Category: Substance Use

Categories : Pain Management Substance UseTags :

Teens More Likely to Use Opioids when Parents Have Prescriptions

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Norwegian study of more than 21 000 young people found that those whose parents had persistent opioid prescriptions faced more than double the risk of persistent opioid use

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If a parent has persistent opioid prescriptions, their adolescent or young adult offspring has more than double the risk of persistent opioid use, according to a new study published October 23rd in the open-access journal PLOS Medicine by Anna Marcuzzi of the Norwegian University of Science and Technology, Norway, and colleagues.

The prescription of strong analgesics such as opioids is not recommended for young people. However, despite potential adverse long-term consequences, opioids are often prescribed for non-malignant pain in this population.

In the new study, researchers analysed data from 21 470 adolescents and young adults aged 13-29 years who participated in the population-based Young-HUNT or HUNT Study in Norway in 2006-2008 or 2017-2019. Each participant was linked with at least one parent who also participated in the HUNT study, and opioid prescription data were obtained from the Norwegian Prescription Database.

24.4% of young people had at least one opioid prescription during the seven-year follow-up period, while 1.3% had persistent opioid prescriptions, defined as prescriptions in at least three out of four quarters of a year. When a mother had persistent opioid prescriptions over a five-year period (two years before and three years after offspring participation), their offspring had 2.60 times the risk of persistent opioid use compared to those whose mothers had no prescriptions. When a father had persistent opioid prescriptions, their offspring had 2.37 times the risk of persistent opioid use. The association was also present but weaker for non-persistent opioid prescription – offspring whose mothers had two or more prescriptions had 1.34 times the risk of receiving any opioid prescription, while those whose fathers had two or more prescriptions had 1.19 times the risk, compared to offspring whose parents had no prescriptions. There was no clear evidence that parental chronic musculoskeletal pain status influenced these associations.

The authors note that because parental opioid prescriptions were measured both before and after offspring HUNT participation, some parental opioid prescriptions could have begun after offspring opioid use. However, they conclude that there is an association between parental and offspring opioid prescriptions.

“The study findings suggest that family-based strategies should be considered when managing pain conditions in adolescents and young adults to avoid potentially unnecessary opioid use,” they say.

The authors add, “Despite restrictive opioid policies, one in four adolescents and young adults received an opioid prescription during the seven years follow-up.”

“Adolescents whose parents had two or more opioid prescriptions had a more than two-fold higher risk of persistent opioid use (ie, multiple prescriptions in a year) than if the parents had no opioid prescriptions.”

Provided by PLOS

Categories : Ethics and Law Substance UseTags :

INHSU 2025: Global Drug Policy and Harm Reduction Leaders Meet in Cape Town

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With drug use projected to rise 40% in Africa by 2030, a global conference will amplify pioneering policy responses and proven health interventions from across Africa and beyond.

14–17 October 2025 | Century City Conference Centre, Cape Town

By 2030, the number of people who use drugs in Africa is projected to rise by 40%, according to the United Nations Office on Drugs and Crime (UNODC). Without stronger drug policy and harm reduction responses, the region faces escalating rates of overdose, HIV, hepatitis C, and other harms.

The warning signs are already here: around 11% of the estimated 1.26 million people who inject drugs across sub-Saharan Africa are living with HIV and an estimated 15% currently have hepatitis C, a liver condition that can cause liver cancer and death.

New research also shows that more than 40% of people who inject drugs in sub-Saharan Africa have experienced a recent non-fatal overdose – more than double the global average of 18.5%.

“While the scale of the challenge is undeniable, pioneering efforts by a few African governments show what harm reduction leadership can look like,” says Angela McBride, Executive Director of the South African Network of People Who Use Drugs (SANPUD), INHSU board member, and co-convener of INHSU 2025. “Harm reduction means putting health and human rights before punishment – shifting away from criminalisation and towards evidence-based, rights-affirming policies.”

These evidence-based policies include decriminalising drug use, expanding needle and syringe programs (NSP) to provide sterile equipment to prevent the spread of blood-borne viruses, increasing access to opioid agonist therapy (OAT) – medication to treat opioid dependence and reduce cravings and withdrawal from opioids like heroin – and ensuring access to HIV and hepatitis B and C testing and treatment.

Africa responds to the crisis

Across the continent, examples of this leadership are starting to emerge – from new legislation in Kenya to large-scale service delivery in Mauritius.

  • In South Africa, the Central Drug Authority is implementing the National Drug Master Plan, acknowledging that the country’s drug crisis is worsening and calling for stronger cross-sector responses. The plan recognises harm reduction and OAT must be expanded if HIV and hepatitis C are to be contained. Ms Nandi Mayathula-Khoza, Chairperson of the Central Drug Authority, will be presenting on the new plan during the conference.
  • In Kenya, parliament is currently debating a Harm Reduction Bill. If passed, it would be a landmark move, embedding access to NSP, HIV-related healthcare services, and other evidence-based services into national law for the first time.
  • Finally, in Mauritius, government-backed harm reduction has already achieved coverage levels rarely seen in the region. More than half of people who inject drugs are receiving OAT, supported by a pioneering “social contracting” model that channels government funds directly to NGOs to deliver NSP and other services on the ground.

Learning both ways

These policy shifts will be a focus of INHSU 2025’s Policy Day, which will bring together decisionmakers from across Africa to debate and share reform strategies. The wider conference will then welcome more than 600 global experts – including researchers, clinicians, policymakers, and people with lived experience of drug use – to showcase African-led harm reduction successes alongside international innovations such as long-acting depot buprenorphine (LADB), a monthly treatment for opioid dependence, and community-led hepatitis C testing and treatment programs that are transforming outcomes worldwide.

“The evidence consistently shows that harm reduction works – what we need now is political will,” says Dr Andrew Scheibe, medical doctor and technical advisor with TB HIV Care in Cape Town, INHSU board member, and fellow co-convener of INHSU 2025. “Harm reduction reduces infections, prevents overdose, and connects people to healthcare, yet access across Africa remains the exception rather than the rule. INHSU 2025 will showcase how we can bridge that gap and deliver the services people urgently need.”

Funding, prisons, and women’s health

Beyond drug policy reform and harm reduction, the conference will focus on other areas with profound impacts on the lives of people who use drugs, including incarceration, gender specific health disparities, and shifts in funding.

Prisons and detention settings will feature prominently, with Professor Louisa Degenhardt (National Drug & Alcohol Research Centre, Australia) presenting a multistage systematic review on the global epidemiology of injecting drug use, HIV, viral hepatitis, and tuberculosis among people who are incarcerated.

Women face extreme stigmatisation and complex barriers to healthcare, especially during pregnancy. Women who use drugs will also be a core focus, with multiple presentations from speakers across Africa and globally. Neliswa Gogela (Groote Schuur Hospital/University of Cape Town, South Africa) will present on HIV and HCV Care for Women Who Use Drugs with other presentations from Tanzania and Kenya.Finally, Kennedy Kipkoech (University of Cape Town and University of Bristol, UK) will present new modelling on the potential impact of the suspension of US PEPFAR funding for OAT on HIV and hepatitis C transmission among people who inject drugs. PEPFAR has saved an estimated 26 million lives, prevented 7.8 million babies from being born with HIV, and supported millions of orphans and vulnerable children across sub-Saharan Africa (Lancet EClinicalMedicine, 2025).

“These issues go to the heart of what drives health inequities for people who use drugs,” says Emma Day, Executive Director of INHSU. “Incarceration increases risk of acquiring HCV, HIV and other infectious diseases. Women who use drugs are among the most stigmatised populations and gender responsive models are needed to appropriately support them. And without sustainable funding, harm reduction progress across Africa is at risk. INHSU 2025 is about confronting these systemic challenges head-on and building a stronger, more equitable response.”

View the full program here

Categories : Gender Substance UseTags :

Care for Women and Harm Reduction Services Under the Spotlight

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Facing off a dual burden of high disease risk and low service access

Photo by Sydney Sims on Unsplash

CAPE TOWN, 08 OCTOBER 2025: South African and international leaders in public health will gather on Friday, 10 October 2025 at the University of Cape Town to convene an in-person scientific seminar: Agents of change and women who use drugs. Women who use drugs (WWUD) in South Africa face compounded health and social vulnerabilities that leave them disproportionately excluded from essential health services. Compared to men, women experience heightened stigma, intimate partner violence, reproductive health challenges, and structural barriers such as childcare responsibilities and lack of women-centred care.1,2 Scientific discussions among academics will focus on how women can be supported through access to harm reduction programming and drug policy reform.  

 Seminar: Agents of change and women who use drugs

·        Date    : 10 October 2025

·        Time    : 13:30 – 15:30 (SAST)

·        Venue  : Neurosciences Institute Auditorium, UCT/Groote Schuur Hospital, Cape Town

·        Registration

Recent evidence highlights both the scale of drug use and the urgent need for tailored harm reduction. National estimates suggest there are approximately 82 500 people who inject drugs (PWID) in South Africa, with women comprising between 16% and 27% of this population.3 Led by TB HIV Care, a 2023 bio-behavioural survey across four South African sites documented extremely high HIV prevalence among PWID: 72.1% in Tshwane, 49.3% in eThekwini, 45.4% in Mashishing, and 30.3% in Mbombela. Hepatitis C (HCV) prevalence was similarly alarming, reaching 89% in Tshwane and over 75% in multiple sites.3

“The evidence consistently shows that harm reduction works,” says Dr Andrew Scheibe, medical doctor and technical advisor with TB HIV Care in Cape Town, INHSU board member, and fellow co-convener of the upcoming INHSU 2025 conference. “Harm reduction reduces infections, prevents overdose, and connects people to healthcare, yet access across Africa remains the exception rather than the rule.”

Sex-based disparities are stark. While HIV prevalence among PWID overall has ranged from 14% to over 70%, women consistently show higher prevalence rates than men. One multi-city study found 18% HIV prevalence among female PWID, compared to 13% among males.4 More recent research in Durban confirmed that women face greater barriers to accessing sexual and reproductive health, harm reduction, and HIV services, often due to fear of arrest, intimate partner control, and lack of programming designed for women.5

“Everyone in our communities deserve health, dignity, and care,” says Mfezi Mcingana, Programme Director: Key Populations at TB HIV Care. “People who use drugs are part of our communities and supporting their access to healthcare, not punishment, builds a safer, healthier society for all”, Mcingana concludes.

Despite the magnitude of risk, women remain underrepresented in harm reduction programmes. In opioid agonist therapy (OAT), fewer than 10% of participants are women.6 Needle and syringe programmes (NSPs) and OAT are limited in coverage, mostly urban-based, and not designed with women’s needs in mind. The absence of services aimed at women perpetuates cycles of preventable morbidity, mortality, and infectious disease transmission.

“While the scale of the challenge is undeniable, pioneering efforts by a few African governments show what harm reduction leadership can look like,” says Angela McBride, Executive Director of the South African Network of People Who Use Drugs (SANPUD), INHSU board member, and co-convener of INHSU 2025. “Harm reduction means putting health and human rights before punishment, shifting away from criminalisation and towards evidence-based, rights-affirming policies.”

To address this gap, investment in women-centred harm reduction is essential. Priorities include scaling up OAT and NSPs with women-specific entry points, integrating sexual and reproductive health services into harm reduction sites, providing childcare support, and ensuring protection from intimate partner violence. Without these interventions, WWUD in South Africa will continue to be excluded from public health progress and national HIV/HCV response goals.

References:

  1. Shirley-Beavan, S., Roig, A., Burke-Shyne, N., Daniels, C. and Csak, R. (2020). Women and barriers to harm reduction services: a literature review. Harm Reduction Journal, 17(74). Available here.
  2. Harm Reduction International & South African Network of People Who Use Drugs (SANPUD) (2020). Barriers to harm reduction for women who use drugs in South Africa. London: Harm Reduction International. Available here.
  3. SANPUD (2023). South African bio-behavioural survey and population size estimation among people who inject drugs. Johannesburg: South African Network of People Who Use Drugs. Available here.
  4. Scheibe, A., Young, K., Moses, L., Basson, R., Versfeld, A., Spearman, C.W. and Sonderup, M.W. (2016). HIV prevalence and risk among people who inject drugs in South Africa. International Journal of Drug Policy, 30, pp.107–113. Available here.
  5. Milford, C., Cavanagh, T., Bosman, S., Chetty, T. and Rambally, G. (2024). Access to and acceptability of sexual and reproductive health, harm reduction and other essential health services among people who inject drugs in Durban, South Africa. Harm Reduction Journal, 21(123). Available here.
  6. INHSU (2021). Gender and opioid substitution therapy access in Tshwane, South Africa. International Network on Health and Hepatitis in Substance Users. Available here.
Categories : Substance UseTags :

Flavoured Marijuana Vapes Becoming New Face of Teen Drug Use, Sparking Addiction Fears

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Flavoured marijuana vaping is now the most common form of use among American teenagers who vape cannabis, according to new findings from the University of Michigan.

The research, published in the Journal for Adolescent Health, found particularly sharp increases among younger teens between 2021 and 2024. Among eighth graders who vaped marijuana, the percentage using flavoured solutions jumped from 47% in 2021 to 63% in 2024. The trend was similar for older students, with use climbing from 41% to 53% for 10th graders and from 36% to 50% for 12th graders.

“The findings suggest that these products are gaining traction among youth; in fact, since the pandemic onset in 2020 youth appear to be turning toward these products while reducing their use of all other drugs,” said Richard Miech, principal investigator of the Monitoring the Future study at U-M’s Institute for Social Research.

The overall percentage of marijuana users who chose to vape the drug also grew over the study period. Among eighth graders who had used marijuana in the past 12 months, the percentage who vaped it increased from 48% to 57%. In 10th grade, the number went from 60% to 66%, and among 12th graders, it rose from 58% to 67%.

“Flavoured vaping solutions offer a discreet mode of cannabis use, with flavours apparently enhancing their appeal,” Miech said. “The study results suggest that a growing proportion of youth find the newly available flavours – especially fruit flavours – more attractive than the standard cannabis taste.

“Vaping does not produce the distinctive odor that comes from smoking cannabis, and vaping devices can be quickly concealed if an authority figure appears unexpectedly.”

More addictive?

This increase in those who vaped highlights growing public health concerns about changing patterns of substance use among teens.

“As for health consequences for cannabis use, one of the most potentially serious is addiction,” Miech said. “Should cannabis use become more popular among youth in future years, then a greater number will end up with an addiction that can impair their social and academic life. Many people may not realize that more adolescents meet the criteria for cannabis use disorder than for alcohol use disorder, with 5% affected by cannabis compared to 3% for alcohol.”

These results point to flavored marijuana vaping solutions as a critical area for future research and policy development. The study’s authors suggest that these findings underscore the need for targeted policies, interventions and educational campaigns to address and mitigate this escalating concern among young people.

“Our survey includes questions on both cannabis’s perceived risk and its social acceptability,” Miech said. “Interestingly, perceived risk among adolescents actually increased over the study period from 2021-24, and social acceptability has gone down. That being said, our questions so far have been about cannabis use in general, and not flavoured cannabis solutions, which students may view differently.”

Would restricting flavoured vapes work?

Recent trends in adolescent cannabis vaping raise concerns about the best way to protect youth. Restricting flavors may seem like an easy solution, but it is by no means a guaranteed success, researchers said.

Teens who seek flavored cannabis products could easily shift to unflavored options or return to smoking cannabis in traditional forms. At the same time, adults in states with legal cannabis may resist limits on flavor choices, and industry lobbying could block such policies.

“An alternative approach to restricting supply of cannabis flavours is to restrict demand,” Miech said. “That is, to reduce teens’ interest and willingness to use cannabis, including flavoured vaping solutions. A demand reduction approach has been very effective for cigarettes.”

Evidence from previous studies on cigarette use supports this approach. In 1998, 35% of 12th graders had used cigarettes in the past month. By 2024, that number dropped to 3%. Cigarettes remained legal and available, but broad-based media campaigns, public education and tighter rules on marketing to youth drove the change.

Source: University of Michigan

Categories : Respiratory Diseases Substance UseTags :

Inhaling Cannabis May Greatly Increase Risk of Lung Disease

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For those looking to reduce their chances of developing lung disease, say experts at UC San Francisco, then it may be smart to avoid inhaling cannabis.

A new study in the Journal of General Internal Medicine found that inhaling marijuana every day is associated with a 44% increased chance of developing asthma. It also increases the odds of developing a common set of lung diseases known as chronic obstructive pulmonary disease (COPD) by 27%.

The risk of COPD, which includes emphysema and chronic bronchitis, may be understated. The disease takes decades to develop, and the researchers did not have detailed information on how long people in the study had been using cannabis.

Researchers defined “inhaling” as smoking, vaping, and so-called “dabbing,” which involves breathing in the vapors of concentrated marijuana. The study found an association between elevated risks to a person’s lungs and doing any of those things with cannabis even for those who had never smoked cigarettes.

For those who never smoked cigarettes, inhaling marijuana every day was linked to a 51% increased likelihood of developing asthma. The association with COPD was also elevated, but it was not statistically significant.

The study is the largest yet to examine the association between inhaling cannabis and risks to respiratory health among people who have not smoked cigarettes. Of the 380 000 adult participants, nearly 222 000 had never smoked tobacco. The data comes from the Behavioral Risk Factor Surveillance System, a national survey by the Centers for Disease Control and Prevention (CDC).

Experts say the broad legalization of marijuana across much of the country and the perception that it is healthier than tobacco has led people to minimize the risks.

“The message about smoking tobacco being bad for you has gotten out there, but for cannabis, it’s much less clear,” said Alison Rustagi, MD, PhD, assistant professor at UCSF and first author of the paper.

“If people are looking to reduce their likelihood of developing a chronic lung disease, they should not start using cannabis,” she said. “And if they already smoke cannabis, they should do it less often.”

Source: University of California – San Francisco

Categories : Substance UseTags :

Rates of Alcohol-induced Deaths Among the General Population Nearly Doubled from 1999 to 2024

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With females aged 25-34 showing a 255 percent surge in alcohol-related deaths during this time period

Credit: Pixabay CC0

In an analysis by race, sex, age, and geography, alcohol-induced death rates in 2024 are nearly double those in 1999, with a sharp increase at the onset of the COVID-19 pandemic. Although rates are higher for men, the largest increase in alcohol-induced deaths over the full 25-year period occurred in females aged 25-34, according to a study published on September 17 by Dr Tony Wong and colleagues at UCLA in the open-access journal PLOS Global Public Health.

Alcohol-induced deaths have been increasing over the past two decades. Particularly concerning are increases between 2019 and 2021, when the population was under significant stress from isolation due to the COVID-19 pandemic, and people with alcohol-use disorders were less able to access treatment. Quantifying mortality trends and determining whether alcohol-induced deaths have returned to pre-pandemic levels is essential for understanding long-term temporal patterns and dynamics. To examine these trends, the authors of this study analysed data from the Centers for Disease Control and Prevention’s National Vital Statistics System, focusing on 14 specific alcohol-induced causes of death.

Wong et al. found that rates of alcohol-induced deaths in the United States nearly doubled between 1999 and 2024, reaching their highest level in 2021. Most deaths are due to alcoholic liver disease and, to a lesser degree, alcohol-related mental and behavioural disorders. The largest overall increase in alcohol-induced mortality across all race, sex, age groups occurred in 2021 when fatalities peaked at 54,258 deaths overall. By 2024, fatalities had declined, but the average alcohol-induced mortality rate across U.S. counties remained approximately 25% higher than in 2019.

American Indian/Alaska Native populations (AIAN) remain the most affected, with male AIAN rates of alcohol-induced mortality three times higher than that of white males, and female AIAN mortality rates four times higher than that of white females, over the entire period of investigation.

The largest increase by demographic was among females aged 25-34, which rose from 0.9 deaths per 100 000 in 1999 to 3.2 per 100 000 in 2024 — a 255 percent increase. The second largest increase was in males aged 25-34, from 2.3 fatalities per 100 000 in 1999 to 6.5 in 2024 — a 188 percent increase. As deaths from chronic diseases related to alcohol use, such as certain cancers or cardiovascular events, were not included in this study, the overall fatality counts may be underestimated. These findings underscore the critical need for targeted policies to reduce excessive alcohol consumption and improve access to treatment for those who need it most.

Senior author Maria R D’Orsogna adds: “The rapid rise of alcohol-induced deaths among women is particularly concerning. Although men still die at higher rates, the gender gap appears to be closing. Notably, for the population aged 25-34, the male-to-female mortality ratio has decreased from three-to-one in 1999 to two-to-one in 2024.”

The authors conclude: “The rise in alcohol-induced mortality is widespread and affects the entire country, with particularly large surges arising during the COVID-19 pandemic. In the early months of the pandemic, alcohol-induced deaths among AIAN males increased by as much as 40% in a single month and remained unusually high for nearly four years. Similar trends were observed among AIAN and Black females, whose alcohol-induced death rates rose by over 30% in one month.”

Provided by PLOS

Categories : Metabolic Disorders Substance UseTags :

GLP-1 Receptor Agonists Protect the Liver During Alcohol Consumption

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GLP-1 receptor agonists are also promising for the treatment of alcohol use disorder and alcohol-associated liver disease, as growing evidence suggests they reduce the motivation to drink alcohol. Now, surprising new findings reveal that the medications may have direct protective effects on the liver as well.

In a new study, published in npj Metabolism Health and Disease, Yale School of Medicine (YSM) researchers found that in mice, GLP-1RAs reduced an enzyme that metabolises alcohol. That, in turn, decreased the production of toxic alcohol metabolites.

“This is the first time that GLP-1 receptor agonists have been shown to regulate alcohol metabolism in the liver,” says principal investigator Wajahat Mehal, MD, professor of medicine (digestive diseases) at YSM. “If you’re taking semaglutide, then your body will likely handle alcohol differently.”

However, because these drugs slowed the metabolism of alcohol, the mice also had higher blood alcohol levels, the researchers found.

“GLP-1 receptor agonists seem to have very similar effects in mice and humans,” says Mehal. “If these results are also reproduced in humans, people using GLP-1 receptor agonists might be drinking an amount of alcohol that does not normally put them above the legal blood alcohol level, but because they are taking this drug, it does.”

Further studies in humans are needed to understand these impacts of GLP-1 receptor agonists more fully, he stresses.

GLP-1 receptor agonists decrease toxic alcohol metabolites

In the study, researchers gave mice either a GLP-1 receptor agonist or a placebo. They observed that mice receiving the medication had decreased levels of a liver enzyme known as Cyp2e1, which breaks down alcohol into a toxic metabolite called acetaldehyde.

“This is significant because alcohol itself is actually not the most toxic molecule to the liver,” explains Mehal. Rather, acetaldehyde is one of the major drivers of alcohol-related harm to the liver. “These drugs are resulting in less acetaldehyde.”

The findings suggest that not only might GLP-1 receptor agonists help the liver by acting on the brain to reduce alcohol consumption, but also through slowing metabolism of alcohol in the liver, and in turn reducing the levels of toxic metabolites.

Ongoing clinical trials are currently testing the benefits of semaglutide for people living with alcohol-induced liver disease. The study suggests that GLP-1 receptor agonists may offer greater benefits to the liver than previously thought, and that the drug may still help patients who are not abstaining from alcohol.

“Even if some individuals don’t reduce their alcohol intake while they’re on a GLP-1 receptor agonist, they will probably still have hepatic protection, because fewer toxic metabolites will be produced in the liver,” Mehal says.

GLP-1 receptor agonists increase blood alcohol concentration

In another experiment, the researchers measured blood alcohol concentrations of mice 30 minutes after giving them alcohol. They found that mice who had received a GLP-1 receptor agonist had higher blood alcohol concentrations compared to controls, and that these levels took longer to drop.

More research is needed to better understand the consequences of elevated blood alcohol levels on the rest of the body, Mehal says.

“If the liver is not metabolizing alcohol as quickly, the alcohol load could be shifted to other organs,” he poses. “Then, not only might people have a high blood alcohol level, but may also experience more cognitive effects like discoordination.”

The number of people taking these drugs is rapidly increasing—as many as one in eight adults in the U.S. have used or are currently using a GLP-1 receptor agonist. Meanwhile, about half of U.S. adults drink alcohol and 6% report drinking heavily.

As the use of these medications for a range of conditions continues to rise, it is increasingly important to study the interactions between these medications and alcohol, Mehal says.

“There already are large numbers of people who are taking GLP-1 receptor agonists and are drinking either social amounts or excess amounts of alcohol,” says Mehal. “We need to know the effects of these drugs in that setting.

Source: Yale School of Medicine

Categories : Neurology Substance UseTags :

Brain Study Prompts a Rethink of Alcohol Abuse and Relapse

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What compels someone to keep engaging in alcohol use, even if it damages their health, relationships and wellbeing? A new study from Scripps Research offers an important clue: a small midline brain region plays a key role in how animals learn to continue drinking to avoid the stress and misery of withdrawal.

In a new study, published in Biological Psychiatry: Global Open Science on August 5, 2025, the Scripps Research team zeroed in on a set of brain cells in the paraventricular nucleus of the thalamus (PVT) in rats. They found that this region becomes more active, driving strong relapse behaviour, when rats learn to associate environmental stimuli with the easing of withdrawal symptoms by alcohol. By illuminating this brain pathway, the research sheds light on one of the most stubborn features of addiction – drinking not for pleasure, but to escape pain – and could eventually lead to new treatments for substance use disorders (SUDs) as well as other maladaptive behaviours including anxiety. 

“What makes addiction so hard to break is that people aren’t simply chasing a high,” says Friedbert Weiss, professor of neuroscience at Scripps Research and senior author of the study. “They’re also trying to get rid of powerful negative states, like the stress and anxiety of withdrawal. This work shows us which brain systems are responsible for locking in that kind of learning, and why it can make relapse so persistent.”

“This brain region just lit up in every rat that had gone through withdrawal-related learning,” says co-senior author Hermina Nedelescu of Scripps Research. “It shows us which circuits are recruited when the brain links alcohol with relief from stress – and that could be a game-changer in how we think about relapse.”

From behaviour to brain maps

An estimated 14.5 million people in the United States have alcohol use disorder, which encompasses a range of unhealthy drinking behaviours. Like other drug addictions, alcohol addiction is characterised by cycles of withdrawal, abstinence and relapse. 

In 2022, Weiss and Nedelescu used rats to study the types of learning that happen in the brain throughout this cycle. When rats initially begin drinking, they learn to associate pleasure with alcohol and seek more. However, that conditioning becomes far stronger during multiple cycles of withdrawal and relapse. After learning that alcohol eased the unpleasant feelings of withdrawal – negative reinforcement, or a relief of ‘negative hedonic state’ – the animals sought out more alcohol and would remain persistent even when uncomfortable.

“When rats learn to associate environmental stimuli or contexts with the experience of relief, they end up with an incredibly powerful urge to seek alcohol in the presence of that stimuli –even if conditions are introduced that require great effort to engage in alcohol seeking,” says Weiss. “That is, these rats seek alcohol even if that behavior is punished.” 

In the new work, the team wanted to pin down exactly what networks of cells in the brain were responsible for learning to associate environmental cues with the relief of this negative hedonic state.

The researchers used advanced imaging tools to scan entire rat brains, cell by cell, and pinpoint areas that became more active in response to alcohol-related cues. They compared four groups of rats: those that had gone through withdrawal and learned that alcohol relieves a negative hedonic state, and three different control groups that had not.

While several brain areas showed increased activity in the withdrawal-learned rats, one stood out: the PVT, which is known for its role in stress and anxiety.

“In retrospect, this makes a lot of sense,” says Nedelescu. “The unpleasant effects of alcohol withdrawal are strongly associated with stress, and alcohol is providing relief from the agony of that stressful state.” 

The researchers hypothesise that this negative hedonic state, and the activation of the PVT in the brain as a response, is critical for how the brain learns and perpetuates addiction.

A better understanding of addiction

The implications of the new study extend well beyond alcohol, the researchers say. Environmental stimuli conditioned to negative reinforcement – the drive to act in order to escape pain or stress – is a universal feature of the brain, and can drive human behaviour beyond substance use disorders such as anxiety disorders, fear-conditioning and traumatic avoidance learning.

“This work has potential applications not only for alcohol addiction, but also other disorders where people get trapped in harmful cycles,” says Nedelescu.

Future research will zoom in even further. Nedelescu and colleagues at Scripps Research want to expand the study to females and to study neurochemicals released in the PVT when subjects encounter environments associated with the experience of this relief from a negative hedonic state. If they can pinpoint molecules that are involved, it could open new avenues for drug development by targeting those molecules.

For now, the new study underscores a key shift in how basic scientists think about addiction.

 “As psychologists, we’ve long known that addiction isn’t just about chasing pleasure – it’s about escaping those negative hedonic states,” says Weiss. “This study shows us where in the brain that learning takes root, which is a step forward.”

Source: Scripps Research

Categories : Substance UseTags :

Long-term Alcohol Use Suspends Liver Cells in Limbo, Preventing Regeneration

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Excessive alcohol consumption can disrupt the liver’s unique regenerative abilities by trapping cells in limbo between their functional and regenerative states, even after a patient stops drinking, as described in a new study from researchers at University of Illinois Urbana-Champaign and collaborators.

This in-between state is a result of inflammation disrupting how RNA is spliced during the protein-making process, the researchers found, providing scientists with new treatment pathways to explore for the deadly disease. The researchers published their findings in the journal Nature Communications.

The liver has a remarkable ability to regenerate itself after damage or partial removal. However, it loses that ability in patients with alcohol-associated liver disease – the leading cause of liver-related mortality worldwide, resulting in roughly 3 million deaths annually.

“We knew that the liver stops functioning and stops regenerating in patients with alcohol-related hepatitis and cirrhosis, even when a patient has discontinued consuming alcohol, but we didn’t know why,” said U. of I. biochemistry professor Auinash Kalsotra, who co-led the study with Duke University School of Medicine professor Anna Mae Diehl. “The only real life-saving treatment option once a patient reaches the liver failure stage in those diseases is transplantation. But if we understood why these livers were failing, maybe we could intervene.”

Both the Kalsotra and Diehl labs havestudied the molecular and cellular underpinnings of liver regeneration. Over the last five years, they found that in order to regenerate, liver cells reprogram their gene expression to revert to fetal-like progenitor cells, multiply and then reverse the process back to become mature functioning cells again. Armed with this knowledge, the group turned to the question of how those mechanisms were disrupted in alcohol-associated liver disease.

The researchers compared samples of healthy livers and samples of livers with alcohol-associated hepatitis or cirrhosis obtained from Johns Hopkins University Hospital through an initiative supported by the National Institute for Alcohol Abuse and Alcoholism, part of the National Institutes of Health.

The first thing the researchers noticed in diseased livers was that, although damaged cells had begun the process of reverting to the regenerative state, they did not complete the process and instead remained in transitional limbo.

“They are neither functional adult cells nor proliferative progenitor cells. Since they are not functioning, more pressure builds on the remaining cells. So they try to regenerate, and they’re all ending up in this unproductive quasi-progenitor state, and that’s what is causing liver failure,” said U. of I. graduate students Ullas Chembazhi and Sushant Bangru, the co-first authors of the study.

To figure out why the cells were getting stuck in this state, the team investigated which proteins were being made by the liver cells and, in turn, the RNA molecules carrying the instructions for those proteins from the DNA to the cell’s protein-building machinery.

While most studies focus only on the total amounts of RNA or protein in a cell, Kalsotra’s team used deep RNA sequencing technology and computational analyses to zoom in on the splicing of RNA fragments, a key step in stitching together different parts of genetic instructions to make proteins.

“In comparing the samples, we saw RNA was getting mis-spliced broadly in alcohol-related liver disease, across thousands of genes, and it was affecting major functions of proteins,” said Kalsotra.

The researchers found a possible driver of the RNA mis-splicing: Alcohol-damaged liver cells had a deficiency of the protein ESRP2, which binds to RNA to splice it properly.  

“Proteins function at a very specific place in the cell, and that is directed by sequences within the protein that take the protein to that particular spot. We found that, in many cases, the sequence that dictates where the protein localizes within a cell was mis-spliced. That’s why it was important that we did the multiple analyses we did,” said Kalsotra. “There was the same amount of RNA and protein, but the protein was not at the right place to function. Due to mis-splicing, key proteins that are required for productive liver regeneration were getting stuck in the cytoplasm, when they needed to be in the nucleus.”

To verify that ESRP2 deficiency was a likely culprit, the researchers studied mice without the gene that produces ESRP2. They displayed similar liver damage and regeneration failure to that seen in patients with advanced alcohol-related hepatitis.

But why was ESRP2 missing from liver cells from patients with alcohol-related hepatitis? Upon investigation, the researchers found that liver support cells and immune cells, drawn to the liver tissue damaged by alcohol processing, released high amounts of inflammatory and growth factors. Those factors suppress ESRP2 production and activity.

To verify this finding, the researchers treated liver cell cultures with a molecule that inhibits the receptor for one of the inflammation-promoting factors. ESRP2 levels recovered and splicing activity was corrected, pointing to the pathway as a possible treatment target.

“I’m hopeful these findings will become a launching pad for future clinical studies. We can use these mis-spliced RNAs as diagnostic markers or develop treatments that can curb the inflammation. And if we can correct the splicing defects, then maybe we can improve recovery and restore damaged livers,” Kalsotra said.

Source: University of Illinois Urbana-Champaign

Categories : Mental Health Substance UseTags :

Poor Mental Health Can Be Worsened by Cannabis Use

On By ModernMedia

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in partnership with the University of Bath, has found that the reasons why a person chooses to use cannabis can increase their risk of developing paranoia.

Photo by Thought Catalog on Unsplash

The use and potency of cannabis is increasing worldwide, and dependence and cannabis-induced psychosis are also greatly increasing as a result, especially in North America. Two new research papers, both using data from Cannabis & Me – the largest survey of its kind – have identified key risk factors associated with the more severe forms of paranoia in cannabis users.

The first study, published in BMJ Mental Health, explored the relationship between why people first started using cannabis, and how this affected their subsequent use.

3389 former and current cannabis users aged 18 and over responded to a survey examining their reasons for first and continued use, their weekly consumption of cannabis in THC units, and their mental health.

Researchers established several key findings. Respondents who first started using cannabis to self-medicate an illness, including physical pain, anxiety, depression, or because they were experiencing minor psychotic symptoms, all demonstrated higher paranoia scores.

This was in contrast to those respondents who tried cannabis for fun or curiosity, or with their friends, who reported the lowest average paranoia and anxiety scores.

Dr Edoardo Spinazzola, a Research Assistant at King’s IoPPN and the study’s first author said, “This research suggests that using cannabis as a mean to self-medicate physical or mental discomfort can have a negative impact on the levels of paranoia, anxiety, and depression. Most of these subgroups had average scores of depression and anxiety which were above the threshold for referral to counselling.”

Respondents were also asked to provide data on the frequency and strength of the cannabis they were using so that researchers could track their average weekly consumption of Tetrahydrocannabinol (THC) – the principle psychoactive component of cannabis.

The researchers found that the average respondent consumed 206 units of THC a week. This might equate to roughly 10-17 ‘joints’ per week, if the user was consuming an expected 20% THC content that is standard for the most common types of cannabis available in London.

However, respondents who started using cannabis to help with their anxiety, depression, or in cases where they started due to others in their household who were already using cannabis, reported on average 248, 254.7, and 286.9 average weekly THC units respectively.

Professor Tom Freeman, Director of the Addiction and Mental Health Group at the University of Bath and one of the study’s authors said, “A key finding of our study is that people who first used cannabis to manage anxiety or depression, or because a family member was using it, showed higher levels of cannabis use overall.

“In future, standard THC units could be used in a similar way to alcohol units – for example, to help people to track their cannabis consumption and better manage its effects on their health.”

In a separate study, published in Psychological Medicine, researchers explored the relationship between childhood trauma, paranoia and cannabis use.

Researchers used the same data set from the Cannabis & Me survey, with just over half of respondents (52 per cent) reporting experience of some form of trauma.

Analysis established that respondents who had been exposed to trauma as children reported higher average levels of paranoia compared to those who hadn’t, with physical and emotional abuse emerging as the strongest predictors.

Researchers also explored the relationship between childhood trauma and weekly THC consumption. Respondents who reported experience of sexual abuse had a markedly higher weekly intake of THC, closely followed by those who reported experiencing emotional and physical abuse.

Finally, the researchers confirmed that the strong association between childhood trauma and paranoia is further exacerbated by cannabis use, but is affected by the different types of trauma experienced. Respondents who said they had experienced emotional abuse or household discord were strongly associated with increased THC consumption and paranoia scores. Respondents reporting bullying, physical abuse, sexual abuse, physical neglect and emotional neglect on the other hand did not show the same effects.

Dr Giulia Trotta, a Consultant Psychiatrist and Researcher at King’s IoPPN and the study’s first author said, 

“We have not only established a clear association between trauma and future paranoia, but also that cannabis use can further exacerbate the effects of this, depending on what form the trauma takes.

“Our findings will have clear implications for clinical practice as they highlight the importance of early screening for trauma exposure in individuals presenting with paranoia.”

Professor Marta Di Forti, Professor of Drug use, Genetics and Psychosis at King’s IoPPN, Clinical Lead at the South London and Maudsley NHS Foundation Trust’s Cannabis Clinic for Patients with Psychosis, and the senior author on both studies said, “There is extensive national and international debate about the legality and safety of cannabis use.

“My experience in clinic tells me that there are groups of people who start to use cannabis as a means of coping with physical and emotional pain. My research has confirmed that this is not without significant further risk to their health and wellbeing, and policy makers across the world should be mindful of the impact that legalisation , without adequate public education and health support, could have on both the individual, as well as on healthcare systems more broadly.”

Source: King’s College London