Thursday, June 27, 2024

Magic mushrooms are the most-used psychedelic drug

As states change laws, federal policymakers face urgent questions

RAND CORPORATION

Psilocybin mushrooms are the psychedelic substance most often used in the U.S., with its popularity outpacing other psychedelic drugs such as MDMA (known as ecstasy), according to a new RAND report.

Based on a new national survey, researchers found that about 12% of respondents reported using psilocybin at some point over their lives and 3.1% reported using the substance over the past year. An estimated 8 million American adults used psilocybin in 2023.

Psychedelic substances such as psilocybin mushrooms and MDMA long have been touted as holding promise for treating various mental health conditions, with enthusiasm about the substances growing during the past decade. Although clinical research continues to grow, less attention has focused on the changing policy landscape for some psychedelics.

The report, which looks broadly at emerging issues involving the use and supply of psychedelics for nonclinical purposes, suggests that as state and local officials ease regulations on the substances, federal policymakers must decide whether they want psychedelics to follow in the footsteps of the for-profit cannabis model or take another path.

“The current situation with psychedelics reminds me of where we were with cannabis policy 12 years ago” said Beau Kilmer, lead author of the report and a senior policy researcher at RAND, a nonprofit research organization. “Now is the time for federal policymakers to decide if they want to shape these policy changes or stay on the sidelines.”

Researchers caution that there is concern that if efforts to expand non-clinical supply of psychedelics do not go well, it could generate a backlash that may have a chilling effect on research and potential therapeutic uses.

“Based on what happened with clinical research on psychedelics after the 1960s, this is not an idle concern,” said Kilmer, codirector of the RAND Drug Policy Research Center.

The RAND report is based on several sources of information, including a December 2023 survey of a representative sample of 3,791 American adults who were asked about their use of a variety of substances, including psychedelics. The survey included several questions specific to psilocybin use and how it was obtained. The researchers also analyzed data from the National Survey on Drug Use and Health and the National Incident-Based Reporting System.

Researchers interviewed legal experts, policy advocates, regulators, clinical researchers, mental health providers, and representatives from organizations working in the emerging psychedelics industry for the U.S. and abroad. The work also included discussions with members of Indigenous communities about their spiritual medicines.

“Policy changes may affect Indigenous people who have longstanding traditions with certain spiritual medicines that are commonly referred to as psychedelics,” said Michelle Priest, coauthor of the report and an assistant policy researcher at RAND. “Engaging respectfully with Indigenous community members who are authorized to speak on these topics can help craft policies that benefit from generations of wisdom while protecting Indigenous rights.”

Despite the federal prohibition on supply and possession outside approved clinical research and some religious exemptions, some state and local governments are loosening their approaches to psychedelics, including approaches that legalize some forms of supply to adults for any reason.

For states considering alternatives to prohibiting the supply of psychedelics, the report highlights how there are many options besides the for-profit approach. For example, states could allow people to forage or grow their own, or allow them to join non-profit collectives or cooperatives. There also is the supervised use model that’s operating in Oregon for psilocybin and is expected to be up and running in Colorado in 2025.

One difference from cannabis policy debates, the researchers note, is the role of supervision in policy discussions surrounding psychedelics. Even in places that do not adopt the supervision model being implemented in Oregon and Colorado, policymakers will likely confront many decisions surrounding the regulation of facilitators and supervision settings.

The RAND report found that unlike people who use cannabis and many other drugs, those who use psychedelics typically do so infrequently. The RAND survey found that 0.9% of respondents reported using psilocybin during the past month, compared to 20% of respondents reporting cannabis use during the past month.

Researchers estimate that among all American adults, the total number of use days in the past month for cannabis was on the order of 650 million, whereas the comparable figure for hallucinogens was closer to 7 million.

Among those reporting past year use of psilocybin in the RAND survey, 47% reported microdosing the last time they used. Microdosing involves using small amounts of psilocybin or other psychedelics -- often 1/10th to 1/20th of a typical dose.

Researchers say one takeaway from the analysis is the extent to which infrequent users drive the market for psychedelics. For cannabis, the market for infrequent users is negligible, accounting for about 5% of the total use days in the past month. For psychedelics, that figure is closer to 60%.

“While price is a major policy lever when we think about regulating cannabis and alcohol, it will likely play a much smaller role for psychedelics since infrequent users currently drive the market and they tend to spend relatively little on these substances,” said Rajeev Ramchand, coauthor of the report and codirector of the RAND Epstein Family Veterans Policy Research Institute.

The researchers found that when they were writing the report, it became clear how little has been published about the markets and patterns of use for many psychedelics -- especially psilocybin. They offer ideas for improving existing surveys such as the National Survey on Drug Use and Health, and recommend conducting qualitative research (ideally longitudinally) with those who use psychedelics and those who produce and distribute these substances in legal or illegal settings.

Support for the study was provided by a gift to RAND from the Sergey Brin Family Foundation and internal RAND support.

Other authors of the study are Rhianna C. Rogers, Ben Senator and Keytin Palmer.

The RAND Social and Economic Well-Being division seeks to actively improve the health, and social and economic well-being of populations and communities throughout the world.

RAND Health Care promotes healthier societies by improving health care systems in the United States and other countries.

DOI

10.7249/RRA2825-1

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Considering Alternatives to Psychedelic Drug Prohibition

ARTICLE PUBLICATION DATE

27-Jun-2024

PALEONTOLOGY

Ammonites went out with a diverse bang—and not a long, slow fizzle—in the Late Cretaceous

A new study used museum collections to map ammonite diversity around the globe before their total extinction and found they were not in decline prior to their extinction alongside non-avian dinosaurs 66 million years ago

NATURAL HISTORY MUSEUM OF LOS ANGELES COUNTY

Ammonites basking under the Late Cretaceous sun. Artwork by Callum Pursall — IMAGE:
AMMONITES BASKING UNDER THE LATE CRETACEOUS SUN. ARTWORK BY CALLUM PURSALL (@CPURSALL ON X)
view more
CREDIT: ARTWORK BY CALLUM PURSALL

Los Angeles, CA (June 27, 2024) —A new study published in the journal Nature Communications led by paleontologists at the University of Bristol along with a team of international researchers, including Dr. Austin Hendy, Curator of Invertebrate Paleontology at the Natural History Museum of Los Angeles County, finds that instead of fizzling out ahead of their extinction, ammonoids were still going strong across the globe in the Late Cretaceous. Made possible by museum collections, the new study compared their diversity across the globe just prior to extinction, unearthing the complex evolutionary history of their final chapter for the first time.

Ammonoids, marine mollusks often distinguished by their coiled shells, are one of paleontology’s great icons. They flourished in Earth’s oceans for more than 350 million years until their extinction during the same chance event that wiped out the dinosaurs 66 million years ago. Some paleontologists, however, have argued the diversity of ammonites (the last major lineage of ammonoids) was declining well before their extinction at the end of the Cretaceous Period and that their demise was inevitable.

“Ammonites had an amazing evolutionary history. With their formidable shells and powerful tentacles they innovated the act of swimming. They could grow to as big as a car or to just a few millimeters in diameter. They played equally disparate roles in their ecosystems, from predators near the top of the food web to filter feeding off plankton,” said Hendy.

“Understanding how and why biodiversity has changed through time is very challenging,” said lead author Dr. Joseph Flannery-Sutherland. “The fossil record tells us some of the story, but it is often an unreliable narrator. Patterns of diversity can just reflect patterns of sampling, essentially where and when we have found new fossil species, rather than actual biological history. Analyzing the existing Late Cretaceous ammonite fossil record as though it were the complete, global story is probably why previous researchers have thought they were in long-term ecological decline.”

To overcome this issue, the team assembled a new database of Late Cretaceous ammonite fossils to help fill in the sampling gaps in their record. “We drew on museum collections to provide new sources of specimens rather than just relying on what had already been published,” said co-author Cameron Crossan, a 2023 graduate of the University of Bristol’s Palaeobiology MSc program. “This way, we could be sure that we were getting a more accurate picture of their biodiversity prior to their total extinction.”

Using their database, the team then analyzed how ammonite speciation—forming distinct new species—and extinction rates varied in different parts of the globe. If ammonites were in decline through the Late Cretaceous, then their extinction rates would have been generally higher than their speciation rates wherever the team looked. Instead, the team found that the balance of speciation and extinction changed both through geological time and between different geographic regions.

“These differences in ammonoid diversification around the world is a crucial part of why their Late Cretaceous story has been misunderstood,” said senior author Dr. James Witts of the Natural History Museum, London. “Their fossil record in parts of North America is very well sampled, but if you looked at this alone, then you might think that they were struggling while they were actually flourishing in other regions. Their extinction really was a chance event and not an inevitable outcome.”

Environmental Factors vs Competition
So, what was responsible for the continued success of ammonites through the Late Cretaceous? To answer this question, the team looked at potential factors that might have caused their diversity to change over time. They were particularly interested in whether their speciation and extinction rates were driven mainly by environmental conditions like ocean temperature and sea level or by biological processes like pressure from predators and competition between ammonites.

“What we found was that the causes of ammonite speciation and extinction were as geographically varied as the rates themselves,” said co-author Dr. Corinne Myers of the University of New Mexico. “You couldn’t just look at their total fossil record and say that it was driven entirely by changing temperature, for example. It was more complex than that and depended on where in the world they were living.”

JOURNAL

Nature Communications

DOI

10.1038/s41467-024-49462-z

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Late Cretaceous ammonoids show that drivers of diversification are regionally heterogeneous

ARTICLE PUBLICATION DATE

27-Jun-2024

Ammonites’ fate sealed by meteor strike that wiped out dinosaurs

UNIVERSITY OF BRISTOL

Fig 1 — IMAGE:
AMMONITES BASKING UNDER THE LATE CRETACEOUS SUN.
view more
CREDIT: CALLUM PURSALL (@CPURSALL ON X)

Ammonites were not in decline before their extinction, scientists have found.

The marine molluscs with coiled shells and one of palaeontology’s great icons flourished in Earth’s oceans for more than 350 million years until they died out during the same chance event that wiped out the dinosaurs 66 million years ago.

Some palaeontologists have argued that their demise was inevitable and that ammonite diversity was decreasing long before they went extinct at the end of the Cretaceous.

However new research, published today in Nature Communications and led by palaeontologists at the University of Bristol, shows that their fate was not set in stone. Instead, the final chapter in ammonite evolutionary history is more complex.

“Understanding how and why biodiversity has changed through time is very challenging,” said lead author Dr Joseph Flannery-Sutherland. “The fossil record tells us some of the story, but it is often an unreliable narrator. Patterns of diversity can just reflect patterns of sampling, essentially where and when we have found new fossil species, rather than actual biological history.

“Analysing the existing Late Cretaceous ammonite fossil record as though it were the complete, global story is probably why previous researchers have thought they were in long-term ecological decline.”

To overcome this issue, the team assembled a new database of Late Cretaceous ammonite fossils to help fill in the sampling gaps in their record. “We drew on museum collections to provide new sources of specimens rather than just relying on what had already been published,” said co-author Cameron Crossan, a 2023 graduate of the University of Bristol’s Palaeobiology MSc programme. “This way we could be sure that we were getting a more accurate picture of their biodiversity prior to their total extinction.”

Using their database, the team then analysed how ammonite speciation and extinction rates varied in different parts of the globe. If ammonites were in decline through the Late Cretaceous, then their extinction rates would have been generally higher than their speciation rates wherever the team looked. What the team instead found was that the balance of speciation and extinction changed both through geological time and between different geographic regions.

“These differences in ammonoid diversification around the world is a crucial part of why their Late Cretaceous story has been misunderstood,” said senior author Dr James Witts of the Natural History Museum, London. “Their fossil record in parts of North America is very well sampled, but if you looked at this alone then you might think that they were struggling, while they were actually flourishing in other regions. Their extinction really was a chance event and not an inevitable outcome.”

To find out what was responsible for the continued success of ammonites through the Late Cretaceous, the team looked at potential factors might have caused their diversity to change through time. They were particularly interested in whether their speciation and extinction rates were driven mainly by environmental conditions like ocean temperature and sea level (the Court Jester Hypothesis), or by biological processes like pressure from predators and competition between ammonites themselves (the Red Queen Hypothesis).

“What we found was that the causes of ammonite speciation and extinction were as geographically varied as the rates themselves,” said co-author Dr Corinne Myers of the University of New Mexico. “You couldn’t just look at their total fossil record and say that their diversity was driven entirely by changing temperature, for example. It was more complex than that and depended on where in the world they were living.”

“Palaeontologists are frequently fans of silver bullet narratives for what drove changes in a group’s fossil diversity, but our work shows that things are not always so straightforward,” Dr Flannery Sutherland concluded. “We can’t necessarily trust global fossil datasets and need to analyse them at regional scales. This way we can capture a much more nuanced picture of how diversity changed across space and through time, which also shows how variation in the balance of Red Queen versus Court Jester effects shaped these changes.”

Ammonites basking under the Late Cretaceous sun. Artwork by Callum Pursall (@cpursall on X)

The paper:

‘Late Cretaceous ammonoids show that drivers of diversification are regionally heterogeneous’ by Joseph Flannery-Sutherland, Cameron Crossan, Corinne Myers, Austin Hendy, Neil Landman and James Witts in Nature Communications.

JOURNAL

Nature Communications

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Late Cretaceous ammonoids show that drivers of diversification are regionally heterogeneous

ARTICLE PUBLICATION DATE

27-Jun-2024

Prehistoric Pompeii discovered: Most pristine trilobite fossils ever found shake up scientific understanding of the long extinct group

UNIVERSITY OF BRISTOL

Researchers have described some of the best-preserved three-dimensional trilobite fossils ever discovered. The fossils, which are more than 500 million years old, were collected in the High Atlas of Morocco and are being referred to by scientists as “Pompeii” trilobites due to their remarkable preservation in ash.

The trilobites, from the Cambrian period, have been the subject of research by an international team of scientists, led by Prof Abderrazak El Albani, a geologist based at University of Poitiers and originally from Morocco. The team included Dr Greg Edgecombe, a palaeontologist at the Natural History Museum.

Dr Greg Edgecombe comments: “I’ve been studying trilobites for nearly 40 years, but I never felt like I was looking at live animals as much as I have with these ones. I’ve seen a lot of soft anatomy of trilobites, but it’s the 3D preservation here that is truly astounding.

“An unexpected outcome of our work is discovering that volcanic ash in shallow marine settings could be a bonanza for exceptional fossil preservation.”

Due to their hard, calcified exoskeleton often being well-preserved in the fossil record, trilobites are some of the best studied fossil marine animals. Over 20,000 species have been described by palaeontologists over the past two centuries.

However, until now, comprehensive scientific understanding of this phenomenally diverse group has been limited by the relative scarcity of soft tissue preservation. Owing to the fact the Moroccan trilobites were encased in hot ash in sea water, their bodies fossilised very quickly as the ash transformed to rock – meeting a similar end to the inhabitants of Pompeii following the eruption of Mount Vesuvius.

The ash moulds preserved each segment of their bodies, their legs and even the hair-like structures that ran along the appendages. The trilobites’ digestive tract was also preserved after it filled with ash. Even small “lamp shells” attached to the trilobites’ exoskeleton remained attached by fleshy stalks as they were in life.

Lead author, Prof Abderrazak El Albani, comments: “As a scientist who has worked on fossils from different ages and locations, discovering fossils in such a remarkable state of preservation within a volcanic setting was a profoundly exhilarating experience for me.

“I think pyroclastic deposits should become new targets for study, given their exceptional potential for trapping and preserving biological remains, including delicate soft tissues.

“These findings are anticipated to lead to significant discoveries about the evolution of life on our planet Earth.”

Using CT scanning and computer modelling of virtual X-ray slices, the researchers discovered that appendages found at the edge of the mouth had curved spoon-like bases but were so small they had gone undetected in less perfectly preserved fossils. In fact, it had previously been thought that trilobites had three pairs of head appendages behind their long antennae but both Moroccan species in this study showed that there were four pairs.

A fleshy lobe covering the mouth, called a labrum, was documented for the first time in trilobites.

Co-author Harry Berks, from the University of Bristol, added: “The results revealed in exquisite detail a clustering of specialised leg pairs around the mouth, giving us a clearer picture of how trilobites fed. The head and body appendages were found to have an inward-facing battery of dense spines, like those of today’s horseshoe crabs.”

The paper, Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites, will be published online in the journal, Science, on Thursday 27 June, 19:00 BST, and in print on Friday 28 June. The paper can be accessed from that time here.

Notes to editors

Assets

Images are available here.

Microtomographic reconstruction of the head and anterior trunk (“body”) limbs of the trilobite Protolenus (Hupeolenus) in ventral view.

CREDIT

Microtomographic reconstruction of the trilobite Gigoutella mauretanica in ventral view.

CREDIT

Fig 4 [VIDEO]

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JOURNAL

Science

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites

ARTICLE PUBLICATION DATE

27-Jun-2024

From a Pompeii-like ash burial in Morrocco: Pristine 3D anatomy of Cambrian trilobites

AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE (AAAS)

Thanks to being rapidly entombed in volcanic ash – in a “Pompeii-like” process – Cambrian-age trilobites’ anatomy is more discernable than ever, via exquisitely preserved fossils. The fossils uncovered in Morrocco are reported in a new study that reveals microscopic details including of trilobite appendages and the trilobite digestive system. Trilobites are perhaps the most well-known creatures that lived during the Cambrian Period. These extinct marine arthropods’ hard exoskeleton lends itself to high fossilization potential, facilitating the identification of more than 22,000 trilobite species and a robust fossil record spanning the early Cambrian to the Permian extinction. While this bounty of fossils has led to great insight into the external morphology of these animals, knowledge of their anatomy, particularly their rarely preserved soft tissue appendages and internal organs, is greatly limited. Here, Abderrazak El Albani and colleagues report several exceptionally well-preserved and anatomically complete Cambrian-age trilobite fossils from the Tatelt formation in Morrocco. According to El Albani et al., the trilobites were fossilized through rapid ash burial from a single pyroclastic flow event that swept through a shallow marine environment. This scenario led to their instantaneous burial and pristine, 3D preservations of both the exoskeleton and soft anatomy contained therein. Using microtomographic x-ray imaging, the authors were able to observe anatomical features, including the trilobites’ articulated and undistorted exoskeleton, antennae, post-antennal appendages, digestive system, and other soft tissues. El Albani et al. also describe previously unknown anatomical features, such as their novel feeding structures, a slit-like mouth opening, and specialized head appendages that form a complex feeding apparatus around the mouth. Moreover, the findings suggest that other volcanic ash deposits in marine settings, such as that entombed the Tatelt trilobites, may have significant potential for preserving soft-bodied creatures or anatomy with fine details, highlighting the potential for further discoveries in similar deposits.

JOURNAL

Science

DOI

10.1126/science.adl4540

ARTICLE TITLE

Rapid volcanic ash entombment reveals the 3D anatomy of Cambrian trilobites

ARTICLE PUBLICATION DATE

28-Jun-2024

Last surviving woolly mammoths were inbred but not doomed to extinction

CELL PRESS

Wrangel Island tusk — IMAGE:
WRANGEL ISLAND TUSK
view more
CREDIT: LOVE DALÉN

The last population of woolly mammoths was isolated on Wrangel Island off the coast of Siberia 10,000 years ago, when sea levels rose and cut the mountainous island off from the mainland. A new genomic analysis reveals that the isolated mammoths, who lived on the island for the subsequent 6,000 years, originated from at most 8 individuals but grew to 200–300 individuals within 20 generations. The researchers report June 27 in the journal Cell that the Wrangel Island mammoths’ genomes showed signs of inbreeding and low genetic diversity but not to the extent that it can explain their ultimate (and mysterious) extinction.

“We can now confidently reject the idea that the population was simply too small and that they were doomed to go extinct for genetic reasons,” says senior author Love Dalén (@love_dalen), an evolutionary geneticist at the Centre for Palaeogenetics, a joint collaboration between the Swedish Museum of Natural History and Stockholm University. “This means it was probably just some random event that killed them off, and if that random event hadn't happened, then we would still have mammoths today.”

In addition to shedding light on woolly mammoth population dynamics, this analysis of Wrangel Island mammoths could help inform conservation strategies for present-day endangered animals.

“Mammoths are an excellent system for understanding the ongoing biodiversity crisis and what happens from a genetic point of view when a species goes through a population bottleneck because they mirror the fate of a lot of present-day populations,” says first author Marianne Dehasque (@MariDehasque) of the Centre for Palaeogenetics.

To understand the genomic consequences of the Wrangel Island bottleneck on the mammoth population, the team analyzed the genomes of 21 woolly mammoths—14 from Wrangel Island, and 7 from the mainland population that predated the bottleneck. Altogether, the samples spanned the last 50,000 years of the woolly mammoth’s existence, providing a window into how mammoth genetic diversity changed through time.

Compared to their mainland ancestors, the Wrangel Island mammoth genomes showed signs of inbreeding and low genetic diversity. In addition to overall low genetic diversity, they showed reduced diversity in the major histocompatibility complex, a group of genes known to play a critical role in the vertebrate immune response.

The researchers showed that the population’s genetic diversity continued to decline throughout the 6,000 years that the mammoths inhabited Wrangel Island, though at a very slow pace, suggesting that the population size was stable up until the very end. And although the island’s mammoth population gradually accumulated moderately harmful mutations throughout its 6,000-year tenure, the researchers showed that the population was slowly purging the most harmful mutations.

“If an individual has an extremely harmful mutation, it's basically not viable, so those mutations gradually disappeared from the population over time, but on the other hand, we see that the mammoths were accumulating mildly harmful mutations almost up until they went extinct,” says Dehasque. “It’s important for present day conservation programs to keep in mind that it’s not enough to get the population up to a decent size again; you also have to actively and genetically monitor it because these genomic effects can last for over 6,000 years.”

Though the mammoth genomes analyzed in this study straddle a large timespan, they do not include the final 300 years of the species’ existence. However, the researchers have unearthed fossils from the mammoth’s final period and plan to conduct genomic sequencing in the future.

“What happened at the end is a bit of a mystery still—we don't know why they went extinct after having been more or less fine for 6,000 years, but we think it was something sudden,” says Dalén. “I would say there is still hope to figure out why they went extinct, but no promises.”

###

This research was supported by the Swedish Research Council, the Science for Life Laboratory, the National Genomics Infrastructure, and UPPMAX.

Cell, Dehasque et al. “Temporal dynamics of woolly mammoth genome erosion prior to extinction” https://cell.com/cell/fulltext/S0092-8674(24)00577-4

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.

JOURNAL

Cell

DOI

10.1016/j.cell.2024.05.033

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Temporal dynamics of woolly mammoth genome erosion prior to extinction

ARTICLE PUBLICATION DATE

27-Jun-2024