Breakthrough Study May Produce Medicine to Stop Alcohol Cravings, Organ Damage

Breakthrough Study May Produce Medicine to Stop Alcohol Cravings, Organ DamageA new study out of the University of Iowa has identified a single protein that is central to both cravings for alcohol and the damage it causes to the heart and liver—potentially opening the door to a new treatment for alcohol addiction and related harm.

About 20 percent of women and 40 percent of men abuse alcohol or have experienced alcohol dependence in their lifetimes, while the number of alcohol-attributable deaths in the U.S. currently stands at around 88,000 per year. The new study investigates the role of the protein RGS6 in alcohol addiction and related harm, building on previous work conducted by the same team.

Past research from pharmacology professor Rory Fisher’s lab at the University of Iowa found that this protein may have an important role to play in brain pathways involved in the development and maintenance of addiction to alcohol. Other results have also implicated it in the process of cell death in heart muscles.

These findings served as a starting point for the new study, which used mice lacking in the protein to investigate its effects on alcohol consumption and harm. The team found that, in comparison to “wild-type” mice that had the protein, those lacking RGS6 consumed less alcohol when provided with unlimited access, were less affected by alcohol-related reward and were less susceptible to the effects of withdrawal. This means that alcohol wouldn’t have the same pleasurable effects for these mice, and when they stopped drinking, they experienced less severe withdrawal symptoms and for a shorter period of time.

The effect of RGS6 on craving, alcohol-related reward and withdrawal is due to its ability to regulate levels of dopamine in the brain, which is one of the key neurotransmitters associated with addictive behaviors. The mice deficient in it have altered expression of the genes controlling dopamine levels, and naturally had less dopamine in their brains’ striatum than the other mice. Additionally, when the scientists antagonized the dopamine receptors or inhibited their transport, the mice began seeking alcohol again—adding further weight to the theory.

The second part of the experiment involved continually dosing the mice lacking RGS6 with alcohol, and showed that these mice experienced less heart and liver damage than the wild-type mice. In addition, the effect of alcohol on the stomach lining was also reduced. This effect had a different mechanism, with the protein playing a role in a pathway responsible for “programmed cell death” related to harmful compounds called reactive oxygen species.

Fisher commented that, “To our knowledge, RGS6 is the only gene with a demonstrated ability to promote alcohol-seeking behaviors while simultaneously worsening the damaging effects of alcohol consumption on the heart, stomach, intestine and liver.”

New Treatment for Alcohol Addiction and Related Organ Damage?

Of course, the immediate implication of the role of RGS6 is that it could be used to create a medicine that both reduces alcohol cravings and protects against organ damage. This is definitely possible, and although it may take some time for the necessary research and development to be conducted, it’s suggested by the authors in the conclusion to the study. However, because the effects of the protein are related to two different mechanisms, it could be that two different treatments would be required.

Despite this limitation, there are currently only three approved medications to treat alcohol addiction: disulfiram, naltrexone and acamprosate. Disulfiram produces an extremely unpleasant reaction when mixed with alcohol, but, in part due to low compliance with the dosing schedule, there’s very little evidence that it’s effective at promoting abstinence or reducing relapse. Naltrexone is used to reduce cravings. It works through an interaction with opioid receptors and has been shown to reduce cravings and relapse while boosting abstinence. Acamprosate is assumed to work by blocking receptors that play a role in cravings and has also been shown to be effective at reducing relapse rates.

No medicines are available to protect against or treat the organ damage caused by alcohol, though, and this could be one of the core advantages of a treatment based on preventing RGS6’s effects.

Medicines Come and Go, But Counseling Is Always Advised

With new breakthrough treatments being discovered and some existing treatments—specifically disulfiram—having poor evidential support, it’s clear that the medicines recommended for alcohol abuse treatment are subject to change. A treatment based on RGS6 may improve the options available, but it’s a long way from being ready. However, through all this, psychological intervention remains an essential component of treatment—ordinarily being suggested alongside any medication-based approach—because it enables you to get to the root of your drinking problem. Medications ultimately serve as tools to tackle the physical elements of the issue, but all addicts know that the problem is a psychological one, and counseling and rehab are the only ways to tackle that crucial element.

Posted on April 28th, 2015

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