Do People’s Lives ‘Flash Before Their Eyes’ When They Die?

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By chance, neuroscientists were able to record the activity of a dying human brain and discovered brain wave patterns similar to dreaming, memory recall, and meditation. An analysis of this case, reported in Frontiers in Aging Neuroscience suggests a possible explanation for near-death experiences.

Imagine reliving your entire life in the space of seconds. Like a flash of lightning, you are outside of your body, watching memorable moments you lived through. This process, known as ‘life recall’, can be similar to what it’s like to have a near-death experience. What happens inside your brain during these experiences and after death are questions that have puzzled neuroscientists for centuries. However, the present study suggests that your brain may remain active and coordinated during and even after the transition to death, and may in fact be programmed to orchestrate the whole ordeal.

When an 87-year-old patient developed epilepsy, Dr Raul Vicente of the University of Tartu, Estonia and colleagues used continuous electroencephalography (EEG) to detect the seizures and treat the patient. During these recordings, the patient had a heart attack and passed away. This unexpected event allowed the scientists to record the activity of a dying human brain for the first time ever.

“We measured 900 seconds of brain activity around the time of death and set a specific focus to investigate what happened in the 30 seconds before and after the heart stopped beating,” said Dr Ajmal Zemmar, a neurosurgeon at the University of Louisville, US, who organised the study.

“Just before and after the heart stopped working, we saw changes in a specific band of neural oscillations, so-called gamma oscillations, but also in others such as delta, theta, alpha, and beta oscillations.”

Brain oscillations (aka ‘brain waves’) are patterns of rhythmic brain activity normally present in living human brains. These different types of oscillations, including gamma, are involved in high-cognitive functions, such as concentrating, dreaming, meditation, memory retrieval, information processing, and conscious perception, just like those associated with memory flashbacks.

“Through generating oscillations involved in memory retrieval, the brain may be playing a last recall of important life events just before we die, similar to the ones reported in near-death experiences,” Dr Zemmar speculated. “These findings challenge our understanding of when exactly life ends and generate important subsequent questions, such as those related to the timing of organ donation.”

Though this is the first study to ever measure live brain activity during the process of dying in humans, similar changes in gamma oscillations have been previously recorded in rats kept in controlled environments. This raises the possibility that, during death, the brain organises and executes a biological response that could be conserved across species.

The interepretation of this however is complicated by the fact that these measurements are based on a single case and stem from the brain of a patient who had suffered injury, seizures and swelling. Nonetheless, Dr Zemmar plans to investigate more cases and sees these results as a source of hope.

“As a neurosurgeon, I deal with loss at times. It is indescribably difficult to deliver the news of death to distraught family members,” he said.

“Something we may learn from this research is: although our loved ones have their eyes closed and are ready to leave us to rest, their brains may be replaying some of the nicest moments they experienced in their lives.”

Source: Frontiers

Heart Attack Survivors at Lower Risk of Parkinson’s

Credit: American Heart Association

Heart attack survivors may be slightly less likely to develop Parkinson’s disease later in life, according to new research published in the Journal of the American Heart Association.

Parkinson’s disease (PD) is a common neurodegenerative disorder. While a number of non-motor manifestations arise, the typical clinical features involve a movement disorder consisting of bradykinesia, resting tremor, and rigidity, with postural instability occurring at a later stage. The cause of PD is not known, but a number of genetic risk factors have now been characterised, as well as several genes which cause rare familial forms of PD. Secondary parkinsonism, which has symptoms similar to Parkinson’s disease, may be caused by stroke, psychiatric or cardiovascular medications, or other illness.

“We have previously found that following a heart attack, the risk of neurovascular complications such as ischaemic stroke or vascular dementia is markedly increased, so the finding of a lower risk of Parkinson’s disease was somewhat surprising,” said lead study author Jens Sundbøll, MD, PhD. “These findings indicate that the risk of Parkinson’s disease is at least not increased following a heart attack and should not be a worry for patients or a preventive focus for clinicians at follow-up.

“It is not known whether this inverse relationship with risk of Parkinson’s disease extends to people who have had a heart attack. Therefore, we examined the long-term risk of Parkinson’s disease and secondary parkinsonism among heart attack survivors,” Dr Sundbøll said.

Drawing on Danish National Health Service data, the researchers compared the risk of PD and secondary parkinsonism among roughly 182 000 patients who had a first-time heart attack between 1995 and 2016 (average age 71 years old; 62% male) and more than 909 000 matched controls. 

Over a maximum continual follow-up of 21 years, after adjusting for a wide range of potential confounding factors, the analysis found that, when compared to the control group:

  • there was a 20% lower risk of PD among people who had a heart attack; and
  • a 28% lower risk of secondary parkinsonism among those who had a heart attack.

“For physicians treating patients following a heart attack, these results indicate that cardiac rehabilitation should be focused on preventing ischaemic stroke, vascular dementia and other cardiovascular diseases such as a new heart attack and heart failure, since the risk of Parkinson’s appears to be decreased in these patients, in comparison to the general population,” Dr Sundbøll said.

Certain risk factors are common to both heart attack and PD, with higher risk found among elderly men and lower risk among people who drink more coffee and are more physically active. Interestingly, however, some classic heart attack risk factors – such as smoking, high cholesterol, hypertension and Type 2 diabetes – are associated with a reduced risk of PD.

In general, more heart attack patients smoke and have high cholesterol, either of which may explain the slightly reduced risk of PD among heart attack survivors.

“There are very few diseases in this world in which smoking decreases risk: Parkinson’s disease is one, and ulcerative colitis is another. Smoking increases the risk of the most common diseases including cancer, cardiovascular disease and pulmonary disease and is definitely not good for your health,” Dr Sundbøll noted.

One limitation of the study is that there was not enough information about smoking and high cholesterol levels among the participants, which may have influenced the findings. The study participants were almost entirely white, limiting the generalisability to other ethnic groups.

Source: American Heart Association

Injectable Nanoparticles That Could Slow Internal Bleeding

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Researchers at MIT have found the ideal size for injectable nanoparticles that could slow traumatic internal bleeding, buying more time for a patient to reach a hospital for further treatment.

In a rat study, the researchers showed that polymer nanoparticles particles in an intermediate size range, (about 150nm in diameter) were the most effective at stopping bleeding. These particles also were much less likely to travel to the lungs or other off-target sites, which larger particles often do. The results were published in ACS Nano.

“With nano systems, there is always some accumulation in the liver and the spleen, but we’d like more of the active system to accumulate at the wound than at these filtration sites in the body,” said senior author Paula Hammond, Professor at MIT.

Nanoparticles that can stop bleeding, also called haemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that attracts platelets, the blood cells that initiate blood clotting.

In this study, the researchers used a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. Most of the previous studies of polymeric particles to stop bleeding have focused on particles ranging in size from 300–500nm. However, few, if any studies have systematically analysed how size affects the function of the nanoparticles.

“We were really trying to look at how the size of the nanoparticle affects its interactions with the wound, which is an area that hasn’t been explored with the polymer nanoparticles used as haemostats before,” Hong says.

Studies in animals have shown that larger nanoparticles can help to stop bleeding, but those particles also tend to accumulate in the lungs, which can cause unwanted clotting there. In the new study, the MIT team analysed a range of nanoparticles, including small (< 100nm), intermediate (140–220nm), and large (500–650nm).

They first analysed the nanoparticles in the lab to see how how they interacted with platelets in various conditions, to see how well platelets bound to them. They found that, flowing through a tube, the smallest particles bound best to platelets, while the largest particles stuck best to surfaces coated with platelets. However, in terms of the ratio particles to platelets, the intermediate-sized particles were the lowest.

“If you attract a bunch of nanoparticles and they end up blocking platelet binding because they clump onto each other, that is not very useful. We want platelets to come in,” said lead author, Celestine Hong, an MIT graduate student. “When we did that experiment, we found that the intermediate particle size was the one that ended up with the greatest platelet content.”

The researchers injected the different size classes of nanoparticles into mice to see how long they would circulate for, and where they would end up in the body. As with previous studies, the largest nanoparticles tended accumulated in the lungs or other off-target sites.

The researchers then used a rat model of internal injury to study which particles would be most effective at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, and that those particles also showed the greatest accumulation rate at the wound site.

“This study suggests that the bigger nanoparticles are not necessarily the system that we want to focus on, and I think that was not clear from the previous work. Being able to turn our attention to this medium-size range can open up some new doors,” Prof Hammond said.

The researchers now hope to test these intermediate-sized particles in larger animal models, to get more information on their safety and the most effective doses. They hope that eventually, such particles could be used as a first line of treatment to stop bleeding from traumatic injuries long enough for a patient to reach the hospital.

Source: Massachusetts Institute of Technology

Vegetable Intake Does Not Reduce Cardiovascular Risk, Study Finds

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A long-term study on almost 400 000 people in the UK finds little or no evidence that differences in the amount of vegetables consumed affects the risk of cardiovascular disease. 

When known socio-economic and lifestyle confounding factors are corrected for, the small apparent positive effect that remains could likely also be explained away by further confounders.

Getting enough vegetables is important for maintaining a balanced diet and avoiding a wide range of diseases. But might a diet rich in vegetables also lower the risk of cardiovascular disease (CVD)? Unfortunately, new results from a powerful, large-scale new study study in Frontiers in Nutrition found no evidence for this.

The notion of CVD risk being lowered by vegetable consumption might seem plausible at first, as their ingredients such as carotenoids and alpha-tocopherol (vitamin E) have properties that could protect against CVD. But so far, prior evidence for an overall effect of vegetable consumption on CVD has been inconsistent.

The study, which drew on UK Biobank data, found a higher consumption of cooked or uncooked vegetables is unlikely to affect the risk of CVD. The study authors also explained how confounding factors might explain previous spurious, positive findings.

“The UK Biobank is a large-scale prospective study on how genetics and environment contribute to the development of the most common and life-threatening diseases. Here we make use of the UK Biobank’s large sample size, long-term follow-up, and detailed information on social and lifestyle factors, to assess reliably the association of vegetable intake with the risk of subsequent CVD,” said Prof Naomi Allen, UK Biobank’s chief scientist and co-author on the study.

The UK Biobank, follows the health of half a million adults in the UK by linking to their healthcare records. Upon their enrolment in 2006-2010, these volunteers were  interviewed about their diet, lifestyle, medical and reproductive history, and other factors.

The researchers used the responses at enrolment of 399 586 participants (of whom 4.5% went on to develop CVD) to questions about their daily average consumption of uncooked versus cooked vegetables. They analysed the association with the risk of hospitalization or death from myocardial infarction, stroke, or major CVD. They controlled for a wide range of possible confounding factors, including socio-economic status, physical activity, and other dietary factors.

Crucially, the researchers also assessed the potential role of ‘residual confounding’, that is, whether unknown additional factors or inaccurate measurement of known factors might lead to a spurious statistical association between CVD risk and vegetable consumption.

The mean daily intake of total vegetables, raw vegetables, and cooked vegetables was 5.0, 2.3, and 2.8 heaped tablespoons per person. The risk of dying from CVD was about 15% lower for those with the highest intake compared to the lowest vegetable intake. However, this effect was greatly weakened when possible confounding factors were taken into account. Controlling for factors such as socio-economic status reduced the predictive statistical power of vegetable intake on CVD by over 80%, suggesting that more precise measures of these confounders would have explained away any residual effect of vegetable intake.

Dr Qi Feng, the study’s lead author, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”

The researchers suggest that subsequent studies should further assess whether particular types of vegetables or their method of preparation might affect the risk of CVD.

Source: Frontiers

No Difference Between Paramedics’ Advanced Airway Management Strategies

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Similar outcomes were seen for patients with out-of-hospital cardiac arrest (OHCA) regardless of the advanced airway management strategy used by paramedics, results from the Taiwanese SAVE trial showed.

There was no generally no difference in clinical outcomes between groups that had the initial strategies of endotracheal intubation or supraglottic airway device insertion:

Sustained return of spontaneous circulation (ROSC) two hours after resuscitation: 26.9% vs 25.8%; survival to hospital discharge: 8.5% vs 8.4%; cerebral performance category score ≤ 2: 3.9% vs 4.8%.

Only prehospital ROSC suggested an advantage to standard endotracheal intubation (10.6% vs 6.4%), according to the researchers, whose study was published in JAMA Network Open.

Endotracheal intubation is a difficult procedure to get right. The SAVE paramedics, all experienced in both methods of advanced airway management, employed direct laryngoscopy and achieved a 77% rate of first-attempt airway success with endotracheal intubation (vs 83% with the supraglottic device). Average scene time (18.4 vs 16.9 minutes) and call-to-airway time (15.9 vs 13.9 minutes) were both longer with endotracheal intubation.

“It is unclear whether a stepwise and algorithmic endotracheal intubation training program could reduce the time in the field and the time for advanced airway insertion, and further research is warranted,” the authors said.

For the SAVE trial conducted from 2016 to 2019, researchers randomly split four EMS teams in Taipei into two clusters, each assigned to initial endotracheal intubation or supraglottic i-gel device insertion when responding to OHCAs over a biweekly period. In case the first advanced airway attempt failed, rescue airway management was allowed using a number of techniques.

The 936 OHCA patients in the study had a median age of 77 years, and 60.8% were men.

However, subgroup analysis showed that prehospital ROSC rates favoured endotracheal intubation in patients with nonshockable rhythm, nonpublic collapse, witnessed arrest, call-to-airway time under 14 minutes, and age 77 years or older.

However, different in-hospital management between groups could have affected the results. The two study arms were unequal in size, and the study could have been underpowered because of inaccurate sample size representation at the study outset. However, the researchers lamented that “even if we had realised that the sample size was inadequate at that time, we would not have been able to recruit more cases because of the outbreak of COVID.”

Source: MedPage Today

Political Factors Drove Hydroxychloroquine and Ivermectin COVID Prescriptions

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Hydroxychloroquine and ivermectin, two COVID treatments that have been shown to be ineffective for those purposes, were more heavily prescribed in the second half of 2020 in parts of the US that voted for the Republican party, according to a new research letter published in JAMA Internal Medicine.

“We’d all like to think of the health care system as basically non-partisan, but the COVID pandemic may have started to chip away at this assumption,” said lead author Michael Barnett, assistant professor of health policy and management.

The study compared prescription rates for hydroxychloroquine and ivermectin with rates for two control medications, methotrexate sodium and albendazole, which are similar drugs but have not been proposed as COVID treatments. Comparing different US counties, researchers looked at deidentified medical claims data from January 2019 through December 2020 from roughly 18.5 million adults as well as census and voting data.

Overall, hydroxychloroquine prescribing volume from June through December 2020 was roughly double what it had been in the previous year, while the volume of ivermectin prescriptions was seven-fold higher in December 2020 than the previous year. In 2019, prescribing of hydroxychloroquine and ivermectin did not differ according to county Republican vote share. However, that changed in 2020.

After June 2020 – coinciding with when the US Food and Drug Administration revoked emergency use authorisation for hydroxychloroquine – prescribing volume for the drug was significantly higher in counties with the highest Republican vote share as compared to counties with the lowest vote share.

As for ivermectin, prescribing volume was significantly higher in the highest versus lowest Republican vote share counties in December 2020 a 964% increase on the overall prescribing volume in 2019. The spike lined up with with a number of key events, such as the mid-November 2020 release of a now-retracted manuscript claiming that the drug was highly effective against COVID, and a widely publicised US Senate hearing in early December that included testimony from a doctor promoting ivermectin as a COVID treatment.

Neither of the control drugs had differences in overall prescribing volume or in prescribing by county Republican vote share.

The authors concluded that the prescribing of hydroxychloroquine and ivermectin may have been influenced by physician or patient political affiliation. “This is the first evidence, to our knowledge, of such a political divide for a basic clinical decision like infection treatment or prevention,” said Barnett.

Source: Harvard T.H. Chan School of Public Health

Endocrine-disrupting Chemicals Present in Many Pregnancies

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Researchers in Europe have shown that up to 54% of pregnant women in Sweden were exposed to complex mixtures of endocrine-disrupting chemicals disruptive to brain development.

While current risk assessment tackles chemicals and their allowable exposures on an individual basis, these findings show the need to take mixtures into account for future risk assessment approaches. The study was published in Science.

A growing body of evidence has shown that industrially produced chemicals have endocrine disrupting properties and can thus be dangerous to human and animal health and development. A huge number of new compounds is released every year into the environment during the production of plastic derivatives and other goods.

While exposures for individual chemicals falls below thresholds, exposure to the same chemicals in complex mixtures can still impact human health. However, all current exposure thresholds, are based on chemicals being examined individually. Therefore, an alternative strategy needed to be tested, in which the actual mixtures measured in real life exposures could be tested as such in both the epidemiological and experimental setting. The EDC-MixRisk project set out to tackle this unmet need.

“The uniqueness of this comprehensive project is that we have linked population data with experimental studies, and then used this information to develop new methods for risk assessment of chemical mixtures,” said Carl-Gustaf Bornehag, professor at Karlstad University, Project Manager of the SELMA study.

The study was conducted in three steps:

  1. A mixture of chemicals in the blood and urine of pregnant women was identified in the Swedish pregnancy cohort SELMA, associated with delayed language development in children at 30 months. This critical mixture included a number of phthalates, bisphenol A, and perfluorinated chemicals.
  2. Experimental studies uncovered the molecular targets through which human-relevant levels of this mixture disrupted the regulation of endocrine circuits and of genes involved in autism and intellectual disability.
  3. The findings from the experimental studies were used to develop new principles for risk assessment of this mixture.

“It is striking that the findings in the experimental systems well reflected what we found in the epidemiological part, and that the effects could be demonstrated at normal exposure levels for humans,” said Joëlle Rüegg, professor of environmental toxicology at Uppsala University.

“Human brain organoids (advanced in vitro cultures that reproduce salient aspects of human brain development) afforded, for the first time, the opportunity to directly probe the molecular effects of this mixture on human brain tissue at stages matching those measured during pregnancy. Alongside other experimental systems and computational methods, we found that the mixture disrupts the regulation of genes linked to autism (one of whose hallmarks is language impairment), hinders the differentiation of neurons and alters thyroid hormone function in neural tissue,” said Giuseppe Testa, principal investigator of the EDC-MixRisk responsible for the human experimental modelling.

“One of the key hormonal pathways affected was thyroid hormone. Optimal levels of maternal thyroid hormone are needed in early pregnancy for brain growth and development, so it’s not surprising that there is an association with language delay as a function of prenatal exposure,” said Barbara Demeneix, professor of physiology and endocrinology at the Natural History Museum in Paris.

By combining these techniques, the researchers were able to show that 54% of children included in the SELMA study were at risk of delayed language development (at age 30 months) as they were prenatally exposed to a mixture of chemicals at levels that were above the levels predicted to impact neurodevelopment. Yet this risk fell below the exposure limits for individual chemicals.

Source: EURION Cluster

Soluble Fibre is Associated with Lower Dementia Risk

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Drawing on a decades-long cohort study, researchers in Japan have found that higher levels of dietary fibre, particularly soluble fibre, are associated with a lower risk of dementia.

Fibre is known to have vital importance for a healthy digestive system and also has cardiovascular benefits like reduced cholesterol. In a new study published in Nutritional Neuroscience, researchers have shown that a high-fibre diet is also associated with a reduced risk of developing dementia, adding to evidence that fibre is also important for a healthy brain.

“Dementia is a devastating disease that usually requires long-term care,” says lead author of the study Professor Kazumasa Yamagishi. “We were interested in some recent research which suggested that dietary fibre may play a preventative role. We investigated this using data that were collected from thousands of adults in Japan for a large study that started in the 1980s.”

Between 1985 and 1999, 3739 participants who were generally healthy and aged between 40–64 completed dietary information surveys. They were then followed up from 1999 until 2020, and it was noted whether they developed dementia that required care.

Participants were assigned into four groups according to the amount of fibre in their diets. They found that the groups who ate higher levels of fibre had a lower risk of developing dementia.

The team also examined whether there were differences for the two main types of fibre: soluble and insoluble fibres. Soluble fibres, found in foods such as oats and legumes, are important for the beneficial bacteria that live in the gut as well as providing other health benefits. Insoluble fibres, found in whole grains, vegetables, and some other foods, are known to be important for bowel health. The researchers found that the link between fibre intake and dementia was more pronounced for soluble fibres.

The team has some ideas as to what might underlie the link between dietary fibre and the risk of dementia.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” said Professor Yamagishi. “One possibility is that soluble fibre regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia. It’s also possible that dietary fibre may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels. The work is still at an early stage, and it’s important to confirm the association in other populations.”

Source: University of Tsukuba

Cough Suppressant Could Lead to New Arrhythmia Treatment

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An over-the-counter cough suppressant can knock some heart cells out of arrhythmia, a discovery that could lead to a new treatment for long QT syndrome. The finding, which was published in Nature Cardiovascular Researchwas made using stem cells from patients with the disorder.

The QT interval on an electrocardiogram (ECG) represents the duration of the ventricular action potential, and this physiologically correlates with the duration of the ventricular depolarisation and repolarisation. Cardiac events and fatal arrhythmias may occur when the QT interval is prolonged either congenitally or through acquired causes. In people with long QT syndrome, cardiac cells are not always ready to produce the next beat, a situation that can knock the heart out of its normal rhythm, which may be life-threatening. For many people with long QT, no treatment can correct the heart cells or prevent arrhythmia.

Using mice to investigate how human heart arrhythmias can be stopped is difficult, so Masayuki Yazawa, PhD at the University of Columbia, turned to patient-derived reprogrammed stem cells, which can be made into heart cells in the lab.

The road to the discovery began several years ago when Dr Yazawa found that heart cells in the lab would resume a normal rhythm when a certain enzyme was inhibited. But the drugs used to inhibit the enzyme also had other unintended effects, such as liver toxicity, so alternatives were needed.

Looking through published research, the team learned that the enzyme could be inhibited through an intermediary molecule inside heart cells called SIGMAR1. Further reading suggested that SIGMAR1 could be targeted by a cough suppressant, dextromethorphan.

Dr Yazawa’s team found that the cough suppressant, when added to heart cells, successfully prepared the heart cells for the next beat and soothed the cells’ irregular rhythm.

The cough suppressant reset heart cells from people with Timothy syndrome, a genetic disorder that also causes other heart abnormalities, and from people with more common forms of long QT syndrome.

Dr Yazawa cautioned that it’s premature to use dextromethorphan to treat long QT patients; the drug has a short half-life and would have to be used long term, which might still have unknown adverse side effects.

“But our study shows that drugs targeting SIGMAR1 have potential to treat a wide array of patients with long QT syndrome,” said Dr Yazawa, “and we will continue to look for better options.”

Source: Columbia University

LSD Microdosing Study Shows no Benefit

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Published in Addiction Biology, a study into the effects of LSD “microdosing” found no evidence to back up proponents’ claims that it can improve mood and cognitive function. 

The study’s lead author, Chicago University Professor Harriet de Wit, noted that the study doesn’t disprove microdosing’s possible benefits, and that more investigation is needed. The study does show that taking small doses of LSD is safe. Prof De Wit said the findings demonstrate the important role clinicians can play when it comes to therapeutics claims about recreational drugs.

“These drugs are already being used out in the world, and it’s important for us to test them under controlled conditions, ensure their safety and see whether there’s some validity to the benefits people claim,” she said. “That’s something that has been missing from the conversation.”

The researchers studied the effects of four repeated low doses of LSD, administered under lab conditions every three to four days. One group of participants received 13 micrograms of the drug, a second group received 26 micrograms, and the third received a placebo. To put these low doses into context, the doses of LSD that are used to “trip” or to get high are typically 100–200 micrograms, she said.

LSD was chosen for the study because it’s the most commonly used psychedelic drug in microdosing.

Participants received the drugs during five-hour, supervised laboratory sessions. They also attended a drug-free follow-up session three to four days after the last dose. Participants were not told what kind of drug was being tested in the study – whether it was a stimulant, a tranquiliser or a hallucinogen – or that the study was about microdosing.

“We removed any expectations that this was a psychedelic drug,” Prof de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”

To assess their mood and mental performance, the participants completed cognitive and emotional tasks both during the drug administration sessions and at the drug-free follow-up session. Some participants who received the higher dose reported feeling a modest “high” during the drug sessions, but the effects were mild.

The drug did not improve mood or affect participants’ performance on cognitive tests, either during the drug sessions or at the follow-up session.

Prof De Wit said the results came as a disappointing surprise. “Because so many people claim to have experienced benefits from microdosing, we expected to document some kind of beneficial effect under laboratory conditions,” she said.

Neurobiological reasons had also suggested that LSD might improve mood, because LSD acts through serotonin receptors, where traditional antidepressants are known to act.

“We can’t say necessarily that microdosing doesn’t work,” Prof de Wit said. “All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn’t see a robust effect.”

People who microdose often have strong expectations of beneficial effects. “It is possible that these expectations contribute to the apparent benefits, or they may interact with the pharmacological effect of the drug,” she said.

LSD was confirmed to be safe, an unsurprising find which is in line with previous human and animal studies.

In fact, de Wit noted, participants appeared to build a tolerance to LSD over the course of the study, with the strongest “high” reported at the first session, and the perception of a drug effect diminishing at each subsequent session. That’s a good sign because it confirms the drug does not stay in the body or accumulate over time, she said.

Getting authorisation to use a controlled substance made the experiment challenging, as did the participants’ necessary time commitment. However, Prof de Wit emphasised the importance of such research, especially as practices like microdosing become commercialised.

“There are a lot of companies getting into the drug business, either with psychedelic drugs, or drugs like cannabidiol,” she noted. “And really there’s not very much empirical support to back up their claims. So, I think we have a responsibility to investigate and validate the claims.”

Source: University of Chicago