Category: From Newswise – Addiction

Newswise — According to the Substance Abuse and Mental Health Services Administration, approximately 40 million people in the United States had a substance use disorder in 2020. In addition, over the last decade, the prevalence of opioid addition has increased to epidemic levels. Unfortunately, therapeutic interventions for the treatment of addiction remain limited.

Florida Atlantic University’s Randy D. Blakely, Ph.D., and Maureen K. Hahn, Ph.D., have received a patent from the U.S. Patent and Trademark Office for a novel method to identify therapeutic agents to treat addiction. The invention, related to the fields of pharmacology, medicine, neurology and psychiatry, targets the protein MBLAC1, which the Blakely lab identified as the mammalian form of a gene the group first identified in worms as a modifier of signaling by the neurotransmitter dopamine. 

“The majority of drug addiction research has focused on dopamine signaling and how changes downstream of dopamine action eventually lead to compulsive drug seeking,” said Blakely, executive director of the FAU Stiles-Nicholson Brain Institute, the David J.S. Nicholson Distinguished Professor in Neuroscience, and a professor of biomedical science in FAU’s Schmidt College of Medicine. “However, we found evidence in the worm model C. elegans that a gene expressed in glial cells supports the health and function of dopamine neurons and suspected its actions in humans might also relate to addiction.”

Glia are non-neuronal cells in the brain and peripheral nervous system well known to support neuronal metabolism and the rapid transmission of impulses.

“We now know that glial cells support brain function in many more ways, including aspects of the plasticity and drug responses of nearby neurons. Dopamine neurons are no exception,” said Blakely.

Over the past two decades, the Blakely lab has utilized the simple but powerful worm model for its ability to yield insights into the genes and proteins that regulate dopamine signaling. In 2012, the group identified a new gene they named swip-10, as the loss of this gene produces “Swimming-induced paralysis” or Swip. DNA analysis of swip-10 revealed conserved sequences that comprise a Metallo-b-lactamase Domain (MBD), an element that was also found in an uncharacterized human gene termed MBLAC1. 

“Metallo-b-lactamases are well known to microbiologists for the ability of bacteria to degrade antibiotics such as penicillin and thereby contribute to antibiotic resistance,” said Blakely. “However, in more complex organisms, MBD has been repurposed to digest many other molecules. So, we suspected that drugs targeting human MBD-containing proteins would likely have non-microbial effects, perhaps even medically relevant ones.”

Indeed, prior to the Blakely lab identifying swip-10, scientists studying addiction were learning that the beta-lactam antibiotic ceftriaxone could diminish several brain changes that arise with chronic use of addictive drugs. What they didn’t know was what protein ceftriaxone bound to in the brain. In 2018, the Blakely lab reported that the protein made by the MBLAC1 gene is a major, if not exclusive, target for ceftriaxone. More recent data from mice engineered to eliminate MBLAC1 protein expression demonstrate a requirement for the protein in the ability of cocaine to establish long-term behavioral changes that reflect brain alterations scientists believe contributes to the drug’s abuse liability.

Remarkably, the Blakely lab has discovered that loss of swip-10 also causes age-dependent neurodegeneration.

“We think these findings link to recent studies implicating MBLAC1 as a contributor to risk for certain forms of Alzheimer’s disease as well as the ability of ceftriaxone to display neuroprotection in animal models,” said Hahn, co-inventor on the patent and a research associate professor of biomedical science in FAU’s Schmidt College of Medicine. “We are very excited that what began as a simple genetic screen using worms may be leading us to insights into a number of different brain disorders.”

– FAU –

About Florida Atlantic University: Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located along the southeast Florida coast. In recent years, the University has doubled its research expenditures and outpaced its peers in student achievement rates. Through the coexistence of access and excellence, FAU embodies an innovative model where traditional achievement gaps vanish. FAU is designated a Hispanic-serving institution, ranked as a top public university by U.S. News & World Report and a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.fau.edu.

 

Newswise — On average, young adults in Canada spend several hours on their smartphones every day. Many jump from TikTok to Netflix to Instagram, putting their phone down only to pick up a video game controller. A growing body of research is looking into the potential dangers of digital media overuse, as well as potential benefits of moderate digital media use, from a mental health standpoint.

A recent McGill University study of 425 Quebecers between the ages of 18 and 25 has found that young adults who have more frequent psychotic experiences also tend to spend more time using digital media. Interestingly, the study, which surveyed the participants over a period of six months, also found that spending more time on digital media did not seem to cause any change in the frequency of psychotic experiences over time, said lead author and psychiatry resident at McGill, Vincent Paquin.

By “psychotic experiences,” the researchers refer to a range of unusual thoughts and perceptions, such as the belief of being in danger and the experience of hearing and seeing things that other people cannot see or hear. These experiences are relatively common, affecting about 5% of young adults.

“Our findings are reassuring because they do not show evidence that digital media can cause or exacerbate psychotic experiences in young people,” said Paquin. “It is important to keep in mind that each person is different. In some situations, digital media may be highly beneficial for a person’s well-being, and in other cases, these technologies may cause unintended harms.”

Accessing mental health services through digital media

The researchers hope their findings will help improve mental health services for young people. By better understanding the types of digital contents and activities that matter to young people, mental health services can be made more accessible and better aligned with individual needs, they say.

“It is important for young people, their families, and for clinicians and policymakers to have scientific evidence on the risks and benefits of digital media for mental health, Paquin said. “Considering that young adults with more psychotic experiences may prefer digital technologies, we can use digital platforms to increase their access to accurate mental health information and to appropriate services.”

Newswise — PISCATAWAY, NJ — It’s “liquid courage,” not necessarily “beer goggles”: New research indicates that consuming alcohol makes you more likely to approach people you already find attractive but does not make others appear more attractive, according to a report in the Journal of Studies on Alcohol and Drugs.

The conventional wisdom of alcohol’s effects is that intoxication makes others seem better looking. But, according to the new study, this phenomenon has not been studied systematically. Earlier research typically had participants simply rate other’s attractiveness while sober and while intoxicated based on photos.

But this new study added a more realistic element: the possibility of meeting the people being rated.

To conduct the research, lead investigator Molly A. Bowdring, Ph.D., of the Stanford Prevention Research Center in Palo Alto, Calif. (affiliated with University of Pittsburgh at the time of this study), and her dissertation advisor, Michael Sayette, Ph.D., brought in 18 pairs of male friends in their 20s to the laboratory to rate the attractiveness of people they viewed in photos and videos.

Participants were told that they may be given the opportunity to interact with one of those people in a future experiment. After providing attractiveness ratings, they were asked to select those with whom they would most like to interact.

Pairs of men came into the lab on two occasions. On one occasion, both men received alcohol to drink (up to about a blood alcohol concentration of .08%, the legal limit for driving in the United States) and on the other occasion, they both received a nonalcoholic beverage. The researchers had friend pairs in the lab to mimic the social interactions that would typically take place in a real drinking situation.

The researchers did not find evidence of beer goggles: Whether or not participants were intoxicated had no effect on how good looking they found others. “The well-known beer goggles effect of alcohol does sometimes appear in the literature but not as consistently as one might expect,” observes Sayette.

However, drinking did affect how likely the men were to want to interact with people they found attractive. When drinking, they were 1.71 times more likely to select one of their top-four attractive candidates to potentially meet in a future study compared with when they were sober.

Alcohol may not be altering perception but rather enhancing confidence in interactions, giving the men liquid courage to want to meet those they found the most attractive, something they may be much less likely to do otherwise.

These results could have implications for therapists and patients, the authors note.

“People who drink alcohol may benefit by recognizing that valued social motivations and intentions change when drinking in ways that may be appealing in the short term but possibly harmful in the long term,” says Bowdring.

Newswise — Cocaine use continues to be a public health problem, yet despite concerted efforts, no drugs have been approved to resolve cocaine addiction. Research suggests that the attention-deficit/hyperactivity disorder drug methylphenidate (MPH; Ritalin®) could serve as a cocaine-replacement therapy, but clinical results have been mixed. Although several labs have produced MPH derivatives for testing, parts of the molecule remained chemically inaccessible. Now, researchers reporting in ACS Central Science have cleared that hurdle.

According to the Centers for Disease Control and Prevention, more than 5 million Americans reported actively using cocaine in 2020, and almost 25,000 Americans died of a cocaine-related overdose in 2021. Although small-molecule drugs have proven effective in treating other drug addictions — for example, methadone as a therapy for heroin abuse — no such medication exists for cocaine abuse. MPH has been considered a potential treatment because it behaves similarly to the illicit drug, increasing dopamine levels in the brain by blocking dopamine reuptake. Additionally, clinical studies have shown that MPH has a lower risk of abuse than cocaine. Although studies in animals have shown that MPH can reduce cocaine dependence, studies in humans have offered more mixed results. Thus, researchers are developing libraries of MPH derivatives, searching for molecules with improved clinical efficacy. Until recently, however, it was difficult to create derivatives of one chemical component of MPH: its piperidine ring. W. Dean Harman and colleagues wanted to address this shortcoming by taking an organometallic approach.

Using a tungsten-based reagent, the researchers synthesized a library of MPH analogues specifically modified at the piperidine ring with a variety of chemical groups. And whereas MPH is a mixture of four isomers — otherwise identical molecules with small structural differences — the new method allowed the researchers to synthesize and purify compounds that were predominantly comprised of a single isomer. This could be important in clinical studies, as different isomers of some drugs can have significant impacts on therapeutic efficacy or safety. Whether any of these MPH analogues prove effective against cocaine addiction remains to be determined, but the researchers noted that the new protocol could be widely applicable to pharmaceutical development, given the ubiquity of the piperidine ring in small-molecule drugs.

The authors acknowledge funding from the National Institute of General Medical Sciences of the National Institutes of Health and the National Science Foundation.

The paper’s abstract will be available on Aug. 30 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acscentsci.3c00556

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

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Newswise — INDIANAPOLIS—Researchers from Indiana University School of Medicine have discovered a neglected brain region that could play a critical role in how likely a person with drug use disorders is to relapse, even after a long withdrawal period. Their findings were published recently in Biological Psychiatry.

“Past studies in the field of addiction research have focused on the medial prefrontal cortex, which is the part of the brain that controls decision making, but no effective prevention or treatment for drug relapse is available,” said Yao-Ying Ma, MD, PhD, associate professor of pharmacology and toxicology and an investigator with the Stark Neurosciences Research Institute at IU School of Medicine. “We focused instead on the supplementary motor cortex, and found this area plays a bigger role in the risk of relapse. It could be a new target for therapeutics to prevent relapse.”

Researchers studied cocaine-seeking behaviors in animal models, measuring excitability levels in the motor cortex after 45 days of withdrawal. They found hyperexcitability in the motor cortex was increased at this point and used an intervention to calm the excitability taking place in that part of the brain.

“One of the biggest challenges for patients with addiction is preventing relapse,” Ma said. “We know they need medication, community involvement, psychological support and other resources to help, but for many people who go back to take a drug, it just feels like an automatic behavior. If we can understand whether addiction behavior is subconscious or conscious behavior, we can find better ways to treat and prevent addiction and relapse.”

The supplementary motor cortex is typically known for directing how the body moves, so Ma said the finding that it plays a big role in addiction is novel and exciting.

“This brain region has never really gotten too much attention in addiction research, so we’re excited about this finding and how it can change the way we treat addiction by using less invasive methods, such as transcranial magnetic stimulation, as well as the trajectory of our work moving forward,” Ma said.

In the future, the team will study the effect of other addictive substances to see if the supplementary motor cortex is involved in other types of drug use disorders, such as opioid and alcohol use disorders.

The first author of the study, Donald Huang, was Ma’s PhD student. Huang recently received his PhD in Medical Neuroscience from IU School of Medicine and now works as a postdoctoral researcher at the University of Chicago.

About Indiana University School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

Newswise — Levels of grey matter in two parts of the brain may be linked to a desire to start smoking during adolescence and the strengthening of nicotine addiction, a new study has shown.

A team of scientists, led by the universities of Cambridge and Warwick in the UK and Fudan University in China, analysed brain imaging and behavioural data of over 800 young people at the ages of 14, 19 and 23.

They found that, on average, teenagers who started smoking by 14 years of age had markedly less grey matter in a section of the left frontal lobe linked to decision-making and rule-breaking. 

Grey matter is the brain tissue that processes information, and contains all of the organ’s neurons. While brain development continues into adulthood, grey matter growth peaks before adolescence.  

Low grey matter volume in the left side of the ventromedial prefrontal cortex may be an “inheritable biomarker” for nicotine addiction, say researchers – with implications for prevention and treatment. 

In addition, the scientists found that the opposite, right part of the same brain region also had less grey matter in smokers.

Importantly, loss of grey matter in the right prefrontal cortex appears to speed up only after someone has started smoking. This region is linked to the seeking of sensations.

The team argue that less grey matter in the left forebrain could lower cognitive function and lead to “disinhibition”: impulsive, rule-breaking behaviour arising from a limited ability to consider consequences. This may increase the chances of smoking at a young age.

Once a nicotine habit takes hold, grey matter in the right frontal lobe shrinks, which may weaken control over smoking by affecting “hedonic motivation”: the way pleasure is sought and managed. Excessive loss of grey matter in the right brain was also linked to binge drinking and marijuana use. 

Taken together, the findings point to a damaged “neurobehavioural mechanism” that can lead to nicotine use starting early and becoming locked into long-term addiction, say researchers. The study used data from the IMAGEN project and is published today in the journal Nature Communications.

“Smoking is perhaps the most common addictive behaviour in the world, and a leading cause of adult mortality,” said Prof Trevor Robbins, co-senior author from Cambridge’s Department of Psychology.

“The initiation of a smoking habit is most likely to occur during adolescence. Any way of detecting an increased chance of this, so we can target interventions, could help save millions of lives.”

Annual deaths from cigarettes are expected to reach eight million worldwide by the end of the decade. Currently, one in five adult deaths each year are attributed to smoking in the US alone.

“In our study, reduced grey matter in the left prefrontal cortex is associated with increased rule-breaking behaviour as well as early smoking experiences. It could be that this rule-breaking leads to the violation of anti-smoking norms,” said Robbins.

Co-author Prof Barbara Sahakian from Cambridge’s Department of Psychiatry said: “The ventromedial prefrontal cortex is a key region for dopamine, the brain’s pleasure chemical. As well as a role in rewarding experiences, dopamine has long been believed to affect self-control. 

“Less grey matter across this brain region may limit cognitive function, leading to lower self-control and a propensity for risky behaviour, such as smoking.”

The study used data gathered by the IMAGEN project from sites in four European countries: UK, Germany, France and Ireland. The researchers compared brain imaging data for those who had smoked by age 14 with those who had not, and repeated this for the same participants at ages 19 and 23.

Those with smoking experience by 14 years of age had significantly less grey matter in the left prefrontal cortex, on average. Additionally, those who started smoking by age 19 also had less grey matter in their left prefrontal cortex at 14, indicating a potential causal influence.

The scientists also looked at the right ventromedial prefrontal cortex. Grey matter loss occurs in everyone as they age. However, those who smoked from age 14 as well as those smoking from age 19 both ended up with excessive grey matter loss in the right frontal lobe.

For the right prefrontal cortex, 19-year-old smokers who did not start during adolescence had similar grey matter levels at age 14 to those who never smoked at all. This suggests a rapid reduction in the right ventromedial prefrontal cortex only begins with the onset of smoking.

Data at age 23 showed that grey matter volume in the right prefrontal cortex shrank at a faster pace in those who continued to smoke, suggesting an influence of smoking itself on prefrontal function.

Researchers also analysed data from two questionnaires completed by participants to investigate the personality traits of novelty seeking and sensation seeking.

“Both questionnaires examine the pursuit of thrilling experiences, but they measure distinct behaviours,” said Robbins. “The sensation seeking scale focuses on pleasurable experiences, while the novelty seeking questionnaire includes items on impulsiveness and rule-breaking.”

Less grey matter in the left prefrontal cortex was associated with novelty seeking, particularly disorderly and rule-breaking behaviour, while reduced grey matter volume in the right prefrontal cortex was linked to sensation seeking only.

Lead author Prof Tianye Jia from Fudan University added: “Less grey matter in the left frontal lobes is linked to behaviours that increase the likelihood of smoking in adolescence.

“Smokers then experience excessive loss of grey matter in the right frontal lobes, which is linked to behaviours that reinforce substance use. This may provide a causal account of how smoking is initiated in young people, and how it turns into dependence.”

BYLINE: Darrell Ward

Newswise — COLUMBUS, Ohio – Gene therapy might offer a one-time, sustained treatment for patients with serious alcohol addiction, also called alcohol use disorder, according to a new study led by a researcher at The Ohio State University Wexner Medical Center and College of Medicine.

The animal study, published in the journal Nature Medicine, also involved researchers at the Oregon Health and Science University, the Oregon National Primate Research Center and the University of California San Francisco.

The study used an accepted primate model to show that sustained release of glial-derived neurotrophic factor (hGDNF) in a region of the brain called the ventral tegmental area (VTA) may prevent a return to excessive alcohol use after a period of abstinence. Furthermore, it may do so without disrupting other motivated behaviors.

“This gene-therapy approach targets changes in dopamine function in the brain’s mesolimbic reward pathway that are caused by chronic alcohol use,” says co-principal investigator and co-corresponding author Krystof Bankiewicz, MD, PhD, professor of Neurological Surgery and director of the Brain Health and Performance Center at Ohio State. “Our findings suggest that this treatment can prevent relapse without requiring long-term treatment adherence by patients.”

People with alcohol use disorder (AUD) commonly experience repeated cycles of abstinence followed by relapse, even when using one of the few FDA-approved drug therapies, Bankiewicz notes.

Excessive alcohol use alters certain nerve tracts in the brain that involve the release of the neurotransmitter dopamine. These neurons make up the mesolimbic reward pathway, which plays a major role in alcohol and drug addiction.

These alterations become more pronounced as AUD develops. They include reduced levels of dopamine release, reduced sensitivity of dopamine receptors and increased dopamine uptake. These changes lead to below-normal levels of dopamine in the pathway. 

Scientists think this “hypodopaminergic” state can compel excessive alcohol users to resume drinking after periods of abstinence.

“At this time, there are no therapies that target circuits in the brain that are altered by sustained, heavy alcohol use,” says co-principal investigator and co-corresponding author Kathleen Grant, PhD, chief and professor of Behavioral Neuroscience at the Oregon National Primate Research Center.

How the study was done

This study used an accepted rhesus macaque model of AUD to examine the practicality and effectiveness of delivering a viral vector into the brain to induce continuous expression of GDNF, diminish alcohol use and prevent post-abstinence resumption of drinking.

Eight male rhesus macaques were involved; the vector was an adenoassociated virus vector that carried a gene for human glial-derived neurotrophic factor (AAV2-hGDNF).

All eight animals were first habituated to the consumption of 4% alcohol. Then four animals were infused with the hGDNF vector directly into the VTA, located in the floor of the midbrain. Neurons in the VTA connect with the mesolimbic reward pathway. The remaining four animals served as controls. They were infused with sterile saline using the same surgical procedure.

Key findings included:

• The infusion of AAV2-hGDNF significantly blunted the intake of alcohol across multiple 4-week abstinence and 4-week alcohol-reintroduction cycles;
• Blood ethanol levels were undetectable in GDNF-treated subjects and remained undetectable for most weeks through the study’s end;
• Control subjects showed consistently elevated monthly and weekly alcohol intake and blood ethanol levels across cycles, as a group and individually. 

“Overall, our findings indicate that GDNF gene therapy could diminish reintroduction-associated alcohol intake in our primate model,” Bankiewicz says. “We believe this approach shows merit for further study as a promising therapy for AUD and possibly other substance-abuse disorders.”

Alcohol Use Disorder

• An estimated 28.6 million American adults ages 18 and older (11.3% in this age group) and 894,000 adolescents ages 12 to 17 (3.4% of this age group) had AUD in 2021, according to the National Survey on Drug Use and Health.
• An estimated 12% of all alcohol consumers meet the criteria for AUD as defined by the Diagnostic and Statistical Manual for Mental Disorders 5th edition.
• 140,000 deaths per year in the United States are attributed to alcohol use disorder, according to the Centers for Disease Control and Prevention.

This study was supported by grants from the National Institutes of Health (AA024757, AA013510, AA014091, AA010760, AA019431, OD011092, AA026117).

Other researchers involved in this study were Victor S. Van Laar, Jerusha Naidoo, Piotr Hadaczek, Lluis Samaranch, The Ohio State University; Matthew M. Ford, Lauren E. Vanderhooft, Jodi L. McBride, Oregon National Primate Research Center, Oregon Health & Science University; Brianna George, Katherine M. Holleran, Emily G. Peck, Monica H. Dawes, Sara R. Jones, Wake Forest School of Medicine; Kousaku Ohno, John Bringas, John R. Forsayeth, University of California San Francisco.

# # #

Newswise — People who drink heavily experience heightened pleasurable effects throughout a drinking episode, which may be what motivates them to continue drinking, and not, as is commonly believed, that they require more alcohol in order to experience these effects. So suggests a first-of-its-kind study of real-world, real-time drinking experiences and motivations of different types of drinkers just published in Alcohol: Clinical and Experimental Research.

Researchers found that high-risk drinkers felt greater positive effects of alcohol compared to light drinkers, suggesting they are more sensitive to alcohol stimulation and reward. Sedation did not differ across groups. These findings held even when accounting for differences in alcohol consumption across the groups.

Light drinkers reported feeling the effects of their drinking more than other groups in the first fifteen minutes of a drinking episode. Heavy drinkers felt the drinks more one to three hours after they began drinking, and drinkers with moderate to severe alcohol use disorder reported greater feeling at 90 minutes to three hours after they began drinking. Respectively, the groups averaged three, seven, and nine drinks per drinking episode. Both high-risk drinking groups drank throughout the three-hour period, with half of heavy drinkers and two-thirds of drinkers with moderate to severe alcohol use disorder drinking beyond three hours.

Researchers used a smartphone-based assessment tool to collect real-time feedback from participants about their alcohol use and their drinking experiences and motivations throughout a drinking episode, as well as before and after it. One hundred drinkers categorized as either light drinkers, heavy drinkers, or drinkers with moderate to severe alcohol use disorder were included in the study. As they started drinking, and at seven different intervals in the first three hours after they began drinking, participants completed smartphone-based questionnaires about how many drinks they had consumed, whether they were feeling stimulated or sedated, how much they ‘felt’ the effects of the drink, whether they liked the effects, and whether they wanted more.

The study’s high response rate, about 90%, supports the utility of the smartphone-based assessment tool called HR-EMA with light drinkers and high-risk drinkers. HR-EMA, or High-Resolution Ecological Momentary Assessment, is designed to capture data in real-time in the participant’s natural environment. The study estimated Blood Alcohol Concentration (BAC), factoring in participants’ weight, gender, self-reported number of drinks, and average metabolism rate; emerging biosensor technologies may be able to provide more accurate BAC data for future studies. Additionally, the authors recommend that future studies involve a wider range of individuals, including people with psychiatric conditions.

Assessing real-time positive subjective effects of alcohol using high-resolution ecological momentary assessment (HR-EMA) in risky versus light drinkers. D. Fridburg, Z. Lee, A. Fischer, J. Cursio, A. King. (pp. x- xx)

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Newswise — Brain imaging of neuron activity in certain areas of the brain may predict whether an individual is likely to successfully respond to interventions to reduce their drinking. In a study published in Alcohol: Clinical and Experimental Research, individuals whose baseline imaging showed decreased activity in areas of the brain associated with reward processing and impulsivity and increased activity in regions responsible for complex cognitive processes and emotional regulation were more likely to reduce their drinking following an intervention.

The study examined differences in pre-intervention resting state functional connectivity (rsFC) between people with alcohol use disorder who reduced their alcohol consumption and those who did not. Resting-state functional connectivity is an indirect measure of neuron activity between areas of the brain while the brain is not engaged in specific cognitive, emotional, or other tasks.

Functional Magnetic Resonance Imaging (MRI) showed significant differences in baseline resting state functional connectivity in regions of the brain associated with reward processing, stimulus prioritization, and complex problem-solving in those who responded well to interventions compared to those who did not. People with alcohol use disorder who reduced their drinking after the intervention also showed decreased activity in the regions associated with impulsivity and alcohol valuation and increased activity in the regions responsible for higher-order cognitive processes and emotional regulation.

The patterns suggest that individuals who responded well to the intervention may have greater internal motivation or less severe disruption to the brain from their alcohol use disorder which may allow them to better engage in the intervention to reduce alcohol use and increase positive behaviors.

The Canadian study conducted functional MRIs on 46 adults with alcohol use disorder aged 21 to 55 immediately followed by a brief, approximately one-hour-long intervention aimed at reducing their alcohol use, with the option of 3 additional visits if participants chose. Three months later, researchers assessed changes in participants’ alcohol use.

Both male and female participants who responded to the intervention reduced the amount they drank per week, from 34 drinks per week at baseline to 15 at three months for male participants and 20 drinks per week to six for female participants. For those who did not respond to the intervention, the weekly number of drinks remained relatively flat for men and increased for women from 19 drinks per week at baseline to 24 drinks per week after 3 months.

The authors note that while the resting state functional connectivity patterns identified in the study may contribute to positive health behavior, the analysis is exploratory and further investigation is needed.

Resting-state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study. S.K. Syan, C. McIntyre-Wood, E. Vandehei, M. Vidal, T. Hargreaves, E. Levitt, M. Scarfe, E. Marsden, E. MacKillop, H. Sarles-Whittesley, M. Amlung, L. Sweet, J. MacKillop. (p. x-xx)

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BYLINE: Myra Wright

Newswise — WINSTON-SALEM, N.C. – Aug. 3, 2023 – According to the 2021 National Survey on Drug Use and Health, 4.8 million people (ages 12 and up) reported using cocaine within the previous 12 months, and 24,486 people died from an overdose involving cocaine. Because there are no FDA-approved medications for cocaine use disorder, there is an urgent need to develop therapeutic interventions.

In a new preclinical study from Wake Forest University School of Medicine, scientists provide the first evidence that changes in the gut microbiome have significant effects on cocaine use and cravings after withdrawal.

The study appears online in the journal Neuropsychopharmacology.

“In patients with a history of cocaine use disorder, there is a significant risk of relapse, and there are no effective medication treatments to reduce this risk. So, our study examines how the gut microbiome can impact drug seeking over time,” said Drew Kiraly, M.D., Ph.D., associate professor of physiology, pharmacology and psychiatry at Wake Forest University School of Medicine and Atrium Health Wake Forest Baptist.

The gut microbiome refers to the population of trillions of bacteria that live in the gastrointestinal tract of humans and animals. The connection between the microbiome and good health is well established, but more research is needed on how changes in the microbiome impact cravings for cocaine.

For the study, the research team administered antibiotics in a rodent model to measure the behavioral effects of a reduced microbiome. They found that animals with a depleted microbiome took more cocaine and worked harder to seek drugs after abstinence. This suggests that the rewarding effects of cocaine were affected by the gut microbiome. In addition to the behavioral changes, the research team also found that microbiome depletion significantly changed important neurobiological markers in reward-related brain structures.

The scientists also discovered that the effects of microbiome depletion could be reversed with the addition of molecules produced by beneficial bacteria in the gut microbiome that are important for brain health known as the short-chain fatty acids.

Kiraly said these findings provide an important foundation for future studies on specific microbial composition and how metabolite levels work on drug-seeking and other motivated behaviors.

“We might one day be able to target specific parts of the microbiome to help reduce drug relapse,” Kiraly said.

This research was supported by National Institutes of Health grants DA051551, DA044308, DA050906, DA053105 and NS124187.