A Single Dose of Ketamine May Ease Chronic Fatigue, New Study Finds
Millions of people live with chronic fatigue that no treatment can touch. Now a small but notable study from Rutgers Health and the National Institutes of Health suggests ketamine could change that. The research, published in Pharmacological Reports, found that a single low dose infusion of ketamine reduced fatigue scores by 21% within three days. The effect peaked at 24 hours, when fatigue dropped by nearly 39%. The results are preliminary. But for a condition that has long resisted medical intervention, even a modest signal carries weight.
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| Key Takeaway | Detail |
|---|---|
| Study type | Randomized, double blind, crossover trial |
| Participants | 10 adults with chronic fatigue from cancer survivorship, fibromyalgia, ME/CFS, or lupus |
| Ketamine dose | 0.5 mg/kg, single IV infusion |
| Fatigue reduction at 24 hours | Nearly 39% |
| Fatigue reduction at 3 days | 21% (exceeding the 20% threshold for a positive result) |
| Comparator | Midazolam (active placebo), which also showed some fatigue reduction |
| Lead researcher | Leorey Saligan, PhD, Rutgers School of Nursing |
| Next step | Larger clinical trial in breast cancer survivors |
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Why Ketamine for Fatigue?
The connection between ketamine and fatigue traces back to the glutamate system. Saligan’s earlier research found that blood levels of a glutamate receptor called mGluR5 predicted chronic fatigue in cancer patients who had completed therapy. Ketamine blocks glutamate receptors. That made it a logical candidate for testing whether that pathway could become a treatment target.
Chronic fatigue affects cancer survivors, people with fibromyalgia, those living with lupus, and the millions who have ME/CFS. The standard recommendation is exercise. That approach works well for patients who can motivate themselves to start and maintain a program. Most cannot. The debilitating nature of the condition makes the recommended treatment feel nearly impossible to begin.
What the Trial Showed
The trial enrolled 10 participants. Each received a ketamine infusion and, two weeks later, an injection of midazolam, a sedative that served as the active comparator. Researchers set a clear bar before the trial began: a 20% drop in fatigue scores within three days would justify further study.
Ketamine cleared that bar. But the picture grew more complex. Midazolam also reduced fatigue, despite having no established role in treating the condition. That overlap made it hard to isolate the specific effect of ketamine. The original study aimed to enroll 59 participants, a number that would have provided more statistical clarity. The COVID pandemic and strict eligibility criteria limited recruitment to just 10.
A Bridge, Not a Cure
Saligan does not envision ketamine as a long term fatigue medication. Instead, he sees its most promising role as a bridge. The idea is that a short energy boost could help patients engage with other strategies that offer lasting relief. Think of it as a neurological reset that makes participation in exercise programs or behavioral therapies feel achievable.
This concept mirrors how ketamine already functions in mental health treatment. Clinicians use it to create a window of relief from severe depression, allowing patients to engage more fully in therapy. A similar approach for chronic fatigue would represent a meaningful shift in treatment philosophy.
Building on a Decade of Research
This trial is not the first time Saligan has explored the fatigue connection. In 2016, his team analyzed data from two double blind, placebo controlled crossover trials involving 36 patients with treatment resistant bipolar disorder. That earlier work found ketamine significantly lowered fatigue scores compared to placebo from 40 minutes after treatment through Day 14. The effect remained significant even after controlling for changes in depressive symptoms, suggesting the fatigue relief was not simply a byproduct of mood improvement.
The new study extends that line of inquiry beyond psychiatric populations and into the broader chronic fatigue landscape. A larger trial in breast cancer survivors is now being planned. For those navigating the daily weight of chronic fatigue, this research offers a reason to pay attention. The evidence remains early. But the direction is clear, and more answers are on the way.
