This is your brain (waves) on drugs

By Nathan M Doner

28 October 2020

Picture of Human Brain and Circuits

Clinical depression is among the world’s most prevalent mental disorders, but many people who suffer from this chronic and debilitating disease do not respond to the antidepressants prescribed by their physicians.  These individuals must endure a trial-and-error process to find the right medication that can take months or even years, leaving them with unresolved or worsening mental health issues in the meantime. 

Worse yet, up to one third of patients with clinical depression ultimately do not respond to any of the antidepressants prescribed by their physicians, in a condition termed treatment-resistant depression (TRD).

Efforts are underway to find new types of drugs that work on patients with TRD, but some of the “new” drugs under consideration may come as a surprise. For decades, scientists ignored the therapeutic potential of recreational drugs such as ketamine, psilocybin, LSD, and MDMA because of their illegality and the negative public perceptions about drug abuse. Now there is a resurgence of research into these drugs as the need for alternative antidepressants becomes more urgent.

Ketamine is a “club drug” that has performed very well in clinical trials of TRD. A version of it called esketamine was recently approved in the US for treatment of TRD and is currently under review at Health Canada. To treat TRD, the drug is taken by nasal spray in combination with other antidepressants but due to its potential for abuse, it cannot be taken home from the doctor’s office or clinic.

A team of researchers led by Prof. Melissa Perreault in the Department of Molecular and Cellular Biology recently set out to gain a better understanding of how ketamine works by studying its effect on brain waves. Graduate students Joshua Manduca and Rachel-Karson Thériault, who co-authored the study, measured brain waves in rats – using a strain of the animal that exhibits depression-like behaviours – by implanting electrode arrays into specific brain regions.

“We put in the arrays, give them a drug, and then look into different brain regions to see what the functional changes are in these regions,” says Manduca.

A rat with implanted electrodes to measure its brain waves (photo courtesy of J. Manduca)

A rat with implanted electrodes to

measure its brain waves

(photo courtesy of J. Manduca)

The team found that brain waves change upon ketamine administration, and this gives them important hints about how the brain is affected by the drug. For instance, low doses of ketamine helped normalize a type of brain wave measure called fast gamma coherence, which can be altered in people with depression. 

While more research is required to fully understand the underlying mechanisms of ketamine’s effect on the brain, it is clear that the drug alters brain waves in a reproducible way.  

Excitingly, this means that brainwave patterns could serve as a potential biomarker to help identify drugs that are effective against TRD.  Biomarkers are essentially an “indicator” of the body’s physiological state (most of us are familiar with biomarkers in the form of normal versus abnormal blood test results).  In this case, using brain wave patterns as a biomarker could save a patient months or years trying to find an effective anti-depressant.

“Clinicians may one day use simple and non-invasive techniques such as electroencephalography (EEG) or imaging on human patients to measure their brain waves in real-time and quickly determine if their brain responds to a particular treatment,” explains Thériault. 

EEG is already used as a diagnostic tool for seizures, epilepsy, and sleep problems, but for mental disorders it is currently used only as a research tool – largely because clinicians don’t yet have enough data to identify reliable biomarkers. Ongoing research on rat brains in the Perreault lab is expected to help change this, something that could some day transform the way human patients find the right drug to treat their illness.

This is a rapidly advancing field. Stay tuned for more developments.

 

This study was funded by the Canadian Institutes of Health Research.

 

Read the full study in the journal Neuroscience.

Read about other CBS Research Highlights.