Classic hallucinogens similar to LSD, psilocybin and mescaline activate a cell type in the brain that silences other nearby neurons, a new study finds, providing insight into how such drugs reduce anxiety.
The results of the study showed that the hallucinogen DOI (2,5-dimethoxy-4-iodoamphetamine) reduced anxiety in mice and rats while activating the ventral hippocampus and the so-called fast-spiking interneurons found there.
“We don’t know which brain regions or cell types are involved when psychedelics suppress anxiety,” said Alex Kwan, an associate professor of biomedical engineering at Cornell and lead author of the study published today in Neuron. “The idea is that if we understand how the neurobiology is involved, we can develop better drugs that target these pathways.”
“This study provides an understanding of the intracellular triggers that lead to psychedelic drug-induced anxiety relief,” said Vidita Vaidya, senior professor of biological sciences at the Tata Institute of Fundamental Research in Mumbai and corresponding author of the paper.
Pathways in the ventral hippocampus, a brain structure involved in social memory, feelings and emotions, do not appear to produce the hallucinations that characterize DOI, suggesting that some of the therapeutic effects of psychedelics, such as reducing PTSD, depression and anxiety, may be isolated within distinct brain circuits, Vaidya said.
“This opens the possibility of developing psychedelic-inspired drugs that target anxiety without causing powerful hallucinations,” she added.
The study builds on previous research that identified abnormal hyperactivity of neurons in the ventral hippocampus when animals are anxious, particularly those that communicate with the amygdala, a major processing center for emotions.
“There are indications that these cells become more active during anxiety, so drugs may work by silencing some of these cells,” Kwan said.
