Lifting Brain Fog with Guanfacine
It started with a mild cough and a fever that wouldn't break. I thought I'd recover in a week or two, like a regular flu. But after the acute symptoms of COVID-19 subsided, I was left with a lingering visitor that refused to leave: brain fog.
Work became an arduous task. I'm a graphic designer, and my job requires a sharp eye and a sharper mind. But the lines and colors that once danced to my command now blurred into a muddled canvas. Deadlines whooshed by as I struggled to concentrate, my thoughts as elusive as shadows at dusk.
The impact spilled over into my personal life. I used to unwind with books, but reading became an exercise in futility as I'd have to re-read the same paragraph over and over again to remember what I’d just read. Reading words became like putting beads on a string with no knot in the end - by the time I added the 4th bead, the first one had fallen off the string. words slipping through my mind's grasp like water through my fingers.
My primary care provider ran tests, most coming back normal and there just didn’t seem to be a solution that would help lift the fog. But then a friend mentioned a paper they had read on guanfacine and brain fog.
Guanfacine: Clearing the Mind and Lifting the Fog
Guanfacine is a medication that belongs to a class of drugs known as alpha-2 adrenergic agonists. It is primarily used to treat high blood pressure (hypertension) and is also approved for the treatment of ADHD. Guanfacine is available under the brand names Intuniv (extended-release) and Tenex (immediate-release), but it also has generic forms available.
While guanfacine is primarily known for its effectiveness in treating hypertension and ADHD, there is growing interest in its potential benefits for improving cognitive dysfunction and brain fog, often experienced by those with Long COVID and ME/CFS.
Guanfacine: FDA-Approved Treatments and Off-Label Use
Guanfacine has received official approval from the U.S. Food and Drug Administration (FDA) to treat two primary conditions:
Hypertension (High Blood Pressure): Guanfacine was first approved by the FDA for the treatment of hypertension. It is effective in lowering blood pressure by decreasing the heart rate and relaxing the blood vessels, which allows blood to flow more easily.
Attention Deficit Hyperactivity Disorder (ADHD): The extended-release form of guanfacine (Intuniv) is approved for the treatment of ADHD in children and adolescents. It is used to reduce symptoms such as hyperactivity, impulsiveness, and distractibility in patients with ADHD.
Off-Label Use of Guanfacine
Guanfacine is currently used off-label for the treatment of cognitive dysfunction. While it is not FDA-approved for this specific indication, clinicians and researchers have explored its potential benefits in various forms of cognitive impairment, including those associated with conditions like Long COVID and ME/CFS.
Guanfacine's ability to modulate the activity of the prefrontal cortex — an area of the brain involved in attention, working memory, and impulse control — is the basis for its off-label use in conditions such as PTSD, traumatic brain injury, ME/CFS, and now, Long COVID. The drug's action on alpha-2A adrenergic receptors in the brain is thought to potentially improve the cognitive symptoms experienced by some patients with these conditions.
Safety and Efficacy
While guanfacine is FDA-approved (and thus considered safe and effective) for the treatment of hypertension and ADHD, its use for cognitive dysfunction or brain fog is off-label. There is limited published data specifically addressing the safety and efficacy of guanfacine for brain fog, though recent studies highlight its effectiveness in reducing symptoms of brain fog with mild to moderate side effects.
Like most medications, guanfacine can have side effects. Common side effects include drowsiness, dizziness, dry mouth, and constipation. Generally, guanfacine is taken before bed to reduce any drowsiness during the daytime.
The Path Forward
As we continue to navigate the uncharted waters of Long COVID, ME/CFS, and other complex conditions, guanfacine is an emerging treatment option that is showing benefits. Its effects on the central nervous system and the prefrontal cortex of the brain make it a promising candidate worth considering when brain fog and cognitive dysfunction are interfering with daily living. If you're interested in exploring guanfacine as a treatment option, consult with your healthcare provider or visit RTHM Direct to learn how guanfacine may help lift the fog and get you back on the path to better health.
Follow the Science
Studies show that cognitive deficits associated with Long COVID, ME/CFS, and dysautonomia, known as "brain fog", may be helped by existing FDA-approved drugs guanfacine and N-acetylcysteine (NAC). The cognitive deficits seen in these conditions preferentially affect functions of the prefrontal cortex (PFC), which governs higher cognitive abilities like working memory, planning, and decision-making. The prefrontal cortex (PFC) is extra sensitive to inflammation. Think of it as the PFC being like a delicate instrument that reacts strongly to any changes. Acute COVID-19 infection, for example, increases inflammatory factors like kynurenic acid and glutamate carboxypeptidase II in the brain, impairing PFC functioning (2).
Guanfacine and NAC, often taken together, may help normalize PFC physiology and cognition. Guanfacine strengthens PFC connections by inhibiting cAMP signaling that otherwise opens potassium channels and decreases neuronal firing. NAC reduces kynurenic acid levels by inhibiting its production, which allows better neurotransmission in the PFC. In addition, NAC has antioxidant effects that protect mitochondria from calcium overload.
Fesharaki-Zadeh, A., Lowe, N., & Arnsten, F. T. (2023). Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”. Neuroimmunology Reports, 3, 100154. https://doi.org/10.1016/j.nerep.2022.100154 https://medicine.yale.edu/news-article/potential-new-treatment-for-brain-fog-in-long-covid-patients/
Fesharaki Zadeh, A., Arnsten, A. F., & Wang, M. (2023). Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID. Neurology International, 15(2), 725-742. https://doi.org/10.3390/neurolint15020045
Bateman, L., Bested, A. C., Bonilla, H. F., Chheda, B. V., Chu, L., Curtin, J. M., Dempsey, T. T., Dimmock, M. E., Dowell, T. G., Felsenstein, D., Kaufman, D. L., Klimas, N. G., Komaroff, A. L., Lapp, C. W., Levine, S. M., Montoya, J. G., Natelson, B. H., Peterson, D. L., Podell, R. N., . . . Yellman, B. P. (2021). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management. Mayo Clinic Proceedings, 96(11), 2861-2878. https://doi.org/10.1016/j.mayocp.2021.07.004
Connor, D. F., Grasso, D. J., Slivinsky, M. D., Pearson, G. S., & Banga, A. (2013). An Open-Label Study of Guanfacine Extended Release for Traumatic Stress Related Symptoms in Children and Adolescents. Journal of Child and Adolescent Psychopharmacology, 23(4), 244-251. https://doi.org/10.1089/cap.2012.0119
Arnsten, F. T., & Jin, L. E. (2012). Guanfacine for the Treatment of Cognitive Disorders: A Century of Discoveries at Yale. The Yale Journal of Biology and Medicine, 85(1), 45-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313539/
