Engineering One Plant To Grow Five Psychedelics: “We Created a Biological ‘Cocktail’”

Why make one psychedelic when you can make five?

Researchers at the Weizmann Institute of Science have answered that question by engineering a fast-growing model plant to manufacture five natural psychedelics alongside novel synthetic variations.

The altered tobacco plant provides a scalable, eco-friendly platform for psychiatric drug development by successfully unlocking genetic pathways across three biological kingdoms.

The medical demand for sustainable psychedelics

Indigenous cultures have gathered psychedelics from plants, fungi, and animals for thousands of years, using traditional formulations such as ayahuasca from the Psychotria viridis shrub and psilocybin from magic mushrooms for ceremonial and healing rituals.

Today, medical science is experiencing a resurgence of clinical interest in these compounds. Researchers are studying how psychedelics promote neuroplasticity and change brain circuits, in addition to their potential for treating mental health conditions, including anxiety, PTSD, addiction, and major depression.

However, sourcing psychedelics creates an environmental problem: supply chains rely heavily on slow-growing plants, rare fungi, or animal secretions, such as the venom of the Sonoran Desert toad. Harvesting these organisms places intense ecological pressure on wild species and causes habitat loss. Alternatively, lab-based chemical synthesis requires specific, expensive ingredients and generates hazardous waste.

Biotechnology could offer a cleaner solution, but this requires a comprehensive understanding of the biosynthetic pathways that give rise to psychedelics. Although scientists had previously mapped the genes behind compounds including psilocybin, psilocin and bufotenin , the exact plant genes responsible for producing DMT were still unknown.

The new study aimed to solve that by pinpointing the missing plant genes.

“At the heart of the study was the challenge of making DMT,” said corresponding author Dr. Asaph Aharoni, a full professor and head of the Department of Plant and Environmental Sciences at the Weizmann Institute of Science.

Mapping genes to synthesize cross-kingdom psychedelic compounds

To identify the genes, the team used sequencing and chemical profiling to analyze tissues from the Amazonian chacruna shrub and the Australian acacia tree, natural sources of DMT.

They found a pair of functional plant enzymes, called TDC and NMT, which work to turn the common amino acid tryptophan into DMT.

Once they identified the DMT pathway, they moved the genetic instructions into Nicotiana benthamiana, a fast-growing tobacco relative used widely in plant research, which began generating the compound within days.

Using this approach, Aharoni and the team wanted to build a genetic platform inside Nicotiana benthamiana that could produce a further four natural psychedelics and new synthetic variations simultaneously, without needing to add extra chemical building blocks.

Despite their diverse origins across different kingdoms of life, all five compounds belong to the same chemical family and share the exact same starting point: tryptophan, the very same building block that the human body uses to produce serotonin, a neurotransmitter involved in regulating mood and well-being.

They repeated the DMT-engineering process for the remaining four psychedelics, leading them to discover that when the tobacco plant used the genetic instructions to produce 5-MeO-DMT, it did so in very low amounts.

In response, the team used the AI tool AlphaFold3 to map out the shapes of these proteins, which revealed that one molecule didn’t fit well into the active site of one of the plant enzymes.

“We mutated one amino acid in the sequence and got a 40-fold increase in the production of 5-MeO-DMT,” said lead author Dr. Paula (Shirley) Berman, a principal investigator at the Volcani Institute.

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By combining all the psychedelic-creating genes from the plants, fungi, and toads in one model plant, the team created an engineered host that could successfully manufacture a mix of all five natural psychedelics.

This multi-species production was possible because the newly discovered plant enzymes were highly versatile, allowing them to process chemical building blocks from entirely different organisms naturally.

“In effect, we created a kind of biological ‘cocktail’—not by mixing substances externally, but by combining the underlying pathways inside one organism,” Aharoni explained.

To ensure environmental safety, the team temporarily introduced the genes into the leaves rather than permanently altering the plant's genome, preventing the traits from escaping into the wild.

Overcoming biological limits in psychedelic production

Although all five psychedelics were produced, the team quickly realized that their tobacco host had metabolic limitations.

Since all five chemical pathways run at the same time, they compete for the same internal pool of starting material, creating a metabolic bottleneck that reduces overall production efficiency.

Some enzymes in the system also worked faster than others, causing an uneven buildup of uncompleted chemical ingredients inside the leaves.

In the future, the team plans to use synthetic gene regulators to balance the speeds of the different enzymes, in the hope of smoothing out the production bottlenecks.

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Instead of stopping there, however, the researchers chose to push the boundaries of nature even further.

They introduced bacterial genes to create new brominated and chlorinated psychedelics that do not occur naturally. These synthetic modifications change how the psychedelic molecules interact with brain cells, which could help scientists fine-tune their medical strength and minimize unwanted side effects. It also makes the compounds more durable, so that the body does not break them down too quickly.

The novel platform proves that plants can serve as living factories for complex psychedelics, offering a sustainable, cruelty-free alternative that prevents the destruction of ecosystems.

Beyond drug production, the system also gives scientists a tool to study plant biology.

“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 said.

The team is now exploring the possibility of engineering a single plant capable of producing the complete ayahuasca mixture by combining DMT with the other compounds that make up the psychedelic blend.

Speaking with IFLS, Berman noted that a future application could even be to look at growing these therapeutic psychedelics inside edible crops such as tomatoes to provide a source for medical microdosing.

Reference: Berman P, Höfer J, Mehlman H, et al. Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants. Sci Adv. 2026;12(14):eaeb3034. doi: 10.1126/sciadv.aeb3034

This article is a rework of a press release issued by the Weizmann Institute of Science. Material has been edited for length and content.