28. February 2012 by stationmanager.

December 14, 2011 (Scottsdale, Arizona) — Inhibition of the catechol O-methyl-transferase (COMT) enzyme, which decreases synaptic dopamine levels, may be a novel and effective way to fight alcohol dependence, new research suggests.

In a small, open-label study of 25 psychiatric outpatients with AD, 88% of the participants showed anti-craving effects after taking the COMT-inhibitor entacapone (Comtan, Orion Corp.) for 12 weeks.

In addition, entacapone, which was given along with routinely used psychiatric medication, was not associated with any serious treatment-related adverse effects.

“This is the first study of its kind to show COMT inhibition as a potential pharmacological method of combatting alcohol craving,” principal investigator Rahim Shafa, MD, scientific director at MetroWest CNS Research Center in Natick, Massachusetts.

“For decades, a need has been recognized for a tolerable, non–habit forming compound to balance out the hypodopaminergic state of drug craving. In our study population, entacapone was effective to counteract both cue craving and ordinary mental craving, which is usually a product of nostalgia from getting high,” note the investigators.

They add that entacapone was also effective in alleviating alcoholic post-withdrawal dysphoria.

“I would like us to start thinking out of the box about how the reward system operates. That will help us to open up some new avenues for treatment of craving across the board,” said Dr. Shafa.

The results were presented here at the American Academy of Addiction Psychiatry (AAAP) 22nd Annual Meeting & Symposium.

Call for New Medications

The researchers note that of the 18 million Americans who had alcohol problems between 2001 and 2002, only 10% sought treatment, and fewer than 5% received pharmacotherapy.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) “strongly recommends adjunctive pharmacotherapy to the conventional treatment methods and calls for new medication to improve the high relapse rate,” write the investigators.

The COMT-inhibitor entacapone is approved by the US Food and Drug Administration (FDA) to treat Parkinson’s disease in conjunction with carbidopa-levodopa products.

At the 2008 AAAP Annual Meeting, Dr. Shafa presented results of a pilot study showing that more than half of its entacapone-treated patients achieved abstinence from marijuana use.

“COMT is one of the enzymes in the synaptic cleft that degrades available dopamine. By manipulating the enzyme in that study population, we hoped to remove the desire to seek marijuana. And that was the same principle we applied to this study — manipulate COMT to remove the desire for alcohol,” explained Dr. Shafa.

“Basically, we think that craving is a state of low dopamine. When dopamine levels go down in addicted people once drugs are out of their system, that creates a thirst for the drug.”

According to data from the 2009 National Survey on Drug Use and Health, adults with a mental disorder are 4 times more likely to also develop AD than those without a mental disorder.

However, Dr. Shafa noted that conventional anti-craving pharmacological studies often exclude participants with major mental illness. He added that past research has suggested that patients with schizophrenia and bipolar disorder who also have alcohol dependence or another substance use disorder often have high expression of COMT in their genes.

For this study, the investigators enrolled 25 adult psychiatric outpatients (64% men) with alcohol dependence who had “exhausted standard available pharmacologic treatments.”

All participants received entacapone for 12 weeks, in addition to their normal psychiatric medications. The average daily dose of entacapone treatment was 1600 mg.

A serial alcohol ethyl glucuronide urine test and patient interview were used to measure relapse. Abstinence for at least a 4-week period or significantly decreased craving during the first 4 weeks of treatment was considered evidence of overall improvement on the Clinical Global Impression (CGI) scale.

Alternative Treatment Strategy

Results showed that a significant percentage of the participants had improved anti-craving effects (88%, P < .05) by the end of the study.

Of these, 10 were considered “very much improved” on the CGI scale (improvement for all 3 months; mean age, 44.5 years), 3 were “much improved” (improvement for just 2 months; mean age, 41 years), 9 were “slightly improved” (improvement for just 1 month; mean age, 32.5 years), and 3 had no change (mean age, 28.3 years). All 3 of the nonresponders were male.

The 10 “very much improved” patients chose to continue treatment for an extra 6 months and “none had a relapse,” reported Dr. Shafa.

Treatment-related adverse events included palpitation (1 participant), nausea (2 participants), and urine discoloration (all 25 participants).

“Classic pharmacologic treatment of alcohol craving is based on the effect of alcohol on opiate receptor, its interaction with the glutamate system, or its metabolism at the liver,” write the investigators.

“Consideration of dopamine pathway offers an alternative treatment strategy, which could be used independently or potentially combined with one of the above classic approaches, based on more research,” they add.

Dr. Shafa noted that further double blind, placebo-controlled studies are needed to reexamine this concept and to “shed more light” on the situation.

“Still, the advantage of this was that it did not cause many side effects, as you would expect from a Parkinson’s medicine. This was especially important because we were able to give it to mentally ill patients who were able to also continue taking their own medicines.”

Dr. Shafa reported that he is now conducting studies using the same treatment for sugar and chocolate craving.

“Of Considerable Interest”

“I’m really interested in pharmacotherapy for alcohol. Having tried everything else, anything that comes along that might have potential is of considerable interest,” said Jan Campbell, MD, professor of psychiatry at the University of Kansas School of Medicine in Kansas City.

“It also looks like this treatment does not exacerbate comorbid psychiatric disorders, and that’s even more important,” added Dr. Campbell, who was not involved with the research.

She also noted that it looked as though entacapone was very well tolerated.

“It didn’t cause somnolence or weight gain, which are 2 effects we often find. And it’s FDA approved, which means it’s available and on the market. So that’s another plus,” said Dr. Campbell.

“There are all kinds of other things that are potentially on the market, but it’ll probably be a long time before they really get out there.”

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23. February 2012 by stationmanager.

  Recent findings from the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) are challenging traditional views of alcoholism and point to the need for a paradigm shift in prevention and treatment strategies, a leading expert says.

Among other findings, recent data from NESARC, a prospective, population-based study that surveyed 43,000 US adults in 2001–2002 and again in 2004–2005, show that more than half of alcohol-dependent individuals are healthy, functional, young adults — a far cry from the stereotypical middle-aged, white-male, skid-row alcoholic, said Mark L. Willenbring, MD, director of the division of treatment and recovery research at the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

“Much of what we thought we knew about alcoholism was based on middle-aged people, primarily white men in treatment programs and Alcoholics Anonymous, but the NESARC data are turning what we thought we knew about alcoholism completely on its head,” Dr. Willenbring told reporters attending a press conference here at the American Psychiatric Association 162nd Annual Meeting.

“I think that’s where we’re heading with treatment for alcohol dependence. The bulk of people with mild to moderate dependence, who are the majority, can be effectively treated with medication and brief behavioral support in primary care and general psychiatry,” said Dr. Willenbring.

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7. February 2012 by stationmanager.

Survey Results

 Alcoholism ranked behind obesity, cancer, heart disease, drug addiction, AIDS, and depression in a list of the most important health-related issues facing the nation. Alcoholism was considered a top health priority by only 4% and 6% of surveyed physicians and the general public, respectively. Despite this, 74% of the general public who were surveyed indicated that alcoholism affects their daily lives, whether their own addiction, addiction of a friend or family member, or any other experience (Figure 3). Additionally, 41% of the public reported having encouraged a loved one to seek help for an alcohol problem.

Among the 3 survey groups, there were differences as to what was perceived as the most important factors contributing to alcohol addiction. For example, the general public and physician groups both indicated that stress, anxiety, and insecurity about work, family, and other problems were the most important factors contributing to alcohol addiction, whereas people in recovery believed that genetics or family history played the predominate role.

Table 3 lists the other factors contributing to alcohol addiction and the respective attitudes held by each of the 3 survey groups.

Stigma Persists as a Barrier to Seeking and Receiving Treatment

Despite advances in the scientific understanding of alcoholism, the stigma surrounding this disease is still pervasive; these misperceptions may prevent people from seeking and receiving treatment. The vast majority of those surveyed (91% of primary care physicians, 89% of people in alcohol addiction recovery, and 80% of the general public) say that there is a stigma toward alcoholics. That stigma extends to people in recovery. About three quarters (73%) of primary care physicians and individuals in recovery (71%) believe that there is a stigma toward alcoholics in recovery, compared with 51% in the general public survey sample. As a side comparison, when an obese person is losing weight, it is often viewed in a positive light — not so for recovering alcoholics. In all 3 survey populations, denial or refusal to admit severity of the problem and fear of social embarrassment were the top 2 reasons for not seeking help with alcohol addiction (Table 4). In the general public, 66% believe that social embarrassment and fear of discrimination are major barriers to treatment for people with alcohol addiction. The majority of the general public (63%) believes that alcoholism is caused, at least in part, by moral weakness, compared with 43% of physicians and 11% of individuals in recovery.

Obstacles to Screening for Alcoholism

About 50% of the physicians who were surveyed reported asking about drinking habits during routine patient office visits half the time or less. The reasons cited as to why patients are not asked about their drinking habits more often are inadequate resources (48%), denial of any problem with alcohol (41%), and lack of expertise (24%). Forty-nine percent of the primary care physicians reported that they would refer a patient with alcohol addiction to a treatment facility, counselor, another physician, or addiction specialist. Another 20% would refer a patient to support groups, and 13% would recommend a combination of medication and counseling. The survey also revealed opportunities for physicians to drive treatment:

Attitudes on Treatment Medications

The survey revealed that most Americans are open to medications to treat alcoholism. The general public and people in recovery would recommend medications for themselves or their loved ones:

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2. February 2012 by stationmanager.

Teenage drinking and cigarette smoking is at a historic low, but marijuana use and prescription drug abuse continue at high rates, according to a new report looking at trends among teens.

And there’s a new substance raising concerns.

For the first time the study looked at the use of synthetic marijuana, also known as Spice or K2, by 12th graders. More than 11% admitted using it over the last year, information Gil Kerlikoeske, Director of the White House Office of National Drug Control Policy (ONDCP), calls shocking.

“One in nine 12th graders in America have used synthetic marijuana in the last year. Spice and K2 now rank as the second most frequently used illegal drug among high school seniors, second only to marijuana,” Kerlikowske said. “Make no mistake. These drugs are dangerous and can cause serious harm. Poison control center data across America have shown as substantial rise in the number of calls from victims suffering serious consequences from these synthetic drugs.”

ONDCP says poison control centers have fielded nearly 6,000 calls so far this year - already double last year’s number.

According to Kerlikowske, up until a few months ago synthetic marijuana was being sold legally as an alternative to marijuana in convenience stores across the country. That’s when the Drug Enforcement Administration banned the sale of the chemicals used to make it.

Now, he’s calling on parents to talk to their kids about the serious consequences of marijuana, K2 and Spice use.

“We must be clear with our young people,” says Kerlikowske. “Smoked marijuana is not an FDA approved medicine and the National Institute of Health has long documented the harms of marijuana use. Science shows it is addictive. Research shows it impairs driving. Studies show it can degrade academic performance.”

Kerlikowske says ONDCP is working on a federal response to Spice/K2 that includes working with public health agencies to share data and coordinate a response. They are also working with Congress to get new laws passed that will ban these drugs.

The Monitoring the Future (MTF) survey has been tracking students from secondary school to young adults for nearly four decades, measuring their drug, alcohol and cigarette use. Each year the study chronicles the behaviors and attitudes of nearly 50,000 8th, 10th and 12th graders.

Researchers say the drop in alcohol and cigarette use has occurred gradually for a number of years.

“That cigarette use has continued to decline to historically low rates is welcome news given our concerns that decline may have slowed or stalled in recent years,” said NIDA Director Dr. Nora Volkow, Director, National Institute on Drug Abuse who funded the study. “Tobacco and alcohol cause more disability and death in this country than any other drug , so we are heartened that efforts made by the public health community to educate teens and prevent drug abuse seem to be having an impact.”

Fourteen years ago about 75% of 12th-graders admitted drinking alcohol. In 2011, 63.5% say they did. This year almost 27% of eighth-graders surveyed used alcohol compared to approximately 47% in 1994. Over the last 5 years, binge drinking - defined as having five or more drinks in a row over a two-week period - fell among all three grades.

Teen smoking fell in all three grades as well. A little more than 10% of 12th graders say they smoke daily - down significantly from 24.6% in 1997; while just 2.4% of 8th graders reported smoking every day.

“This is very good news for the health and longevity of these young people,” states Lloyd Johnston, research scientist at the University of Michigan and the principal investigator of the study. “Even a reduction of only one percentage point can translate into thousands of premature deaths being prevented.”

Teen smoking peaked in 1996-1997. Since then, the levels have dropped significantly - 71% for 8th graders, 61% in 10th graders and 49% in seniors. In fact, the number of students who have tried smoking at all fell dramatically.

Marijuana use, on the other hand, continues to rise at a steady pace, researchers found. More than 36% of seniors reported using the drug over the past year; almost 7% say they use it daily. Researchers say the rise in use is tied to the perception that the drug is not harmful.

The study also tracked prescription drug trends. Use of the painkiller Vicodin dropped among sophomores, and remained unchanged - but at levels considered high - among seniors.

Researchers say the fact that OxyContin use has remained steady for all three grades over the last five years is cause for concern. Another cause for alarm - amphetamine use is up among high school seniors. They saw no change in the use of Adderall and Ritalin, both ADHD medications, over the last year. But they did see a considerable drop in the number of 8th graders abusing over-the-counter cough medication.

The study was funded by the National Institute on Drug Abuse, part of the National Institutes of Health. Volkow says the institute is launching an updated prescription drug section on their teen website in an effort to educate teenagers about the dangers of prescription drug abuse.

“Teens can go to our PEERx pages to find interactive videos and other tools that help them make healthy decisions and understand the risks of abusing prescription drugs.”

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