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Health & Medicine

Breaking the Hallucinogenic Barrier: Researchers Develop LSD Analogue for Treating Schizophrenia

Researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic’s therapeutic power with reduced hallucinogenic potential.

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Breaking the Hallucinogenic Barrier: Researchers Develop LSD Analogue for Treating Schizophrenia

Researchers at the University of California, Davis have made a groundbreaking discovery in developing a new drug closely related to LSD. The innovative compound, dubbed JRT, has been designed to harness the therapeutic potential of LSD while minimizing its hallucinogenic effects.

JRT’s development is significant as it may provide a much-needed treatment option for conditions like schizophrenia, where psychedelics are not prescribed due to safety concerns. The research, published in Proceedings of the National Academy of Sciences, highlights JRT’s potential as a treatment for other neuropsychiatric and neurodegenerative diseases characterized by synaptic loss and brain atrophy.

To design JRT, researchers simply flipped the position of two atoms in LSD’s molecular structure. This subtle modification resulted in a significant improvement in JRT’s selectivity profile and reduced its hallucinogenic potential while maintaining its neurotherapeutic properties.

The JRT molecule was named after Jeremy R. Tuck, a former graduate student who synthesized it, and is a testament to the innovative spirit of researchers. David E. Olson, corresponding author and director of the Institute for Psychedelics and Neurotherapeutics at UC Davis, explained that “what we did here is a tire rotation.” By modifying LSD in this way, JRT’s therapeutic potential was unlocked while minimizing its hallucinogenic effects.

JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia. Importantly, it did not exacerbate behaviors and gene expression associated with psychosis. This makes JRT a promising treatment option for patients where psychedelic use is precluded.

Olson emphasized that JRT’s development emphasizes the potential for using psychedelics as starting points to create better medicines. “We may be able to create medications that can be used in patient populations where psychedelic use is precluded,” he stated.

The researchers conducted a battery of cellular and mouse assays, which demonstrated JRT’s neuroplastic effects and improved safety profile relative to LSD. Key findings included:

* JRT has extremely high therapeutic potential.
* The molecule was tested in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better.

JRT’s potential for treating schizophrenia is significant as most current treatments have limited effects on anhedonia – the inability to feel pleasure – and cognitive function. Clozapine is one exception but has side effects and is not a first-line drug of choice for people severely afflicted with schizophrenia.

Olson and his team are currently testing JRT’s potential against other neurodegenerative and neuropsychiatric diseases, paving the way for further research and development in this area.

Allergy

The Hidden Dangers of Fire Smoke Exposure

Smoke from wildfires and structural fires doesn t just irritate lungs it actually changes your immune system. Harvard scientists found that even healthy people exposed to smoke showed signs of immune system activation, genetic changes tied to allergies, and even toxic metals inside their immune cells.

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The dangers of fire smoke exposure are well-documented, but until now, the full extent of its impact on our bodies has been unclear. A recent study led by researchers at Harvard T.H. Chan School of Public Health reveals that fire smoke can alter our immune system on a cellular level, leaving lasting changes and increasing our risk of serious health problems.

The study examined blood samples from 31 individuals who had been exposed to fire smoke and compared them to those from 29 non-exposed individuals. The results showed significant changes in the immune cells of those who had been exposed to smoke. These changes included an increase in memory CD8+ T cells, which are crucial for long-term immunity against pathogens, as well as elevated activation and chemokine receptor biomarkers that indicate inflammation and immune activity.

The researchers also found changes in 133 genes related to allergies and asthma in the individuals who had been exposed to smoke. Moreover, their immune cells were more likely to be bound with toxic metals like mercury and cadmium, which can further harm our health.

“This study fills a critical knowledge gap by showing exactly how fire smoke exposure can damage the body,” said Kari Nadeau, corresponding author of the study and chair of the Department of Environmental Health. “Our findings have significant implications for public health leaders and clinicians who need to respond to the growing threat of wildfires.”
The study’s lead author, Mary Johnson, added that the immune system is extremely sensitive to environmental exposures like fire smoke, even in healthy individuals. Knowing exactly how smoke exposure can harm our bodies may help us detect immune dysfunction earlier and pave the way for new therapeutics to mitigate or prevent the health effects of smoke exposure.

The researchers also noted that their study could inform environmental and public health policies and investments, such as increasing public awareness about the dangers of smoke exposure and the importance of following evacuation procedures during wildfires.
The study was funded by several organizations, including the National Institute of Environmental Health Sciences, the National Heart, Lung, and Blood Institute, and the San Francisco Cancer Prevention Foundation.

In conclusion, this study highlights the need for increased caution when it comes to fire smoke exposure. By understanding the full extent of its impact on our bodies, we can take steps to protect ourselves and others from its toxic effects.

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Allergy

The Resilient Enemy: Why Asthma Symptoms Persist Despite Powerful Drugs

Biological drugs have been a game-changer for people with severe asthma, helping them breathe easier and live more comfortably. But researchers at Karolinska Institutet have uncovered a surprising twist: while these treatments ease symptoms, they may not fully eliminate the immune cells that drive inflammation. In fact, some of these cells actually increase during treatment, suggesting the medication is managing symptoms without targeting the root cause. This could explain why asthma often returns when the drugs are stopped, raising questions about how long-term these treatments should be and whether we’re truly solving the underlying problem.

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Asthma has long been a formidable foe for many people, causing symptoms that can range from mild discomfort to life-threatening attacks. While powerful biological drugs have significantly improved the lives of those with severe asthma, a recent study has shed light on why these symptoms often return despite treatment.

Biological drugs, or biologics, have become a crucial tool in managing severe asthma by helping patients keep their symptoms under control. However, researchers at Karolinska Institutet in Sweden discovered that certain immune cells, which play a significant role in asthma inflammation, do not disappear during treatment as previously thought. Instead, these inflammatory cells increase in number.

This finding suggests that biologics might not address the root cause of asthma, but rather manage its symptoms. As such, continued treatment may be necessary to keep the disease under control. This is particularly concerning considering that little is still known about the long-term effects of biologics like mepolizumab and dupilumab, which have been prescribed to asthmatics for less than ten years.

The study analyzed blood samples from 40 patients before and during treatment, using advanced methods such as flow cytometry and single-cell sequencing. Researchers were surprised to find that the levels of inflammatory cells in these patients increased rather than decreased. This could explain why inflammation of the airways often returns when the treatment is tapered or discontinued.

It is essential for researchers and medical professionals to understand the long-term immunological effects of biologics, as this knowledge can lead to more effective treatments and better outcomes for patients with severe asthma. The next stage of the study will involve analyzing samples from patients with a long treatment history and studying lung tissue to see how immune cells are affected in the airways.

The findings of this study have significant implications for the management and treatment of asthma, highlighting the need for continued research into the effects of biologics on the immune system.

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Alternative Medicine

Brewing a Breakthrough: Scientists Turn Beer Yeast into Mini Factories for Smart Drugs

A team of researchers has turned ordinary yeast into tiny, glowing drug factories, creating and testing billions of peptide-based compounds in record time. This green-tech breakthrough could fast-track safer, more precise medicines and reshape the future of pharma.

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The scientific community has made significant strides in recent years towards developing innovative methods for producing and analyzing complex molecules. In an exciting breakthrough, researchers from Ca’ Foscari University of Venice, along with international collaborators, have successfully harnessed the potential of brewer’s yeast to create miniature factories that produce macrocyclic peptides – promising drugs with high therapeutic value.

Macrocyclic peptides are a class of molecules that offer precision targeting, stability, and safety, making them an attractive alternative to traditional drugs. However, conventional methods for discovering and testing these peptides have been complex, slow, and environmentally unfriendly. To overcome these limitations, the researchers engineered brewer’s yeast cells to individually produce different macrocyclic peptides.

Each yeast cell acts as a tiny factory that lights up when producing the compound, allowing scientists to swiftly identify promising peptides. Using advanced fluorescence-based techniques, the team screened billions of micro-factories in just a few hours – a process significantly faster and more ecofriendly than existing methods.

Lead author Sara Linciano explained the innovative approach: “We manipulated yeast cells so that each one functions as a ‘micro-factory’ that becomes fluorescent when producing a specific compound. This allowed us to analyze 100 million different peptides rapidly and effectively.”

The study’s co-leader, Ylenia Mazzocato, highlighted the sustainability of their approach: “By exploiting the natural machinery of yeast, we produce peptide molecules that are biocompatible and biodegradable, making them safe for health and the environment – a truly ‘green pharma’ approach.”

The researchers also demonstrated the excellent binding properties of these peptides using X-ray crystallography. This new method offers significant advancements for drug discovery, especially for challenging targets that conventional drugs cannot easily address.

As Alessandro Angelini, associate professor and study coordinator, emphasized: “We are pushing the boundaries of this technology to create macrocyclic peptides that can deliver advanced therapies directly to specific cells, potentially revolutionising treatments. This could greatly benefit patient health and have substantial scientific and economic impacts.”

This work was part of the National Recovery and Resilience Plan (PNRR), supported by the European Union’s Next Generation EU initiative. The team involved multidisciplinary experts from Ca’ Foscari University of Venice, Kyoto Institute of Technology, Chinese Academy of Sciences, University of Padova, and École Polytechnique Fédérale de Lausanne.

Part of this technology has already been patented by Ca’ Foscari and was recently acquired by the startup Arzanya S.r.l. As Angelini concluded: “Seeing our technology gain international recognition makes me proud. I hope Arzanya S.r.l. can provide our talented young researchers with the opportunity to pursue their passions here in Italy, without necessarily needing to move abroad.”

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