Category: Substance Use

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

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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.

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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

Categories : Substance Use Surgeries & ProceduresTags :

Alcohol Withdrawal Syndrome is a Hidden Surgery Risk

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Alcohol withdrawal syndrome (AWS) is a potentially life-threatening condition that may complicate patients’ recovery after surgery.

Previous studies have estimated that up to 50% of hospitalised patients with AUD will develop some degree of AWS. Up to 7% of these patients may progress to severe withdrawal, including delirium tremens (DT) that can range in severity from irritability and confusion to tremors, nausea, vomiting and seizures.

A new study by surgeons at The Ohio State University Wexner Medical Center and The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) looked at a national sample of 3 million adult surgical patients between 2016-2019.

Of those patients, 16 504 (0.5%) were diagnosed with AWS, including 6591 (0.2%) with DT. 

“We found that alcohol withdrawal syndrome is linked with poorer surgical outcomes, extended hospitalisations and increased costs. These findings underscore the need for standardised perioperative screening and targeted management strategies to reduce these risks,” said study lead author Timothy Pawlik, MD, PhD, professor and chair of Ohio State’s Department of Surgery.

The study findings were published in the Journal of American College of Surgeons.

Patients with AWS were generally younger, male and more likely to have Medicaid, according to Pawlik, who holds the Urban Meyer III and Shelley Meyer Chair for Cancer Research at The Ohio State University College of Medicine.

AWS raises the risk of postoperative complications, especially respiratory failure and sepsis. The study found that patients with AWS had longer hospital stays (median 11 vs 6 days) and higher costs ($44 300 vs $28 800). 

AWS was associated with a $10 030 higher adjusted hospitalisation cost per patient undergoing surgical care, contributing to an overall excess cost of $165.6 million, said study first author Azza Sarfraz, MBBS, a surgical oncology fellow at Ohio State. 

“The lack of standard screening delays early detection and intervention,” Pawlik said. “Developing strategies for early identification, inpatient withdrawal management, and perioperative risk stratification may improve surgical outcomes, lower healthcare costs, and enhance patient care.” 

Source: Ohio State University Wexner Medical Center

Categories : Mental Health Substance UseTags :

Cannabis Potency May Be Driving a Rise in Schizophrenia

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A new article published in the Canadian Medical Association Journal warns of the mental health dangers stemming from the increasing potency of cannabis. In Ontario, there has been a more than 14-fold increase in risk for visiting the emergency department for cannabis-related schizophrenic disorders. After a cannabis-induced psychotic episode, cessation of cannabis use is necessary to reduce the risk of relapse, and in severe cases, antipsychotics may be needed.

“Cannabis from the 2000s is not the same as in 2025,” said coauthor Dr Nicholas Fabiano, MD, resident and researcher with the Department of Psychiatry, University of Ottawa, Ottawa, Ontario. “THC content has increased by 5 times. This is likely a significant driver in the increasing link between cannabis use and schizophrenia.”

  1. Cannabis potency is increasing — The concentration of tetrahydrocannabinol (THC) has increased fivefold in the last 20 years in Canada from about 4% to 20% in most legal dried cannabis.
  2. High-potency and regular cannabis use is linked to increased risk of psychosis — The risk of psychosis is increased in people using high-potency THC (more than 10% THC), people using it frequently, and those who are younger and male. A history of mental disorders (depression, anxiety, etc) also appears to increase the risk.
  3. Cannabis-induced psychosis and cannabis use disorder increase the risk of schizophrenia — A recent study of 9.8 million people in Ontario found a 14.3-fold higher risk of developing a schizophrenia-spectrum disorder in people visiting the emergency department for cannabis use and a 241.6-fold higher risk from visits for cannabis-induced psychosis.
  4. Treatment requires stopping cannabis and taking medication — Continued use of cannabis after a first episode of cannabis-induced psychosis is linked to greater risk of returning symptoms. Antipsychotic medication can help people with severe and prolonged symptoms.
  5. Behavioural options may help with cannabis cessation — Motivational interviewing or cognitive behavioural therapy by a physician or psychologist can help build skills to resist cravings and follow treatment recommendations.

Source: EurekAlert!

Categories : Cancer Substance UseTags :

Oral Cancer Risk is Greatly Elevated in Cannabis Use Disorder

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A recent study by researchers at the University of California San Diego School of Medicine has found that individuals with cannabis use disorder (CUD) are more than three times more likely to develop oral cancer within five years compared to those without CUD. The study, published in Preventive Medicine Reports, highlights the potential long-term health risks associated with problematic cannabis use.

In 2022, 17.7 million people in the US reported daily or near-daily cannabis use. Though CUD requires a formal diagnosis and not all cannabis users develop the disorder, recent research suggests that as many as 3 in 10 cannabis users will develop CUD.

“Cannabis smoke contains many of the same carcinogenic compounds found in tobacco smoke.”

As cannabis becomes more widely available and socially accepted, it is essential to understand its potential health risks. While many consider cannabis to be safer than other drugs, such as tobacco and alcohol, there are still many unknowns about the health impacts of cannabis, particularly how the drug influences cancer risk. The new study sought to determine the relationship between CUD and oral cancer, for which tobacco smoking is known to be a significant risk factor.

“Cannabis smoke contains many of the same carcinogenic compounds found in tobacco smoke, which have known damaging effects on the epithelial tissue that lines the mouth,” said Raphael Cuomo, PhD, associate professor in the Department of Anesthesiology at UC San Diego School of Medicine and member of UC San Diego Moores Cancer Center. “These findings add to a growing body of evidence suggesting that chronic or problematic cannabis use may contribute to cancer risk in tissues exposed to combustion products.”

By analysing the electronic health records from over 45 000 patients, of whom 949 developed CUD, Cuomo found:

  • After adjusting for age, sex, body mass index and smoking status, people had a 325% higher likelihood of contracting oral cancer within five years compared to those without CUD.
  • Tobacco smokers with CUD were 624% more likely to contract oral cancer within five years compared to tobacco smokers without CUD.

Because the association between CUD and oral cancer remained even after controlling for smoking status, and because CUD was associated with greater oral cancer risk even when the analysis was restricted to smokers, the researchers hypothesise that there may be other factors underlying this risk in addition to smoke inhalation. For example, THC, the active compound in cannabis, is known to have immune-suppressing effects, which may contribute to increased cancer risk.

While more research is needed to fully explain the association between cannabis and oral cancer, the study’s results have immediate implications for cancer screening practices and public health messaging. In particular, the findings emphasise the need for further research on the long-term effects of cannabis use and the importance of integrating oral health awareness into substance use disorder treatment and counselling.

Source: University of California – San Diego

Categories : Obstetrics & Gynaecology Substance UseTags :

Updated Review Raises Concern About Cannabis Use in Pregnancy

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Research team finds moderate risk for preterm birth, low birth weight

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An updated systematic review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death. This study by researchers at Oregon Health & Science University appears in JAMA Pediatrics.

Study lead author Jamie Lo, MD, MCR, is a physician-scientist who provides prenatal care for high-risk pregnancies at OHSU.

“Patients are coming to me in their prenatal visits saying, ‘I quit smoking and drinking, but is it safe to still use cannabis?’” said Lo, associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine. “Until direct harms have been proven, they perceive it to be safe to use.”

In fact, cannabis remains one of the most common substances used in pregnancy that’s still illegal under federal law, and, unlike declines in prenatal use of alcohol or nicotine, cannabis use is continuing to increase. Lo said many of her patients are reluctant to give up cannabis during pregnancy because it helps to reduce common prenatal symptoms such as nausea, insomnia and pain.

Researchers updated the systematic review and meta-analysis, drawing on a total of 51 observational studies involving 21.1 million people to examine the potential adverse effects of cannabis use in pregnancy. The researchers found eight new studies since their previous update, raising the certainty of evidence from “very-low-to-low” to “moderate” for increased odds of low birth weight, preterm birth and babies being small for their gestational age.

The updated review also indicated increased odds of newborn mortality, though still with low certainty.

Researchers noted that the new systematic review includes a larger proportion of human observational studies examining people who only use cannabis, but don’t also use nicotine. And even though the evidence is low to moderate for adverse outcomes, Lo noted that the findings are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.

The related research in animal models included standard prenatal ultrasound and MRI imaging that revealed a detrimental effect on the placenta, in terms of blood flow and availability of oxygen in addition to decreased volume of amniotic fluid.

“These findings tell me as an obstetrician that the placenta is not functioning as it normally would in pregnancy,” Lo said. “When the placenta isn’t functioning well, it can affect the baby’s development and growth.”

Even though cannabis remains a Schedule 1 substance under the federal Controlled Substances Act, Oregon is one of several states that have legalised it under state law for medicinal and recreational use. Lo said she recommends a harm-reduction approach to patients. For those who cannot abstain, she advises them to reduce the amount and frequency of use to help reduce the risk of prenatal and infant complications.

“Even using less can mitigate the risk,” she said. “Abstinence is ideal, but it’s not realistic for many patients.”

Source: Oregon Health & Science University

Categories : Substance UseTags :

Repurposed Anti-inflammatory Drug may Help Treat Pain from Alcohol Use Disorder

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A Scripps Research study has found that a drug already FDA-approved for treating inflammatory conditions may help reduce both alcohol intake and pain sensitivity in alcohol use disorder (AUD).

The results, published in JCI Insight, suggest that the drug apremilast, a phosphodiesterase-4 (PDE4) inhibitor, or a compound that blocks an enzyme involved in inflammation, could be repurposed as a dual-acting therapy for AUD, particularly in individuals who have pain during and after alcohol use.

AUD affects an estimated 400 million people aged 15 years or older, according to the World Health Organization. Chronic pain is one of the strongest predictors of alcohol relapse, yet it’s often overlooked in AUD treatment strategies. People with AUD frequently experience mechanical allodynia as well, a condition in which even light touch is perceived as painful. This sensitivity can persist during abstinence and contribute to ongoing alcohol use and relapse.

“Our findings highlight the therapeutic value of apremilast to reduce co-occurring drinking and mechanical allodynia in long-term abstinence – a critical component of harmful drinking and AUD psychopathology,” says senior author Marisa Roberto, a professor of neuroscience at Scripps Research.

Currently FDA-approved for treating psoriasis (a chronic autoimmune skin condition) and psoriatic arthritis (a related joint disease), apremilast has previously been shown to reduce alcohol drinking in both mice and humans. The new study builds on that work by examining whether apremilast could also ease pain linked to alcohol exposure.

To investigate, the research team tested apremilast in a type of rat genetically predisposed to higher alcohol consumption and in a standard genetic strain of rats. Both rat strains were given access to alcohol and treated with either apremilast or a placebo.

Apremilast significantly reduced alcohol intake across strains and biological sexes. It also decreased pain sensitivity in most groups, both immediately after drinking and during abstinence, ranging from 24 hours to four weeks after alcohol had been removed.

“But at specific time points, the patterns of reduction differed between males and females, as well as between strains,” notes first author Bryan Cruz, a postdoctoral fellow at Scripps Research. For example, the pain-relieving effects of apremilast weren’t observed in some of the male rats, underscoring the importance of considering biological sex in future studies.

In another set of experiments, apremilast increased GABAergic transmission. a type of inhibitory signaling that helps regulate pain and stress signalling, in the central amygdala, which is involved in both addiction and pain. This effect was only observed in the standard strain of rats, suggesting that apremilast’s impact on brain signalling may depend on genetic background or vulnerability to AUD.

In both strains of male rats, alcohol exposure increased expression of PDE4 genes in the brain, further supporting a link between inflammation, pain and compulsive alcohol use. While other PDE4 inhibitors have been studied for pain unrelated to alcohol consumption, apremilast may offer a path toward more personalized therapies for those with both AUD and pain. But clinical research is still needed to determine the drug’s efficacy for such conditions in humans.

Going forward, the researchers also plan to explore whether apremilast can mitigate anxiety and other negative emotional states that commonly emerge during alcohol withdrawal.

“For over a decade, it’s been well-established that withdrawal-induced anxiety is a major driver of relapse,” points out Roberto. “Therefore, addressing other key components of the addiction cycle is critical, as many individuals use alcohol to cope not only with physical pain but with emotional distress as well.”

Source: Scripps Research Institute

Categories : Cardiovascular Disease Substance UseTags :

Substantially Higher Risk of Heart Attack in Cannabis Users

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Marijuana is now legal in many places, but is it safe? Two new studies add to mounting evidence that people who use cannabis are more likely to suffer a heart attack than people who do not use the drug, even among younger and otherwise healthy adults. The findings are from a retrospective study of over 4.6 million people published in JACC Advances and a meta-analysis of 12 previously published studies being presented at the American College of Cardiology’s Annual Scientific Session.

Marijuana use has risen in the United States, especially in states where it is legal to buy, sell and use the drug recreationally. In the retrospective study, researchers found that cannabis users younger than age 50 were over six times as likely to suffer a heart attack compared to non-users. The meta-analysis, which is the largest pooled study to date examining heart attacks and cannabis use, showed a 50% increased risk among those who used the drug.

“Asking about cannabis use should be part of clinicians’ workup to understand patients’ overall cardiovascular risk, similar to asking about smoking cigarettes,” said Ibrahim Kamel, MD, clinical instructor at the Boston University Chobanian & Avedisian School of Medicine and internal medicine resident at St. Elizabeth Medical Center in Boston and the study’s lead author. “At a policy level, a fair warning should be made so that the people who are consuming cannabis know that there are risks.”

Kamel and his team conducted the retrospective study using data from TriNetX, a global health research network that provides access to electronic medical records. Their findings indicate that over an average follow-up of over three years, cannabis users had more than a sixfold increased risk of heart attack, fourfold increased risk of ischaemic stroke, twofold increased risk of heart failure and threefold increased risk of cardiovascular death, heart attack or stroke. All study participants were younger than age 50 and free of significant cardiovascular comorbidities at baseline, with blood pressure and low-density lipoprotein (LDL) cholesterol levels within a healthy range and no diabetes, tobacco use or prior coronary artery disease.

For the meta-analysis, the researchers pooled data from 12 previously published research studies that collectively included over 75 million people. The studies were rated as being of moderate to good quality in terms of methodology. Of the 12 studies, 10 were conducted in the United States, one in Canada and one in India. Some of the studies did not include information about participants’ ages, but the average age was 41 years among those that did, suggesting that the pooled sample reflected a relatively young population.

Taken individually, seven of the studies found a significant positive association between cannabis use and heart attack incidence, while four showed no significant difference and one showed a slightly negative association. When the researchers pooled the data from all studies and analysed it together, they found a significant positive association, with active cannabis users being 1.5 times as likely to suffer a heart attack compared with those who aren’t current users.

Cannabis use and heart attack incidence was assessed in a similar manner across the different studies. However, due to inconsistencies in the data available from each study, researchers were unable to account for several potential confounding factors including the duration and amount of cannabis use or the use of tobacco or other drugs. 

“We should have some caution in interpreting the findings in that cannabis consumption is usually associated with other substances such as cocaine or other illicit drugs that are not accounted for,” Kamel said. “Patients should be forthcoming with their doctors and remember that we are their number one advocate and having the full story matters.”

While the mechanisms through which marijuana or its components may impact the cardiovascular system are not fully understood, the researchers hypothesize that it can affect heart rhythm regulation, heighten oxygen demand in the heart muscle and contribute to endothelial dysfunction, which makes it harder for the blood vessels to relax and expand, and can interrupt blood flow. One of the studies included in the meta-analysis found that the risk of heart attack peaked about one hour after marijuana consumption.

Since both studies were limited by their retrospective nature and the meta-analysis was limited by the challenges inherent in pooling data from multiple studies, researchers said that additional prospective studies would help to confirm the findings and determine which groups may face the highest risk. 

A previous study presented at the American College of Cardiology’s Annual Scientific Session in 2023 found that daily marijuana use was associated with an increased risk of developing coronary artery disease. 

The retrospective analysis will simultaneously publish in JACC Advances.

Source: American College of Cardiology