TIFR study uses psychedelic drugs to track neurons that can reduce anxiety

The word “psychedelic” conjures up images of wild, mind-blowing journeys straight out of the 1960s. But what if the same “trippy” substances used in drugs like LSD and magic mushrooms could be used as treatment? mental health Problems? A new study may have paved the way.
A team at the Tata Institute of Fundamental Research (TIFR) in Mumbai have led a unique study from India that used a psychedelic drug to identify a neuron that can activate the ventral hippocampus in the brain – which processes emotional information and regulates stress – in ways that could ease anxiety.
“People’s initial reaction to psychedelics is often alarming. But substances like LSD, a synthetic psychedelic, psilocybin, found in magic mushrooms, and mescaline, extracted from cacti, have been used extensively by traditional healers for thousands of years – from ancient tribes from the Amazon to the Incas of Central and South America . long before they became symbols of rebellion,” says Vidita Vaidya, neuroscientist and professor of biological sciences at TIFR, who led the project.
Targeting the ventral hippocampus could help reduce anxiety at both a cellular and neuronal level, she says. “And with one psychedelic drug “As a tool to achieve this, it opens the door to more targeted treatments for anxiety disorders, as well as the development of psychedelic-inspired medications for treatment-resistant mental illnesses such as post-traumatic stress disorder and depression, without causing hallucinations,” she adds.
The drug used in their study is a synthetic drug called DOI, developed by Alexander Shulgin in 1984. “Due to regulatory hurdles in India, we cannot import LSD or psilocybin to work with. That's why we worked with DOI, which is powerful but is not a common street drug and has not been abused like LSD or psilocybin. However, it falls under the same umbrella of psychedelics that alter states of reality,” says Vaidya, whose journey with DOI dates back to her time as a graduate student. “I looked at it from different angles. It has profound, diverse effects – as an antidepressant, it triggers hallucinations and reduces anxiety. We also examined its ability to alter mitochondria (the energy cells need to function). Our main question was: How does DOI reduce anxiety?”
To confirm that this was indeed the case, the team used an “elevated plus maze” – a device with open and closed arms used to measure anxiety in rodents. “We observed whether they would explore more open and risky areas after injecting DOI. And they did. This was the first step confirming that DOI reduces anxiety in rats and mice.”
But there were still gaps in understanding “where in the brain” this happened. “When my student Prachi Tiwari expressed her desire to delve deeper into this for her doctoral thesis, I told her, 'This is a complex problem that requires multiple approaches,' but she was determined,” says Vaidya.
What began as a challenge five years ago evolved into a collaborative effort that reached far beyond her TIFR lab, collaborating as a multi-institutional study with researchers at Cornell, Yale and Columbia universities. “So it became an international effort, bringing in colleagues from all these universities to conduct experiments where our collaborators could help us provide answers more quickly,” says Vaidya. After several experiments in rodents, the ventral hippocampus was identified as a key target for DOI in reducing anxiety.
But they still faced a challenge. “It’s a part of the brain with millions of different cell types. We suspected it might be a specific group of neurons, but we weren’t sure,” says Vaidya. At that time, Cornell helped identify a “PV-positive neuron” that was hyperactive in the presence of the drug.
Vaidya summed it up with a simple analogy: “Imagine the brain as a map of Mumbai. We knew DOI worked, as if we knew something was happening in a busy city like Mumbai. But we didn't know exactly where. So we had to search neighborhood by neighborhood—until we found Marine Drive, which represents the ventral hippocampus. Even back then it wasn't just any building, but concrete Art Deco buildings. These are our PV-positive neurons. Once we knew this, we could specifically target these neurons to achieve the anxiety-reducing effect without needing the entire drug.”
The discovery was significant because these neurons reduce anxiety without causing hallucinations. “By understanding how these psychedelics work on a deeper level, we can develop drugs that target the parts of the brain responsible for reducing anxiety, without unwanted effects such as hallucinations. Some colleagues are already developing psychedelic-inspired drugs that do not cause hallucinations or motor effects.”
Vaidya, whose scientific career focused on the “neurobiology of emotions,” discussed her findings with experts at NIMHANS to translate the research from the laboratory to clinical trials. “But India currently lacks clinical trials for psychedelic-assisted therapy…Australia, Europe and the US are moving forward with large, carefully controlled trials,” says Vaidya.
Biju Viswanath, additional professor of psychiatry at NIMHANS who specializes in the effects of psychotropic drugs on neural stem cell lines, said current medications for anxiety and depression take weeks to work and that patients are at risk during this waiting period . “Especially since around 50% of patients do not respond to existing pharmacological treatments,” he said. “Exploring a new class of drugs using animal models is a promising approach.”
However, he warns that clinical trials in India may still be a long way off due to their high potential for abuse. Vaidya shares his frustration. “Our regulatory knots make it difficult to conduct this type of research in India,” she says as she prepares to present this research at the 2025 Gordon Research Conference on Neurobiology of Psychedelics in Rhode Island. “We need to stop playing catch-up…Right now we don’t have enough psychedelic researchers. This is not good for a country facing a growing mental health crisis.”