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The first proper brain scan involving the effects of mescaline found the drug ignoring the regions where psychedelic research has spent a decade studying, settling instead on the one structure no one really expected.

Sometime around 3,700 BC, someone in what is now southwest Texas cut two tops off a peyote cactus and dried them. They spent most of the twentieth century in a drawer at the Witte Museum in San Antonio, and when chemists finally analyzed them in the early 2000s, the mescaline was still detectable — roughly 2% alkaloids by weight, 5,700 years on.

Those dried-out cactus tops, where the drug compound is concentrated, remain the oldest plant drug ever to give up a major bioactive compound to chemical analysis. And with thousands of years of use, mescaline remains a bit of a scientific mystery.

Mescaline became a Schedule 1 substance under the Controlled Substances Act in 1970, and the classification effectively ended research on it. LSD and psilocybin eventually clawed their way back into laboratories for scientific research, but mescaline, the older compound by several thousand years, doesn’t have the same level of lab testing.

Now, a new study in Neuroscience Bulletin has become the first to properly look, and the answer is not what most expected.

Researchers at Northeastern University’s Center for Translational Neuroimaging scanned 24 rats, evenly split by sex. After a single dose of mescaline, while the animals were awake (anesthesia flattens the very signals a drug study is trying to read), the drug largely ignored the forebrain. It went almost entirely for the cerebellum, which is a strange location for a psychedelic. 

The cerebellum is the lump at the back and bottom of the brain where balance and motor coordination live. It also holds more than half of all the neurons in the brain, and everything it computes leaves through just three narrow output channels.

An interpretation, proposed by neuroscientist Anna Devor in 2002, is that the cerebellum is the “Great Gate.” As the brain receives sensory information, it acts as a filter that suppresses the sensory information that the brain already predicted and passes along only what it did not expect. A working brain spends most of its time discarding what it saw coming.

Under mescaline, the gate appeared to come off its hinges.

Activity inside the cerebellum dropped sharply, while its connections outward multiplied to the hippocampus, the thalamus, the sensory cortex, and the midbrain. Quieter on the inside, wired to far more on the outside. The researchers read this as a filter that has stopped filtering and started broadcasting, pushing raw sensory information into regions that normally receive it neatly packaged.

“Wouldn’t it be devastating if you didn’t ‘gate’ all of that sensory information out?” senior author Craig Ferris explained in a university press statement.

The clearest evidence for that reading came from a smell test. Rats were given almond odor, a reliably rewarding stimulus, and in the control group, it lit up 48 of the 169 brain regions the team tracked. Under mescaline, the response was essentially abolished, flattened close to nothing across the board.

Broken down by modality, smell, touch, and hearing were all measurably blunted, while the visual system showed no significant change at all — a peculiar result for a compound whose entire cultural reputation rests on what it does to sight. 

The authors put the discrepancy down to species differences, reasonably enough given that rats navigate by nose and whisker, but it remains one of the odder findings in the paper. What makes this significant is the comparison. 

Mescaline, LSD, and psilocybin all act on the same target, the 5-HT2A serotonin receptor, and all three produce broadly similar experiences in people, which has encouraged researchers to treat findings from one as transferable to the others. However, brains don’t seem to cooperate.

Earlier work from this same lab found LSD acting on the prefrontal cortex, thalamus, and hippocampus, and psilocybin engaging cortico-striato-thalamic circuits. Mescaline’s acute signature sat in neither place.

“The power of mescaline to me is that it is doing something different than other psychedelics,” said lead author Noah Cavallaro. “Essentially, the cerebellum is being shut down internally, but it’s talking more to other parts of the brain.”

The distinctiveness is narrower than it first appears, though. The lab’s own psilocybin work also produced pronounced cerebellar hyperconnectivity, so the sprawling network changes are not unique to mescaline; what looks specific to it is the acute suppression, the cerebellum falling quiet while the rest of the brain carried on largely unaffected.

“If two compounds produce similar hallucinogenic symptoms through different neural pathways, comparing them could help us pinpoint what’s actually causing those specific experiences,” Cavallaro said.

That being said, there are some cautions offered in the paper. First, these were rats, and rat and human brains differ most in the cerebellar-cortical wiring. Second, only one dose was tested. Third, the team did not monitor heart rate or breathing during scanning, so ordinary cardiovascular effects cannot be cleanly separated from neural ones.

Lastly, the researchers also flagged recent work showing that the scanner signal itself can run opposite to a brain region’s actual oxygen use, which complicates reading any of these images as direct neural activity. The one previous attempt to image mescaline in humans, a small study decades ago, found a different pattern entirely.

With all that being said, the paper presents a key social issue. Mescaline’s status as a drug has left it largely untested, and only now are we learning about what it can do to the brain, outside of the anecdotes of its users.

After fifty years of regulatory silence, scientists are just starting to answer a question people have arguably been asking since the Neolithic.

Generations of parents have a new piece of scientific evidence to combat couchpotatoism

The post Does Watching TV Really Rot Your Brain? appeared first on Nautilus.

Scientists from the Salk Institute have determined that brain waves in the visual cortex serve as a computational engine, allowing the brain to construct internal representations of the external world that enhance prediction, reconstruction, and perception capabilities.

While the scientists behind the new study focused their work on the visual cortex, they suspect that similar brain waves washing over other areas of the brain’s surface likely serve a similar role for other sensory systems.

Unraveling the Role of Traveling Brain Waves in the Visual Cortex

The human brain uses electricity to communicate between synapses. Research has shown that this electrical activity can travel in waves across the brain’s surface. Called neural traveling waves, the phenomenon’s role in brain function and consciousness is not completely understood.

Previous studies have established that traveling brain waves play a significant role in behavior and attention. In 2020, Salk neuroscientist John Reynolds, PhD, successfully identified traveling brain waves in the visual systems of animals during a wakeful state.

According to a statement from Reynolds, the senior and co-corresponding author on the new paper, and colleagues, the 2020 research effort also found a direct correlation between traveling brain waves in the visual cortex and an animal’s ability to perceive objects directly in front of them. The authors suggest this discovery explained the “classic conundrum” of searching for something like a pair of keys or a phone that was right in front of you the whole time.

Although the connection between traveling brain waves and an awake animal’s ability to perceive objects seemed solid, Reynolds said he was left wondering why. 

Process is Analogous to LLM’s Like ChatGPT

In their newly proposed theory, Reynolds and colleagues suggest that traveling brain waves are not simply “electrical noise” resulting from the brain’s normal relaying of signals. Instead, the Salk Institute team proposes that the neural connections responsible for the generation of traveling brain waves change their physiological structure, or “synaptic weights,” to more accurately reflect the outside world.

“Each sight, smell, sound, and action of an animal alters the connections that generate these waves, building the neural circuitry that the brain uses to construct an internal representation of the external world,” the team’s statement explains.

In the visual cortex, the part of the brain responsible for receiving and processing visual information, the team proposed that traveling brain waves perform four distinct functions. These include modulating visual perception from moment to moment and turning recent visual sensory inputs into “internal representations” of objects, people, and surroundings.

The team proposes that traveling brain waves also help humans generate short-term predictions about their surroundings, and “store and replay patterns that represent memories of events unfolding in time.” Reynolds said the process laid out by his team is analogous to how ChatGPT and other LLMs translate and interpret data.

“They learn statistical structure from language and use that knowledge to generate meaningful and appropriately structured text that reflects the patterns of language,” the researcher explained. “The brain may be doing something functionally similar—a biological generative model built from the ground up by experience.”

“One Step Closer” to Understanding How Our Brains Compute the World

When detailing the potential impact of their proposed role for traveling brain waves in the visual cortex, the team highlights the contrast between a rich and complex world and its general predictability.

“Objects around you exist in 3D space, you see the world in retinal images that change with your eye and body movements, and the laws of physics and physiology overlay this all,” they explain.

Reynold’s team says that traveling brain waves are merely the brain’s way of internalizing these predictable “regularities” and encoding them in its synapse network. If correct, they said that this encoding would allow the brain to “infer the likely causes of sensory input and construct an internal model of the world.”

“This framing brings us one step closer to understanding how our brains compute the busy, messy world around us, turning a complicated sensory onslaught into behaviors and experiences,” they conclude.

The study “Neural traveling waves in cortex: network mechanisms and potential roles in neural computation” was published in Neuron.

Christopher Plain is a Science Fiction and Fantasy novelist and has spent the last six years as Associate News Editor and Head Science Writer at The Debrief. Follow and connect with him on X, learn about his books at plainfiction.com, or email him at christopher@thedebrief.org

Brain-computer interface (BCI) technology is advancing rapidly worldwide. Far more than just the innovative technology promoted by prominent advocates involved in its expansion, like Elon Musk, BCIs are being developed in countries including the United States, Canada, Australia, Germany, Spain, and China.

Beyond their life-changing potential for treating neurological conditions, BCIs could fundamentally reshape what it means to be human, and soon. If that’s the case, is a global BCI coalition needed? 

Before Elon Musk: Jacques Vidal and Thomas Oxley

A common misconception is that Elon Musk and his company, Neuralink, launched the BCI revolution we see today. In reality, the origins of the technology date back to the 1960s. Jacques Vidal published the first paper introducing the term “brain-computer interface” in 1973, demonstrating how electroencephalographic (EEG) signals could be used for direct communication. Vidal’s pioneering work laid the foundation for all modern BCI research.

Fast forward to 2012, when Australian-born physician, neuroscientist, and Synchron founder and CEO Thomas (Tom) Oxley entered the BCI conversation. Oxley was among the first physicians to bring BCI technology into clinical practice at Mount Sinai Hospital. With early funding from DARPA, he and his team began clinical trials in Australia in 2019. Oxley’s minimally invasive Stentrode device attracted significant business and media attention well before Neuralink’s highly publicized demonstrations in 2023.

What the BCI community can thank Elon Musk for is the unprecedented level of global investor attention he has brought to the field. Without that influx of funding, BCI technology might still be in its infancy, and fewer people would have access to devices capable of addressing life-changing healthcare needs.

China’s Rapid Advancement into BCI

Since 2010, China has moved aggressively to advance BCI technology while making clear that the field is a national priority—one viewed as nearly as important as breakthroughs in quantum computing.

Recently, the Chinese BCI company NEO announced approval for the country’s first commercial use of a coin-sized brain-computer interface for patients living with paralysis caused by spinal cord injuries.

Tsinghua University and Shanghai-based Neuracle Technology designed the brain chip to be less invasive than many competing technologies. Rather than penetrating deep into brain tissue, the NEO device is implanted beneath the skull, where its electrodes are attached to the dura mater—the protective membrane surrounding the brain.

The first Chinese-designed and developed brain chip was implanted last November in volunteer Dong Hui. Hui, 39, sustained a spinal cord injury in a car accident six years earlier that left him paralyzed. During a video interview with MIT Technology Review, Hui said excitedly, “I couldn’t believe I was able to write again. I was so excited, I even missed a stroke in my name.”

This past March, Hui became the first person in the world to receive an invasive brain-computer interface approved for use beyond a clinical trial. But what does “commercial” use actually mean?

The NEO device, developed by Neuracle Technology, was reportedly approved by Chinese regulators for use outside clinical trials in certain patients with spinal cord injuries. In practical terms, that means the technology has moved beyond the experimental stage and can now be offered in clinical settings to eligible patients. Hospitals may provide it as a treatment, Neuracle can manufacture and sell the system commercially, and qualifying patients may receive the implant as part of standard clinical care rather than solely through an experimental research program, representing a major milestone for BCI technology.

Another competitor in China’s BCI market is Gestalt, founded by Phoenix Peng. Surprisingly, the two companies are pursuing very different approaches. NEO’s system places sensors directly on the brain’s protective covering, allowing the electrodes to measure electrical activity generated by neurons. This approach can provide stronger and faster signals but requires neurosurgery.

Gestalt, by contrast, is attempting to eliminate the need for surgery. According to Peng, the company aims to use phased-array ultrasound to both read brain activity and stimulate specific neural pathways without requiring invasive procedures. If successful, this approach could make brain-computer interfaces safer, more accessible, and available to a much broader population.

In a recent podcast interview, Peng told The Debrief that this is why he and others in the industry have begun pursuing ultrasound-based BCIs. He noted that such systems are now being developed not only in China but also by several companies in the United States. “The whole technology is just rising up,” Peng said.

Competitors Chime In 

With the Chinese government investing heavily in and prioritizing BCI technology, it is becoming increasingly clear that the country is positioning itself to set the “gold standard” for BCI development worldwide. Last July, the Chinese government announced its intention to establish a global standard, outlining plans to do so through new guidelines issued by the Ministry of Industry and Information Technology, along with the creation of a committee to oversee the development and implementation of those standards.

“China progresses fast and is likely to win the race,” said Dr. Martin Schüttler, the CTO, co-founder, and managing director of CorTec Neuro, in an email to The Debrief. “However, young Chinese implantable BCI companies might run into challenges when demonstrating long-term robustness and efficacy, which validations are difficult to accelerate.”

“From my perspective, the Chinese governmental orchestration of the BCI race provides a major advantage over Europe and the USA, where each BCI company struggles individually with similar challenges,” he adds. As an example, he notes China’s move to define reimbursement of implantable BCI, which occurred months before Neuracle received its market approval. “Therefore, the Chinese government also published a definition of a BCI and issued ethical guidelines for BCI technology,” Schüttler said.

“It also funds BCI initiatives and companies, leading to a boom of start-ups in the field,” he says, though noting that this is not strictly restricted to implants. 

Florian Solzbacher, PhD, co-founder of Blackrock Neurotech, adds more context on BCI commercialization by telling The Debrief that “this is more than just a technology race. This is about which nations and values will lead the world and likely set standards in a completely new, strategically important field of technology.”

“There are several aspects of the current processes for translation and regulatory approval that could be adjusted to new technological capabilities without throwing safety overboard,” Solzbacher adds. “And with all the concern about China’s pace, speed to commercialization alone is not the right metric. The concern, in any market, is whether long-term safety and security, technological maturity, clinical evidence, regulatory oversight, and patient support can keep pace with deployment.”

“One can only hope that China’s pace wakes up our own nation and creates incentives and pressure for the US and EU to coordinate far more effectively and to support translational neurotechnology with far more conviction and focus, without jeopardizing patient safety,” he says.

High Volume in 2026?

This recent commercial BCI announcement from China comes on the heels of Elon Musk declaring that Neuralink will ramp up its efforts in a “high volume” attempt for 2026. 

“This is a big deal,” Musk’s posting on X read. 

But what does high volume really consist of? This past January, Barcelona, Spain-based BCI company and co-founder Carolina Aguilar, INBRAIN Neuroelectronics, one of Neuralink’s competitors, told The Debrief, “At this stage, we interpret ‘high-volume’ realistically as hundreds moving toward low thousands of implants per year.” She also notes that it could eventually reach “tens of thousands”. 

Solzbacher said the challenges presented with scaling “usually come in all areas.”

“It starts with capability, the processes, and the capacity to actually make that many devices,” Solzbacher said in an email to The Debrief, adding that that number—should it reach “tens of thousands, or hundreds of thousands of devices” would require “well-qualified, validated processes.”

With China accelerating the commercial deployment of BCI technology, how do European and American BCI companies view the pace of its advancements, and what impact could this have on the global race for brain technology leadership?

Defense Applications 

The commercialization of brain-computer interfaces is now at the forefront of the brain-chip revolution. Citizens around the world should be engaged in discussions about how this technology will be implemented within their countries. At the same time, the conversation should also acknowledge the role the military-industrial complex has played in funding BCI research through DARPA, as well as how the technology has been explored for potential defense, intelligence, and counterintelligence applications.

DARPA has been one of the leading funders of BCI research for decades. Programs (that we know of) such as Revolutionizing Prosthetics (LUKE Arm), NESD (Neural Engineering System Design), and N3 (Next-Generation Nonsurgical Neurotechnology were created with the goals of restoring movement to wounded service members, enabling direct communication between the brain and computers, and developing high-bandwidth, minimally invasive, or noninvasive neural interfaces. Collectively, these efforts aim to improve decision-making, situational awareness, pilot workload management, and human-machine teaming.

It remains unclear how other nations are integrating BCI technology into their own military-industrial complexes or how these systems may ultimately be employed. That uncertainty underscores the growing need for international collaboration and the establishment of a global BCI framework sooner rather than later. Because of this, continued oversight and transparency are necessary to ensure future applications respect civil liberties and ethical standards, and many believe safeguards should be established to prevent any future civilian-targeted programs from emerging.

Ethics of BCI and Global Counsel 

Humanity may be approaching a tipping point in its biological and technological evolution. Some would describe this as a “singularity”—a historic moment when technology and human development converge in a transformative way, fundamentally reshaping what it means to be human.

On October 8, a private Morgan Stanley report titled Neuralink: AI in Your BrAIn focused on Elon Musk’s Neuralink. The report argues that Musk and his BCI team are positioned at the forefront of a broader technological shift—one for which society may be unprepared. The implications could be profound, potentially changing the fabric of society itself.

The report warns that “the ability for human beings to ‘keep up’ and communicate with the AI apparatus may deteriorate at an exponential rate,” noting that “one of Elon Musk’s many goals in founding Neuralink is to ‘give humanity a chance’ to keep up with AGI.” It also suggests that Musk is using a “back door” into healthcare to enter the consumer market and, in turn, create a “Neuro Elite.”

Such a development could further widen existing wealth and educational gaps, particularly in emerging economies already struggling to keep pace with wealthier Western nations.

“Many countries, particularly those in the Global South, have limited involvement in BCI research and are understandably focused on more immediate public health, economic, and social priorities. As a result, they may have little incentive to invest in developing or enforcing BCI-specific regulations,” says Kerry Bowman, PhD, a bioethicist, environmentalist, and professor at the University of Toronto, in an email to The Debrief.

“At the same time, researchers seeking to avoid restrictive oversight may simply relocate their work to jurisdictions with few or no regulations, creating opportunities for regulatory arbitrage,” Bowman adds.  “Furthermore, meaningful global consensus is complicated by profound cultural differences regarding individual autonomy, collective welfare, human enhancement, and the role of the state. Recognizing these challenges, it remains a good and positive step in the right direction.”

With these concerns on the horizon, Senate Majority Leader Chuck Schumer, along with Senators John Cornyn and Ron Wyden, introduced the Management of Individuals’ Neural Data Act of 2025, or MIND Act, on September 24. The proposed legislation seeks to establish safeguards for brain-computer interface technology by directing federal agencies to develop guidelines addressing ethical concerns, safety, and privacy risks associated with neural data.

As BCIs advance, concerns about their potential ability to influence thoughts, memories, and emotions have become increasingly central to policy discussions.

Without global safeguards and international agreements governing BCI development, scientists could potentially collaborate with foreign adversaries, black-market organizations, or extremist groups seeking to advance radical visions of human enhancement. Technologies developed through such collaborations could then be sold illegally or distributed commercially around the world.

For instance, former Harvard professor Charles Lieber, 67, who was convicted in the United States of concealing ties to a Chinese talent program, is now leading a state-funded brain-computer interface laboratory in Shenzhen, China. Lieber currently directs the Institute for Brain Research, Advanced Interfaces and Neurotechnologies, or i-BRAIN, raising renewed concerns about the geopolitical competition surrounding emerging technologies.

This may appear to be the work of a single controversial scientist, but it also illustrates how quickly advanced technologies, expertise, and intellectual property can move between nations and research communities. The question, therefore, remains: Where do we go from here if a “singularity” arrives, and what might it look like?

“Carbon-based lifestyles and silica-based lifestyles may merge,” Peng offered for this potential event in a podcast interview. “Artificial intelligence and neuroscience are two sides of the same coin. BCI will be the collector between these two shapes of life, probably because AI will have consciousness.”

A Global Coalition? 

One proposed approach would be to create a global coalition of academics and experts representing a broad range of disciplines, including physics, philosophy, neurology, psychology, psychiatry, and other hard and social sciences. What might such a global BCI coalition look like, and how could it be structured to guide research, governance, ethics, and the responsible development of brain-computer interface technologies?

Schüttler suggests that if a global BCI coalition enabled technologies developed in China, the United States, and Europe to be shared and approved across regions, its impact would depend largely on who was involved.

For patients, such a framework could mean faster access to breakthrough treatments, particularly because, according to Schüttler, “Chinese approval processes can be substantially faster.”

For U.S. and European companies, however, it could disrupt existing business models. Companies that have invested heavily in Western clinical trials may face significant challenges if Chinese data becomes widely accepted, since he says “a coalition could risk their business model once they are already committed to costly approval studies.”

The shift could prove even more disruptive for clinical research organizations, since trials in China can often be “cheaper and faster to conduct,” Schüttler says. Ultimately, a global BCI partnership could provide substantial benefits or create major disruptions, depending on “who you are in the game, and at what stage you are.”

By contrast, Solzbacher believes a “coalition needs to be informed and driven by a deep understanding of patient and caregiver needs as well as the underlying technologies and their associated risks and opportunities. Practical and multi-stakeholder, with international representation.”

“Regulators, clinicians, engineers, neuroscientists, companies, ethicists, advocates, and, above all, patients and caregivers,” he says, would allow such a coalition to “work alongside national regulators and support their authority, setting shared expectations on trial design, safety reporting, post-market surveillance, cybersecurity, interoperability, patient access, and long-term device stewardship.”

“The center of gravity must stay on the patients. This field will carry strategic and economic weight regardless,” Solzbacher says. “We need to get this technology to the people who could benefit most, responsibly and with as much urgency as possible.”

Chrissy Newton is a PR professional and the founder of VOCAB Communications. She currently appears on The Discovery Channel and Max and hosts the Rebelliously Curious podcast, which can be found on YouTube and on all audio podcast streaming platforms. Follow her on X: @ChrissyNewton, Instagram: @BeingChrissyNewton, and chrissynewton.com. To contact Chrissy with a story, please email chrissy @ thedebrief.org.

Scientists have identified a brain protein that may help Alzheimer’s spread, revealing a potential new target for slowing the disease’s progression. Alzheimer’s disease is closely linked to the accumulation of a toxic form of the protein Tau inside the brain. As Tau damage reaches additional brain regions, more neurons are harmed, symptoms intensify, and the [...]

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New study shows what happens in our brains as we track multiple conversations

The post Some People Are Better at Eavesdropping Than Others appeared first on Nautilus.

Keith Thomas can move arms and hands, and feel sensation of touch after ‘double neural bypass’ and months of training

A man who was paralysed from the chest down in a swimming accident six years ago has been able to feed himself and drink from a cup thanks to a brain implant that bypasses his spinal cord injury.

Keith Thomas of Massapequa, New York, could not lift his arms off his wheelchair when he agreed to trial the technology in 2021, but after surgery to implant electrodes in his brain and many months of training, he was able to move the limbs again.

Continue reading...

© Photograph: Feinstein Institutes for Medical Research

© Photograph: Feinstein Institutes for Medical Research

© Photograph: Feinstein Institutes for Medical Research

A newly identified protein pathway may link blood-brain barrier deterioration to age-related cognitive decline. The aging brain depends on a microscopic border that works every second to keep danger out and support the nerve cells inside. When that barrier begins to fail, memory, mood, and thinking may suffer. Andrew A. Pieper, MD, PhD, and colleagues [...]

Men and women performed similarly on most multitasking measures, but a difference in conversational engagement may shape how their overall ability is perceived. A person can keep cooking, search for information, and track a visual task without appearing overwhelmed. But if they stop responding during a conversation, others may quickly assume they are losing control. [...]

Scientists at the Weizmann Institute of Science have engineered Nicotiana benthamiana, a fast-growing relative of tobacco, to produce five different psychedelic compounds. 

The achievement, detailed in a study published in Science Advances, brings together biosynthetic pathways that nature distributes across three different kingdoms of life.

The five compounds (DMT, psilocybin, psilocin, bufotenin, and 5-MeO-DMT) are typically sourced from an Amazonian shrub, mushrooms, and the defensive skin glands of a desert toad. Extracting even one of these molecules from its natural source is a slow process. Producing all five in a single, easily cultivated plant had not been achieved before.

A Shared Chemical Ancestor

Despite coming from such different sources, all five of these molecules share a common origin: tryptophan, an amino acid found in every living thing. In humans, tryptophan is the building block for serotonin, which helps explain why these psychedelics interact with serotonin receptors in the brain. This shared chemistry gave the Weizmann team, led by Dr. Paula Berman and Prof. Asaph Aharoni, a logical starting point for their experiments.

The team began by focusing on DMT to address a previously unresolved question. Researchers knew the general biochemical pathway plants use to synthesize DMT, but they had not yet identified all the genes and enzymes responsible for each step. “At the heart of the study was the challenge of making DMT,” Aharoni says.

To identify the necessary genes, the team analyzed genetic material from the Amazonian chacruna shrub and an Australian acacia species. Introducing these genes into Nicotiana benthamiana allowed the plant to produce DMT within days.

Fixing a Bottleneck With One Amino Acid

The researchers applied the same gene transfer approach to the other four psychedelics, but the engineered plants initially produced only trace amounts of 5-MeO-DMT. Protein-design specialists Prof. Sarel Fleishman and Dr. Olga Khersonsky determined that the limitation was due to a poor molecular fit in one enzyme’s active site. Replacing a single amino acid resolved the issue.

“We mutated one amino acid in the sequence and got a 40-fold increase in the production of 5-MeO-DMT,” Berman says.

One Organism, Three Kingdoms

Once all five biosynthetic pathways were functioning separately, the researchers combined them within a single plant. The result was a tobacco relative capable of producing DMT from plants, psilocin and psilocybin from fungi, and bufotenin and 5-MeO-DMT from toads, all at the same time. “In effect, we created a kind of biological ‘cocktail’ — not by mixing substances externally, but by combining the underlying pathways inside one organism,” Aharoni says.

Combining all five pathways reduced the yield of each compound, as they competed for the same pool of tryptophan. The researchers also introduced bacterial enzymes to attach chlorine and bromine atoms to the psychedelic molecules, creating modified psychedelic molecules that do not naturally occur in the engineered plant. Some similar modified molecules have shown antidepressant-like effects in previous studies.

Why the Compounds Exist in the First Place

The bottleneck also highlighted a broader research question about the natural role of these compounds. These molecules likely function as defenses or as tools for interacting with microbes and insects in the organisms that produce them, rather than evolving to affect human consciousness.

“If we can move these pathways into a model plant that grows quickly and is easy to manipulate, we can start asking what these compounds actually do for the plant,” Berman explains.

A Sustainable Supply Line

There is a clear practical benefit to this approach. Plants used for ayahuasca are increasingly threatened by habitat loss and rising demand, and the Sonoran Desert toad is declining due to overcollection and habitat destruction. A fast-growing laboratory plant capable of producing these compounds within a week provides an alternative that does not rely on harvesting wild species.

The Weizmann researchers are now working on a plant that can produce the complete ayahuasca mixture, which includes both DMT and the compound required for it to be active when taken orally. They are also exploring whether these psychedelics could be produced in edible plants capable of delivering carefully regulated doses.

Whether this platform becomes a practical manufacturing system will depend on overcoming the metabolic bottleneck that currently limits production when multiple pathways operate simultaneously.

Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds an MBA, a Bachelor of Science in Business Administration, and a data analytics certification. His work focuses on breaking scientific developments, with an emphasis on emerging biology, cognitive neuroscience, and archaeological discoveries.