A scientific study has shown alcohol dependency can be treated by targeting the dopamine system.
Gautam Naik Oct. 14, 2015 12:27 p.m. ET
Scientists have shown that a drug that normalizes dopamine levels in the brain can reduce alcohol cravings in people dependent on drink.
The finding was based on two studies, one conducted on people and one on rats. In the human trial, patients who took the experimental drug showed a marked reduction in alcohol craving. A separate animal study suggested that the drug works by acting on dopamine levels.
“It is proof of concept” that alcohol dependency can be treated by targeting the dopamine system, said Pia Steensland, neuroscientist at Karolinska Institute in Sweden and co-author of both studies. “We need to do larger trials” to validate the results.
Current drugs for alcohol dependency aren’t especially effective. The population of patients is genetically diverse, so only certain subgroups benefit. Prescription rates are low. As a result, the need for better medicines is huge.
Alcohol makes the brain’s reward system release more dopamine than normal, triggering a feeling of well-being. But as more alcohol is drunk, the more the reward system is desensitized and the less dopamine is released. Eventually, a person drinks more alcohol not just to feel euphoric, but to attain a state of physical and emotional normality. Thus, addiction sets in.
More than 16 million adults in the U.S. have an alcohol-use disorder and nearly 88,000 people die each year from alcohol-related causes, according to the National Institutes of Health. In 2006, alcohol misuse cost the U.S. economy $223.5 billion, the NIH said.
For the human study, published Wednesday in the journal European Neuropsychopharmacology, scientists recruited 56 Swedish alcohol dependent men and women, who typically would drink the equivalent of a bottle of wine a day.
The participants abstained from drink for at least four days. Half were then given a placebo and half got OSU6162, a drug believed to stabilize dopamine levels. The patients were randomized and neither they nor the researchers knew who was getting the experimental drug and who was getting the placebo.
For two weeks, the participants could drink as much as they liked. On day 15, each person was offered a glass of their favorite drink. According to the study, the OSU group reported not enjoying their first sip as much as the placebo group. After the drink was finished, the OSU group reported a lower craving for alcohol compared to the placebo group.
In addition, those with the poorest impulse control—and thus at greater risk of relapse after a period of abstinence—responded best to the experimental drug.
Both the OSU and placebo groups reported only mild side effects. This is significant because other dopamine-based medicines, such as those used to treat schizophrenia, completely block dopamine and can lead to nasty side-effects, such as nausea.
The rights to OSU6162 are owned by Arvid Carlsson, professor emeritus at the Sahlgrenska Academy in Sweden and co-author of the human study. Dr. Carlsson, 92 years old, shared in the 2000 Nobel Prize for medicine for discovering that dopamine is a transmitter in the brain. His team also developed OSU6162.
To better understand how OSU6162 might work, Dr. Steensland and other researchers did a separate study on rats, also published Wednesday in the journal Addiction Biology. Rats that voluntarily drank alcohol over the course of almost a year had lower dopamine levels than animals that drank no alcohol. When OSU6162 was given to the “alcohol rats,” their dopamine levels returned to normal.
The human trial wasn’t designed to comprehensively evaluate whether the experimental drug could help people drink less. But because of the promising early-stage results, Dr. Steensland and her colleagues now hope to do a longer-term trial involving many more patients.
October 14, 2015
Researchers at Karolinska Institutet and the Sahlgrenska Academy in Sweden might be one step closer to finding an effective drug for alcohol dependence. In two separate studies, they show that the dopamine stabilizer OSU6162 can reduce the craving for alcohol in alcohol dependent people and normalises the level of dopamine in the brain reward system of rats that have consumed alcohol over a long period of time. However, thorough clinical studies are needed to determine if the OSU6162 also can help alcohol dependent people drink less alcohol.
“The results of our studies are promising, but there is still a long way to go before we have a marketable drug,” says Pia Steensland, PhD, Associate Professo at the Department of Clinical Neuroscience of Karolinska Institutet, and co-author of both studies. “The socioeconomic costs of alcohol are huge, not to mention the human suffering. It is inspiring to continue working.”
Roughly a million Swedes over 15 years of age drink so much alcohol that they risk damaging their health, and it is estimated that some 300,000 of these people are dependent. Despite the pressing need, there are only a few approved drugs for the treatment of alcohol dependence, but their effects vary from person to person and the prescriptions rates are low. Consequently the hunt for new, more efficacious drugs for alcohol dependence continues.
The studies of OSU6162 are based on the knowledge of how the brain reward system stimulates us to act in the interests of our own survival. Since dopamine creates a feeling of wellbeing, such as when we exercise or eat good food, the memory associates the two so that we will repeat the behaviour. Alcohol makes the brain reward system release more dopamine than normal, creating a pleasant euphoric sensation. However, the more alcohol drunk, the more the reward system is desensitised and the less dopamine is released. With time, greater volumes of alcohol are needed to cause intoxication and eventually to attain a state of physical and emotional normality – addiction has set in.
In the clinical study, which is published in the scientific journal European Neuropsychopharmacology¸ the scientists examined for the first time if OSU6162 can reduce the craving for alcohol in people with alcohol dependence. Half the participants were treated with OSU6162 and half with placebo for a fortnight, after which both groups were exposed to different situations that could be assumed to elicit a craving for alcohol. The results show that the experimental group experienced less of a craving for alcohol after drinking one glass of an alcoholic beverage.
“At the same time, the OSU6162 group reported not enjoying the first zip of alcohol as much as the placebo group,” says Dr Steensland. “One interesting secondary finding was that those with the poorest impulse control, that is those thought to be most at risk of relapse after a period of abstinence, were those who responded best to the OSU6162 treatment.”
A study of rats published at the same time in the scientific journal Addiction Biology adds to the understanding of how OSU6162 works, as it shows that rats that voluntarily consumed alcohol for almost a year had lower levels of dopamine in their brain reward system than rats that had never drunk alcohol. However, when the “alcohol rats” were treated with OSU6162 it was found that the substance counteracted the low concentrations of dopamine in the brain reward system.
More information: ‘The Effects of the Monoamine Stabilizer (-)-OSU6162 on Craving in Alcohol Dependent Individuals: A Human Laboratory Study’, Lotfi Khemiri, Pia Steensland, Joar Guterstam, Olof Beck, Arvid Carlsson, Johan Franck, Nitya Jayaram-Lindström, European Neuropsychopharmacology, online 6 October 2015, doi:org/10.1016/j.euroneuro.2015.09.018.
‘The Monoamine Stabilizer (-)-OSU6162 Counteracts Down-Regulated Dopamine Output in the Nucleus Accumbens of Long-Term Drinking Wistar Rats’, Kristin Feltmann, Ida Fredriksson, Malin Wirf, Björn Schilström, Pia Steensland, Addiction Biology, online 14 October 2015, DOI: 10.1111/adb.12304.