How Classic Psychedelics Impact Brain Cell Dynamics and Anxiety

A classic psychedelic, similar to LSD, psilocybin and mescalin, was found to activate a cell type in the brain that silences other neighboring neurons, a result that provides insight into how such drugs reduce anxiety, according to a new study.

The findings show the psychedelic DOI (2,5-dimethoxy-4-iodoamphetamine) lessened anxiety in mice and rats while activating the ventral hippocampus and so-called fast-spiking interneurons there.

"It hasn't been known what brain areas and cell types are involved when psychedelics suppress anxiety," said Alex Kwan, associate professor of biomedical engineering at Cornell University and senior author of the study, which published today in the journal Neuron. "The idea is that if we know the neurobiology involved, we can design some better drug that would target these pathways."

The work provides an understanding of the cellular trigger for the psychedelic-induced relief of anxiety."

Vidita Vaidya, senior professor of biological sciences at the Tata Institute of Fundamental Research in Mumbai, and the paper's corresponding author

The pathway in the ventral hippocampus – a brain structure involved in social memory, emotion and affect – does not appear to cause the hallucinations that are a hallmark of DOI, suggesting that some of the therapeutic effects of psychedelics – including reducing PTSD, depression and anxiety – may be isolated within discrete brain circuits, Vaidya said.

"That opens up the possibility to design psychedelic inspired drugs that target anxiety without evoking potent hallucinations," she added.

The study builds on earlier research that identified abnormal hyperactivity in the ventral hippocampus when an animal is anxious, particularly neurons that communicate with the amygdala, the major processing center for emotions.

"There's a hint that in the anxiety state, these cells are active, and maybe the drug works by then silencing some of these," Kwan said.