Addiction & Substance Abuse News & Resources

Heavy Drinking And Smoking May Cause ‘Early Aging’ Of The Brain

Addiction News | 23 May 2013

Multiple factors can influence both the type and degree of neurocognitive abnormalities found during early abstinence, including chronic cigarette smoking and increasing age. A new study is the first to look at the interactive effects of smoking status and age on neurocognition in treatment-seeking alcohol dependent (AD) individuals. Findings show that AD individuals who currently smoke show more problems with memory, ability to think quickly and efficiently, and problem-solving skills than those who don’t smoke, effects which seem to become exacerbated with age.

Results will be published in the October 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“Several factors – nutrition, exercise, comorbid medical conditions such as hypertension and diabetes, psychiatric conditions such as depressive disorders and post-traumatic stress disorder, and genetic predispositions – may also influence cognitive functioning during early abstinence,” explained Timothy C. Durazzo, assistant professor in the department of radiology and biomedical imaging at the University of California San Francisco, and corresponding author for the study. “We focused on the effects of chronic cigarette smoking and increasing age on cognition because previous research suggested that each has independent, adverse effects on multiple aspects of cognition and brain biology in people with and without alcohol use disorders. This previous research also indicated that the adverse effects of smoking on the brain accumulate over time. Therefore, we predicted that AD, active chronic smokers would show the greatest decline in cognitive abilities with increasing age.”

“The independent and interactive effects of smoking and other drug use on cognitive functioning among individuals with AD are largely unknown,” added Alecia Dager, associate research scientist in the department of psychiatry at Yale University. “This is problematic because many heavy drinkers also smoke. Furthermore, in treatment programs for alcoholism, the issue of smoking may be largely ignored. This study provides evidence of greater cognitive difficulties in alcoholics who also smoke, which could offer important insights for treatment programs. First, individuals with AD who also smoke may have more difficulty remembering, integrating, and implementing treatment strategies. Second, there are clear benefits for thinking skills as a result of quitting both substances.”

Durazzo and his colleagues compared the neurocognitive functioning of four groups of participants, all between the ages of 26 and 71 years of age: never-smoking healthy individuals or “controls” (n=39); and one-month abstinent, treatment-seeking AD individuals, who were never-smokers (n = 30), former-smokers (n = 21) and active-smokers (n = 68). Evaluated cognitive abilities included cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions, and working memory.

“We found that, at one month of abstinence, actively smoking AD [individuals] had greater-than-normal age effects on measures of learning, memory, processing speed, reasoning and problem-solving, and fine motor skills,” said Durazzo. “AD never-smokers and former-smokers showed equivalent changes on all measures with increasing age as the never-smoking controls. These results indicate the combination of alcohol dependence and active chronic smoking was related to an abnormal decline in multiple cognitive functions with increasing age.”

“These results indicate the combined effects of these drugs are especially harmful and become even more apparent in older age,” said Dager. “In general, people show cognitive decline in older age. However, it seems that years of combined alcohol and cigarette use exacerbate this process, contributing to an even greater decline in thinking skills in later years.”

Durazzo agreed. “Chronic cigarette smoking, excessive alcohol consumption, and increasing age are all associated with increased oxidative damage to brain tissue,” he said. “Oxidative damage results from increased levels of free radicals and other compounds that directly injure neurons and other cells that make up the brain. Cigarette smoking and excessive alcohol consumption expose the brain to a tremendous amount of free radicals. We hypothesize that chronic, long-term exposure to cigarette smoke and excessive alcohol consumption interacts with the normal aging process to produce greater neurocognitive decline in the active-smoking AD group.”

Cigarette smoking is a “modifiable health risk” that is directly associated with at least 440,000 deaths every year in the United States, Durazzo noted. “Chronic smoking, and to a lesser extent, alcohol use disorders are also associated with an increased risk for Alzheimer’s disease,” he said. “So, the combination of these modifiable health risks may place an individual at even greater risk for development of Alzheimer’s disease. Given the above, in conjunction with the findings from our cognitive and neuroimaging research, we completely support programs that routinely offer smoking cessation programs to all individuals seeking treatment for alcohol/substance abuse disorders.”

Brain Scans Help Determine Relapse Risk in Alcoholics

Addiction News | 10 May 2013

Even the most experienced counselors have difficultly spotting a recovering alcoholic in danger of relapse. Brain imaging scans might do a better job, new Yale research suggests.

Alcoholics with abnormal activity in areas of the brain that control emotions and desires are eight times more likely to relapse and drink heavily than alcoholics with more normal patterns of activity or healthy individuals, according to the study published May 1 in the journal JAMA Psychiatry.

“These areas in the prefrontal cortex are involved in regulating emotion and in controlling responses to reward,” said Rajita Sinha, the Foundations Fund Professor of Psychiatry and professor in the Child Study Center and of Department of Neurobiology. “They are damaged by high levels of alcohol and stress and just do not function well.”

Ironically, the damage shows up on fMRI scans when alcoholics imagine being in their own most relaxing scenarios, like sitting at the beach listening to the waves, or taking a bubble bath. In non-alcoholics, these brain regions regulating emotion show markedly reduced activity during relaxing imagery, as anticipated. However, in alcoholics most likely to relapse, those brain regions remain hyperactive. On the other hand, when recovering alcoholics imagine their own recent stressful events, these control regions of the brain show little change, while in non-alcoholics, they show marked activation in response to stress. Such disrupted responses in areas of the brain governing emotions and reward lead to high cravings in the recovering alcoholic and an increased likelihood of subsequent relapse.

These brain scans in the future might serve as a diagnostic test to help professionals identify those most at risk of relapsing and suggest specific interventions to normalize brain function and prevent high rates of alcohol relapse, Sinha said.

“The findings show the prefrontal region is important for maintaining recovery for alcoholism,” Sinha said. “The brain physiology and function has changed due to chronic alcohol use and such changes jeopardize recovery even after initiating standard treatment.”

The research is funded by the National Institute of Alcohol Abuse and Alcoholism at the National Institutes of Health.

Dongju Seo of Yale is first author of the study. Other Yale authors include Cheryl M. Lacadie, Keri Tuit, Adam K. Hong and R. Todd Constable.

Researchers Identify One of Alcohol’s Key Gateways to the Brain

Addiction News | 03 May 2013

Thanks to a rare bacteria that grows only on rocks in the Swiss Alps, researchers at The University of Texas at Austin and the Pasteur Institute in France have been the first to identify how alcohol might affect key brain proteins.

It’s a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain.

“Now that we’ve identified this key brain protein and understand its structure, it’s possible to imagine developing a drug that could block the binding site,” said Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin.

Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper that was recently published in Nature Communications. It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol.

Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol. Researchers couldn’t prove it, however, because they couldn’t crystallize the brain protein well enough, and therefore couldn’t use X-ray crystallography to determine the structure of the protein with and without alcohol present.

“For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography,” said Harris. “But it hasn’t been possible because it is not possible to get a nice crystal.”

The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus. They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch.

“This is something you never would have found with any sort of logical approach,” he said. “You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur’s fascination with bacteria, has this huge collection of obscure bacteria, and over the last few years they’ve been sequencing the genomes, keeping an eye out for interesting properties.”

Harris and Howard asked their French colleagues to collaborate, got the cyanobacteria, changed one amino acid to make it sensitive to alcohol, and then crystallized both the original bacteria and the mutated one. They compared the two to see whether they could identify where the alcohol bound to the mutant. With further tests they confirmed that it was a meaningful site.

“Everything validated that the cavity in which the alcohol bound is important,” said Harris. “It doesn’t account for all the things that alcohol does, but it appears to be important for a lot of them, including some of the ‘rewarding’ effects and some of the negative, aversive effects.”

Going forward, Harris and his lab plan to use mice to observe how changes to the key protein affect behavior when the mice consume alcohol.

They’re also hoping to identify other important proteins from this family of ligand-gated ion channels. In the long term, he hopes to be involved in developing drugs that act on these proteins in ways that help people diminish or cease their drinking.

“So why do some people drink moderately and some excessively?” he said. “One reason lies in that the balance between the rewarding and the aversive effects, and that balance is different for different people, and it can change within an individual depending on their drinking patterns. Some of those effects are determined by the interactions of alcohol and these channels, so the hope is that we can alter the balance. Maybe we can diminish the reward or increase the aversive effects.”

Even A Drink a Day Raises Cancer Risk

Addiction News | 24 April 2013

How many of us enjoy a glass or two of wine at dinner? How many of us have read that moderate drinking of red wine is good for the heart? How many of us know that even moderate drinking might increase our cancer risk?

That eye-catching news turned a few media heads after a recent study was published in the American Journal of Public Health. The authors, including Timothy Naimi, a School of Medicine and School of Public Health associate professor, attribute 6,000 American deaths annually to cancer from moderate drinking, which they define as a drink and a half per day or less. Add in alcohol consumption at all levels and the total surges to 20,000 cancer deaths a year, according to the study. (For perspective, that 20,000 figure represents 3.5 percent of all cancer deaths in the country.)

For men, lethal alcohol-caused cancer typically afflicts the mouth, throat, and esophagus, the researchers say. In women, breast cancer is the most common cancer killer linked to alcohol consumption.

The researchers synthesized risk estimates from hundreds of other studies to come up with their findings. Naimi believes the big takeaway is the total number of deaths, the role of excessive drinking, and the fact that these deaths are preventable. But as everyone knows that drinking to excess is bad for a host of reasons, he understands the headlines generated by the findings on moderate drinking.

Evidence of excessive drinking’s role in cancer is much greater than that for the role of modest drinking, says Naimi, an alcohol epidemiologist specializing in binge and youth drinking and alcohol policy. The idea that limited drinking causes cancer “should be interpreted with caution.…I have nothing against alcohol. My background is as a physician, and my interest is in seeing harm from alcohol minimized.”

But some doctors say the moderate drinking findings need to be taken seriously, and Naimi says there is evidence from the literature he and his team reviewed supporting their concerns. And, he adds, deaths from alcohol “dwarf any small number of people who may derive benefit from low-dose alcohol.” Indeed, among all people who start drinking, 5 to 10 times as many die from it as are benefited by it, according to Naimi, who notes that you can’t predict when people begin drinking whether they’ll wind up an alcoholic: “You don’t know prospectively who’s going to end up as a moderate drinker.”

Nor is he convinced by studies showing heart benefits from moderate drinking. For one thing, he says, those studies have never included the accepted standard in scientific research: a randomized, controlled study comparing moderate drinkers with teetotalers. Also, moderate drinkers tend to come from higher on the socioeconomic ladder, a rung at which people tend to be healthier. In other words, moderate drinking may be “a reflection of people’s social position and good health. It’s not its genesis,” Naimi says.

Studies linking alcohol to cancer are based on calculations using three types of data, he says: the numbers of people who drink at different levels, the prevalence of various cancers at those various drinking levels, and the number of cancer deaths among people at each level. The American Cancer Society lays out the cancers for which the evidence of an alcohol link is strongest, while adding that the precise mechanism for how drinking leads to the disease is not certain.

As for the argument that there’s a certain risk with much of the food we consume—nonorganic fruits and vegetables marinated in pesticides, for example, or brown rice, once thought to be healthy, but now found to contain risky levels of arsenic–Naimi replies, “Alcohol is not a food. Alcohol is a drug,” and one with so-called empty calories that lack nutritional value.

“I wouldn’t put alcohol on a par with fruits and vegetables,” he says—especially as fruits and vegetables won’t kill you the way drunk driving can.

Genetics Determine Severity of Cigarette Addiction

Addiction News | 09 April 2013

Researchers have identified genetic risk factors that may accelerate a teen's progression to becoming a lifelong heavy smoker. 

The team of scientists from the U.S., the U.K. and New Zealand examined earlier studies by other research teams to develop a genetic risk profile for heavy smoking. Then they looked at their own long-term study of 1,000 New Zealanders from birth to age 38 to identify whether individuals at high genetic risk got hooked on cigarettes more quickly as teens and whether, as adults, they had a harder time quitting. 

Study participants who had the high-risk genetic profile were found to be more likely to convert to daily smoking as teenagers and then progress more rapidly to heavy smoking (a pack a day or more).  When assessed at age 38, the higher-risk individuals had smoked heavily for more years, had more often developed nicotine dependence and were more likely to have failed in attempts to quit smoking.

"Genetic risk accelerated the development of smoking behavior," said Daniel Belsky, a post-doctoral research fellow at Duke University's Center for the Study of Aging and Human Development and the Duke Institute for Genome Sciences & Policy. "Teens at a high genetic risk transitioned quickly from trying cigarettes to becoming regular, heavy smokers." 

A person's genetic risk profile did not predict whether he or she would try cigarettes. But for those who did try cigarettes, having a high-risk genetic profile predicted increased likelihood of heavy smoking and nicotine dependence.

The findings appear March 27 in JAMA Psychiatry. They were supported by multiple grants from the U.S. National Institutes of Health, as well as the U.K. Medical Research Council and the New Zealand Health Research Council.

The Duke researchers developed a new "genetic risk score" for the study by examining prior genome-wide associations (GWAS) of adult smokers. These studies scanned the entire genomes of tens of thousands of smokers to identify variants that were more common in the heaviest smokers. The variants they identified were located in and around genes that affect how the brain responds to nicotine and how nicotine is metabolized, but it is not yet known how the specific variants affect gene function.

It makes sense that the genes on which the group based their risk score are involved in nicotine metabolism and sensitivity, said Jed Rose, a Duke nicotine addiction researcher who was not involved in this study. "Addictions are a learned behavior and it requires reinforcement through neural pathways." 

In their first step, the researchers found the genetic risk score they developed was able to predict heavy smoking among individuals in two large databases created by other researchers. 

Then they turned to their New Zealand sample of 880 individuals of European descent to see whether the genetic risk score predicted who initiated smoking, who progressed to heavy smoking, and who developed nicotine dependence and experienced relapse after quitting. 

Genetic risk was not related to whether a person tried smoking, which 70 percent of the sample had. One reason for this was that so-called "chippers" -- smokers who consume cigarettes only on weekends or smoke only one or two per day -- had even lower genetic risk than nonsmokers.

Genetic risk was related to the development of smoking problems. Among teens who tried cigarettes, those with a high-risk genetic profile were 24 percent more likely to become daily smokers by age 15 and 43 percent more likely to become pack-a-day smokers by age 18. 

As adults, those with high-risk genetic profiles were 27 percent more likely to become nicotine dependent and 22 percent more likely to fail in their attempts at quitting. By age 38, a study participant with high-risk genetic profile had smoked about 7,300 more cigarettes (one "pack-year") than the average smoker. 

Study participants who did not become regular, heavy smokers during their teens appeared to be "immune" to genetic risk for adult smoking problems. "The effects of genetic risk seem to be limited to people who start smoking as teens," said Belsky. "This suggests there may be something special about nicotine exposure in the adolescent brain, with respect to these genetic variants."  

"Adolescence is indeed a period of high risk for nicotine addiction," said Denise Kandel, a professor of sociomedical sciences in psychiatry at Columbia University, who was not involved in this study. "The results illustrate why adolescence is of crucial importance for the development and targeting of prevention and intervention efforts. How this genetic risk affects brain functions, which in turn affect reactions to nicotine, remains to be determined."

The risk factor the team developed "may not be sensitive or specific enough to be a clinical test, but it may have public health uses," said Rose, who is the director of the Duke Center for Smoking Cessation and co-developer of the nicotine patch.

"Public health policies that make it harder for teens to become regular smokers should continue to be a focus in antismoking efforts," Belsky said.

Laser Light Zaps Away Cocaine Addiction

Addiction News | 05 April 2013

By stimulating one part of the brain with laser light, researchers at the National Institutes of Health (NIH) and the Ernest Gallo Clinic and Research Center at UC San Francisco (UCSF) have shown that they can wipe away addictive behavior in rats – or conversely turn non-addicted rats into compulsive cocaine seekers.

“When we turn on a laser light in the prelimbic region of the prefrontal cortex, the compulsive cocaine seeking is gone,” said Antonello Bonci, MD, scientific director of the intramural research program at the NIH’s National Institute on Drug Abuse (NIDA), where the work was done. Bonci is also an adjunct professor of neurology at UCSF and an adjunct professor at Johns Hopkins University.

Described this week in the journal Nature, the new study demonstrates the central role the prefrontal cortex plays in compulsive cocaine addiction. It also suggests a new therapy that could be tested immediately in humans, said Billy Chen of NIDA, the lead author of the study.

Any new human therapy would not be based on using lasers, but would most likely rely on electromagnetic stimulation outside the scalp, in particular a technique called transcranial magnetic stimulation (TMS). Clinical trials are now being designed to test whether this approach works, Chen added.

The High Cost of Cocaine Abuse

Cocaine abuse is a major public health problem in the United States today, and it places a heavy toll on society in terms of lost job productivity, lost earnings, cocaine-related crime, incarcerations, investigations, and treatment and prevention programs.

The human toll is even greater, with an estimated 1.4 million Americans addicted to the drug. It is frequently the cause of emergency room visits – 482,188 in 2008 alone – and it is a top cause of heart attacks and strokes for people under 35.

One of the hallmarks of cocaine addiction is compulsive drug taking – the loss of ability to refrain from taking the drug even if it’s destroying one’s life.

What makes the new work so promising, said Bonci, is that Chen and his colleagues were working with an animal model that mimics this sort of compulsive cocaine addiction. The animals, like human addicts, are more likely to make bad decisions and take cocaine even when they are conditioned to expect self-harm associated with it.

Electrophysiological studies involving these rats have shown that they have extremely low activity in the prefrontal cortex – a brain region fundamental for impulse control, decision making and behavioral flexibility. Similar studies that imaged the brains of humans have shown the same pattern of low activity in this region in people who are compulsively addicted to cocaine.

Altering Brain Activity with a Laser

To test whether altering the activity in this brain region could impact addiction, Chen and his colleagues employed a technique called optogenetics to shut the activity on and off using a laser.

First they took light-sensitive proteins called rhodopsins and used genetic engineering to insert them into neurons in the rat’s prefrontal cortex. Activating this region with a laser tuned to the rhodopsins turned the nerve cells on and off.

Turning on these cells wiped out the compulsive behavior, while switching them off turned the non-addicted ones into addicted, researchers found.

What’s exciting, said Bonci, is that there is a way to induce a similar activation of the prelimbic cortex in people through a technique called transcranial magnetic stimulation (TMS), which applies an external electromagnetic field to the brain and has been used as a treatment for symptoms of depression.

Bonci and his colleagues plan to begin clinical trials at NIH in which they will use this technique a few sessions a week to stimulate the prefrontal cortex in people who are addicted to cocaine and see if they can restore activity to that part of the brain and help them avoid taking the drug.

The article, “Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking” is authored by Billy T. Chen, Hau-Jie Yau, Christina Hatch, Ikue Kusumoto-Yoshida, Saemi L. Cho, F. Woodward Hopf and Antonello Bonci. It was published online by the journal Nature on April 3, 2013.

In addition to UCSF, the authors of this study are affiliated with the National Institute on Drug Abuse, the Ernest Gallo Clinic and Research Center and the Solomon H. Snyder Neuroscience Institute, Johns Hopkins School of Medicine. This work was funded by the National Institute on Drug Abuse.

Panel backs approval of implants for addiction treatment

Addiction News | 26 March 2013

A four-rod subdermal implant that slowly releases buprenorphine over 6 months should be approved for maintenance treatment of opioid dependence, although more work is needed to determine optimal dosing strategies and how to address the potential risks of the treatment, the majority of a Food and Drug Administration advisory panel recommended.

At a meeting on March 21, the FDA’s Psychopharmacologic Drugs Advisory Committee voted 10-4, with 1 abstention, to recommend approval, based on the efficacy, safety, and risk-benefit profile in opioid-addicted adults treated with the implants, in two phase III placebo-controlled studies. In those studies, the mean proportion of negative urine tests over 24 weeks, the primary endpoint, was significantly higher among those who received the buprenorphine implant, compared with those who had a placebo implant.

The panel agreed the treatment had a beneficial effect on reducing illicit opioid use, but those voting on both sides pointed out that more information on dosing was needed. The product is indicated for patients who are maintained on 12 mg-16 mg of oral buprenorphine a day. But as addiction treatment specialists on the panel pointed out, some patients are maintained on lower oral doses, and there were no data on how to use the product in such patients. The manufacturer, Titan Pharmaceuticals, plans to study that issue further.

The panel also voted 12-2 with 1 abstention, that the company had adequately characterized the safety profile of treatment with the buprenorphine implants, which was associated with the known side effects of the oral formulation in the trials. But there are also the potential complications associated with surgical implantation and removal of the rods every 6 months, as well as the potential for abuse, misuse and diversion, and accidental exposure, which is addressed in a complex risk management program proposed by the manufacturer.

Using similar technology as contraceptive implants, the product consists of four rods, each measuring 26 mm by 2.5 mm and containing 80 mg of the buprenorphine, a partial mu-opioid receptor agonist that has been available in oral formulations since 2002 for the treatment of opioid dependence. The rods are subdermally implanted in the upper arm with a single-use application by a trained health care provider in an office-based surgical procedure with local anesthesia after the patient has been titrated with an oral dose. The rods stay in place for up to 6 months, at which time they are removed and replaced at another site.

"Clearly, the data need to be further assessed and the safety and dosing improved upon," said Dr. Christopher J. Kratochvil, professor of psychiatry and pediatrics, University of Nebraska, Omaha. But he voted in favor of approval, commenting, "This is will at least be an incremental step forward for a disorder that has very tragic consequences."

"Overall, I thought that benefit was shown and there might be a particular subset of patients who respond best to this intervention," said one of the two panelists with expertise on contraceptive implants, Dr. Geri D. Hewitt, an obstetrician-gynecologist at Ohio State University, Columbus, who voted for approval. "I did not see any evidence of significant harm; I do have questions about dosing and which physicians will be willing to place this and ... it’s going to be important to keep track of adverse event reporting," she added.

Voting against approval, Dr.. Laura F. McNicholas of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia, said she thought the product was approvable, but that approval before a dose-ranging study was conducted would be premature. A major concern she had was running out of sites to implant the rods for patients on long-term treatment, since many of her patients have been taking buprenorphine continuously for years. Many of her patients also are on doses under 12 mg a day, and there was no information on how to dose such patients with the implant, for which there is currently only one dose, she added.

So far, the company has identified four sites on the upper arms as appropriate for implantation and is studying this further.

The two studies enrolled 450 adults (mean age, mid-30s) addicted to an opioid, randomized to treatment with the buprenorphine implant or a placebo implant. The most common drug of abuse was heroin in 52% to 67%, followed by prescription analgesics in 33% to 48%.Over 24 weeks, the mean percentage of opioid-negative urine samples was statistically significantly greater among those who were treated with the buprenorphine implant (about 40% and about 35% among those who received the active drug vs. about 30% and 15%, respectively, among those on the placebo implant.)

About 80% of the patients were adequately treated with four implants, but in some patients, a fifth rod or supplemental treatment with sublingual buprenorphine was needed. Completion rates were lower among those on placebo (31% and 26%, vs. 64% and 66%, respectively). In the two studies, the most common implant site–related adverse events included pruritus, pain, erythema, edema, and hematoma.

The company’s Risk Evaluation and Mitigation Strategy (REMS) includes plans for restricted distribution, a specialty pharmacy only, and a training-certification program for health care providers who implant the rods. (The FDA requires a REMS for a drug when it determines that a risk management strategies beyond the label are needed to ensure the benefits of a drug outweigh its risks.) Both the panel and the FDA reviewers said the REMS needs to be improved.

When asked about the panel’s recommendation, Dr. Robert L DuPont said in an interview that it is a major development in medication-assisted treatment of opiate dependence in light of problems with diversion and nonmedical use of buprenorphine. "This novel dosing strategy removes the risk of diversion in a large population of drug abusing patients that poses a high risk of diversion and misuse," said Dr. DuPont, the first director of the National Institute on Drug Abuse.

"The development of abuse-resistant formulations of controlled substances is one of the best new ideas to turn back the major epidemic of prescription drug abuse."

If approved, the panel recommended that other potential problems with the device should be monitored closely, including removal of implants by nonmedical personnel for diversion (which was not seen in the studies) and the risk of long-term exposure to the components if they are not removed. The panel urged study of whether implants can be inserted in previous implant sites.

Buprenorphine can be administered in an office setting as opposed to a methadone clinic. The currently marketed buprenorphine products are Subutex and Suboxone (buprenorphine with naloxone), both available in generic formulations; and a sublingual formulation approved in 2010. In 2012, 10.7 million prescriptions were dispensed for buprenorphine products for an estimated 1 million patients, mostly the buprenorphine/naloxone combination, according to the FDA. Between January 2003 and December 2012, an estimated 40 million buprenorphine prescriptions were written. The top three categories of prescribers were general practitioners/family physicians/doctors of osteopathy (one category), psychiatrists, and internists.

If approved, the manufacturer plans to market it as Probuphine. The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist might be given a waiver, but not at this meeting.

Discovery Could Yield Treatments For Cocaine Addicts

Addiction News | 20 March 2013

Scientists have found a molecular chain reaction in the brain triggered by cocaine, and say that interrupting this process could provide treatment for addiction. Researchers say cocaine alters the nucleus accumbens, the brain’s pleasure center that responds to stimuli such as food, sex, and drugs.

“Understanding what happens molecularly to this brain region during long-term exposure to drugs might give us insight into how addiction occurs,” says A. J. Robison, assistant professor in the department of physiology and the neuroscience program at Michigan State University.

The researchers found that cocaine causes cells in the nucleus accumbens to boost production of two proteins, one associated with addiction and the other related to learning. The proteins have a reciprocal relationship—they increase each other’s production and stability in the cells—so the result is a snowball effect that Robison calls a feed-forward loop.

In their research published in the Journal of Neuroscience, Robison and colleagues demonstrated that loop’s essential role in cocaine responses by manipulating the process in rodents.

They found that raising production of the protein linked to addiction made animals behave as if they were exposed to cocaine even when they weren’t. They also were able to break the loop, disrupting rodents’ response to cocaine by preventing the function of the learning protein.

“At every level that we study, interrupting this loop disrupts the process that seems to occur with long-term exposure to drugs,” says Robison.

Robison says the study also found signs of the same feed-forward loop in the brains of people who died while addicted to cocaine.

“The increased production of these proteins that we found in the animals exposed to drugs was exactly paralleled in a population of human cocaine addicts,” he says. “That makes us believe that the further experiments and manipulations we did in the animals are directly relevant to humans.”

Robison says the growing understanding of addiction at the molecular level could help pave the way for new treatments for addicts.

“This sort of molecular pathway could be interrupted using genetic medicine, which is what we did with the mice,” he says. “Many researchers think that is the future of medicine.”

Alcohol the Third Leading Cause of global disease and injury

Addiction News | 07 March 2013

A new study by the Centre for Addiction and Mental Health (CAMH) shows that alcohol is now the third leading cause of the global burden of disease and injury, despite the fact most adults worldwide abstain from drinking.

This research, part of the 2010 Global Burden of Disease study, was published in this month’s issue of the journal Addiction. 

“Alcohol consumption has been found to cause more than 200 different diseases and injuries,” said Kevin Shield, the lead author of the study. “These include not only well-known outcomes of drinking such as liver cirrhosis or traffic accidents, but also several types of cancer, such as female breast cancer.”

The study reports the amount and patterns of alcohol consumption by country for 2005, and calculates estimates for these figures for 2010. It reveals vast differences by geographical region in the numbers of people who consume alcohol, the amount they drink, and general patterns of drinking. Some other findings:

*Drinkers in Europe and parts of Sub-Saharan Africa are some of the world’s heaviest consumers of alcohol, on average.

*People in Eastern Europe and Southern Sub-Saharan Africa consumed alcohol in the unhealthiest manner, as they frequently consumed large quantities, drank to intoxication, engaged in prolonged binges, and consumed alcohol mainly outside of meals.

*People in North Africa, the Middle East and South Asia consumed the least amount of alcohol.

*North Americans in general, and Canadians in particular drink more than 50 per cent above the global average, and show a more detrimental drinking pattern than most EU countries, with more bingeing.

*The global burden of disease and injury attributable to alcohol is large and growing. In 2010, it was responsible for 5.5 per cent of this overall burden, third after high blood pressure and tobacco smoking, among 67 risk factors overall.

This study summarizes the results from population surveys, sales or production data, and data on alcohol consumption not covered in official records, from all countries, territories and regions.

Researchers also found that almost 30 per cent of alcohol consumed in 2005 was “unrecorded” alcohol – referring to alcohol not intended for consumption, home-brewed alcohol, and illegally produced alcohol. In some regions, unrecorded alcohol constituted more than half of all alcohol consumed.

“The amount of unrecorded alcohol consumed is a particular problem, as its consumption is not impacted by public health alcohol policies, such as taxation, which can moderate consumption,” said Dr. Jürgen Rehm, a study author and director of CAMH’s Social and Epidemiological Research Department.

“Improving alcohol control policies presents one of the greatest opportunities to prevent much of the health burden caused by alcohol consumption,” said Dr. Shield “To improve these policies, information on how much alcohol people are consuming, and how people are consuming alcohol is necessary, and that is exactly the information this article presents.”

Study Shows Alcohol Consumption Is a Leading Preventable Cause of Cancer Death in the U.S.

Addiction News | 19 February 2013

Researchers from the Boston University School of Medicine (BUSM) and Boston University School of Public Health (BUSPH) have shown that alcohol is a major contributor to cancer deaths and years of potential life lost. These findings, published in the April 2013 issue of the American Journal of Public Health, also show that reducing alcohol consumption is an important cancer prevention strategy as alcohol is a known carcinogen even when consumed in small quantities.

Previous studies consistently have shown that alcohol consumption is a significant risk factor for cancers of the mouth, throat, esophagus and liver. More recent research has shown that alcohol also increases the risk of cancers of the colon, rectum and female breast. While estimates have shown that alcohol accounts for about four percent of all cancer-related deaths worldwide, there is a lack of literature focusing on cancer-related deaths in the U.S.

Timothy Naimi, MD, MPH, from the Department of Medicine at BUSM and colleagues from the National Cancer Institute, the Alcohol Research Group, Public Health Institute and the Centre for Addiction and Mental Health, examined recent data from the U.S. on alcohol consumption and cancer mortality. They found that alcohol resulted in approximately 20,000 cancer deaths annually, accounting for about 3.5 percent of all cancer deaths in the U.S.

Breast cancer was the most common cause of alcohol-attributable cancer deaths in women, accounting for approximately 6,000 deaths annually, or about 15 percent of all breast cancer deaths. Cancers of the mouth, throat and esophagus were common causes of alcohol-attributable cancer mortality in men, resulting in a total of about 6,000 annual deaths.

The researchers also found that each alcohol-related cancer death accounted for an average of 18 years of potential life lost. In addition, although higher levels of alcohol consumption led to a higher cancer risk, average consumption of 1.5 drinks per day or less accounted for 30 percent of all alcohol-attributable cancer deaths.

“The relationship between alcohol and cancer is strong, but is not widely appreciated by the public and remains underemphasized even by physicians,” said Naimi, who served as the paper’s senior author. “Alcohol is a big preventable cancer risk factor that has been hiding in plain sight.”