A drug best known as an anesthetic and a fast-acting treatment for severe depression may also help reduce chronic fatigue, according to a small early study led by researchers from Rutgers Health and the National Institutes of Health.
The findings suggest that ketamine could provide a short-term energy boost for people struggling with long-lasting exhaustion that does not improve with rest.
Chronic fatigue is more than ordinary tiredness.
It is a persistent lack of energy that can make daily activities, work, and social life extremely difficult.
The condition affects millions of people, including those recovering from cancer treatment and those living with illnesses such as fibromyalgia, lupus, or chronic fatigue syndrome.
Because the causes are complex and not fully understood, effective treatments have been limited.
In the study, published in Pharmacological Reports, researchers tested whether a single low dose of ketamine could reduce fatigue symptoms.
Ten participants with chronic fatigue related to cancer survivorship or chronic illnesses received one ketamine infusion. Two weeks later, they received an injection of midazolam, a sedative used as a comparison treatment.
Participants reported noticeable improvements in energy after ketamine. On average, fatigue scores dropped by about 21 percent three days after the infusion.
The strongest effect occurred within 24 hours, when fatigue decreased by nearly 39 percent.
Although the improvement was modest, researchers say even a small change is meaningful for a symptom that has been difficult to treat.
Interestingly, the comparison drug also appeared to reduce fatigue, which made it harder to determine exactly how much of the benefit came from ketamine.
Researchers say this could mean that fatigue levels naturally fluctuate or that the sedative had its own unexpected effect. The study was originally planned to include many more participants, but recruitment was limited by the COVID-19 pandemic and strict eligibility requirements.
Scientists became interested in ketamine for fatigue after earlier research suggested that certain brain pathways involving glutamate receptors might play a role in the condition. Ketamine blocks these receptors, which may explain its potential effect on energy and motivation.
Experts do not expect ketamine to become a long-term treatment for fatigue. Instead, it might serve as a short-term “jump start,” helping patients feel well enough to engage in other therapies known to improve energy, such as exercise programs or rehabilitation. Many people with chronic fatigue struggle to begin these activities because they feel too exhausted.
Ketamine is already approved for medical use and has been widely studied for depression, which could speed up future research. A nasal spray form is already available for depression treatment, and newer versions of the drug are being developed with fewer side effects.
While the results are preliminary and larger studies are needed, researchers say the findings offer cautious optimism. For people living with chronic fatigue, even temporary relief could improve quality of life and open the door to recovery strategies that were previously out of reach.
