BETTER LIVING THROUGH CHEMISTRY
Ketamine could treat Parkinson’s movement disorders
By Dr. Tim Sandle
January 12, 2025
DIGITAL JOURNAL
Alzheimer's, the most common form of dementia, is thought to affect 50 million people worldwide and usually starts after age 65 - Copyright AFP/File Philippe LOPEZ
University of Arizona researchers have revealed new insights into one of the most common complications faced by Parkinson’s disease patients: uncontrollable movements that develop after years of treatment.
Parkinson’s disease is a neurological disorder of the brain that affects a person’s movement. The disease develops when the level of dopamine (3,4-dihydroxyphenethylamine), a chemical in the brain that’s responsible for bodily movements, begins to dwindle.
To counter the loss of dopamine, a drug called levodopa is administered and later gets converted into dopamine in the brain. However, long-term treatment with levodopa induces involuntary and uncontrollable movements known as levodopa-induced dyskinesia.
A study published in the science journal Brain has uncovered new findings about the nature of levodopa-induced dyskinesia and how ketamine, an anesthetic, can help address the challenging condition.
Over the years, the brain of a Parkinson’s patient adapts to the levodopa treatment, which is why levodopa causes dyskinesia in the long term. In the new study, the research team found that the motor cortex – the brain region responsible for controlling movement – becomes essentially “disconnected” during dyskinetic episodes. This finding challenges the prevailing view that the motor cortex actively generates these uncontrollable movements.
Because of the disconnect between motor cortical activity and these uncontrollable movements, there’s probably not a direct link, but rather an indirect way in which these movements are being generated. The researchers recorded activity from thousands of neurons in the motor cortex.
The study was led by Abhilasha Vishwanath, a postdoctoral research associate in the U of A Department of Psychology.
“There are about 80 billion neurons in the brain, and they hardly shut up at any point. So, there are a lot of interactions between these cells that are ongoing all the time,” Vishwanath said.
The research group found that these neurons’ firing patterns showed little correlation with the dyskinetic movements, suggesting a fundamental disconnection rather than direct causation.
This new understanding of dyskinesia’s underlying mechanism is complemented by findings regarding the therapeutic potential of ketamine, a common anesthetic. The research demonstrated that ketamine could help disrupt abnormal repetitive electrical patterns in the brain that occur during dyskinesia. This could potentially help the motor cortex to regain some control over movement.
Ketamine works like a one-two punch. It initially disrupts these abnormal electrical patterns occurring during dyskinesia. Then, hours or days later, ketamine triggers much slower processes that allow for changes in the connectivity and activity of brain cells over time, known as neuroplasticity, that last much longer than ketamine’s immediate effects. Neuroplasticity is what that enables neurons to form new connections and strengthen existing ones.
With one dose of ketamine, beneficial effects can be seen even after a few months.
These findings gain additional significance in light of an ongoing Phase 2 clinical trial at the U of A, where a group of researchers from the Department of Neurology are testing low doses of ketamine infusions as a treatment for dyskinesia in Parkinson’s patients. Early results from this trial appear promising, Vishwanath said, with some patients experiencing benefits that last for weeks after a single course of treatment.
Research alert: Ketamine use on the rise in U.S. adults; new trends emerge
University of California - San Diego
A recent study analyzing data from the National Survey on Drug Use and Health (NSDUH) found that past-year recreational ketamine use among adults has increased dramatically since 2015, including significant shifts in associations with depression and sociodemographic characteristics such as race, age and education status. Ketamine use has shown promise in clinical trials therapy for several mental illnesses, including treatment-resistant depression, and the new research suggests that ongoing monitoring of recreational use trends is crucial to balancing these clinical benefits against the risk of unmonitored recreational use.
Key findings include:
- Overall past-year recreational ketamine use increased by 81.8% from 2015 to 2019 and by 40% from 2021 to 2022.
- Adults with depression were 80% more likely to have used ketamine in the past year in 2015-2019, but this association weakened in later years. In 2021-2022, ketamine use increased only among those without depression.
- In 2021-2022, adults aged 26-34 were 66% more likely to have used ketamine in the past year compared to adults aged 18-25. Those with college degrees were more than twice as likely to have used ketamine compared to people with a high school education or less.
- People were more likely to use ketamine if they used other substances, such as ecstasy/MDMA, GHB, and cocaine.
The researchers recommend expanding prevention outreach to settings like colleges, where younger adults may be at heightened risk, as well as providing education on the harms of polydrug use, particularly in combination with opioids. As medical ketamine becomes more widely available, they also emphasize the need for continued surveillance of recreational ketamine use patterns and further research to understand the factors that contribute to ketamine use.
The study, published online in the Journal of Affective Disorders, was led by Kevin Yang, M.D., a third-year resident physician in the Department of Psychiatry at UC San Diego School of Medicine. The research was supported by the National Institute on Drug Abuse of the National Institutes of Health.
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Journal
Journal of Affective Disorders
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