AUGUSTA, Ga. — A 50-year-old blood pressure drug could be repurposed to treat the detrimental effects of PTSD, according to new findings.
So far, clonidine, which is commonly used for treating high blood pressure and ADHD. Previous PTSD studies have examined clonidine because the drug acts on receptors that stimulate the sympathetic nervous system, which refers to a person’s “fight or flight” modes. These same receptors are thought to have a link to PTSD, playing an active role in traumatic memory. Clonidine’s sister drug, guanfacine, acts similarly and has also been studied in relation to PTSD. However, the findings from clinical trials have been conflicting, since clonidine has produced significant results while guanfacine hasn’t.
With that in mind, scientists at the Medical College of Georgia at Augusta University are now focusing on clonidine. While the two drugs bind to the same receptors, they function differently, according to Qin Wang, MD, Ph.D., neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.
Their work suggests that clonidine could provide immediate relief to those suffering from anything ranging from pandemic-related PTSD to more severe trauma from experiences like war. Moreover, they also indicate that other new treatments could become targets for study based on the impact they have on the activation of a protein called cofilin.
How does the drug alter memory?
The new works used genetically modified mice, along with neurons from human stem cells that have the potential to make several different cell types. In the hippocampus, the learning and memory hub of the brain, they found that a novel axis on a “fight or flight” receptor called ɑ2A is crucial for maintaining fearful memories associated with a place or circumstance. Within this axis, they found that a protein called spinophilin interacts with cofilin. Spinophilin controls protrusions on neuron junctions called dendritic spines, which store memories.
“Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger,” Wang says in a university release, adding that the spines morph from a slender profile to a more mushroom-like shape.
“The mushroom spine is very important for your memory formation,” she adds.
However, for the shape to form, cofilin levels have to be low in the junction where the spines are. Clonidine may be able to help with this by encouraging cofilin to interact with the receptor that stops the dendritic spine from being able to take a mushroom shape. The sister drug is not capable of producing these results.
Mice taking clonidine display less trauma from past events
Mice treated with clonidine had a significantly less severe response after receiving a mild shock and revisited the specific place where the shock took place, compared to untreated mice. Guanfacine did not produce similar results. Since mice can’t explain it for themselves, Wang admits that the team doesn’t know what the treated mice remember from their traumatic experience. However, based off their lack of reaction to circumstantial stimulus, it seems that there may be some benefits.
“The interpretation is that they don’t have as strong a memory,” Wang says, noting that the goal is not to erase painful memories, but diminish their disruption in a person’s life.
PTSD has always been a significant threat to mental health, especially among military veterans. However, it has become an even bigger problem during the COVID-19 pandemic. Wang says that, because of this, these findings could be groundbreaking for the countless lives affected by PTSD.
The findings appear in the journal Molecular Psychiatry.
