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Research Highlights

Research News
Friday, March 13, 2020
Author:

Alcoholics Anonymous (AA) is as effective as established behavioral treatments for some people with alcohol use disorder (AUD), according to an extensive review of NIAAA-supported research and other studies.  As reported March 11 in the Cochrane Database of Systematic Review, researchers used a meta-analysis to show that AA and other 12-step facilitation interventions are effective in helping individuals with AUD reduce alcohol consumption, maintain continuous abstinence, and reduce alcohol-related consequences.

The new comprehensive analysis evaluated 35 studies which examined the outcomes of 10,080 participants and used a variety of methods to measure AA's effectiveness on AUD, including the length of time participants abstained from alcohol; the amount they reduced their drinking, if they continued drinking; the consequences of their drinking; and health care costs.  Across these measures, AA performed at least as well as other behavioral treatments, and AA was more effective in increasing abstinence. 

“Fewer than 1 in 10 people with AUD receive any help in a given year,” says Dr. George F. Koob, NIAAA Director. “It’s important that clinicians and consumers make decisions about treatment for AUD based on scientific evidence, and this carefully conducted meta-analysis suggests that AA should be on the list of options to consider.”

Insofar as the symptoms of AUD vary from person to person, the effectiveness of treatment approaches can also vary among individuals.  More research is needed to determine which individuals would benefit most from AA or other treatment strategies.

Reference:

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Kelly JF, Humphreys K, Ferri M.

Cochrane Database Syst Rev. 2020 Mar 11;3:CD012880. doi: 10.1002/14651858.CD012880.pub2. Review.

Research News
Thursday, February 6, 2020
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The National Institute on Alcohol Abuse and Alcoholism sadly announces the death of Richard L. Veech, MD, DPhil, Chief of the NIAAA Laboratory of Metabolic Control. Dr. Veech joined NIH after earning his bachelor’s and medical degrees at Harvard and his DPhil at Oxford under the tutelage of Hans Krebs. While in the process of completing his graduate work at Oxford and planning his start at NIH, he survived the crash of a commercial airliner wherein most passengers and crew were killed. Despite serious injury to himself, he was responsible for saving several fellow passengers, for which he was officially certified a Hero by the State of New Hampshire.

 

Dr. Veech began his 50-year NIH career as a Medical Officer in NIMH, joined NIAAA in 1974 and became Lab Chief in 2000. He published broadly and deeply and achieved world-wide recognition as a father of metabolomics and advocate for the possible health benefits of ketones. His name will always be associated with cell metabolism, energy metabolism and ketones. He was particularly interested in the relationship between cellular electrolyte balance and metabolism, as reflected in his controversial Donnan near-equilibrium hypothesis linking membrane voltage and ion changes to metabolism, redox and the free energy of ATP.  He was attempting to write an Equation of State for the cell in health and disease.

 

He is also listed as an inventor on 26 US patents, most involving electrolyte composition of parenteral fluids or therapeutic uses of ketone bodies, but notably including one on an environmentally friendly treatment to discourage barnacle attachment to marine structures. 

 

Dr. Veech has long been recognized as a leading basic scientist and an astute and compassionate physician. He will be missed. 

Research News
Monday, January 13, 2020
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People with a genetic variant of a neurotransmitter gene may have an increased risk of addiction to alcohol and other substances later in life if they were exposed to childhood stress, such as divorce or emotionally distant parents, and other adverse experiences, according to recent research.
 
The study led by researchers at the University of Oklahoma College of Medicine in collaboration with researchers from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, focused on an inherited variant of the gene for the enzyme catechol‐O‐methyltransferase (COMT).  “This is a well-known genetic variant of COMT, common worldwide, that leads to lower activity of this enzyme, and that has been previously observed to alter brain responses to stress and cognitive challenges,” stated study co-author, David Goldman, M.D., Chief of NIAAA’s Laboratory of Neurogenetics. COMT does so by helping the body manage levels of neurotransmitters, including dopamine, that are released when a person drinks alcohol or takes a drug like amphetamine.
 
The study included 480 healthy young adults ages 18–30 years of age who had experienced varying amounts of early-life adversity during childhood and adolescence. The researchers found that people who experienced early life stress and had the genetically less active COMT variant were more vulnerable and started drinking at a younger age. This heightened vulnerability often led to consumption of alcohol and illicit drugs prior to the age of 15 years, a predictor for alcohol and other substance use disorders in later life.
 
These findings demonstrate the interplay between a person’s genetic makeup and adverse environmental factors during childhood to alter the risk of alcohol and other substance use disorders later in life. Although no single gene alone strongly predicts risk of addiction, some genes predict risk more strongly in the context of environmental exposures.
 
Reference:
 
Lovallo WR, Cohoon AJ, Sorocco KH, Vincent AS, Acheson A, Hodgkinson CA, Goldman D. (2019) Early-life adversity and blunted stress reactivity as predictors of alcohol and drug use in persons with COMT (rs4680) Val158Met genotypes. Alcohol Clin Exp Res. 43(7):1519-1527. PMID: 31150143
Research News
Thursday, August 8, 2019
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A new study led by researchers at the National Institute and Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), identifies regions of the rat genome that are associated with a behavior that is highly predictive of addiction onset and progression.  The region in the rat genome with the strongest association with the behavior corresponded to a human gene associated with substance use disorders.  A report of the study is online in Proceedings of the National Academies of Science.
 
This finding underscores the value of preclinical models in unraveling the complexity of addiction-related behaviors in humans,” said NIAAA Director George F. Koob, Ph.D.  “It also highlights the power of genomics in identifying new genes and mechanisms for complex disorders such as addiction that are influenced by multiple genes.  This supports the hypothesis that progress in elucidating the mechanisms of genetically complex addictions can be made by understanding specific aspects of addiction vulnerability.
 
Addiction scientists have long known that diverse environmental and genetic factors play important roles in the vulnerability to addiction and how it progresses in an individual.  Preclinical and clinical research has firmly established that the behavioral traits of novelty-seeking and impulsive behavior are predictive of addiction onset and progression across species.
 
In the current study, scientists at the University of Michigan in Ann Arbor led by Huda Akil, Ph.D., bred rats to exhibit either high or low degrees of arousal in response to novel environment.  Dr. Akil is co-senior author of the study with David Goldman, M.D., NIAAA Clinical Director and Chief of the NIAAA Laboratory of Neurogenetics. First author Zhifeng Zhou, Ph.D. is also an intramural NIAAA scientist.
 
The hyperarousal behavior is measured by measuring rats’ movement in a new environment,” explains Dr. Goldman.  “We used genomic techniques to identify seven DNA regions that account for two-thirds of the genetic variability in the rats’ hyperarousal behavior.  This is a surprising finding, because behaviors such as arousal are thought to be genetically complex and influenced by hundreds or even thousands of genes, rather than being strongly influenced by as few as seven genes.
 
The region in the rat genome with the strongest association with the behavior contains the gene apba2.  The researchers conducted genetic association analyses in humans with alcohol and other substance use disorders (SUD) to see if the human form of this gene, APBA2, was associated with novelty seeking and SUD. They found significant APBA2 genotype frequency differences between controls and cases with SUD, and association of this gene to novelty seeking. The authors conclude, “The converging evidences of our human genetic association analysis and the molecular and behavioral analyses of other studies link apba2 to response to novelty and at least to the early stage of drug-seeking behavior seen in externalizing disorders.
 
Citation:
Zhou Z, et al (2019). Exploratory locomotion, a predictor of addiction vulnerability, is oligogenic in rats selected for this phenotype. PNAS. 116 (26): 13107-13115.
Research News
Wednesday, June 19, 2019
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In clinical trials for alcohol use disorder (AUD), abstinence and no heavy drinking days are currently the only end points approved by the U.S. Food and Drug Administration. However, many individuals who do not achieve these end points may still reduce their drinking to less harmful levels during treatment.

A recent study published in Alcoholism: Clinical and Experimental Research suggests that reductions in drinking risk levels could be useful end points for evaluating the effectiveness of AUD treatment for a given patient. Researchers conducted a secondary analysis of data collected from more than 1,000 individuals enrolled in NIAAA’s Combined Pharmacotherapies and Behavioral Interventions study, also known as COMBINE. The COMBINE study, a clinical trial of medications and behavioral treatments for fourth edition Diagnostic and Statistical Manual of Mental Disorders alcohol dependence (as defined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition) launched in 2001 and was conducted at 11 academic sites throughout the United States.

Researchers examined the COMBINE data for associations between reductions in drinking risk levels established by the World Health Organization (WHO) and improvements in physical health and quality of life.

WHO defines four levels of drinking risk, from low risk to medium, high, and very high risk.

The researchers found that during treatment, reductions of one and two levels of WHO drinking risk (for example, reducing alcohol consumption from high risk to medium or low risk) were associated with significant reductions in blood pressure, improvements in liver enzyme levels, and significantly better quality of life measures. The researchers concluded that their findings suggest a reduction in WHO drinking risk levels could be a meaningful surrogate marker of improvement in how a person “feels and functions” after AUD treatment. They also note that “extending treatment options to target reductions in drinking, rather than complete abstinence, could expand the reach of alcohol treatment and have an important impact on public health.”

References:

Witkiewitz, K.; Kranzler, H.R.; Hallgren, K.A.; O’Malley, S.S.; Falk, D.E.; Litten, R.Z.; Hasin, D.S.; Mann, K.F.; and Anton, R.F. Drinking risk level reductions associated with improvements in physical health and quality of life among individuals with alcohol use disorder. Alcoholism: Clinical and Experimental Research42(12):2453–2465, 2018. PMID: 30395350

This article first appeared in the NIAAA Spectrum.  

 

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