Mice tripping on psychedelics help explain neural origins of hallucinations

A new study is helping clarify what is going on in our brains when we hallucinate. To do this, researchers from the University of Oregon dosed mice with a powerful psychedelic drug and with unprecedented detail zoomed in on how the animal's brains subsequently generated visual hallucinations.

Prior research has found that strong visual hallucinations, deriving from either schizophrenia or psychedelic drugs such as LSD, can be suppressed by blocking the activity of serotonin-2A receptors in the brain. So, in order to better understand how our brains specifically generate these visual hallucinations researchers administered mice with a powerful psychedelic drug called DOI (4-iodo-2,5-dimethoxyphenylisopropylamine).

DOI is a member of a class of drugs called serotonergenic psychedelics and, alongside LSD, psilocybin and DMT, it stimulates activity in serotonin-2A receptors. DOI is often used in research conditions as it is not currently a schedule one drug in the United States, unlike its better known psychedelic counterparts. DOI is also considered to be stronger than LSD, with a much longer effect duration. Essentially, it is not a pleasant or easy drug for humans to experience. This is why DOI has only rarely popped up in recreational contexts since its discovery in 1972.

Using processes known as calcium imaging and single-unit electrophysiology, the researchers closely monitored mouse brains after administering DOI. Comparing neural activity when shown images on a screen, to neural activity when the animals were presumed to be hallucinating, the study was able to clearly measure the differences in brain activity between regular visual processing and visual hallucinations.

Two big observations were made in the study. Under the influence of DOI the mice displayed erratic and unusual neuronal firing rhythms. But perhaps even more importantly, the researchers noticed a reduction in visual cortex neural signaling. This suggests the drug was lowering the volume of visual information being processed in the brain.

"You might expect visual hallucinations would result from neurons in the brain firing like crazy, or by mismatched signals," says Cris Niell, senior author on the new study. "We were surprised to find that a hallucinogenic drug instead led to a reduction of activity in the visual cortex."

The hypothesis is that this drug-induced stifling of activity in the visual cortex actually results in other parts of the brain over interpreting a smaller volume of visual information and filling the gaps with details that we ultimately perceive as hallucinations. The researchers suggest this process can be reflected in the way we begin to hallucinate after long periods in the dark. It's our brain overcompensating.

Of course, the huge limitation to this study is the fact that the researchers can never be sure the animal is actually visually hallucinating or not, however, they do suggest that certain altered behavioral patterns, including odd paw movements and head twitches, can signal a mouse may be visually hallucinating. It is also fundamentally unclear whether these two neural alterations are causing visual hallucinations, are merely disruptions generated by the psychedelic drug, or both.

"I don't feel like we've necessarily found the smoking gun for the entire underlying cause of hallucinations, but this is likely to be a piece of it," says Niell. "The data we've collected will provide a foundation for additional studies going forward. In particular, we plan to use genetic manipulation to study particular parts of this circuit in more detail."

The research is more valuable than simply offering an academic insight into the nature of visual hallucinations. Activity in serotonin-2A receptors has been strongly implicated in the visual distortions suffered by those with schizophrenia. So this research may eventually lead to better ways to help reduce the acute hallucinatory load from mental health disorders such as schizophrenia.

The new research was published in the journal Cell Reports.

Source: Cell Press via MedicalXpress