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How Psychedelic Drugs Create Such Weird Hallucinations

The new study was done in mice, so it is only a first step toward understanding how hallucinations happen. But hallucinogenic drugs seemed to put the primary visual region of the mouse brains into a weak, disorganized state, the study found. Neurons fired feebly, with strange timing.

And without good information coming from this primary processing region, the brain might try to fill in the blanks itself, said study researcher Cris Niell, a neuroscientist at the University of Oregon.

"The brain might start over-interpreting, or misinterpreting," Niell told Live Science. "And that could end up as a hallucination."

Believe your eyes

So far, that idea is just a hypothesis. Niell and his colleagues were interested in studying the role of a particular receptor, the serotonin 2A receptor, in the visual system. These receptors play a role in perception. Hallucinogenic drugs like LSD or psilocybin (the active ingredient in "magic mushrooms") target these receptors, which also seem to be involved in the hallucinations experienced by people with schizophrenia. [11 Odd Facts About Magic Mushrooms]

But few studies have looked at the role of these receptors on a neuron-by-neuron basis. That's what Niell and his team set out to do. They dosed mice with a hallucinogenic drug called DOI (4-iodo-2,5-dimethoxyphenylisopropylamine), which has long been used in animal studies. The mice were then shown computer screens with simple geometric patterns, such as horizontal and vertical lines, while researchers either measured the activity of individual neurons using electrodes or used an advanced microscopic-imaging technique to actually see neurons firing.

Compared with mice who had not been given DOI, the drugged mice showed a weakness in the strength of neural signaling in the primary visual cortex. This area is the first place where visual information gets processed as it hits the brain, Niell said.

"The responses were dialed down," he said, "but the information being conveyed was the same."

The neurons also showed unusual timing. Typically, Niell said, the neurons of the visual cortex explode with a burst of activity when exposed to a stimulus, then drop down to a lower level of ongoing activity. But for mice on DOI, that quick initial burst was disrupted, he said.

Laying the groundwork

Another odd effect was that mice previously trained to recognize horizontal or vertical lines showed stronger neural effects from the drugs, Niell said. It's unclear what this means, but the finding could indicate that being familiar with a stimulus could influence how the hallucinogen acts.

Mice, of course, can't say whether they're hallucinating, Niell said. That makes it hard to translate the results directly to humans.

"This is laying the groundwork for future studies," he said.

Among the questions: If the mice are hallucinating, is the cause the weakened signal in the primary visual cortex, or is it the strange disruptions to the neurons' firing? Are the changes the researchers saw in the neurons a direct result of the hallucinogenic drug? Or could the drug's effects on other brain regions cause the visual processing changes indirectly?

The researchers plan to look into the questions using techniques that would target DOI specifically to the visual region. They're also working to train mice to recognize certain patterns as a way to get the rodents to indicate what they're seeing. As the tools of neuroscience grow more advanced, it's increasingly possible to zoom in on the brain at different levels of processing, Niell said.

"Some of the measurements we made couldn't have been done 10 or 20 years ago," he said.

The findings are published today (March 26) in the journal Cell Reports.

Originally published on Live Science.