Brain fog is the popular term for persistent impairment of cognitive function after COVID-19. It’s a complication familiar to many long-haulers. Thoughts are difficult to process, working memory becomes cloudy, and concentration and focus wane. While the condition is often debilitating and no approved therapies currently exist, Yale University investigators have found that two common drugs, taken together, may provide relief.* 

Guanfacine and N-acetylcysteine

Guanfacine (Tenex) was federally approved for treatment of attention deficit hyperactivity disorder (ADHD) in 2009 after pioneering work by Yale neuroscientist and psychologist Amy Arnsten, Ph.D. The drug is also commonly used for treating traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), which are other disorders of the brain’s prefrontal cortex. 

Arnsten has now teamed up with Yale psychiatrist and neurologist Arman Fesharaki-Zadeh, M.D., Ph.D., who’s been combining guanfacine with N-acetylcysteine (NAC) to successfully treat Long COVID patients. NAC is a common antioxidant and anti-inflammatory supplement also used for TBI.

The prefrontal cortex, situated at the front of the brain’s frontal lobe, is involved in executive function, working memory, and concentration. Arnsten says it’s especially vulnerable to stress and inflammation because it must sustain its own neural activity without any sensory input. Its neural circuits “have very special molecular needs” that Inflammation can disrupt, causing brain fog. According to scientists:

• Guanfacine strengthens neural connections to protect the brain against stress and inflammation. Studies have shown its ability to restore executive function and memory.
• NAC’s potent antioxidant and anti-inflammatory properties are also effective at protecting the prefrontal cortex. Fesharaki-Zadeh has seen improvement in energy and memory.

What the researchers did

From the time he treated his first Long COVID patient in June 2020, Fesharaki-Zadeh saw the similarity between TBI symptoms and brain fog, and the combined potential of NAC and guanfacine. As he describes in Neuroimmunology Reports, he has since treated a dozen people with Long COVID brain fog using the medication duo. Of these patients:

• 11 were female,
• Ages ranged from 21-73 years,
• 11 were Caucasian and one was African American, and
• All had been living with brain fog for 3-14 months post-COVID.

Patients were prescribed sustained-release guanfacine and NAC for an indefinite period of time. The dosages consisted of:

• 1 milligram (mg) of guanfacine before sleeping; 2 mg after a month if well-tolerated, plus
• 600 mg of NAC each day

What they found

The results of Arnsten’s and Fesharaki-Zadeh’s case study showed that: 

• Eight (8) out of 12 patient cases experienced significantly reduced brain fog, with better executive function, working memory, and focus, and could resume normal workloads.
• Four (4) patients discontinued treatment: two for unknown reasons and two for dizziness/hypotension (typical adverse effects of guanfacine).

One patient, a nurse who stopped guanfacine for a short time due to dizziness, saw a return of cognitive dysfunction. When she resumed the medication, her brain fog again lifted and her dizziness disappeared. She has since returned to normal work hours.

“This was not a placebo-controlled trial,” Arnsten noted, “but anecdotes like this make one more confident that the relief is really due to the drug and not the placebo effect.”

What it means

The authors say that large, placebo-controlled trials are needed to confirm these results and better understand the drugs’ actions. Meanwhile, they encourage people with Long COVID-related brain fog to explore guanfacine and NAC with their doctors . “If patients have a physician who can read our paper, we’re hoping that they can access help right now,” Arnsten said.

“There’s a paucity of treatment out there for Long COVID brain fog,” added Fesharaki-Zadeh, “ so when I kept seeing the benefits of this treatment in patients, I felt a sense of urgency to disseminate this information. You don’t need to wait to be part of a research trial. You can ask your physician—these drugs are affordable and widely available.” 

*Blackman, I. & Yale University. (2022, December 16). Potential new treatment for ‘brain fog’ in long COVID patients. MDLinx. https://www.mdlinx.com/news/potential-new-treatment-for-brain-fog-in-long-covid-patients