On Apr. 1, April Fools' Day, a study found that tobacco leaves could be used to produce substances to treat depression, anorexia, and alcohol addiction. It was not a joke. Researchers actually produced natural hallucinogens found in mushrooms, plants, and toads in tobacco leaves. All of them have long been used as hallucinogens, and recently have drawn attention as therapeutic substances effective for mental disorders.
On the day, a team led by Asaph Aharoni, a professor in the Department of Plant and Environmental Sciences at the Weizmann Institute of Science in Israel, said it had succeeded in simultaneously producing five tryptamine-class hallucinogens derived from plants, animals, and fungi in the leaves of a plant in the tobacco genus. The findings were published in the international journal Science Advances.
Tobacco leaves are emerging as an all-purpose pharmaceutical factory. A wide variety of medicines have already been produced from tobacco leaves, from influenza and COVID-19 vaccines to an Ebola vaccine, immune boosters, and even breast milk nutrients. Tobacco leaves grow fast, making it easy to mass-produce therapeutic substances. The purification process is simple, which is an added safety advantage. In particular, it is expected to help underdeveloped countries lacking a pharmaceutical industry base.
◇ Hallucinogens from mushrooms and toads, produced in tobacco leaves
In fairy tales, there are scenes where a witch throws everything unpleasant—like poisonous mushrooms, toxic herbs, and toads—into a big pot and brews a magic potion that bewitches people. In reality, humanity has long used substances from nature as hallucinogens. A prime example is psilocybin from magic mushrooms.
Magic mushrooms have been used for religious rituals and healing from Siberian nomads to the Mayans of South America. Psilocybin is converted in the body into psilocin, which acts on the serotonin hormone that induces feelings of happiness to produce hallucinatory effects.
Recently, natural hallucinogens have been transforming into treatments for mental illness. In 2023, a team at the University of California, San Diego (UCSD) released findings that psilocybin from magic mushrooms was effective in treating anorexia, which involves rejecting food. Earlier studies also found that the hallucinogenic components of mushrooms helped treat depression and alcohol addiction that did not respond to existing drugs.
Scientists at the Weizmann Institute conducted experiments to produce five natural hallucinogens in tobacco leaves. They are psilocybin and psilocin from magic mushrooms; dimethyltryptamine (DMT) from two tropical plants; and bufotenin and 5-methoxy-DMT secreted from the skin glands of the Sonoran Desert toad. The researchers injected nine genes—including hallucinogen biosynthesis genes from mushrooms, plants, and toads and cofactor enzyme genes extracted from rice and watercress—into Nicotiana benthamiana, a plant in the tobacco genus, and confirmed that five hallucinogens were produced simultaneously in the leaves.
The researchers noted that hallucinogens have traditionally relied on wild flora and fauna such as plants, mushrooms, and toads, and said harvesting these organisms to obtain therapeutic psychoactive compounds raised concerns about habitat destruction and overharvesting. Replacing wild organisms with the cultivation of tobacco leaves to obtain these compounds could prevent ecological damage.
◇ Suited for mass production, with component upgrades
Choosing tobacco leaves as factories for hallucinogens was a masterstroke. Benthamiana is native to Australia and belongs to the same Nicotiana genus as Nicotiana tabacum, which is used to make cigarettes, but it is a different species. Weizmann scientists used this plant to produce hallucinogens because it makes a lot of the amino acid tryptophan. All natural hallucinogens are synthesized from tryptophan as the starting material.
Tobacco leaves were already used to produce vaccines during the COVID-19 pandemic. In Feb. 2022, Canadian biotech company Medicago and British pharmaceutical company GSK plc won approval in Canada for COVIFENZ, the world's first COVID-19 vaccine made from tobacco leaves.
Medicago inserted coronavirus genes into Benthamiana to produce virus-like particles. The particles extracted from tobacco leaves look identical to the virus on the outside but lack genetic material and therefore do not replicate in the human body. That makes them safer. Also, human-infecting viruses do not infect plants, so no additional purification steps are needed. In 2024, U.S. scientists also produced breast milk nutrients in tobacco leaves because they considered it safe enough for infants.
The bigger advantage is speed. Tobacco is known for its rapid growth. If seedlings are planted in early May, they grow over 2 meters in two months. Making vaccines by injecting viruses into eggs takes six months, but a tobacco-leaf vaccine takes six weeks. COVID vaccines made with mRNA (messenger ribonucleic acid) have similar production speeds, but for mass production, cultivating plants is far easier.
The Israeli team did not simply transfer the genes that make hallucinogens into tobacco leaves. They also performed an upgrade of sorts. In nature, the hallucinogen 5-methoxy-DMT secreted by toads occurs at concentrations that are too low. The researchers used the artificial intelligence tool AlphaFold 3 to identify problems in the toad's synthetic enzyme protein. The AI detected structural defects in the protein based on genetic information. After inducing mutations in the gene to correct them and introducing it into tobacco leaves, yields increased 40-fold compared with the toad.
◇ Agriculture that makes medicines, pharming
The pharmaceutical industry called the results further proof of the potential of pharming. Pharming combines the English words pharmaceutical and farming. Literally, it refers to agricultural technologies that obtain therapeutic substances from genetically modified plants or animals.
In a report released late last year, global market research firm Research and Markets projected that the global pharming market, valued at $2.56 billion (3.8577 trillion won) in 2024, would grow 8% annually to reach $4.06 billion (6.1172 trillion won) by 2030.
Pharming using tobacco leaves proved its efficacy even before COVID vaccines. In Japan, an influenza vaccine was made from tobacco leaves, and in Korea, BioApp became the first in the world to produce a vaccine against African swine fever virus from tobacco leaves. Pharming could become a new growth engine for tobacco companies that know tobacco farming better than anyone.
Medicago, which produced a COVID vaccine from tobacco leaves, received investment from Philip Morris International, a Swiss tobacco company. British American Tobacco (BAT), a British tobacco company, also developed a COVID vaccine from tobacco leaves with its U.S. subsidiary Kentucky BioProcessing (KBP). KBP and Medicago also took part in developing ZMapp, an Ebola virus treatment, in 2014. ZMapp consisted of three types of antibodies that attack the Ebola virus, all produced in leaves of the Nicotiana benthamiana species.
The livestock industry has also joined pharming. In 2009, the U.S. Food and Drug Administration (FDA) approved ATryn (brand name), an anticoagulant developed by U.S. company GTC Biotherapeutics and extracted from goat's milk. It is a protein drug that blocks thrombin, which clots blood, preventing thrombosis (blood clots). GTC injected the human antithrombin gene into goat embryos and implanted them into surrogate mothers' wombs. The female genetically modified goats born this way secreted human antithrombin protein in their milk.
Kanuma, approved in the United States and Europe in 2015, is also a pharming medicine made from the egg whites of genetically modified chickens. It treats a fatal genetic disorder in which fat accumulates in organs. The human fat-dissolving enzyme gene was inserted into chicken DNA.
References
Science Advances (2026), DOI: https://doi.org/10.1126/sciadv.aeb3034
Nature Food (2024), DOI: https://doi.org/10.1038/s43016-024-00996-x
Nature Medicine (2023), DOI: https://doi.org/10.1038/s41591-023-02455-9
Nature Medicine (2021), DOI: https://doi.org/10.1038/s41591-021-01370-1