High doses of ketamine can temporarily switch off the brain
Study in sheep aimed at better understanding brain activity in
Huntington's disease

Date:
June 11, 2020
Source:
University of Cambridge
Summary:
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.



FULL STORY ========================================================================== 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.


==========================================================================
In a 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 anaesthetic 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 frequency 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," said Professor Jenny Morton at the University of
Cambridge's Department of Physiology, Development and Neuroscience,
who led the research.

"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." She added: "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 working properly. The team want to understand why human patients
respond differently to various drugs if they carry the gene for this
disease. Sheep were used because they are recognised 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 anaesthetic range. Initially,
the same response was seen as 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.



========================================================================== "This wasn't just reduced brain activity. After the high dose of ketamine
the brains of these sheep completely stopped. We've never seen that
before," said Morton. Although the anaesthetised sheep looked as though
they were asleep, their brains had switched off. "A few minutes later
their brains were functioning normally again -- it was as though they had
just been switched off and on." 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. The study is published
today in the journal Scientific Reports.

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.

To conduct the experiment sheep were put into veterinary slings, which are commonly used to keep animals safe during veterinary procedures. Different doses of ketamine were given to 12 sheep and their brain activity recorded
with EEG.

Ketamine was chosen for the study because it is widely used as a safe anaesthetic and pain-relief drug for treating large animals including
dogs, horses and sheep. It is also used medically, and is known as a 'dissociative anaesthetic' because patients can appear awake and move
around, but they don't feel pain or process information normally --
many report feeling as though their mind has separated from their body.

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.

"Our purpose wasn't really to look at the effects of ketamine, but to use
it as a tool to probe the brain activity in sheep with and without the Huntington's disease gene," said Morton. "But our surprising findings
could help explain how ketamine works. If it disrupts the networks
between different regions of the brain, this could make it a useful tool
to study how brain networks function - - both in the healthy brain and
in neurological diseases like Huntington's disease and schizophrenia."
Ketamine has recently been proposed as a new treatment for depression
and post- traumatic stress disorder. Beyond its anaesthetic actions,
however, very little is known about its effects on brain function.

"We think of anaesthetic drugs as just slowing everything down. That's
what it looks like from the outside: the animals basically go to sleep
and are unresponsive, and then they wake up very quickly. But when we
looked at the brain activity, it seems to be a much more dynamic process,"
said Morton.


========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
story is licensed under a Creative_Commons_License. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. A. U. Nicol, A. J. Morton. Characteristic patterns of EEG
oscillations in
sheep (Ovis aries) induced by ketamine may explain the psychotropic
effects seen in humans. Scientific Reports, 2020; 10 (1) DOI:
10.1038/ s41598-020-66023-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200611094127.htm

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