The effects of sustained drug abuse can manifest in many ways. Loss of memory and reduced cognitive functions are some of the effects that can persist for years. Neurobiologists at the University of California San Diego have now identified a mechanism in the brain that generates drug-induced cognitive impairments.
The researchers investigated how methamphetamine and phencyclidine (PCP or “angel dust”), which take effect by activating different targets in the brain, induce a similar reduction in cognitive ability. How could the same difficulties in memory emerge in response to drugs that trigger different actions in the brain?
The results of this investigation, led by Assistant Project Scientist Marta Pratelli in Professor Nicholas Spitzer’s laboratory, appear in Nature Communications. They showed that meth and PCP caused neurons to change the way they communicate through a process known as neurotransmitter switching.
Neurotransmitter switching is a form of brain plasticity, an evolving area of research investigating how the brain changes function and structure in response to experience. In recent years, Spitzer and his colleagues have also identified roles for neurotransmitter switching in autism spectrum disorder, post-traumatic stress disorder and in exercise.
Examining the cerebral cortex of mice, the investigators found that meth and PCP each caused a switch from the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the same neurons in the prelimbic region, an area of the frontal cortex involved in executive functions. This switch was linked to a decrease in memory task performance since drug-treated mice performed well in the tasks when the expression of GABA was blocked.
Further experiments showed that even after repeated exposure to the drugs, the researchers were able to reverse this neurotransmitter switch using molecular tools to locally decrease the brain’s electrical activity or using clozapine, an antipsychotic drug. Each of these treatments reversed the memory loss, restoring the performance of mice in the cognitive tasks.
“These results suggest that targeted manipulation of neuronal activity may be used to ameliorate some of the negative effects of repeated drug abuse,” said Pratelli.
In this new study, the researchers found that a drug-induced increase in the release of dopamine, a neurotransmitter involved in reward, and an increase in the electrical activity of neurons in the cerebral cortex, were required to produce the neurotransmitter switch.
“This study reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs,” said Spitzer.
The researchers note in their paper that a deeper understanding of brain mechanisms tied to loss of memory from drug use could boost prospects for new treatments, not only resulting in therapy for meth and PCP consumption, but for other disorders as well.
Researchers exploring the role memory plays in alcohol consumption believe it could help people reduce their intake. They published their findings in Food Quality and Preference.
Previous work has found people don’t eat as much food when they are reminded of an earlier meal just before tucking in. The latest study, led by the University of Portsmouth, wanted to further investigate the relationship between memory and consumption, but with alcohol instead.
The team carried out a study involving 50 women aged 18 to 46-years-old who were randomly split into two groups: The first group were asked to recall a recent alcohol experience in detail, and the second had to recall a car journey, as a control. Participants were then asked to consume a vodka-based drink, at a rate that felt comfortable to them.
Participants watched a mood-neutral program while drinking to provide a more naturalistic environment and distract them from any suspicion that their rate of consumption was being recorded.
The findings revealed individuals asked to recall a previous drinking episode took longer to consume the alcoholic beverage, which suggests a lower motivation for alcohol.
Dr Lorenzo Stafford, a multisensory researcher at the University of Portsmouth, said: “Following on from previous work, we think an important part of the observed effect was that individuals in the alcohol memory cue condition had to estimate the number of alcohol calories they consumed.
“Our theory is that females may have had less desire for alcohol because they wish to avoid excess calories, which could also be linked to work showing that females are more likely to change their consumption habits because they are more receptive to the risks alcohol poses to health and weight.”
Despite this, it is estimated that more than a quarter (28%) of drinkers consume more than the recommended 14 units a week in England alone.
The study also found that those individuals who drink regularly – categorising them at a high risk – consumed the alcohol faster than those in the low risk group. The authors say this demonstrates that the speed of consumption is a valid measure of alcohol motivation.
In two related studies, Dr Stafford and his colleagues found that strong health warning labels on alcohol products also reduced desire for alcohol and slowed down their drinking rate. While these approaches were more effective than memory cues, they could both offer a potentially useful way to help avoid excess alcohol consumption.
The paper, , recommends further research to help understand the alcohol memory effect in males, especially as males typically consume more alcohol than females and are therefore at a heightened risk.
A team of researchers led by the University of California, Irvine has discovered that an antioxidant found in rosemary extract can reduce volitional intakes of cocaine by moderating the brain’s reward response, offering a new therapeutic target for treating addiction.
The study, recently published online in the journal Neuron, describes team members’ focus on a region of the brain called the globus pallidus externus, which acts as a gatekeeper that regulates how we react to cocaine. They discovered that within the GPe, parvalbumin-positive neurons are crucial in controlling the response to cocaine by changing the activity neurons releasing the pleasure molecule dopamine.
“There are currently no effective therapeutics for dependence on psychostimulants such as cocaine, which, along with opioids, represent a substantial health burden,” said corresponding author Kevin Beier, UC Irvine associate professor of physiology and biophysics. “Our study deepens our understanding of the basic brain mechanisms that increase vulnerability to substance use disorder-related outcomes and provides a foundation for the development of new interventions.”
Findings in mice revealed that globus pallidus externus parvalbumin-positive cells, which indirectly influence the release of dopamine, become more excitable after being exposed to cocaine. This caused a drop in the expression of certain proteins that encode membrane channels that usually help keep the globus pallidus cell activity in check. Researchers found that carnosic acid, an isolate of rosemary extract, selectively binds to the affected channels, providing an avenue to reduce response to the drug in a relatively specific fashion.
“Only a subset of individuals are vulnerable to developing a substance use disorder, but we cannot yet identify who they are. If globus pallidus cell activity can effectively predict response to cocaine, it could be used to measure likely responses and thus serve as a biomarker for the most vulnerable,” Beier said. “Furthermore, it’s possible that carnosic acid could be given to those at high risk to reduce the response to cocaine.”
The next steps in this research include thoroughly assessing negative side effects of carnosic acid and determining the ideal dosage and timing. The team is also interested in testing its efficacy in reducing the desire for other drugs and in developing more potent and targeted variants.
A new study on psychiatric hospitalisations, out now in Drug and Alcohol Dependence, found that while most hospitalisations did not involve any substances, methamphetamine-related hospitalisations have increased even as the overall number of psychiatric hospitalisations remained stable.
Additionally, researchers detail that psychiatric hospitalisations caused by methamphetamine use was highest in a region which has higher reported methamphetamine use, but were also shifting geographically.
“Rates of methamphetamine-involved psychiatric hospitalisations were by far the highest in the Mountain West,” said Susan Calcaterra, MD, MPH, professor at the University of Colorado Anschutz Medical Campus and study lead author. “As expected, this mirrors rates of self-reported methamphetamine use and methamphetamine-related overdose deaths in the Mountain West,” Calcaterra said. “Psychiatric hospitalisations involving methamphetamine use is really taking off in the Midwest and Northeast, in particular.”
Study underscores need for clinic-based harm-reduction tactics
While rates of methamphetamine-related psychiatric hospitalisations increased 68% over the study period, opioid-related hospitalizations decreased by 22%. Methamphetamine rate increases may be attributed to methamphetamine’s ubiquity and affordability, as well as the lack of resources available to manage methamphetamine use. Why opioid-involved psychiatric hospitalizations declined is less clear but may be related to the lethality of fentanyl.
“An important takeaway from this study is the need for resources to address the mental and physical treatment of methamphetamine use,” Calcaterra said.
“While the vast majority of psychiatric hospitalisations in this timeframe did not involve substance use, the significant increase in methamphetamine use means we have to better consider harm reduction in clinical settings,” she said.
“Evidence-based interventions such as contingency management, which involves offering incentives for abstinence, harm reduction education, provision of naloxone for overdose reversal and access to expanded mental health treatments are proven to help mitigate dangerous effects from methamphetamine use, especially when contaminated with fentanyl much like the campaigns aimed at public awareness around opioid use.”
A good night’s sleep is essential for children’s health and development, but childhood sleep patterns may also be linked to future substance use. A new study, led by a team of Penn State researchers, found that adolescents were more likely to have consumed alcohol or tried marijuana by age 15 if they went to bed later and slept fewer hours during childhood and adolescence. The team published their findings in Annals of Epidemiology.
“The study suggests that there might be some critical ages when sleep can be a target for intervention,” said Anne-Marie Chang, associate professor of biobehavioural health at Penn State and senior author of the paper. “If we improve sleep in the school-age population, not only could that show improvements in sleep health but in other aspects like the decision to engage in risky behaviours like alcohol and other substance use.”
The research team explored childhood sleep at different developmental stages within the same sample of children to see if there’s an impact on later substance use, which few studies have investigated. They focused on two different facets of sleep health – total duration of sleep and time of sleep or bedtime. The researchers explained that if children, especially school-aged children, go to bed later, it could affect their ability to sleep well.
“Sleep is multifaceted. It’s important for children because it helps with growth and development. The brain is more plastic during younger ages and you want healthy sleep to support neural development,” said David Reichenberger, co-lead author and who earned his doctoral degree in biobehavioural health at Penn State during the time of the research. “Poor sleep health could have downstream effects on their physical health as well as decision making, which could in turn be related to their decision to engage in substance use.”
The study drew on data from 1514 children in the Future of Families and Child Wellbeing Study, a diverse longitudinal birth cohort of children from 20 cities across the United States. Parents reported their child’s regular weekday bedtime at ages three, five and nine. They also reported their child’s sleep duration at ages five and nine.
When the research team evaluated the relationship between childhood bedtime and sleep duration with future alcohol and marijuana use as teens, they found a longitudinal association. Teens were 45% more likely to try alcohol by age 15 if they had a later bedtime at age nine when compared to other children with earlier bedtimes at age nine. However, bedtime at age five wasn’t associated with future alcohol use, nor was sleep duration at ages five or nine. When it came to marijuana use, later bedtime at age five was associated with 26% increased odds of trying marijuana by age 15, while sleeping an hour less at age nine was associated with 19% increased odds of trying marijuana by age 15.
The research team also examined data from adolescents at age 15, who self-reported their bedtime, sleep duration and alcohol and marijuana use. They found that teens with a later bedtime had a 39% greater chance of drinking alcohol and a 34% greater chance of trying marijuana. Sleeping one hour less was associated with 28% increased odds of ever trying alcohol but wasn’t associated with marijuana use.
“Sleep at ages closer to adolescence is the most crucial in terms of future substance use risk. It’s that stage of development when children are rapidly changing and their brain is maturing,” Reichenberger said, noting that previous research by other groups suggests that shorter sleep duration and later bedtimes may increase impulsivity and impair decision making, which could influence substance use choices.
The findings highlight the critical role of sleep across multiple aspects of long-term health and wellbeing, researchers said. For school-age children, creating an environment that’s conducive for sleep and establishing an age-appropriate bedtime are key elements for cultivating good sleep.
“Exploring the connection between sleep and substance use is a critical area of research because we continue to struggle with an epidemic of opioid addiction and substance use,” Chang said. “It’s an important area to continue to research and to disseminate our research findings to the broader population, families and health care professionals.”
At the start of the COVID pandemic in 2020, scientists quickly recognised that a handful of characteristics, including age, smoking history, high body mass index (BMI) and the presence of other diseases such as diabetes, increased the risk of severe disease and death. But one suggested risk factor remains unconfirmed more than four years later: cannabis use. Evidence has emerged over time indicating both protective and harmful effects.
Now, a new study by researchers at Washington University School of Medicine in St. Louis points decisively to the latter: Cannabis is linked to an increased risk of serious illness for those with COVID.
The study, published in JAMA Network Open, analysed the health records of 72 501 people seen for COVID at Midwestern US health centres during the first two years of the pandemic. The researchers found that people who reported using any form of cannabis at least once in the year before developing COVID were significantly more likely to need hospitalisation and intensive care than were people with no such history. This elevated risk of severe illness was on par with that from smoking.
“There’s this sense among the public that cannabis is safe to use, that it’s not as bad for your health as smoking or drinking, that it may even be good for you,” said senior author Li-Shiun Chen, MD, DSc, a professor of psychiatry. “I think that’s because there hasn’t been as much research on the health effects of cannabis as compared to tobacco or alcohol. What we found is that cannabis use is not harmless in the context of COVID. People who reported yes to current cannabis use, at any frequency, were more likely to require hospitalisation and intensive care than those who did not use cannabis.”
Cannabis use was different than tobacco smoking in one key outcome measure: survival. While smokers were significantly more likely to die of COVID than nonsmokers, a finding that fits with numerous other studies, the same was not true of cannabis users, the study showed.
“The independent effect of cannabis is similar to the independent effect of tobacco regarding the risk of hospitalisation and intensive care,” Chen said. “For the risk of death, tobacco risk is clear but more evidence is needed for cannabis.”
The study analysed deidentified electronic health records of people who were seen for COVID at BJC HealthCare hospitals and clinics in Missouri and Illinois between Feb. 1, 2020, and Jan. 31, 2022. The records contained data on demographic characteristics such as sex, age and race; other medical conditions such as diabetes and heart disease; use of substances including tobacco, alcohol, cannabis and vaping; and outcomes of the illness: specifically, hospitalisation, intensive-care unit (ICU) admittance and survival.
COVID patients who reported that they had used cannabis in the previous year were 80% more likely to be hospitalised and 27% more likely to be admitted to the ICU than patients who had not used cannabis, after taking into account tobacco smoking, vaccination, other health conditions, date of diagnosis, and demographic factors. For comparison, tobacco smokers with COVID9 were 72% more likely to be hospitalized and 22% more likely to require intensive care than were nonsmokers, after adjusting for other factors.
These results contradict some other research suggesting that cannabis may help the body fight off viral diseases such as COVID.
“Most of the evidence suggesting that cannabis is good for you comes from studies in cells or animals,” Chen said. “The advantage of our study is that it is in people and uses real-world health-care data collected across multiple sites over an extended time period. All the outcomes were verified: hospitalisation, ICU stay, death. Using this data set, we were able to confirm the well-established effects of smoking, which suggests that the data are reliable.”
The study was not designed to answer the question of why cannabis use might make COVID worse. One possibility is that inhaling marijuana smoke injures delicate lung tissue and makes it more vulnerable to infection, in much the same way that tobacco smoke causes lung damage that puts people at risk of pneumonia, the researchers said. That isn’t to say that taking edibles would be safer than smoking joints. It is also possible that cannabis, which is known to suppress the immune system, undermines the body’s ability to fight off viral infections no matter how it is consumed, the researchers noted.
“We just don’t know whether edibles are safer,” said first author Nicholas Griffith, MD, a medical resident at Washington University. Griffith was a medical student at Washington University when he led the study. “People were asked a yes-or-no question: ‘Have you used cannabis in the past year?’ That gave us enough information to establish that if you use cannabis, your health-care journey will be different, but we can’t know how much cannabis you have to use, or whether it makes a difference whether you smoke it or eat edibles. Those are questions we’d really like the answers to. I hope this study opens the door to more research on the health effects of cannabis.”
More evidence shows potential connection between cannabis exposure in womb and adolescent behavioural problems
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Scientists are trying to understand how cannabis may affect long-term neurodevelopment from in utero exposure. Previous work by Washington University in St. Louis researchers Sarah Paul and David Baranger in the Behavioral Research and Imaging Neurogenetics (BRAIN) lab led by Ryan Bogdan found associations between prenatal cannabis exposure and potential mental health conditions in childhood and adolescence, but potential biological mechanisms that could possibly explain this association were unclear.
In research published in Nature Mental Health this month, Bogdan, professor of psychological and brain sciences, and senior scientist Baranger outline some of those potential mechanisms, the intermediate biological steps that could play into how prenatal cannabis exposure leads to behavioural issues down the line.
“We see evidence that cannabis exposure may influence the developing brain, consistent with associations with mental health,” Baranger said.
Trying to draw out the long-term impacts of cannabis exposure during pregnancy is not a simple knot to untangle. There are many confounding factors that affect mental health and behavior.
For example, say someone was exposed in utero to cannabis and later develops attention deficit disorder as a teen – how do you differentiate that as an inherited trait or a trait influenced by environmental factors, versus a trait that cannabis exposure somehow contributed to early on in development? It is also possible that all three potentially could contribute to eventual psychopathology.
Another complication is the increasing prevalence of the drug, including among the pregnant population, where cannabis use has increased from 3% to 7% from 2002 to 2017.
Researchers have statistical methods to filter out some of those confounding factors that they used in the previous study, but now they can point to specific biological measurements that further signal a connection to cannabis exposure and adolescent behavioral problems.
Bogdan said that nothing can establish causation with certainty, “but we can look at the plausibility of causation and identifying biological correlates that are associated with exposure and these mental health outcomes suggests it’s plausible.”
Researchers have been using data on the children and their mothers from the Adolescent Brain and Cognitive Development (ABCD) Study, an ongoing research project that includes nearly 12 000 children across the country. As part of that study, they collected data about each mother’s substance use prior to the birth as well as the neuroimaging data of their offspring when they were between 9 and 10 and 11 and 12 years old. Some 370 children were exposed to cannabis prior to the mother’s knowledge of pregnancy, and 195 were exposed before and after learning of pregnancy.
The researchers looked at a variety of neuroimaging measurements that factor into brain development, including measures of brain thickness and surface area, as well as measures reflecting water diffusion in and outside of cells. The patterns found in the group exposed to cannabis are consistent with potential reductions in neuroinflammation.
“It’s possible what we’re seeing is an anti-inflammatory effect of cannabis, which is leading to differences in how the brain is being pruned during neurodevelopment,” Bogdan said.
Much has been touted about the anti-inflammatory effects of cannabis, but it’s not always good to reduce inflammation. It’s all about the timing: too much of a reduction of inflammation at the wrong time could affect how the brain is pruned and primed.
Another theory is that cannabis exposure leads to accelerated aging. But don’t expect to find the smoking gun of biological clues pinning mental health problems to early cannabis exposure.
It might not even be about cannabis effects on pruning but the post-combustion products from smoking cannabis that set off accelerated aging and the downstream cognitive effects, Bogdan said.
Or, it could all come down to sociological factors, he added.
Trying to find the one-to-one connection that proves that prenatal cannabis exposure has negative effects during the teenage years is a challenge and may not be possible with retrospective studies. Baranger notes that the major limitation of this data set is that it was retrospective; mothers reported what their cannabis use was 10 years ago, so he’s looking forward to new data from prospective, longitudinal studies that will offer more recent, accurate and detailed information about cannabis use in pregnancy.
“That will potentially give us more answers to these questions in the future,” Baranger said.
Baranger said these results reaffirm that if someone is thinking about using cannabis while pregnant, they should “talk to their doctor about their choices and what other options there might be.”
Rehab centres in South Africa have been admitting an increasing number of codeine users in recent years. Now, the country’s medicines regulator has published a draft guideline as part of a broader effort to track suspicious codeine sales.
South Africa’s medicines regulator – the South African Health Products Regulatory Authority (SAHPRA) – has released a new draft guideline which it says will help stem the misuse of codeine. The opioid, which is found in certain pain relief medicines and cough syrups, is used by some people in large doses to get high.
Under the new draft guideline, the regulator can request sales data (and other information) from manufacturers, suppliers or distributors of any scheduled medicines. This would allow them to track the flow of codeine all the way “from the manufacturer to the dispensary, be it a clinic, pharmacy, hospital, or doctor’s practice”, SAHPRA’s communications officer, Nthabi Moloi, told Spotlight.
Why is this important? Until now, health authorities have struggled to detect suspicious sales of codeine, which is found in both prescription and over-the-counter medicines. This problem manifests in two ways. For one, recreational users can often get a continuous supply of codeine directly from pharmacies. While people are only permitted to purchase a limited amount of the drug, many bypass this simply by buying from different pharmacies. It’s largely impossible to flag these individuals since there is no centralised data on what medicines people buy across vendors (though attempts have been made to address this).
The second issue relates to wholesale supply. Following a Carte Blanche investigation flighted last year, SAHPRA confirmed that a pharmacy group was making illicit bulk sales of codeine-based cough syrups. While patients are only allowed to get codeine from a licensed health worker or pharmacist, it’s thus no surprise that it can also be found on the black market.
The new draft guideline aims to tackle both of these problems by allowing SAHPRA to request information from companies and health workers about how much codeine they’re producing, selling or dispensing and who it is being provided to. This would “enable SAHPRA to detect anomalies in the distribution of medicines prone to abuse, such as abnormally large orders by dispensaries” Moloi explains.
It is the “first phase”, she says, of the codeine care initiative – which is an effort to centralise data on all codeine sales along the entire supply chain nationally. The plan is to ensure that the regulator can flag anything from an individual who is buying large amounts of codeine from multiple vendors to a wholesaler who is selling the drug to illicit dealers.
Codeine rehab admissions triple since 2019
The draft guideline, which is now available for public comment, comes at a time in which rates of codeine addiction are soaring throughout South Africa, according to admissions data from drug and alcohol treatment facilities. Most rehabilitation centres around the country are connected to a programme called the South African Community Epidemiology Network on Drug Use (SACENDU), which collects anonymised patient data from the different centres. Professor Nadine Harker, who oversees this project says “if you look at treatment admissions over time, there has been an increase [in codeine-related admissions] over the years – steadily but definitely”.
Indeed, SACENDU’s bi-annual reports show that in the first half of 2019, 277 people who went to SACENDU-linked rehab sites said they had been misusing codeine. This amounted to 3% of all admissions. But by the first half of 2023, this percentage had tripled to 9% – totalling 749 people. (In absolute terms the number slightly less than tripled).
Even before this uptick, health workers were concerned. In the mid-2010s, a survey of 238 (mostly private sector) doctors was conducted across South Africa. It found that 85% of these practitioners were worried about the easy availability of codeine in pharmacies.
Part of the concern is driven by the fact that people who use codeine-based medicines over a long time can develop a range of health complications, including stomach ulcers and liver damage (this is particularly when the medicines contain additional substances like paracetamol). And some people are more vulnerable than others, as genetic factors play a big role in how codeine affects a person.
Why is the problem getting worse?
Part of the spike in codeine use appears to be driven by a trend among young people, who sometimes mix codeine-based cough syrups with cooldrinks. The combination is often referred to as lean, and has become a popular party drug among high school students. Research shows that codeine’s low price and general accessibility is one reason for its popularity. Harker for instance notes that it’s often available at home, where kids “can pick it up out of their mom’s medicine cabinet”.
In other cases, people appear to be relying on the drug not for recreation but to cope with psychological distress. For instance, a 2022 study for which women were interviewed at rehab centres in the Western Cape and Eastern Cape found that many had turned to pharmaceutical products to deal with everything from trauma caused by physical abuse to grief over the loss of a child.
“I just wanted the pain to go away. I wanted my mind to switch off… [the tablets] actually made me dead inside if I can say that,” one woman explained.
A lack of awareness about the dangers of codeine also seems to play a role: 94% of doctors who were surveyed agreed that patients “do not fully understand the risk of dependence in taking over-the-counter medicines containing codeine”. The lack of regulatory control may contribute to this impression: one study at South African rehab centres found that “many participants were of the view that [over-the-counter] codeine-containing medicines were not drug[s] per se due to their free availability to purchase without any real regulations or protocols guiding their sale”.
Shouldn’t we just make codeine prescription-only?
Currently, the law states that codeine-based pills can be bought over the counter only under specific conditions. For one, they have to contain another active ingredient like paracetamol or ibuprofen, and each pill can contain a maximum of 10 milligrams of codeine. A person can only buy one pack and it must contain at most 5 days’ worth of medicine (with no more than 80 milligrams a day). Anything more and a script is needed.
Liquid codeine, like cough syrups, can be bought without a script if it contains no more than 10 milligrams of codeine per teaspoon (the maximum daily dose is 80 milligrams). The bottle itself may not contain more than 100 millilitres of syrup.
Products like Gen-payne, Myprodol, and Stopayne all contain small amounts of codeine – typically in combination with other painkillers such as paracetamol or ibuprofen. (Photo: Towfiqu Barbhuiya/Unsplash)
Some researchers that spoke to Spotlight argue these restrictions are too lenient, and that codeine should be ‘up-scheduled’, meaning that it would only be available if a patient has a script, regardless of the dose or combination. By doing this, children may find it harder to get a hold of cough syrups for lean, and people may generally become more aware of the addictiveness of the drug when used over the long-term.
Indeed, there are some studies which have found this approach to be effective in other countries. Research published in the journal Addiction found that when authorities in Australia made codeine prescription-only in 2018, a large poisoning information centre in the country began to receive significantly fewer calls about codeine-related incidents (both from health workers and members of the public).
But there are also potential downsides to this strategy. For one, as Spotlight has previously reported, increased regulation may make life harder for poorer patients seeking pain relief. This is given that they would have to spend more money for a consultation and prescription if they needed codeine-based painkillers.
Andy Gray, who chairs an advisory scheduling committee at SAHPRA, details a second issue: “I’m not convinced that up-scheduling would solve the issue if what we’re dealing with [in South Africa] is illegal behaviour… If [codeine] is being smuggled out of manufacturers or wholesalers, scheduling is not going to make a difference”.
Dr Andrew Scheibe, a harm reduction researcher at the University of Pretoria, notes a third related problem that may occur. “If people do have codeine-dependence and they’re unable to access the codeine, they might likely shift to accessing opioids… on the black market”.
Scheibe highlights the United States as an example, where prescription opioids like oxycodone and fentanyl have been at the centre of a major drug epidemic. “When they tried to increase restrictions on access to those opioids then people started using heroin,” he notes. A 2022 study found that this had taken place among opioid users interviewed in Connecticut, Kentucky and Wisconsin.
Whatever the answer, researchers agree that some basic steps need to be taken to educate the public. Harker says “a lot of awareness raising needs to happen at various levels, for instance at pharmacies”. She notes that “when someone purchases codeine over the counter, it’s important for a pharmacist to engage [with them and] make the consequences known to the individual if they use it outside of the dosages indicated… And we don’t do that enough from the medical or pharmacist’s side”.
Xylazine, only intended for animals, is being added to opioids and cocaine, with deadly effects. Photo by Colin Davis on Unsplash
Xylazine is an FDA-approved sedative and pain reliever for use in animals, but it has severe adverse effects when used in humans. Now, it is now being added illicitly to opioids, like fentanyl and heroin, as well as cocaine – leading to a sharp rise in overdose deaths.
Scripps Research chemical biologists have developed a vaccine to block the effects of xylazine’s toxicity. The vaccine works by training the immune system to attack the drug, which is described in a new paper published in Chemical Communications.
“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says study senior author Kim D. Janda, PhD, professor of chemistry at Scripps Research. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”
The rapid increase in lethal drug overdoses attributed to xylazine combined with fentanyl prompted the White House Office of National Drug Control Policy to declare this combination an emerging threat to the United States. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. However, naloxone – typically administered to reverse the effects of opioids – does not tackle the impact of xylazine, highlighting the need for effective measures to treat acute toxicity caused by xylazine.
Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. The drug also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, that can require amputation in some cases – giving it the nickname “zombie drug.”
Although no treatment currently exists, targeted vaccines may offer a solution. Antibodies from vaccination can target toxins as well as viruses and bacteria. But sometimes molecules are too small to initiate an immune response, as is the case with xylazine. So, to circumvent this problem, the researchers created a vaccine using a design principle that Janda pioneered, which relies on pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant.
In this study, the scientists combined a xylazine hapten with multiple different protein types, to see which combination would create a robust immune response against xylazine. The team tested three vaccine formulations (termed TT, KLH and CRM197, based on the protein involved) to see which vaccine cocktail could help rodents after being challenged with xylazine. One of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing.
The scientists also examined how these vaccines would limit xylazine blood brain barrier, (BBB) permeation, a filtering mechanism that scrutinizes drug penetration. When xylazine was injected, it immediately crossed into the brain to bind with receptors. Antibodies typically cannot navigate the BBB; however, two of the three vaccines (TT and KLH) showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.
A provisional patent has been filed on the research. In the future, his team will build off this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that naloxone cannot do.
“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”
Smokers are on average more extraverted, but less conscientious and agreeable
Cigarette smokers, cigar smokers, and non-smokers each have distinct personality profiles, according to a study published July 3, 2024 in the open-access journal PLOS ONE by Dritjon Gruda from Universidade Catolica Portuguesa, Portugal, and Jim McCleskey from Western Governors University, USA.
Tobacco use remains a formidable global public health challenge, responsible for more than 8 million deaths annually, including those attributed to second-hand smoke exposure. Emerging research underscores the critical role of psychological factors, including personality traits, in shaping tobacco consumption patterns. To further explore this issue, Gruda and McCleskey examined the association between Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism) and cigar or cigarette smoking in a sample of 9918 older adults across 11 European countries.
Photo by Sara Kurfess on Unsplash
The results showed that smoking is associated with lower scores in conscientiousness and agreeableness and higher extraversion scores than not smoking. The authors speculate that relatively low conscientiousness among smokers may reflect a lack of self-discipline and disregard for long-term health risks, characteristic of more impulsive behaviours, while reduced agreeableness could help explain why smokers often persist despite societal disapproval. They also suggest that the higher extraversion observed may suggest that these individuals enjoy the social nature of smoking.
The analysis also determined personality differences between types of smokers, finding that cigar smokers tend to exhibit lower neuroticism and higher openness compared to both cigarette smokers and non-smokers, underlining that the motivations and contexts of tobacco use are varied.
These findings suggest that personality traits are antecedents of smoking behaviour, with implications for targeted public health interventions and social policies aimed at combating the global tobacco epidemic. According to the authors, future research should explore these relationships in younger cohorts, potentially informing early intervention strategies that preempt the onset of smoking based on predisposition to certain personality types. Further studies could also expand the scope to include other forms of tobacco products such as chewing tobacco or more recent smoking trends such as e-cigarettes and vaping.
The authors add: “Basically what we found is: ‘tell me what you smoke, and I’ll tell you who you are.’”
