Columbia University neuroscientist​ gives new perspective on drug abuse and addiction

“I grew up in the hood in Miami in a poor neighborhood. I came from a community in which drug use was prevalent. I kept a gun in my car. I engaged in petty crime. I used and sold drugs. But I stand before you today also — emphasis on also — a professor at Columbia University who studies drug addiction.”

That’s how Dr. Carl Hart, a neuroscientist and professor of psychology and psychiatry, opened a recent TED talk he gave about his research into addiction. After his difficult youth, Hart said he toed the drug war line for a number of years: “I fully believed that the crime and poverty in my community was a direct result of crack cocaine.” He bought into the notion, pushed by policymakers in the 1980s and 1990s, that you could get hooked on crack and other drugs after just one hit.

But his research has disabused him of these notions. He recruited cocaine and meth users into his lab, and over a period of several days offered them some options: they could either receive hits of their drug of choice, or they could take payments of five dollars instead. Crucially, the payments offered were less than the value of the drugs they could consume.

Contrary to the notion of the craven drug fiend who will do literally anything for one more hit, Hart found that half of cocaine and meth users opted for the money over the drugs. And when he increased the payments to 20 dollars, closer to 80 percent of meth users chose the money. The lesson? “Attractive alternatives dramatically decrease drug use,” he said in his talk.

This speaks to another point Hart made, which is worth quoting at length:

80 to 90 percent of people who use illegal drugs are not addicts. They don’t have a drug problem. Most are responsible members of our society. They are employed. They pay their taxes. They take care of their families. And in some cases they even become president of the United States.

He’s right, of course. Among people who have ever used marijuana, only 9 percent become addicted. That rate is 11 percent for cocaine and 17 percent for stimulants like meth. Even the vast majority of people who use heroin — 77 percent of them — never get addicted to the drug.

When it comes to his own kids, Hart, who is black, is less worried about drugs and more worried about the people who enforce drug laws. He says that the effects of drugs at the individual-level are predictable and easy to understand: you smoke some weed, you will experience X effects after Y amount of time. But interactions with the police are a different story. “I don’t know how to keep my children safe with the police because, particularly when it comes to Black folks, interactions with police are not predictable,” he said in a recent Q&A hosted by the Drug Policy Alliance and reported in Ebony magazine.

Thanks to Kebmodee for bringing this to the It’s Interesting community.

The Likely Cause of Addiction Has Been Discovered, and It Is Not What You Think

by Johann Hari
Author of ‘Chasing The Scream: The First and Last Days of the War on Drugs’

It is now one hundred years since drugs were first banned — and all through this long century of waging war on drugs, we have been told a story about addiction by our teachers and by our governments. This story is so deeply ingrained in our minds that we take it for granted. It seems obvious. It seems manifestly true. Until I set off three and a half years ago on a 30,000-mile journey for my new book, Chasing The Scream: The First And Last Days of the War on Drugs, to figure out what is really driving the drug war, I believed it too. But what I learned on the road is that almost everything we have been told about addiction is wrong — and there is a very different story waiting for us, if only we are ready to hear it.

If we truly absorb this new story, we will have to change a lot more than the drug war. We will have to change ourselves.

I learned it from an extraordinary mixture of people I met on my travels. From the surviving friends of Billie Holiday, who helped me to learn how the founder of the war on drugs stalked and helped to kill her. From a Jewish doctor who was smuggled out of the Budapest ghetto as a baby, only to unlock the secrets of addiction as a grown man. From a transsexual crack dealer in Brooklyn who was conceived when his mother, a crack-addict, was raped by his father, an NYPD officer. From a man who was kept at the bottom of a well for two years by a torturing dictatorship, only to emerge to be elected President of Uruguay and to begin the last days of the war on drugs.

I had a quite personal reason to set out for these answers. One of my earliest memories as a kid is trying to wake up one of my relatives, and not being able to. Ever since then, I have been turning over the essential mystery of addiction in my mind — what causes some people to become fixated on a drug or a behavior until they can’t stop? How do we help those people to come back to us? As I got older, another of my close relatives developed a cocaine addiction, and I fell into a relationship with a heroin addict. I guess addiction felt like home to me.

If you had asked me what causes drug addiction at the start, I would have looked at you as if you were an idiot, and said: “Drugs. Duh.” It’s not difficult to grasp. I thought I had seen it in my own life. We can all explain it. Imagine if you and I and the next twenty people to pass us on the street take a really potent drug for twenty days. There are strong chemical hooks in these drugs, so if we stopped on day twenty-one, our bodies would need the chemical. We would have a ferocious craving. We would be addicted. That’s what addiction means.

One of the ways this theory was first established is through rat experiments — ones that were injected into the American psyche in the 1980s, in a famous advert by the Partnership for a Drug-Free America. You may remember it. The experiment is simple. Put a rat in a cage, alone, with two water bottles. One is just water. The other is water laced with heroin or cocaine. Almost every time you run this experiment, the rat will become obsessed with the drugged water, and keep coming back for more and more, until it kills itself.

The advert explains: “Only one drug is so addictive, nine out of ten laboratory rats will use it. And use it. And use it. Until dead. It’s called cocaine. And it can do the same thing to you.”

But in the 1970s, a professor of Psychology in Vancouver called Bruce Alexander noticed something odd about this experiment. The rat is put in the cage all alone. It has nothing to do but take the drugs. What would happen, he wondered, if we tried this differently? So Professor Alexander built Rat Park. It is a lush cage where the rats would have colored balls and the best rat-food and tunnels to scamper down and plenty of friends: everything a rat about town could want. What, Alexander wanted to know, will happen then?

In Rat Park, all the rats obviously tried both water bottles, because they didn’t know what was in them. But what happened next was startling.

The rats with good lives didn’t like the drugged water. They mostly shunned it, consuming less than a quarter of the drugs the isolated rats used. None of them died. While all the rats who were alone and unhappy became heavy users, none of the rats who had a happy environment did.

At first, I thought this was merely a quirk of rats, until I discovered that there was — at the same time as the Rat Park experiment — a helpful human equivalent taking place. It was called the Vietnam War. Time magazine reported using heroin was “as common as chewing gum” among U.S. soldiers, and there is solid evidence to back this up: some 20 percent of U.S. soldiers had become addicted to heroin there, according to a study published in the Archives of General Psychiatry. Many people were understandably terrified; they believed a huge number of addicts were about to head home when the war ended.

But in fact some 95 percent of the addicted soldiers — according to the same study — simply stopped. Very few had rehab. They shifted from a terrifying cage back to a pleasant one, so didn’t want the drug any more.

Professor Alexander argues this discovery is a profound challenge both to the right-wing view that addiction is a moral failing caused by too much hedonistic partying, and the liberal view that addiction is a disease taking place in a chemically hijacked brain. In fact, he argues, addiction is an adaptation. It’s not you. It’s your cage.

After the first phase of Rat Park, Professor Alexander then took this test further. He reran the early experiments, where the rats were left alone, and became compulsive users of the drug. He let them use for fifty-seven days — if anything can hook you, it’s that. Then he took them out of isolation, and placed them in Rat Park. He wanted to know, if you fall into that state of addiction, is your brain hijacked, so you can’t recover? Do the drugs take you over? What happened is — again — striking. The rats seemed to have a few twitches of withdrawal, but they soon stopped their heavy use, and went back to having a normal life. The good cage saved them. (The full references to all the studies I am discussing are in the book.)

When I first learned about this, I was puzzled. How can this be? This new theory is such a radical assault on what we have been told that it felt like it could not be true. But the more scientists I interviewed, and the more I looked at their studies, the more I discovered things that don’t seem to make sense — unless you take account of this new approach.

Here’s one example of an experiment that is happening all around you, and may well happen to you one day. If you get run over today and you break your hip, you will probably be given diamorphine, the medical name for heroin. In the hospital around you, there will be plenty of people also given heroin for long periods, for pain relief. The heroin you will get from the doctor will have a much higher purity and potency than the heroin being used by street-addicts, who have to buy from criminals who adulterate it. So if the old theory of addiction is right — it’s the drugs that cause it; they make your body need them — then it’s obvious what should happen. Loads of people should leave the hospital and try to score smack on the streets to meet their habit.

But here’s the strange thing: It virtually never happens. As the Canadian doctor Gabor Mate was the first to explain to me, medical users just stop, despite months of use. The same drug, used for the same length of time, turns street-users into desperate addicts and leaves medical patients unaffected.

If you still believe — as I used to — that addiction is caused by chemical hooks, this makes no sense. But if you believe Bruce Alexander’s theory, the picture falls into place. The street-addict is like the rats in the first cage, isolated, alone, with only one source of solace to turn to. The medical patient is like the rats in the second cage. She is going home to a life where she is surrounded by the people she loves. The drug is the same, but the environment is different.

This gives us an insight that goes much deeper than the need to understand addicts. Professor Peter Cohen argues that human beings have a deep need to bond and form connections. It’s how we get our satisfaction. If we can’t connect with each other, we will connect with anything we can find — the whirr of a roulette wheel or the prick of a syringe. He says we should stop talking about ‘addiction’ altogether, and instead call it ‘bonding.’ A heroin addict has bonded with heroin because she couldn’t bond as fully with anything else.

So the opposite of addiction is not sobriety. It is human connection.

When I learned all this, I found it slowly persuading me, but I still couldn’t shake off a nagging doubt. Are these scientists saying chemical hooks make no difference? It was explained to me — you can become addicted to gambling, and nobody thinks you inject a pack of cards into your veins. You can have all the addiction, and none of the chemical hooks. I went to a Gamblers’ Anonymous meeting in Las Vegas (with the permission of everyone present, who knew I was there to observe) and they were as plainly addicted as the cocaine and heroin addicts I have known in my life. Yet there are no chemical hooks on a craps table.

But still, surely, I asked, there is some role for the chemicals? It turns out there is an experiment which gives us the answer to this in quite precise terms, which I learned about in Richard DeGrandpre’s book The Cult of Pharmacology.

Everyone agrees cigarette smoking is one of the most addictive processes around. The chemical hooks in tobacco come from a drug inside it called nicotine. So when nicotine patches were developed in the early 1990s, there was a huge surge of optimism — cigarette smokers could get all of their chemical hooks, without the other filthy (and deadly) effects of cigarette smoking. They would be freed.

But the Office of the Surgeon General has found that just 17.7 percent of cigarette smokers are able to stop using nicotine patches. That’s not nothing. If the chemicals drive 17.7 percent of addiction, as this shows, that’s still millions of lives ruined globally. But what it reveals again is that the story we have been taught about The Cause of Addiction lying with chemical hooks is, in fact, real, but only a minor part of a much bigger picture.

This has huge implications for the one-hundred-year-old war on drugs. This massive war — which, as I saw, kills people from the malls of Mexico to the streets of Liverpool — is based on the claim that we need to physically eradicate a whole array of chemicals because they hijack people’s brains and cause addiction. But if drugs aren’t the driver of addiction — if, in fact, it is disconnection that drives addiction — then this makes no sense.

Ironically, the war on drugs actually increases all those larger drivers of addiction. For example, I went to a prison in Arizona — ‘Tent City’ — where inmates are detained in tiny stone isolation cages (‘The Hole’) for weeks and weeks on end to punish them for drug use. It is as close to a human recreation of the cages that guaranteed deadly addiction in rats as I can imagine. And when those prisoners get out, they will be unemployable because of their criminal record — guaranteeing they with be cut off even more. I watched this playing out in the human stories I met across the world.

There is an alternative. You can build a system that is designed to help drug addicts to reconnect with the world — and so leave behind their addictions.

This isn’t theoretical. It is happening. I have seen it. Nearly fifteen years ago, Portugal had one of the worst drug problems in Europe, with 1 percent of the population addicted to heroin. They had tried a drug war, and the problem just kept getting worse. So they decided to do something radically different. They resolved to decriminalize all drugs, and transfer all the money they used to spend on arresting and jailing drug addicts, and spend it instead on reconnecting them — to their own feelings, and to the wider society. The most crucial step is to get them secure housing, and subsidized jobs so they have a purpose in life, and something to get out of bed for. I watched as they are helped, in warm and welcoming clinics, to learn how to reconnect with their feelings, after years of trauma and stunning them into silence with drugs.

One example I learned about was a group of addicts who were given a loan to set up a removals firm. Suddenly, they were a group, all bonded to each other, and to the society, and responsible for each other’s care.

The results of all this are now in. An independent study by the British Journal of Criminology found that since total decriminalization, addiction has fallen, and injecting drug use is down by 50 percent. I’ll repeat that: injecting drug use is down by 50 percent. Decriminalization has been such a manifest success that very few people in Portugal want to go back to the old system. The main campaigner against the decriminalization back in 2000 was Joao Figueira, the country’s top drug cop. He offered all the dire warnings that we would expect from the Daily Mail or Fox News. But when we sat together in Lisbon, he told me that everything he predicted had not come to pass — and he now hopes the whole world will follow Portugal’s example.

This isn’t only relevant to the addicts I love. It is relevant to all of us, because it forces us to think differently about ourselves. Human beings are bonding animals. We need to connect and love. The wisest sentence of the twentieth century was E.M. Forster’s — “only connect.” But we have created an environment and a culture that cut us off from connection, or offer only the parody of it offered by the Internet. The rise of addiction is a symptom of a deeper sickness in the way we live — constantly directing our gaze towards the next shiny object we should buy, rather than the human beings all around us.

The writer George Monbiot has called this “the age of loneliness.” We have created human societies where it is easier for people to become cut off from all human connections than ever before. Bruce Alexander — the creator of Rat Park — told me that for too long, we have talked exclusively about individual recovery from addiction. We need now to talk about social recovery — how we all recover, together, from the sickness of isolation that is sinking on us like a thick fog.

But this new evidence isn’t just a challenge to us politically. It doesn’t just force us to change our minds. It forces us to change our hearts.

Loving an addict is really hard. When I looked at the addicts I love, it was always tempting to follow the tough love advice doled out by reality shows like Intervention — tell the addict to shape up, or cut them off. Their message is that an addict who won’t stop should be shunned. It’s the logic of the drug war, imported into our private lives. But in fact, I learned, that will only deepen their addiction — and you may lose them altogether. I came home determined to tie the addicts in my life closer to me than ever — to let them know I love them unconditionally, whether they stop, or whether they can’t.

When I returned from my long journey, I looked at my ex-boyfriend, in withdrawal, trembling on my spare bed, and I thought about him differently. For a century now, we have been singing war songs about addicts. It occurred to me as I wiped his brow, we should have been singing love songs to them all along.

The full story of Johann Hari’s journey — told through the stories of the people he met — can be read in Chasing The Scream: The First and Last Days of the War on Drugs, published by Bloomsbury. The book has been praised by everyone from Elton John to Glenn Greenwald to Naomi Klein. You can buy it at all good bookstores and read more at http://www.chasingthescream.com.

Johann Hari will be talking about his book at 7pm at Politics and Prose in Washington DC on the 29th of January, at lunchtime at the 92nd Street Y in New York City on the 30th January, and in the evening at Red Emma’s in Baltimore on the 4th February.

Thanks to Da Brayn for bringing this to the attention of the It’s Interesting community.

http://www.huffingtonpost.com/johann-hari/the-real-cause-of-addicti_b_6506936.html

Richard A. Friedman: Why can’t doctors identify killers?

MASS killers like Elliot Rodger teach society all the wrong lessons about the connection between violence, mental illness and guns — and what we should do about it. One of the biggest misconceptions, pushed by our commentators and politicians, is that we can prevent these tragedies if we improve our mental health care system. It is a comforting notion, but nothing could be further from the truth.

And although the intense media attention might suggest otherwise, mass killings — when four or more people are killed at once — are very rare events. In 2012, they accounted for only about 0.15 percent of all homicides in the United States. Because of their horrific nature, however, they receive lurid media attention that distorts the public’s perception about the real risk posed by the mentally ill.

Anyone who watched Elliot Rodger’s chilling YouTube video, detailing his plan for murderous vengeance before he killed six people last week near Santa Barbara, Calif., would understandably conflate madness with violence. While it is true that most mass killers have a psychiatric illness, the vast majority of violent people are not mentally ill and most mentally ill people are not violent. Indeed, only about 4 percent of overall violence in the United States can be attributed to those with mental illness. Most homicides in the United States are committed by people without mental illness who use guns.

Mass killers are almost always young men who tend to be angry loners. They are often psychotic, seething with resentment and planning revenge for perceived slights and injuries. As a group, they tend to avoid contact with the mental health care system, so it’s tough to identify and help them. Even when they have received psychiatric evaluation and treatment, as in the case of Mr. Rodger and Adam Lanza, who killed 20 children and seven adults, including his mother, in Connecticut in 2012, we have to acknowledge that our current ability to predict who is likely to be violent is no better than chance.

Large epidemiologic studies show that psychiatric illness is a risk factor for violent behavior, but the risk is small and linked only to a few serious mental disorders. People with schizophrenia, major depression or bipolar disorder were two to three times as likely as those without these disorders to be violent. The actual lifetime prevalence of violence among people with serious mental illness is about 16 percent compared with 7 percent among people who are not mentally ill.

What most people don’t know is that drug and alcohol abuse are far more powerful risk factors for violence than other psychiatric illnesses. Individuals who abuse drugs or alcohol but have no other psychiatric disorder are almost seven times more likely than those without substance abuse to act violently.

As a psychiatrist, I welcome calls from our politicians to improve our mental health care system. But even the best mental health care is unlikely to prevent these tragedies.

If we can’t reliably identify people who are at risk of committing violent acts, then how can we possibly prevent guns from falling into the hands of those who are likely to kill? Mr. Rodger had no problem legally buying guns because he had neither been institutionalized nor involuntarily hospitalized, both of which are generally factors that would have prevented him from purchasing firearms.

Would lowering the threshold for involuntary psychiatric treatment, as some argue, be effective in preventing mass killings or homicide in general?

It’s doubtful.

The current guideline for psychiatric treatment over the objection of the patient is, in most states, imminent risk of harm to self or others. Short of issuing a direct threat of violence or appearing grossly disturbed, you will not receive involuntary treatment. When Mr. Rodger was interviewed by the police after his mother expressed alarm about videos he had posted, several weeks ago, he appeared calm and in control and was thus not apprehended. In other words, a normal-appearing killer who is quietly planning a massacre can easily evade detection.

In the wake of these horrific killings, it would be understandable if the public wanted to make it easier to force treatment on patients before a threat is issued. But that might simply discourage other mentally ill people from being candid and drive some of the sickest patients away from the mental health care system.

We have always had — and always will have — Adam Lanzas and Elliot Rodgers. The sobering fact is that there is little we can do to predict or change human behavior, particularly violence; it is a lot easier to control its expression, and to limit deadly means of self-expression. In every state, we should prevent individuals with a known history of serious psychiatric illness or substance abuse, both of which predict increased risk of violence, from owning or purchasing guns.

But until we make changes like that, the tragedy of mass killings will remain a part of American life.

Richard A. Friedman is a professor of clinical psychiatry and the director of the psychopharmacology clinic at the Weill Cornell Medical College.

End The War On Drugs, Say Nobel Prize-Winning Economists

war_on_drugs_thumb

The decades-long global war on drugs has failed and it’s time to shift the focus from mass incarceration to public health and human rights, according to a new report endorsed by five Nobel Prize-winning economists.

The report, titled “Ending the Drug Wars” and put together by the London School of Economics’ IDEAS center, looks at the high costs and unintended consequences of drug prohibitions on public health and safety, national security and law enforcement.

“The pursuit of a militarized and enforcement-led global ‘war on drugs’ strategy has produced enormous negative outcomes and collateral damage,” says the 82-page report. “These include mass incarceration in the US, highly repressive policies in Asia, vast corruption and political destabilization in Afghanistan and West Africa, immense violence in Latin America, an HIV epidemic in Russia, an acute global shortage of pain medication and the propagation of systematic human rights abuses around the world.”

The report urges the world’s governments to reframe their drug policies around treatment and harm reduction rather than prosecution and prison.

It is also aimed at the United Nations General Assembly, which is preparing to convene a special session on drug policy in 2016. The hope is to push the U.N. to encourage countries to develop their own policies, because the report declares the current one-size-fits-all approach has not proved to be effective.

“The UN must recognize its role is to assist states as they pursue best-practice policies based on scientific evidence, not undermine or counteract them,” said Danny Quah, a professor of economics at LSE and a contributor to the report. “If this alignment occurs, a new and effective international regime can emerge that effectively tackles the global drug problem.”

In addition to contributions from Quah and a dozen other foreign and drug policy experts, the report has been endorsed by five past winners of the Nobel Prize in Economics: Kenneth Arrow (1972), Sir Christopher Pissarides (2010), Thomas Schelling (2005), Vernon Smith (2002) and Oliver Williamson (2009). Also signing on to the report’s foreword are a number of current and former international leaders, including George Shultz, secretary of state under President Ronald Reagan; Nick Clegg, British deputy prime minister; and Javier Solana, the former EU high representative for common foreign and security policy.

Guatemalan President Otto Perez Molina, who has announced that his government may present a plan to legalize production of marijuana and opium poppies by the end of 2014, has also publicly backed the report. Molina plans to discuss the report at the U.N.

A recent Pew survey suggests that Americans may be ready to refocus the U.S. end of the drug war, with 67 percent favoring policies that would provide drug treatment.

“The drug war’s failure has been recognized by public health professionals, security experts, human rights authorities and now some of the world’s most respected economists,” said John Collins, the International Drug Policy Project coordinator at LSE IDEAS. “Leaders need to recognize that toeing the line on current drug control strategies comes with extraordinary human and financial costs to their citizens and economies.”

http://www.huffingtonpost.com/2014/05/06/end-drug-war_n_5275078.html?utm_hp_ref=politics

Thanks to Dr. Lutter for bringing this to the attention of the It’s Interesting community.

First cases of flesh-eating drug Krokodil surface in US

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A man prepares heroin in Zhukovsky, Russia, near Moscow. To produce krokodil, which has a comparable effect to heroin but is much cheaper to make, users mix codeine with gasoline, paint thinner, iodine, hydrochloric acid and red phosphorous.

Krokodil, a flesh-eating drug which first surfaced in Russia more than a decade ago, has reportedly been found in the United States.

Similar to morphine or heroin, krokodil is made by mixing codeine with substances like gasoline, paint thinner, oil or alcohol. That mixture is then injected into a vein, potentially causing an addict’s skin to turn greenish, scaly and eventually rot away.

Dr. Frank LoVecchio, co-medical director at Banner Good Samaritan Poison and Drug Information Center in Arizona, told CBS5 that the first two cases of people using the drug have been reported in the state. He declined to comment on the patients’ conditions.

“As far as I know, these are the first cases in the United States that are reported,” LoVecchio said, adding that the cases are believed to be linked. “So we’re extremely frightened.”

Users of krokodil — or desomorphine — had previously only been found in large numbers in Russia, where 65 million doses of the opiate were seized during the first three months of 2011, Russia’s Federal Drug Control Service told Time.

“This is really frightening,” Dr. Aaron Skolnik, a toxicologist at Banner Good Samaritan Poison and Drug Information Center told MyFoxPhoenix.com. “This is something we hoped would never make it to the U.S. because it’s so detrimental to the people who use it.”

To produce the potentially deadly drug, which has a comparable effect to heroin but is much cheaper to make, users mix codeine with gasoline, paint thinner, iodine, hydrochloric acid and red phosphorous. Codeine, a controlled substance in the United States used to treat mild to moderate pain, is widely available over the counter in Russia.

In 2010, up to a million people, according to various estimates, were injecting the resulting substance into their veins in Russia, thus far the only country worldwide to see it grow into an epidemic, Time reports.

The drug’s sinister moniker — also known as crocodile — refers to the greenish and scaly appearance of a user’s skin at the site of injection as blood vessels rupture and cause surrounding tissues to die. According to reports, the drug first appeared in Siberia and parts of Russia around 2002, but has spread throughout the country in recent years.

Officials at the Washington-based National Institute on Drug Abuse told FoxNews.com in 2011 that they had not heard of the drug prior to an inquiry by FoxNews.com.

Dr. Ellen Marmur, chief of dermatological and cosmetic surgery at the Mount Sinai Medical Center in New York City, told FoxNews.com in 2011 she had never seen any cases involving krokodil, but said it reminded her of “skin popping,” or when intravenous drug users inject a substance directly into their skin due to damaged veins.

“This looks to me a lot like skin popping, what drug users used to do back in the day with heroin and other drugs,” Marmur said. “It just kills the skin, that’s what you’re seeing, big dead pieces of skin.”

Those large pieces of dead skin are referred to as eschars, Marmur said, leaving the user prone to infection, amputation and other complications.

Marmur said at the time that she was concerned the drug could eventually make its way into the United States.

“It’s horrible,” she continued. “These people are the ultimate in self-destructive drug addiction. Once you’re an addict at this level, any rational thinking doesn’t apply.”

Dr. Lewis Nelson, a medical toxicologist at Bellevue Hospital Center in New York, also said in 2011 that he doubted krokodil would reach the United States due to the availability of other cheap, powerful drugs such as black tar heroin and Oxycontin.

“It’s not going to become a club drug, I can guarantee you that,” he said.

http://www.foxnews.com/health/2013/09/26/first-cases-flesh-eating-drug-krokodil-surface-in-us/

Cocaine Vaccine Passes Key Testing Hurdle of Preventing Drug from Reaching the Brain – Human Clinical Trials soon

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Researchers at Weill Cornell Medical College have successfully tested their novel anti-cocaine vaccine in primates, bringing them closer to launching human clinical trials. Their study, published online by the journal Neuropsychopharmacology, used a radiological technique to demonstrate that the anti-cocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high.

“The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain,” says the study’s lead investigator, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College. “We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug,” he says. “Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect.”

Dr. Crystal says he expects to begin human testing of the anti-cocaine vaccine within a year.

Cocaine, a tiny molecule drug, works to produce feelings of pleasure because it blocks the recycling of dopamine — the so-called “pleasure” neurotransmitter — in two areas of the brain, the putamen in the forebrain and the caudate nucleus in the brain’s center. When dopamine accumulates at the nerve endings, “you get this massive flooding of dopamine and that is the feel good part of the cocaine high,” says Dr. Crystal.

The novel vaccine Dr. Crystal and his colleagues developed combines bits of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into an animal, its body “sees” the cold virus and mounts an immune response against both the virus and the cocaine impersonator that is hooked to it. “The immune system learns to see cocaine as an intruder,” says Dr. Crystal. “Once immune cells are educated to regard cocaine as the enemy, it produces antibodies, from that moment on, against cocaine the moment the drug enters the body.”

In their first study in animals, the researchers injected billions of their viral concoction into laboratory mice, and found a strong immune response was generated against the vaccine. Also, when the scientists extracted the antibodies produced by the mice and put them in test tubes, it gobbled up cocaine. They also saw that mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.

In this study, the researchers sought to precisely define how effective the anti-cocaine vaccine is in non-human primates, who are closer in biology to humans than mice. They developed a tool to measure how much cocaine attached to the dopamine transporter, which picks up dopamine in the synapse between neurons and brings it out to be recycled. If cocaine is in the brain, it binds on to the transporter, effectively blocking the transporter from ferrying dopamine out of the synapse, keeping the neurotransmitter active to produce a drug high.

In the study, the researchers attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be seen using positron emission tomography (PET). The tool measured how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine.

The PET studies showed no difference in the binding of the tracer to the dopamine transporter in vaccinated compared to unvaccinated animals if these two groups were not given cocaine. But when cocaine was given to the primates, there was a significant drop in activity of the tracer in non-vaccinated animals. That meant that without the vaccine, cocaine displaced the tracer in binding to the dopamine receptor.

Previous research had shown in humans that at least 47 percent of the dopamine transporter had to be occupied by cocaine in order to produce a drug high. The researchers found, in vaccinated primates, that cocaine occupancy of the dopamine receptor was reduced to levels of less than 20 percent.

“This is a direct demonstration in a large animal, using nuclear medicine technology, that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high,” says Dr. Crystal.

When the vaccine is studied in humans, the non-toxic dopamine transporter tracer can be used to help study its effectiveness as well, he adds.

The researchers do not know how often the vaccine needs to be administered in humans to maintain its anti-cocaine effect. One vaccine lasted 13 weeks in mice and seven weeks in non-human primates.

“An anti-cocaine vaccination will require booster shots in humans, but we don’t know yet how often these booster shots will be needed,” says Dr. Crystal. “I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.”

Co-authors of the study include Dr. Anat Maoz, Dr. Martin J. Hicks, Dr. Shankar Vallabhajosula, Michael Synan, Dr. Paresh J. Kothari, Dr. Jonathan P. Dyke, Dr. Douglas J. Ballon, Dr. Stephen M. Kaminsky, Dr. Bishnu P. De and Dr. Jonathan B. Rosenberg from Weill Cornell Medical College; Dr. Diana Martinez from Columbia University; and Dr. George F. Koob and Dr. Kim D. Janda from The Scripps Research Institute.

The study was funded by grants from the National Institute on Drug Abuse (NIDA).

Thanks to Kebmodee and Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

Largest psychiatric genetic study in history shows a common genetic basis that underlies 5 types of mental disorders

Protein_CACNA1C_PDB_2be6
Structure of the CACNA1C gene product, a calcium channel named Cav1.2, which is one of 4 genes that has now been found to be genetically held in common amongst schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disoder. Groundbreaking work on the role of this protein on anxiety and other forms of behavior related to mental illness has previously been established in the Rajadhyaksha laboratory at Weill Cornell Medical Center.
http://weill.cornell.edu/research/arajadhyaksha/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481072/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192195/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077109/

From the New York Times:
The psychiatric illnesses seem very different — schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disorder. Yet they share several genetic glitches that can nudge the brain along a path to mental illness, researchers report. Which disease, if any, develops is thought to depend on other genetic or environmental factors.

Their study, published online Wednesday in the Lancet, was based on an examination of genetic data from more than 60,000 people worldwide. Its authors say it is the largest genetic study yet of psychiatric disorders. The findings strengthen an emerging view of mental illness that aims to make diagnoses based on the genetic aberrations underlying diseases instead of on the disease symptoms.

Two of the aberrations discovered in the new study were in genes used in a major signaling system in the brain, giving clues to processes that might go awry and suggestions of how to treat the diseases.

“What we identified here is probably just the tip of an iceberg,” said Dr. Jordan Smoller, lead author of the paper and a professor of psychiatry at Harvard Medical School and Massachusetts General Hospital. “As these studies grow we expect to find additional genes that might overlap.”

The new study does not mean that the genetics of psychiatric disorders are simple. Researchers say there seem to be hundreds of genes involved and the gene variations discovered in the new study confer only a small risk of psychiatric disease.

Steven McCarroll, director of genetics for the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T., said it was significant that the researchers had found common genetic factors that pointed to a specific signaling system.

“It is very important that these were not just random hits on the dartboard of the genome,” said Dr. McCarroll, who was not involved in the new study.

The work began in 2007 when a large group of researchers began investigating genetic data generated by studies in 19 countries and including 33,332 people with psychiatric illnesses and 27,888 people free of the illnesses for comparison. The researchers studied scans of people’s DNA, looking for variations in any of several million places along the long stretch of genetic material containing three billion DNA letters. The question: Did people with psychiatric illnesses tend to have a distinctive DNA pattern in any of those locations?

Researchers had already seen some clues of overlapping genetic effects in identical twins. One twin might have schizophrenia while the other had bipolar disorder. About six years ago, around the time the new study began, researchers had examined the genes of a few rare families in which psychiatric disorders seemed especially prevalent. They found a few unusual disruptions of chromosomes that were linked to psychiatric illnesses. But what surprised them was that while one person with the aberration might get one disorder, a relative with the same mutation got a different one.

Jonathan Sebat, chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at the University of California, San Diego, and one of the discoverers of this effect, said that work on these rare genetic aberrations had opened his eyes. “Two different diagnoses can have the same genetic risk factor,” he said.

In fact, the new paper reports, distinguishing psychiatric diseases by their symptoms has long been difficult. Autism, for example, was once called childhood schizophrenia. It was not until the 1970s that autism was distinguished as a separate disorder.

But Dr. Sebat, who did not work on the new study, said that until now it was not clear whether the rare families he and others had studied were an exception or whether they were pointing to a rule about multiple disorders arising from a single genetic glitch.

“No one had systematically looked at the common variations,” in DNA, he said. “We didn’t know if this was particularly true for rare mutations or if it would be true for all genetic risk.” The new study, he said, “shows all genetic risk is of this nature.”

The new study found four DNA regions that conferred a small risk of psychiatric disorders. For two of them, it is not clear what genes are involved or what they do, Dr. Smoller said. The other two, though, involve genes that are part of calcium channels, which are used when neurons send signals in the brain.

“The calcium channel findings suggest that perhaps — and this is a big if — treatments to affect calcium channel functioning might have effects across a range of disorders,” Dr. Smoller said.

There are drugs on the market that block calcium channels — they are used to treat high blood pressure — and researchers had already postulated that they might be useful for bipolar disorder even before the current findings.

One investigator, Dr. Roy Perlis of Massachusetts General Hospital, just completed a small study of a calcium channel blocker in 10 people with bipolar disorder and is about to expand it to a large randomized clinical trial. He also wants to study the drug in people with schizophrenia, in light of the new findings. He cautions, though, that people should not rush out to take a calcium channel blocker on their own.

“We need to be sure it is safe and we need to be sure it works,” Dr. Perlis said.

Smoking Smothers Your Genes

sn-epigenetic

Cigarettes leave you with more than a smoky scent on your clothes and fingernails. A new study has found strong evidence that tobacco use can chemically modify and affect the activity of genes known to increase the risk of developing cancer. The finding may give researchers a new tool to assess cancer risk among people who smoke.

DNA isn’t destiny. Chemical compounds that affect the functioning of genes can bind to our genetic material, turning certain genes on or off. These so-called epigenetic modifications can influence a variety of traits, such as obesity and sexual preference. Scientists have even identified specific epigenetic patterns on the genes of people who smoke. None of the modified genes has a direct link to cancer, however, making it unclear whether these chemical alterations increase the risk of developing the disease.

In the new study, published in Human Molecular Genetics, researchers analyzed epigenetic signatures in blood cells from 374 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition. EPIC, as it’s known, is a massive study aimed at linking diet, lifestyle, and environmental factors to the incidence of cancer and other chronic diseases. Half of the group consisted of people who went on to develop colon or breast cancer 5 to 7 years after first joining the study, whereas the other half remained healthy.

The team, led by James Flanagan, a human geneticist at Imperial College London, discovered a distinct “epigenetic footprint” in study subjects who were smokers. Compared with people who had never smoked, these individuals had fewer chemical tags known as methyl groups—a common type of epigenetic change—on 20 different regions of their DNA. When the researchers extended the analysis to a separate group of patients and mice that had been exposed to tobacco smoke, they narrowed down the epigenetic modifications to several sites located in four genes that have been weakly linked to cancer before. All of these changes should increase the activity of these genes, Flanagan says. It’s unclear why increasing the activity of the genes would cause cancer, he says, but individuals who don’t have cancer tend not to have these modifications.

The study is the first to establish a close link between epigenetic modifications on a cancer gene and the risk of developing the disease, says Robert Philibert, a behavioral geneticist at the University of Iowa in Iowa City. “To the best of my knowledge, no previous genome-wide epigenetics study has taken such efforts from initial discovery to replication to experimental validation,” adds Lutz Breitling, an epidemiologist at the German Cancer Research Center in Heidelberg, Germany.

The work may lead to new ways to asses cancer risks from smoking. “Previous research into smoking has often asked people to fill out questionnaires, … which have their obvious drawbacks and inaccuracies,” Flanagan says. The new study, he says, may make it possible for doctors to quantify a person’s cancer risk simply through an epigenetic analysis of their DNA.

http://news.sciencemag.org/sciencenow/2012/12/smoking-smothers-your-genes.html

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.