New clues about how ketamine could lead to psychosis.

New clues about how ketamine could lead to psychosis.

Researchers looked into whether ketamine could cause mental changes like psychosis. They discovered that ketamine increases ambient noise, which may obstruct the brain’s ability to process sensory signals.

As rats were used in the study, more research is required to determine whether the results apply to people. Changes in reality perception, such as persistent delusions, hallucinations, and disorganized thought, are characteristics of schizophrenia. Almost 24 million people around the world are affected by the illness.

There is still no known cause for schizophrenia. Yet, research points to environmental, psychological, and genetic variables as potential causes of the illness.

By blocking NMDA receptors in the brain, the drug ketamine causes a mental state resembling psychosis in healthy humans. As a result, the central nervous system develops an imbalance of excitatory and inhibitory signals, which impacts sensory experience.

According to experts, schizophrenia-related perception abnormalities may be related to similar changes in NMDA receptors. Yet, it hasn’t been made clear how this might be the case.

Ketamine and psychosis

Recently, scientists investigated how ketamine alters sensory perception in rat brains.

They discovered that ketamine increased “background noise” in the brain, which reduced the clarity or intensity of sensory information. They remarked that this might help to explain why persons with schizophrenia or psychosis experience reality differently. The European Journal of Neuroscience published their findings.

These results, according to Dr. Sam Zand, a Las Vegas-based psychiatrist who was not involved in the study, “indicate that malfunction in NMDA receptors may play a role in the development of psychosis.”

“The work offers fresh understandings into the process by which ketamine may cause psychotic symptoms. The results might influence the creation of novel medications for psychosis that target NMDA receptors or brain noise, the researcher continued.

Study design

Seven male lab rats were used in the study to examine how ketamine affected their ability to perceive sensory information. To do this, they first implanted electrodes into rats’ brains to capture electrical activity.

They then recorded the brain’s reactions before and after administering ketamine while simulating their own whiskers. To be more precise, the scientists studied how ketamine affected beta and gamma oscillations in a neuronal network. They carries messages from sensory organs to the brain.

Gamma waves have a frequency range of 30-80 Hz, while beta oscillations have a frequency range of 17-29 Hertz (Hz). Processing sensory data requires the use of frequencies.

In the end, the scientists discovered that even before they stimulated the rats’ whiskers, ketamine enhanced power in both beta and gamma oscillations.

However, they also discovered that the amplitude of the rats’ beta and gamma oscillations dropped post-stimulus and after ketamine administration, which is associated with hampered perception.

They also observed that ketamine enhanced gamma frequency noise, which is related to a reduced capacity for sensory signal processing.

The researchers hypothesised that their findings suggest that increased background noise, which in turn may be brought on by damaged NMDA receptors leading to an imbalance of inhibition and excitation in the brain, may be a trigger for the distorted reality experienced in psychosis and schizophrenia.

According to Dr. Sofya Kulikova, senior research fellow at the HSE University in Perm, Russia, and one of the study’s authors, “The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders.”

Research limitations

The study was not conducted by Dr. Howard Pratt, a psychiatrist and mental health medical director at Community Health of South Florida. He made it clear that:

The main drawback of these results is that, although a strong association, causation has not yet been shown. There are many potential explanations for conditions like psychosis, including increases in dopamine, which is the focus of treatment for those with a diagnosis of schizophrenia. I’m interested to see what happens as the investigation expands past animal studies.

We also discussed the study’s shortcomings with Dr. James Giordano, the Pellegrino Institute professor of neurology and biochemistry at Georgetown University Medical Center who was not engaged in the study.

The fact that the study solely looked at ketamine-induced effects, he said, “is a key limitation. While valuable and practical for understanding ketamine’s activity in a rat model, it may not provide direct translation to comprehend non-drug-induced dissociative, and psychotic states in humans.”

Dr. Giordano went on to say that it is possible that the effects of ketamine on humans, while undoubtedly dissociative and exhibiting some psychotic traits, are not entirely representative of or identical to the neurological mechanisms underlying other forms of psychosis and schizophreniform disorders.

Possible clinical repercussions

The study’s ramifications, according to Dr. Giordano, are that “[t]hese findings are useful in that evidence of ketamine’s actions at defined brain networks may enable better understanding— and improved clinical applications—of its effects in humans.”

The researcher added, “In addition, by highlighting the functions of these brain nodes and networks involved in mediating dissociative experiences, we may create improved understanding — and possibly treatments for — specific types of drug-induced psychoses, and perhaps other psychotic illnesses, such as forms of schizophrenia, as well.

Larger Trials Needed

Dan Iosifescu, MD, MSc, associate professor of psychiatry at New York University School of Medicine in New York City, commented on the study and said that if the results “were based on a larger study” it would be very important because such patients are currently being denied access to a beneficial treatment due to a theoretical risk of psychosis.

A low risk of psychosis exacerbation following IV ketamine, according to Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved in the study, is still possible given that the review is based on a small sample.

Veraart concurred, stating that “well-designed randomised controlled trials should be conducted to ascertain the efficacy, safety, and tolerability of ketamine in depressed individuals with a propensity to psychosis before administration on a large scale is pushed.”

The study received no particular funding. Outside of the submitted work, Veraart has received speaker honoraria from Janssen. Disclosures from the other authors are provided in the original publication. Iosifescu has advised clinics on the most effective ways to administer IV ketamine therapy as a consultant to the Centers of Psychiatric Excellence.


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