Psychedelic drugs may improve mental health in part by reducing inflammation. In mice, psychedelics reversed signs of anxiety and an accumulation of inflammatory immune cells around the brain, potentially explaining why these drugs have shown promise in treating mental health conditions.
It was once widely believed that there was little to no communication between the immune system and the brain, yet a burgeoning body of evidence now indicates that isn’t the case. In fact, the immune system may play a role in various mental health conditions. We know that people with , or have higher levels of inflammation, for instance.
Now, at Harvard University and his colleagues have found that brain cells called astrocytes – which influence inflammation – undergo certain changes when the body experiences fear, which can also lead to more anxiety. This relationship may have evolved to prepare the body for a possible injury after experiencing a fearful and dangerous situation, he says.
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To study this neuroimmune reaction, they examined mice experiencing chronic stress. Three rodents were restrained in tubes for 6 hours a day for 18 days, leading to signs of anxiety. The researchers then genetically analysed astrocytes in the animals’ amygdala, a brain region involved in fear. The astrocytes had reduced activity in a gene that drives production of a protein called EGFR, which is known to regulate inflammation.
Using a gene editing tool on a separate group of nine mice, the researchers deactivated this gene in the amygdala astrocytes. They then triggered fear and anxiety in the mice by restraining them in tubes for 6 hours a day for a week, before subjecting them to electrical foot shocks paired with a noise and flashing light – mimicking a stressful event that could induce PTSD. When the mice were later exposed to just the noise and light, they froze in fear as expected – but the mice with the deactivated gene spent about 15 per cent more time frozen than nine control mice with intact genes. This suggests that astrocytes use EGFR to regulate fear.
Further experiments revealed that decreases in EGFR were associated with an accumulation of inflammatory immune cells in the protective tissues around the brain and that this influx seemed to drive anxiety in the mice.
The researchers then treated 10 mice with psychedelic drugs after restraining them daily for 18 days. Half of the animals received psilocybin while the rest received MDMA. Compared with five mice that weren’t treated with drugs, those on psychedelics had about 75 per cent fewer inflammatory immune cells in the protective tissues around their brains – about the same amount as animals that weren’t restrained. They also spent less time frozen in fear when exposed to the flashing light and noise associated with electric shocks. In fact, they froze to the same degree as rodents that had never been restrained, suggesting psychedelic drugs mitigate the effects of chronic stress.
There are two key takeaways from these findings, says Wheeler. First, that the immune system does seem to play a role in mental health conditions, and second, that the therapeutic effect of psychedelic drugs may be partly due to their anti-inflammatory properties, he says.
“We still don’t really understand how psychedelics produce these very long-lasting [mental health] effects,” says at Johns Hopkins University in Maryland. “But this may give us a really compelling window into one of the main mechanisms.” It also “opens up a whole new realm of possibility for how we might be able to use psychedelic treatment for non-psychiatric conditions” associated with inflammation, he says.
Studies are already under way to investigate psychedelics as a treatment for inflammatory bowel disease, chronic Lyme disease and fibromyalgia – all of which are characterised by excess inflammation. “We don’t view these drugs as a magic bullet for inflammatory diseases, but we think they may have some applicability,” says Wheeler.
Nature
