Tag: alcohol

Categories : Metabolic DisordersTags :

GLP-1 Agonist Users Report Reduced Alcohol Cravings

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In social media posts on the community network Reddit, users reported reduced cravings for alcohol when taking drugs intended to treat Type 2 diabetes and obesity. Across a number of threads – with titles such as “Did scientists accidentally invent an anti-addiction drug?” and “I don’t know if this is a side effect but … Mounjaro makes me drink less!!!!!” – users reported a changing relationship with beer, wine, and liquor.

An analysis of those posts, together with a remote study of individuals with obesity who reported using semaglutide and tirzepatide, found that the drugs decreased cravings and reduced alcohol consumption, according to a study by Virginia Tech researchers published in Scientific Reports.

“These findings add to a growing literature that these medications may curb dangerous drinking habits,” said Warren Bickel, Virginia Tech Carilion Behavioral Health Research Professor at the Fralin Biomedical Research Institute at VTC and corresponding author.

Combing Reddit for users’ experiences

Scientists with the Fralin Biomedical Research Institute’s Addiction Recovery Research Center combined two different studies to build on existing research, including studies that showed the drugs were effective in reducing alcohol consumption in animal models.

The first was an analysis of more than 68 000 Reddit posts from 2009-23 that included terms linked to GLP-1 approved medications.

Semaglutide is a GLP-1 agonist, a class of drugs that reduce blood sugar and energy intake by mimicking the actions of hormones released after eating.

Among the keywords included in the search were Mounjaro, Wegovy, Ozempic, and Trulicity.

After cleaning the resulting data – such as eliminating comments with fewer than 100 characters – the set was narrowed to 33 609 posts from 14 595 unique users.

The study was unique in using Reddit to analyse the reported experience of thousands of users.

On examining alcohol-related discussions, researchers found that 962 individuals made 1580 alcohol-related posts.

Of those, 71.7% addressed reduced cravings, reduced usage, and other negative effects due to drinking.

In a second study, 153 participants who self-reported having obesity were recruited from various social media platforms.

Roughly a third of these participants represented the control group, a third were taking either a semaglutide injection or tablet, and a third were using tirzepatide.

Participants on semaglutide or tirzepatide reported drinking significantly fewer drinks, on average, than those in the control group who were not on any medication for diabetes or weight loss.

In addition, researchers found that both the average number of drinks and the odds of binge drinking were found to be significantly lower.

Results also found that the stimulative and sedative effects of alcohol intoxication are reduced when taking these medications.

“Participants reported drinking less, experienced fewer effects of alcohol when they did drink it, and decreased odds of binge drinking,” said Alexandra DiFeliceantonio, assistant professor at Fralin Biomedical Research Institute and one of the study’s co-authors.

Researchers believe theirs is the first published report following tirezepatide, sold under the brand name Mounjaro, which was approved in 2022 and is used for treatment of Type 2 diabetes and weight loss.

Why this matters

Case studies and reports in the popular press hint at the drugs’ unexpected side effect of reducing addictive behaviors, including the desire to consume alcohol.

The US Food and Drug Administration has approved only three medications to treat alcohol use disorder: disulfiram, naltrexone, and acamprosate.

They have shown only modest success, have poor compliance, and are underprescribed.

The authors suggest further randomized controlled trials to explore the therapeutic potential of GLP-1 agonists and GIP/GLP-1 combination drugs to treat alcohol use disorder, which affects 5.9% of individuals in the United States ages 12 and older.

In addition, the participants identified as mostly white and female, and further studies in more diverse populations are needed to examine sex and race differences.

“Although evidence supporting the use of these medications for alcohol use disorder is growing, the field still needs to learn considerably more about them, particularly in identifying the underlying mechanisms. We plan to contribute to that effort,” Bickel said.

The drugs are a promising development in the study of alcohol use disorder. Data from the National Survey on Drug Use and Health indicate 15.7 million people in the United States meet the criteria for the chronic, relapsing brain disorder that is a significant contributor to global mortality yet remains one of the most undertreated conditions, Bickel said.

Source: Virginia Tech

Categories : Cardiovascular Disease Substance UseTags :

Alcohol Metabolites Play a Complex Role in Cardiovascular Harms and Benefits

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Although past research has indicated that moderate alcohol consumption can reduce cardiovascular disease (CVD) risk, more recent studies suggest that moderate levels of drinking may be hazardous to heart health. A new analysis now sheds new insight on this complex relationship between alcohol consumption and the progression of CVD, showing that a few particular alcohol metabolites strongly influence its protective effects.

Published in the journal BMC Medicine, the study observed a total of 60 alcohol consumption-related metabolites, identifying seven circulating metabolites that link long-term moderate alcohol consumption with an increased risk of CVD, and three circulating metabolites that link this same drinking pattern with a lower risk of CVD.

The findings from the study led by Boston University School of Public Health and Friedman School of Nutrition Science and Policy at Tufts University (Friedman School) detail the molecular pathway of long-term alcohol consumption and show that further research on these metabolites is needed for targeted prevention and treatment of alcohol-related CVD.

“The study findings demonstrate that alcohol consumption may trigger changes of our metabolomic profiles, potentially yielding both beneficial and harmful outcomes,” says Dr Chunyu Liu, assistant professor of biostatistics at BUSPH and co-corresponding/co-senior author of the study along with Dr.Jiantao Ma, assistant professor in the Division of Nutrition Epidemiology and Data Science at the Friedman School.

“However, rather than definitively settling that debate, this study underscores the intricate effects of alcohol consumption on cardiovascular health and generates a useful hypothesis for future investigations,” Dr Liu says.

The researchers analysed blood samples to measure the association between the cumulative average consumption of beer, wine, and liquor and 211 metabolites among Framingham Heart Study Offspring Study participants, who are the children of participants in the long-running Boston University-based Framingham Heart Study, over 20 years.

Of the 2428 participants, 636 developed CVD over the study period. Among the 60 drinking-related metabolites, 13 metabolites had a stronger association with alcohol consumption in women than in men, perhaps due to higher blood alcohol levels from women’s generally smaller body size versus the same amount of alcohol.

Consuming different types of alcohol was also linked to different metabolomic responses, with beer consumption generating a slightly weaker association overall than wine and liquor.

In roughly two-thirds of the 60 metabolites, higher plasma levels were detected in participants who consumed greater amounts of alcohol. Branched-chain amino acids (BCAAs), were among the metabolites not associated with alcohol consumption.

The researchers then calculated two alcohol consumption-associated metabolite scores, which had opposite associations with the development of CVD.

“While our study presents intriguing findings, validation through state-of-the-art methods and large and diverse study populations is crucial,” Dr Ma says.

“To enhance reliability, we aim to conduct larger-scale research involving a more diverse racial and ethnic background, as the current study participants are all white. In addition, we will expand our study to integrate with other molecular markers such as genetic information to illustrate the complex relationships between alcohol consumption, metabolite features, and cardiovascular risk.”

Source: Boston University School of Public Health

Categories : NeurologyTags :

Why do Some People get a ‘Red Wine’ Headache?

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For some people, drinking red wine even in small amounts causes a headache, which typically occurs within 30 minutes to three hours after drinking as little as a small glass of wine. Researchers have examined why this happens – even to people who don’t get headaches when drinking small amounts of other alcoholic beverages. In their work, published in the journal Scientific Reports, the researchers posit that a flavanol found naturally in red wines can interfere with the proper metabolism of alcohol and can lead to a headache.

The headache culprit: Quercetin, a flavanol

This flavanol is called quercetin and it is naturally present in all kinds of fruits and vegetables, including grapes. It’s considered a healthy antioxidant and is even available in supplement form. But when metabolized with alcohol, it can be problematic.

“When it gets in your bloodstream, your body converts it to a different form called quercetin glucuronide,” said wine chemist and corresponding author Andrew Waterhouse, professor emeritus with the UC Davis Department of Viticulture and Enology. “In that form, it blocks the metabolism of alcohol.”

Acetaldehyde toxin buildup leads to flushing, headache, nausea

As a result, people can end up accumulating the toxin acetaldehyde, explains lead author Apramita Devi, postdoctoral researcher with the UC Davis Department of Viticulture and Enology.

“Acetaldehyde is a well-known toxin, irritant and inflammatory substance,” said Devi. “Researchers know that high levels of acetaldehyde can cause facial flushing, headache and nausea.”

The medication disulfiram prescribed to alcoholics to prevent them from drinking causes these same symptoms. Waterhouse said that’s because the drug also causes the toxin to build up in the body when normally an enzyme in the body would break it down. About 40% of the East Asian population also has an enzyme that doesn’t work very well, allowing acetaldehyde to build up in their system.

“We postulate that when susceptible people consume wine with even modest amounts of quercetin, they develop headaches, particularly if they have a preexisting migraine or another primary headache condition,” said co-author Morris Levin, professor of neurology and director of the Headache Center at the University of California, San Francisco. “We think we are finally on the right track toward explaining this millennia-old mystery. The next step is to test it scientifically on people who develop these headaches, so stay tuned.”

Sunlight increases headache-causing flavanol in grapes

Waterhouse said levels of this flavanol can vary dramatically in red wine.

“Quercetin is produced by the grapes in response to sunlight,” Waterhouse said. “If you grow grapes with the clusters exposed, such as they do in the Napa Valley for their cabernets, you get much higher levels of quercetin. In some cases, it can be four to five times higher.”

Levels of quercetin can also differ depending on how the wine is made, including skin contact during fermentation, fining processes and aging.

Clinical trial on wine headaches

Scientists will next compare red wines that contain a lot of quercetin with those that have very little to test their theory about red wine headaches on people. This small human clinical trial, funded by the Wine Spectator Scholarship Foundation, will be led by UCSF.

Researchers said there are still many unknowns about the causes of red wine headaches. It’s unclear why some people seem more susceptible to them than others. Researchers don’t know if the enzymes of people who suffer from red wine headaches are more easily inhibited by quercetin or if this population is just more easily affected by the buildup of the toxin acetaldehyde.

“If our hypothesis pans out, then we will have the tools to start addressing these important questions,” Waterhouse said.

Source: University of California – Davis

Categories : AddictionTags :

Fathers’ Parental Leave may Protect against Hospitalisation for Alcohol Consumption

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Fathers who have been on parental leave have a significantly reduced risk of being hospitalised due to alcohol consumption. This is shown by a study published in Addiction from researchers at the Department of Public Health Sciences, Stockholm University.

The aim of the study was to assess whether fathers’ parental leave influences alcohol-related morbidity and mortality. In order to try to find out if that is the case, the researchers have investigated the effects of parental leave policy that was implemented in Sweden in 1995. The policy encouraged fathers to use parental leave by reserving 30 days of leave for their use alone and resulted in the proportion of fathers using parental leave increasing from 43% to 75%.

“Our findings were pretty remarkable considering the severity of the studied outcome. Although alcohol-related hospitalizations were rather uncommon, we found that after the policy was implemented there was a 34% decrease in these hospitalizations among fathers in the two years after birth, as well as smaller decreases up to 8 and 18 years after birth,” says Helena Honkaniemi, researcher at the Department of Public Health Sciences, Stockholm University.

“Most changes were found among hospitalisations for alcohol intoxication and alcohol-related mental and behavioural disorders. Additional analyses evaluating actual changes in parental leave use from before to after the policy suggest that these health consequences could be explained by the increase in fathers’ parental leave use, rather than other underlying trends,” says Helena Honkaniemi.

However, no changes were found for alcohol-related mortality.

Co-author Associate Professor Sol Juárez believes that the results of the study could be useful for policymakers.

“Policymakers should consider that fathers’ parental leave not only promotes more gender-equal participation in childcare, but can also reduce alcohol-related harms,” Juárez says.

The study “Alcohol-related morbidity and mortality by fathers’ parental leave: A quasi-experimental study in Sweden” draws on Swedish register data of all fathers of singleton children born from January 1992 to December 1997, three years before and after the policy was implemented.

Source: Stockholm University

Categories : Obstetrics & Gynaecology Substance UseTags :

Before Birth, Substance Use by Father can Also Increase Risk of Intellectual Disability for Child

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Children of a parent with alcohol or drug use disorder have a greater risk of intellectual disability, even if the problem only lies with the father, researchers from Karolinska Institutet report. According to the study, which is published in the journal eClinicalMedicine, preventive measures should be directed at both parents.

A woman’s consumption of alcohol during pregnancy has been well established as increasing the risk of the child developing. Research from Karolinska Institutet now shows that all forms of substance abuse, both in the mother and the father, and not only during pregnancy, can constitute a risk factor.

Previous efforts aimed at mothers

“Preventative measures, such as educating healthcare professionals and public health recommendations, have focused for decades on mothers with alcohol-related problems,” says Lotfi Khemiri, researcher at Karolinska Institutet. “Our findings highlight the importance of also directing such measures towards fathers with different types of substance use disorder.”

The study drew on data from Swedish registries with almost two million babies born between 1978 and 2002 and their parents. The researchers found that 1.2% of babies born to parents without such a disorder were diagnosed with an intellectual disability, compared with 3% of the babies who had one parent with a diagnosis related to a substance use disorder (alcohol or drug abuse).

Higher risk before birth

The elevated risk was greater if the parent had received a diagnosis before or during pregnancy rather than after birth. A substance use disorder diagnosis registered before birth was associated with more than twice the risk of intellectual disability in the baby, regardless of which parent had the diagnosis. The correlation was weaker but still statistically significant after adjustment of socioeconomic factors and psychiatric comorbidity in the parents.

“Since it was an observational study, we can draw no conclusions about the underlying mechanism, but we suspect that both genetic and environmental factors, including harmful effects of substance abuse on foetal development, may play a part,” says Dr Khemiri. “We hope that the results will contribute to the preventative efforts, as well as to the improved diagnosis of children with an intellectual disability and to timely intervention directed both to the child as well as parents in need of substance use disorder treatment.”

Alcohol a major risk factor

Intellectual disability was observed to be much more likely in alcohol-related problems during pregnancy, where the risk was five and three times higher depending on whether it was the mother or father who had the alcohol use disorder diagnosis.

Source: Karolinska Institutet

Categories : Cardiovascular DiseaseTags :

Regular Alcohol Drinking may Raise Blood Pressure Even in Non-Hypertensive Adults

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An analysis of seven international research studies found that, even in adults without hypertension, blood pressure (BP) readings may climb more steeply over the years as the number of daily alcoholic drinks rise. The findings, published in the journal Hypertension, also found no beneficial effects to a low level of alcohol intake.

Pooling seven international research studies, this analysis confirms for the first time a continuous increase in blood pressure measures in both participants with low and high alcohol intake. Even low levels of alcohol consumption were associated with detectable increases in blood pressure levels that may lead to a higher risk of cardiovascular events.

“We found no beneficial effects in adults who drank a low level of alcohol compared to those who did not drink alcohol,” said senior study author Marco Vinceti, MD, PhD, a professor of epidemiology and public health at the University of Modena and Reggio Emilia University and an adjunct professor at Boston University’s School of Public Health. “We were somewhat surprised to see that consuming an already-low level of alcohol was also linked to higher blood pressure changes over time compared to no consumption – although far less than the blood pressure increase seen in heavy drinkers.”

“Our analysis was based on grams of alcohol consumed and not just on the number of drinks to avoid the bias that might arise from the different amount of alcohol contained in ‘standard drinks’ across countries and/or types of beverages,” said study co-author Tommaso Filippini, MD, PhD, an associate professor of epidemiology and public health in the Medical School of the University of Modena and Reggio Emilia in Italy, and affiliate researcher at the University of California Berkeley School of Public Health.

Researchers reviewed the health data for all participants across the seven studies for more than five years. They compared adults who drank alcohol regularly with non-drinkers and found:

  • Systolic BP rose 1.25mmHg in people who consumed an average of 12 grams of alcohol per day, rising to 4.9mmHg in people consuming an average of 48 grams of alcohol per day.
  • Diastolic BP rose 1.14mmHg in people consuming an average of 12 grams of alcohol per day, rising to 3.1mmHg in people consuming an average of 48 grams of alcohol per day. These associations were seen in males but not in females. Diastolic blood pressure measures the force against artery walls between heartbeats and is not as strong a predictor of heart disease risk in comparison to systolic.

“Alcohol is certainly not the sole driver of increases in blood pressure; however, our findings confirm it contributes in a meaningful way. Limiting alcohol intake is advised, and avoiding it is even better,” Vinceti said.

Although none of the participants had high blood pressure when they enrolled in the studies, their blood pressure measurements at the beginning did have an impact on the alcohol findings.

”We found participants with higher starting blood pressure readings, had a stronger link between alcohol intake and blood pressure changes over time. This suggests that people with a trend towards increased (although still not ‘high’) blood pressure may benefit the most from low to no alcohol consumption,” said study co-author Paul K. Whelton, MD, MSc, at Tulane University’s School of Public Health.

Study details and background:

  • Researchers analysed data from seven, large, observational studies involving 19 548 adults (65% men), ranging in age from 20 to their early 70s at the start of the studies.
  • The studies were conducted in the United States, Korea and Japan, and published between 1997 and 2021. None of the participants had previously been diagnosed with high blood pressure or other cardiovascular diseases, diabetes, liver disease, alcoholism or binge drinking.
  • Usual alcoholic beverage intake was recorded at the beginning of each study and the researchers translated this information into a usual number of grams of alcohol consumed daily. The researchers used a new statistical technique that allowed them to combine results from several studies and plot a curve showing the impact of any amount of alcohol typically consumed on changes in blood pressure over time.

Other co-authors and authors’ disclosures are listed in the manuscript.

Source: American Heart Association

Categories : Metabolic DisordersTags :

Even Modest Alcohol Intake Does not Reduce Diabetes, Obesity Risk

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Having only one or two alcoholic drinks per day does not protect against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.

It is widely accepted that excessive alcohol consumption causes a wide range of health issues and is thus a major public health concern. Whether modest alcohol consumption has beneficial health effects remains controversial, however, due to the limited power of observational studies.

The researchers used mendelian randomisation (MR), which can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.

“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, PhD, from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc) as well as increased risk of type 2 diabetes.”

The researchers assessed self-reported alcohol intake data from 408 540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes. An extra drink per week was associated with an increased of 8% for diabetes risk and 10% for obesity risk.

These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.

Source: The Endocrine Society

Categories : Metabolic Disorders Substance UseTags :

Women’s Lean Body Mass and Age Speed up Blood Alcohol Elimination

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The rate at which women eliminate alcohol from their bloodstream is largely predicted by their lean body mass, although age plays a role, too, scientists found in a new study published in the journal Alcohol Clinical and Experimental Research. Since women with obesity also have more lean body mass, older women with obesity clear alcohol from their systems 52% faster than younger women of healthy weights, the study found.

“We believe the strong relationship we found between participants’ lean body mass and their alcohol elimination rate is due to the association that exists between lean body mass and lean liver tissue – the part of the liver responsible for metabolising alcohol,” said research group leader M. Yanina Pepino, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.

To explore links between body composition and alcohol elimination rates, the team conducted a secondary analysis of data from a study performed at and another at Indiana University, Indianapolis. Both projects used similar methods to estimate the rate at which alcohol is broken down in the body.

The combined sample from the studies used in the analysis included 143 women who ranged in age from 21 to 64 and represented a wide range of body mass indices – from healthy weights to severe obesity. Among these were 19 women who had undergone different types of bariatric surgery. Lean body mass is total body weight minus fat.

In a subsample of 102 of these women, the researchers had measured the proportions of lean and fat tissue in their bodies and calculated their body mass indices. Based on their BMI, those in the subsample were divided into three groups: normal weight (BMI of 18.5–24.9), overweight BMI (25–29.9) and obese (BMI 30+).

As the researchers expected, women with higher BMI had not only more fat mass than women of healthy weights, they also had more lean mass. On average, the group with obesity had 52.3 kg of lean mass, compared with 47.5 kg for the normal weight group.

The two studies both used an alcohol clamp technique, where participants received an intravenous infusion of alcohol at a rate controlled by a computer-assisted system. The system calculated personalised infusion rates based upon each participant’s age, height, weight and gender and was programmed so they would reach a target blood alcohol concentration of .06% within 15 minutes and maintain that level for about two hours

Using a breathalyser, breath samples were collected at regular intervals throughout the experiments to estimate participants’ blood alcohol concentration and provide feedback to the system.

“We found that having a higher fat-free body mass was associated with a faster alcohol elimination rate, particularly in women in the oldest subgroups,” said Neda Seyedsadjadi, a postdoctoral fellow at the university and the first author of the study.

“The average alcohol elimination rates were 6 grams per hour for the healthy weight group, 7 grams for the overweight group, and 9 grams for the group with obesity,” she said. “To put this in perspective, one standard drink is 14 grams of pure alcohol, which is found in 12 ounces of beer, 5 ounces of table wine or 1.5 ounces shot of distilled spirits.”

The interaction between participants’ age and lean body mass accounted for 72% of the variance in the time required to eliminate the alcohol from their system, the team found.

Pepino, who also holds an appointment as a health innovation professor at Carle Illinois College of Medicine, has conducted several studies on alcohol response in bariatric surgery patients.

The findings also shed light on alcohol metabolism and body composition in women who have undergone weight loss surgery. Researchers have long known that bariatric surgery alters women’s response to alcohol but were uncertain if it affected how quickly they cleared alcohol from their systems.

Some prior studies found that these patients metabolised alcohol more slowly after they had weight loss surgery. The new study’s findings indicate that these participants’ slower alcohol elimination rates can be explained by surgery-induced reductions in their lean body mass. Weight loss surgery itself had no independent effects on patients’ alcohol elimination rates, the team found.

Source: University of Illinois at Urbana-Champaign

Categories : Pain ManagementTags :

Scientists Probe Links Between Chronic Alcohol Use and Pain Sensitivity

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The links between alcohol and pain are complex. Research published in the British Journal of Pharmacology suggests that chronic alcohol consumption may increase drinkers’ pain sensitivity through two different molecular mechanisms – the first driven by alcohol intake and the second by alcohol withdrawal.

The research also suggests potential new drug targets for treating alcohol-associated chronic pain and hypersensitivity.

“There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence,” says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine, and a professor of neuroscience at Scripps Research. “Pain is both a widespread symptom in patients suffering from alcohol dependence, as well as a reason why people are driven to drink again.”

Over time, alcohol use disorder (AUD) can trigger the development of numerous chronic diseases, including heart disease, stroke, liver disease and some cancers. Among the many impacts of long-term alcohol consumption is pain: more than half of people with AUD experience persistent pain of some type. This includes alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms.

Studies have also found that AUD is associated with changes in how the brain processes pain signals, as well as changes to how immune system activation occurs. In turn, this pain can lead to increased alcohol consumption. Moreover, during withdrawal, people with AUD can experience allodynia, in which a harmless stimulus is perceived as painful.

Roberto and her colleagues were interested in learning the underlying causes of these different types of alcohol-related pain. In the new study, they compared three groups of adult mice: animals that were dependent on alcohol (excessive drinkers), animals that had limited access to alcohol and were not considered dependent (moderate drinkers), and those that had never been given alcohol.

In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity. Separately, about half of the mice that were not dependent on alcohol also showed signs of increased pain sensitivity during alcohol withdrawal but, unlike the dependent mice, this neuropathy was not reversed by re-exposure to alcohol.

When Roberto’s group then measured levels of inflammatory proteins in the animals, they discovered that while inflammation pathways were elevated in both dependent and non-dependent animals, specific molecules were only increased in dependent mice. This indicates that different molecular mechanisms may drive the two types of pain. It also suggests which inflammatory proteins may be useful as drug targets to combat alcohol-related pain.

“These two types of pain vary greatly, which is why it is important to be able to distinguish between them and develop different ways to treat each type,” says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.

Roberto’s group is continuing studies on how these molecules might be used to diagnose or treat alcohol-related chronic pain conditions.

“Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies,” says co-senior author Nicoletta Galeotti, PhD, associate professor of preclinical pharmacology at the University of Florence.

Source: Scripps Research Institute

Categories : Substance UseTags :

A Hormone Injection Sobers Up Drunk Mice

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Researchers have found that a simple injection of hormone called fibroblast growth factor 21 (FGF21) protects mice against ethanol-induced loss of balance and righting reflex, effectively sobering them up.

“We’ve discovered that the liver is not only involved in metabolising alcohol but that it also sends a hormonal signal to the brain to protect against the harmful effects of intoxication, including both loss of consciousness and coordination,” says co-senior study author Steven Kliewer of the University of Texas Southwestern Medical Center, regarding the study results published in the journal Cell Metabolism.

“We’ve further shown that by increasing FGF21 concentrations even higher by injection, we can dramatically accelerate recovery from intoxication. FGF21 does this by activating a very specific part of the brain that controls alertness,” says Kliewer.

The consumption of ethanol produced by the natural fermentation of simple sugars in ripening fruits and nectars can cause intoxication, impairing mobility and judgement. Animals that consume fructose and other simple sugars have evolved liver enzymes to break down ethanol.

FGF21 is a hormone that is induced in the liver by a variety of metabolic stresses, including starvation, protein deficiency, simple sugars, and ethanol. In humans, ethanol is by far the most potent inducer of FGF21 described to date. Previous studies showed that FGF21 suppresses ethanol preference, induces water drinking to prevent dehydration, and protects against alcohol-induced liver injury.

In the new study, Kliewer and co-senior study author David Mangelsdorf of the University of Texas Southwestern Medical Center show that FGF21 plays a broader role in defending against the harmful consequences of ethanol exposure than previously thought. In mice, FGF21 stimulated arousal from intoxication without changing the breakdown of ethanol. Mice lacking FGF21 took longer than their littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduced the time needed for mice to recover from ethanol-induced unconsciousness and lack of muscle coordination.

Surprisingly, FGF21 did not counteract sedation caused by ketamine, diazepam, or pentobarbital, indicating specificity for ethanol. FGF21 mediated its anti-intoxicant effects by directly activating noradrenergic neurons in the locus coeruleus region in the brain, which regulates arousal and alertness. Taken together, the results suggest that the FGF21 liver-brain pathway evolved to protect against ethanol-induced intoxication. According to the authors, this pathway may modulate a variety of cognitive and emotional functions to enhance survival under stressful conditions.

Whether activation of the noradrenergic system contributes to FGF21’s other effects is yet to be determined. Although both FGF21 and noradrenergic nervous system activity are induced by ethanol in humans, additional studies will also be required to determine whether FGF21’s anti-intoxicant activity translates to humans.

“Our studies reveal that the brain is the major site of action for FGF21’s effects,” Mangelsdorf says. “We are now exploring in greater depth the neuronal pathways by which FGF21 exerts its sobering effect.”

Source: Cell Press