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.

This week in science and technology news we’re covering at The Debrief: For decades, physicists have argued about Richard Feynman’s Sprinkler Problem, involving the question of how a reverse sprinkler would operate. Now we may finally know the answer… elsewhere, new studies reveal how breathwork may trigger psychedelic-like states, emotional breakthroughs, and psychological insights without drugs. Meanwhile, a stone sphere unearthed at an archaeological site in Azerbaijan is reportedly unlike anything previously documented in the South Caucasus.

Also, in an exclusive feature, University of Toronto bioethicist KM Bowman, Ph.D., writes for The Debrief about his firsthand experience with uncontacted indigenous tribes: “Through the haze stood a man. Barely clothed, carrying what appeared to be a weapon of some form, he remained motionless for only a few seconds before silently disappearing back into the forest.” In his essay, Bowman shares his experience and asks whether governments can protect “the uncontacted.”

Finally, here’s a look at more stories The Debrief is tracking right now…

For thousands of years, humans have deliberately manipulated their breathing in search of something outside the ordinary waking mind. Now, scientists are finding measurable evidence that the right pattern of breathing may push consciousness into territory normally associated with psychedelic drugs.

In the first randomized controlled study to directly examine breathwork-induced altered states of consciousness, researchers found that a single 90-minute session of intense, continuous breathing produced significantly stronger psychedelic-like effects than meditation, including mystical experiences, feelings of oneness, visual changes, and powerful emotional breakthroughs.

Even more intriguingly, participants reported greater psychological understanding and behavioral changes a week later.

Published in Frontiers in Psychology, the findings add to a growing body of research investigating whether deliberately altering respiration can provide a drug-free pathway into altered states of consciousness,  possibly reproducing some of the psychological effects increasingly associated with psychedelic therapy.

The study focused on conscious connected breathing, or CCB, a form of high-ventilation breathwork involving continuous breathing without pauses between inhalation and exhalation.

Unlike the slow, deliberate breathing commonly associated with relaxation, high-ventilation breathwork intentionally increases the rate or depth of respiration.

During trials, participants continuously breathed through their mouths, actively inhaling and passively exhaling while listening to music that progressed from loud and fast-paced to progressively slower and softer over 90 minutes.

“Results from this preliminary experimental study indicate that breathwork is associated with larger acute psychedelic-like effects than meditation,” researchers write. “These exploratory relationships and preliminary observations provide greater context around breathwork-induced ASCs and support the feasibility of ASC-focused breathwork research for future confirmatory trials.”

Putting Breathwork Head-to-Head With Meditation

Breathing techniques have played a role in spiritual and contemplative practices for millennia. Yogic traditions include both slow and rapid breathing methods, while intentional respiration also appears in Qigong, Sufi dhikr, and shamanic practices.

Researchers say the scientific study of high-ventilation breathwork remains in its “embryonic” stage. However, that is slowly beginning to change.

As The Debrief previously reported, researchers using MRI and physiological measurements found that intense circular breathwork could produce altered states resembling those associated with psychedelics. The intensity of participants’ subjective experiences was tracked with changes in cerebral blood flow and autonomic nervous system activity.

However, those earlier investigations lacked a control group.

The new research, called the Airways to Alteration, or A2A, trial, attempted to address that limitation by directly comparing high-ventilation breathwork with an established contemplative practice: body scan meditation.

Researchers recruited 24 relatively healthy adults between 18 and 65. All had previously practiced conscious connected breathing without experiencing an adverse event.

Twelve participants were randomly assigned to the breathwork group. The remaining 12 underwent a 40-minute guided body scan meditation.

The researchers deliberately chose meditation as an active comparison rather than simply asking a control group to do nothing. Both groups lay on mats, used eye masks, listened to music, and participated in similar orientation and grounding procedures.

Meditation itself has also been associated with altered states and mystical experiences. In effect, the researchers were comparing two practices capable of shifting subjective awareness.

What happened next, however, was markedly different.

Breathwork Produced Stronger Mystical Experiences

Immediately after the sessions, participants completed several standardized psychological questionnaires commonly used in psychedelic research.

The breathwork group scored significantly higher in overall mystical experience, oneness, positive mood, and “ineffability”—the feeling that an experience is difficult or impossible to adequately describe in words.

On the study’s measure of total mystical experience, the median score for breathwork participants was 14. The meditation group scored 8.5.

The difference in emotional breakthrough was even more striking.

Participants who completed breathwork had a median Emotional Breakthrough Inventory score of 336. Those who meditated had a median score of 57.5.

Researchers also examined five dimensions commonly associated with altered states of consciousness. Breathwork participants reported significantly higher levels of “oceanic boundlessness” and “visionary restructuralisation.”

Oceanic boundlessness encompasses experiences including feelings of oneness, spiritual insight, bliss, and a loosening of the ordinary sense of self. Visionary restructuring includes changes in visual perception and imagery.

One participant described experiencing “very interesting visual hallucinations” alongside a “very cathartic emotional release.”

Another said the session produced stronger psychedelic qualities than they had experienced during previous breathwork sessions.

“The experience was emotional and cathartic,” the participant reported, noting that “at one time, I cried but not with sadness, more with a strong feeling of what life is all about and how incredible it is and how lucky we are.”

Not everyone described the experience as psychedelic. One participant said they remained fully present throughout the session and primarily experienced a physical and psychological release.

Still, the overall pattern revealed that compared with meditation, intense breathwork was associated with substantially stronger acute alterations in consciousness.

The Effects Didn’t Necessarily End When the Breathing Stopped

What may be the study’s most consequential finding emerged a week later. Researchers asked participants to complete a Psychological Insight Scale designed to assess meaningful personal realizations following psychedelic experiences.

The breathwork group reported a median psychological insight score of 33.67. The meditation group scored 5.83. Self-reported behavioral change followed a similar pattern. Breathwork participants had a median score of 50, compared with 5.5 among those who meditated.

Both differences represented large effect sizes.

The results suggest that the altered state produced during breathwork may be associated with psychological changes that go beyond the acute experience.

“Amongst the secondary outcomes, the breathwork group self-reported substantially greater psychological insight and accompanied behavioral change compared to the meditation group, with large effect sizes observed for both measures,” the researchers explain. “This finding suggests that breathwork could be connected to meaningful psychological breakthroughs, accompanied by translation of these insights into tangible behavioral modifications.”

The researchers caution that these personal accounts are anecdotal and that the qualitative portion of the study was limited. Still, the reports appeared broadly consistent with the measurable differences in mental insight and self-reported behavioral change.

A Surprising Connection to Sleep

The study also uncovered an unexpected difference involving sleep. Both groups showed improvements in stress, anxiety, depression, and overall mental well-being. However, researchers found a considerable difference between the two groups: breathwork produced significantly greater improvements in sleep-related impairment.

Median sleep impairment scores in the breathwork group dropped from 54.8 before the intervention to 39.2 afterward. Scores among meditation participants remained comparatively stable.

More intriguingly, improvements in sleep were correlated with the intensity of participants’ mystical experiences, feelings of oneness, and oceanic boundlessness.

In other words, participants who reported deeper altered states also tended to report greater improvements in sleep.

Exactly how the two may be connected remains unclear. The researchers note that sleep is itself an altered state of consciousness and plays an essential function in memory consolidation and insight, including the mental reorganization that can lead to new understanding. Still, the apparent link between deeper breathwork-induced altered states and improved sleep remains preliminary.

Breathwork Is Not Simply a Psychedelic Without the Drug

Despite the comparisons, researchers caution against treating every altered state of consciousness as the same phenomenon.

A psychedelic state induced by psilocybin, a hyperventilation-driven state produced through breathwork, and deep meditative absorption may overlap on psychological questionnaires. That does not mean the brain achieves those states through identical mechanisms.

Nevertheless, the similarities are difficult to ignore.

Previous research has found that high-ventilation breathwork can produce effects on standardized altered-consciousness measurements within the range observed after moderate-to-high doses of psilocybin.

The earlier neuroimaging research covered by The Debrief also found that the depth of breathwork-induced altered states tracked with changes in cerebral blood flow and autonomic nervous system activity.

This latest study takes that research one step further. Rather than simply demonstrating that breathwork can produce psychedelic-like experiences, the controlled comparison suggests those experiences are substantially more intense than the effects produced by body scan meditation under broadly similar environmental conditions.

Promising Results, but Major Limitations

Researchers repeatedly emphasize that the A2A trial was a small, exploratory study and does not yet provide evidence that breathwork is a proven replacement for psychedelic-assisted therapy.

All participants had prior breathwork experience, which may have led them to enter the experiment with expectations about what would happen. The study was also open-label, and participants knew whether they were breathing intensely or meditating.

Additionally, the breathwork session lasted 90 minutes compared with 40 minutes for meditation. Breathwork participants also listened to more intense music and were explicitly told about the possibility of expanded states of consciousness, emotional expression, and unusual physical sensations.

Those differences could have influenced the results.

The study also excluded people with a range of cardiovascular, respiratory, neurological, and psychological conditions. No adverse events were reported, but researchers acknowledge this was unsurprising, as participants had already practiced the technique without prior adverse reactions.

For that reason, the findings should not be interpreted as evidence that intense breathwork is safe or appropriate for everyone.

Future experiments will need to recruit people who have never practiced breathwork and tease apart the different ingredients involved.

The findings also leave several important questions unanswered. How much of the altered state is driven by rapid breathing itself, and how much comes from the music or group setting? Perhaps most importantly, researchers still need to determine how strongly the expectation of a profound experience shapes what a person ultimately experiences.

Yet, for a field increasingly interested in whether altered states can be harnessed for therapeutic purposes, the outcomes yield an interesting possibility.

Under carefully controlled conditions, consciously manipulating something as fundamental as breathing appears capable of profoundly changing how people experience themselves and the world around them.

“A logical next step would be replicating our study in breathwork-naïve participants to help mitigate expectancy effects and determine whether such ASCs emerge as profoundly as in experienced practitioners,” researchers write. “Future research contrasting HVB effects across participants with varying experience levels and in different environments is essential for informing the public about safe breathwork engagement.”

Tim McMillan is a retired law enforcement executive, investigative reporter and co-founder of The Debrief. His writing typically focuses on defense, national security, the Intelligence Community and topics related to psychology. You can follow Tim on Twitter: @LtTimMcMillan.  Tim can be reached by email: tim@thedebrief.org or through encrypted email: LtTimMcMillan@protonmail.com