Tobacco plant altered to produce five psychedelic drugs

Scientists have engineered tobacco plants to produce five powerful psychedelic compounds normally found in other plants, fungi and animals in a single crop. They argue that using plants to manufacture the drugs would be simpler and more sustainable than existing processes, making research into therapeutic uses and production of future medicines easier.

Asaph Aharoni at the Weizmann Institute of Science in Israel and his colleagues modified Nicotiana benthamiana plants using a technique called agroinfiltration, which involves using a bacterium to introduce genes from other organisms into a plant. The modified plant then makes the proteins encoded by those genes, but the DNA isn’t incorporated into the plant’s genome, so the effect is short-lived.

With the addition of nine genes, the plants were able to produce psilocin and psilocybin, usually found in mushrooms; DMT from various plants; and bufotenin and 5-methoxy-DMT, compounds secreted by the Colorado river toad (Incilius alvarius).

Plants could easily be altered permanently with changes that become inheritable, but doing so could be problematic, given that the compounds produced are commonly used as recreational drugs, says Aharoni. “It’s a little bit tricky if we have it inherited, and then people will ask for seeds,” he says. “We can do it also in tomato, potato, corn.”

The medical uses of psychedelic compounds are becoming more popular and better understood, says Aharoni, but harvesting them from natural sources risks populations threatened by habitat loss and overexploitation. The drugs are chemically synthesised for use in research, but producing them in tobacco plants, which are easily cultivated in greenhouses, would be much simpler.

The idea of growing drugs through pharmaceutical farming, or “pharming”, certainly isn’t new. Plant-produced protein drugs have been approved in the US since 2012, and as far back as 2002, maize has been modified to produce a pharmaceutical protein. Another research team used tobacco plants in 2022 to synthesise cocaine, discovering that it could produce about 400 nanograms of cocaine per milligram of dried leaf – about a 25th of the level in a coca plant.

Rupert Fray at the University of Nottingham, UK, says around 25 per cent of prescription drugs are derived wholly or partially from plants, and there are massive opportunities to create “green factories” that can grow new compounds in greenhouses.

“If you want to understand something, you’ve got to be able to build something, so showing that you can make it in tobacco plants is useful,” says Fray. “As a technical accomplishment, to show that you understand the pathways and can do it, I think it has value.”