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Psychedelic Drug DOI Identifies Neuron to Reduce Anxiety in TIFR Study

• Researchers at TIFR have identified a specific neuron in the ventral hippocampus that, when activated, can alleviate anxiety in rodents. • The study used the synthetic psychedelic drug DOI to target and trace the PV-positive neuron responsible for reducing anxiety without hallucinations. • This discovery could lead to more targeted treatments and the development of psychedelic-inspired medications for treatment-resistant mental health conditions. • The research team collaborated with multiple institutions, including Cornell, Yale, and Columbia universities, to validate their findings.

A team at the Tata Institute of Fundamental Research (TIFR) in Mumbai has identified a specific neuron that, when targeted, can reduce anxiety. The study, a first-of-its-kind from India, used a psychedelic drug to trace and activate the ventral hippocampus, an area of the brain that processes emotional information and regulates stress.

Identifying the Target Neuron

The research, led by neuroscientist Vidita Vaidya, focused on the ventral hippocampus and its role in anxiety reduction. "Targeting the ventral hippocampus could help reduce anxiety at both cellular and neural levels," Vaidya explained. The team used a synthetic psychedelic drug called DOI, designed by Alexander Shulgin, to pinpoint the specific neurons responsible for the anxiolytic effect.
To confirm DOI's anxiety-reducing properties, the team used an 'elevated plus maze' with rodents. The rodents injected with DOI explored more open and risky areas, confirming the drug's effect. Further investigation was needed to understand where in the brain this was happening.

Collaborative Effort

The project grew into a multi-institutional study with researchers from Cornell, Yale, and Columbia universities. Through trials on rodents, the ventral hippocampus was identified as a key target for DOI in reducing anxiety. Cornell helped identify a "PV-positive neuron" that was hyperactive when the drug was present.
Vaidya explained the discovery with an analogy: "Think of the brain as a map of Mumbai... We had to search neighbourhood by neighbourhood—until we found Marine Drive, which represents the ventral hippocampus... That’s our PV-positive neurons."

Implications for Mental Health Treatment

The discovery is significant because these neurons 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," Vaidya noted. Some colleagues are already designing psychedelic-inspired drugs that don’t produce hallucinations or motor effects.
Vaidya is discussing her findings with experts at NIMHANS to move the research from lab to clinical trials. However, she notes that India currently lacks clinical trials for psychedelic-assisted therapy. Biju Viswanath, a psychiatry professor at NIMHANS, said current medications for anxiety and depression take weeks to be effective, leaving patients at risk during that waiting period. He added that around 50% of patients don’t respond to existing pharmacological treatments, making the exploration of new agents a promising approach.
Despite the potential, regulatory hurdles in India make it difficult to conduct this kind of research. Vaidya is preparing to present this research at the 2025 Gordon Research Conference on Neurobiology of Psychedelics at Rhode Island.
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[1]
TIFR study uses psychedelic drug to trace neuron that can reduce anxiety - Times of India
timesofindia.indiatimes.com · Oct 6, 2024

A study at Tata Institute of Fundamental Research used psychedelic drug DOI to identify a neuron activating the ventral ...

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