New Delhi: The term “psychedelic” often conjures up images of counter-culture and altered states of consciousness. But could these substances, traditionally associated with recreational drug use, hold a key to unlocking new treatments for anxiety and other mental health disorders? A groundbreaking new study suggests they might.
Researchers at the Tata Institute of Fundamental Research (TIFR) in Mumbai have conducted a pioneering study, the first of its kind in India, using a psychedelic compound to pinpoint a specific neuron capable of activating the ventral hippocampus. This brain region plays a crucial role in processing emotional information and regulating stress responses, offering a potential pathway to alleviating anxiety.
“People’s first reaction to psychedelics is often alarmist,” explains Vidita Vaidya, a neuroscientist and professor of biological sciences at TIFR, who led the research team. “But substances like LSD, psilocybin, and mescaline have a long history of use in traditional healing practices, predating their association with recreational drug use.” She notes that ancient cultures, from Amazonian tribes to the Incas, have utilized these substances for centuries.
Targeting the ventral hippocampus offers the potential to reduce anxiety at both cellular and neural levels. “And using a psychedelic drug as a tool to achieve this opens the door to more targeted treatments for anxiety disorders, as well as the development of psychedelic-inspired medications for treatment-resistant mental health conditions like PTSD and depression without triggering hallucinations,” Vaidya explains.
The study utilized a synthetic psychedelic called DOI, developed in 1984 by Alexander Shulgin. “Because of regulatory hurdles in India, we can’t import LSD or psilocybin to work with,” Vaidya clarifies. “That’s why we worked with DOI, which is potent but isn’t a common street drug and hasn’t been abused like LSD or psilocybin. However, it belongs to the same umbrella of psychedelics which alter states of reality.” Vaidya’s research with DOI extends back to her doctoral studies. “I’ve looked at it from multiple angles. It has profound, diverse effects — as an antidepressant, it produces hallucinations, reduces anxiety. We’ve also studied its ability to change mitochondria (the energy that cells need to function). Our main question was, how does DOI reduce anxiety?”
To confirm DOI’s anxiety-reducing effects, the team employed an ‘elevated plus maze,’ an apparatus used to measure anxiety levels in rodents. “We observed whether after being injected with DOI, they’d explore more open and risky areas. And they did. This was the first step, it confirmed that DOI reduces anxiety in rats and mice.”
The shift was gradual, then sudden, in understanding precisely *where* this process was occurring within the brain. “When my student Prachi Tiwari expressed her desire to delve deeper into this for her PhD thesis, I told her, ‘this is a meaty problem that’ll need multiple approaches,’ but she was determined,” says Vaidya.
What began five years ago as an intensive challenge evolved into a collaborative effort, extending beyond the TIFR lab to involve researchers from Cornell, Yale, and Columbia universities. “So, it became an international effort as we brought in peers from all these universities to conduct experiments that our collaborators could help us answer faster,” says Vaidya. Through numerous trials on rodents, the ventral hippocampus emerged as a key target for DOI’s anxiety-reducing effects.
However, a significant hurdle remained: identifying the specific cell types within the ventral hippocampus responsible for this effect. “It’s a part of the brain with millions of different cell types. We suspected it might be a specific group of neurons but weren’t sure,” explains Vaidya. Cornell University researchers played a crucial role in identifying a “PV-positive neuron” that exhibited hyperactivity in the presence of the drug.
Vaidya offers an analogy to illustrate the discovery: “Think of the brain as a map of Mumbai. We knew that DOI worked, kind of like knowing something is happening in a busy city like Mumbai. But we didn’t know exactly where. So, we had to search neighbourhood by neighbourhood—until we found Marine Drive, which represents the ventral hippocampus. Even then, it wasn’t just any building, but the specific Art Deco ones. That’s our PV-positive neurons. Once we knew that, we could target just those neurons, to get the anxiety-reducing effect without needing the whole drug.”
The implications of this discovery are significant, particularly given that these neurons appear to reduce anxiety without triggering hallucinations. “By understanding how these psychedelics work at a deeper level, we can design drugs that target those parts of the brain responsible for reducing anxiety without unwanted effects like hallucinations. Some colleagues are already designing psychedelic-inspired drugs that don’t produce hallucinations or motor effects.”
Vaidya, whose career has focused on the ‘neurobiology of emotion,’ is currently in discussions with experts at NIMHANS (National Institute of Mental Health and Neuro Sciences) to explore the possibility of moving the research from the lab to clinical trials. “But India currently lacks clinical trials for psychedelic-assisted therapy…Australia, Europe and the US are moving forward with major, carefully controlled trials,” Vaidya laments.
- Key Findings
- DOI reduces anxiety in rodents by activating PV-positive neurons in the ventral hippocampus.
- Targeting these neurons may lead to anxiety-reducing drugs without hallucinogenic side effects.
- India faces regulatory hurdles in conducting clinical trials for psychedelic-assisted therapies.
Biju Viswanath, additional professor of psychiatry at NIMHANS, specializing in the effects of psychotropics on neural stem cell lines, points out that current medications for anxiety and depression can take weeks to become effective, leaving patients vulnerable during that period. “Especially since around 50% of patients don’t respond to existing pharmacological treatments,” he notes. “Exploring a new class of agents using animal models is a promising approach.”
However, Viswanath cautions that clinical trials in India may be a significant way off due to the high potential for abuse associated with these substances. Vaidya shares this frustration. “Our regulatory knots make it hard to conduct this kind of research in India,” she says, as she prepares to present her research at the 2025 Gordon Research Conference on Neurobiology of Psychedelics in Rhode Island. “We need to stop playing catch-up…Right now, we have too few psychedelic researchers. That’s not good for a nation facing a growing mental health crisis.”
The initial reactions online have been mixed. An X.com post commented, “Finally, some hope for those of us struggling with anxiety! #mentalhealth #TIFR”. Conversely, a Facebook comment raised concerns: “Psychedelics? Are we sure this is safe? #mentalhealthresearch #India”. Another user on instagram voiced “Its amazing india is leading on mental healt research” showing divided opinion of the new study.