alcohol withdrawal

Medication Targeting Brain Stress Response May Help Cardiovascular Symptoms of Alcohol Withdrawal

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Summary: Prazosin, an FDA-approved medication for the treatment of hypertension may help to prevent relapse in people with cardiovascular and behavioral symptoms of alcohol withdrawal, a new study reports.

Source: Research Society on Alcoholism

Prazosin, a medication FDA-approved for hypertension and used off-label for alcohol use disorder, may help prevent drinking relapse in people with cardiovascular or behavioral symptoms of alcohol withdrawal, according to a new study involving active-duty soldiers. Alcohol use disorder (AUD) is highly prevalent among soldiers.

Prazosin reduces the noradrenergic signaling that is key to regulating the brain stress response. Overactivity of the noradrenergic system produces irritability, anxiety, “fight or flight” responses, and sleep disturbance.

Noradrenergic activity can increase during abstinence from drinking; consequently, it contributes to mood disturbances, insomnia, and other distressing symptoms of alcohol withdrawal and to the “relief cravings” that can lead to relapse.

Elevated noradrenergic activity produces elevated blood pressure and heart rate symptomatic of alcohol withdrawal. Previous research has pointed to the potential of prazosin for reducing alcohol use and cravings.

For the study in Alcohol: Clinical & Experimental Research, investigators designed a randomized control trial of prazosin among US active-duty soldiers.

Between 2015 and 2018, researchers enrolled 102 soldiers in this placebo-controlled study. The soldiers were undergoing mandated outpatient treatment for hazardous drinking and were expected to achieve abstinence. That program overlapped with the first nine weeks of the study.

Participants were interviewed about their alcohol consumption and were randomized to receive prazosin or placebo for 13 weeks. The soldiers kept diaries recording their number of drinks per day, drinking days per week, and heavy drinking days per week. On weeks nine and 13, they completed questionnaires assessing their alcohol cravings, sleep, and depression symptoms.

Those who met diagnostic criteria for PTSD (48 soldiers) were assessed for symptom severity. Researchers tracked participants’ blood pressure, heart rate, and suicidal thinking. They used statistical analysis to compare outcomes of treatment versus placebo among the soldiers, also considering cardiovascular symptoms or PTSD.

The soldiers’ alcohol use had declined steeply even before they were randomized. Nevertheless, on average, those taking prazosin experienced a modest but significant reduction in drinks per day compared to those taking placebo. The differences were more striking among specific subgroups.

This shows the outline of wine bottles
Prazosin reduces the noradrenergic signaling that is key to regulating the brain stress response.

The 15 soldiers with elevated heart rates were at or near zero drinks by week nine and sustained this through the final four weeks of the study (after the outpatient program ended).

Those taking the placebo, in contrast, experienced an alcohol rebound during the latter period. The 27 soldiers on prazosin who had raised blood pressure reported a reduced number of drinks and drinking days compared to those on placebo, with the contrast more notable in the final four weeks.

Overall, prazosin did not appear to reduce alcohol cravings more than placebo, a finding that may reflect the particular conditions of this study. Still, within the prazosin group, soldiers with PTSD did experience relief from cravings. This is likely a result of the medication’s countering effect on excessive noradrenergic signaling in PTSD. Depression symptoms were marginally lower among the prazosin group than the placebo controls.

Among soldiers with elevated cardiovascular measures, the benefit of prazosin in reducing drinking was notable despite the participants’ low alcohol consumption at the start of the study.

The study findings endorse a “personalized medicine” approach for treating people with AUD at high risk of relapse, including those who experience cardiovascular or behavioral symptoms consistent with alcohol withdrawal. Additional research is needed.

MUTATION STOPS WORMS FROM GETTING DRUNK.

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Neuroscientists at The University of Texas at Austin have generated mutant worms that do not get intoxicated by alcohol, a result that could lead to new drugs to treat the symptoms of people going through alcohol withdrawal.

The scientists accomplished this feat by inserting a modified human alcohol target into the worms, as reported this week in The Journal of Neuroscience.

“This is the first example of altering a human alcohol target to prevent intoxication in an animal,” says corresponding author, Jon Pierce-Shimomura, assistant professor in the university’s College of Natural Sciences and Waggoner Center for Alcohol and Addiction Research.

An alcohol target is any neuronal molecule that binds alcohol, of which there are many.

One important aspect of this modified alcohol target, a neuronal channel called the BK channel, is that the mutation only affects its response to alcohol. The BK channel typically regulates many important functions including activity of neurons, blood vessels, the respiratory tract and bladder. The alcohol-insensitive mutation does not disrupt these functions at all.

“We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function,” says Pierce-Shimomura.

The scientists believe the research has potential application for treating people addicted to alcohol.

“Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target to prevent problems in alcohol abuse disorders,” says Pierce-Shimomura. “However, it remains to be seen which aspects of these disorders would benefit.”

 

Unlike drugs such as cocaine, which have a specific target in the nervous system, the effects of alcohol on the body are complex and have many targets across the brain. The various other aspects of alcohol addiction, such as tolerance, craving and the symptoms of withdrawal, may be influenced by different alcohol targets.

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The worms used in the study, Caenorhabditis elegans, model intoxication well. Alcohol causes the worms to slow their crawling with less wriggling from side to side. The intoxicated worms also stop laying eggs, which build up in their bodies and can be easily counted.

Unfortunately, C. elegans are not as ideal for studying the other areas of alcohol addiction, but mice make an excellent model. The modified human BK channel used in the study, which is based on a mutation discovered by lead author and graduate student Scott Davis, could be inserted into mice. These modified mice would allow scientists to investigate whether this particular alcohol target also affects tolerance, craving and other symptoms relevant to humans.

Pierce-Shimomura speculated that their research could even be used to develop a ‘James Bond’ drug someday, which would enable a spy to drink his opponent under the table, without getting drunk himself. Such a drug could potentially be used to treat alcoholics, since it would counteract the intoxicating and potentially addicting effects of the alcohol.