Engineered tobacco plant can produce five psychedelics, including psilocybin and DMT

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Compounds in psychedelic drugs like DMT, psilocybin, and psilocin are naturally produced in certain plants, fungi, and animals, and have a long history of use in spiritual and therapeutic contexts. Now, a considerable amount of research is going into determining how these compounds can be translated into a therapeutic context for several mental health conditions. But to do this, researchers need to find a more sustainable way to source these compounds, as current methods raise ecological and ethical concerns.

One research team has been tinkering around with different ways to produce psychedelic compounds in plants, allowing for more sustainable and scalable production. In their new study, published in Science Advances, they describe how they mapped the DMT biosynthetic pathway and engineered a type of tobacco plant to produce five different natural psychedelics.

Psychedelics for mental health?

The better-known hallucinogenic psychedelics contain a class of compounds called indolethylamine, made up of tryptamine and its derivatives. These compounds have been shown to promote neuroplasticity and modulate serotonin, and have shown to have therapeutic potential for depression, anxiety, posttraumatic stress disorder (PTSD), and addiction. In 2019, the drug psilocybin even received the Food and Drug Administration's "Breakthrough Therapy" designation for major depressive disorder.

"The expanding clinical interest in psychedelics as therapeutics has sparked the need for scalable and versatile production platforms and structural diversification. Traditionally, the supply of psychedelics relies on natural producers, mainly plants, fungi, and the Sonoran Desert toad. Harvesting these organisms for their psychoactive compounds raises ecological and ethical concerns, being increasingly threatened by habitat loss and overexploitation.

"While synthetic routes for these compounds are available and, in some cases, relatively straightforward, they still require compound-specific reactants, can lead to unwanted intermediates and products, and require several processing steps," the study authors explain.

Mapping pathways for synthetic production

The new study focused on engineering plants to produce five major natural psychedelics: DMT, psilocin, psilocybin, bufotenin, and 5-MeO-DMT. They first had to identify and characterize the key biosynthetic enzymes from certain plants, fungi, and the Sonoran Desert toad and combine enzymes from different species to reconstruct entire biosynthetic pathways. They then used genetic engineering to introduce these enzymes into a type of tobacco plant (Nicotiana benthamiana), which was chosen because it is easily cultivated and produces tryptophan.

After the genes required for production of the compounds were identified, they were introduced to the plant by a process called agroinfiltration, where plant leaves are injected with a suspension of bacterium to induce the expression of genes. The team used AlphaFold3, an AI model that predicts 3D structures and interactions of molecules, to guide their design of a mutant protein that substantially enhanced indolethylamine production by improving efficiency of the enzymes needed to produce it.

The team also created halogenated indolethylamine analogs with potential therapeutic value, which are not typically found in nature.

"Several halogenated indolethylamine derivatives have demonstrated therapeutic potential for mental disorders. For example, 5-chloro- and 5-fluoro-DMT induce head-twitch responses in mice, while 5-bromo-DMT displays sedative effects, and its 5,6-dibromo analog shows antidepressant-like activity," the study authors write.

The team's final proof of concept was the tobacco plant containing all five natural indolethylamine compounds. They say all five compounds were detected in the plant one week after infiltration. However, all compounds, perhaps unsurprisingly, were present in lower concentrations compared to their original sources.

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A platform to build upon

The researchers have been able to further tweak their model and increase DMT production, saying, "Notably, rational design of a single amino acid substitution in wild-type AtCOMT, guided by AlphaFold3 structural modeling, resulted in a remarkable 40-fold increase in 5-MeO-DMT 10 production in N. benthamiana."

They note that, ultimately, their model was meant as a kind of platform to determine feasibility. There are many possibilities, including further enzyme engineering and pathway balancing to improve yields, stable integration of pathways into crop plants for large-scale production, and adaptation for edible plants or microdosing applications. The team also says this work could set the ground for parallel and simultaneous production of psychedelic indolethylamines in microbial systems.

The study authors write, "Blending catalytic functions across the tree of life, coupled with metabolic engineering guided by rational protein design of mutant enzymes, enabled substantially more efficient plant production of the indolethylamine components. This work establishes a versatile platform for concurrent biosynthesis and diversification of psychoactive indolethylamines, paving the way for their production in plants."

Written for you by our author Krystal Kasal, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Publication details

Paula Berman et al, Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants, Science Advances (2026). DOI: 10.1126/sciadv.aeb3034

Journal information: Science Advances

Key concepts

genetically engineered organismsSynthesis

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