A clinical trial to test better treatment options for chronic heroin addiction is expected to begin in Vancouver at the end of this year. Led by researchers from Providence Health Care and the University of British Columbia, it’s the only clinical trial of its kind in North America.

The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) is a carefully controlled three-year clinical trial that will test whether hydromorphone (Dilaudid(R)), a licensed pain medication, is as effective as diacetylmorphine, the active ingredient of heroin, at engaging the most vulnerable long-term street heroin users, so they will enroll in treatment programs and end their use of illicit drugs.

The intent of the SALOME project is to determine whether some participants become healthier and reduce their illicit drug use or are able to switch to other forms of treatment. SALOME also intends to test if, after stabilizing patients on injectable medications, they can transition to oral formulations without losing effectiveness.

This study builds on the North American Opiate Medication Initiative (NAOMI), which was North America’s first-ever clinical trial of prescribed heroin that took place from 2005 to 2008. NAOMI, which also was led by researchers from Providence Health Care and UBC, was a randomized trial aimed at testing whether medically prescribed heroin (diacetylmorphine) was more effective than methadone therapy for individuals with chronic heroin addiction who were not benefiting from other conventional treatments.

The results, published in the New England Journal of Medicine, showed that patients treated with the prescribed heroin were more likely to stay in treatment or quit heroin altogether and more likely to reduce their use of illegal drugs and other illegal activities than patients treated with oral methadone.

In the NAOMI study, the researchers also provided a small sample of patients with injectable hydromorphone, (Dilaudid(R)). An unexpected finding was that injection patients could not accurately discriminate whether they were receiving prescribed heroin or hydromorphone. The researchers also observed similar results and benefits with both these drugs although the small number of participants receiving hydromorphone did not permit any definite and scientifically valid conclusions to be drawn as to the efficacy of hydromorphone as a viable treatment option.

Should hydromorphone be proven to be as affective as heroin, the benefits of this form of injectable treatment may be more feasible and achievable without the emotional and regulatory barriers often presented by heroin maintenance.
SALOME, led by Dr. Michael Krausz, the Providence Health Care/UBC B.C. Leadership Chair in Addiction Research and Dr. Eugenia Oviedo-Joekes, Providence Health Care researcher and an assistant professor in UBC’s School of Population and Public Health, will enroll 322 individuals with chronic heroin dependency who currently are not sufficiently benefiting from conventional therapies, such as methadone treatment, at one site based in Vancouver, BC.

In the first stage, half of the 322 participants will receive injectable prescribed heroin, and the other half will receive injectable hydromorphone. Stage I will involve six-months of treatment. All volunteers retained in injection treatment at the end of Stage I will be eligible to enter Stage II.

In Stage II, half of the participants will then continue injection treatment exactly as in Stage I on a blinded basis while the other half will switch to the oral equivalent of the same medication (prescribed heroin or hydromorphone). Stage II will also involve six-months of treatment.

Throughout the treatment period, social workers will be assigned to both groups to assist them with reaching other addiction services and community resources such as counseling, housing and job training services.

Some 60,000 to 90,000 persons are affected by opioid addiction in Canada. This study will enroll the most chronically drug-dependent members of Vancouver’s population — those who are not benefiting from other treatments, such as methadone therapy and abstinence-based programs, and continue injecting street heroin.

The SALOME study is funded by the Canadian Institutes of Health Research, the Government of Canada’s agency responsible for funding health research in Canada, Providence Health Care and the InnerChange Foundation.

Quotes:
Dr. Perry Kendall, BC’s Provincial Health Officer -
“SALOME addresses critical social and ethical concerns dealing with addiction. Opioid-dependent people are in need of treatment options to avoid marginalization from the health care system and this study aims to answer questions that could lead to improvements in the health of persons with chronic addictions and identify new ways of reintegrating this population into society.”

“If the SALOME study shows that hydromorphone can go head-to-head with heroin as an alternative therapy for people who have failed optimally provided methadone, then I think this should be part of the treatment continuum that’s available through licensed physicians.”

Dianne Doyle, Providence Health Care President and CEO -
“Providence Health Care is supporting this research because it is so aligned with our mission, vision and values. We have a very long tradition of providing compassionate care to the most marginalized and needy in our community, including those suffering from addictions.”

“What we need to get from this research is a better understanding of what the right approaches are to treating addicted populations. In particular our hope would be that we could find a new approach for those people who are addicted and not benefiting from current approaches to care. This treatment option would be one more component of a range of services offered by Providence Health Care and Vancouver Coastal Health, all of which are intended to reduce the harm to individuals and others from drug use, and to support recovery from addiction and mental illness.”

About Providence Health Care

Providence Health Care is one of Canada’s largest faith-based health care organizations, operating 15 facilities within Vancouver Coastal Health. Guided by the principle “How you want to be treated,” PHC’s 1,200 physicians, 6,000 staff and 1,500 volunteers deliver compassionate care to patients and residents in British Columbia. Providence’s programs and services span the complete continuum of care and serve people throughout B.C. PHC operates one of two adult academic health science centres in the province, performs cutting-edge research in more than 30 clinical specialties, and focuses its services on six “populations of emphasis”: cardiopulmonary risks and illnesses, HIV/AIDS, mental health, renal risks and illness, specialized needs in aging and urban health.

About the University of British Columbia

The University of British Columbia (UBC) is one of North America’s largest public research and teaching institutions, and one of only two Canadian institutions consistently ranked among the world’s 40 best universities. Surrounded by the beauty of the Canadian West, it is a place that inspires bold, new ways of thinking that have helped make it a national leader in areas as diverse as community service learning, sustainability and research commercialization. UBC offers more than 50,000 students a range of innovative programs and attracts $550 million per year in research funding from government, non-profit organizations and industry through 7,000 grants.

To view the first video of the SALOME project, please visit the following link: http://www.youtube.com/watch?v=fFgV_bt8QAU&feature=youtu.be

To view the second video of the SALOME project, please visit the following link: http://www.youtube.com/watch?v=S8xfkkeHpdE&feature=related

Source:  www.marketwatch.com  13th Oct. 2011

The number of Americans who died from overdoses of prescription painkillers more than tripled in the past decade, according to the Centers for Disease Control and Prevention (CDC). More people now die from painkillers than from heroin and cocaine combined.

An estimated 14,800 people died in the United States from painkiller overdoses in 2008, a more than threefold jump from the 4,000 deaths recorded in 1999, the CDC said in a new report. Prescription and illegal drugs caused 36,450 deaths in 2008, compared with 39,973 deaths from motor vehicle crashes, according to the Associated Press.

The CDC said painkiller abuse and deaths are rising because the drugs are easier than ever to obtain. They cited the growth of “pill mills,” clinics that prescribe opioids without first conducting medical exams, and “doctor shopping,” or receiving multiple prescriptions from different doctors.   According to the CDC, enough painkillers were prescribed in 2010 to medicate every American adult around the clock for a month. “Right now, the system is awash in opioids—dangerous drugs that got people hooked and keep them hooked,” said CDC Director Thomas Frieden.

“Prescription drug abuse is a silent epidemic that is stealing thousands of lives and tearing apart communities and families across America,” Gil Kerlikowske, Director of National Drug Control Policy, said in a CDC news release. He noted health care providers and patients should be educated on the risks of prescription painkillers. “Parents and grandparents should properly dispose of any unneeded or expired medications from the home and to talk to their kids about the misuse and abuse of prescription drugs,” he noted.

Source: ww.drugfree.org.  2nd Nov.2011

• Marijuana is the most commonly used illicit drug in the United States.
• New research shows that the use and misuse of alcohol and marijuana are influenced by a common set of genes.
Marijuana is the most commonly used illicit drug in the United States. Roughly eight to 12 percent of marijuana users are considered “dependent” and, just like alcohol, the severity of symptoms increases with heavier use. A new study has found that use and misuse of alcohol and marijuana are influenced by a common set of genes.
Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
“Results from a large annual survey of high-school students show that in 2008, 41.8 percent of 12th graders reported having used marijuana,” explained Carolyn E. Sartor, a research instructor at Washington University School of Medicine and corresponding author for the study. “Although many may have used the drug on only a few occasions, 5.4 percent of 12th graders reported using it daily within the preceding month.”
“The active ingredient in marijuana is THC, which mimics natural cannabinoids that the brain produces,” added Christian Hopfer, associate professor at the University of Colorado School of Medicine. “The cannabinoid system is critical for learning, memory, appetite, and pain perception. Most users of marijuana will not develop an ‘addiction’ to it, but perhaps one in 12 will. What is not commonly appreciated about marijuana use is that strong evidence has emerged that it increases the risk of developing mental illnesses and possibly exacerbates pre-existing mental illnesses.”
“Like any drug, marijuana can be used in a way that negatively impacts quality of life, interfering with functioning at school or work or leading to problems with family and friends,” said Sartor. “Although at least three of six symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) are needed to meet full criteria for cannabis (marijuana) dependence … the presence of even one or two of these symptoms could create distress or interfere with day-to-day functioning. There is strong evidence for a genetic component to use and dependence on marijuana as well as alcohol, and the use (and misuse) of these substances frequently occur together.”
Researchers examined 6,257 individuals (2,761 complete twin pairs and 735 singletons) listed in the Australian Twin Registry, 24 to 36 years of age. Alcohol and marijuana use histories were gathered in telephone diagnostic interviews and used to derive levels of alcohol consumption, frequency of marijuana use, and DSM-IV alcohol and cannabis dependence symptoms.
“Our findings indicate that … many of the same genetic factors that contribute to alcohol use also contribute to marijuana use,” said Sartor. “Likewise, alcohol dependence symptoms and cannabis dependence symptoms can be traced to some of the same genetic influences. For both alcohol and marijuana, the majority of genetic factors that contribute to use also contribute to dependence symptoms.”
“In other words,” said Hopfer, “the genetic influences on drug use are not specific to individual drugs, but seem to influence a general tendency to engage in drug use. This is important to note because there is a tendency to study drugs in isolation – alcohol, tobacco, marijuana, cocaine, etc. These findings add support to the notion of common mechanisms underlying all addictions.”
“The fact that very little of the environmental influences on alcohol and marijuana use, or on alcohol and cannabis dependence symptoms, could be traced to common sources indicates that there may be important distinctions between those environmental factors that influence alcohol-related outcomes and those that influence marijuana-related outcomes,” said Sartor. “Identifying alcohol- and marijuana-specific risk factors is an important next step in this line of research.”
“Marijuana research is relatively sparse compared to alcohol or nicotine research,” added Hopfer. “However, if you look at reports of at least adolescents and young people using, it becomes clear that marijuana use, including daily marijuana use, is quite common and the effects of this are not well understood. The mental illness/marijuana connection has not received much press, although I think the evidence has grown substantially that marijuana is a causal risk factor for the development of mental illness.”

Source: http://www.attcnetwork.org/explore/priorityareas/science/tools/asmeDetails.asp?ID=643

Slovenian study identifies which chemicals in the blood best identify dependent drinkers in the sense of not missing those who are dependent, confirming when they have stopped drinking, and not falsely identifying non-dependent people as dependent.

Summary

The aim of this study was to determine the value of biochemical tests for glutamate dehydrogenase (GLDH) in the blood as way of diagnosing alcohol dependence, in particular as compared to or in combination with other biochemical markers including gama-glutamyltransferase (GGT), aspartate-aminotranferase (AST), alanine-aminotransferase (ALT) and erythrocyte mean cell volume (MCV). All these levels were assessed three times in 238 alcohol dependent patients admitted to hospital (on admission, after 24 hours and after seven days) and also in healthy members of the public.
Main findings All the values were significantly higher in the patients than in healthy persons. GLDH exhibited the fastest decrease in levels after the resumption of abstinence. 24 hours of non-drinking is sufficient for a reliable evaluation of the fall in GLDH activity, even more so when alcohol dependants had not drunk for three to seven days, offering a way to confirm the cessation of drinking. The time course of changes in GLDH and AST were more applicable than for GGT after a week, but GLDH changes were most reliable. GLDH was the most specific marker with almost 90% specificity, correctly identifying nine in 10 of the healthy subjects as non-dependent. A decision tree combining MCV,
GGT and GLDH markers was selected as the best diagnostic procedure because of its simplicity, easy examination and moderate cost. It gave a model with 84.5% accuracy, excellent specificity at 90% (correctly identifying 9 in 10 healthy subjects as non-dependent) and very high sensitivity at almost 80% (correctly identifying 8 in 10 alcohol dependent patients as dependent).

Conclusions

The high accuracy of our classification model provides an opportunity to apply it as a helping method in finding and diagnosing alcohol dependence in everyday practice, with our exclusion criteria and differential diagnostic cautions taken into consideration. We strongly believe that watching changes in the activity of laboratory markers of alcoholism is an effective yet overlooked aid.
Thanks for their comments on this entry in draft to Matej Kravos of the Psychiatric Hospital Ormoz in Slovenia. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Source: Kravos M., Malešic I.
Alcohol and Alcoholism: 2010, 45(1), p. 39–44. Revised 22 Aug.2011

Using an integrative meta-analysis approach, researchers from the Center for Bioinformatics at Peking University in Beijing have assembled the most comprehensive gene atlas underlying drug addiction and identified five molecular pathways common to four different addictive drugs.
This novel paper appears in PLoS Computational Biology on January 4, 2008.
Drug addiction is a serious worldwide problem with strong genetic and environmental influences. So far different technologies have revealed a variety of genes and biological processes underlying addiction. However, individual technology can be biased and render only an incomplete picture. Studying individual or a small number of genes is like looking at pieces of a jigsaw puzzle – only when you gather most of the pieces from different places and arrange them together in an orderly fashion do interesting patterns emerge.
The team, led by Liping Wei, surveyed scientific literature published in the past 30 years and collected 2,343 items of evidence linking genes and chromosome regions to addiction based on single-gene strategies, microarray, proteomics, or genetic studies. They made this gene atlas freely available in the first online molecular database for addiction, named KARG (http://karg.cbi.pku.edu.cn), with extensive annotations and friendly web interface.
Assembling the pieces of evidence together, the authors identified 18 molecular pathways that are statistically enriched in the addiction-related genes. They then identified five pathways that are common to addiction to four different substances. These common pathways may underlie shared rewarding and response mechanisms and may be targets for effective treatments for a wide range of addictive disorders.

http://www.plos.org/

Source:News-Medical.net 7th Jan.2008

A new study suggests that abuse of prescription opioids may be a first step on the path toward misuse of heroin and other injected drugs.
Science Daily reports that the researchers found four out of five injection drug users misused an opioid drug before they injected heroin. They also found that almost one out of four young injection drug users first injected a prescription opioid, and most later switched to injecting heroin.
The study, published in the International Journal of Drug Policy, found that risk factors for misusing opioid drugs include family history of drug misuse, and a past history of receiving prescriptions for opioids.
“Participants were commonly raised in households where misuse of prescription drugs, illegal drugs, or alcohol, was normalized,” lead researcher Dr. Stephen Lankenau, from Drexel University in Philadelphia, said in a news release. “Access to prescription medications – either from a participant’s own source, a family member, or a friend – was a key feature of initiation into prescription drug misuse.”
The study included 50 injection drug users between the ages of 16 to 25. They had all misused a prescription drug at least three times in the past three months. Nearly three-fourths of participants had been prescribed an opioid, often for dental procedures or sports injuries. Most had family members who misused one or more substances. The authors called on parents to carefully monitor and safeguard prescription drugs, especially opioids, in their home

Source: International Journal of Drug Policy June 2011

Lying in a hospital bed, 24-year-old Stacey Rhymes cuddles a childhood toy before putting out an arm to her mother.

‘Hold my hand, Mum,’ she whispers, then slips into a coma. A few hours later, on a spring afternoon earlier this year, the girl with a whole life ahead of her was dead.

The once radiantly pretty Stacey had drunk herself to death on cut-price bottles of wine bought from corner shops, supermarkets and local pubs. She had started drinking at 17 and seven years later her body simply gave up under the constant assault from alcohol.

 Her mother, Louise, says: ‘I now want the world to know exactly what happened to Stacey and why. It was a terrible way to go.   ‘Her stomach was like a balloon, as if she was nine months pregnant. Her long hair was falling out, her urine was coloured black and she could not eat. She was scared to look in the mirror because her eyes were canary yellow. The only way to stop the pain at the end was morphine.’

The story of Stacey Rhymes is a salutary one. She is one of the youngest people in modern Britain to die of alcohol abuse. And her mother, speaking for the first time, is determined that the loss of her daughter will not be in vain.
 
She has set up a Facebook website in memory of Stacey to highlight the dangers of alcohol – and particularly its increased availability following New Labour’s 24-hour drinking laws – which now kills more young women than cervical cancer, and more people, generally, than hard drugs.

A film clip about Stacey on YouTube, put there by her mother, has been watched by 16,000 people in a fortnight. It is now one of the most viewed in Britain by children and teenagers.

At the family’s terrace home, in Bramcote, on the outskirts of Nottingham, where Stacey grew up with her brother, Jay, now 19, sister Katie, 21, and stepfather, Terry, her mother says: ‘Alcohol is as treacherous as a Class A drug. Yet it’s available at all hours and at rock-bottom prices.

‘This morning, I saw a pack of four cans of lager at the supermarket for 92p. You can’t get four cans of children’s pop for that! Young children should be warned about alcohol in the way they are warned about drugs.  ‘I want them to be shown a photograph of Stacey’s face when she was dying. She was killed by alcohol – a drug that is as easy and cheap to buy as a packet of sweets.’

Since the relaxation of licensing laws in November 2005 – which allowed round-the-clock sales of drink in pubs, clubs, shops and supermarkets – the cost to the nation both socially and financially has been huge. Coupled with low prices for alcohol, there is now an orgy of drunkenness that rivals the gin epidemic of early Victorian times.

The facts are stark. The numbers dying from alcohol-related health problems is rising. In 1999, there were 4,000 deaths. Today, the figure has doubled, with the age of the victims going down, too. Hospitals admit for emergency treatment more than 9,000 drunken teenagers every year.

According to Alcohol Concern, 800,000 children below the age of 15 drink regularly in Britain. Nearly two-thirds of them will have had alcohol in the past month – with one in seven consuming enough to make them sick. One in three think, it is acceptable to get drunk once a week.

Campaigners say that one in ten eight-year-old boys (double the figure ten years ago) and a quarter of 11-year-old girls (ten per cent more than in 1995) have also experimented with alcohol.    Staff at the casualty department of Alder Hey Children’s Hospital in Liverpool will not be surprised by these statistics. A survey by the hospital – which admits only under-17s – showed that more than half the children treated after binge-drinking had bought their alcohol from a pub or a shop.

Nearly three-quarters of patients are girls, and the favourite tipple is vodka. Every week, seven or eight drunken youngsters are treated at the hospital – a quarter so ill that they have to be put on a ward or go into intensive care.

According to Pat McLaren, an Alder Hey spokeswoman: ‘They come in on a Friday and Saturday night in particular. Some are found unconscious on the street or even beaten up. We get them sober and contact their parents. We try to get them to change their ways.’

Alder Hey and Liverpool are not alone. Cases of liver cirrhosis in 20 to 30-year-olds – who often started drinking as children – have doubled in less than a decade.  Eight women in Britain die each day from liver disease – often at ages younger than men with the same condition because their bodies are more sensitive to alcohol poisoning.

As Professor Ian Gilmore, President of the Royal College of Physicians, warns: ‘The damage to society from alcohol is greater than from drugs.’   Dr Gray Smith-Laing, a gastroenterologist at Medway Maritime Hospital in Gillingham, Kent, says: ‘The young of all social backgrounds think it is cool to get completely legless, yet nothing could be more uncool. This is a classless and sexless phenomenon. We have not seen the peak yet.’

Young women such as Stacey Rhymes make up half his caseload. Some have irreversible liver damage from drinking. One woman of 26 he treated recently died of liver cirrhosis.  Dr Smith-Laing says: ‘We need a dramatic rise in the price of alcohol so it is no longer affordable for the young.’
 
It is against this frightening background that Stacey’s mother has bravely decided to speak out.

She reaches for a pile of treasured childhood photographs. They show Stacey on her first birthday; at eight in a white hat at a family wedding. There is one of her with bright, clear eyes and long thick hair smiling at the camera  - she is just 17, and it is a few months before she began to drink.

Louise, 43, says: ‘Stacey had a wonderful childhood and we were a close family. There wasn’t a lot of money, but we did old-fashioned things. We went to the park for picnics and walks around Nottingham.  ‘She had lots of friends and when she left school at 16, she got a job in a local pub as a waitress. She met a boy, and there was even talk of an engagement.’

But things were soon to change. ‘For no apparent reason, Stacey began to drink. She had arguments with the boyfriend about it. She lost the job she loved and her boyfriend, too. She was just drinking all the time. She became foul-mouthed. She stole money from us, her family, to buy the alcohol,’ says Louise. ‘Stacey would go out drinking at night then lie in bed all day. I couldn’t get her up, even though I tried before I left for work.

‘In the end, we found her a housing association flat in Nottingham, where she moved. We thought it would be a fresh start.’ Nothing could be further from the truth.

‘Stacey then got in with a bad crowd. Her friends were all drinkers, too. She would lie in bed with a bottle. A few times, she burned the bedclothes with her cigarettes. She got involved in a serious brawl, and was sent to prison for eight weeks.

‘We were horrified, but she came out looking far better. She had not been able to drink while inside. We took her back to her flat where there were eight weeks – £800-worth – of giro cheques from the benefits’ office. Stacey spent every penny on drink. She was evicted from her flat due to debts on the rent.’   Stacey wouldn’t move back home because her mother and stepfather, a self-employed builder, refused to allow her to drink. Revolted by what alcohol had done to their daughter, they are now teetotal.   Instead, Stacey found a place at a hostel in Derby, five miles from Nottingham. ‘That lasted five days before she was thrown out for drinking,’ recalls her mother.

By now, her life was out of control. For a time, Stacey lost contact with her family. She lived rough in Derby. In desperation, Louise tried to get her daughter sectioned under the mental health laws so she would be taken into hospital. ‘But the authorities said she was quite normal, just an alcoholic.’ she recalls today.   Stacey was now drinking five litres of wine a day and some cider, too. She no longer dressed fashionably, put on weight and didn’t eat properly. ‘Her stomach was huge and she was very ill,’ her mother says.

On March 28 this year, Stacey was admitted to Derby Hospital – to Ward 308 which deals with alcohol-induced liver problems. She had been to her GP because her face had gone yellow and she was having trouble walking because her limbs were swollen. The doctor told her to go to hospital immediately  -  it took her a week to do so.

Dr Jan Freeman, a consultant in whose care she was put, says: ‘Stacey was at the end of the road. She could have been saved only by a liver transplant. Like lots of young people, she never thought it would happen to her. Well, Stacey’s death shows it can happen to some.’    There is no doubt that Stacey was well looked after in the hospital but, during the next seven weeks, until her death on May 22, she managed to discharge herself three times and return to drinking.

Once, she walked out in her pyjamas, hailed a taxi then disappeared. Derby police put out appeals for the public to look for her. Her parents searched, too.    He mother recalls: ‘We got her back to the hospital on each occasion. The last time was on May 17. She had been staying with a drinking buddy. She rang up saying she was being sick and it was streaked with blood. Her skin was itching, a symptom of alcohol poisoning.

‘I knew that we would lose her, because of her colour. I thought she wouldn’t make it over the weekend. But three days later, she had picked up and told us she was scared of dying. I told her that if she stopped drinking, she would live.’    It was, of course, a white lie. The next day, the hospital rang Louise to say Stacey had a hole in her stomach, caused by acid from a ruptured peptic ulcer. There was nothing more the doctors could do.   Within 24 hours, the family were called to the hospital for the final time. Stacey died in her mother’s arms of abdominal bleeding and alcohol-related liver disease.

As confirmation of Stacey’s tragic story, Nick Sheron, a liver specialist at Southampton General Hospital and secretary of campaign group, Alcohol Health Alliance, says drink-induced liver disease – once the preserve of middle-aged men – is affecting all ages and both sexes.

He explains: ‘If they are alive, it is never too late to stop drinking. But, often the symptoms show up so late that half the patients die before they have a chance to change their ways.

‘In the Sixties and Seventies, wine used to be nine percent proof, now it is 13 percent. Beer was 3.2 percent, now a lager is five percent. The size of a wine glass is bigger, too  -  from 125ml to 175ml, and in some cases 250ml. That is a third of a bottle.’

Dr Sheron warns that alcohol is being used as a drug, instead of a part of a social event or accompaniment to a meal. ‘The young drink to get wasted as quickly as possible. They think if they can remember the night before it is not a good night out, and 24-hour licensing is one of the problems,’ he cautions.

With prices so low, Professor Mark Bellis, director of the Department of Public Health at John Moores University in Liverpool, adds: ‘A young person with £10-a-week to spend can get drunk three times a week.’   The scale of the crisis cannot be over-stated. Alcohol abuse, leading to either injury or disease, now costs the NHS £1billion annually with 40 per cent of casualty departments’ admissions being drink-related.

Significantly, the London Ambulance Service says that alcohol-related emergency calls have increased by 12 per cent since 24-hour drinking laws were introduced.   As spokeswoman Anna Lowman says: ‘One of the aims of the new laws was to eradicate the 11pm to 2am disorder flashpoint when the pubs and off-licences used to close. But this is still our busiest period. Fourteen per cent of all calls during these hours are linked to drinking.’

Yet this is not the only catastrophic side-effect. The Cabinet Office admits the real cost of drinking is £20billion a year if you include suicides, alcohol-fuelled crime, anti-social behaviour, depressive illness, family breakdown and domestic violence.

Only this month, the Local Government Association – representing councils – warned the 24-hour drinking plan to emulate a European style cafe-culture in Britain had failed miserably. It costs £100 million a year to oversee the late licensing system, provide staff to clean town centres of vomit or urine (often both) and help for the ‘walking wounded’ at the end of a night’s hard drinking.

At Stacey Rhymes’ funeral in Bramcote, held near the park where the family used to picnic, there were 150 mourners – some were her old school friends. As her mother says: ‘Stacey chose her way – and they theirs. They have got married, have children and careers. They are enjoying life. My daughter drank herself to death.   ‘She never had any problems getting her hands on another bottle. In many ways, she was a victim of our times.’

 Source  Newspaper cutting  – sent to NDPA not identified.

Adolescents’ use of marijuana may increase the risk of heroin addiction later in life, a new study suggests. Researchers say the work adds to “overwhelming” evidence that people under 21 should not use marijuana because of the risk of damaging the developing brain.
The idea that smoking cannabis increases the user’s chance of going on to take harder drugs such as heroin is highly contentious. Some dub cannabis a “gateway” drug, arguing that peer pressure and exposure to drug dealers will tempt users to escalate their drug use. Others insist that smoking cannabis is unrelated to further drug use.
Now research in rats suggests that using marijuana reduces future sensitivity to opioids, which makes people more vulnerable to heroin addiction later in life. It does so by altering the brain chemistry of marijuana users, say the researchers.
“Adolescents in particular should never take cannabis – it’s far too risky because the brain areas essential for behaviour and cognitive functioning are still developing and are very sensitive to drug exposure,” says Jasmin Hurd, who led the study at the Karolinska Institute in Sweden.
But Hurd acknowledges that most people who use cannabis begin in their teens. A recent survey reported that as many as 20% of 16-year-olds in the US and Europe had illegally used cannabis in the previous month.

“Teenage” rats

In order to explore how the adolescent use of cannabis affects later drug use, Hurd and colleagues set up an experiment in rats aimed to mirror human use as closely as possible.
In the first part of the trial, six “teenage” rats were given a small dose of THC – the active chemical in cannabis – every three days between the ages of 28 and 49 days, which is the equivalent of human ages 12 to 18. The amount of THC given was roughly equivalent to a human smoking one joint every three days, Hurd explains. A control group of six rats did not receive THC.
One week after the first part was completed, catheters were inserted in all 12 of the adult rats and they were able to self-administer heroin by pushing a lever.
“At first, all the rats behaved the same and began to self-administer heroin frequently,” says Hurd. “But after a while, they stabilised their daily intake at a certain level. We saw that the ones that had been on THC as teenagers stabilised their intake at a much higher level than the others – they appeared to be less sensitive to the effects of heroin. And this continued throughout their lives.”
Hurd says reduced sensitivity to the heroin means the rats take larger doses, which has been shown to increase the risk of addiction.

Drug memory

The researchers then examined specific brain cells in the rats, including the opioid and cannabinoid receptors. They found that the rats that had been given THC during adolescence had a significantly altered opioid system in the area associated with reward and positive emotions. This is also the area linked to addiction.
“These are very specific changes and they are long-lasting, so the brain may ‘remember’ past cannabis experimentation and be vulnerable to harder drugs later in life,” Hurd says.
Neurologist Jim van Os, a cannabis expert at the University of Maastricht in the Netherlands told New Scientist the research was a welcome addition to our understanding of how cannabis affects the adolescent brain.
“The issue of cross-sensitisation of cannabis/opioid receptors has been a controversial one, but these findings show the drug’s damaging effects on the reward structures of the brain,” van Oshe says. “There is now overwhelming evidence that nobody in the brain’s developmental stage – under the age of 21 – should use cannabis.”

Source: On line edition of Neuropsychopharmacology. Reported in NewScientist.com July 2006

27 October 2006

People addicted to cocaine have an impaired ability to perceive rewards and exercise control due to disruptions in the brain’s reward and control circuits, according to a series of brain-mapping studies and neuropsychological tests conducted at the U.S. Department of Energy’s Brookhaven National Laboratory.
“Our findings provide the first evidence that the brain’s threshold for responding to monetary rewards is modified in drug-addicted people, and is directly linked to changes in the responsiveness of the prefrontal cortex, a part of the brain essential for monitoring and controlling behavior,” said Rita Goldstein, a psychologist at Brookhaven Lab. “These results also attest to the benefit of using sophisticated brain-imaging tools combined with sensitive behavioral, cognitive, and emotional probes to optimize the study of drug addiction, a psychopathology that these tools have helped to identify as a disorder of the brain.”
Goldstein will present details of these studies at a press conference on neuroscience and addiction at the Society for Neuroscience (SfN) annual meeting in Atlanta, Georgia, on Sunday, October 15, 2006, 2 to 3 p.m., and at a SfN symposium on Wednesday, October 18, 8:30 a.m.
Goldstein’s experiments were designed to test a theoretical model, called the Impaired Response Inhibition and Salience Attribution (I-RISA) model, which postulates that drug-addicted individuals disproportionately attribute salience, or value, to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli – with a concomitant decrease in the ability to inhibit maladaptive drug use. In the experiments, the scientists subjected cocaine-addicted and non-drug-addicted individuals to a range of tests of behavior, cognition/thought, and emotion, while simultaneously monitoring their brain activity using functional magnetic resonance imaging (fMRI) and/or recordings of event-related potentials (ERP).
In one study, subjects were given a monetary reward for their performance on an attention task. Subjects were given one of three amounts (no money, one cent, or 45 cents) for each correct response, up to a total reward of $50 for their performance. The researchers also asked the subjects how much they valued different amounts of monetary reward, ranging from $10 to $1000.
More than half of the cocaine abusers rated $10 as equally valuable as $1000, “demonstrating a reduced subjective sensitivity to relative monetary reward,” Goldstein said.
“Such a ‘flattened’ sensitivity to gradients in reward may play a role in the inability of drug-addicted individuals to use internal cues and feedback from the environment to inhibit inappropriate behavior, and may also predispose these individuals to disadvantageous decisions – for example, trading a car for a couple of cocaine hits. Without a relative context, drug use and its intense effects – craving, anticipation, and high – could become all the more overpowering,” she said.
The behavioral data collected during fMRI further suggested that, in the cocaine abusers, there was a “disconnect” between subjective measures of motivation (how much they said they were engaged in the task) and the objective measures of motivation (how fast and accurately they performed on the task).
“These behavioral data implicate a disruption in the ability to perceive inner motivational drives in cocaine addiction,” Goldstein said.
The fMRI results also revealed that non-addicted subjects responded to the different monetary amounts in a graded fashion: the higher the potential reward, the greater the response in the prefrontal cortex. In cocaine-addicted subjects, however, this region did not demonstrate a graded pattern of response to the monetary reward offered. Furthermore, within the cocaine-addicted group, the higher the sensitivity to money in the prefrontal cortex, the higher was the motivation and the self-reported ability to control behavior.
The ERP results showed a similarly graded brain response to monetary reward in healthy control subjects, but not in cocaine-addicted individuals.
“The dysfunctional interplay between reward processing and control of behavior observed in these studies could help to explain the chronically relapsing nature of drug addiction,” Goldstein said. “Our results also suggest the need for new clinical interventions aimed at helping drug abusers manage these symptoms as part of an effective treatment strategy.”

Source: Medical Research News 18th Oct.2006

EDINBURGH: The Scottish Executive’s anti-drug abuse policy was criticized sharply yesterday following a report that the government recommended heroin-substitute methadone is 97% ineffective.

Methadone, a drug used for recovery from heroin addiction, has a success rate of no more than 3.4%, according to Professor Neil McKeganey, chief researcher for Glasgow University’s Centre for Drug Misuse Research. McKeganey has just concluded a study on the effectiveness of the £12m a year Methadone programme.

The study observed a group of 695 heroin addicts who started taking treatment in 2001 at 33 different addiction centers across Scotland. A large percentage of this group was given methadone-based care while the rest were put on rehabilitation. Their progress was recorded over interviews 33 months after they started the treatment to see if they had become drug-free over a 90-day period.

The group given only-methadone had a very poor 3.4 percent recovery rate from drug addiction; whereas the group placed in residential rehabilitation (with no methadone throughout the treatment) showed a 29% success rate.

A key difference in methadone’s success rates between Scotland and England was also pointed out. While England emphasizes on getting people off drugs entirely, Scotland’s drug policy lacks any such direction; as a result, addicts simply substitute methadone with heroin.

McKeganey’s previous research had revealed a greater inclination to commit crimes among methadone patients when compared with addicts placed on abstinence programmes. People in the latter group also showed twice the level of interest in finding a job.

While the report makes no recommendation, sharp reactions have come in from various quarters demanding the Executive at least review its drug policy if not entirely scrap methadone. Tory leader Anabel Goldie said she recommended more investment in residential rehabilitation centres.

Meanwhile an official at the Greater Glasgow NHS facility said methadone may not be suitable for everyone but many addicts do benefit from it. He also said the government was looking to offer “a wider package of support” that would include rehabilitation, education and training, to addicts.

Source: Earthtimes.org. 30.10.06

Mount Sinai researchers have discovered how cocaine corrupts the brain and becomes addictive. These findings — the first to connect activation of specific neurons to alterations in cocaine reward — were published in Science on October 15. The results may help researchers in developing new ways of treating those addicted to the drug.

Led by Mary Kay Lobo, PhD, Postdoctoral Fellow in the Department of Neuroscience at Mount Sinai School of Medicine and first author of the study, researchers found that the two main neurons (D1 and D2) in the nucleus accumbens region of the brain, an important part of the brain’s reward center, exert opposite effects on cocaine reward. Activation of D1 neurons increases cocaine reward whereas activation of D2 neurons decreases cocaine reward.
“The data suggest a model whereby chronic exposure to cocaine results in an imbalance in activity in the two nucleus accumbens neurons: increased activity in D1 neurons combined with decreased activity in D2 neurons,” said Dr. Lobo. “This further suggests that BDNF-TrkB signaling in D2 neurons mediates this decreased activity in D2 neurons.”
The study was conducted using optogenetics, a technology to optically control neuronal activity in freely moving rodents.

Opposite cocaine reward similar to those found when activating each neuron is achieved by disrupting brain-derived neurotrophic factor, which is a protein in the brain known for its involvement in neuronal survival, learning, and memory and drug abuse signaling through its receptor TrkB in D1 or D2 neurons.

“This new information provides fundamentally novel insight into how cocaine corrupts the brains reward center, and in particular how cocaine can differentially effect two neuronal subtypes that are heterogeneously intermixed in the nucleus accumbens,” said Eric Nestler, MD, PhD, Chair of Neuroscience, Nash Family Professor, and Director of The Friedman Brain Institute at Mount Sinai and co-author on the study. “We can use this information to potentially develop new therapies for cocaine addiction, possibly aimed at altering neuronal activity selectively in either neuronal subtype.”

Source: ScienceDaily (Oct. 18, 2010)

Scientists at the University of Liverpool have found that high levels of a stress hormone in recovering alcoholics could increase the risk of relapse.

The study showed that cortisol, a hormone produced by the adrenal gland in response to stress, is found in high levels in chronic alcoholics, as well as those recovering from the condition.

Researchers found that this could result in impaired memory, attention and decision-making functions, which could decrease the patient’s ability to engage with treatment.

Chronic alcoholism is a disabling addictive disorder, characterised by compulsive and uncontrolled consumption of alcohol despite the negative effects it has on health, relationships and social standing. Alcohol damages almost every organ of the body including the brain where it causes memory loss and impairs decision-making and attention span.

Cortisol plays an important role in the regulation of emotion, learning, attention, energy utilization, and the immune system.

The research showed that high levels of this hormone are present in alcoholic patients and continue to be elevated during withdrawal from alcohol and after long periods of abstinence.

Lead author of the review, Dr Abi Rose, from the School of Psychology, Health and Society at the University of Liverpool, said: “Both drinking and withdrawal from alcohol can affect cortisol function in humans.

“Cortisol dysfunction, including the high levels of cortisol observed during alcohol withdrawal, may contribute to the high rates of relapse reported in alcohol dependence, even after many months of abstinence.

“Drugs targeting the effects of cortisol in the brain might reduce the chances of relapse and reduce the cognitive impairments that interfere with treatment.”

The study is published in Alcoholism: Clinical & Experimental Research. The research is in collaboration with Kings College London, University of Bern, and the University of Kentucky.

Source: www.clickliverpool.com 26.09.2010

Cocaine is one of the oldest drugs known to humans, and its abuse has become widespread since the end of the 19th century. At the same time, we know rather little about its effects on the human brain or the mechanisms that lead to cocaine addiction. The latest article by Dr. Marco Leyton, of the Montreal Neurological Institute (MNI), McGill University and the McGill University Health Centre, which was published in the journal Biological Psychiatry on May 15, 2009, not only demonstrates a link between cocaine and the reward circuits in the brain but also associates the susceptibility to addiction with these mechanisms.

The results of this study show that sniffing cocaine triggers high levels of dopamine secretion in a central region of the brain called the striatum. Dopamine is known to play a critical role in the brain’s response to reward as well as in its response to addictive drugs.
This study was carried out in ten non-addicted users of cocaine, all of whom sniffed cocaine on one test day and placebo powder on another. Participants underwent blood tests before and after taking the drug, and dopamine release in the brain was measured using PET scans.
“The ability of cocaine to activate dopamine release varies markedly from person to person. Our study suggests that this is related to how much of the drug the person consumed in the past,” explained Dr. Leyton. The more cocaine someone has used in his or her lifetime, the more the brain will secrete dopamine during subsequent cocaine use. “It’s possible therefore that the intensity of the reward-circuit response is related to increased susceptibility to addiction,” stated Dr. Leyton.
Although the relationship between the intensity of dopamine secretion and the frequency of drug use has been demonstrated, researchers still do not fully understand its mechanism of action. Is it the repeated stimulation of the reward circuit that leads to addiction, or is it an inherent sensitivity to addiction that leads to the increased secretion of dopamine? This question is not easy to answer, especially since other factors come into play, such as other aspects of the subject’s personal history.
Whatever the answer, the relationship between dopamine and cocaine means that this hormone could be a potential target for treatment against addiction. More research is required before treatments are available, but this study opens a new door in this direction.
This study was funded with a grant from the Canadian Institutes for Health Research. Salary support was given by the Fond de recherche en santé du Québec
This study is a collaboration between several laboratories of the McGill University Health Centre and McGill University, involving : Dr Sylvia M.L. Cox, Dr Chawki Benkelfat, Dr Alain Dagher, Dr J. Scott Delaney, France Durand, Samuel A. McKenzie, Dr Theodore Kolivakis, Kevin F. Casey, Dr Marco Leyton.

Source: McGill University Health Centre (2009, May 20).

Environmental conditions play a major role in treating drug addiction and in preventing relapses, according to new research. For the first time, researchers from the Institut de physiologie et biologie cellulaire (CNRS/Université de Poitiers) have shown that positive and stimulating environmental conditions make it easier to treat cocaine addiction.

Even though numerous data exist on the mechanisms of cocaine addiction, there are as yet no effective therapies, making it very urgent that new strategies for treating the disease be developed. According to a study by Marcello Solinas and Mohamed Jaber, carried out by a group of researchers at the Institut de physiologie et biologie cellulaire in Poitiers, exposing mice to an “enriched environment (1)” during cocaine withdrawal removes abnormal behavior related to addiction. An enriched environment, for mice, is an environment which stimulates their curiosity, providing social and physical activity as well as exploration.
After addicting animals to cocaine, the researchers then exposed them to an enriched environment made up of large cages with a small house, a running wheel, tunnels and other appealing toys which were changed weekly.
Three models of animal addiction were used:
behavioral sensitization, which measures the progressive increase in the stimulating effects of cocaine after chronic administration;
the location preference, which measures the ability of a context (associated with cocaine consumption) to lead to drug-seeking behavior, and the renewal of this drug-induced location preference;
measurements of cocaine’s ability to lead to a relapse after a period of withdrawal.
The result was that after thirty days of exposure to an enriched environment, addiction behavior typical of these three models had disappeared.
To identify the brain areas involved in the beneficial effect of an enriched environment, the researchers used an approach from functional neuro-anatomy. They showed that the absence of relapse in “enriched” mice was associated with a decrease in the cocaine-induced activation of a set of brain structures involved in dopaminergic transmission and associated with relapse.
These results, which have both a medical and societal impact, suggest that the living conditions of drug addicts should be taken into account in determining their therapy. A real effort should be made to create enriched environmental conditions, providing patients with different types of social, physical and intellectual stimulation. This also suggests that under deprived environmental conditions, treating addiction can be very challenging.
Note:
1) A number of earlier studies had shown that when animals are raised in an enriched environment prior to drug exposure, their vulnerability to addiction was reduced. In such conditions, the enriched environment can be seen as preventive.

Source: Proceedings of the National Academy of Sciences, 2008; 105 (44): 17145 DOI: 10.1073/pnas.0806889105

Addictive drugs are known to induce changes in the brain’s reward circuits that may underlie drug craving and relapse after long periods of abstinence. Now, new research in the September 9 issue of the journal Neuron, uncovers a specific neural mechanism that may be linked to persistent drug-seeking behavior and could help to guide strategies for development of new therapies for cocaine addiction.

Previous research has shown that the ventral tegmental area (VTA) is a brain region that is activated when cocaine users experience a craving for cocaine after being exposed to cocaine-associated cues. The medial prefrontal cortex (mPFC), which receives input from the VTA via circuits that use the “reward” neurotransmitter dopamine, has also been implicated in drug craving after cocaine withdrawal. Further, increases in the level of brain-derived neurotrophic factor (BDNF) have been observed in the VTA and mPFC in rats after withdrawal from repeated cocaine exposure.
“BDNF plays a key role in modulating the structure and function of synapses, the sites of communication between neurons. Therefore, increased BDNF after cocaine withdrawal may drive synaptic changes that contribute to compulsive drug seeking behavior,” explains senior author, Dr. Mu-ming Poo from the University of California, Berkeley. “It has been shown that increased BDNF in the VTA after cocaine withdrawal in rats promotes the drug-dependent motivational state. However, nothing is known about the potential BDNF effect on synaptic function and plasticity in mPFC neurons after cocaine withdrawal.”
Dr. Poo and colleagues designed a study to examine how BDNF and the mPFC might contribute to relapse after cocaine addiction. The researchers found that the gradual increase in BDNF expression in the rat mPFC after terminating repeated cocaine exposure significantly enhanced the activity-induced potentiation of specific synapses. Dr. Poo’s group went on to uncover the specific cellular mechanism linking increased BDNF with enhanced synaptic plasticity and demonstrated that interference with the key molecule in the BDNF signaling process reduced behavioral sensitivity after cocaine withdrawal in rats.
“In short, our results demonstrate that elevated BDNF expression after cocaine withdrawal sensitizes the excitatory synapses in the mPFC to undergo activity-induced persistent potentiation that may contribute to cue-induced drug cravings and drug-seeking behavior,” concludes Dr. Poo. Although a clear correlation between rat and human behaviors of cocaine craving and relapse remains to be established, the cellular mechanism uncovered in this study does appear to have behavioral relevance and may represent a direct brain sensitization that is involved in triggering relapse.
The researchers include Hui Lu, Pei-lin Cheng, Byung Kook Lim, Nina Khoshnevisrad, and Mu-ming Poo, University of California, Berkeley, Berkeley, CA.

Source: . Neuron, 67(5) pp. 821 – 833 DOI: 0.1016/j.neuron.2010.08.012

Teens may smoke to “self-medicate” against depression, but researchers in Canada say smoking may increase depressive symptoms in some adolescents.

Lead author Michael Chaiton of the Ontario Tobacco Research Unit of the University of Toronto and co-author Jennifer O’Loughlin of the University of Montreal Hospital Research Centre say the study involved 662 high-school teenagers who completed as many as 20 questionnaires from grades 7-11 about their use of cigarettes to affect mood.

Study participants were divided into groups of: teens who never smoked; smokers who did not use cigarettes to self-medicate, improve mood or physical state; and smokers who used cigarettes to self-medicate. Study participants were asked to rate on a rating scale depressive symptoms such as: felt too tired to do things; had trouble going to sleep or staying asleep; felt unhappy, sad, or depressed; felt hopeless about the future; felt nervous or tense; and worried too much about things.

Smokers who used cigarettes as mood enhancers had higher risks of elevated depressive symptoms than teens who had never smoked, researchers concluded.

Source: Journal of Addictive Behaviors.Sept 2010

Researchers at King’s College London’s Institute of Psychiatry say a personality-based intervention for substance abuse that was delivered by teachers was successful in reducing drinking rates, particularly binge drinking, among adolescents.

In the article titled “Personality-Targeted Interventions Delay Uptake of Drinking and Decrease Risk of Alcohol-Related Problems When Delivered by Teachers,” principal Investigator Dr. Patricia Conrod and colleagues evaluated 2,506 adolescents, with a mean age of 13.7, using the Substance Use Risk Profile scale; a 23-item questionnaire which assesses personality risk for substance abuse along four dimensions including sensation-seeking, impulsivity, anxiety-sensitivity, and hopelessness.

Of the 1,159 students identified by researchers as being at high risk for substance abuse, 624 received intervention as part of the Adventure Trial and a matched high risk group of 384 received no intervention. School based interventions consisted of two 90 minute group sessions conducted by a trained educational professional. In order to adequately evaluate the students, the teachers attended a 3-day rigorous workshop, followed by 4 hour supervision and feedback session. An 18 point checklist was used to determine whether the teachers demonstrated a good understanding of the aims and components of the programs.

Although the trial is designed to evaluate mental health symptoms, academic achievement, and substance use uptake over a 2 year period, the authors have focused their findings on the six month outcomes of drinking and binge-drinking rates, quantity by frequency of alcohol use, and drinking-related problems. Reporting on the efficacy of the intervention at six months, author and Trial Coordinator Maeve O’Leary-Barrett writes, “Receiving an intervention significantly decreased the likelihood of reporting drinking alcohol at follow-up, with the control group 1.7 times more likely to report alcohol use than the intervention group (odds ratio, 0.6).”

Furthermore, receiving an intervention also predicted significantly lower binge-drinking rates in students who reported alcohol use at baseline (odds ratio, 0.45), indicating a 55 percent decreased risk of binge-drinking in this group compared with controls. In addition, high-risk intervention-school students reported lower quantity by frequency of alcohol use and drinking-related problems compared with the non-treatment group at follow-up.

The Adventure Trial is the first to evaluate the success of the personality-targeted interventions as delivered by teachers. The findings at six months suggest that this approach may provide a sustainable school-base prevention program for youth at risk for substance abuse.

In the JAACAP article, Principal Investigator Dr. Patricia Conrod and colleagues comment on the success of their program by stating, “In-house personality-targeted interventions allow schools to implement early prevention strategies with youth most at risk for developing future alcohol-related problems and provide the potential for follow-up of the neediest individuals.”

Source: Journal of the American Academy of Child and Adolescent Psychiatry. Sept. 2010

A typical drug user’s transition to addiction could result from a persistent impairment of synaptic plasticity in a key structure of the brain, suggests a new French study.
The research, by the teams of Pier Vincenzo Piazza and Olivier Manzoni, at the Neurocentre Magendie in Bordeaux, appears in the journal Science.

This study is the first demonstration that a correlation exists between synaptic plasticity and the transition to addiction. The results from the teams at Neurocentre Magendie call into question the hitherto held idea that addiction results from pathological cerebral modifications, which develop gradually with drug usage.

Their results show that addiction may, instead, come from a form of anaplasticity, i.e. from incapacity of addicted individuals to counteract the pathological modifications caused by the drug to all users.

The voluntary consumption of drugs is a behaviour found in many species of animals. However, it had long been considered that addiction, defined as compulsive and pathological drug consumption, is behaviour specific to the human species and its social structure.

In 2004, the team of Pier Vincenzo Piazza showed that the behaviours which define addiction in humans, also appear in some rats which will self administer cocaine. Addiction exhibits astonishing similarities in men and rodents, in particular the fact that only a small number of consumers (humans or rodents) develop a drug addiction. The study of drug dependent behaviour in this mammal model thus opened the way to the study of the biology of addiction.

Today, thanks to a fruitful collaboration, the teams of Pier Vincenzo Piazza and Olivier Manzoni are reporting discovery of the first known biological mechanisms for the transition from regular but controlled drug taking to a genuine addiction to cocaine, characterised by a loss of control over drug consumption.

Chronic exposure to drugs causes many modifications to the physiology of the brain. And researchers wanted to find out which of these modifications is responsible for the development of an addiction.
The addiction model developed in Bordeaux provides a unique tool to answer this question. Thus it allows comparing animals who took identical quantities of drugs, but of which only few become addicted.

By comparing addict and non-addict animals at various time points during their history of drug taking, the teams of Pier Vincenzo Piazza and Olivier Manzoni have demonstrated that the animals which developed an addiction to cocaine exhibit a permanent loss of the capacity to produce a form of plasticity known as long-term depression (or LTD).

LTD refers to the ability of the synapses (the region of communication between neurons) to reduce their activity under the effect of certain stimulations. It plays a major role in the ability to develop new memory traces and, consequently, to demonstrate flexible behaviour.

After short-term usage of cocaine, LTD is not modified. However, after a longer use, a significant LTD deficit appears in all users. Without this form of plasticity, which allows new learning to occur, behaviour with regard to the drug becomes more and more rigid, opening the door to development of a compulsive consumption.

The brain of the majority of users is able to produce the biological adaptations which allow to counteract the effects of the drug and to recover a normal LTD.
By contrast, the anaplasticity (or lack of plasticity) exhibited by the addicts leaves them without defences and hence the LTD deficit provoked by the drug becomes chronic.

This permanent absence of synaptic plasticity would explain why drug seeking behaviour becomes resistant to environmental constraints (difficulty in procuring the substance, adverse consequences of taking the drug on health, social life, etc.) and consequently more and more compulsive. Gradually, control of the taking of the drug is lost and addiction appears.

For Pier-Vincenzo Piazza and his collaborators, these discoveries also have important implications for developing new treatment of addiction.

“We are probably not going to find new therapies by trying to understand the modifications caused by a drug in the brains of drug addicts,” explain the researchers, “since their brain is anaplastic.” For the authors, “The results of this work show that it is in the brain of the non-addicted users that we will probably find the key to a true addiction therapy.

Indeed,” the authors estimate, “understanding the biological mechanisms which enable adaptation to the drug and which help the user to maintain a controlled consumption could provide us with the tools to combat the anaplastic state that leads to addiction”. (ANI)

Source: www.sify.com/news 2010-06-29

Researchers have found that a specific and remarkably small fragment of RNA appears to protect rats against cocaine addiction – and may also protect humans.
The discovery could lead to better ways of predicting drug abuse risk and treating addictions

In the study, researchers at The Scripps Research Institute in Jupiter, Florida found that cocaine consumption increased levels of a specific microRNA sequence in the brains of rats, named microRNA-212.

As its levels increased, the rats exhibited a growing dislike for cocaine, ultimately controlling how much they consumed.
On the other hand, as levels of microRNA-212 decreased, the rats consumed more cocaine and became the rat equivalent of compulsive users.

The study’s findings suggest that microRNA-212 plays a pivotal role in regulating cocaine intake in rats and perhaps in vulnerability to addiction.
Interestingly, the same microRNA-212 identified in this study, is also expressed in the human’s dorsal striatum, a brain region that has been linked to drug abuse and habit formation.

“This study enhances our understanding of how brain mechanisms, at their most fundamental levels, may contribute to cocaine addiction vulnerability or resistance to it,” Nature quoted National Institute on Drug Abuse (NIDA) Director Dr. Nora D. Volkow, as saying.

“This research provides a wonderful example of how basic science discoveries are critical to the development of new medical treatments and targeted prevention,” he added.

Rats with a history of extended cocaine access can demonstrate behavior similar to that observed in humans who are dependent on the drug.
Current data show that about 15 percent of people who use cocaine become addicted to it.
The findings suggest that microRNAs may be important factors
contributing to this vulnerability.

“The results of this study offer promise for the development of a totally new class of anti-addiction medications. Because we are beginning to map out how this specific microRNA works, we may be able to develop new compounds to manipulate the levels of microRNA-212 therapeutically with exquisite specificity, opening the possibility of new treatments for drug addiction,” said Paul J. Kenny, senior author on the study.
The study is published in the journal Nature. (ANI)

Source:www.sify.com/news 9th July 2010-07-10

Neuropharmacologists ran clinical trials to find that a drug called topiramate is an effective therapeutic medication for decreasing heavy drinking and diminishing the physical and psychosocial harm caused by alcohol dependence.

The drug works by blocking the right amount of the feel good effects of alcohol (brought on by increased levels of dopamine), making drinking less enjoyable and thus reducing cravings and helping to stop heavy drinking.

Topiramate was also found to lower blood pressure and cholesterol levels which may lead to a decrease in heart disease in alcohol dependent patients.

Alcoholism affects over 17 million people. Without proper treatment, it’s a devastating disease that can ruin lives and relationships. A new therapy that comes in a pill is bringing new hope to alcoholics.

There was a time in Christine Flemming’s life when alcohol came before her kids.
“I can’t remember when my daughter was very little, because I was drinking so much,” said Flemming. “That affected me a lot.”

Flemming needed help, but traditional treatment methods didn’t work. Now she’s on a new kind of therapy in the form of a pill called topiramate. It has changed her life. “I can tell you that it cuts my cravings, and I don’t feel like I have to drink,” Flemming said. “I don’t feel like that’s something I need in my life and I have to do.”

Alcohol increases levels of dopamine, a chemical in the brain that makes us feel good. The drug works by blocking the right amount of the feel-good effects from alcohol to reduce cravings and help stop heavy drinking. During clinical trials, neuropharmacologists were surprised to learn it also lowers blood pressure and cholesterol levels, which may lead to a decrease in heart disease in alcohol dependent patients.

“Most of the morbidity due to alcoholism is caused by secondary effects of all these other systems, so to have a drug that begins to correct all those other physical abnormalities is extremely helpful,” said Bankhole Johnson, Ph.D., a Neuropharmacologist at the University of Virginia in Charlottesville, Va.

The drug helped improve Fleming’s health and end her dependence on alcohol. She cut her drinking from 15 beers a day to just three, so time with her kids is now a priority.
“It’s made a big difference,” Flemming said. “It’s made a really big difference, and I feel like I’m actually there for my family.”

Qualifying patients can find out how to receive the drug by contacting their primary care doctors.

WHAT IS TOPIRAMATE? Topiramate is a drug originally discovered in 1979. It is prescribed as an epilepsy medication and for migraine headaches. It is also used for a number of other purposes, including as a treatment for people with alcoholism.

Researchers believe that topiramate works in two ways. First, it reduces the release of dopamine that follows the consumption of alcohol. This reduces the positive feeling that people receive from alcohol, and thus reduce the incentive to drink. Second, topiramate interferes with the protein glutamate which normally excites dopamine neurons and again, lessening the ýfeel goodý effect of dopamine from alcohol.

WHAT IS ALCOHOL? Alcohol is created through the natural process of fermentation. This happens when yeast and sugar from vegetables and grains change the sugar into alcohol. When you drink alcohol, it is absorbed into your bloodstream, where it can affect the central nervous system, which is the control center for your entire body.

Alcohol slows down this control center with its sedative effect. In moderation it can reduce anxiety, but it also blocks some of the commands the brain sends to other parts of the body, so it alters your senses. That’s why, when drunk, people often have trouble walking, talking, and some may even “black out,” forgetting what they said or did. Drinking an excessive amount of alcohol can even be fatal.

Source www.ScienceDaily June 2010

Levels of the serotonin transporter are low in the brains of users of ecstasy, according to a US National Institute of Drug Abuse-funded study by Toronto’s Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids) published today in the journal Brain.

Ecstasy (MDMA) is a stimulant drug widely used recreationally that is also being tested in clinical trials for the treatment of post-traumatic stress disorder.
Led by Dr. Stephen Kish at CAMH, this study provides confirmation of a previous finding from Johns Hopkins University that levels of the serotonin transporter (SERT) are low in cerebral cortex of chronic ecstasy users. The subjects were “typical” ecstasy users who used about two tablets of the drug twice a month.

SERT is a protein responsible for regulating levels of serotonin, a neurotransmitter important for mood and impulse control. Ecstasy interacts with SERT to cause the release of serotonin, an action that probably explains some of the behavioral effects of the drug such as increased sociability.

Scientists have long suspected that ecstasy might harm brain cells that use serotonin, but 12 years of brain scan studies have produced contradictory results, even within the same laboratory.
The CAMH study used a large subject size (49 drug users, 50 control subjects), confirmed by hair analysis that ecstasy users actually used the drug, and used an imaging probe that could measure SERT throughout the brain.
“We were surprised to discover that SERT was decreased only in the cerebral cortex and not throughout the brain, perhaps because serotonin nerves to the cortex are longer and more susceptible to changes. This finding is almost identical to newer data from Johns Hopkins and is the first time that one laboratory has actually been able to replicate results of another independent laboratory in a SERT study of ecstasy users.” said Dr. Kish.

Drug hair analysis indicated that many ecstasy users, probably unknowingly, also used methamphetamine, which might itself damage serotonin cells; however, low SERT was found both in ecstasy users who used and who did not use methamphetamine. Dr. Jason Lerch at SickKids showed that those ecstasy users who also used methamphetamine had a slightly thinner cerebral cortex.

Does low SERT equal “structural brain damage”? “Not necessarily” said co-author Dr. Isabelle Boileau of CAMH. “There is no way to prove whether low SERT is explained by physical loss of the entire serotonin nerve cell, or by a loss of SERT protein within an intact nerve cell.”
Dr. Kish suggests that low SERT might explain why many ecstasy users need to keep increasing the dose to experience the same effects, since SERT is necessary for the action of ecstasy. “Most of the ecstasy users of our study complained that the first dose is always the best, but then the effects begin to decline and higher doses are needed. The need for higher doses, possibly caused by low SERT, could well increase the risk of harm caused by this stimulant drug,” said Dr. Kish.

Media Contact: Michael Torres, Media Relations, CAMH ; 416 595 6015 or email media@camh.net

Source: www.camh.net 18th May 2010

We know that there are people alive today who find it impossible to quit different kinds of behaviour once they have started it. What is it that makes one person quit cold turkey, and another smoke even while they are being treated for cancer?

Is there an addiction gene? Addiction in the genes is a hotly debated subject among scientists and researchers.

Scientists and researchers are going further back than ever before to unearth present truths. Addiction runs in the family. Again and again, they have found addictive behaviours carried down the family tree. This was their first clue that addiction may be hereditary.

There doesn’t appear to be a single ‘addict’ gene that causes specific types of people to fall into the addiction trap. There are however, several that combine to form a strong susceptibility to the behavioural patterns that addict’s exhibit. This is the addiction and genetics debate.

When a person with these genetic markers is exposed to a drug, or a habit, it can change the chemistry in their brain. This change leads to compulsive behaviour and eventual addiction. We are familiar with the concept that some illnesses – both physical and mental – can be hereditary, but it appears that this can also be applied to addiction.

Naturally, even if addiction is in the genes, there are other external factors that play their part. Why is it, for example, that a man becomes a drug addict, when his sister has never so much as smoked? External circumstances, stimuli and environmental factors also play their part in affecting people who are genetically prone to addiction.

The addiction and the genetic factor discussion will play on for years to come. The science is still quite new, and there are those out there that would prefer to blame addiction on personality disorders instead of genetics. Even if a definitive link is found, there is a still a long way to go before this information can be used to treat addiction sufferers and their families. For the time being at least, traditional addiction treatment and rehabilitation is still the most effective way to proceed.

Alcoholism, gambling, sexual and drug addiction could all be the result of inherited genes and generations of vulnerability. If you believe that addiction runs in the family, analyse yourself honestly. If it appears that you have a vulnerability to addictive behaviour, seek professional assistance. Obtaining assistance early on may help to limit any long-term damage.

Source: www.articlealley.com 5.5.2010

The brain’s nucleus accumbens (NAC) is a core region of the mesocorticolimbic dopaminergic system and is interconnected with the ventral tegmental area (VTA) and the prefrontal cortex. The mesocorticolimbic system is thought to be central to the reinforcing effects of many drugs and plays an important role in addiction. A new study has found that alcohol abuse elevated the expression of a distinct set of genes in the NAC and VTA, while nicotine blunted this effect in the VTA.

Results will be published in the July 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“In spite of their differences in pharmacology, alcohol and tobacco consumption are often intimately linked,” said Traute Flatscher-Bader, a postdoctoral research fellow at The University of Queensland and corresponding author for the study. “Nonetheless, the molecular mechanisms that underlie alcohol and nicotine abuse, and particularly their co-abuse, are still incompletely understood.”

“One thing that researchers have encountered is that it is often difficult to find ‘pure’ alcoholics, that is, alcoholics that only abuse alcohol and nothing else,” agreed Simon Worrall, director of postgraduate coursework programs in molecular biology at The University of Queensland. “Many alcoholics are poly-drug abusers, with the most common other drug being nicotine. Thus, many studies which have studied the effects of alcohol on the brain and other organs have been compromised because they have not taken account of the effects of nicotine addiction which is often superimposed on the effects of alcohol addiction.”

In the first part of the current study, Flatscher-Bader and her colleagues used DNA microarray technique to study the expression of many thousands of genes in the brains of non-smoking and smoking alcoholics and non-drinking smokers.

“We examined the impact of alcoholism and smoking on gene expression in the NAC in 20 chronic alcohol abusers and controls with and without recent smoking history,” said Flatscher-Bader. “The results revealed that in this brain region, the abuse of alcohol and nicotine had distinct effects on the expression of genes. In addition, altered expression of a number of genes was associated with both alcohol and nicotine abuse. Within the latter group was a set of genes which play a crucial role in a molecular pathway regulating cell structure.”

The researchers then went on to investigate in more detail the altered expression of six selected genes within the pathway regulating cell structure in two brain regions, using 30 cases comprised again of smoking and non-smoking controls and alcohol abusers. For this part of the study they used the method called “real time polymerase chain reaction.”

“This expanded investigation revealed that one of the genes, called RHOA, was elevated by alcohol abuse and its highest expression was evident in the smoking alcoholics in both brain regions,” said Flatscher-Bader. “The RHOA gene had previously been implicated in the initiation of tobacco smoking. In the NAC, the expression of a further four of the six selected genes was increased by alcohol abuse. Interestingly, the highest expression for each of the genes in the NAC was in the smoking alcoholics. In the other brain region called the VTA, alcohol abuse had a similar effect and elevated the expression of all six selected genes. In contrast to the NAC, however, concurrent smoking dampened the induction of five of these alcohol-sensitive genes in the VTA.”

“Many studies have analyzed the changes in gene expression in this brain system to try to untangle the molecular pathology of alcohol addiction,” said Worrall, “but this is amongst the first to take into account the effect of co-administration of nicotine with alcohol.

Flatscher-Bader stressed that there are several cell types in the brain and there are several steps between gene expression and impact on cell structure and function. “It has to be emphasized that our study is important as a first step in identifying molecular pathways underlying the effects of alcohol abuse and smoking and their co-joint abuse on the human NAC and VTA, “she said. “It now needs to be tested if our findings are, indeed, associated with changes to neuronal structure and function.”

“A better understanding of the molecular basis of withdrawal may help in the development of new treatments to ameliorate the symptoms,” added Dr Worrall. “Not many previous studies took into account the potential effects of nicotine addiction that may be superimposed on top of those from alcohol, so these results may help clinicians better use present therapy/drugs to treat patients abusing both alcohol and/or nicotine and may also lead to the development of new drugs.”

Source: www.medicalnewstoday.com 5.5.2010

 Around 44 0000 people have been recorded as entering specialised drug treatment centres in Europe in 2008 in 29 countries; data mainly cover outpatient and inpatient treatment centers
 Most clients enter treatment on their own initiative or under the pressure of family and friends (43 %); 27 % go to drug treatment through health or social services, including other drug treatment centres; around 20 % are referred to treatment by the criminal justice system, and the remaining through other referral sources
 The most frequent reason for entering treatment in 2008 (or most recent year available), is the use of heroin (48 % of all drug users and around 200 000 people), followed by cannabis (21 % and around 85 000 people) and cocaine use, (17 % and around 70 000 people), use of stimulants other than cocaine (5 % and around 22 000 clients) and other drugs use, which include hypnotics and sedatives, hallucinogens, volatile and other substances
 Among those who have entered treatment for the first time in their life the proportion of heroin users is lower and that of cocaine, cannabis users and clients consuming stimulants other than cocaine (mainly amphetamine and methamphetamine) is higher
 Differences between countries are relevant with 18 countries reporting more than 50 % of primary opioid users among drug clients, 8 countries with more than 20 % of primary cannabis clients and 3 countries with more than 20 % of cocaine clients.
 Stimulants other than cocaine, which will be the subject of one of 2010 selected issue are concentrated in some countries, namely the Scandinavian countries (amphetamine), Czech Republic and Slovakia (methamphetamine)
 Clients are mainly males (4 males for every female), with a mean age 31 years (those who have entered treatment for the first time are on average 1 year younger)
 Most clients start their drug use before the age of 20, around one third of the clients inject their primary drug, and the frequency of use varies by the main drug (the highest proportion of daily users is found among opioid clients and the lowest among users of stimulants other than cocaine)
 Social conditions of drug users entering treatment are generally poorer than in the general population (education, living and labour conditions)
 Differences are reported by primary drug and by country regarding gender, age distribution and patterns of drug use

 Recent comparable data on young people’s use of alcohol and drug come largely from surveys of 15- to 16-year-old school students. The European School Survey Project (ESPAD) conducted surveys in 1995, 1999, 2003 and more recently, 2007. The 2007 survey (Hibell et al., 2009) provides comparable data from 25 EU Member States as well as Norway and Croatia. Five countries conducted their own school surveys in 2008 (Belgium-Flemish Community, Spain, Italy, Sweden, United Kingdom-England)
 The latest ESPAD survey data from 2007 reveal that the highest lifetime prevalence of cannabis use among 15- and 16-year-old school students is in the Czech Republic (45 %) (Figure EYE-1 part (ii)). High lifetime prevalence estimates, ranging from 26 % to 32 %, are also reported in Estonia, France, the Netherlands, the Slovak Republic and the United Kingdom.
 Increases in cannabis use occurred in a number of European countries between 1995 and 2003 but have, in general, come to a halt or decreased more recently. Seven countries mainly located in Northern and Southern Europe (Greece, Cyprus, Malta, Romania, Finland, Sweden, Norway) reported overall stable and low lifetime prevalence of cannabis use during the whole period. Other western European countries, as well as Croatia and Slovenia, have shown a significant increase of lifetime cannabis use up to 2003 and since then nine of these reported a decrease of more than three percentage points, two were stable and none reported an increase. In most of central and eastern Europe the increasing trend observed between 1995 and 2003 seems not to have been reversed yet. In this region, two out of eight countries report increases of more than three percentage points since 2003, six or more a stable situation and none a significant decrease. In the five countries that conducted national school surveys in 2008, all reported stable or lower lifetime prevalence of cannabis use than reported in 2007 (Table EYE-11).
 Increases in lifetime cannabis use between 1995 and 2003 in Europe were in some countries accompanied by increases in the prevalence of cigarette smoking among school students. Since 2003, both trends have reversed, suggesting a possible link between tobacco and cannabis smoking.
 Estimates of the prevalence of other drug use among school students are much lower than those for cannabis use. For example, lifetime prevalence of cocaine use among 15- to 16-year-old school students is between 1 % and 2 % in half of the 28 reporting countries. Most of the remaining countries report prevalence levels of between 3 % and 4 %, while Spain, France, and the United Kingdom report 5 %. Among the five countries that conducted school surveys in 2008, two reported a decrease of 1%, one reported an increase of 1%, and two reported no change since the last survey (Table EYE-11). However, caution is required interpreting trends with such low prevalence.
 In the countries conducting their own national school surveys, drug prevalence questions may be considered comparable to the ESPAD questions but other aspects of the method mean the data are not strictly comparable.
Source: EMDDA July 10 2010

Some people can drink a lot of alcohol without becoming addicted, and specific genes may help explain why, researchers say.
In a new study of Australian twins, scientists found that separate genes appear to be responsible, to some degree, for dependence on alcohol — addiction — and how much people drink. Understanding how these genetic factors work together should give researchers more insight into treatment of alcoholism in its various forms, said study co-author John B. Whitfield, a researcher at Royal Prince Alfred Hospital in Australia.
Alcoholism and alcohol consumption may appear to be similar, but researchers are increasingly studying them separately. Consumption refers to the amount of alcohol that someone drinks, while addiction refers to a person’s inability to go without a drink.
“The transition from social alcohol consumption to alcohol dependence is a gradual process, and it is often hard to notice it,” said Dr. Alexei B. Kampov-Polevoi, an assistant professor of psychiatry at Mount Sinai School of Medicine. “As a result, many alcoholics and their family members continue to think that a person ‘just drinks too much’ while this person already developed alcohol dependence and requires treatment.”
Whitfield and his colleagues examined statistics about alcohol use from three studies of Australian twins completed between 1980 and 1995. The number of twins in the studies declined from 8,184 in 1980 to 3,378 in 1995.
The findings appear in the August issue of Alcoholism: Clinical & Experimental Research.
The researchers found twins who were genetically similar were more likely to consume similar amounts of alcohol. According to the study, some genes affected both addiction and alcohol intake, while some just affected addiction.
“We found (as others have also found) that alcohol dependence is partly, but not entirely, due to genetic differences between people who are affected by it and those who are not,” Whitfield said. “We also found that variation in the amount of alcohol that people habitually drink is subject to genetic influence, and that there is some — but not complete — overlap between the genes affecting these two things.”
Howard J. Edenberg, professor of biochemistry and molecular biology at Indiana University, said the findings — that genes separately affect alcoholism and drinking — are “reasonable.” But “that is a long way from identifying individual genes that actually are involved,” said Edenberg, whose own research is looking into that area.
So what should ordinary folks take from this study? “There is no direct and new message for people with alcoholism in their families; they are at higher risk than average but this has been known for some time and there is only a statistical risk, not a certainty by any means,” Whitfield said. “The more positive message for such people, and the community at large, is that we are learning more about alcohol use and alcohol-related problems and their causes.”
Source : HealthDay News 18th August 2004

New research suggests that people who smoke and drink heavily are more at risk for oral cancer, the Researchers from King’s College in London, England, found an increase in oral cancer among men and women in their 20s and 30s who smoke and binge drink.

The researchers said that when tobacco smoke combines with alcohol, it produces dangerous levels of cancer-causing chemicals that attack the lining of the mouth.

“Our data show that smoking, drinking and poor diet are major risk factors, and that the younger people start smoking and drinking, the higher the risk,” said Newell Johnson, a professor of oral pathology at King’s College

Source: Daily Telegraph, London reported Nov. 9.2004

Young men who report an unstable pattern of alcohol consumption including binge drinking have an elevated risk for experiencing hypomania, study results show. Notably, the effect was independent of total alcohol consumption and the presence of clinical alcohol use disorders.
“This fits with the idea that instability in different biological and behavioral systems is a core feature of risk for hypomania and finally risk for bipolar disorders,” say study authors Thomas Meyer (Newcastle University, UK) and Larissa Wolkenstein (University of Tübingen, Germany) in the journal Comprehensive Psychiatry.
Recent studies have suggested that vulnerability to hypomania is related to instability in certain psychologic processes. For example, individuals at risk for hypomania do not generally sleep less than others, but report a much more unstable sleeping pattern. Similarly fluctuations in self-esteem are much more characteristic of vulnerability to hypomania than are consistently low or high levels of self-esteem.
In the current study, the researchers assessed whether alcohol use might show a similar relationship to hypomania. They recruited 120 male students who completed the Hypomanic Personality Scale and were independently interviewed with the FORM 90 to assess alcohol consumption. The latter comprised an interview about a typical weekly drinking pattern and a calendar to assess drinking behavior over the last 90 days, noting special days with unusual drinking behavior.
The researchers found that intra-individual fluctuations in alcohol consumption predicted hypomania after accounting for clinical diagnoses of abuse or dependency. In addition, vulnerability for hypomania was significantly associated with mean standard ethanol content per drinking day.
Discussing their findings, the researchers note a recent theory that bipolar disorder is related to a hypersensitivity to reward-related cues, which is due to a dysregulation of the behavioral activation system.
“To extend this work further, it would be reasonable to look more closely at the motivational and affective processes associated with drinking alcohol and bipolar disorder and how mood and drinking are related,” Meyer and Wolkenstein comment.
Source: MedWire (www.medwire-news.md) 19 March 2010

Compared to drugs such as heroin and cocaine, many people consider marijuana a relatively benign substance. But two studies in this issue demonstrate disturbing similarities between marijuana’s effects on the brain and those produced by highly addictive drugs such as cocaine and heroin. One study, described on page 2050, indicates that marijuana withdrawal activates the same stress system in the brain triggered by withdrawal of opiates and alcohol, while the other, reported on page 2048, indicates that marijuana activates the same reward pathway as heroin.

Source : Science 27 June 1997: Vol. 276. no. 5321, pp. 1967 – 1968

Recurrent drinking is common among patients with alcohol dependence who have received treatment. This study assessed whether certain types of relapses are more likely to recur, are more severe, or are more amenable to a particular psychosocial therapy.
Researchers examined data from 592 of 952 outpatients with alcohol dependence who had been randomized in a larger trial to receive motivational enhancement therapy, cognitive-behavioral therapy, or twelve-step facilitation therapy. These 592 subjects had experienced a relapse (i.e., drinking after being abstinent for at least 14 days) and completed the relapse-onset section of the Relapse Questionnaire, which assesses patient-perceived influences that contribute to relapse.
• Relapses were divided into 3 types: negative affect/family influences, craving/cued, and social pressure. When relapses recurred, they were often (about half the time) the same type as the initial relapse. Social pressure relapses were most likely to repeat (58% of the time). Negative affect relapses were the most severe (i.e., associated with a greater number of drinks consumed per day).
• The 3 therapies affected the overall risk of relapse similarly. However, motivational enhancement therapy offered less protection than the other therapies against social pressure relapse.
Comments:
This study provides a typology that can help clinicians efficiently assess relapse risk among patients with alcohol dependence. Clinicians who understand their patients’ prior types of relapses have the opportunity to provide individualized relapse prevention counseling or referral.
Peter Friedmann, MD, MPH

Source:Zywiak WH, Stout RL, Longabaugh R, et al. Relapse-onset factors in Project MATCH: the Relapse Questionnaire. J Subst Abuse Treat. 2006;31(4):341–345.

A researcher at the University of Buffalo’s Research Institute on Addictions (RIA) has found a change in the brain that occurs after drug use and that may contribute to drug addiction.
The finding, reported in the January issue of Biological Psychiatry, demonstrates that repeated exposure to different types of drugs of abuse, such as cocaine, nicotine, amphetamine and alcohol, lead to a persistent or long-term reduction in the electrical activity of dopamine neurons in the brain.
Dopamine neurons are the origin of the reward pathway responsible for the “feel good” experience that is such a strong component of drug use and abuse.
“A persistent reduction in dopamine neuron electrical activity after repeated exposure to different types of drugs appears to be the result of excessive excitation of dopamine neurons,” according to Roh-Yu Shen (photo), a neuroscientist and the lead investigator on the study. “This represents a new and potentially critical neural mechanism for addiction and provides a working model that suggests how the reward pathway function is altered and how these changes can be responsible for triggering intense craving and compulsive drug-seeking.”

Source. January 2007 issue of Biological Psychiatry

Summary

DURHAM, N.C. — Within the mind of every smoker trying to quit rages a battle between the higher-order functions of the brain wanting to break the habit and the lower-order functions screaming for another cigarette, say researchers at Duke University Medical Center. More often than not, that cigarette gets lit.
Brain scans of smokers studied by the researchers revealed three specific regions deep within the brain that appear to control dependence on nicotine and craving for cigarettes. These regions play important roles in some of the key motivations for smoking: to calm down when stressed, to achieve pleasure and to help concentration.
“If you can’t calm down, can’t derive pleasure and can’t control yourself or concentrate, then it will be extremely difficult for you to break the habit,” said lead study investigator Jed E. Rose, Ph.D., director of the Duke Center for Nicotine and Smoking Cessation Research. “These brain regions may explain why most people try to quit several times before they are successful.”
Understanding how the brain responds to cigarette cravings can help doctors change nicotine cessation treatments to address all three of these components of withdrawal, Rose said. Drugs or therapies that target these regions may help smokers stave off the cravings that often spoil their attempts to quit.
The team’s findings are now online in the journal Neuropsychopharmacology. The research was funded by Phillip Morris USA.
Approximately one in five Americans smokes. Even though 70 percent of smokers report that they would like to quit, only 5 percent do so successfully.
In this study, the researchers manipulated the levels of nicotine dependence and cigarette craving among 15 smokers and then scanned their brains using positron emission tomography, or PET scans, to see which areas of the brain were most active.
Three specific regions of the brain demonstrated changes in activity when the smokers craved cigarettes versus when they did not.
One region that lights up, called the thalamus, is considered to be the key relay point for sensory information flowing into the brain. Some of the symptoms of withdrawal among people trying to quit stem from the inability to focus thoughts and the feeling of being overwhelmed, and could thus be explained by changes in this region, according to the researchers. The researchers found that changes in this region were most dramatic among those who said they smoked to calm down when under stress.
Another region that lights up is a part of the pleasure system of the brain. Changes in this region, called the striatum, were most notable in people who smoked to satisfy craving and for pleasurable relaxation, the researchers said.
A third region that lights up, called the anterior cingulate cortex, is vital to cognitive functions such as conflict, self regulation, decision making and emotion. People whose brain scans showed the most differences in this region also reported that they smoked to manage their weight.
“This knowledge gives us new clues about brain mechanisms underlying addiction to cigarettes and could allow us design better methods to help smokers quit,” Rose said.
Rose and his colleagues are now planning to perform brain scans on smokers undergoing nicotine replacement therapy, such as the nicotine patch, to determine how these treatments affect the same regions of the brain.
Other researchers participating in the study were Frederique M. Behm, Alfred N. Salley, James E. Bates, R. Edward Coleman, Thomas C. Hawk and Timothy G. Turkington.

Source: www.dukemednews March 2007

* Popular and clinical lore support the strong connection between smoking and alcohol consumption.

* Adolescent smokers appear to have a greater vulnerability to developing alcohol-use disorders.

* Results indicate that smoking “primes” the brain for subsequent addiction to alcohol and possibly other drugs.

Both academic studies and casual observation support the view that smokers tend to drink, and drinkers tend to smoke. New research using nationally representative data from the U.S. finds that smokers – particularly adolescent smokers – clearly have a greater vulnerability to alcohol-use disorders (AUDs) than do non-smokers.

Results are published in the December issue of Alcoholism: Clinical & Experimental Research.

“Smoking and alcohol – separately, or together – account for more than 20 percent of deaths in the United States,” said Richard A. Grucza, an epidemiologist at Washington University School of Medicine and corresponding author for the study. “Cigarettes and alcohol are also known to be ‘gateway’ drugs, that is, the overwhelming majority of illegal drug users begin their use with one or both of these legal drugs.”

“We have known about the link between cigarette smoking and alcohol use for a while, but we have not really asked the question, as the authors here asked, whether use of one could increase the vulnerability of becoming addicted to the other,” said Kevin W Chen, associate professor at the University of Maryland School of Medicine.

“Ours was the first,” added Grucza, “to examine quantity of drinking in relationship to smoking and AUDs. Our central questions were: Can this association be explained by the fact that smokers are heavier drinkers, or is there something else going on? In other words, do smokers appear to be more sensitive to the effects of alcohol?” The short answer appears to be yes.

Researchers examined data from an aggregate of 2002 through 2004 U.S. National Surveys on Drug Use and Health. Randomly selected, household-dwelling adolescents and young adults (n=74,836) were selected from the non-institutionalized and civilian American population and queried about their drinking and smoking practices.

Results indicate that smokers – particularly adolescent smokers -have a greater vulnerability to AUDs than do non-smokers.

“In general, smokers were at more than a 50 percent higher risk, although the differences were larger in younger adolescents and among light drinkers,” said Grucza. “For example, among 15- to 17-year-olds who drank fewer than eight drinks in the month before the survey, more than 20 percent reported an AUD, compared with about five percent among the non-smoking group with the same level of drinking. We conclude that, although smokers do drink higher rates of alcohol, this alone does not explain their higher vulnerability to AUDs.”

Grucza said that these findings go beyond the popular view that bad behaviors like smoking and drinking to excess simply tend to “go together,” especially during adolescence. “It seems that smoking makes the adolescent brain more vulnerable to other addictions,” he said. “Addictive drugs all act on a part of the brain that is described as the ‘central reward circuitry.’” Once this system is exposed to one drug, the brain may become more sensitive to the effects of other drugs, as demonstrated by a number of rodent studies.

“Studies like this will set up an alert – for those who consider adolescent smoking tolerable – to rethink the issue, or perceive the problem differently,” noted Chen. “Although we do not know the exact causal relation between the two, the damage to our health is so severe that we need to create a more objective image to reject both smoking and drinking among adolescents.”

“Ours is the first study to – establish a correlation between adolescent smoking and AUDs that cannot be explained by heavier drinking,” said Grucza. “Now we, and hopefully others, need to investigate whether or not smoking actually causes adolescents to be more susceptible to AUDs. Our results are in line with an emerging literature that shows adolescence may be a unique window of vulnerability for addictions development. If it is proven that nicotine directly impacts vulnerability to alcoholism and other addictions, then that is a new, strong message to add to the health-education arsenal. However, even if this correlation is completely non-causal, these results can help to identify kids who are at risk for AUDs.”

Source:Alcoholism: Clinical & Experimental Research. (ACER) Article Date: 30 Nov 2006 – 13:00 PDT

Research Summary

Smoking among young adults has plummeted since California implemented a groundbreaking tobacco-control plan 12 years ago, according to new research from the University of California at San Diego.

The California Tobacco Control Program, established in 1989, has been credited with reducing smoking among all adult smokers, but the decline among young adults has been especially striking, researchers said. Notably, cessation rates among young Californians were higher than among young adults in New York and New Jersey, which have similarly high tobacco prices but lack comprehensive stop-smoking campaigns, as well as compared to young adults in tobacco-growing states (TGS).

“We were surprised to find that, since the advent of the California campaign, young people have increased their rate of quitting by 50 percent, far more than their older counterparts,” said study author Karen Messer, Ph.D. “It used to be that smokers over age 50 were the ones quitting because they understood the health consequences of smoking …
“These young adults have grown up in a tobacco-controlled climate, where smoking isn’t the norm and isn’t socially supported. We may be seeing the first generation who believe it’s not cool to smoke, which could pay huge dividends in their future health.”

Another UCLA study focused on tobacco consumption trends. “We found that there is a national trend of declining cigarette consumption for all age groups, but the most significant by far was observed in California smokers over age 35,” noted researcher Wael K. Al-Delaimy, M.D., Ph.D.
“The data suggest that — compared with states with no tobacco control initiatives (TGS) or states with an increased cigarette price as the principal tobacco control measure (NY/NJ) – California’s comprehensive tobacco control program is more effective in decreasing cigarette consumption for those over age 35.”

Source: journal Tobacco Control April 2007

Nicotine reaches the brain as quickly as 10 seconds after inhalation, triggering feelings of pleasure, increasing heart rate and raising blood pressure.
But alongside the nicotine, smokers breathe in a deadly cocktail of chemicals including arsenic, formaldehyde and polonium.
“Cigarette smoke contains at least 69 different cancer-causing chemicals and thousands of other poisons which can increase the risk of several different types of cancer,” said Ed Yong of Cancer Research.
“Nicotine itself doesn’t cause cancer, it just keeps the smokers hooked,” he added.
Tobacco is so addictive that doctors writing in the Lancet medical journal this year said it should be classified as an illegal drug, on a par with amphetamines and barbiturates.
The government says 70 per cent of smokers want to give up but are held back by the power nicotine has over them.
Only one in five who try quitting manage to abstain for a year, while just three per cent succeed in breaking the habit by willpower alone, according to statistics compiled by health charity Action on Smoking and Health (ASH).
One in six smokers say they light up within five minutes of waking up, with half having their first cigarette inside the first 30 minutes of the day.
The government says 106,000 people die a year in Britain from smoking-related illnesses.
From July 1 smoking is banned in enclosed public spaces across all of the United Kingdom when England introduces its own prohibition to match those already in place in Scotland, Wales and Northern Ireland.
But while this may help many adults give up, there are some groups who will need much greater assistance, says ASH.
Around a quarter of all adults smoke but among the most disadvantaged, such as single parents on benefit, the rates are as high as 70 per cent.
“It’s a response to stress,” said ASH director Deborah Arnott. “If your life is very stressful then smoking seems to help in some way.”
She said such disadvantaged groups should be prescribed nicotine patches for longer periods than the usual maximum of 12 weeks to help them quit.
“It’s the nicotine they are addicted to, but it’s the smoke that’s killing them,” she said.
Prime Minister Gordon Brown cut the value added tax on nicotine replacement products to five per cent in his last budget as chancellor of the exchequer.
The tax break will last for a year but ASH says the price reduction should be made permanent to help the most addicted and disadvantaged.

Source: www.smh.com.au June 30, 2007

For years, scientists described the human brain as a machine with parts, each part dedicated to controlling different activities. If a part was injured, the function it controlled would be lost permanently. But as Norman Doidge shows in his new book, The Brain That Changes Itself, (Viking) new neurological evidence has emerged showing that the brain can be trained to rewire itself after an injury, such as a stroke or ear or eye damage. Through interviews with neuroscientists and neuron-rehabilitation patients, Doidge also finds that the brain is capable of improving learning disabilities and intellectual and even moral performance through techniques such as repetition of learning and implementation of regular habits. The more we know about these processes, the more doctors can help patients to find other ways perform lost functions.

Doidge is a psychiatrist, psychoanalyst, and researcher on the research faculty at Columbia University’s Center for Psychoanalytic Training and Research, in New York, and the University of Toronto’s Department of Psychiatry.

Source: Hudson Institute August 2007

For years, scientists have known that some people are biologically more susceptible to drug addiction than others, but they have only been able to speculate why.
In the August 15, 2007 issue of the Journal of Neuroscience, researchers at the University of Chicago report on a study that may help answer this question.
They discovered that rats most likely to self-administer addictive drugs had a particular receptor in the brain that is more responsive than the same receptor in rats least likely to self-administer addictive drugs.
This receptor, known as the nicotinic acetylcholine receptor (nAChR), increases excitability within in the brain’s reward centers. In the animals that were more likely to take addictive drugs, the effects of these receptors were much stronger, leading to more profound excitation of the cells and pathways associated with reward.
Stress, and the associated increases in stress hormones, will promote drug-taking behavior regardless of whether an animal is more or less susceptible, say the researchers. They showed that stress also increases the responses of nAChRs within the brain’s reward areas.
“We tested the exploratory behavior of rats in an unfamiliar cage. Rats that explore a new environment for a prolonged period of time were more interested in addictive drugs,” says Daniel McGehee, PhD, associate professor and lead researcher on this study. ” Those rats also had stronger nAChR responses, meaning their brains responded differently to the drugs. We measured receptor activity in the brain’s reward centers that are known to be activated by addictive drugs.”
“This study provides valuable insight into the mechanism of addiction,” says McGehee. “It raises the possibility that nicotinic receptors may be important targets for the treatment of multiple addictions, not just nicotine. Unfortunately, blocking these receptors may also interfere with healthy behaviors that depend upon the same brain circuitry. Precisely where these findings will lead drug treatment strategies is unclear, but this work provides insight into the role of nicotinic receptors in the vulnerability to multiple classes of addictive drugs.”

Source: University of Chicago Medical Center. Published on Eureka Alert August 2007

Drug users who can’t kick the habit can blame a dysfunctional brain for their addiction, according to new research.
A study by the University of Melbourne has found long-term drug users have more difficulty controlling impulses because their frontal cortex is impaired.

The two-year study found opiate users needed to use more of their brains to resist impulses in a test of self control than those who were clean. The findings shed new light on why drug addicts find it so hard to quit, despite the health consequences.
“Drugs can capture and hijack some parts of the brain,” said Dr Murat Yucel, a lead researcher in the study. In this study we found the frontal cortex, an area that is essential for exercising control over thoughts and behaviours, was working inefficiently. These findings may help explain why it takes addicted individuals enormous effort to exercise control over their drug taking behaviour in the face of adverse consequences and why they are vulnerable to relapse back into uncontrolled, compulsive patterns of use.”
The study – published in the journal, Molecular Psychiatry, last month – also found drug users’ brain cells in the frontal region were less healthy than normal. The research shows drug taking is not a matter of choice for long-term users, who have a reduced biological capacity to stop, Dr Yucel says.
Researchers will next examine whether reduced brain function is a consequence of addiction or a contributing factor that makes some people more vulnerable to drug abuse. Co-researcher Dan Lubman said the study would likely lead to the development of new strategies for the treatment of addiction.
“These findings tell us that we need to provide a combination of pharmaceutical and psychological treatments that will help bolster the efficiency of the frontal cortex and hence the individual’s ability to stop their urge to use drugs,” he said.

Source: www.yahoo7News.com Aug. 2007

• Marijuana is the most commonly used illicit drug in the United States.
• New research shows that the use and misuse of alcohol and marijuana are influenced by a common set of genes.
Marijuana is the most commonly used illicit drug in the United States. Roughly eight to 12 percent of marijuana users are considered “dependent” and, just like alcohol, the severity of symptoms increases with heavier use. A new study has found that use and misuse of alcohol and marijuana are influenced by a common set of genes.
Results will be published in the March 2010 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
“Results from a large annual survey of high-school students show that in 2008, 41.8 percent of 12th graders reported having used marijuana,” explained Carolyn E. Sartor, a research instructor at Washington University School of Medicine and corresponding author for the study. “Although many may have used the drug on only a few occasions, 5.4 percent of 12th graders reported using it daily within the preceding month.”
“The active ingredient in marijuana is THC, which mimics natural cannabinoids that the brain produces,” added Christian Hopfer, associate professor at the University of Colorado School of Medicine. “The cannabinoid system is critical for learning, memory, appetite, and pain perception. Most users of marijuana will not develop an ‘addiction’ to it, but perhaps one in 12 will. What is not commonly appreciated about marijuana use is that strong evidence has emerged that it increases the risk of developing mental illnesses and possibly exacerbates pre-existing mental illnesses.”
“Like any drug, marijuana can be used in a way that negatively impacts quality of life, interfering with functioning at school or work or leading to problems with family and friends,” said Sartor. “Although at least three of six symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) are needed to meet full criteria for cannabis (marijuana) dependence … the presence of even one or two of these symptoms could create distress or interfere with day-to-day functioning. There is strong evidence for a genetic component to use and dependence on marijuana as well as alcohol, and the use (and misuse) of these substances frequently occur together.”
Researchers examined 6,257 individuals (2,761 complete twin pairs and 735 singletons) listed in the Australian Twin Registry, 24 to 36 years of age. Alcohol and marijuana use histories were gathered in telephone diagnostic interviews and used to derive levels of alcohol consumption, frequency of marijuana use, and DSM-IV alcohol and cannabis dependence symptoms.
“Our findings indicate that … many of the same genetic factors that contribute to alcohol use also contribute to marijuana use,” said Sartor. “Likewise, alcohol dependence symptoms and cannabis dependence symptoms can be traced to some of the same genetic influences. For both alcohol and marijuana, the majority of genetic factors that contribute to use also contribute to dependence symptoms.”
“In other words,” said Hopfer, “the genetic influences on drug use are not specific to individual drugs, but seem to influence a general tendency to engage in drug use. This is important to note because there is a tendency to study drugs in isolation – alcohol, tobacco, marijuana, cocaine, etc. These findings add support to the notion of common mechanisms underlying all addictions.”
“The fact that very little of the environmental influences on alcohol and marijuana use, or on alcohol and cannabis dependence symptoms, could be traced to common sources indicates that there may be important distinctions between those environmental factors that influence alcohol-related outcomes and those that influence marijuana-related outcomes,” said Sartor. “Identifying alcohol- and marijuana-specific risk factors is an important next step in this line of research.”
“Marijuana research is relatively sparse compared to alcohol or nicotine research,” added Hopfer. “However, if you look at reports of at least adolescents and young people using, it becomes clear that marijuana use, including daily marijuana use, is quite common and the effects of this are not well understood. The mental illness/marijuana connection has not received much press, although I think the evidence has grown substantially that marijuana is a causal risk factor for the development of mental illness.”

Source: http://www.attcnetwork.org/explore/priorityareas/science/tools/asmeDetails.asp?ID=643

Smoking marijuana as a teenager could raise the risk of developing schizophrenia and psychotic symptoms as a young adult, according to a new study that compared the prevalence of mental illness among marijuana users and non-users.

Bloomberg News reported March 2 that researcher John McGrath of the University of Queensland, Australia, and colleagues studied 3,801 young-adult sibling pairs and concluded that those who used marijuana the longest (six or more years) were twice as likely to develop schizophrenia or delusional disorders. They also were four times more likely than non-users to score highly on a test gauging psychotic-like experiences.

Higher scores on the test also were seen among those who used marijuana for less than three years.

Source: www.jointogether.org  March 2010

Nicotine addiction relies on brain receptors that have been difficult to fully study and characterize. Scientists at the University of Colorado in Boulder have demonstrated that an immunolabeling technique can effectively analyze receptor subunits.

Background: Nicotine’s effects on the brain are triggered upon its binding to nicotinic acetylcholine receptors, each of which consists of five subunits: two alphas, one beta, one delta and one gamma. Different combinations of these subunits produce different receptor subtypes, which may vary in their pharmacology, biophysical properties, and distribution. To more fully understand how to interfere with nicotine’s effects in the brain, scientists must first understand where these different receptors are and how they work. Two of the most important subunits, a4 and b2, have been hard to study because current study methods can only locate the fully assembled receptor unit. Researchers wanted to know if an alternative strategy of immunolabeling (i.e., using antibodies to tag individual proteins), which has been fraught with technical challenges, would be able to identify, map, and quantify separate subunits.

Study Design: Scientists at the University of Colorado worked with brain sections of mice genetically engineered to express particular a4 and b2 subunit combinations. Using a sensitive immunolabeling technique, they explored the expression of the a4 and b2 subunits at both the gene and protein levels. Additional mice strains, missing the subunits under study, were used as controls.

What They Found: The two predominant nicotinic receptor subtypes (a4 and b2) were reliably detected using immunolabeling. Expression of the a4 subunit protein was almost universally dependent on b2, whereas most, but not all, b2 subunit protein expression was a4-dependent.

Comments from the Authors: Immunolabeling using specific antibodies offers a powerful approach for mapping the distribution of nicotine receptor subunits and can produce reliable quantitative results.

What’s Next: Similar studies can be designed to locate other nicotine receptor subtypes. In many cases, the antibody recognition sites are inside the cell membrane. It will likely take alternative biochemical approaches to uncover these less accessible sites. A better understanding of receptor composition and function may eventually have important implications for developing interventions at the receptor level.

Source: The study, led by Dr. Paul Whiteaker of the Institute for Behavioral Genetics at the University of Colorado, Boulder, with Dr. Jon Lindstrom of the University of Pennsylvania, was published in volume 499, number 6, pages 1016-1038 (2006) of the Journal of Comparative Neurology.

An analysis that compared the DNA of drug abusers with that of non-abusing controls has identified 89 genes that are likely to contain variants that contribute to addiction vulnerability.

Background: Vulnerability to addiction is a complex trait with strong genetic influences. Since the mid-1990s, scientists have been developing methods and tools to identify and evaluate the functional role of genes and their variants. The impact of such efforts has been greatly enhanced by the Human Genome and International HapMap Projects. By 2001, the first low-resolution genome-wide association studies from the NIDA-IRP’s Molecular Neurobiology Branch were published. Genetic research technology is now able to reliably scan the genome of individuals for genetic variants linked to specific functions.

Study Design: From 1990 to 2005, thousands of people participated in studies at NIDA-IRP’s Molecular Neurobiology Branch, providing self-reports and DSM Diagnostic Interview Schedule scores. From among this pool, researchers identified 980 African-American and European-American “drug abusers” (heavy lifetime use of illegal substances) and 740 controls (no significant history of addictive substances, no abuse, no dependence). Pooled DNA samples, prepared from blood extracted from each group were used to examine a panel of close to 640,000 genetic variations.

What They Found: Using strong statistical models that focused on the overlaps between the samples, this screen identified 89 genes that display clusters of genetic variants that are likely involved in addiction vulnerability. Most of these genes are expressed in the brain. Twenty-one of these genes influence cell adhesion, and nearly all of those are expressed in brain regions implicated in memory processes.

Comments from the Authors: The nature of the addiction-associated genes identified in this study, especially those involved in cell adhesion, suggest the critical role played by dysfunctional nerve cell connections in the addicted brain.

What’s Next: Other genes that emerged from the analysis are being tested in the context of where they are located in the brain and their likely functions: enzymes, transporters, receptors, protein processing, and transcriptional regulation. Results like these highlight characteristics that are common to human addiction and may facilitate efforts to develop targeted prevention and treatment strategies.

Source:The study, led by Drs. George Uhl and Qing-Rong Liu of the Molecular Neurobiology Branch at the National Institutes of Health Intramural Research Program at NIDA in Baltimore, was published in volume 141B, pages 1-8 (2006) of the American Journal of Medical Genetics Part B (Neuropsychiatric Genetics).

In this national fellowship report, project directors from the first 10 Reclaiming Futures sites share the lessons they learned in creating and implementing a model for helping teens in trouble overcome drugs, alcohol and crime.

The directors offer specific steps for planning and instigating the changes, provide real-life examples from diverse communities across the nation, and provide a road map for communities to adopt the six-step model all at once or one step at a time.

The report recommends screening each teen for drug and alcohol problems, assessing the severity of his/her drug and alcohol use, providing prompt access to a treatment plan coordinated by a service team; and connecting the teen with employers, mentors, and volunteer service projects.

The report describes how judges, probation officers, treatment specialists, families and community members can take steps right now to improve the future of these youth.

Upon completion of a brief survey, the full report is available as a PDF to download at no cost.

http://www.reclaimingfutures.org/?q=judicial_report_survey&reportname=ProjectDirectors

Publication Year: 2007

Publisher

Reclaiming Futures
Portland State University
527 SW Hall, Suite 400
Portland, or 97201
Phone: 503.725.8911
Website: http://www.reclaimingfutures.org

People with a certain gene variant appear to be at higher risk of cocaine addiction, according to researchers from the Institute of Psychiatry.
Medical News Today reported March 13 that some people have a gene that stops the production of DAT, which regulates removal of extra dopamine in the brain. Cocaine works by limiting DAT, overloading the brain with dopamine.
People who have the DAT-limiting gene were found to be more likely to become addicted to cocaine; those with two copies of the gene were at even higher risk.
“This study is the first large-scale search for a genetic variant influencing the risk of developing cocaine addiction or dependence,” said lead researcher Gerome Breen. “The target we investigated, DAT, is the single most important in the development of cocaine dependence. It made sense that variation within the gene encoding DAT would influence cocaine dependence.”
Source: Proceedings of the National Academy of Sciences.March 2006

Long-term cocaine use can alter the function of genes in the brain, leaving “pleasure circuits” stuck in the open position and increasing craving for the drug, according to a new animal study conducted by researchers at the Mount Sinai School of Medicine.
Reuters reported Jan. 9 that researcher Ian Maze and colleagues found that the gene 9A — which produces an enzyme responsible for switching other genes on and off — was repressed in the brains of mice given repeated doses of cocaine. Researchers also found that restoring the activity of gene 9A reversed cocaine preference and craving in lab mice.
“This finding is opening up our understanding about how repeated drug use modifies in long-lasting ways the function of neurons,” said Nora Volkow, director of the National Institute on Drug Abuse.
Source: Science. Jan. 8, 2010

For the first time, federal researchers have broken down the disease of alcoholism into five distinct subtypes, which experts say should help provide more targeted treatment for problem drinkers.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) reported June 28 that the five new subtypes include “Young Adult,” “Young Antisocial,” “Functional,” “Intermediate Familial,” and “Chronic Severe.”
“Our findings should help dispel the popular notion of the ‘typical alcoholic,’” said study lead author Howard B. Moss, M.D., associate director of NIAAA’s Clinical and Translational Research division. “We find that young adults comprise the largest group of alcoholics in this country, and nearly 20 percent of alcoholics are highly functional and well-educated with good incomes. More than half of the alcoholics in the United States have no multigenerational family history of the disease, suggesting that their form of alcoholism was unlikely to have genetic causes.”
“Clinicians have long recognized diverse manifestations of alcoholism, and researchers have tried to understand why some alcoholics improve with specific medications and psychotherapies while others do not,” added NIAAA Director Ting-Kai Li, M.D. “The classification system described in this study will have broad application in both clinical and research settings.”
Moss and colleagues developed their subtypes based on survey respondents’ family history of alcoholism, age of onset of regular drinking and alcohol problems, symptom patterns of alcohol dependence and abuse, and the presence of additional addictive and mental disorders.
They found that 31.5 percent of alcoholics in the U.S. fall under the Young Adult subtype, who have relatively low rates of other drug or mental-health problems, low rates of family alcoholism, and rarely seek help for their drinking. The Young Antisocial subtype accounts for 21 percent of alcoholics, the researchers said; this category includes drinkers in their mid-20s who tend to have early onset of drinking, a family history of alcoholism, mental-health problems, and co-occurring tobacco or illicit-drug use. This group was more likely to have sought help for drinking than the Young Adult subtype.
Members of the Functional subtype, accounting for 19.5 percent of alcoholics, are typically middle-aged and well-educated, with stable jobs and families. They are relatively likely to have a family history of alcoholism and a personal history of major depressive illness in their lives, and about half are smokers. A similar percentage (19 percent) of American alcoholics fall into the Intermediate subtype, who are middle-aged and more likely to have a family history of alcoholism and mental illness than the Functional subtype. Most are smokers, problems with other drug use is relatively common, and about a quarter have sought help for their drinking.
The final subtype identified by Moss and colleagues, Chronic Severe, covers 9 percent of alcoholics. Most are middle-aged, with early onset drinking, high rates of antisocial personality disorders and criminality, and a strong family history of alcoholism. This subtype is typified by the highest rates of mental-health problems, smoking, and illicit-drug use, and two-thirds of this group has sought treatment for their drinking problems
Source: Drug and Alcohol Dependence. June 2007

Clinical studies, like those by Barbara Mason at Scripps Institute, have documented a marijuana withdrawal syndrome among a minority of users. Are we prepared to say that marijuana is addictive? Why didn’t we identify this syndrome years ago?

Nora Volkow: Absolutely, there is no doubt that some users can become addicted to marijuana. In fact, well over half of the close to 7 million Americans classified with dependence or abuse of an illicit drug are dependent on or abuse marijuana. It is important to clarify that while withdrawal is one of the criteria used to diagnose an addiction (which also includes compulsive use in spite of known adverse consequences), it is possible for an individual to suffer withdrawal symptoms without he or she being addicted to an abused substance.

Now, to answer your specific question, the reason for the relatively late realization that people who abuse marijuana can develop a cannabis withdrawal syndrome (CWS) if they try to quit is probably the result of at least two factors. First is the fact (which you hint at already) that a clinically relevant cannabis withdrawal syndrome may only be expected in a subgroup of cannabis-dependent patients. This may be partially explained by marijuana’s uptake into and slow release from fat cells, which can occur over days or weeks after last use. Thus, cessation of marijuana use may not be so abrupt, and could thereby diminish signs of withdrawal. The second factor relates to the small to negligible associations between recalled and prospectively assessed withdrawal symptoms, which may have precluded many previous, recall-based studies from detecting or properly characterizing CWS. It is also worth pointing out that other addictions (e.g., cocaine) were also not initially thought of as capable of triggering withdrawal symptoms.”
Source: http://addiction-dirkh.blogspot.com/2009/12/q-with-nora-volkow.html?

People with clinical addictions know first-hand the ravages the disease can take on almost every aspect of their lives.
So why do they continue addictive behaviors, even after a period of peaceable abstinence Some answers appear rooted in regions of the brain active during decision making.
“It’s perhaps not just that people are slaves to pleasure, but that they have trouble thinking through a decision,” said Charlotte Boettiger, an assistant professor of psychology at the University of North Carolina at Chapel Hill, and lead author of a study in the December issue of the Journal of Neuroscience that took a novel tack in addiction imaging research. Our data suggest there may be a cognitive difference in people with addictions,” Boettiger said. “Their brains may not fully process the long-term consequences of their choices. They may compute information less efficiently.”
The study also found that a variant of the COMT gene, which controls the level of the neurotransmitter dopamine in the cortex, was associated with a tendency to make impulsive decisions and with high activity in certain brain areas during decision making. Current medications for addictions are not universally effective; many either mimic the addictive substance to help people get through withdrawal periods or block the substance to prevent its effects. For stimulants, such as methamphetamines, there are no therapies yet, Boettiger said.
“What’s exciting about this study is that it suggests a new approach to therapy. We might prescribe medications, such as those used to treat Parkinson’s or early Alzheimer’s disease, or tailor cognitive therapy to improve executive function,” said Boettiger, who led the study as scientist at the University of California, San Francisco’s Gallo Clinic and Research Center. I am very excited about these results because of their clinical implications,” said Dr. Howard Fields, a professor of neurology at UCSF and an investigator in the Gallo Center.
“The genetic findings raise the hopeful possibility that treatments aimed at raising dopamine levels could be effective treatments for some individuals with addictive disorders,” said Fields, who is senior author of the study. Most addiction imaging studies have focused on the brain response to drug-related stimuli.
Boettiger used functional magnetic resonance imaging (fMRI), which shows brain activity while a subject performs a function, to see what happened inside their heads when sober alcoholics and people in a non-alcoholic control group made decisions between immediate and delayed rewards. Boettiger recruited 24 subjects; 19 provided fMRI data, nine were recovering alcoholics in abstinence and 10 had no history of substance abuse. Another five were included in the genotyping analysis.
At the fMRI research facility at the University of California, Berkeley, the subjects were asked to decide between receiving a small monetary award immediately or wait for a larger payoff. The scenarios were hypothetical, but the tasks measured rational thinking and impulsivity; sober alcoholics chose the “now” reward almost three times more often than the control group, reflecting more impulsive behavior. While decisions were being made the imaging detected activity the predicted individual choice in regions associated with decision making — the posterior parietal cortex, the dorsal prefrontal cortex, the anterior temporal lobe and the orbital frontal cortex.
People who sustain damage to the orbital frontal cortex generally suffer impaired judgment; they manage money poorly and act impulsively. Boettiger’s study revealed reduced activity in the orbital frontal cortex in the brains of subjects who preferred “now”over “later,” most of whom had a history of alcoholism. The orbital frontal cortex activity may be a neural equivalent of long-term consequences. “Think of the orbital frontal cortex as the brakes,” Boettiger said. “With the brakes on, people choose for the future; without the brakes they choose for the short-term gain.”

The dorsal prefrontal cortex and the parietal cortex often form cooperative circuits, and this study found that high activity in both is associated with a bias toward choosing immediate rewards.
The frontal and parietal cortex are also involved in working memory — being able to hold data in mind over a short delay. When asked to choose between $18 now or $20 in a month, the subjects had to calculate how much that $18 (or what it could buy now) would be worth in a month and then compare it to $20 and decide whether it would be worth the wait. The parietal cortex and the dorsal prefrontal cortex were much more active in people unwilling to wait. This could mean, Boettiger said, that the area is working less efficiently in those people.
The COMT gene has two common variants with a single amino acid difference at position 158; valine (Val) or methionine. The Val form of the gene is associated with lower dopamine levels, and Boettiger’s study showed that people with two copies of the Val allele (resulting in the lowest dopamine levels) had significantly higher frontal and parietal activity and chose now over later significantly more often.
“We have a lot to learn,” Boettiger said. But the data take a significant step toward being able to identify subtypes of alcoholics, which could help tailor treatments, and may people who are at risk for developing addictions and provide earlier intervention. The bigger picture, Boettiger said, is that her study provides more evidence that addiction is a disease, something even some of her peers do not yet believe.
“It’s not unlike chronic diseases, such as diabetes,” she said. “There are underlying genetic and other biological factors, but the disease is triggered by the choices people make.”
“It wasn’t that long ago that we believed schizophrenia was caused by bad mothers and depression wasn’t a disease. Hopefully, in 10 years, we’ll look back and it will seem silly that we didn’t think addiction was a disease, too.”

http://www.unc.edu/

Source: News-Med.net 30th Dec. 2007

Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People’s Republic ofChinaThe research reveals that a subject’s brain with low beta-endorphin levels becomes accustomed to the presence of an exogenous surplus, diminishing its own supply and triggering dependence on an external source–in this case, alcohol.
According to a study by the research group “Alcoholism and drug addiction”, of the University of Granada, although there are no specific reasons to become alcoholic, many social, family, environmental, and genetic factors may contribute to its development. Thanks to this study, researchers have shown that the lack of endorphin is hereditary, and thus that there is a genetic predisposition to become addicted to alcohol. Beta-endorphin is a kind of “morphine” released by the brain in response to several situations, such as pain. In this way, beta-endorphins can be considered “endogenous analgesics” to numb or dull pains.
Researchers have focused on the low beta-endorphin levels in chronic alcohol abusers. According to José Rico Irles , professor of Medicine of the UGR, and head of the research group, this low beta-endorphin level determines whether someone may become an alcoholic. When a subjects’ brain with low beta-endorphin levels gets used to the presence of an exogenous surplus, then, when its own production stops, a dependence starts on the external source: alcohol.
Who may become and alcohol abuser?
A total of 200 families of the province of Granada participated in the research. There was at least one chronic alcoholic parent in each family. From birth, each subject presented predetermined beta-endorphin levels. However, children of this population group aged between 6 months and 10 years old, registered lower beta-endorphin levels than other children of the same age. “These levels were even lower in children whose both parents were alcohol abusers”, the researcher states. According to researcher, although alcohol consumption does not affect all people in the same way, differences in endorphin levels make some subjects more vulnerable to alcohol. Therefore, they are more likely to become alcohol dependent.
Beta-endorphins constitute a useful biological marker to identify specifically those subjects who have a higher risk of developing alcohol abuse, the research claims. Regarding the results of this study, professor Rico states the following: “alcohol-abuse prevention must consist of locating and identifying genetically predisposed subjects.” More campaigns for children and teenagers should be launched before these young people make contact with alcohol. Alcohol awareness is fundamental to prevent addiction, the researcher affirms, because alcohol is a drug with reversible effects up to a point.
In relation to the “botellculture” (Botell’s a Spanish custom in which young people congregate in a park, street or any open public place to share alcoholic drinks and converse before entering bars, nightclubs, discos, etc.), José Rico states that some of these “social drinkers” could have low beta-endorphin levels and, therefore, a higher predisposition to become “solitary drinkers” and to develop alcohol abuse.

http://www.ugr.es/

Source:Newa-Medical.net 21st Dec. 2008

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different
technologies have revealed a variety of genes and pathways underlying addiction; however, each individual
technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg. cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

Discussion
The addiction-related genes, (common) pathways, and networks were traditionally studied experimentally. The
explosion of genomic and proteomic data in recent years both enabled and necessitated bioinformatic studies of
addiction. Integration of data from multiple sources could remove biases of any single technology platform, and
statistical and network analysis of the integrated data could uncover high-level patterns not detectable in any individual
study. For instance, our analysis revealed not only many pathways already implicated in addiction [34–38], but also
new ones such as GnRH signaling pathway and gap junction, as well as the coupled positive feedback loops through
CAMKII. They could serve as interesting hypotheses for further experimental testing.

The collection of addiction-related genes and pathways in KARG, the first bioinformatic database for addiction, is the
most comprehensive to date. However, as new technologies continue to be developed and used, more and more genes will
be linked to addiction. In 2004, a paper asked why proteomics technology was not introduced to the field of drug addiction
[5]; since then eleven studies have identified about 100 differentially expressed proteins in drug addiction. Tillingarray
technology, another new strategy for whole-genome identification of transcription factors binding sites, has been
used to identify targets of CREB, an important transcription factor implicated in drug addiction [39]. In addition, as 100 K
and 500 K SNP arrays have been introduced recently, whole genome association studies will also identify more closely
packed and unbiased hypothesis-free vulnerable positions [40]. We will continue to integrate new data and update the
gene list and molecular pathways toward a better understanding of drug addiction.

Source: Li CY, Mao X, Wei L (2008) Genes and (common) pathways underlying drug addiction. PLoS Comput Biuo 4(1):e2. doi:10.1371/journal.p.c

The above article is of extreme interest – and in order to make the details more informative for non-specialist readers Dr. Stuart Reece from Australia has written the following explanations:

The paper means that many addiction have several links in common at the molecular level.

Many major pathways to intracellular signalling are commandeered by the various addictions which have much in common. The addictions documented are tobacco, alcohol, opiates (heroin morphine methadone) and cocaine.

The paper is a computational biology paper which means that supercomputers are used to study 2343 items which have been published in the molecular literature relating to the molecular alterations induced by drug addiction.

Its very essence and principal strongly supports my long-standing contention that molecular research could be much better undertaken in this area, and much more aggressively pursued. This paper is from China.

Of course one of the most difficult parts about addiction is the way in which behaviour which initially is volitional, becomes altered to be habitual and refractory to what would normally be the messages to desist the addictive and destructive behaviours.

What is so revolutionary about the paper -beyond providing a very concise synthesis of several vast scientific literatures – is two things:

1) The way in which the institution of irreversible (or at least refractory) changes are described at the molecular level – in other words the institution of hard core addiction and perturbed memories and behaviours
and
2) The critically important list of molecular pathways which are identified as key components of the cell machinery which are commandeered and effectively pirated or hijacked.

The paper suggests that when fast and slow acting feedback loops interact within the cell (particularly neuron and glial cell) circuitry changes can become irreversible. This is the molecular correlate of the behavioural change which so disturbs the world, addicts and other people.

The list of the major pathways which are perturbed by addiction is absolutely central to any modern understanding of this subject, and strongly expose the terrible fallacies of the legalization arguments. A brief list of some of these and concise notes as to their significance is as follows.

1) CAMKII – Calcium-calmodulin kinase II – this is a key co-stimulating and triggering factor of many of the key cell reactions, particularly relating to synaptic transmission, growth, movement, cell division and growth, coagulation and thousands of reactions in the cell.

2) Synaptic Transmission – this is the basic building block of neural transmission and the molecular substrate of thinking,. remembering, feeling and everything neural. Indeed the article highlights also gap junction formation. These are critical communicating points not only of physical adhesion but also for new synapse formation and cellular cross-talk as occurs between neurons and glial cells in the brain. Important communications have recently been worked out where not only are neurons involved in neural process, but glial cells also have important active and supportive and facilitatory (controlling role). Gap junctions are key features of this regulation and cross talk. synapses are formed subsequent to gap junction formation and intracellular cross talk. If these are disturbed than the key synapses, on which depend memory emotion mood and perception cannot form normally and the neural circuit looses its plasticity. This is particularly true of the new nerve cells entering the circuit and providing key contributions to plasticity which is the molecular substrate of learning.

3) Glutamate and dopamine dependent neural stimulation are also featured which are key transmitters of synaptic information in the brain and long known to be involved in addiction. Importantly they are also involved in age dependent decline in brain function, and this explains the obvious clinical and experimental parallels between brain ageing and the plethora of neuropsychiatric disorders in all the various drug addictions (ie. tobacco, alcohol, cocaine, opiates and especially cannabis).

4) MAP Kinases / ERK kinases (mitogen activated and extracellular related kinases – kinases add a high energy phosphate group to various substrates particularly enzymes which typically up-regulate their activity). These are key pathways long known to be related to cell growth. They are also involved in cancer induction. This fits again with the pro-ageing phenomena mentioned above, and also the incidence of cancer in various addictions (tobacco, alcohol and cannabis).

5) Gonadotrophins releasing hormone. Whilst much work has centred on stress as a trigger for relapse into drug use often focussing on CRH (corticotrophin releasing hormone and the cortisol system in the adrenal cortex) , relatively little has examined the role of the stress system as relates to gonadal function. This is curious to some extent as the loss of the menstrual period in the female, the lowered sperm count in males, loss of libido, osteoporosis (in part gonadally determined in that sex steroids are known in both male and female to be related to maintenance of bone density) and their impact on cardiovascular disease (with females enjoying much greater protection than males, which has long been attributed to the influence of estrogen) have all been recognized for a long period. This finding suggests that just as the general systemic stress system is activated by addiction so is the gonadal one. This might account for several of the findings of addiction, and relate to many of the differences in addiction between the sexes.

6) PKA PKC (protein kinases A and C) are also major intracellular kinases and pivotal points of intracellular cell signalling for a host of pathways. Their implication implies massive pirating of the intracellular transduction cascades.

7) The insulin signalling pathway (Table 1). I had not seen evidence of the involvement of this pathway before in the addiction literature. It is the great star of the ageing literature – more has been written on this pathway in the ageing literature than any other pathway. It is a prime candidate to mediate the pro-ageing effects of addition which my clinic is increasingly documenting, and has also been noted (in part) by studies from the NIH, Johns Hopkins and Boston University hospitals. This is a very important finding and again means the nemesis of the lying legalization juggernaut. It is important to realize that this has tremendous popular appeal. by getting the message out that addiction makes you old ugly decrepit and demented – young people – particularly young females who are normally pre-occupied with beauty – should be warned away from its horrors. This was particularly evident with the interest shown by a north American fashion magazine in the publication of our own work on premature hair graying in drug addiction.

VEGF (Vascular endothelial growth factor). This is a key molecule which has an established role in the formation of new blood vessels. It is also involved in cancer development, and stem cell activity. Brain stem cell growth (neurogenesis) has been shown to be blood dependent. Whilst the exact reasons for the blood to be involved in stem cell action, VEGF has been shown to be one of the key factors which facilitates neurogenesis. BDNF (brain derived growth factor ) is another principal determinant of neurogenesis, although many other factors have also been listed). since these new nerve cells are key to memory and mood and brain circuit activity, inhibition or impeding of this process by interfering with VEGF pathways, suggests irreversible damage to these key cells. It should be noted that it is not yet possible to image neurogenesis either clinical or in the living experimental animal, although this is an area of intense investigation in many labs around the world.

9) Protein folding abnormalities . This leads to prion diseases like Jacob Kreuzefeldt disease and mad cow disease. Alzheimer’s disease is also a disease in part of protein misfolding. This is what leads to the development of the senile plaques which are made up of insoluble beta amyloid particles which form macroaggregates and are associated with cell tangles and synaptic dysfunction in Alzheimer’s disease. The exact molecular pathogenesis of this disorder is however not well understood. This is a terrible blow to the legalizers. To suggest that addiction is related to protein folding disorders is a terrible thing, particularly when this is an area of such active investigation globally. There are whole research departments which are devoted to abnormalities of protein folding.

Source: Chuan-Yun Li, Xizeng Mao, Liping Wei*
Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People’s Republic ofChina

NIDA Research Reveals Subconscious Signals Can Trigger Drug Craving Circuits

Using a brain imaging technology called functional magnetic resonance imaging (fMRI), scientists have discovered that cocaine-related images trigger the emotional centers of the brains of patients addicted to drugs — even when the subjects are unaware they’ve seen anything. The study, published Jan. 30 in the journal PLoS One, was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

A team of researchers at the University of Pennsylvania, led by Dr. Anna Rose Childress and Dr. Charles O’Brien, showed cocaine patients photos of drug-related cues like crack pipes and chunks of cocaine. The images flashed by in just 33 milliseconds — so quickly that the patients were not consciously aware of seeing them. Nonetheless, the unseen images stimulated activity in the limbic system, a brain network involved in emotion and reward, which has been implicated in drug-seeking and craving.

“This is the first evidence that cues outside one’s awareness can trigger rapid activation of the circuits driving drug-seeking behavior,” said NIDA director Dr. Nora Volkow. “Patients often can’t pinpoint when or why they start craving drugs. Understanding how the brain initiates that overwhelming desire for drugs is essential to treating addiction.”

To verify that the patterns of brain activity triggered by the subconscious cues reflected the patients’ feelings about drugs, Childress and her colleagues gave the patients a different test two days later, allowing them to look longer at the drug images. The patients who demonstrated the strongest brain response to unseen cues in the fMRI experiment also felt the strongest positive association with visible drug cues. Childress notes, “It’s striking that the way people feel about these drug-related images is accurately predicted by how strongly their brains respond within just 33 milliseconds.”

Childress and her colleagues also found that the regions of the brain activated by drug images overlapped substantially with those activated by sexual images. This finding supports the scientific consensus that addictive drugs usurp brain regions that recognize natural rewards needed for survival, like food and sex.

According to Childress, these results could improve drug treatment strategies. “We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system. We are looking at the potential for new medications that reduce the brain’s sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges.”

Source: http://www.plosone.org/doi/pone.0001506 29.01.08

Study could potentially help clinicians treat marijuana addiction

Research by a group of scientists studying the effects of heavy marijuana use suggests that withdrawal from the use of marijuana is similar to what is experienced by people when they quit smoking cigarettes. Abstinence from each of these drugs appears to cause several common symptoms, such as irritability, anger and trouble sleeping – based on self reporting in a recent study of 12 heavy users of both marijuana and cigarettes.

“These results indicate that some marijuana users experience withdrawal effects when they try to quit, and that these effects should be considered by clinicians treating people with problems related to heavy marijuana use,” says lead investigator in the study, Ryan Vandrey, Ph.D., of the Department of Psychiatry at the Johns Hopkins University School of Medicine.

Marijuana is the most widely used illicit drug in the United States. Admissions in substance abuse treatment facilities in which marijuana was the primary problem substance have more than doubled since the early 1990s and now rank similar to cocaine and heroin with respect to total number of yearly treatment episodes in the United States, says Vandrey.

He points out that a lack of data, until recently, has led to cannabis withdrawal symptoms not being characterized or included in medical reference literature such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV) or the International Classification of Diseases, 10th edition (ICD-10). Since the drafting of the DSM-IV in 1994, an increasing number of studies have surfaced suggesting that cannabis has significant withdrawal symptoms. What makes Vandrey’s recent study unique is that it is the first study that compares marijuana withdrawal symptoms to withdrawal symptoms that are clinically recognized by the medical community – specifically the tobacco withdrawal syndrome.

“Since tobacco withdrawal symptoms are well documented and included in the DSM-IV and the IDC-10, we can infer from the results of this comparison that marijuana withdrawal is also clinically significant and should be included in these reference materials and considered as a target for improving treatment outcomes,” says Vandrey.

Vandrey added that this is the first “controlled” comparison of the two withdrawal syndromes in that data was obtained using rigorous scientific methods – abstinence from drugs was confirmed objectively, procedures were identical during each abstinence period, and abstinence periods occurred in a random order. That tobacco and marijuana withdrawal symptoms were reported by the same participants, thus eliminating the likelihood that results reflect physiological differences between subjects, is also a strength of the study.

Interestingly, the study also revealed that half of the participants found it easier to abstain from both substances than it was to stop marijuana or tobacco individually, whereas the remaining half had the opposite response. “Given the general consensus among clinicians that it is harder to quit more than one substance at the same time, these results suggest the need for more research on treatment planning for people who concurrently use more than one drug on a regular basis,” says Vandrey.

Vandrey’s study, which appears in the January issue of the journal Drug and Alcohol Dependence, followed six men and six women at the University of Vermont in Burlington and Wake Forest University School of Medicine in Winston-Salem, N.C., for a total of six weeks. All were over 18 (median age 28.2 years), used marijuana at least 25 days a month and smoked at least 10 cigarettes a day. None of the subjects intended to quit using either substance, did not use any other illicit drugs in the prior month, were not on any psychotropic medication, did not have a psychiatric disorder, and if female, were not pregnant.

For the first week, participants maintained their normal use of cigarettes and marijuana. For the remaining five weeks, they were randomly chosen to refrain from using either cigarettes, marijuana or both substances for five-day periods separated by nine-day periods of normal use. In order to confirm abstinence, patients were given daily quantitative urine toxicology tests of tobacco and marijuana metabolites. Withdrawal symptoms were self reported on a daily basis Monday through Friday using a withdrawal symptom checklist that listed scores for aggression, anger, appetite change, depressed mood, irritability, anxiety/nervousness, restlessness, sleep difficulty, strange dreams and other, less common withdrawal symptoms. Patients also provided an overall score for discomfort they experienced during each abstinence period.

Results showed that overall withdrawal severity associated with marijuana alone and tobacco alone was of similar frequency and intensity. Sleep disturbance seemed to be more pronounced during marijuana abstinence, while some of the general mood effects (anxiety, anger) seemed to be greater during tobacco abstinence. In addition, six of the participants reported that quitting both marijuana and tobacco at the same time was more difficult than quitting either drug alone, whereas the remaining six found that it was easier to quit marijuana or cigarettes individually than it was to abstain from the two substances simultaneously.

Vandrey recognizes that the small sample size is a limitation in this study, but the results are consistent with other studies indicating that marijuana withdrawal effects are clinically important.

Source: http://www.eurekalert.org/pub_releases/2008-01/jhmi-mwa012408.php :
Eric Vohr evohr1@jhmi.edu Johns Hopkins Medical Institutions

Although detoxification cannot, in itself, be considered a treatment for addiction, it is one of the most pivotal phases. In order to facilitate entry into recovery and/or rehabilitation programs, a detoxification treatment has to be experienced as easy and safe by the patient. In consideration of the many inconveniences related to standard withdrawal treatments, there is an interest in developing alternative pharmacological strategies. The main rationales for using anticonvulsants in substance-abuse patients are their lack of addiction potential, evidence support a role of kindling mechanisms in withdrawal syndromes and their efficacy in comorbid psychiatric disorders. The available data currently support the utilization of carbamazepine as a treatment for detoxification from benzodiazepines, alcohol and opiates, and as a useful agent to reduce cocaine consumption. The use of valproate is well corroborated for alcohol detoxification and it seems to be a promising treatment for the reduction of cocaine use; however, it has been found to be ineffective against benzodiazepine withdrawal symptoms. Some preliminary data suggest that lamotrigine could be useful in opiate and cocaine dependence. Gabapentin shows potential as a treatment for cocaine dependence, and some case reports have stimulated interest in this agent for alcohol and benzodiazepine detoxification. Due to its particular pharmacological profile, topiramate is one of the most interesting newer anticonvulsants. It has been found to be efficacious in opiate and possibly benzodiazepine detoxification and also has theoretical potential as a preventive therapy.

Source: Drugs Today (Barc). 2004 Jul;40(7):603-19. . Daniele.Zullino@inst.hospvd.ch

University of Washington researchers say that animal studies show that methamphetamine use causes lasting changes in the brain’s dopamine system, making it especially difficult for users to stop using the drug.
HealthDay News reported April 9 that researcher Nigel Bamford and colleagues found that long-term methamphetamine use depressed the synaptic dopamine-release system in the corticostriatal area of the brain — a condition that gets temporarily reversed when a dose of methamphetamine is administered.
Researchers said that methamphetamine appears to cause long-term changes in certain dopamine receptors and with the neurotransmitter acetylcholine. The findings “might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance,” Bamford and colleagues wrote.
Source: April 10, 2008 issue of the journal Neuron.

Kudzu and its extracts and flowers have been used in traditional Chinese folk medicine to treat alcoholism for about 1,000 years. Kudzu contains daidzin, an anti-drinking substance. Daidzin inhibits human aldehyde dehydrogenase 2 (ALDH-2), which metabolizes alcohol into acetaldehyde. Inhibiting ALDH-2 promotes the accumulation of acetaldehyde, which has aversive effects. A recent test of a synthetic ALDH-2 inhibitor (CVT-10216) on rodents shows that it reduces drinking and prevents relapse by increasing acetaldehyde while drinking and later decreasing dopamine in the brain region that controls relapse during abstinence.

Results will be published in the November issue of Alcoholism: Clinical & Experimental Research .

“I think the over-arching issue here is medical treatment,” said Ivan Diamond, vice president of neuroscience at Gilead Science, Professor Emeritus of neurology, cellular and molecular pharmacology and neuroscience at the University of California, San Francisco, and corresponding author for the study.

“Alcoholism is a medical disorder, not just a problem of will power,” he said. “Physicians treat medical disorders in order to prevent harm, while not necessarily curing the disease being treated – for example, drug treatment of hypertension, statins for high cholesterol, insulin for diabetes – and the same will become true for treating alcoholism. Heavy drinking causes harm. We need to prevent heavy drinking in order to prevent harm.”

Diamond added that relapse may be the biggest problem facing physicians today. “We are talking about a patient who has the motivation to undergo a very unpleasant detoxification to try to stop drinking, and then gets into trouble afterward,” he said. “Nearly 80 percent of abstinent alcoholics or addicts relapse within a year. Current therapies for alcoholism help, but we can do much better.”

“Extracts of various parts of the kudzu vine have been used in many Chinese herbal medicine formulas and are said to be helpful in treating a variety of maladies, including alcoholism and intoxication,” said Ting-Kai Li, a professor in the department of psychiatry at Duke University Medical Center, and former director of the National Institute on Alcohol Abuse and Alcoholism. “Recent research has found that several compounds of the isoflavone family – puerarin, daidzin, daidzein – in the kudzu extract decrease alcohol intake in experimental animals.”

“Drs. Wing Ming Keung and Bert Vallee at Harvard were the first to confirm kudzu’s effects and isolate daidzin as the most potent of the isoflavones in kudzu,” added Diamond. “They went further by searching for the basis of daidzin’s anti-drinking properties, discovering that daidzin was a selective inhibitor of ALDH-2. Based on x-ray crystallographic studies of daidzin binding to ALDH-2, our team set out to design a compound that would interact more efficiently with ALDH-2, finally choosing CVT-10216 as our best candidate to date.”

Diamond and his colleagues administered CVT-10216 to groups of rats bred for moderate and high levels of drinking, after having exposed them to various scenarios of alcohol administration: two-bottle choice, deprivation-induced drinking, operant self-administration, and cue-induced reinstatement. The researchers then tested for blood acetaldehyde levels, alcohol-induced dopamine release in the nucleus accumbens, and effects of the inhibitor on drinking behavior and relapse.

“We had several key findings,” said Diamond. “We found that, one, CVT-10216 is a highly selective reversible inhibitor of ALDH2 without apparent toxicity. This means that it does not cause serious damage to other proteins and functions. Two, treatment with our ALDH-2 inhibitor increases acetaldehyde in the test tube and in living animals.” Acetaldehyde’s aversive effects can include a flushing reaction and feeling ill, which tend to reduce drinking. “And three, we found that our ALDH-2 inhibitor suppresses drinking in a variety of rodent drinking models.”

But that’s not the whole story, Diamond added. “Most importantly, we also found that CVT-10216 prevents the usual increase in drinking (binge drinking) that occurs after five days of abstinence, and also prevents relapse to drink, even when alcohol is not present. This means that something else besides acetaldehyde helps to suppress craving for, and prevent relapse to, drinking alcohol. We believe that ‘something else’ is dopamine.” He said that current concepts suggest that increased dopamine in the nucleus accumbens drives craving and relapse into drinking.

“Alcohol-induced increases in dopamine in the nucleus accumbens are prevented by CVT-10216 in a dose-dependent manner,” said Diamond. “This means the drug has a therapeutic effect in the brain, probably on the desire to drink. Importantly, CVT-10216 does not reduce basal dopamine levels when there is no stimulation to increase dopamine levels. This is consistent with our findings that CVT-10216 does not appear to affect moderate drinking, and does not have adverse side effects at the therapeutic doses used.”

“The findings show promise that CVT-10216 might be better tolerated than Antabuse™,” said Li. “How this happens is yet unknown, but suggests that the compound may be useful in treating alcohol relapse and perhaps for other psychoactive, potentially addictive compounds.”

Diamond agreed: “Disulfiram or Antabuse™ has been around for 50 years,” he explained. “It is called an ALDH-2 inhibitor, but it actually inhibits far more than that. Most believe that disulfiram would not be approved today as a new drug for alcoholism because of its many toxicities. Instead, we have developed CVT-10216, a reversible inhibitor with a very favorable profile, so far.” Diamond hopes this novel compound will become an effective therapeutic agent for alcoholism.

“The goal of medicine is harm reduction,” emphasized Diamond. “Excessive drinking causes harm while moderate drinking appears to be safe. Increasing numbers of doctors believe abstinence is an unrealistic goal. It sounds like heresy, but it isn’t. Therefore, an ideal drug might be able to prevent uncontrolled relapse, convert heavy drinkers into moderate drinkers, and avoid the harmful consequences of excessive alcohol intake. If our compound works and is safe to use, then I think most physicians would not hesitate to prescribe a new drug to prevent relapse and reduce heavy drinking. My goal is to make this happen.”

Ivan Diamond, M.D., Ph.D University of California, San Francisco.
Ting-Kai Li, M.D. Duke University Medical Center Alcoholism: Clinical & Experimental Research

Source: Medical News Today August 2009

Alcoholism Is Not Just A Medical Condition.
posted by Peter O’Loughlin on 14 Aug 2009
Professor Diamond’s views on alcoholism and relapse although interesting are not necessarily accurate. First the comment that alcoholism is a medical problem is a rather narrow concept of what is a complex mental and physical disorder, (DSM 1V & ICD-10) which causes serious medical problems. It is also a fact that alcoholics undergo personality changes. Therefore merely to treat the medical side of this condition is unlikely in and of itself to prevent relapse. Evidence in support of that can be found in a variety of Cochrane reviews of other ‘magic bullets’.

It is also debateable whether substances which appear to have desirable outcomes on rodents can be effective on human beings. As far as I’m aware the former, unlike the latter has no imagination or co-occurring mental disorders.

Professor Diamond’s comment regarding relapse rates does not tell the whole story. Whilst it is true that most relapses occur in the first year or two, that does not take into account the numbers who continue their battle with alcoholism and subsequently learn how to live their life without it.

There is no doubt that medicine has an important part to play in recovery, but there is also an abundance of evidence that many people find lasting sobriety without it. It is also true that abstinence alone is insufficient to prevent relapse, that for alcoholics to remain sober and to learn to live in a manner that they find personally satisfying, their mental and spiritual health needs have to be addressed. Abstinence alone is very fragile; recovery on the other hand is an ongoing process.

Drug addiction accelerates aging in addicts.

Addictive drugs have been shown to impair stem cell regeneration and potentate programmed cell death leading to accelerated aging.

Drug addicts are known to suffer many pathologies including cancer and elevated mortality.

Surveys of addicts aged between 19 and 45 years in Australia disclosed higher levels of infections, dental and mental pathologies and hair graying consistent with aging were present in addicts.

Degenerative changes related to aging like skin thinning, wrinkling, dementias, muscle wasting, cardiovascular disease, psychiatric disturbances were common in addicted populations.

Source: Clinical Correlates of Accelerated Aging in Addiction, Reece S & Lavin M 2009)

Current figures underestimate the number of children who may be at risk of harm from parental substance use. Researchers writing in the open access journal BMC Public Health have generated new estimates using five national surveys which include measures of binge, hazardous and dependent drinking, illicit drug use and mental health.

Previous UK estimates were that 250-350,000 children live with problem drug users and 780,000 – 1.3 million with problem drinkers. However, the problem, according to the researchers, is that “these estimates are based on drug users in treatment or derive from problem drinking estimates in other countries.” The study, funded by Action on Addiction and the Wates Foundation and conducted by Dr Victoria Manning and colleagues at the National Addiction Centre, entailed a secondary analysis of national household surveys that enabled a focus on parenting and substance use. The new figures indicate that approximately 3.4 million children in the UK live with at least one binge drinking parent, 2.6 million with a hazardous drinker and around one million with a parent who uses illicit drugs.
Manning said: “In order to meet the needs of both parental substance misusers and their children, we first need to understand the true nature and scale of the problem. Without knowing the number of potentially at-risk families, we are unable to assist them until they come to the attention of agencies at crisis point.”
Around 335,000 children were estimated to be living with a drug dependent user, 72,000 with an injecting drug user, and 108,000 with an adult who had overdosed. The authors suggest the risk of harm may increase for the 500,000 children living with parents who have both mental health and substance misuse problems. According to Manning, “Whilst harm from parental substance use is not inevitable, we need to raise awareness of how recreational substance use, and in particular binge episodes, can affect parenting capacity. Substance use affects our judgement, emotions and how we respond to situations. Parental substance misuse can lead to inadequate child monitoring, modelling behaviour and poor standards of child care.”
The authors encourage the involvement of mainstream services to support vulnerable families by improving access to treatment, family interventions and parenting skills training to minimize the risk of harm.

Source: Victoria Manning, David W Best, Nathan Faulkner and Emily Titherington. New estimates of the number of children living with substance misusing parents: results from UK national household surveys. BMC Public Health, 2009;

Regardless of the explanation, the findings suggest “that there are very long-term benefits to a higher drinking age,” Norberg said.

From the Vietnam era until the mid-1980s, many states allowed people to purchase alcohol at the age of 18. However, a federal law pressured states to boost the drinking age to 21, and all did with the exception of Louisiana, which finally followed suit in the 1990s.

In the new study, Norberg and colleagues looked at surveys of 33,869 people born in the United States between 1948 and 1970. They examined the records to see if there were differences in alcoholism and drug abuse rates depending on when states allowed individuals to buy booze.

The study findings appear in an early online edition of the December issue of Alcoholism: Clinical and Experimental Research.

After adjusting their statistics to prevent things like the ethnicity of the respondents from skewing the results, the researchers found that those who lived in states that allowed drinking before age 21 were 1.3 times more likely to have suffered recently from alcoholism. They were also 1.7 times more likely to have had a recent drug abuse problem.

Norberg said lower drinking ages might have a “peer effect,” since that makes it easier to find friends of one’s age to drink with. “If the drinking age is at 21, it will be a little harder to find some friends to go out with. You’ll probably drink less often and have a smaller number of drinks.”

Francesca M. Filbeya, et alCraving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue.

These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems
related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis
dependence.

The relationship between craving and drug use behavior is an integral piece of the addiction puzzle. Craving is considered the intense desire for a rewarding object or experience. Cue elicited
craving, induced by exposure to alcohol- or drug-related cues, is a particularly potent form of craving. Previous investigators have reported that subjective craving increases after exposure to cues specific to a variety of drugs of abuse, including cocaine (e.g., tactile cues, videos, i.v. administration, images, guided imagery) heroin (e.g., images) alcohol (e.g., alcohol taste, images, alcohol-related words), and tobacco (e.g., visual and tactile presentations) .

Cue-elicited craving for alcohol and tobacco in particular have important clinical implications and have been the focus of psychosocial and pharmacological intervention efforts.

The advent of functional neuro-imaging has allowed studies of cue-elicited craving to elucidate the neurobiological mechanisms that accompany increased craving. Such neuro-imaging studies
have associated craving with increased activation of reward pathways . The reward circuits involve the dopamine projection from the ventral tegmental area (VTA) to striatal areas (e.g., nucleus accumbens) and the prefrontal cortex (PFC), the repeated activation of which underlies the attribution of incentive salience to otherwise neutral stimuli . Other reward-related areas, including the insula and cingulated gyrus show increased activity with the presentation of drug-related stimuli. Presentation of these stimuli is also associated with increased activity in brain structures that underlie reward and emotion regulation, such as the thalamus and amygdala.

The few published studies of cue-elicited craving for marijuana suggest that it is a reliable and valid phenomenon, analogous to cue-elicited craving for other drugs of abuse. Marijuana-related cues presented in a variety of sensory modalities, elicit increases in self-reported craving. For example, auditory-presented imagery scripts induce craving in marijuana smokers, and the magnitude of this craving varies as a function of the amount of marijuana-related content presented in the script . Craving also increases when abstinent frequent marijuana users are exposed to an auditory script that is paired with a tactile cue, such as a used marijuana pipe or bong .

Importantly, in this paradigm, cue presentation increases craving beyond the effects induced by abstinence. Additionally, marijuana related visual cues elicit greater craving in chronic heavy users than in controls; physiologically, users demonstrate greater skin conductance and larger late positivity of visual event-related brain potentials than controls in response to these stimuli .

The present study was designed to examine the effects of marijuana-related cues on the activation of reward circuitry, and to examine the relationship between these effects and the behavioral symptoms of cannabis dependence. We hypothesized that among regular marijuana users, marijuana-related cues compared with neutral cues, would elicit greater blood oxygen level dependent (BOLD) activity in reward structures (i.e., VTA, striatum, anterior cingulate, and insula). Furthermore, we hypothesized that the magnitude of this response would be associated with the number of problems related to marijuana use.

Results

Compared with the neutral cue, presentation of the marijuana cue elicited significantly greater BOLD activation in a large cluster encompassing several areas, including the VTA, dorsal anterior cingulate cortex, cerebellum, thalamus, pre- and postcentral gyri, inferior frontal gyrus/insula, thalamus, amygdala,

fusiform gyrus, pre- and postcentral gyri, inferior parietal lobe, and superior temporal gyrus (cluster-corrected z_2.3, P_0.05)

BOLD response in several of these differentially activated areas was also significantly positively correlated with total marijuana problem scale (MPS) score (cluster-corrected z _ 2.3, P _ 0.05). These areas included the orbitofrontal cortex (OFC) and nucleus accumbens (NAc) The analyses of correlations with the Structured Clinical Interview for DSM Disorders (SCID) total symptom count, subjective urge ratings, frequency, and duration of use did not meet the significance threshold.

Source: 13016–13021 _ PNAS _ August 4, 2009 _ vol. 106 _ no. 31 www.pnas.org_cgi_doi_10.1073_pnas.0903863106

A tiny genetic mutation is the key to understanding why nicotine–which binds to brain receptors with such addictive potency–is virtually powerless in muscle cells that are studded with the same type of receptorBy all rights, nicotine ought to paralyze or even kill us, explains Dennis Dougherty, the George Grant Hoag Professor of Chemistry at Caltech and one of the leaders of the research team. After all, the receptor it binds to in the brain’s neurons–a type of acetylcholine receptor, which also binds the neurotransmitter acetylcholine–is found in large numbers in muscle cells. Were nicotine to bind with those cells, it would cause muscles to contract with such force that the response would likely prove lethal. Obviously, considering the data on smoking, that is not what happens. The question has long been: Why not?

“It’s a chemical mystery,” Dougherty admits. “We knew something subtle had to be going on here, but we didn’t know exactly what.” That subtlety, it turns out, lies in the slight tweaking of the structure of the acetylcholine receptor in muscle cells versus its structure in brain cells.
The shape of the acetylcholine receptor, and the way the chemicals that bind with it contort themselves to fit into that receptor, is determined by a number of different weak chemical interactions. Perhaps most important is an interaction that Dougherty calls “underappreciated”–the cation-π interaction, in which a positively charged ion and an electron-rich π system come together.

Back in the late 1990s, Dougherty and colleagues had shown that the cation-π interaction is indeed a key part of acetylcholine’s ability to bind to the acetylcholine receptors in muscles. “We assumed that nicotine’s charge would cause it to do the same thing, to have the same sort of strong interaction that acetylcholine has,” says Dougherty. “But we found that it didn’t.”
This would explain why smoking doesn’t paralyze us; if the nicotine can’t get into the muscle’s acetylcholine receptors, it can’t cause the muscles to contract.

But how, then, does nicotine work its addictive magic on the brain? It took another decade for the scientists to be able to peek at what happens in brain cells’ acetylcholine receptors when nicotine arrives on the scene. Turns out that in brain cells, unlike in muscle cells, nicotine makes the exact same kind of strong cation-π interaction that acetylcholine makes in both brain and muscle cells. “In addition,” Dougherty notes, “we found that nicotine makes a strong hydrogen bond in the brain’s acetylcholine receptors. This same hydrogen bond, in the receptors in muscle cells, is weak.”

The cause of this difference in binding potency, says Dougherty, is a single point mutation that occurs in the receptor near the key tryptophan amino acid that makes the cation-π interaction. “This one mutation means that, in the brain, nicotine can cozy up to this one particular tryptophan much more closely than it can in muscle cells,” he explains. “And that is what allows the nicotine to make the strong cation-π interaction.”

Dougherty says the best way to visualize this change is to think of the receptor as a box with one open side. “In muscle cells, this box is slightly distorted, so that the nicotine can’t get to the tryptophan,” he says. “But in the brain, the box is subtly reshaped. That’s the thing: It’s the shape, not the composition, of the box that changes. This allows the nicotine to make strong interactions, to become very potent. In other words, it’s what allows nicotine to be addictive in the brain.”

“Several projects in our labs are converging on the molecular and cellular mechanisms of the changes that occur when the brain is repeatedly exposed to nicotine,” adds study coauthor Henry Lester, the Bren Professor of Biology at Caltech. “We think that the important events begin with the rather tight and selective interaction between nicotine and certain receptors in the brain. This Nature paper teaches us how this interaction occurs, at an unprecedented level of resolution.”
Dougherty notes that these findings might one day lead to better drugs to combat nicotine addiction and other neurological disorders. “The receptor we describe in this paper is an important drug target,” he says. “It might help pharmaceutical companies develop a better drug than nicotine to do the good things nicotine does–enhance cognition, increase attention–without being addictive and toxic.”

Source: Xiu et al. Nicotine binding to brain receptors requires a strong cation–π interaction. Nature, March 26, 2009; DOI: 10.1038/nature07768 Science Daily 29.03.09

Context  While both environmental and genetic factors are important in the etiology of psychoactive substance use (PSU), we know little of how these influences differ through development.
Objective To clarify the changing role of genes and environment in PSU from early adolescence through middle adulthood.
Design  Retrospective assessment by life history calendar, with univariate and bivariate structural modeling.
Setting  General community.
Participants  A total of 1796 members of male-male pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.
Main Outcome Measures  Levels of use of alcohol, caffeine, cannabis, and nicotine recorded for every year of the respondent’s life.
Results  For nicotine, alcohol, and cannabis, familial environmental factors were critical in influencing use in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances.
Conclusions  These results support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important through early and middle adulthood.Kenneth S. Kendler, MD; Eric Schmitt, BS; Steven H. Aggen, PhD; Carol A. Prescott, PhD

Source: Arch Gen Psychiatry. 2008;65(6):674-682.

Scientists at Oregon Health Sciences University have discovered that mice lacking a certain brain cell receptor for the chemical messenger dopamine are supersensitive to alcohol, cocaine and methamphetamine. Their findings appear in the September 19, 1997, issue of the journal Cell and detail the increased locomotor activity of mice who lack the D4 receptor.”Branching nerve cells communicate with each other by secreting chemical messengers like dopamine that bind to receptors on neighboring nerve cells in a lock-and-key fashion,” explains, David Grandy, Ph.D., OHSU scientist and senior author of the article. “Dopamine is one of the primary chemical messengers, or neurotransmitters, and plays numerous complex roles in both movement and emotional states. Disturbances in the dopamine system are known to be associated with human disorders such as Parkinson’s disease, schizophrenia and addiction. Dopamine producing neurons continue to be the focus of research because of their widespread importance in regulating complex locomotor, emotional and motivational states.”
Grandy further explains that dopamine producing neurons are involved in mediating some of the positive reinforcing properties shared by drugs of abuse such as alcohol, cocaine, methamphetamine and opiates.
“We examined mice that were genetically engineered to lack the D4 dopamine receptor to investigate the role of this receptor in mediating the effects of various drugs,” says Grandy. “We discovered that mice given either alcohol, cocaine or methamphetamine displayed a dramatic increase in locomotor activity compared to normal mice. Prior to their treatment with these drugs, the mutant mice tended to be less active than normal mice. Following treatment their activity level increased greatly compared to normal mice.
“Based on the observation that mice lacking the D4 receptor show a supersensitivity to certain drugs of abuse, we speculate that the D4 receptor is implicated in modulating the effects of such drugs,” says Grandy. “Consequently, the D4 receptor may be a new target for the treatment of drug abuse.”
Grandy explains that humans show a wide variability in the gene that encodes the D4 receptor, and there are reports that some forms of the D4 gene may predispose an individual to drug taking and novelty seeking behaviors. The D4 receptor has been the focus of intense interest since its discovery in 1990 because of its high affinity for the antipsychotic drug clozapine, which is used to treat schizophrenia. Recently, several new D4-selective drugs that are similar to clozapine have been developed and are currently undergoing clinical trials for the treatment of schizophrenia. In addition to shedding light on the role that the D4 receptor plays in an organism*s response to drugs like alcohol, cocaine and methamphetamine, the new research reported by Grandy and his colleagues underscores the relevance of this receptor to antipsychotic drug development.

Source: Oregon Health Sciences University (1997, September 23). OHSU Scientists Discover Mice Lacking Dopamine Receptor Are Supersensitive To Alcohol, Cocaine And Methamphetamine. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/1997/09/970923034045.htm

As a follow up to previous work showing that gene therapy can reduce drinking in rats trained to prefer alcohol, scientists at the U.S. Department of Energy’s Brookhaven National Laboratory have used the same technique to cut drinking in rats with a genetic predisposition for heavy alcohol consumption. The findings, along with additional results on the effects of long-term ethanol consumption on certain aspects of brain chemistry, are published in the May 2004 issue of Alcoholism Clinical and Experimental Research.”Though we are still early in the process, these results improve our understanding of the mechanism or mechanisms of alcohol addiction and strengthen our hope that this treatment approach might one day help people addicted to alcohol,” said Panayotis (Peter) Thanos, who lead the study in Brookhaven Lab’s medical department.
Genetically predisposed alcohol-preferring rats are a much better model for human alcoholism than the rats used previously, which the scientists had to train to prefer alcohol. Without any training, the genetic alcohol-preferring rats drink, on average, more than five grams of ethanol per kilogram of body weight per day when given a free choice between alcohol and plain water. Genetically non-preferring rats, in contrast, typically consume less than one gram of ethanol per kilogram of body weight per day.
In this study, both groups were treated with gene transfer to increase the level of a brain receptor for dopamine, a chemical important for transmitting feelings of pleasure and reward and known to play a role in addiction. After the gene treatment, the alcohol-preferring rats exhibited a 37 percent reduction in their preference for alcohol and cut their total alcohol consumption in half — from 2.7 grams per kilogram of body weight before treatment to 1.3g/kg after. Non-preferring rats also reduced their drinking preference and intake after gene treatment, but not in nearly as dramatic a fashion. The greatest reductions in alcohol preference and consumption were observed within the first few days after gene treatment, and both preference and consumption returned to pre-treatment levels by day 20.
The gene administered was for the dopamine D2 receptor, a protein shown in various studies to be relevant to alcohol and drug abuse. For example, low levels of dopamine D2 receptors in the brain have been postulated to lead to a reward deficiency syndrome that predisposes certain people to addictive behaviors, including drug and alcohol abuse. The alcohol-preferring rats used in this study have about 20-25 percent lower levels of dopamine D2 receptors when compared to the non-preferring rats, which may, in part, explain their tendency toward heavy drinking.
The scientists delivered the gene by first inserting it into a virus that had been rendered harmless. They then injected the virus directly into the rats’ nucleus accumbens, the brain’s pleasure center. The idea behind this type of gene therapy is to use the virus as a vector to carry the gene to the brain cells, which can then use the genetic instructions to make the D2 receptor protein themselves.
As an additional measure in this study, the scientists used micro-positron emission tomography (microPET) imaging to non-invasively assess the effects of chronic alcohol consumption on D2 receptor levels in alcohol-preferring and non-preferring rats. They measured D2 levels seven weeks after the gene therapy treatment (well after the effects of gene therapy had worn off). D2 receptor levels in alcohol-preferring rats were significantly lower (about 16 percent) compared to that in non-preferring rats. These levels were similar to previous data in naïve preferring and non-preferring rats.
In future studies, the D2 connection to alcoholism will be examined in transgenic mice that are totally depleted of D2. In addition, the scientists plan to develop a second generation D2 vector approach that will provide a longer period of treatment.
“These findings further support our hypothesis that high levels of D2 are causally associated with a reduction in alcohol drinking and may serve as a protective factor against alcoholism,” Thanos said.
###
This study was funded by the Office of Biological and Environmental Research within the Department of Energy’s Office of Science and by the National Institute of Alcohol Abuse and Alcoholism within the National Institutes of Health.
One of the ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization. Visit Brookhaven Lab’s electronic newsroom for links, news archives, graphics, and more: http://www.bnl.gov/newsroom
Previous related study: http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr090501.htm

Source: Brookhaven National Laboratory (2004, May 6). Gene Therapy Reduces Drinking In Rats With Genetic Predisposition To ‘Alcoholism’. ScienceDaily. Retrieved August 17, 2008, from http://www.sciencedaily.com¬ /releases/2004/05/040506070752.htm

Drug addicts find it harder than non-addicts to derive pleasure from everyday life, new Australian research shows.
The study took in 33 heroin addicts on opiate replacement, whose brain activity was measured as they looked at pictures of drug and non-drug related scenes.
Associate Professor Dan Lubman said the addicts showed elevated responses to drug-related images compared with a control group of non-drug users, but the key finding was their disinterest in otherwise pleasurable non-drug scenes.  “Looking at pictures of heroin, needles, people injecting heroin, and social drug use … the heroin group found the drug pictures much more pleasant and rewarding, it lit up the brain activity,” said Dr Lubman, of Melbourne University’s Orygen Youth Health Research Centre.  “Whereas they were under-responsive and found the emotionally pleasant pictures much less pleasant.”
Dr Lubman said the alternative images included attractive people engaged in fun activities, delicious food, and “things that people normally rank as being quite pleasurable … there were also a few puppy dogs in there”.
The same drug addicts were assessed again six months later to see who had kicked their habit, with surprising results as the critical factor was not those who enjoyed drug-related pictures the most.  “It was actually the under-responsiveness to emotional positive pleasurable stimulus that predicted who was using the most heroin,” Dr Lubman said.
He said the findings held implications for drug treatment programs and the public, who often grappled with an addict’s inability to stop using.  Dr Lubman said the results suggested drug users had a reduced ability to enjoy everyday pleasures, and their brains remained excited by the prospect of continued drug use.
It also showed why threats of punishment, which Dr Lubman calls the “big stick” approach, may not work in discouraging addicts. “They haven’t got anything else in their lives to turn to,” he said.
“Our research shows the focus should be not only just the drugs but getting them (addicts) to be passionate about something else in some way, because that’s the best predictor about whether they will stop using.”
Dr Lubman said he expected similar results to be associated with all drugs of addiction, including alcohol, and further research was needed to explain a possible “chicken and egg” problem.  Which came first, addiction leading to less pleasure in life or drug taking to overcome a pre-existing lack of enjoyment?
“There is evidence to suggest that people who are vulnerable to addictions already have an underlying emotional problem,” Dr Lubman said.
The research findings were published in the journal Archives of General Psychiatry.

Source:  www.theage.com.au  Feb. 3rd 2009

Sometimes, small changes do add up. In the case of addictive diseases, tiny variations in a few genes can increase or decrease the likelihood of some people developing a dependency on heroin. Now, by examining a select group of genetic variants in more than 400 former severe heroin addicts, Rockefeller University researchers have identified several genetic variations in American and Israeli Caucasians that influence the risk for becoming addicted to one of the world’s most powerful substances.
In a collaborative effort with statistical geneticists and several methadone clinics, scientists led by Mary Jeanne Kreek, head of the Laboratory of the Biology of Addictive Diseases, analyzed 1,350 variations in 130 genes and found nine, from six genes, that were either more or less common in recovering heroin addicts when compared to Caucasians with no history of drug abuse. These small changes in the gene sequences can cause significant changes in protein function that can influence addictive behavior — changes that may affect people of different ethnic background differently.
“The idea of ‘personalized medicine’ makes this field really exciting but also very complicated,” says Orna Levran, a senior research associate in the Kreek laboratory and first author of the study. “Although seven of these variants increase the risk for developing heroin addiction in Caucasians, the same seven may not have the same effect in other populations. So ethnicity and, more precisely, genetic information in each individual may become important factors for treating and diagnosing addictions to different drugs.”
In their analysis, Kreek, Levran and their colleagues looked at a string of letters called nucleotides, the building blocks that make up genes. In each of the six genes, at least one letter is replaced by another, a genetic variation known as a single nucleotide polymorphism, or SNP. The researchers found that all of the single-letter variations exist in parts of the genes that do not translate into proteins but instead may have a regulatory or a structural effect.
Out of the nine SNPs, the group found six in the μ, δ and κ opioid receptors, a finding that reinforces the idea, and many other findings of the Kreek laboratory, that opiate receptors play a major role in severe heroin addiction. The remaining three SNPs were found in genes coding for the serotonin receptor 3B, casein kinase 1 epsilon, which acts as a regulator of the circadian clock genes, and galanin, which modulates appetite and alcohol consumption. This is the first study to show that specific variants in these genes are associated with heroin addiction, explains Levran.
The SNPs in the κ opioid receptor and casein kinase 1 genes were found more in the control group than the heroin addicts’ group, suggesting that they conferred protection from heroin addiction — not vulnerability to develop addiction.
“Individually, these SNPs probably have a small effect,” explains Levran, “but collectively, we are seeing that they could have a larger effect. One of the goals now is to find all of these gene variants and assess how they influence people of different ethnic backgound.”

Source: Rockefeller University (2008, October 5). Variations In Key Genes Increase Caucasians’ Risk Of Heroin Addiction. ScienceDaily. Retrieved March 11, 2009, from http://www.sciencedaily.com¬ /releases/2008/10/081002211720.htm

Abstract Achieving abstinence in the treatment of cannabis dependence has been difficult. To date the most successful treatments have included combinations of motivational enhancement treatment plus cognitive–behavioural coping skills training and/or contingency management approaches rewarding abstinence. Although these approaches are theoretically based, their mechanisms of action have not been explored fully. The purpose of the present study was to explore mechanisms of behaviour change from a cannabis treatment trial in which cognitive–behavioural and contingency management approaches were evaluated separately and in combination. A ‘dismantling’ design was used in the context of a randomised clinical trial. 240 dependent adult cannabis smokers who responded to advertisements attended an out-patient treatment research facility located in a university medical centre. They were randomly assigned to one of four nine-week treatment conditions:
• supportive case management, the control condition used as a benchmark for the other treatments;
• motivational enhancement therapy plus cognitive–behavioural coping skills training;
• standalone contingency management procedures rewarding cannabis abstinence with vouchers for retail goods or services, with no other therapeutic inputs;
• and a combination of contingency management with the motivational and cognitive–behavioural therapies.
The main outcome measure was total abstinence over the past 90 days based on the patients’ own accounts and verified by urinalysis. These measures were recorded every 90 days for the 12 months after treatment ended. Standalone contingency management led to the highest in-treatment abstinence rate, but the lowest in the last six months of the follow-up. Regardless of the treatment, abstinence in near-term follow-ups was predicted most clearly by abstinence during treatment, but long-term abstinence was predicted by use of coping skills and especially by post-treatment self-efficacy for abstinence.
 Though an exploration of the mechanisms of change in cannabis treatment in general, the study’s innovation This seems the first study to establish how contingency management works by linking it to psychological and behavioural changes, and then linking these to abstinence outcomes using a methodology which can tease out potential causal mechanisms. Inclusion of motivational and cognitive–behavioural approaches in the same study makes it possible to compare these mechanisms against those of probably the most influential and widespread structured therapies for substance use problems. (and the focus for this commentary) was to probe the psychological processes underlying contingency management, building on previously reported abstinence outcomes from the same study. The key message is that these procedures do not produce lasting change simply by mechanically reinforcing the habit of non-use. More important is whether the experience fosters confidence that one can resist relapse, along with the motivation to transform ‘can’ in to ‘will’, and strategies to effectively implement this resolution. In other words, what the patient makes of their spell on the contingencies and how they interpret it determines whether it will result in a transient, reward-driven spell of reduced substance use, or more lasting change. What the patient makes of the contingencies can in turn be influenced by integrating test results and rewards in to accompanying therapy, leading to greater longer term success than either on its own.
On the basis of the study, this message can only be considered a tentative working hypothesis. But it is consistent with other studies (1 2 3 4 5) which also found that the in-treatment boost Interestingly, in several studies this boost was deflated somewhat when contingency management was combined with cognitive-behavioural therapy, yet once the rewards ended this combination was at least as or more effective. to abstinence provided by rewards does not persist, leaving contingency management with longer term outcomes at best equivalent to cognitive-behavioural approaches, and sometimes slightly worse. More generally, when rewards end, patients often quickly revert to their previous behaviours. Even during the rewards period, typically impacts are limited to the targeted behaviours and/or the targeted drugs. This is what would be expected if patients interpret the procedures as a chance to do what it takes (and no more) to make some money or win some prizes. In particular, the authors suggest that lasting change is less likely if patients see abstinence as foisted on/enticed out of them by the rewards, rather than something they have shown they can achieve by their own efforts.
Within the study, this hypothesis emerged from an analysis which showed that the way contingency management enhanced cannabis abstinence after treatment, was by having enhanced it during treatment. However, when other variables were taken in to account, the distinct contribution of in-treatment abstinence was relatively weak. More significant were variables contingency management did not directly affect – the individual’s growing confidence in their ability to resist cannabis use and their deployment of strategies to help them do so. Each bolstered the other, especially when growing motivation to change gave impetus to the process. These variables were directly impacted by the treatments which included motivational and cognitive–behavioural elements, especially when combined with contingency management.
The upshot it seems was that though it led to the highest abstinence rates Both in terms of the average number of days abstinent and the number of patients who remained completely abstinent. during treatment, by the final follow-up a year later patients subject only to the rewards were least likely to have sustained abstinence over the past three months. After the other three This applied even to the case management option, one deliberately devoid of structured therapeutic content. treatments, abstinence rates improved, culminating in a final rate of around 20% or more. After standalone contingency management ended, the abstinence rate rapidly fell to barely more than half the level during treatment.
This transience did not apply when contingency management was combined with motivational/cognitive-behavioural therapy – in the longer term, the most effective of the options. Contingency management brought these patients in to contact with qualified and specially trained and supervised therapists who melded the urinalysis results and the rewards in to the therapeutic encounter, and who were in a position to influence the patient’s interpretation of and response to the contingencies. In contrast, standalone contingency management involved relatively fleeting contact with a research assistant who administered tests and rewards.
When contingency management and cognitive-behavioural therapy have merely run in parallel no longer term advantage from combining the two has materialised. But when, as in the featured study, therapists have integrated the contingency programme in to their sessions, the combination has proved the most powerful intervention in the longer term.
Though this study breaks new ground, others have also indicated that contingency management may not work in the same way as other therapies. Most relevant is a study which used vouchers to reward drug-free urine tests and consumption of the opiate blocking medication naltrexone to maintain abstinence from opiates after detoxification. As expected, during the 12 weeks of treatment the rewards encouraged patients to take their medication The difference was substantial but fell just short of statistical significance. and stay free of opiate drugs. But this did not presage lasting change. Within 12 weeks of the rewards ending, there was little difference between these patients and those not offered vouchers, by another 12 weeks, virtually none. A clue to the reason came in the observation that across the 12 weeks of treatment, motivation and readiness to change drug use behaviour increased slightly among patients not offered vouchers, but were significantly eroded Tests showed that this was not due to patients who had attained abstinence no longer feeling the need to change. among those rewarded for abstinence.
In other studies, motivation has not been eroded relative to other treatments, but neither has it been enhanced by reinforcing abstinence, indicating that the greater abstinence rates ‘bought’ by the rewards do not reflect increased motivation to remain abstinent. In one, supplementing motivational and coping skills therapy with rewards actually halved what without the rewards was a substantial increase in confidence in ability to refrain from smoking cannabis.
The potential for contingency management type rewards to erode motivation is well recognised outside the substance misuse sector. An analysis aggregating results from 128 studies found that tangible rewards offered for engaging in, completing, or doing well at a task undermined intrinsic motivation. The effect was greatest when represented by what people actually did after the rewards ended, the equivalent of post-treatment substance use in contingency management studies. However, the same analysis found that it is possible for rewards – and especially verbal recognition – to be given in such a way that they acknowledge the individual’s achievements and bolster feelings of mastery rather than of being controlled. In these cases the undermining effect can be reversed and intrinsic motivation enhanced.
Such findings help explain why in several studies contingent rewards or punishments for engaging in treatment did improve attendance and compliance, but, contrary to the usual pattern, ‘engagement’ elicited in this way did not improve substance use or other outcomes. It also helps explain why occasionally this does not happen, for example, when rewards are experienced as a non-controlling signal of the individual’s own achievements, and are embedded in a caring therapeutic environment which accompanies them with verbal and public recognition. Another exception is a study which achieved greater and more lasting abstinence by rewarding recovery-oriented activities rather than directly rewarding abstinence. In this case the rewards were delivered within a collaborative therapeutic relationship and empowered rather than controlled the patient. With their therapist, they could select activities to be rewarded in line with their own recovery plan and ability to complete the task. The broader findings referred to above also help us understand the oft-reported power of the verbal praise delivered by drug court judges to offenders, precisely the sort of unexpected, non-controlling verbal recognition which the analysts would expect to enhance motivation by reinforcing the offender’s sense of control.
Current British trials have absorbed the lessons of this US research and at least one Personal communication from Dr John Marsden of the National Addiction Centre, March 2008. is attempting to extend the substance use reductions gained by contingency management by exploring this experience in accompanying therapy. The trial is also using a newly developed questionnaire Marsden J., Mitcheson L., Stillwell G., Litt M., Shoptaw S. Treatment Incentives Experiences Scale. 2008. to track how patients interpret the contingencies, including whether they attribute their successes to the rewards or to themselves, and impacts on their confidence in their recovery.

Source: Litt M.D., Kadden R.M., Kabela-Cormier E. et al. Request reprint
Addiction: 2008, 103(4), p. 638–648

A naturally occurring hallucinogen advocated by some clinicians as a potent anti-addiction drug has been rigorously studied for the first time, confirming its ability to block alcohol craving in rodents, and clarifying how it works in the brain. The new research findings about the drug Ibogaine open the way for development of other drugs to reverse addiction without Ibogaine’s side effects, potentially adding to the small arsenal of drugs that effectively combat addiction.

Derived from a West African shrub, Ibogaine has been championed for years by a cadre of clinicians and drug treatment advocates impressed with its ability to reverse withdrawal symptoms and craving for alcohol and various drugs of abuse. It has been used outside of the U.S. to treat addiction by American and other clinicians. But its side effects, including hallucinations, which made it popular in the 1960s drug culture, and evidence of toxicity to certain nerve cells in rodent studies have discouraged careful studies of its clinical potential against drug and alcohol addiction. The FDA has not approved use of Ibogaine in the U.S.
Scientists at UCSF’s Ernest Gallo Clinic and Research Center have now shown definitively in experiments with mice and rats that Ibogaine does reduce alcohol consumption, and they have determined that it does so by increasing the level of a brain protein known as glial cell line-derived neurotrophic factor, or GDNF. In a separate study, they demonstrated that GDNF by itself decreases alcohol consumption.
The research is being published in the January 19 issue of The Journal of Neuroscience.
“By identifying the brain protein that Ibogaine regulates to reduce alcohol consumption in rats, we have established a link between GDNF and reversal of addiction — knowledge of a molecular mechanism that should allow development of a new class of drugs to treat addiction without Ibogaine’s side effects,” said Dorit Ron, PhD, UCSF associate professor of neurology and also principal investigator at the Gallo Center. Ron is co-senior author of the paper with Patricia Janak, PhD, UCSF assistant professor of neurology and also principal investigator at the Gallo Center.
In their research, the scientists first carried out classic behavioral studies showing that Ibogaine reduced alcohol consumption. They induced the rats to consume alcohol in daily drinking sessions and then demonstrated that their drinking declined precipitously when they received Ibogaine. The drug was administered either by injection or directly into the same brain region where GDNF levels were shown to increase.
The research also showed that Ibogaine was quite effective in preventing relapse, or “falling off the wagon” — the vulnerability of recovered alcoholics or addicts to return to uncontrolled drinking or drug use when exposed to the drug of abuse months or even years after breaking the habit.
In this analysis, the researchers provided alcohol to rats until they had become “experienced” daily drinkers. They then withheld alcohol for two weeks, which normally leads to greatly increased drinking when when alcohol is again available. When they administered Ibogaine, they found that the heightened craving and consumption was significantly reduced.
“The discovery that Ibogaine reduced binge drinking after a period of abstinence was an exciting finding for us because this is the type of behavior in alcoholics for which very few effective drugs exist,” Janak said.
The scientists confirmed in a cell model that Ibogaine stimulated GDNF activity. Finally, they showed that a known inhibitor of GDNF blocked Ibogaine’s ability to decrease alcohol craving in the rats, suggesting a direct link between Ibogaine’s desirable actions and GDNF.
“If we can alter the GDNF pathway, we may well have a new treatment against alcohol and drug addiction without the unwanted side effects of Ibogaine,” Ron said.

Source:
Colleagues in the research and coauthors on the paper are postdoctoral fellows Dao-Yao He, PhD, Nancy N.H. McGough, PhHD; Ajay Ravindranathan, PhD; Jerome Jeanblanc, PhD; Marian Logrip, BA, UCSF neurology graduate student; and Khanhky Phamluong, BA, research associate, all at the Gallo Center.
The research is supported by funds provided by the State of California through UCSF for medical research on alcohol and substance abuse, and by the Department of Defense.

Source: University Of California, San Francisco (2005, January 23). Controversial Drug Shown To Act On Brain Protein To Cut Alcohol Use. ScienceDaily. Retrieved May 31, 2009, from

Scientists at Melbourne’s Howard Florey Institute have discovered a system in the brain that stops an alcoholic’s craving for alcohol, as well as prevent relapse once they have recovered from alcohol addiction.

The ‘Orexin’ system is a group of cells in a part of the brain called the hypothalamus. These cells produce Orexin, which was originally implicated in the regulation of feeding, but it soon became apparent that Orexin was also involved in the ‘high’ felt after drinking alcohol or taking illicit drugs.
In studies conducted with rats, Dr Andrew Lawrence and his Florey colleagues used a drug that blocked Orexin’s euphoric effects in the brain and the results were remarkable.
“In one experiment, rats that had alcohol freely available to them stopped drinking it after receiving the Orexin blocker.” Dr Lawrence said.
“In another experiment, rats that had gone through a detox program and were then given the Orexin blocking drug, did not relapse into alcohol addiction when they were reintroduced to an environment in which they had been conditioned to associate with alcohol use.
“Orexin reinforces the euphoria felt when drinking alcohol, so if a drug can be developed to block the Orexin system in humans, we should be able to stop an alcoholic’s craving for alcohol, as well as preventing relapse once the alcoholic has recovered,” he said.
Dr Lawrence said that this research could also lead to treatments for eating disorders, such chronic over-eating, which leads to obesity.
“Our research shows that alcohol addiction and eating disorders set off common triggers in the brain, so further investigations may uncover drug targets in the Orexin system to treat both conditions,” Dr Lawrence said.
The Florey scientists are now conducting multiple experiments to discover the precise circumstances that activate the Orexin system.
“To explore this discovery further we are now investigating how different experimental paradigms and environmental situations impact on the Orexin system, which will hopefully pinpoint therapeutic drug targets,” Dr Lawrence said.
“Before a therapeutic Orexin-blocking drug can be developed, we need to ensure that it will be safe to use in the long-term and that issues surrounding a person’s compliance in taking the drug are considered,” he said.
According to the World Health Organisation, alcohol is one of the most widely used and abused substances in the world and causes as much, if not more death and disability as measles, malaria, tobacco, or illegal drugs.
Dr Lawrence and his colleagues were the first in the world to demonstrate the Orexin system’s involvement in alcohol addiction and their research paper was recently published in the prestigious British Journal of Pharmacology. Dr Lawrence’s paper was downloaded 658 times by researchers from around the world in the first three months of its publication, making it the most downloaded research paper in that issue and supporting the research’s importance.
The Howard Florey Institute is Australia’s leading brain research centre. Its scientists undertake clinical and applied research that can be developed into treatments to combat brain disorders, and new medical practices. Their discoveries will improve the lives of those directly, and indirectly, affected by brain and mind disorders in Australia, and around the world. The Florey’s research areas cover a variety of brain and mind disorders including Parkinson’s disease, stroke, motor neuron disease, addiction, epilepsy, multiple sclerosis, autism and dementia.

Source: Howard Florey Institute (2006, December 13). Research Offers Hope For Alcoholics. ScienceDaily. Retrieved May 31, 2009, from http://www.sciencedaily.com¬ /releases/2006/12/061212213910.htm

Alcohol-dependent patients who received the medication topiramate had fewer heavy drinking days, fewer drinks per day and more days of continuous abstinence than those who received placebo, according to a study in the October 10 issue of JAMA.

According to background information in the article, a previous, shorter trial indicated that topiramate, a medication used in the treatment of seizures, may be beneficial for the treatment of alcohol dependence.
Bankole A. Johnson, D.Sc., M.D., Ph.D., of the University of Virginia, Charlottesville, Va., and colleagues conducted a multisite, 14-week, randomized controlled trial to determine the efficacy of topiramate compared with placebo. The study, which included 371 men and women age 18 to 65 years diagnosed with alcohol dependence, was conducted between January 2004 and August 2006 at 17 U.S. sites. The participants received up to 300 mg/day of topiramate (n = 183) or placebo (n = 188), along with a weekly psychosocial treatment to promote adherence with the study medication and the treatment regimen.
Treating all dropouts as relapse to baseline, topiramate compared with placebo recipients showed greater reduction of percentage of heavy drinking days from baseline to week 14 (from an average of 81.9 percent to 43.8 percent for topiramate vs. 82.0 percent to 51.8 percent for placebo; average difference, 8.44 percent). Prespecified analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days (average difference, 16.19 percent).
The researchers also found that topiramate compared with placebo treatment was associated with a significantly higher rate of achieving 28 or more days of continuous nonheavy drinking and 28 or more days of continuous abstinence. Adverse events that were more common with topiramate vs. placebo included paresthesia (abnormal skin sensations), taste perversion, anorexia, and difficulty with concentration.
“Our finding in this study that topiramate is a safe and consistently efficacious medication for treating alcohol dependence is scientifically and clinically important. Alcoholism ranks third and fifth on the U.S. and global burdens of disease, respectively. Discovering pharmacological agents such as topiramate that improve drinking outcomes can make a major contribution to global health. Because topiramate pharmacotherapy can be paired with a brief intervention deliverable by nonspecialist health practitioners, a next step would be to examine its efficacy in community practice settings,” the authors conclude.
Article Reference: JAMA. 2007;298(14):1641-1651
Editorial: Medications to Treat Alcohol Dependence
In an accompanying editorial, Mark L. Willenbring, M.D., of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Md., writes that alcohol dependence is a disease that needs greater attention in the health care community.
“Alcohol dependence is the third leading modifiable cause of death in the United States, accounting for about 85,000 deaths per year. Reducing incidence, shortening the course, and reducing the severity of episodes are valuable and important goals. Reducing the public health burden will involve addressing the needs of a broader range of patients than can be treated by the specialty treatment system. In particular, it will be important to reduce disability caused by currently untreated episodes of dependence among those with the nonrelapsing form of the illness.”
“By historical standards, the pace of medication development for treating this disorder is increasing, and a variety of medications with different modes of action are now available. A solid understanding of the neurobiology of alcohol addiction is providing the framework for multiple avenues of further medication development. The behavioral platform required to support medication treatment is similar to that for depression, attention-deficit/hyperactivity disorder, diabetes, and other chronic illnesses, and thus could potentially fit into general medical practice.”
Source: JAMA and Archives Journals (2007, October 10). Medication Shows Promise As A Treatment For Alcohol Dependence. ScienceDaily. Retrieved May 31, 2009

 COST OF SUBSTANCE  The breakdown on federal and state money for substance abuse and addiction (numbers don’t add up to 100% due to rounding):
     95.6% Health care/assistance/prosecution
      2.4% Prevention/treatment/research
      1.4% Regulation/compliance
      0.7% Interdiction (federal only)
Source: The National Center on Addiction and Substance Abuse at Columbia University
 
Most of the taxpayer money devoted to combating alcohol and drug abuse goes to cleaning up its consequences, while only about 2% of the funding is used for prevention, says a report from the National Center on Addiction and Substance Abuse (CASA) at Columbia University.
The study found that 96% of the $467.7 billion a year that federal, state and local governments spend on substance abuse is used to deal with consequences such as crime and homelessness.
Of that money, according to the report, governments spend the most on health care costs associated with substance abuse (58%) followed by the costs of prosecuting and jailing the offenders (13.1%).
“The killer finding is that we are spending 96 cents of every dollar we spend on substance abuse and addiction to shovel up the human wreckage,” says Joseph Califano Jr., founder and chairman of CASA. “We’re making this really tiny investment in prevention and treatment when we have enough experience to know that prevention and treatment can reduce the shoveling-up burden.”
Researchers determined spending amounts by analyzing federal, state and local budgets for the year 2005, the most recent year that complete data were available, Califano says.
“These governments have it backwards,” he says. “They’re wasting billions of dollars of taxpayers’ money and not making some relatively simple investments that could sharply reduce the consequences of drug and alcohol addiction.”
Califano says the main reason that federal and state governments aren’t ready to change priorities is because there is a stigma attached to alcohol and drug addiction.
To reduce the amount spent on substance abuse, Califano says, the government needs to “mount major prevention programs,” with a focus on kids.
He adds that increasing taxes on alcohol and training doctors to talk to patients about their substance use also will help decrease associated costs.
“This is a problem we can deal with. We know a lot more about it than we knew years ago,” Califano says.
Source: USA Today 27th May 2009

Researchers have demonstrated that a naturally occurring brain protein known as Brain Derived Neurotrophic Factor (BDNF) can be manipulated to produce increased activity in the brain similar to when opiates are ingested, the Deseret News reported May 28.
Neurobiologist Hector Vargas-Perez and colleagues at the University of Toronto and Brigham Young University (BYU) found that an increased presence of BDNF is associated not only with greater brain activity, such as when an epileptic fit occurs, but also with chronic exposure to drugs of abuse. The increase in BDNF – known to be involved in the release of dopamine in the brain — occurs within a specific area of the brain known as the ventral tegmental area (VTA).
The researchers found that repeatedly increasing BDNF levels in the brains of non drug-dependent lab rats changed their behavior to resemble that of drug-dependent rats.
“If we can understand how the brain’s circuitry changes in association with drug abuse we can find ways to medically counteract the effects of dependency” in humans, said researcher Scott Steffensen of BYU. Lead author Hector Vargas-Perez of the University of Toronto said that the study “reveals the mechanism behind drug addiction.”
Source: online edition of the journal Science. May 28, 2009

Researchers studying fruit flies have discovered a gene that raises tolerance for alcohol and could be the basis for gene therapy for alcoholism, ABC News reported May 23.
The study found that when the gene — dubbed “happyhour” by researchers — was switched off by blocking its action with an anticancer drug called Tarceva, the flies became more sensitive to alcohol and drank less. The drug, like the gene, acts on a cellular network called the EGF pathway.
“People who are very sensitive to alcohol tend to drink less — that’s the person who gets drunk on one glass of wine,” noted Brown University psychiatrist Robert Swift. “The person who can drink everybody under the table — that’s that person who is more likely to become an alcoholic.”
Researcher Ulrike Heberlein of the University of California at San Francisco and colleagues found the gene by studying mutant fruit flies that could outdrink other flies. In past studies, Heberlein’s team discovered a gene called “cheapdate” that makes flies highly sensitive to alcohol.
“I’m very much looking forward for [Tarceva] to be tested in humans, and it’s quite possible one wouldn’t need the doses used in chemotherapy to treat addicts,” said Heberlein.
Source: journal Cell. May 21, 2009

By Patrick Zickler
NIDA NOTES Staff Writer

Smokers who want to quit can get help with a variety of treatments, including counselling, nicotine replacement therapy (patches, gum, lozenges, or inhalers and medications. Some smokers use these treatments and succeed; for many. however, the discomfort of withdrawal and craving for nicotine lead to relapse. Recent NIDA funded research suggests that our genes may partly explain this variable success.

The research evaluated the effect of an enzyme, designated CYP2B6, on craving and relapse. This enzyme breaks down nicotine in the brain. Some peoples’ genes produce a more active form of the enzyme. while others have a less active form. Dr. Caryn Lerman at the NIDA- and NCI supported Transdisciplinary Tobacco Use Research Centre (TTURC) at the University of Pennsylvania, found that among smokers enrolled in a smoking cessation program, those with the genetic variant that decreases activity of CYP2B6 reported greater craving than did those with the more active form of the enzyme. Moreover, those with the less active enzyme were 1.5 times more likely to resume smoking during treatment.

The same enzyme helps break down bupropion, an antidepressant medication that acts on the brain’s dopamine system—where nicotine exerts much of its addictive influence—and helps some smokers quit. Dr. Lerman, along with colleagues at Georgetown University in Washington, DC., the State University of New York at Buffalo, and Brown University in Providence, Rhode Island, also investigated the relationship of CYP2B6 activity with bupropion treatment. They found that bupropion nearly tripled the success rate for women with the less active enzyme.

These findings provide initial evidence that smokers who have decreased CYP2B6 activity experience greater craving for nicotine than those with the more active form of this enzyme,” Dr. Lerman says. “Perhaps of greater interest is the preliminary evidence that, among women, bupropion may overcome the effect this genetic predisposition has on relapse.”

Genes, Treatment, and Abstinence

Most people—about 70 percent of the U.S. population—inherit two copies of the ‘C’ variant of the gene that influences CYP2B6 activity. The rest of the population inherits from one or both parents the less common form of the gene—the “T’ variant associated with decreased CYP2B6 activity. Among the 426 participants (232 men, 194 women) in the TTURC study, 128 (29.6 percent) had one or two copies of the T form of the gene. All participants received counselling to quit smoking; 229 received bupropion (300 mg/day) and 197 received placebo throughout the 10-week study. The participants provided weekly reports on craving and smoking rates. Abstinence (7 consecutive days without smoking) was verified with blood tests. At the end of treatment, participants who received counselling and bupropion had higher abstinence rates than those who received counselling and placebo. With one exception. participants with the less active enzyme had lower abstinence rates than those with the more active enzyme. Women with the less active enzyme who received bupropion showed the largest treatment effect, with 54 percent achieving abstinence, up from a 19-percent rate among women in the placebo group, notes Dr. Lerman.

This study suggests that properly selected treatment matched to a patient’s characteristics can improve a smoker’s chance of quitting

Theories To Explain Outcomes

The higher abstinence rate with bupropion for women with the lower activity enzyme may he due, in part, to reduced susceptibility to low moods that accompany nicotine withdrawal; overall. women reported more negative feelings than did men when asked to rate their mood during withdrawal. “This rate may reflect better management of the negative moods and craving that abstinence can create. But more study is needed to clarify the mechanisms by which bupropion influences smokers’ success in quitting”, Dr. Lerman says.
Researchers theorize that the association between the less active enzyme and increased craving could be the result of nicotine’s remaining longer in the brains of smokers with the less active enzyme. When nicotine lingers in the brains of these smokers, it may change their brain cells more profoundly than those of smokers with the more active enzyme. If so, the changes might produce more severe addiction marked by more intense craving during abstinence and increased risk of relapse.

“This study offers additional evidence of the important role genes play in smoking and treatment,” says Dr. Joni Rutter of NIDAs Division of Neuroscience and Behavioural Research, ‘While illustrating the increased craving and vulnerability to relapse that may be associated with inherited traits, it also suggests that properly selected treatment matched to a patient’s characteristics in this case, Bupropion for some women can improve a smoker’s chance of quitting.’

Source:Lerman, C., et al. Pharmacogenetic investigation of smoking cessation treatment, Pharmacogenetics
12(8):627-634, 2002.

Australian researchers have found that one in three teenagers who smoke marijuana become psychologically dependent on the drug by their early 20s, the Independent reported April 1.

But the study also found that the dependence is mental, rather than physical. In examining marijuana dependence among 1,601 20- and 21-year-olds, the researchers found that the key factor in becoming dependent was frequency of use.

Report Shows Link Between Addiction, Mental Illness

A new report, Serious Mental Illness and Its Co-Occurrence with Substance Use Disorders, illustrates the association between mental illness and addiction among adults aged 18 or older, according to a July 29 news release from the Substance Abuse and Mental Health Services Administration (SAMHSA).

According to the SAMHSA report, 33.2 million adults aged 18 or older had a serious mental illness or addiction in 2002. The rate of serious mental illness was 19.0 percent among those with alcohol dependence or misuse, 29.1 percent among those with illegal drug dependence or misuse and 30.1 percent among adults who had both drug and alcohol dependence.

“The time has come to ensure that all Americans who experience co-occurring mental and substance use disorders have an opportunity for treatment and recovery,” SAMHSA Administrator Charles Curie said. “Clearly our systems of services must continue to evolve to reflect the growing evidence base that promotes integrated treatment and supportive services. Both disorders must be addressed as primary illnesses and treated as such.”

According to the report, 47.9 percent of adults with both serious mental illness and an addiction received some type of treatment. However, only 11.8 percent of these adults received both mental health and addiction treatment services.
Source: News Release from SAMHSA July 29 2004

 Some people can drink a lot of alcohol without becoming addicted, and specific genes may help explain why, researchers say. In a new study of Australian twins, scientists found that separate genes appear to be responsible, to some degree, for dependence on alcohol — addiction — and how much people drink. Understanding how these genetic factors work together should give researchers more insight into treatment of alcoholism in its various forms, said study co-author John B. Whitfield, a researcher at Royal Prince Alfred Hospital in Australia.

Alcoholism and alcohol consumption may appear to be similar, but researchers are increasingly studying them separately. Consumption refers to the amount of alcohol that someone drinks, while addiction refers to a person’s inability to go without a drink.

“The transition from social alcohol consumption to alcohol dependence is a gradual process, and it is often hard to notice it,” said Dr. Alexei B. Kampov-Polevoi, an assistant professor of psychiatry at Mount Sinai School of Medicine. “As a result, many alcoholics and their family members continue to think that a person ‘just drinks too much’ while this person already developed alcohol dependence and requires treatment.”

Whitfield and his colleagues examined statistics about alcohol use from three studies of Australian twins completed between 1980 and 1995. The number of twins in the studies declined from 8,184 in 1980 to 3,378 in 1995. The findings appear in the August issue of Alcoholism: Clinical & Experimental Research.

The researchers found twins who were genetically similar were more likely to consume similar amounts of alcohol. According to the study, some genes affected both addiction and alcohol intake, while some just affected addiction.

“We found (as others have also found) that alcohol dependence is partly, but not entirely, due to genetic differences between people who are affected by it and those who are not,” Whitfield said. “We also found that variation in the amount of alcohol that people habitually drink is subject to genetic influence, and that there is some – but not complete – overlap between the genes affecting these two things.”

Howard J. Edenberg, professor of biochemistry and molecular biology at Indiana University, said the findings – that genes separately affect alcoholism and drinking – are “reasonable.” But “that is a long way from identifying individual genes that actually are involved,” said Edenberg, whose own research is looking into that area.

So what should ordinary folks take from this study? “There is no direct and new message for people with alcoholism in their families; they are at higher risk than average but this has been known for some time and there is only a statistical risk, not a certainty by any means,” Whitfield said. “The more positive message for such people, and the community at large, is that we are learning more about alcohol use and alcohol-related problems and their causes.”

US researchers have linked the behaviour of seeking drugs after a period of abstinence to specific nerve cells in a part of the brain called the nucleus accumbens. Previous studies have shown that drug addiction depends on the mesocorticolimbic dopamine system innervating the nucleus accumbens. Dr Udi Ghitza and colleagues from Rutgers University tested whether the accumbens neurons exhibit responses to external stimuli previously associated with self-administration of cocaine by rats. The rats learnt that on hearing a tone they could press a lever and self-administer cocaine. No cocaine was available if the animal pressed the lever in the absence of the tone.
Microelectrodes were attached to the brains of the animals and these recorded the activity of single neurons in the nucleus accumbens.

After two weeks of self-administration of cocaine, the lever was removed and no tone sounds were made. The animals abstained from the drug for almost a month. When the lever was returned to the cage, the animals ignored it when no cocaine and no tone were provided. However, when the original tone was made, the animals began to press the lever at a high rate even though no cocaine was available. During this relapse into drug seeking, the neurons – in an area of nucleus accumbens known at the shell – were activated by the tone. The rats eventually stopped pressing the lever when the tone was made. However, nucleus accumbens neurons still responded to the tone. Dr Mark West, one of the co-authors, says, This activity may reflect the processing of memories that persist even after a long abstinence and may partially explain why environmental cues can provoke a relapse. This  suggests that the existence of a neuroadaptation that may make individuals more vulnerable to assuming drug-taking behaviour.”

A study issued by the Substance Abuse and Mental Health Services Administration’s (SAMHSAs) Center for Substance Abuse Treatment (CSAT) this month found that drug-and alcohol-dependent women who are pregnant or have children significantly reduce their alcohol or drug use as well as criminal behaviour following residential substance abuse treatment. Treatment also produced improved birth outcomes for pregnant women. The study, 1993-2000 Residential Treatment Programs for Pregnant and Parenting Women, evaluated residential substance abuse treatment programs designed for pregnant women or women with infants or older children. The report examined 50 programs that provided on-site residential care for both parents and their children.

Among women in treatment, use of crack declined from 51 percent before treatment to 27 percent six months after treatment. Similar declines were noted in use of marijuana (from 48 percent before treatment to 15 percent after treatment); powder cocaine (34 percent to 9 percent); methamphetamine (21 percent to 6 percent); heroin (17 percent to 6 percent); and alcohol (65 percent to 25 percent). Over 60 percent of women reported being completely drug-and alcohol- free throughout the first six months following discharge from residential care. An additional 13 percent relapsed at some time after discharge but were completely alcohol-and drug-free in the past 30 days. Women who stayed in treatment longer than three months were more likely to remain alcohol-and drug-free than were those who left within the first three months of treatment (68 percent vs. 48 percent).

Criminal Outcomes

As compared to the 12 months prior to treatment, the percentage of clients arrested for alcohol or drug offenses (selling drugs, public intoxication, driving drunk, etc.) declined from 28 percent to 7 percent during the six months following discharge. A decline from 32 percent to 11 percent was seen in the percentage of clients arrested for non-substance offenses, such as shoplifting, burglary, prostitution or assault. Women who remained in treatment longer than three months were less likely to be arrested than were those who left treatment prior to three months – 9 percent vs. 20 percent.

Relationships And Parenting

The percentage of clients living with an alcohol-or drug-involved spouse or partner declined from 45 percent prior to treatment to 12 percent after, according to the report. The percentage of clients reporting that they and their family use drugs together declined from 26 percent to 4 percent.
Clients who had physical custody of one or more children increased from 54 percent before entering treatment to 75 percent after treatment. Clients who had children living in foster care declined from 28 percent before treatment to 19 percent after treatment.

The governor said Thursday that Vermont will stop paying for OxyContin for certain welfare recipients because of the prescription painkillers growing link to crime and addiction. Gov. Howard Dean also encouraged physicians to find substitutes for the drug and suggested pharmacies might want to stop stocking it. “I would ask physicians to consider very carefully their use of this drug,’ said Dean, himself a physician. OxyContin is a federally approved pain reliever that is a synthetic morphine with a derivative of opium. But when tablets are crushed and mixed with water, snorted or injected, they can give the user a high similar to that of heroin. Since 1998, Oxy and oxycodone, the narcotics active ingredient, have been linked to more than 100 deaths nationwide.

If ever an incident illuminated why the argument that legalization of illicit drugs will eliminate crime is completely ludicrous, this is it. Here is a legal narcotic drug that regulation has failed to keep from the street, and because it is legally manufactured and distributed, was easy to divert Now,one state, Vermont, is refusing to participate in the distribution of this drug – even for prescribed medical purposes, for those on welfare. Oh that states were that astute when it comes to refusing to allow the ILLEGAL drug, marijuana, to be distributed under the medical use claim. The Sonoma County California. DA recently returned to an individual claiming medical necessity FIVE pounds (the equivalent of approximately 2,800 joints of unknown potency) for purported medical use.

The majority of alcohol research to date has focused primarily on men, or on combined samples of men and women. Even fewer psychopathological studies – which examine emotional, behavioural and psychological problems – have focused exclusively on women with drug dependencies. Of those that have, the focus has been on single substances of abuse, such as cocaine. A study in the July issue of Alcoholism: Clinical & Experimental Research examines the psychopathology of pregnant women with co-occurring alcohol and drug dependencies.
Drug-dependent women present for treatment with a variety of medical, psychosocial and emotional problems. Rates of homelessness, poverty, unemployment, and prostitution are high in this patient population. Many of these women have histories of emotional, physical and sexual abuse. Yet societal stigmatization typically prompts pregnant women to conceal substance use, which makes identification and intervention difficult. In fact, many alcohol- and drug-abusing women avoid prenatal care altogether. Furthermore, in many states, delivery of a drug-positive infant results in legal sanctions that include termination of parental rights and criminal prosecution. Taken together, this myriad of problems and concerns make pregnant drug-dependent women a very vulnerable population in need of more intensive, user-friendly services that focus not only on their alcohol and drug problems, but their other needs and concerns as well.
Pregnancy  can have multiple effects on alcohol/drug-dependent women,’ added Roy W. Pickens, Associate Vice President for Research, and professor of psychiatry, at Virginia Commonwealth University. “On the one hand, concern about the effects of alcohol/drug use may cause a pregnant woman to be more willing to seek and complete treatment. On the other hand, pregnancy adds to the unfounded social stigma of being alcohol/drug dependent, which may keep a woman from entering treatment.”
In the study, the psychopathology of 170 pregnant women in treatment for drug dependency was measured using the Minnesota Multiphasic Personality Inventory – Revised (MMPI-2). The MMPI-2 uses 567 self- report items to measure different aspects of psychopathology, including depression, anxiety, impulsivity, aggression and suspiciousness. The majority of the women (79%) were drug dependent only; less than one quarter (21%) were both alcohol and drug dependent.

“Our findings show that cocaine- and/or heroin-dependent pregnant women who also have problems with alcohol come into treatment with more psychological problems than those who don’t also have alcohol problems,’ said Miles. “Specifically, they had more symptoms of depression and anxiety as well as problems controlling impulsivity and aggression. They were also more likely to misinterpret life experiences and react in atypical ways to their environment. These findings emphasize the need for universal screening for alcohol problems in drug-using pregnant women and, for those who screen positive, to make sure treatment is offered and tailored to meet their needs.”
“These findings illustrate that all drug-dependent individuals are not the same’ agreed Pickens. “In fact, these differences are sometimes important in the selection of treatment approaches. The study suggests that alcohol dependence, in particular, is a factor related to psychiatric/personality disorders in the drug dependent individual. This difference needs to be recognized by treatment providers, the individuals’ relatives, and the general public.’
It is unclear exactly how many pregnant women use alcohol and/or drugs during pregnancy, or how many seek help for their dependencies. Alcohol dependence affects more than one in five women in general, according to Miles. U.S. Department of Health and Human Services 1996 data reveal that 5.5 percent of women used illicit drugs during pregnancy, while 18.8 percent reported alcohol use during pregnancy. Pickens said a more recent study found that a similar proportion (5 to 6%) of women had used illicit drugs during pregnancy, while a greater proportion (25%) had used alcohol. Because research consistently shows that alcohol use during pregnancy is the leading known cause of mental retardation, said Miles, its use should not be overlooked, even when women are using other drugs.
“The rates at which pregnant drug-using women seek treatment vary widely,” said Miles, “depending upon availability of services, practitioner attitudes and legal consequences.” For example, prior to the creation of the Baltimore Center for Addiction and Pregnancy (CAP), where this research was conducted, less than five percent of pregnant drug-abusing women followed through with an initial referral to “standard’ drug treatment. (CAP uses what is considered an “intensive” approach: residential treatment followed by 6.5 hours per day of outpatient treatment for the duration of pregnancy.) Subsequent to CAP’s establishment, Miles estimated that approximately 50 percent of the pregnant drug-dependent women referred to CAP actually followed through with the referral.

“The women seeking treatment at CAP have severe cocaine and/or opiate dependence as well as limited financial, family/social and medical resources” said  Miles. “They are also older women with several previous pregnancies” Most of the women were also single (75%), African American (80%), and had a mean age of 29 years. Miles noted there were difficulties generalizing the study’s findings to younger women with more varied sociodemographic characteristics.

“This kind of program is often so focused on illicit drug use,” said Miles, that alcohol problems often go undetected or receive less emphasis in treatment. Yet this study found that alcohol seems to be uniquely associated with greater psychopathology. The women with co occurring alcohol and drug problems present for treatment with more emotional problems such as depression and anxiety, and such problems are associated with poorer treatment participation, retention and outcome. We need to intensify efforts to keep these women in care. One strategy would be to provide residential treatment for a longer period of time, perhaps even for the duration of pregnancy. This would allow greater opportunities for maintaining abstinence from alcohol and other drugs while at the same time providing a safe and supportive environment that may aid in reducing their emotional distress. Unless we recognize the unique psychological and emotional symptoms associated with different drugs of choice, the end result is likely to be premature treatment dropout and potentially negative
outcomes for both mother and baby.”

Withdrawal from marijuana, as with other addictive drugs, produces symptoms such as irritability, nervousness, depression, restlessness, sleep difficulty, and decreased appetite, all of which are alleviated when use recommences. A paper published in the journal Psychopharmacology (2003) examined the use of the drug Nefazodone to treat anxiety associated with marijuana withdrawal and found that though it eased some symptoms of withdrawal the patients remained significantly agitated and uncomfortable. The authors noted that Nefazodone can caused blurred vision, dizziness, and light headedness, but stressed that more research was needed to determine if higher doses of the drug would be more effective in relieving withdrawal symptoms. They concluded by stating: “Given the mounting evidence of marijuana withdrawal symptoms, the vast numbers of daily users, and the difficulty treatment-seekers have in maintaining abstinence, it is clear that more behavioural and pharmacological treatment options for marijuana-dependent individuals are needed.”
This paper illuminates the addictiveness of marijuana, the difficulty of treatment and, unfortunately, the growing number of marijuana users [many of whom are now attaining the drug under the guise of medicinal use]. Delta-9 THC (Dronabinol) is the major psychoactive ingredient in cannabis and is so highly addictive that it is outlawed in Europe, even as a prescription drug. Because of the high THC content of cannabis today (often ten+ times more potent than it was 20 years ago) addiction is likely to occur much more rapidly today than it has in the past and perhaps is associated with the plethora of adverse consequences leading to emergency medical and psychiatric episodes.

Researchers have uncovered a genetic factor that could  predispose certain youths to binge drinking, according to the National Institute on Alcohol Abuse and pr Alcoholism (NIAAA). Researchers from NIAAA and George Washington University in Washington, D.C., found that college students with a particular variant of the serotonin ‘ transporter gene (5-I-FIT) drank more alcohol per occasion, drank more often just to get drunk, and were more likely to engage in binge drinking than students without the variant. The research was based on interviews with 262 college students, ages 17 to 23, about their alcohol consumption. The team of scientists then analyzed the genetic profiles of the participants. The 5-HTT gene is involved in recycling the chemical serotonin after it is secreted into the synapse of a cell. Rather than having one long and one short variant of the serotonin-transporter gene, study participants found to be predisposed to harmful drinking behaviour had duplicate copies of the short version.

‘Taken together with other research, this finding suggests that genetically mediated differences in serotonergic response play an important role in mediating patterns of alcohol intake,” said Paolo B. DePetrillo, M.D., a clinical investigator at NIAAA. The study also found that students with at least one copy of the long variant of the gene were more likely to consume fewer drinks at one sitting, even though they went out to drink as often as the other students. “This research provides important new evidence that the risk of developing a maladaptive pattern of alcohol consumption is influenced by genetically determined neurobiological differences that exert their effects during young adulthood,” said Ting-Kai Li, M.D., director of NIAAA.

A 15-year study has resulted in the identification of a specific gene that may increase the risk of alcohol  dependence. The $65 million federally-funded Collaborative Study on  the Genetics of Alcoholism (COGA) included 10,000 participants with a history of alcohol addiction. The research was conducted at six locations. In St. Louis, scientists isolated a gene on chromosome 15 that appears to be connected to alcohol addiction. The gene is involved in the regulation of gamma-amino butyric acid (GABA), which is a chemical in the brain that helps to send messages between neurons. Previous research has shown that GABA alters behaviour and is linked to psychiatric disorders.
Stimulating GABA receptors will increase behavioural effects of alcohol, like motor coordination and reduction of anxiety, said Danielle Dick, a professor of psychiatry at Washington University School& of Medicine in St. Louis and principal author of the study. For another component of the study, researchers are examining a different area of the genome, chromosome 4, to determine whether genes there are connected with alcohol metabolism and brain activity. Researchers involved in the study expect to find several genes associated with alcohol dependence. Such identification could lead to new avenues for medications. “It is important to say that these genes all influence your risk,’ Dick said. ‘There is no one alcoholism gene” The National Institutes of Alcohol Abuse and Alcoholism funded the study. The findings appear in the Jan. 14 issue of the journal Alcoholism: Clinical and Experimental research.

A University of Michigan (U-M) study finds that more people in their mid-30s misuse alcohol and illegal drugs than previously believed. The study of 7,541 people in their 30s found that more than 32 percent of the men drank heavily, which was defined as consuming five drinks or more at one time. In addition, 13 percent of the men and 7 percent of the women used marijuana. The study also showed that 6 percent of the women and 7 percent of the men misused prescription drugs.

“We found that substance abuse was surprisingly prevalent at the start of midlife. And we also found that it is not restricted to stereotypical drug users with low socioeconomic status,” said study author Alicia Merline of the U-M Institute for Social Research. For instance, the study found that professionals are just as likely to use marijuana as people in other job classifications. The research also revealed that participants who used illegal drugs or drank heavily in high school were more likely to misuse those same substances later in midlife.

In a study involving twins, researchers found that addiction to alcohol is often influenced by genetics as well as family environment. For the study, researchers from Palo Alto Veterans – Affairs Health Care System in Menlo Park, Ariz., interviewed 1,213 identical and non-identical male twins  with an average age of 50, 1,270 of the twins’ children, ages 12 to 26, and 862 mothers of those children.

The researchers found that children of twins who had a history of alcohol addiction were more likely to show signs of alcohol misuse or dependence than children of non alcoholic fathers. But while children of alcohol-abusing identical twins whose co-twin was alcohol-dependent were more likely to be alcohol-dependent than children of non alcoholic twins, children of an identical twin with no history of alcohol abuse whose co-twin was alcohol-dependent were no more likely to abuse alcohol than the children of non alcoholic twins. These findings support the hypothesis that family environment effects do make a difference in accounting for offspring outcomes, in particular, that a low-risk environment (i.e., the absence of parental alcoholism) can moderate the impact of high genetic risk regarding offspring for the development of alcohol-use disorders,” the study’s authors said.

New research suggests that individuals who stop using methamphetamine may experience brain abnormalities similar to those seen in people with depression and anxiety disorders, according to a Jan. 5 press release from the National Institute on Drug Abuse (NIDA).

For the study, Dr. Edythe London and colleagues at the University of California at Los Angeles, the University of  California Irvine, and NIDA’s Intramural Research Program used positron emission tomography (PET) to image brain activity in methamphetamine users. .The researchers compared the glucose metabolism in the brains of 18 people who did not use the drug to the brain activity of 17 individuals addicted to methamphetamine for an average of 10 years, but who had stopped using the drug for four to seven days before the test. After reviewing the PET scans, the researchers found that in methamphetamine users, the glucose metabolism was lower in brain regions linked to depressive disorders, depressed mood and sadness, but higher in brain regions linked to anxiety and drug cravings.

In addition, questionnaires given to all participants showed that methamphetamine users had higher ratings of depression and anxiety than non users. Based on the study’s results, the researchers recommended that practitioners provide therapy for depression and anxiety in order to improve the success rate for methamphetamine users receiving addiction treatment. The study’s findings are published in the January 2004 issue of the Archives of  General Psychiatry.

A definitive review of the addictive propensity of marijuana was undertaken by Eliot L. Gardner under the auspices of the US National Institute on Drug Abuse, National Institutes of Health, and the Department of Health and Human Services.The author stated that “Cannabinoids are euphorigenic (psychoactive) in humans and have addictive liability, but were long considered to be devoid of pharmacological action on these brain reward processes or on drug-seeking and drug-taking behaviours. Work with cannabinoids over the last 15 years, however, makes it clear that they interact with these brain processes and influence drug-seeking and drug-taking behaviours in a manner strikingly similar to that of other addictive drugs.” Further, the author states that “cannabinoid withdrawal appears to activate the same brain withdrawal processes as activated by withdrawal from other addictive drugs.”

Gardner reviewed 224 scientific papers addressing various aspects of addiction, withdrawal, and cannabis use and withdrawal. Of these studies 75 were published in the 1970’s and 80’s and the remaining 149 were published after 1989. The conclusion after examining this plethora of data was that “cannabinoids act on the brain reward processes and reward-related behaviours in strikingly similar fashion to other addictive drugs.

Using an experimental addiction treatment first investigated at the U.S. Department of Energy’s Brookhaven National Laboratory, a team of scientists from Brookhaven, the New York University (NYU) School of Medicine, and a national addiction treatment center in Mexico report prolonged abstinence and the elimination of drug craving in eight out of 20 hard-core, long-term cocaine addicts who enrolled in the study. This is the first human clinical data showing that gamma vinyl-GABA (GVG, vigabatrin) holds promise as a pharmacological treatment for cocaine addiction.
“It is extremely gratifying to see these early human results bear out what we’ve observed in our extensive preclinical animal studies with GVG,” said Brookhaven neuroanatomist Stephen Dewey, who has been using animal models and brain imaging techniques to investigate GVG’s effects on neurochemistry and addictive behavior for more than ten years. These animal experiments have shown that GVG can block drug-induced increases in brain dopamine (a chemical associated with reward and pleasure, which is elevated by all addictive drugs), drug-seeking behavior, drug self-administration and sensitization, and drug craving — even that triggered by environmental cues.

“This promising work on a potential treatment for drug addiction illustrates the value of the Department of Energy’s basic research in physics, chemistry, and imaging sciences,” said Secretary of Energy Spencer Abraham. “The advanced technologies developed in the DOE laboratories are being applied to a number of critical national health issues, including the problem of drug abuse.”
Said lead author Jonathan Brodie, a psychiatrist and biochemist at NYU who also collaborated on the animal experiments, “These human clinical data support the need for a larger double-blind placebo-controlled trial that will more carefully examine the risk/benefit relationship for GVG in the treatment of cocaine addiction — a life-threatening disease for which there are currently no effective pharmacological treatments.”
 

The study was conducted in June and July of 2003 at a Mexican-government- designated addiction treatment center in Baja California (the Clinica Integral de Tratamiento Contra Las Adicciones in Mexicali, B.C.) at the suggestion of Emilia Figueroa, a physician familiar with Dewey’s preclinical at work on GVG. GVG is approved for use in the treatment of epilepsy in Mexico (and many other countries), but not in the United States because it can sometimes cause a reduction in the field of vision. The protocol was approved by the state of Baja California and the Mexican federal government.Twenty daily cocaine abusers who expressed an interest in breaking their drug dependence were enrolled and given an escalating daily dose of GVG, starting with one gram twice a day, and reaching two grams twice a day by day seven of the trial. The subjects were treated as outpatients, allowed to return home each day and go about their normal lives. They were encouraged to participate in group and individual therapy programs, and all were required to provide urine samples for drug screening twice weekly and complete daily questionnaires on drug use and craving.Eight subjects dropped out within the first 10 days, stating that they did not wish to stop their cocaine use. Of the 12 who continued treatment with GVG, eight achieved periods of abstinence of more than 28 consecutive days, the duration set as a benchmark for successful treatment. All eight were tapered off GVG after completion of the trial, and remained drug-free at the time  of publication. Four other patients stayed in the trial for periods ranging from 25 to 43 days but continued to use cocaine, albeit in significantly reduced amounts. None of the study participants reported any visual disturbances.Those who completed the study reported that their craving for cocaine was eliminated within two to three weeks. They showed profound behavioral gains in self-esteem, family relationships, and work activities.‘The success rate achieved in this small study — 8 out of 20 remaining in the trial and drug-free –is comparable to that of other experimental cocaine addiction treatment protocols. But the prolonged duration of abstinence far exceeds what other pharmacological treatments have achieved,’ said Frank Vocci, Director, Division of Treatment Research and Development, National Institute on Drug Abuse.‘The resu!ts are particularly impressive considering that the study subjects remained in the same neighborhood, where the drug is readily available, and with all the cues and social pressures that supported their addiction for so many years,” said Figueroa.

The scientists hope that larger scale trials on GVG will be conducted at NIDA sponsored addiction research centers in the U.S. to investigate its efficacy as a treatment for addiction as well as any side effects.In October 2002, Catalyst Pharmaceutical Partners of Coral Gables, Florida, received an exclusive worldwide license from Brookhaven Science Associates, operator of Brookhaven National Laboratory, for the use of the drug vigabatrin for its application in treating drug addiction.

Researchers identify symptoms of marijuana withdrawal 60 percent have significant symptoms.Irritability, anxiety and physical tension, plus decreases in appetite and mood, were experienced by regular marijuana users who quit the drug for four weeks during a study conducted at McLean Hospital in Belmont, Mass.
Sixty percent of those in the study experienced “significant symptoms’ of withdrawal, said the researchers, Elena M.Kouri and Harrison Pope. Kouri and Pope are Harvard researchers.
“Most people think marijuana is a benign drug, and there is disagreement in the scientific community about whether withdrawal causes significant symptoms. This study shows that using marijuana for a long time has consequences,” said KouriSource:www.researchmatters.harvard.edu/july 2003

The 2002 National Survey of Substance Abuse Treatment Centers found that nearly half of the 1.1 million people receiving addiction treatment have more than one addiction, the Fitchburg Sentinel & Enterprise reported Oct. 6.

“The day of the single addiction is almost a dinosaur. Most people are addicted to more than one substance these days,” said Wayne Rushlow, a licensed mental health therapist and substance abuse counselor in Leominster, Mass., and the surrounding area. “If people can’t get one, they have the other to fall back on.”

According to the report, released by the Substance Abuse and Mental Health Services Administration (SAMHSA), 48 percent of the 1,136,287 people receiving treatment in 2002 were treated for both drug and alcohol dependency.

Rushlow said multiple addictions are a result of people experimenting with drugs at a younger age, starting at age 10.”They start with lesser drugs and, being adolescents, they get bored. It escalates very quickly and by the time they reach 21, they’ve run the gamut,” Rushlow said.

The study also showed that 49 percent of rehabilitation facilities provided special programs for people diagnosed with dual addiction and mental disorders.


Source:The Fitchburg Sentinel & Enterprise reported Oct. 6. 2003

In a study on laboratory rats, scientists discovered that certain nerve cells in a specific region of the brain play a key role in drug addiction relapse.Individuals who recover from addiction often face environmental stimuli associated with drug use, such as hearing a particular song or walking through a certain neighborhood. These triggers could provoke a return to drug use.In studying how environmental stimuli cause relapses, researchers at Rutgers studied the nerve cells in the nucleus accumbens, a brain region found to be involved in the addictive effects of drugs.

“We’ve identified a part of the brain that appears to process these memories,” said Mark West, a professor of psychology at Rutgers. “This might be one of the brain areas that a very skilled pharmacological approach could target.”

For the study, rats were able to self-administer cocaine by pressing a lever. When the animals pressed the lever, a tone sounded, which they came to associate with the drug. At the end of three weeks, the cocaine and lever were removed. A month later, the researchers returned the lever. But the rats ignored it until the tone sounded again.The researchers found that the nerve cells in the accumbens responded instantaneously when the tone was sounded.

“When we started to play the tone that had been paired with cocaine, the animals began to press the lever at a fairly high rate,” said West. “It indicated that the animals had a persistent memory — they remembered the significance of the tone. We interpreted the resumption of lever pressing as a behavioral relapse.”

Researchers said the study’s findings could help in the development of new addiction therapies and intervention strategies.The study is published in the Aug. 13 issue of the Journal of Neuroscience.


Source:Ghitza, U., Fabbricatore, A., Prokopenko, V., Pawlak, A., & West, M.
(2003) Persistent Cue-Evoked Activity of Accumbens Neurons after
Prolonged Abstinence from Self-Administered Cocaine.
Journal of Neuroscience, 23(19): 7239-7245.

Some brands of cigarette are likely to be far more habit-forming than others because of the amount of highly addictive “freebase” nicotine they produce. Scientists have found wide differences between different cigarette brands in the amount of freebase nicotine. which is quickly absorbed Through the lungs and carried in the bloodstream to the brain. Just as smoking ‘crack” causes vapourised cocaine to reach the brain within seconds, freebase nicotine also has an almost instantaneous effect on the central nervous system, making addiction more likely.

The researchers, from the Oregon Health and Science University in Portland, compared Ii cigarette brands available in the US and found that some contained between I and 20 times higher levels of freebase nicotine than expected. Brands were compared with a laboratory “reference’ cigarette containing I per cent freebase nicotine. The results ranged from 1 per cent or 2 per cent to 36 per cent for a speciality brand called American Spirit. The popular Marlboro brand contained up to 9.6 per cent freebase nicotine. Other well-known brands included Camel (2.7 per cent), Winston (5 to 6.2 per cent) and Gauloises Blondes (5.7 to 7 per cent).

Professor James Pankow who led the study reported in the journal Chemical Research in
Toxicology, said: “During smoking, only the freebase form can [ from a particle into the air in the respiratory tract. Gaseous nicotine is known to deposit super-quickly in the lungs. From there, its transported rapidly to the brain. “Since scientists have shown that a drug becomes more addictive when it is delivered to the brain more rapidly, freebase nicotine levels in cigarette smoke are thus at the heart of the controversy regarding the tobacco industry’s use of additives such as ammonia and urea.” A 1997 study led by Professor Pankow linked ammonia additives in tobacco with increased freebase nicotine levels in cigarettes. Separate measurements were made of the first three puffs and about eight subsequent puffs. In many cases, the freebase content was higher in the first puffs. Marlboro, for instance, had a freebase nicotine level of 9.6 per cent in the first three puffs and 2.7 per cent in later puffs.
Source: Author James Pankow Reported in Chemical research in Toxicology, 2003