High doses of this depression drug can temporarily switch off the brain

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In a new study, researchers have identified two brain phenomena that may explain some of the side-effects of ketamine.

Their measurements of the brain waves of sheep sedated by the drug may explain the out-of-body experience and state of complete oblivion it can cause.

The research was conducted by a team at the University of Cambridge.

In the study aimed at understanding the effect of therapeutic drugs on the brains of people living with Huntington’s disease, researchers used electroencephalography (EEG) to measure immediate changes in the animals’ brain waves once ketamine—an anesthetic and pain relief drug—was administered.

Low-frequency activity dominated while the sheep were asleep.

When the drug wore off and the sheep regained consciousness, the researchers were surprised to see the brain activity start switching between high and low-frequency oscillations.

The bursts of different frequencies were irregular at first but became regular within a few minutes.

As the sheep came round from the ketamine, their brain activity was really unusual.

The timing of the unusual patterns of sheep brain activity corresponded to the time when human users report feeling their brain has disconnected from their body.

The team says it’s likely that the brain oscillations caused by the drug may prevent information from the outside world being processed normally.

The findings arose as part of a larger research project into Huntington’s disease, a condition that stops the brain from working properly.

The team wants to understand why human patients respond differently to various drugs if they carry the gene for this disease.

Sheep were used because they are recognized as a suitable pre-clinical model of disorders of the human nervous system, including Huntington’s disease.

Six of the sheep were given a single higher dose of ketamine, 24mg/kg. This is at the high end of the anesthetic range. Initially, the same response was seen with a lower dose.

But within two minutes of administering the drug, the brain activity of five of these six sheep stopped completely, one of them for several minutes—a phenomenon that has never been seen before.

The researchers think that this pause in brain activity may correspond to what ketamine abusers describe as the ‘K-hole’ – a state of oblivion likened to a near-death experience, which is followed by a feeling of great serenity.

Ketamine abusers are known to take doses many times higher than those given to the sheep in this research. It is also likely that progressively higher doses have to be taken to get the same effect.

The researchers say that such high doses can cause liver damage, may stop the heart, and be fatal.

At lower doses ketamine has a pain-relieving effect, and its use in adult humans is mainly restricted to field situations such as frontline pain-relief for injured soldiers or victims of road traffic accidents.

Ketamine has recently been proposed as a new treatment for depression and post-traumatic stress disorder. Beyond its anesthetic actions, however, very little is known about its effects on brain function.

One author of the study is Professor Jenny Morton at the University of Cambridge’s Department of Physiology.

The study is published in the journal Scientific Reports.

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