clearly, US priorities have nothing to do with fighting a war on drugs.

source: http://www.atimes.com/atimes/South_Asia/LG01Df02.html

THE ORIGINS OF THE ENGLISH DRUG „SCENE“ 1890-1930

The drug subculture which developed as part of the rise in narcotic drug use in the
1960s has received much attention. Academic sociologists and the media found this, as
an area of deviant behaviour, a subject of considerable intellectual interest and also of
popular fascination. Drug taking as an alternative way of life, where, as Jock Young
puts it, „drug use is given a different meaning from that existing previously“, has
become part of the sociology of deviance. Issues such as the formation and role of the
altemative subculture, the social reaction against deviant drug use, and the particular
importance of the changing social class of drug takers as providing justification for a
moral response, have attracted attention. The transformation of the typical drug user
in the 1960s from a middle-class middle-aged female into a young working-class male
had, it is argued, much to do with the social reaction evoked, and the type of legal and
social controls put into effect.‘ In the 1980s, the link with unemployment has again
been stressed; and the reappearance of cocaine as a „smart“ drug has also provided
another source of sensationalism for the popular press. However, the widespread
assertion that drug taking has now become more „normal“ would seem to downgrade
the ’60s emphasis on drug use as a subcultural activity.2 Certainly, the „junkie“
stereotype is less prominent in media coverage.

Read more:medhist00064-0055

Morphine makes lasting — and surprising — change in the brain

Morphine, as little as a single dose, blocks the brain’s ability to strengthen connections at inhibitory synapses, according to new Brown University research published in Nature

The findings, uncovered in the laboratory of Brown scientist Julie Kauer, may help explain the origins of addiction in the brain. The research also supports a provocative new theory of addiction as a disease of learning and memory.

„We’ve added a new piece to the puzzle of how addictive drugs affect the brain,“ Kauer said. „We’ve shown here that morphine makes lasting changes in the brain by blocking a mechanism that’s believed to be the key to memory making. So these findings reinforce the notion that addiction is a form of pathological learning.“

Kauer, a professor in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown, is interested in how the brain stores information. Long-term potentiation, or LTP, is critical to this process.

In LTP, connections between neurons – called synapses, the major site of information exchange in the brain – become stronger after repeated stimulation. This increased synaptic strength is believed to be the cellular basis for memory.

In her experiments, Kauer found that LTP is blocked in the brains of rats given as little as a single dose of morphine. The drug’s impact was powerful: LTP continued to be blocked 24 hours later – long after the drug was out of the animal’s system.

„The persistence of the effect was stunning,“ Kauer said. „This is your brain on drugs.“

Kauer recorded the phenomenon in the ventral tegmental area, or VTA, a small section of the midbrain that is involved in the reward system that reinforces survival-boosting behaviors such as eating and sex – a reward system linked to addiction. The affected synapses, Kauer found, were those between inhibitory neurons and dopamine neurons. In a healthy brain, inhibitory cells would limit the release of dopamine, the „pleasure chemical“ that gets released by naturally rewarding experiences. Drugs of abuse, from alcohol to cocaine, also increase dopamine release.

So the net effect of morphine and other opioids, Kauer found, is that they boost the brain’s reward response. „It’s as if a brake were removed and dopamine cells start firing,“ she explained. „That activity, combined with other brain changes caused by the drugs, could increase vulnerability to addiction. The brain may, in fact, be learning to crave drugs.“

Kauer and her team not only recorded cellular changes caused by morphine but also molecular ones. In fact, the researchers pinpointed the very molecule that morphine disables – guanylate cyclase. This enzyme, or inhibitory neurons themselves, would be effective targets for drugs that prevent or treat addiction.

Pharmacist education in MMT.!, syringes,

Pharmacists have the unique knowledge, skills and responsibilities for assuming an important role in substance abuse prevention education and assistance…  Pharmacists, as health care providers, should be actively involved in reducing the negative effects that substance abuse has on society, health systems and the pharmacy profession.

— American Society of Health-System Pharmacists (2003)

Competency framework

Unless they have taken special training, most pharmacists are unaware of the clinical and practice issues surrounding methadone and their impact on client safety because they have had little or no exposure to them during their undergraduate pharmacy education.

The role of the pharmacist in MMT is unusual and there is no similar model in other therapeutic areas. Daily interactions with clients, along with direct clinical assessments, supervised dose administration and close monitoring do not usually occur in other types of pharmacy care. Pharmacists require a set of key competencies to ensure client safety in methadone maintenance treatment.

The panel recommends that:

15. Pharmacy managers/owners, hospital pharmacy directors and the Ontario College of Pharmacists support and encourage pharmacists providing methadone services to have education in and/or demonstrate knowledge and skills in core competency areas. These areas include:

a. Substance use disorders, including opioid dependence. [IV]

b. The varied models of substance abuse treatment, including harm reduction and its implications for pharmacy. [IV]

c. The impact of attitudes and stigma on client care. [III]

d. Methadone maintenance treatment clinical guidelines and their rationale, particularly with respect to practices to protect client safety, including:

• assessing initial and increased doses for appropriateness
• assessing methadone-dosing histories (for missed doses and irregularities in pattern of pickup) before dispensing a dose of methadone to a client
• ensuring the safe provision of “carries” (take-home doses) to clients
• dealing with intoxicated clients, including understanding the risks of polysubstance abuse. [IV]

Pharmacists need to understand substance use disorders, particularly addiction, and to understand the difference between “use” and “use disorders.” Pharmacists need to be able to identify individuals with substance use disorders and to help motivate them to seek change and treatment. As one of the most accessible health care professionals, the pharmacist can play an important role and refer patients to appropriate services and substance use treatment programs. Many MMT clients have concurrent substance use disorders with substances such as alcohol, benzodiazepines or cocaine. Pharmacists should understand the risks associated with polysubstance use and the risk of toxicity.

Although pharmacists may already be involved in harm reduction, for example, by providing sterile needles and syringes to people who use injection drugs, further involvement could include offering advice to people with substance use problems about health issues and how to minimize health risks. A random survey of 2,017 Canadian pharmacists by Myers et al. (1998) found that while more than 88 per cent of pharmacists were comfortable with the harm reduction role in providing needles and syringes, this comfort did not extend to providing methadone services. This may be due to a misunderstanding of the benefits of methadone maintenance treatment and its role as a harm reduction approach. Educational initiatives need to address such misunderstandings and other negative attitudes or misperceptions that may be held by pharmacists.

Pharmacists must have a good understanding of the critical safety issues associated with methadone. Methadone has a unique pharmacological profile that makes it useful in the treatment of opioid dependence; however, it is different from other opioids and the implications of its long half-life can lead to risks of accumulation contributing to methadone overdose and deaths.

The initiation phase of methadone treatment can be a time of high risk for toxicity and pharmacists’ understanding of dosing recommendations is critical at this stage. Pharmacists need to exercise particular vigilance in monitoring client dosing for appropriateness. For example, where clients have missed several doses (defined as three or more), or fewer (one or two) during periods of methadone dose escalation, pharmacists must understand the concept of loss of tolerance and risks to clients if the usual regular methadone dose is administered (CPSO, 2005).

Pharmacists also have to understand the safety issues associated with “carries.” Having a written carry agreement with the client is one way to help the client understand these issues as well. Pharmacists should be aware of some of the signs that indicate a formerly stable client on a high level of carries is relapsing to instability (e.g., missing observed dosing days, lost carries) (CPSO, 2005).

Pharmacists in Ontario need to be familiar with the CPSO’s most recent Methadone Maintenance Guidelines (2005), the OCP’s Policy for Dispensing Methadone (2006), and CAMH’s Methadone Maintenance: A Pharmacist’s Guide to Treatment (Isaac et al., 2004).

Understanding the risks of polysubstance use and knowing how to deal with intoxicated clients are particularly important core competency areas for pharmacists, with significant safety implications. The pharmacist should have an understanding of the impact that polysubstance use (for example, use of benzodiazepines, alcohol and cocaine) can have on the client taking MMT. Through dialogue and checking for signs of excessive dosing or substance use such as sedation, slurring of speech, smelling of alcohol and unsteady gait, the pharmacist should be able to assess if a client is intoxicated before dosing.

Recommendations from the coroner have highlighted the need for assessing clients for intoxication because deaths have occurred through combination of methadone and other drugs, including alcohol (OCP, 2008).

In an Australian survey (Peterson et al., 2007), pharmacists identified the risk of overdose associated with methadone alone and in combination with other psychoactive drugs as the greatest problematic issue for pharmacists in deciding to provide a methadone service.

In a survey of 148 pharmacists in Australia (Koutroulis et al., 2000), when asked about how they would respond to clients who presented intoxicated for their methadone dose, 44 per cent said they would withhold the dose and inform the client of this. This is the desirable course of action. However, 32 per cent of pharmacists said they would provide the usual dose, 16 per cent would dispense a reduced dose without the client knowing and nine per cent said they would blind the dose with a placebo. Only two per cent of the pharmacists indicated that they would breathalyse an intoxicated client.

Pharmacists who withheld the methadone dose were more likely to inform the prescriber (74 per cent) than pharmacists who dispensed the usual or modified dose. In a focus group, the reasons for dispensing to an intoxicated client were categorized as follows:

• insufficient communication between prescriber and pharmacist
• downplaying the risk of toxicity
• personal beliefs and values
• fear of what the client would do if dose refused
• difficulty in recognizing intoxication and lack of education and training.

Further, Koutroulis et al.’s survey suggested that pharmacists who had more than 10 methadone clients were more likely to provide the usual methadone dose than pharmacists with 10 or fewer clients.

Educational offerings

Many physicians and pharmacists don’t think they see addicts in their practice. The reality is they probably are treating them for other disorders, but the patient just hasn’t been identified as an addict. This also means that dependence treatment needs to become part of regular pharmacy practice as well.

— Open discussion, physicians and pharmacists (Raisch et al., 2005)

The panel recommends that:

16. All pharmacy students receive education on substance abuse, including opioid dependence, its treatment and practical intervention strategies, in their undergraduate curriculum. [IV]

Future pharmacists need to be adequately educated on substance use so that they are prepared upon graduation to care for patients with substance abuse disorders. In particular, opioid dependence and its treatment should be required components in the curriculum. Pharmacists who have had education in this area are likely to feel more comfortable providing pharmaceutical care to this group of clients.

Currently there are two faculties of pharmacy in Ontario, at the University of Toronto and at the University of Waterloo. The Waterloo faculty initiated their program in January 2009; therefore, their plans for curriculum on substance abuse education are still in the development phase.

At Toronto’s Faculty of Pharmacy, pharmacy students receive a rigorous scientific and clinical education over four years but receive little or no education on substance abuse and its treatment. Since the early 1990s, an elective fourth-year problem-based course has been offered (Busto et al., 1994). This course has one 2-hour segment on opioid abuse and treatment. It includes a didactic component, as well as an MMT client interview and discussion of stigma and attitudes. The course is elective and only a small proportion of the fourth-year class has taken this course offering.

Over the last five years enrolment in this elective has increased from 9.7 per cent of the class (13/134 students) in 2003–2004 to 34.2 per cent of the class (79/231 students) in 2008–2009 (personal communication, Dr. B. Sproule, April 29, 2009). Clearly, most future pharmacists have no exposure to substance use, opioid dependence and treatment with methadone.

The lack of specific undergraduate educational activities about substance abuse results in a missed opportunity to positively influence the knowledge, skills and attitudes of future pharmacists in this area.

As the most accessible of all health care professionals, pharmacists have an important role to play to help prevent and treat substance abuse disorders in their clients (Tommasello, 2004). Preparation for this role should begin in the undergraduate pharmacy training.

Experiential learning and other innovative teaching methods, for example, involving real patients (or simulated cases), audiovisual vignettes or other online modules may enhance pharmacy students’ understanding of substance dependence issues and attitudes.

One college of pharmacy in the United States, in addition to a required substance abuse course, offers an elective to illustrate addiction recovery principles. Students taking the elective are asked to give up a habit that is causing them problems for six weeks and they meet weekly to discuss the addiction recovery process. This course has been offered for 15 years and 50 per cent of the substance abuse course students are enrolled (Baldwin, 2008).

From the client consultation interviews

Clients’ need for pharmaceutical care

“I would have liked to know more about methadone before I started. It would have helped me make a better decision. You shouldn’t just tell a sick person ‘this will make you better.’ ” “There has been a lack of care and communication and confusion with my HIV meds. The methadone wasn’t holding me due to medication interactions.” “I felt sick for weeks and didn’t know it was because my dose was too high.”

The panel recommends that:

17. Professional organizations, addiction and mental health agencies and pharmacists’ employers promote the development of, and provide encouragement for all practising pharmacists to participate in, educational events on substance abuse and opioid dependence, including the growing problem of prescription opioid abuse. [III]

Most pharmacists receive little training on opioid dependence and treatment in their undergraduate experience, and it is important that all pharmacists further their knowledge in this area, even if they are not yet providing MMT services. There are indications that abuse and dependence on prescription opioids is increasing in Ontario and Canada. There was an increased number of patients addicted to prescription opioids entering the CAMH methadone maintenance program following the rapid expansion in the availability of MMT in Ontario in the 1990s (Brands et al., 2002; Brands et al., 2000). More recently, the number of individuals seeking detoxification treatment from controlled-release oxycodone at CAMH has also increased significantly (Sproule et al., 2009). In addition, in a cohort study of illicit opioid users, the proportion using prescription opioids increased from the year 2002 to 2005, with regional differences noted across Canada (Fischer et al., 2006). Pharmacists need to increase their knowledge base in prescription opioid addiction, particularly to understand the difference between addiction and physical dependence. Continuing education programs on pain treatment rarely (or inadequately) discuss the issue of opioid abuse and dependence.

A survey in British Columbia of 257 pharmacists (Cohen & McCormick, 2008) found that a slight majority reported training on how to identify signs of prescription drug misuse or abuse. This training was more common in younger pharmacists. The mean amount of training was 13.6 hours. Many pharmacists learned to identify prescription drug misuse through personal experience: they detected multi-doctoring using the provincial PharmaNet prescription drug profile or by recognizing early refills of prescriptions. Most intervened by calling the physician to confirm prescriptions or by confronting the customer directly. The primary reason they gave for not intervening was concern over how the customer might react (i.e., they were afraid that the client would be confrontational or they feared for their own safety). Pharmacists recommended additional training on prescription drug misuse.

Jones et al. (2005) surveyed 42 community pharmacists in Wales and found that at one month after a structured educational evening event there was little maintained change in attitudes. This suggests that changing attitudes is a long-term process. There is a need for reinforcing changes through continuing education.

Practising pharmacists (484) in Florida were surveyed while attending continuing education programs (Lafferty et al., 2006). Of the respondents, 67.5 per cent reported participating in two or fewer hours of addiction/ substance abuse education in pharmacy school and 29.2 per cent said they had received no addiction education. Pharmacists who had more education counselled clients more frequently and felt more confident in dealing with substance abuse clients. Of those surveyed, 53 per cent reported they had never referred a patient to substance abuse treatment in their whole career.

Brooks et al. (2001) conducted a survey in the United States of 556 pharmacists, comparing those who had taken training in addiction treatment to those who had not, and found that those who had taken training would more likely refer clients to community resources and be more involved in working with their chemically dependent clients.

The panel recommends that:

18. The Ontario College of Pharmacists revise the current requirements for pharmacies providing MMT services to mandate earlier training to promote safety. The designated manager and one pharmacist must complete the training within six months of starting to dispense methadone. [IV]

19. CAMH or another approved provider of methadone training develop a brief electronic document (e.g., one page) outlining the key safety features of providing MMT services that can be made available for immediate use by pharmacies initiating MMT services. [IV]

20. CAMH produce an electronic version of its most recent pharmacist’s guide to methadone maintenance treatment that can be purchased online and downloaded immediately so that pharmacies initiating MMT services can access it without delay. [IV]

21. CAMH make the online component of its Opioid Dependence Treatment Course available immediately upon enrolment to pharmacists new to providing MMT services, with the stipulation that these pharmacists attend the workshop component within six months of beginning the course. [IV]

22. CAMH or another approved provider of methadone training monitor and respond to waiting lists for training programs by, for example, offering the training more frequently or by exploring other delivery methods, such as webinars or video conferencing, to help meet the needs of pharmacists in remote areas. [IV]

Since undergraduate training on substance abuse and opioid dependence is lacking, most pharmacists do not have an adequate knowledge base from which to provide MMT services safely.

Having the most essential knowledge and references easily accessible and as early as possible will help facilitate pharmacies starting a methadone service and assist those who are deciding whether to provide MMT.

The online component of the CAMH Opiate Dependence Treatment Interprofessional Education Program would provide a good introduction to providing service, and a brief methadone information sheet would complement this program. The methadone information sheet could include some of the key points in providing MMT service, for example, observing dosing, diluting dose in orange drink, identifying the client, assessing the client for intoxication and informing the prescriber of missed doses.

Having a current version of the CAMH Pharmacist’s Guide available in a downloadable format would enable pharmacists to have this mandatory reference as soon as they need it. The other two references pharmacists dispensing methadone require, the CPSO Methadone Maintenance Guidelines and the OCP Policy for Dispensing Methadone, are currently available electronically.

The panel recommends that:

23. The Ontario College of Pharmacists and providers of methadone training collaborate on ongoing training requirements based on needs identified during the College’s pharmacy inspection process. [IV]

The Ontario College of Pharmacists undertakes regular inspections of community pharmacy practice in the province. Practice issues related to methadone service provision identified during these inspections could be shared with educational service providers for consideration in future training initiatives. This would be an effective mechanism for updating methadone training to reflect current practice issues in the field.

The panel recommends that:

24. CAMH or another approved provider of methadone education deliver methadone training in a manner consistent with interprofessional education principles. [IV]

Since MMT practice is best delivered in a collaborative manner (Health Canada, 2002), a multidisciplinary approach in education will prepare pharmacists to work effectively with other health professionals as a team.

The panel recommends that:

25. The Ontario College of Pharmacists and community colleges providing pharmacy technician training develop core competency requirements for regulated pharmacy technicians providing MMT services. [IV]

Pharmacy technicians are important members of the pharmacy team. They may be involved with preparing and dispensing methadone, and interact with MMT clients in the pharmacy. Core competencies should be developed and educational programs designed to optimize the role of pharmacy technicians in the safe delivery of methadone services. This issue may be particularly important in view of the new regulated status for pharmacy technicians that will be implemented soon in Ontario, where pharmacy technicians will be able to take more responsibility for dispensing.

The panel recommends that:

26. CAMH or another approved provider of methadone education undertake a needs assessment of pharmacists who have participated in the initial MMT training, and then use this information to develop an updated or advanced MMT course for pharmacists. [IV]

27. Professional pharmacy organizations, the Ontario College of Pharmacists, pharmacy managers/owners and hospital pharmacy directors encourage pharmacists to take courses on motivational interviewing, intervention strategies to use with difficult patients, and concurrent disorders, to enhance pharmacists’ skills in dealing with opioid-dependent clients. [IV]

Pharmacists who are already in MMT practice and have taken initial MMT training may wish to update and improve their skills. Since pharmacist training is recommended by the Ontario College of Pharmacists every five years, a new, higher level course would meet the needs of this experienced group of providers. Pharmacists who have taken initial MMT training should be surveyed for their input about topics to include within this higher level course. This advanced training could include, for example, methadone use in pregnancy, in patients with concurrent disorders (e.g., pain, psychiatric disorders, HIV) and in other special populations.

Any interaction with a client has therapeutic potential. Pharmacists using motivational techniques in their interactions with clients may enhance clients’ treatment. The issue of dealing with difficult, demanding clients has been identified by pharmacists as an area in which they would like more training (Cohen & McCormick, 2008). Training in de-escalation techniques to avoid potentially unsafe interactions could help pharmacists achieve greater satisfaction in their practice, as well as improve client outcomes.

The panel recommends that:

28. Drug information service providers ensure that staff is trained on and familiar with common issues in MMT treatment and have a mechanism to refer to experts when necessary. [IV]

Pharmacies must subscribe to a drug information provider service. The staff at the drug information provider should be able to respond to general questions on MMT and substance abuse. To do this they would require training in MMT to understand the patient safety issues and relevant guidelines. For more complex questions, the drug information service should have an arrangement with expert service providers to assist in consultation.

The panel recommends that:

29. Professional pharmacy organizations develop a mechanism in conjunction with the Ontario College of Pharmacists to ensure that pharmacists dispensing methadone are informed in a timely fashion of new educational resources available. [IV]

A timely direct communication via e-mail from the Ontario College of Pharmacists, the Ontario Pharmacists’ Association or another professional pharmacy organization is recommended when any new methadone-related item is posted on the website of either the OCP or the CPSO.

The panel recommends that:

30. Professional pharmacy organizations, CAMH and funding agencies develop a mentorship program to link new methadone service providers with experienced providers. [IV]

31. Professional pharmacy organizations and CAMH promote the CAMH Addiction Clinical Consultation Service to pharmacists providing MMT services. [IV]

The Addiction Clinical Consultation Service (ACCS) is a service provided by CAMH. It is designed to serve health and social service professionals, including pharmacists, who have client-specific questions related to substance abuse. The accs is not designed to deal with health emergencies or immediate or legal issues. The health care worker calls a central phone number and, depending on the question, accs may provide referral to a consultant team member (physician, therapist/counsellor or pharmacist) who will communicate with the health care worker within four hours. Awareness of the service should be promoted to support pharmacists providing methadone services.

How Methadone Clinics Work!

Methadone maintenance is somewhat of a mystery to clinicians not involved in addiction medicine, and opioid addicts don’t fare well in the emergency medical system. Many nurses and physicians have trouble dealing with them objectively and don’t want to be involved. Well-managed methadone maintenance is, however, a different story. Few EPs dole out methadone, but maintenance patients show up in the ED with legitimate complaints. Patients on high-dose methadone can experience painful conditions or injuries requiring additional analgesia. It’s not easy, but if one can put aside preconceived notions about addiction, methadone maintenance presents a fascinating challenge to the EP.

Figure. Clients line…

Most  have treated methadone maintenance therapy (MMT) clients in the ED, and have dealt with withdrawal, missed appointments, and overdose. I have visited a few methadone clinics, and the whole concept is fascinating, giving great insight into a government-sponsored medical entity.

Treatment Improvement Protocol Series 43: Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Program

This massive document summarizes the consensus of the U.S. Health and Human Services on MMT, which is administered through the Substance Abuse and Mental Health Services Administration and the Center for Substance Abuse Treatment, branches of HHS. This 14-chapter document has everything you want to know about MMT.

Edit by Exilope: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hssamhsatip&part=A82676

Initial Screening: Anyone can walk into an MMT clinic and request treatment. Initial screening exams and interviews determine the applicant’s eligibility and the process includes an assessment of their readiness to accept treatment. Ongoing, if not daily interventions, are required to keep the patient in the system and off the opioid. The addiction severity index collects basic information, and it can be used to track progress. Much of the information is supplied by the addict, and truthfulness on their part is paramount for success.

Comment: I suspect most people don’t walk in off the street thinking about MMT for the first time. All potential clients likely consider it many times or talk about it with fellow addicts. They are often prompted to try MMT by those who have been through the process, some more than one time. One would assume that an opioid addict who shows up at the clinic has hit rock bottom or finally has accepted they have an addiction they cannot control. Many are in overt withdrawal. They are ready to sign up.

First impressions are lasting ones. The HHS recommends a plethora of warm and fuzzy approaches to help the addict adjust and feel supported. A nonconfrontational and nonaccusatory attitude is stressed. Unlike the ED, MMT clinics want to be in the business of dispensing methadone. Clinics are usually prepared to provide immediate information, if not methadone treatment, on the first day.

A variety of preprinted documents are handed out that describe the services, rules, and expectations of the program. Policies are in place to deal with disruptive and violent clients and pregnant women. Clinics also try to identify treatment barriers and offer financial assistance and psychiatric crisis intervention. Many patients also have underlying psychiatric disorders, legal difficulties, child care issues, and transportation and family concerns. Cultural, ethical, and spiritual factors also complicate MMT. Those patients who seem in crisis can be referred for inpatient medical facility or psychiatric care. The correlation between opioid addiction and the risk of suicide is well known, and initial screening and periodic assessment helps determine that ongoing risk.

Admission Issues: A significant delay between the first contact, initial screening, and methadone treatment, especially failure to quickly address withdrawal, adversely affects the number of applicants who enter the program. It’s difficult to deal with an opioid addict in withdrawal; his patience wears thin, and he wants treatment now. Recognizing the realities of crowding and limited resources, MMT clinics can provide an interim maintenance program without formal screening or actual admission to the site. By federal regulation, medication can be administered for up to 120 days with only minimal screening procedures.

Violent or threatening patients can be turned down, but I have been amazed at how understanding and supportive some of the staff are; it’s similar to the mentality emergency physicians use to treat those who are not the nicest people. MMT, like emergency medicine, is a service industry, and the customers often possess the mentality of the McDonald’s client. They want it now, they want it their way, and they don’t want to pay much for it. Frustrated clients who elope are, however, a loss for everyone. Programs are not free, and cash and insurance are accepted, but often the down-and-out addict qualifies for local aid.

Information, Collection, and Dissemination: During the first few visits, a substance abuse history is obtained, and treatment options are discussed. Consent to treat is elicited, and addicts must sign a bevy of documents that provide further information on the multifaceted MMT process. Patients must be 18 or have parental approval. Otherwise, the services are confidential even to family members. Confidential information is not given to any inquiry except the court. The specifics of the individual’s opioid addiction, including recent pattern changes and binges, are gathered. Other drugs such as benzodiazepines and alcohol are often confounding issues, and the patient’s daily pattern of opioid abuse is determined, essentially by his own admission.

The opioid withdrawal history and the energy required to maintain the addiction is sought. Many patients are in withdrawal when they come to the clinic, making historical information open to exaggeration, but many downplay their use (like the alcohol history obtained in the ED). Some withhold a history of other addictions, perhaps thinking they might supplement the methadone if needed. Blood tests for specific drugs are not required nor usually performed to quantify use. A serum drug level is of no value in this scenario. Questioning the history can intimidate the prospective client and set up an adversarial relationship at the beginning. Again, unlike the ED, MMT clinics put a lot of trust in the truthfulness of the addict.

Medical Assessment: The aim of medical assessment is to determine the safety of methadone use. The drug is often dispensed on the first visit because of withdrawal. It is generally required that someone be addicted for one year before admission. There appears to be some flexibility in this criterium, especially for prisoners, pregnant women, or those previously treated. There may be uncertainty about past narcotic use, but generally a broad definition is accepted for opioid addiction, and one need not administer Narcan to test for withdrawal.

Generally, the staff obtains a medical history that documents drug-related diseases such as hepatitis, AIDS, tuberculosis, or STDs. Within 14 days of admission, a basic physical examination is performed, including blood tests for HIV, syphilis, and hepatitis. Federal regulations do not require a full panel of laboratory tests; that appears to be a state issue. Patients usually are tested randomly by a urine screen immunoassay test for additional drug abuse at least eight times each year per SAMHSA. Because methadone does not yield a positive opioid result unless specifically tested, a positive opioid screen usually means exogenous drugs.

Multiple Substance Abuse: It is common knowledge that opioid addicts often abuse other substances, especially alcohol, amphetamines, benzodiazepines, prescription opioids, cocaine, sedatives, and marijuana. CNS depressants are particularly dangerous when combined with opioids. Patients generally are asked to report other substances they used in the past. The accuracy of this form depends, of course, on patient honesty. Alcohol is a favorite of most, and heroin addicts particularly like to add cocaine for additional euphoria. Benzodiazepines are commonly used to boost methadone and enhance the high. Patients also self-medicate because of withdrawal symptoms or because they are anxious, depressed, or lonely.

MMT clients all know using an exogenous substance can kill them and defeat the purpose of MMT. Using exogenous drugs negatively affects attendance rates and cooperation with other programs. Interestingly, patients are not frequently discharged from MMT because they abuse other substances. The main goal is to retain the patient in MMT, allowing for human frailty, lack of self-control, and poor judgment. MMT clients are given multiple chances despite violating explicit rules and regulations.

Drug Testing: Clients are randomly tested for other drugs, usually with an immunoassay urine screen. This is not a perfect system because it only identifies those using other substances frequently and only detects drugs that show up on a urine screen. Of course, it has to be your urine, and there is always someone around who wants to give a clean sample for the right price.

Periodic drug testing provides objective evidence of treatment success and monitors patient progress. Typical urine testing evaluates for commonly abused substances with a qualitative immunoassay technique that has cutoff concentrations. Testing drug levels in the blood is not helpful because tolerance, time of use, and the need to send the test to a reference lab does not allow for meaningful interpretation of data. Most drugs remain in the system and are excreted in the urine for two to four days following use. Measuring methadone serum levels during treatment has minimal value and is not done routinely, but this may be used to identify a rapid or slow metabolizer. Obviously, urine tests are not quantitative; they merely give positive or negative results.

Urine collection may be monitored to avoid contamination or substitution. There are no firm and fast rules for the method of testing, and direct observation is not mandatory. The most common test is an enzyme-multiplied immunoassay technique (EMIT), which uses antibodies to specific drugs or metabolites. Oxycodone is often not identified with this test; nor are clonazepam, Seroquel, hallucinogens, fentanyl, Demerol, dextromethorphan, propoxyphene, and a variety of street drugs. On-site dipstick urine testing is common, but some clinics will confirm the initial clinic screen via a reference laboratory. Many clinics test patients at intake to prove they used opioids recently. The continued use of heroin or other opioids may prompt an increase in the methadone dose because it’s common to supplement during withdrawal.

Retaining Patients in MMT: The longer the patient stays in MMT, the less likely he will revert to using opioids. Staying in MMT for more than a year is associated with constructive lifestyles changes, decreased criminal behavior, and less transmission of infectious diseases. Older patients and those not in the criminal justice system tend to stay in the program longer. Those who have tried it before and failed are better candidates for retention the next time around.

But the key to MMT success, as this HHS publication notes, is: Adequate individualized medication dosages are probably the most important factor in patient retention because they contribute to patient comfort and satisfaction by reducing withdrawal symptoms and craving. The serum half-life of methadone is stated to be 24 to 36 hours, but in reality there is an extremely wide range (13-58 hours). Excessive methadone use occurs when daily visits and individual dose adjustment are not made.

Take-Home Medication: Methadone is usually dispensed daily in a liquid form, and ingestion is witnessed. This keeps patients from diverting tablets. Methadone diversion is a huge problem in this country, but that methadone is usually not obtained from clinics. A single take-home dose is common on Sundays and holidays. After six months to a year, compliant and reliable patients can take home one to four weeks of methadone, but initially, doses are only dispensed daily at the clinic. The requirement to show up every day can be problematic.

Figure. Christine Ad…

Dosing Schedule: A dose of 30 mg to 40 mg of methadone is the upper limit for the initial dose, per regulation. Initial dosing should be followed by increases over subsequent days until withdrawal symptoms are suppressed. A steady state of a dose is not reached for three to five, sometime seven days after a dosage change. The goal is to reach 80 mg to 120 mg methadone per day, a level that has been proven to improve compliance to the program. Using smaller doses or failing to increase the dose when withdrawal is still present is ineffectual and counterproductive. Withdrawal often prompts exogenous drug use or elopement.

The actual schedule is not set in stone, but daily dose increases of 5 mg to 10 mg a day for the first five to seven days to reach 60 mg a day are common. The 60 mg per day dose is maintained under daily observation to reach a steady state. The first week or two of MMT are the most dangerous for the patient and the time during which most fatalities occur. With daily observation and individual dose adjustments, induction is safe and effective as long as the patient is truthful and abstains from other drugs.

The quoted serum half-life of methadone can be misleading, and provides only a rough estimate to forecast dosing requirements and effectiveness. Methadone is eliminated more quickly from the blood and the effects wear off sooner until sufficient levels are obtained to saturate tissues, especially the liver. Smokers have increased clearance, and significant liver damage slows clearance. The optimal dose can only be determined by observing the individual daily, debriefing him on how he feels, and altering dosages in a safe, effective manner.

There is no uniformly suitable dose range or limit for all patients. Some require 400 mg to 700 mg a day while others do well on 80 mg to 120 mg a day. During induction, clinical observation and patient symptoms are the best indicators of whether a dose is too small or large. When this protocol is followed, methadone induction is safe and effective.

Comment: There are eight MMT clinics in Philadelphia, usually for heroin addiction, but more frequently for prescription opioid addiction. Most opioid addicts know the concepts of MMT well, and visit various clinics off and on throughout their addiction. The rules of MMT are straightforward, and each state is allowed some latitude on various issues. Some addicts have learned to work or abuse the system, but MMT is a godsend, if not a true lifeline, for many opioid addicts.

Addiction to hydrocodone, hydromorphone, and oxycodone is likely more widespread than street heroin. There is little difference between the prescription pill addict and the hardcore street heroin user on everyday issues or potential benefit from MMT. The well-to-do business man, the bored housewife, the professional athlete, or the Hollywood celebrity seem to prefer pills over the needle. Some physicians readily prescribe a slew of addicting medications, prescriptions are stolen or altered, and anyone can buy a few Percocet at the local high school. The Internet provides drugs as well as directions on use and how to beat drug tests and avoid overdose. Of course, heroin can be smoked and snorted as well, but there is less of a stigma involved with popping a pill than buying a bag of heroin on a lonely street corner.

I am quite impressed with the understanding approach to MMT and the dedication of the clinic personnel. Methadone manufacturers stress that their product should be used only under strict HHS guidelines, and they actually reference the Federal Register code in the package insert. The dangers of inappropriate methadone use are well-reported in the literature, but it’s likely an underused drug for chronic pain control.

Society has written off many opioid addicts or would drop them in a heartbeat at any sign of deceit or additional drug use. Not so for MMT clinics; they bend over backwards to give everyone yet another chance. Using additional substances during MMT is very common. Klonopin, Xanax, Soma, and Seroquel are popular in my area to boost methadone’s high, and none show on a urine screen. It’s easy to buy any of these on the street, usually right outside the door of the clinic. It’s best to never underestimate the ingenuity or resourcefulness of an opioid addict so MMT works best in an environment of mutual trust and truthfulness. Lying to the counselor about past or present drug use or beating the drug test is tempting, but in the end, it can be a fatal error.

New report: Drug prohibition, stricter law enforcement key sources of violence and gun crime

Canada’s war on drugs has failed to curb the illicit drug trade, and proposed legal interventions to disrupt the drug market may actually boost rates of drug-related violence, according to the latest report by the Urban Health Research Initiative. The report’s findings are significant in the context of Bill C-15.

Read the full Report: violence-eng

Science-Based Views of Drug Addiction and Its Treatment

MORE THAN TWO THIRDS OF
people with addiction see a
primary care or urgent care
physician every 6 months, and many
others are regularly seen by other medical
specialists.1,2

These physicians are
therefore in a prime position to help patients
who may have drug abuse problems
by recognizing and diagnosing the
addiction, helping to direct patients to
a program that can meet their treatment
needs, and helping to monitor
progress after specialty treatment and
during recovery.3-6

Many physicians,
however, find the domain of drug abuse
particularly daunting and often avoid
the issue with their patients. This is understandable
given the relatively short
shrift drug abuse is given in formal
medical education. There is a widespread
misperception that drug abuse
treatment is not effective, which may
account for the reluctance of physicians
to even broach the subject of drug
abuse or treatment with their patients.
On the other hand, over the past 15
to 20 years, advances in science have
revolutionized our fundamental understanding
of the nature of drug abuse
and addiction and what to do about it.
In addition, there are now extensive
data showing that addiction is eminently
treatable if the treatment is welldelivered
and tailored to the needs of
the particular patient.

There is an array
of both behavioral and pharmacological
treatments that can effectively
reduce drug use, help manage drug
cravings and prevent relapses, and restore
people to productive functioning
in society.7-9
Of course, not all drug abuse treatments
are equally effective, and there
is no single treatment appropriate for
all patients. Fortunately, recent scientific
advances have provided insights
both into the nature of drug abuse and
addiction and into the principles that
characterize the most effective treatment
approaches and programs.10 These
treatment principles should make the
primary care or nonaddiction specialty
care physician’s tasks of screening
and referral much easier.

Read more: 20.03.10

Drug Abuse: a Hedonic Homeostatic Dysregulation?

Most definitions of drug addiction or substance dependence include (i) descriptions of „overwhelming involvement with the use of a drug (compulsive use)“ (1) and (ii) a number of symptoms or criteria that reflect a loss of control over drug intake and a narrowing of the number of different behavioral responses toward drug-seeking (2). Drug addiction can be equated with substance dependence as defined by the American Psychiatric Association (3). However, it is important to distinguish between what is termed substance use, substance abuse, and substance dependence (addiction) (4).

In humans, most drug users do not become drug abusers or drug-dependent (4). Similarly, stable drug intake can be observed in animals without pronounced signs of dependence, even with intravenous drug administration under limited-access situations. Many factors such as availability (route of administration), genetics, history of drug use, stress, and life events contribute to the transition from drug use to drug addiction. The current challenge is to discover what neurobiological elements convey the individual differences in vulnerability to this transition to drug addiction.

In this article we will draw from recent formulations in behavioral neuroscience and other disciplines to construct a framework to view addiction as a continuous process of hedonic homeostatic dysregulation. Multiple sources of reinforcement are identified in the spiralling cycle of addiction, and the symptoms of this hedonic dysregulation form the well-known criteria for substance dependence or addiction (2, 3). Critical neurotransmitters, hormones, and neurobiological sites have been identified that may mediate the hedonic dysregulation and may provide the substrates that convey both vulnerability to, and protection against, drug addiction (5) (Fig. 1).

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Fig. 1. Diagram describing the spiralling distress-addiction cycle from four conceptual perspectives: social psychological, psychiatric, dysadaptational, and neurobiological. (A) The three major components of the addiction cycle, preoccupation-anticipation, binge-intoxication, and withdrawal-negative affect, and some of the sources of potential self-regulation failure in the form of underregulation and misregulation. (B) The same three major components of the addiction cycle with the different criteria for substance dependence from DSM-IV incorporated. (C) The places of emphasis for the theoretical constructs of sensitization and counteradaptation. (D) The hypothetical role of different neurochemical and endocrine systems in the addiction cycle. Small arrows refer to increased functional activity. DA, dopamine, CRF, corticotropin-releasing factor. Note that the addiction cycle is conceptualized as a spiral that increases in amplitude with repeated experience, ultimately resulting in the pathological state known as addiction. (fuer groesseres Bild unten gucken!)

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Spiralling Distress and the Addiction Cycle

Important elements that may be involved in the failure to self-regulate drug use, as well as other behaviors such as compulsive gambling and binge eating, have derived from social psychology (6). It is of interest to conceptualize how these regulation failures ultimately lead to addiction in the case of drug use or an addiction-like pattern with nondrug behaviors. Lapse-activated causal patterns, that is, patterns of behavior that contribute to the transition from an initial lapse in self-regulation to a large-scale breakdown in self-regulation, can lead to spiralling distress (6). Spiralling distress describes how, in some cases, the first self-regulation failure can lead to emotional distress, which sets up a cycle of repeated failures to self-regulate, and where each violation brings additional negative affect (6). For example, a failure of strength may lead to initial drug use or relapse, and other self-regulation failures can be recruited to prevent an exit from the addiction cycle. Here, spiralling distress will be used to describe the progressive dysregulation of the brain reward system within the context of repeated addiction cycles (Fig. 1A).

Psychiatry and experimental psychology, in effect, address the same addiction cycle (Fig. 1B), and neurobiology has begun to identify the neurobiological elements that contribute to the break with hedonic homeostasis, known as addiction. Although animal models provide a critical part of the study of the neurobiology of addiction, no animal models incorporate all the elements of addiction. Alternatively, animal models can be established and validated for different symptoms or constructs associated with addiction (7). There is much evidence for valid animal models of many of the criteria in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (3) and the sources of reinforcement associated with addiction (7).

Neurobiology of Drug Reinforcement

The focus for the neurobiological mechanism for the positive-reinforcing effects of drugs of abuse has been the mesocorticolimbic dopamine system and its connections in the basal forebrain (8, 9). For cocaine, amphetamine, and nicotine, the facilitation of dopamine neurotransmission in the mesocorticolimbic dopamine system appears to be critical for the acute reinforcing actions of these drugs [for reviews, see (8, 9)]. Multiple dopamine receptors including D-1, D-2, and D-3 have been implicated in this reinforcing action (10, 11). Neuropharmacological studies support both a dopamine-dependent and a dopamine-independent contribution to the positive-reinforcing effects of opiates such as heroin (8, 9, 12). Ethanol appears to interact with ethanol-sensitive elements in multiple neurotransmitter receptor systems, and these interactions may contribute to ethanol’s positive-reinforcing actions (13). The neurotransmitters and receptor systems implicated include actions on the -aminobutyric acid (GABA), glutamate, dopamine, serotonin, and opioid peptide systems, all of which are within the mesocorticolimbic dopamine system and its connections to the nucleus accumbens and amygdala (13). Limited study has implicated the release of dopamine in the nucleus accumbens in the positive-reinforcing actions of tetrahydrocannabinol (THC) (14).

A major question still challenging drug abuse research, however, is whether the neurobiology of reward and drug reinforcement changes with chronic use and during the manifestation of an abstinence syndrome when the drug is no longer self-administered. Historically, substance dependence has focused on the manifestation of an abstinence syndrome upon abrupt cessation of drug administration that was characterized by physical signs such as the well-documented tremor and autonomic hyperactivity of ethanol withdrawal and the discomfort and pain associated with opiate withdrawal. However, recent conceptualizations of abstinence symptoms have begun to focus on aspects of abstinence that are common to all drugs of abuse and may be considered more motivational in nature and perhaps are best described as a negative affective state (5, 15, 16). These symptoms include various negative emotions such as dysphoria, depression, irritability, and anxiety (3, 15, 16).

Consistent with these clinical observations, animal studies in which intracranial self-stimulation was used as a measure of reward function have revealed pronounced decreases in reward (or increases in the reward threshold) associated with withdrawal from all major drugs of abuse tested to date (Fig. 2). These effects vary with dose and duration of exposure to the drug, but can last as long as 96 hours after withdrawal from the drug in rodent models (15, 16).

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Fig. 2. Changes in reward threshold associated with chronic administration of three major drugs of abuse. Reward thresholds were determined by a rate-independent discrete trials threshold procedure for intracranial self-stimulation (ICSS) of the medial forebrain bundle. (A) Rats equipped with intravenous catheters were allowed to self-administer cocaine for 12 hours before withdrawal and reward threshold determinations. Elevations in threshold were dose-dependent with longer bouts of cocaine self-administration yielding larger and longer-lasting elevations in reward thresholds (51). Asterisks refer to significant differences between treatment and control values. Values are mean ± SEM. (B) Elevations in reward thresholds with the same ICSS technique after chronic exposure to ethanol of about 200 mg% in ethanol vapor chambers (52). (C) Elevations in reward thresholds measured with the same ICSS technique after administration of very low doses (in milligrams per kilogram of body weight) of the opiate antagonist naloxone to animals made dependent on morphine with two, 75-mg morphine (base) pellets implanted subcutaneously (53). (fuer groesseres Bild unten gucken!)

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The significance of drug abstinence syndromes remains controversial as a basis for compulsive use (1, 7), but increasing evidence both in animal and human studies suggests that the presence of a negative affective state may not only signal the beginning of the development of dependence (17), but may contribute to vulnerability to relapse and may also have motivational significance. Rats made dependent on opiates and ethanol show increases in drug self-administration (18). Thus, exposure to sufficient amounts of drug to produce dependence as measured by elevations in reward thresholds can increase the motivation for a drug. This increase could result from additive or even synergistic sources of positive and negative reinforcement (19) and may contribute to the addiction cycle.

Neural Substrates for Sensitization and Counteradaptation of Reward

At the neurobiologial level, two neuroadaptive models have been conceptualized to explain the changes in motivation for drug-seeking that reflect compulsive use: counteradaptation and sensitization. Counteradaptation hypotheses (20) were intimately linked to the development of hedonic tolerance by the formulation known as opponent process theory (21). In contrast, sensitization, a progressive increase in a drug’s effect with repeated administration, has been conceptualized to be a shift in an incentive-salience state (21).

Both of these conceptual positions focus on neurobiological changes at the molecular, cellular, and system levels, and both may involve what have been described as „within-system“ and „between-system“ changes (8). At the neurochemical level, changes associated with the same neurotransmitters implicated in the acute reinforcing effects of drugs that are altered during the development of substance dependence would be examples of within-system changes.

Counteradaptive, within-system neurochemical events include decreases in dopaminergic and serotonergic neurotransmission in the nucleus accumbens during drug withdrawal (22). At the molecular and cellular levels, changes in opiate receptor function during withdrawal from chronic opiates and decreased GABAergic and increased glutamatergic transmission during ethanol withdrawal have been observed [(23), and Nestler and Aghajanian (24) in this issue)]. Sensitization to the locomotor stimulant effects of psychomotor stimulants and opiates also appears to involve within-system activation of the mesolimbic dopamine system. There appears to be a time-dependent chain of adaptations within the mesolimbic dopamine system that leads to the long-lasting changes produced by sensitization (25).

Changes in other neurotransmitter systems that are not linked to the acute reinforcing effects of the drug but are recruited during chronic drug administration have been conceptualized as between-system adaptations. Examples of between-system counteradaptations include increases in dynorphin function in the nucleus accumbens during chronic cocaine administration, increases in anti-opioid peptides associated with chronic opioid administration, and augmentation of brain stress systems such as corticotropin-releasing factor (CRF) associated with cocaine, opiates, ethanol, and THC (15, 16, 26).

Recent neuroanatomical, neurochemical, and neuropharmacological observations have provided support for a distinct brain circuit within the basal forebrain that may mediate both the within-system and between-system neurochemical changes associated with drug reward. The extended amygdala (27) is a hypothesized macrostructure consisting of several basal forebrain structures that share similarities in morphology, neurochemistry, and connectivity (27). Support for the role of the extended amygdala in the acute reinforcing effects of drugs of abuse can be found in a series of in vivo microdialysis and neuropharmacological studies that showed selective activation of dopamine in the shell of the nucleus accumbens by most of the major drugs of abuse (28). In addition, GABAergic and opioidergic mechanisms in the central nucleus of the amygdala may participate in the acute reinforcing actions of ethanol (29). Also, the central nucleus of the amygdala may function in counteradaptation of the brain reward system during the development of drug dependence. Chronic administration of drugs can alter both CRF and proopiomelanocortin gene expression in the amygdala (30). An increased CRF response in the central nucleus of the amygdala is associated with acute withdrawal from ethanol, opiates, cocaine, and THC (31).

Limited data suggest a specific role for parts of the extended amygdala in sensitization. The mesolimbic dopamine system is clearly involved, but no specific subregion has been delineated. Glucocorticoids can activate the mesolimbic dopamine system by increasing dopamine synthesis, decreasing dopamine metabolism, and decreasing catecholamine uptake (5). The participation of a specific subprojection of the mesolimbic system in sensitization is under investigation.

Relapse: Neural Substrates and Vulnerability

Relapse and vulnerability to relapse are key elements in the maintenance of a chronic relapsing disorder such as addiction [see O’Brien (32), this issue]. Animal models predictive of relapse are being developed. Studies suggest that stresslike stimuli and neuropharmacological agents that activate the mesocorticolimbic dopamine system can rapidly reinstate intravenous drug self-administration that has been previously extinguished (33), and drugs that modulate dopamine receptors can block reinstatement of cocaine self-administration in rats (11). Naltrexone and acamprosate decrease relapse rates in alcoholics (34) and can modify excessive drinking in rodents in various models (35). Thus, a rich source for study of the neurobiological mechanisms of relapse will be the same neurotransmitters and neurocircuitry implicated in the within- and between-system adaptations of sensitization and counteradaptation.

The vulnerability to relapse will have both genetic and environmental bases resulting in a susceptible host, from a medical perspective (36). Animal studies have begun to address both these contributions. While genetic vulnerability is beyond the scope of this review, there are rodent strains that show preferences for drinking ethanol, and there is mounting evidence of alterations in the same reward neurotransmitters that may form the basis of such preferences (37). In addition, new techniques such as quantitative trait loci analysis and the study of knock-out and transgenic mice are revealing potential genetic sites associated with vulnerability (38).

Environmental factors involved in vulnerability have largely focused on the role of stress. An atypical responsivity to stress in former opiate- and cocaine-dependent subjects has been well documented and hypothesized to be linked to chronic relapse (39). Exposure to repeated stressors also increases the propensity to develop initial intravenous drug self-administration (acquisition) (40) and can facilitate reinstatement of drug self-administration after extinction (relapse) (33). These effects appear to be directly linked to activation of the hypothalamic pituitary adrenal axis. Suppression of stress-induced corticosterone secretion abolishes the enhanced behavioral responsiveness to amphetamine and morphine produced by different stressors (41). Consistent with these observations, repeated administration of corticosterone can substitute for stress and increase the behavioral effects of psychostimulants (41). It is hypothesized that glucocorticoid hormones function in the long-term maintenance of the sensitized state and may even represent a within-system change (41). In addition, vulnerability to drug-taking may be influenced by a history of drug experience and the presence of competing nondrug reinforcers altering the response to drug reinforcers (42).

The combination of genetic and environmental factors can dramatically change an animal’s response to drugs. A comparison of rats that show a high and low locomotor response to forced exposure in a novel environment revealed that high responders (HRs) show a greater propensity to develop intravenous drug self-administration compared with low responders (LRs) (43). This greater sensitivity to drugs in HRs shows a correlation with dysregulation of the hypothalamic pituitary adrenal axis (a prolonged secretion of corticosterone in response to stress) and with a higher sensitivity to the behavioral and dopamine-activating effects of glucocorticoids (41) (Fig. 3). Indeed, stress has been hypothesized to cause HR rats to express enhanced responses to drugs (43, 44). What is largely unknown is how these genetic and environmental factors combine to contribute to the development of what constitutes substance dependence (addiction) in humans. In addition, identification of the vulnerability for different parts of the addiction cycle using animal models will provide clues to relapse vulnerability in human addicts. With the use of animal models, studies of the interaction of genetics, of stress, and of the initial response to drugs on various features of the addiction cycle other than drug-taking will be informative.

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Fig. 3. (A) The effects of adrenalectomy on cocaine self-administration in rats. Animals were trained to self-administer cocaine by nose-poking and subjected to a dose-effect function. Adrenalectomy produced a flattening of the dose-effect function, with decreases of cocaine intake at all the doses (54). (B) Corticosterone-induced changes in extracellular concentrations of dopamine in high-responding (HR) and low-responding (LR) animals. HR animals that drank the corticosterone solution (100 mg/ml) in the dark period showed a faster and higher increase in accumbens dopamine than LR animals (55). (fuer groesseres Bild unten gucken!)

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Homeostasis of Reward, Self-Regulation, and „Natural“ Addictions

The concept of homeostasis contends that an organism maintains equilibrium in all of its systems, including the brain reward system, that is, the organism uses physiological and cognitive or behavioral capabilities to function within the appropriate limits of physiology with the help of its own resources. Environmental factors that challenge homeostasis are met with counter actions. Allostasis refers to the concept of physiology where an organism must vary all of the parameters of its internal milieu and match them appropriately to perceived and anticipated environmental demands in order to maintain stability (45). If the threats to the system continue to produce disequilibrium, the process of allostasis continues to regulate where the organism must mobilize enormous amounts of energy to maintain apparent stability at a now pathological „set point.“ The system is at the limit of its capability, and thus a small challenge can lead to breakdown (45). This is the beginning of spiralling distress and the addiction cycle. When the organism has reached a state of dysregulation so severe that it cannot recover by mobilizing its own resources, allostasis has reached the point of what is normally considered illness. The state of dysregulation of the reward system may produce loss of control over drug intake, compulsive use, or drug addiction. The mechanisms that contribute to this allostasis are normal mechanisms for homeostatic regulation of reward that have spun out of the physiological range (that is, sensitization and counteradaptation).

Addiction Cycle: Sensitization and Counteradaptation

The role of sensitization in dependence has been elaborated where a shift in an incentive-salience state, described as „wanting,“ progressively increases with repeated exposure to drugs of abuse (21). This shift is largely attributed to a pathological overactivity of mesolimbic dopamine function and, as such, represents a break with homeostasis. Other factors such as increased secretion of glucocorticoids may function in the long-term maintenance of this sensitized state (41).

Early theories of counteradaptation with chronic drug administration were based on the concept of homeostasis (20) and later extended to hedonic processes in opponent process theory (21) (Fig. 4). This theory may explain the affective withdrawal component of the addiction cycle and also may explain how repeated drug-taking can lead to spiralling distress. Indeed, the onset of a negative affective state can be used to define addiction (17). In addition, the negative affective state may have motivating properties in maintaining drug-seeking behavior, not only by direct negative reinforcement (that is, the drug is taken to relieve the negative state) but also by changing the set point for the efficacy of reinforcers and thus add motivational effectiveness to both positive drug effects and conditioned positive drug effects (7, 15, 16, 21). At least two common neurochemical elements, activation of limbic CRF systems and a decrease in mesolimbic DA function, are common neurochemical correlates of the early parts of drug withdrawal (15, 16, 31).

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Fig. 4. Diagram illustrating an extension of Solomon and Corbit’s opponent-process model of motivation to incorporate the conceptual framework of this article (21). All panels represent the affective response to the presentation of the stimuli (that is, drug administration). (A) The original description of the affective stimulus, which was argued to be a sum of both an a-process and a b-process and represents the initial experience with no prior drug history. (B) The same affective stimulus in an individual with an intermittent history of drug use that may result in sensitized response. The shaded line illustrates the sametrace of the initial experience in (A). The dotted line represents the sensitized response. (C) Change in the affective stimulus hypothesized to exist in the heavily dependent individual (that is, after chronic exposure) where there is a major change in the hedonic set point. This represents a change sufficient to be considered a major break with hedonic homeostasis. The light dotted line represents the sensitized response observed in (B). (D) The hypothesized state of protracted abstinence and enhanced vulnerability to relapse with a history of chronic continuous experience. The change in this panel reflects the change in the affective response in an organism with a history of depen-dence where there is both a change in set point that is long-lasting and a residual sensitization. The bar to the right of each diagram illustrates the total peak-to-peak contrast between the lowest point in negative affect to the highest point in positive mood produced by a drug at any point in the addiction cycle. An alternative hypothesis still under consideration is that even during an intermittent sensitization pattern of drugtaking, the affective after-reaction (b-process) also may get progressively larger and larger (21). „On“ refers to the „time on“ of the hedonic stimulus, in this case the drug action. „Off“ refers to the „offset“ of the drug action. (fuer groesseres Bild unten gucken!)

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At first glance, the two processes of sensitization and counteradaptation may appear to make opposite predictions about the course of drug dependence and the neurobiology of drug dependence. However, if drug dependence is viewed in the context of spiralling distress, then it is possible that both processes are active, although perhaps not concurrently, at different parts of the cycle (Figs. 1 and 4). The neurobiology of a heavily dependent person (Fig. 4C) will be very different from that of a nondependent person (Fig. 4A) and may reflect a state of severe allostasis (with a change in set point) and the part of the addiction cycle associated with negative affect and spiralling distress (Fig. 1C). For example, enhanced dopaminergic and opioidergic neurotransmission may be involved in the preoccupation-anticipation stage and result in sensitization (Figs. 1C and 4B), but compromised dopamine, serotonin, and opioidergic neurotransmission, as well as increases in stress neurotransmitters, may be responsible for the negative affective state of withdrawal (Figs. 1D and 4C). The combination of a change in hedonic set point produced by repeated counteradaptation and a separate mechanism for sensitization would provide a dramatic motivational force for continuing drug dependence (Fig. 4, C and D).

This view is similar to that of incentive motivational theory (46) and incorporates some aspects of incentive-salience theory (21). Under the current formulation, counteradaptation creates a need state that may or may not easily be labeled by subjective responses but, rather, reflects a chronic break with homeostasis such as a decrease in hedonic set point. Sensitization, in contrast, creates a facilitated incentive motivation or incentive salience that reflects enhanced responses to drug incentive stimuli (that is, wanting or craving).

According to this formulation, sensitization is assigned a relatively minor role in the ongoing process of spiralling distress, but a more important role in triggering the beginning of instability (vulnerability to drug-taking, as in the form of cross-sensitization to stress) or retriggering of instability as in the process of relapse (reentrance into the cycle of spiralling distress). Indeed, a dependent person is almost by definition already sensitized. However, there is little evidence of sensitization in drug-dependent people, and most clinical evidence points to tolerance, not sensitization. Human addicts consume enormous amounts of ethanol, opiates, and even stimulants that would easily be toxic to nonaddicted individuals (47). In addition, most of the animal studies of sensitization have focused either on locomotor activity as a dependent variable or in the drug reward domain on acquisition of drug self-administration (21). If sensitization is to gain a role as extensive as that outlined herein, more data will be required to show a link between these measures of enhanced sensitivity to drugs of abuse (locomotor activity and acquisition of drug self-administration) and other measures of dependence.

Implications for the Concept of Addiction and Treatment

The present conceptualization of addiction has important implications for the treatment of drug addiction. The social psychological components of failure to self-regulate may impact on different parts of the addiction cycle (Fig. 1A), and these different components may be reflected in changes in different components of reward neurocircuitry (Fig. 1D). For example, failure of strength may reflect increases in stress system activity, whereas failure of monitoring or attention may reflect cognitive changes that are influenced by the widely distributed brain monoamine systems.

The present conceptualization also provides a framework for studying the components of addiction most often neglected in animal studies. The role of neurobiology in different processes, such as social psychological self-regulation failures, positive and negative reinforcement, sensitization, and counteradaptation, changes dramatically over the course of transition from drug use to abuse to addiction. In addition, different drugs may act differentially on parts of the spiralling distress-addiction cycle. Young, type II alcoholics (48) may be more involved in the preoccupation-anticipation and binge components than terminal alcoholics, where a major need state has usurped most other sources of motivation. In contrast, users of opiates and nicotine may assume this need-state component at a much earlier stage (49). Studies of the neurobiology of such differences will be critical for future interventions at both the prevention and treatment levels.

There is clearly a neurobiological basis for multiple sites of treatment intervention. Eliminating affective withdrawal and the reward need state are critical (such as methadone for opiate addiction), as well as eliminating the changes that lead to facilitated incentive salience (such as naltrexone for alcohol addiction). Various forms of behavioral therapies and psychotherapy have been shown to be effective in treating addiction, particularly in combination with pharmacotherapy [(34) and O’Brien (32), this issue]. These therapies ultimately act on the same dysregulated hedonic circuitry to help return and maintain it within homeostatic boundaries. In addition, vulnerability to addiction can be conveyed at any part of the spiralling distress of the addiction cycle and should not be simply relegated to initial drug responses.

Although beyond the scope of the present review, dysregulation of hedonic homeostasis can also occur with compulsive use of nondrug reinforcers. Similar patterns of spiralling distress-addiction cycles have been observed with pathological gambling, binge eating, compulsive exercise, compulsive sex, and others (6). The same neurobiological dysregulations and breaks with homeostasis may be occurring within the same neurocircuitry implicated in drug dependence. With the advent of more sophisticated measures of brain function in humans, such questions may be pursued.

The implications of this homeostatic view for everyday existence forces one to return to social psychology, but with a biological perspective. The brain hedonic system may be a limited resource (50). One can expend this resource rapidly in a binge of drug-taking or other compulsive behavior, but at a great risk for entrance into the spiralling dysregulation of the addiction cycle. Alternately, one can adopt a more regulated, „hedonic Calvinistic“ approach (51) where use of the reward system is restricted within the homeostatic boundary (that is, without the development of subsequent negative affect). Such an ascetic view may or may not fall within certain cultural norms, but probably makes biological sense.

REFERENCES AND NOTES

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CIA Drug Ops conspiracy (unaired)

American Drug War: the last white hope