The Athlete's Way

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Hyperactive Dopamine Response Linked to Alcoholism

People energized by alcohol are genetically predisposed to drink more heavily.

Does drinking alcohol make you more energized or sedated? Do you feel more talkative and social when you drink or does it make you sleepy? A study released on August 2, 2013 found that those who are energized by alcohol have a hyperactive dopamine response to alcohol and are genetically predisposed to drink more heavily.

A new study from McGill University suggests that people who are at risk for becoming alcoholics have a distinctive brain response when drinking alcohol in comparison to those at low risk for alcohol-use problems. People at high risk showed a greater dopamine response in a brain pathway that increases desire for rewards according to lead author of the study Professor Marco Leyton, of McGill University's Department of Psychiatry.

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These recent findings, published in the journal Alcoholism: Clinical & Experimental Research, could help shed light on why some people are more at risk of suffering from alcoholism and could mark an important step toward the development of treatment options.

According to the CDC there are approximately 80,000 deaths linked to excessive alcohol use every year in the United States. This makes excessive alcohol use the 3rd leading lifestyle-related cause of death for the nation. Excessive alcohol use is responsible for 2.3 million years of potential life lost (YPLL) annually, or an average of about 30 years of potential life lost for each death. In 2006, there were more than 1.2 million emergency room visits and 2.7 million physician office visits due to excessive drinking. The economic costs of excessive alcohol consumption in 2006 were estimated at $223.5 billion.

"There is accumulating evidence that there are multiple pathways to alcoholism, each associated with a distinct set of personality traits and neurobiological features," said Leyton. "These individual differences likely influence a wide range of behaviors, both positive and problematic. Our study suggests that a tendency to experience a large dopamine response when drinking alcohol might contribute to one (or more) of these pathways."

For the McGill study, researchers recruited 26 healthy social drinkers (18 men, 8 women), 18 to 30 years of age. The higher-risk subjects were then identified based on personality traits and having a higher tolerance to alcohol (they did not feel as drunk despite having drunk the same amount). Finally, each participant underwent two positron emission tomography (PET) brain scan exams after drinking either juice or alcohol (about 3 drinks in 15 minutes).

"We found that people vulnerable to developing alcoholism experienced an unusually large brain dopamine response when they took a drink," said Leyton. "This large response might energize reward-seeking behaviors and counteract the sedative effects of alcohol. Conversely, people who experience minimal dopamine release when they drink might find the sedative effects of alcohol especially pronounced."

The Genetic Roots of Alcoholism

study from December 2012 (also published in Alcoholism: Clinical & Experimental Research) expanded on previous research that found the OPRM1 genotype moderates the pleasant and stimulating effects to alcohol among alcohol-dependent (AD) individuals. People without the OPRM1 response find alcohol to be a downer and are more susceptible to its sedative properties.

"People's response to drugs of abuse, including alcohol, varies dramatically," said Lara A. Ray, assistant professor in the department of psychology at the University of California, Los Angeles who was a corresponding author for the study. She adds, "Some research has suggested that the quality and intensity of a person's response to alcohol can predict whether they develop problems with alcohol. For example, individuals who experience stronger stimulant and rewarding effects from alcohol are more likely to drink heavily, thus increasing their chances of developing an alcohol use disorder.”

"We have known for a long time that alcoholism runs in families, which implies a genetic risk," said Dr. Raymond F. Anton, Distinguished Professor and director of the Center for Drug and Alcohol Programs at the Medical University of South Carolina. "There is currently great interest in how medications work in different people based on their individual genetic makeup, which is called 'personalized medicine.' If you think about it, alcohol is a pharmacological agent that works on the brain in certain defined ways which we know about. So it would make sense that it would work differently in different people, most of which is likely based on genetic differences."

"The gene we investigated, OPRM1, has received considerable attention in the alcohol research field both in terms of risk for alcoholism and for responsiveness to treatment with Naltrexone," noted Ray. "This study is the first to have tested the effects of this gene on response to alcohol in AD individuals. Furthermore, the finding that more severely AD patients exhibited greater reduction in tension in response to alcohol supports the theory that as alcoholism progresses, people are driven to drink primarily for negative reinforcement, namely, alleviation of negative mood or aversive physiological states from abstinence. On a related note, patients in the early stages of alcoholism or who report drinking for reward, or to 'feel good,' may be especially good candidates for an opioid blocker such as Naltrexone or possibly Nalmefene."

Nalmefene and Harm Reduction Options

An April 2013 study found a drug called Nalmefene to be a potential new treatment option for alcohol abuse. Researchers in Germany found Nalmefene to be an effective and safe tool for reducing alcohol consumption in alcohol dependent individuals. The study was published in the journal Biological Psychiatry.

"Our new findings may mark a true paradigm shift in the treatment of men and women who suffer from alcohol related disorders. While abstinence should be the best bet, a reduction in consumption may be a valuable alternative for the many patients who cannot attain abstinence or are not (yet) capable of doing so," said Dr. Karl Mann at Central Institute of Mental Health in Germany, who led the research.

Traditionally, abstinence has been viewed as the primary goal when treating alcohol dependence. However, relapse rates remain alarmingly high for those seeking total abstinence through traditional 12-step programs and rehab. To address these concerns and provide opportunities for improved patient outcomes there is a movement towards “harm reduction” by many addiction specialists.

Mann and his colleagues conducted a clinical trial to investigate the effectiveness of nalmefene in reducing alcohol consumption. They recruited 604 alcohol-dependent patients, half of whom randomly received nalmefene. The other half received visually-identical placebo pills. Neither patients nor their doctors knew which treatment they were receiving. Patients were instructed to take one tablet on days when they perceived a risk of drinking alcohol. Participants were followed by the study investigators for 24 weeks.

The research findings are promising. Nalmefene was significantly better than the placebo in reducing alcohol consumption. Nalmefene also improved patients' clinical status and liver enzymes. The drug was generally well-tolerated, with most side effects characterized as mild or moderate and quickly resolved. "With Nalmefene, we seem to be able to 'block the buzz' which makes people continue to drink larger amounts. With such a harm reduction approach, a new chapter in treating alcoholism could be opened," said Mann.

These findings provide evidence that an "as-needed" prescription of nalmefene may be an effective treatment for alcohol dependence for some. Unlike medications that must be taken every day, the as-needed approach targets medication administration to periods where alcohol use is more likely and may help break the cycle of alcohol dependence and binge drinking.

Conclusion: More Research Needed on Alcohol Gene Interactions

"Although preliminary, the results are compelling," said Dr. Leyton. "A much larger body of research has identified a role for dopamine in reward-seeking behaviors in general. For example, in both laboratory animals and people, increased dopamine transmission seems to enhance the attractiveness of reward-related stimuli. This effect likely contributes to why having one drink increases the probability of getting a second one – the alcohol-induced dopamine response makes the second drink look all the more desirable. If some people are experiencing unusually large dopamine responses to alcohol, this might put them at risk."

Leyton concludes, "People with loved ones struggling with alcoholism often want to know two things: How did they develop this problem? And what can be done to help? Our study helps us answer the first question by furthering our understanding of the causes of addictions. This is an important step toward developing treatments and preventing the disorder in others."

Back in 2012, Dr. Anton of University of South Carolina concluded about his study: "What these data show, and something I have been talking about for a long time, is the need for the research field to invest heavily in understanding alcohol by gene interactions. There should be a large-scale national study to evaluate thousands of individuals like the ones studied here. We have the genetic tools and the clinical research methods to make the link between individual differences and alcohol response/effects – which lies at the root cause of why some people become dependent/addicted and others do not."

Christopher Bergland is a world-class endurance athlete, coach, author, and political activist.

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