Tiny sea creatures reveal the ancient origins of neurons

Our brain cell components were forming in shallow seas around 800 million years ago

Peer-Reviewed Publication

CENTER FOR GENOMIC REGULATION

 

IMAGE: CONFOCAL MICROSCOPY IMAGE OF NUCLEI, COLOURED BY DEPTH, OF TRICHOPLAX SP. H2, ONE OF THE FOUR SPECIES OF PLACOZOAN FOR WHICH THE AUTHORS OF THE STUDY CREATED A CELL ATLAS FOR. view more 

CREDIT: SEBASTIAN R. NAJLE/CENTRO DE REGULACIÓN GENÓMICA

A study in the journal Cell sheds new light on the evolution of neurons, focusing on the placozoans, a millimetre-sized marine animal. Researchers at the Centre for Genomic Regulation in Barcelona find evidence that specialized secretory cells found in these unique and ancient creatures may have given rise to neurons in more complex animals. 

Placozoans are tiny animals, around the size of a large grain of sand, which graze on algae and microbes living on the surface of rocks and other substrates found in shallow, warm seas. The blob-like and pancake-shaped creatures are so simple that they live without any body parts or organs. These animals, thought to have first appeared on Earth around 800 million years ago, are one of the five main lineages of animals alongside Ctenophora (comb jellies), Porifera (sponges), Cnidaria (corals, sea anemones and jellyfish) and Bilateria (all other animals). 

The sea creatures coordinate their behaviour thanks to peptidergic cells, special types of cells that release small peptides which can direct the animal’s movement or feeding. Driven by the intrigue of the origin of these cells, the authors of the study employed an array of molecular techniques and computational models to understand how placozoan cell types evolved and piece together how our ancient ancestors might have looked and functioned. 

Reconstructing ancient cell types 

The researchers first made a map of all the different placozoan cell types, annotating their characteristics across four different species. Each cell type has a specialised role which comes from certain sets of genes. The maps or ‘cell atlases’ allowed researchers to chart clusters or ‘modules’ of these genes. They then created a map of the regulatory regions in DNA that control these gene modules, revealing a clear picture about what each cell does and how they work together. Finally, they carried out cross-species comparisons to reconstruct how the cell types evolved. 

The research showed that the main nine cell types in placozoans appear to be connected by many "in-between" cell types which change from one type to another. The cells grow and divide, maintaining the delicate balance of cell types required for the animal to move and eat. The researchers also found fourteen different types of peptidergic cells, but these were different to all other cells, showing no in-between types or any signs of growth or division. 

Surprisingly, the peptidergic cells shared many similarities to neurons – a cell type which didn’t appear until many millions of years later in more advanced animals such as and bilateria. Cross-species analyses revealed these similarities are unique to placozoans and do not appear in other early-branching animals such as sponges or comb jellies (ctenophores). 

Evolutionary stepping stones 

The similarities between peptidergic cells and neurons were threefold. First, the researchers found that these placozoan cells differentiate from a population of progenitor epithelial cells via developmental signals that resemble neurogenesis, the process by which new neurons are formed, in cnidaria and bilateria. 

Second, they found that peptidergic cells have many gene modules required to build the part of a neuron which can send out a message (the pre-synaptic scaffold). However, these cells are far from being a true neuron, as they lack the components for the receiving end of a neuronal message (post-synaptic) or the components required for conducting electrical signals.  

Finally, the authors used deep learning techniques to show that placozoan cell types communicate with each other using a system in cells where specific proteins, called GPCRs (G-protein coupled receptors), detect outside signals and start a series of reactions inside the cell. These outside signals are mediated by neuropeptides, chemical messengers used by neurons in many different physiological processes. 

“We were astounded by the parallels," says Dr. Sebastián R. Najle, co-first author of the study and postdoctoral researcher at the Centre for Genomic Regulation. "The placozoan peptidergic cells have many similarities to primitive neuronal cells, even if they aren't quite there yet. It's like looking at an evolutionary stepping stone." 

The dawn of the neuron 

The study demonstrates that the building blocks of the neuron were forming 800 million years ago in ancestral animals grazing inconspicuously in the shallow seas of ancient Earth. From an evolutionary point of view, early neurons might have started as something like the peptidergic secretory cells of today’s placozoans. These cells communicated using neuropeptides, but eventually gained new gene modules which enabled cells to create post-synaptic scaffolds, form axons and dendrites and create ion channels that generate fast electrical signals – innovations which were critical for the dawn of the neuron around one hundred million years after the ancestors of placozoans first appeared on Earth. 

However, the complete evolutionary story of nerve systems is still to be told. The first modern neuron is thought to have originated in the common ancestor of cnidarians and bilaterians around 650 million years ago. And yet, neuronal-like cells exist in ctenophores, although they have important structural differences and lack the expression of most genes found in modern neurons. The presence of some of these neuronal genes in the cells of placozoans and their absence in ctenophores raises fresh questions about the evolutionary trajectory of neurons. 

“Placozoans lack neurons, but we’ve now found striking molecular similarities with our neural cells. Ctenophores have neural nets, with key differences and similarities with our own. Did neurons evolve once and then diverge, or more than once, in parallel? Are they a mosaic, where each piece has a different origin? These are open questions that remain to be addressed”, says Dr. Xavier Grau-Bové, co-first author of the study and postdoctoral researcher at the Centre for Genomic Regulation. 

The authors of the study believe that, as researchers around the world continue to sequence high-quality genomes from diverse species, the origins of neurons and the evolution of other cell types will become increasingly clear. “Cells are the fundamental units of life, so understanding how they come into being or change over time is key to explain the evolutionary story of life. Placozoans, ctenophores, sponges and other non-traditional model animals harbour secrets that we are only just beginning to unlock,” concludes ICREA Research Professor Arnau Sebé-Pedros, corresponding author of the study and Junior Group Leader at the Centre for Genomic Regulation.

Video of placozoan moving unde [VIDEO] | 

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JOURNAL

Cell

DOI

10.1016/j.cell.2023.08.027 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Stepwise emergence of the neuronal gene expression program in early animal evolution

ARTICLE PUBLICATION DATE

19-Sep-2023

 

Glacier Loss Day indi­cates record break­ing glacier melt

In the summer of 2022, one of Tyrol's largest glaciers experienced its most significant loss of mass on record. Last year, the Hintereisferner in Tyrol, Austria, reached its Glacier Loss Day (GLD) earlier than ever before

Peer-Reviewed Publication

UNIVERSITY OF INNSBRUCK

 

IMAGE: VIEW OF HINTEREISFERNER ON 23 JUNE 2018 (LEFT) AND 23 JUNE 2022 (RIGHT). 2018 IS CONSIDERED A BAD YEAR FOR THE MASS BALANCE OF THE GLACIER. IN 2022, HOWEVER, THE SITUATION WAS EVEN DRAMATICALLY WORSE, AS THERE WAS HARDLY ANY PROTECTIVE SNOW COVER LEFT ALREADY IN JUNE. view more 

CREDIT: WWW.FOTO-WEBCAM.EU

The Hintereisferner, located at the back of the Tyrolean Ötztal, has been closely monitored for more than 100 years, and there have been continuous records of its mass balance since 1952. This makes it one of the best-studied glaciers in the Alps and has been key to glacier and climate research at the University of Innsbruck for decades. Since 2016, the researchers have also been surveying the glacier with a worldwide unique system: the surface of the glacier is scanned daily with a terrestrial laser scanner returning the glacier surface elevation changes. This way, the change in the volume of the Hintereisferner is monitored in real time. Innsbruck glaciologist Annelies Voordendag led the measurement on site at the Hintereisferner, the results of the researchers’ investigations have now been published as highlighted article in the journal The Cryosphere.

“Already in the early summer of 2022, it became clear that the day when the ice the glacier gained during the winter starts melting away would be reached very soon. We call this day the ‘Glacier Loss Day’ or GLD for short. It can be compared to the Earth Overshoot Day, which marks the date when we use up more natural resources than the Earth can renew in a year”, explains Annelies Voordendag. Monitoring a glacier's volume and mass alterations on a daily basis provides a quick assessment of its condition in a given year.

Observing glaciers’ health

When the GLD arrives, it means the glacier is no longer in balance with the natural conditions for that year. The earlier the GLD happens, the more time is left in the remaining summer that the glacier likely will lose volume and thus, mass. “We track the daily volume changes with the automated terrestrial laser scanninng setup overlooking the glacier and derive the day that the mass gained during winter has been lost”, says Voordendag. In 2022 the GLD was measured on the 23rd of June. In the two previous years, Glacier Loss Day was reached only in the middle of August. Also in years with negative balance extremes - such as 2003 and 2018 - this day was not reached until the end of July. Even if not every summer in the future will necessarily be like the one in 2022, the trend is clear for the glaciologists, because the developments lie outside normal fluctuation ranges: "These are clear signals of anthropogenic climate change. The consequences of our greenhouse gas emissions are already hitting us hard today," adds glaciologist Rainer Prinz from the “Ice and Climate” working group in Innsbruck. The future projections of development do not present an encouraging outlook either. Only half of the Hintereisferner will be left in 10 to 20 years,” the team summarizes in their study. These are clear climate change signals that are due to anthropogenic global warming and the consequences of our greenhouse gas emissions, which are already fully affecting us today.”

The terrestrial laser scanner's container housing at Hintereisferner in October 2022.

CREDIT

Eva Fessler

The "Ice and Climate" group has been working for many years in the "outdoor laboratory" on the Hintereisferner in the Ötztal.

CREDIT

Rainer Prinz

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JOURNAL

The Cryosphere

DOI

10.5194/tc-17-3661-2023 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Brief communication: The Glacier Loss Day as an indicator of a record-breaking negative glacier mass balance in 2022

Images of simulated cities help artificial intelligence to understand real streetscapes

Researchers from Osaka University develop a way to train data-hungry models to accurately assess images of urban landscapes, without the need for real models or images of actual cities

Peer-Reviewed Publication

OSAKA UNIVERSITY

 

IMAGE: OVERVIEW OF THE PROPOSED METHOD. A 3D CITY MODEL IS AUTOMATICALLY GENERATED ACCORDING TO THE SPECIFIED PARAMETERS USING PROCEDURAL MODELING, AND ANNOTATION DATA AND TRAINING IMAGES ARE GENERATED FROM THE 3D CITY MODEL USING A GAME ENGINE AND AN IMAGE TRANSLATION TECHNIQUE, RESPECTIVELY. view more 

CREDIT: 2023 TAKUYA KIKUCHI ET AL., ADVANCED ENGINEERING INFORMATICS

Osaka, Japan – Recent advances in artificial intelligence and deep learning have revolutionized many industries, and might soon help recreate your neighborhood as well. Given images of a landscape, the analysis of deep-learning models can help urban landscapers visualize plans for redevelopment, thereby improving scenery or preventing costly mistakes.

To accomplish this, however, models must be able to correctly identify and categorize each element in a given image. This step, called instance segmentation, remains challenging for machines owing to a lack of suitable training data. Although it is relatively easy to collect images of a city, generating the ‘ground truth’, that is, the labels that tell the model if its segmentation is correct, involves painstakingly segmenting each image, often by hand.

Now, to address this problem, researchers at Osaka University have developed a way to train these data-hungry models using computer simulation. First, a realistic 3D city model is used to generate the segmentation ground truth. Then, an image-to-image model generates photorealistic images from the ground truth images. The result is a dataset of realistic images similar to those of an actual city, complete with precisely generated ground-truth labels that do not require manual segmentation.

“Synthetic data have been used in deep learning before,” says lead author Takuya Kikuchi. “But most landscape systems rely on 3D models of existing cities, which remain hard to build. We also simulate the city structure, but we do it in a way that still generates effective training data for models in the real world.”

After the 3D model of a realistic city is generated procedurally, segmentation images of the city are created with a game engine. Finally, a generative adversarial network, which is a neural network that uses game theory to learn how to generate realistic-looking images, is trained to convert images of shapes into images with realistic city textures This image-to-image model creates the corresponding street-view images.

“This removes the need for datasets of real buildings, which are not publicly available. Moreover, several individual objects can be separated, even if they overlap in the image,” explains corresponding author Tomohiro Fukuda. “But most importantly, this approach saves human effort, and the costs associated with that, while still generating good training data.”

To prove this, a segmentation model called a ‘mask region-based convolutional neural network’ was trained on the simulated data and another was trained on real data. The models performed similarly on instances of large, distinct buildings, even though the time to produce the dataset was reduced by 98%.

The researchers plan to see if improvements to the image-to-image model increase performance under more conditions. For now, this approach generates large amounts of data with an impressively low amount of effort. The researchers’ achievement will address current and upcoming shortages of training data, reduce costs associated with dataset preparation and help to usher in a new era of deep learning-assisted urban landscaping.

Data generated at each step using the developed framework. Left figure: parameter settings and other elements used in this study. Right figure: examples of data generated using the parameter settings.

Comparison of the detection accuracy of models trained on datasets generated by the proposed method and models trained on real images. It is possible to use the proposed method to achieve similar or superior results to the model trained on real images. The areas where the model trained on generated images obtained better results than the model trained on real images are indicated by the red dashed lines.

CREDIT

2023 Takuya Kikuchi et al., Advanced Engineering Informatics

The article, “Development of a synthetic dataset generation method for deep learning of real urban landscapes using a 3D model of a non-existing realistic city,” was published in Advanced Engineering Informatics at DOI: https://doi.org/10.1016/j.aei.2023.102154

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/e

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JOURNAL

Advanced Engineering Informatics

DOI

10.1016/j.aei.2023.102154 

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Development of a synthetic dataset generation method for deep learning of real urban landscapes using a 3D model of a non-existing realistic city

SOCIAL DEVELOPMENT GOALS 

New foresight report identifies urgent policy actions needed to put SDGs back on track

Ahead of the UN’s SDG Summit (18-19 September), ground-breaking analyses shows how by enacting five ‘extraordinary turnarounds’ SDGs implementation can be accelerated

Reports and Proceedings

THE CLUB OF ROME

Ahead of the UN’s SDG Summit (18-19 September), Earth4All, an international team of economists and scientists, and the Foundation for European Progressive Studies (FEPS), unveil groundbreaking research showing that policymakers can ensure the implementation of SDGs by 2050. The report ‘SDGs for All: Strategic scenarios’ equips policymakers with practical solutions designed to accelerate SDG implementation and to respond to the planetary emergency. It concludes that policymakers can step up the implementation of the SDGs by 2030 and beyond and achieve wellbeing for all. But this is only possible by enacting five ‘extraordinary turnarounds’ that break with current trends.

 

UN Secretary-General António Guterres has urged world leaders to come to the Summit “not with beautiful speeches, but with concrete actions, plans and commitments to accelerate the implementation of the 2030 Agenda and the Paris Agreement on Climate Change”.

 

The report responds to the UN Secretary-General’s call for more rigorous strategic analysis and foresight to support policymaking. It brings together analysis from leading scientists, economists and modelers, offering proven ways to implement the SDGs and dramatically improve the course of policymaking at major upcoming global meetings, including the UN SDG Summit, the UNFCCC COP28 and the UN Summit of the Future.

 

The ‘SDGs for All’ report is built around the future scenarios and the five extraordinary turnarounds first explored in Earth for All: A Survival Guide for Humanity, published in 2022.  The two scenarios are:

 

• ‘Too Little Too Late’ (TLTL) – a decision-making as usual approach resulting in deepening wealth inequality, growing social tensions and limited efforts to address climate and ecological risks. As a result, global temperature increases to 2.5°C by 2100 putting the stability of the earth system at risk. Wellbeing continues to dramatically decline globally, and it takes until 2100 to eradicate extreme poverty.   
• ‘The Giant Leap'  (GL) – an alternative, achievable path costing 2-4% GDP per annum empowers society to make ambitious decisions by implementing five extraordinary turnarounds simultaneously across poverty, inequality, empowerment, food and energy. As a result, temperatures would stabilise below 2°C, material consumption is reduced, extreme poverty is eradicated by 2050, social tensions fall dramatically, inequality is reduced, and wellbeing rises exponentially. If policymakers around the world embrace this ‘Giant Leap’, huge improvements for people and planet are possible.

 

“The Giant Leap scenario offers a way out of the current planetary emergency and a pathway for attaining the majority of SDGs by 2050.  However, this will require a radical transformation away from today’s extractive economy dominated by GDP growth to wellbeing economies that place a value on people, planet and prosperity”, comments Sandrine Dixson-Declève, co-president of The Club of Rome, co-author of Earth for All and co-lead of the Earth4All initiative.

 

The report models how progress towards achieving the SDGs would be in both scenarios.

• Poverty – In Too Little Too Late 20% of the global population live in poverty by 2050 – compared to 7% in the Giant Leap.
• Inequality – income gender parity is achieved in the Giant Leap, but severely worsens under Too Little Too Late with owners accounting for 75% of incomes.
• Emissions - CO2 emissions reach net zero under the Giant Leap in the 2040s. Compared to 2 Tonnes of CO2 per person in the Too Little Too Late scenario by 2050 – which would in result in 17 billion tonnes of carbon emitted globally per year.
• Public spending – An additional $8.8 trillion is spent globally on public services per year by 2050 in the Giant Leap - equivalent to $6,000 per person per year. Whereas the spending is $4,800 per person per year in Too Little Too Late in 2050.  

A key red flag in the report is that by 2050, the level of global warming is too high in both scenarios, with devastating consequences in every corner of the globe. However, global warming eventually plateaus below 2°C under the Giant Leap and gives a chance for humanity to thrive again. The reality of overshooting above 1.5°C in both scenarios gives serious cause for concern regarding the lack of planetary emergency plans currently in place to address climate change and the resulting increase in shocks and stresses.

The modelling has also shown that gender equality is woefully off track; at current rates it would take 257 years to reduce the overall gender gap.

“This must serve as a wake-up call for society”, said Maria João Rodrigues, President of the Foundation for European Progressive Studies. She continued: “The upcoming UN SDG Summit will mark the half-way point to the 2030 deadline for achieving the SDGs, and that is why we asked Earth4All to analyse the progress made and what we need to do to get back on track with their unique system dynamics model. Action can no longer be avoided, it must be done in a systemic way and adopted on both international and national levels.”

 

Sandrine Dixson-Declève, co-president of The Club of Rome, co-author of Earth for All and co-lead of the Earth4All initiative, concluded: “Our economic and financial systems are broken and we are reaching dangerous levels of inequality. The Too Little Too Late scenario when applied to the SDG’s condemns future generations to a dangerously destabilised planet. The climate system is likely to cross multiple tipping points and social tensions are likely to increase. This must be avoided at all costs. By contrast our Giant Leap scenario significantly reduces this risk, thereby contributing to greater resilience and the possible emergence from emergency.

 

“Although the achievement of the SDGs especially SDG13 and SDG5 is in grave danger, failing to meet them is not an option. The recipe for success: SDG implementation must be coupled with emergency planning to prepare for future shocks and stresses and leaders must take up the call for radical transformation.”

 

To achieve the pace and scale of change required for meaningful SDG progress by 2050, the report identifies several urgent policy levers which need to be implemented simultaneously:

• Significant new investments are essential – they must be accompanied by massive increases in public spending, along with higher taxation of extremely wealthy individuals and private corporations.
• Fundamental reform of the International Monetary Fund’s process for allocating Special Drawing Rights (SDRs) – to support countries that need them most. And dealing with the sovereign debt overhang is also essential to give low-income countries more fiscal space and relief.
• Governments must quickly reverse the steady erosion of workers’ rights and implement new safety nets such as a universal basic dividend.
• Governments must massively scale up investment in women and girls to reverse the huge declines in terms of income, safety, education and health.
• Global food systems must be radically transformed, starting with the repurposing of agricultural subsidies towards supporting low-carbon and regenerative agriculture practices to improve food production efficiency and sustainability. Food supply chains must shift towards localised food production, and farmworker rights must be prioritised and protected.
• Global energy systems must shift from inefficient fossil energy systems to a clean and optimised energy system that reduces consumption in high-income countries, ensures electricity access to all, and enhances greater efficiencies across the global energy system.

 

Earth4All and FEPS will present the findings of the SDGs for All report to the UN and stakeholders prior to and during the SDG Summit.

---

METHOD OF RESEARCH

Computational simulation/modeling

ARTICLE TITLE

SDGs for All: Strategic scenarios

ARTICLE PUBLICATION DATE

14-Sep-2023

DECRIMINALIZE DRUGS

Overdose deaths from fentanyl laced stimulants have risen 50-fold since 2010

The trend marks the fourth wave in the US overdose crisis, which began with prescription opioid deaths in the early 2000s and has since continued with other drugs

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - LOS ANGELES HEALTH SCIENCES

 

IMAGE: A SIMPLIFIED SCHEMA OF THE FOUR WAVES OF THE US OVERDOSE MORTALITY CRISIS. WAVES 1 AND 2 INCLUDE DEATHS INVOLVING COMMONLY PRESCRIBED OPIOIDS, AND HEROIN, RESPECTIVELY, BUT EXCLUDING FENTANYL CO-INVOLVED DEATHS. WAVE 3 AND WAVE 4 SHOW FENTANYL DEATHS NOT INVOLVING, AND INVOLVING, STIMULANTS RESPECTIVELY AS DISTINCT TRENDS. DATA FROM CDC WONDER. view more 

CREDIT: FRIEDMAN AND SHOVER, 2023, DOI: 10.1111/ADD.16318

New UCLA-led research has found that the proportion of US overdose deaths involving both fentanyl and stimulants has increased more than 50-fold since 2010, from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021. 

 

By 2021, stimulants such as cocaine and methamphetamine had become the most common drug class found in fentanyl-involved overdoses in every US state.  This rise in fentanyl/stimulant fatalities constitutes the ‘fourth wave’ in the US’s long-running opioid overdose crisis –the death toll of which continues to rise precipitously. 

 

“We’re now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis,” said lead author Joseph Friedman, an addition researcher at the David Geffen School of Medicine at UCLA. “Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for healthcare providers. We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use.”

The findings are published in the peer-reviewed journal Addiction.

The analysis illustrates how the US opioid crisis began with an increase in deaths from prescription opioids (wave 1) in the early 2000s and heroin (wave 2) in 2010.  Around 2013, an increase in fentanyl overdoses signalled the third wave.  The fourth wave – fentanyl overdoses with stimulants – began in 2015 and continues to grow.

Further complicating matters is that people consuming multiple substances may also be at increased risk of overdose, and many substances being mixed with fentanyl are not responsive to naloxone, the antidote to an opioid overdose.  

The authors also found that fentanyl/stimulant overdose deaths disproportionately affect racial/ethnic minority communities in the US, including Black and African American people and Native American people. For instance, in 2021, the prevalence of stimulant involvement in fentanyl overdose deaths was 73% among 65 to 74-year-old Non-Hispanic Black or African American women living in the western US and 69% among 55 to 65-year-old Black or African American men living in the same area.  The rate among the general US population in 2021 was 49%.

There are also geographical patterns to fentanyl/stimulant use.  In the northeast US, fentanyl tends to be combined with cocaine; in the southern and western US, it appears most commonly with methamphetamine. 

 

“We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country,” Friedman said.

 

The study was funded by the UCLA Medical Scientist Training Program (National Institute of General Medical Sciences training grant GM008042) and the National Institute on Drug Abuse at the National Institutes of Health (K01DA050771). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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JOURNAL

Addiction

DOI

10.1111/add.16318 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Charting the fourth wave: Geographic, temporal, race/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010–2021

ARTICLE PUBLICATION DATE

14-Sep-2023

The fourth wave of the US overdose crisis: fentanyl and stimulants

Peer-Reviewed Publication

SOCIETY FOR THE STUDY OF ADDICTION

 

IMAGE: A SIMPLIFIED SCHEMA OF THE FOUR WAVES OF THE US OVERDOSE MORTALITY CRISIS. WAVES 1 AND 2 INCLUDE DEATHS INVOLVING COMMONLY PRESCRIBED OPIOIDS, AND HEROIN, RESPECTIVELY, BUT EXCLUDING FENTANYL CO-INVOLVED DEATHS. WAVE 3 AND WAVE 4 SHOW FENTANYL DEATHS NOT INVOLVING, AND INVOLVING, STIMULANTS RESPECTIVELY AS DISTINCT TRENDS. DATA FROM CDC WONDER. view more 

CREDIT: FRIEDMAN AND SHOVER, 2023, DOI: 10.1111/ADD.16318.

New research published in the scientific journal Addiction has found that the proportion of US overdose deaths involving both fentanyl and stimulants has increased more than 50-fold since 2010, from 0.6% (235 deaths) in 2010 to 32.3% (34,429 deaths) in 2021.  By 2021, stimulants (such as cocaine and methamphetamine) had become the most common drug class found in fentanyl-involved overdoses in every US state.  This rise in fentanyl/stimulant fatalities constitutes the ‘fourth wave’ in the US’s long-running opioid overdose crisis –the death toll of which, continues to rise precipitously. 

“We’re now seeing that the use of fentanyl together with stimulants is rapidly becoming the dominant force in the US overdose crisis,” says lead author Dr Joseph Friedman, of the University of California, Los Angeles.  “Fentanyl has ushered in a polysubstance overdose crisis, meaning that people are mixing fentanyl with other drugs, like stimulants, but also countless other synthetic substances. This poses many health risks and new challenges for healthcare providers. We have data and medical expertise about treating opioid use disorders, but comparatively little experience with the combination of opioids and stimulants together, or opioids mixed with other drugs. This makes it hard to stabilize people medically who are withdrawing from polysubstance use.”

People consuming multiple substances may also be at increased risk of overdose, and many substances being mixed with fentanyl are not responsive to naloxone, the antidote to an opioid overdose.  

The authors also found that fentanyl/stimulant overdose deaths disproportionately affect racial/ethnic minority communities in the US, including Black and African American people and Native American people. For instance, in 2021, the prevalence of stimulant involvement in fentanyl overdose deaths was 73% among 65 to 74-year-old Non-Hispanic Black or African American women living in the western US and 69% among 55 to 65-year-old Black or African American men living in the same area.  The rate among the general US population in 2021 was 49%.

There are also geographical patterns to fentanyl/stimulant use.  In the northeast US, fentanyl tends to be combined with cocaine; in the southern and western US, it appears most commonly with methamphetamine.  Friedman says, “We suspect this pattern reflects the rising availability of, and preference for, low-cost, high-purity methamphetamine throughout the US, and the fact that the Northeast has a well-entrenched pattern of illicit cocaine use that has so far resisted the complete takeover by methamphetamine seen elsewhere in the country.”

The analysis illustrates how the US opioid crisis began with an increase in deaths from prescription opioids (wave 1) in the early 2000s and heroin (wave 2) in 2010.  Around 2013, an increase in fentanyl overdoses signalled the third wave.  The fourth wave – fentanyl overdoses with stimulants – began in 2015 and continues to grow.

-- Ends –

Research reported in this press release was supported in part by the National Institute on Drug Abuse of the National Institutes of Health under award number K01DA050771. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

This paper is Open Access on the Wiley Online Library: https://onlinelibrary.wiley.com/doi/10.1111/add.16318  or you may request a copy from Jean O’Reilly, Editorial Manager, Addiction, jean@addictionjournal.org.

To speak with authors Dr. Joseph Friedman and Dr. Chelsea Shover, please contact them at the University of California, Los Angeles by email (joseph.robert.friedman@gmail.com, CLShover@mednet.ucla.edu).

An Addiction Audio podcast with Dr. Friedman is available here (link will be live from 14 September):
https://shows.acast.com/addiction-audio/episodes/poly-drug-use-and-us-opioids-with-joseph-friedman

Full citation for article: Friedman J and Shover C. (2023) Charting the Fourth Wave: Geographic, Temporal, Race/Ethnicity, and Demographic Trends in Polysubstance Fentanyl Overdose Deaths in the United States, 2010-2021. Addiction. DOI: 10.1111/add.16318

Funding: Dr. Friedman received support from the UCLA Medical Scientist Training Program (National Institute of General Medical Sciences training grant GM008042). Dr. Shover was funded by the National Institute on Drug Abuse (K01DA050771).

Declaration of interests:  None.

Addiction is a monthly international scientific journal publishing peer-reviewed research reports on alcohol, substances, tobacco, and gambling as well as editorials and other debate pieces. Owned by the Society for the Study of Addiction, it has been in continuous publication since 1884.

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JOURNAL

Addiction

DOI

10.1111/add.16318 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Charting the Fourth Wave: Geographic, Temporal, Race/Ethnicity, and Demographic Trends in Polysubstance Fentanyl Overdose Deaths in the United States, 2010-2021

ARTICLE PUBLICATION DATE

14-Sep-2023