Clonidine works on adrenergic receptors in the brain, which are known for their role in fight-or-flight responses and are believed to be activated in post-traumatic stress disorder.
New evidence suggests that clonidine, a blood pressure medication, could be used to mitigate the effects of post-traumatic stress disorder (PTSD), according to a study published in Molecular Psychiatry.
Clonidine is commonly used to lower high blood pressure and for the treatment of ADHD and has been studied in PTSD because it works on adrenergic receptors in the brain. These receptors are known for their role in fight or flight responses and are believed to be activated in PTSD, and to also play a role in consolidating a traumatic memory. A related drug, guanfacine, has also been studied in PTSD.
Psychotherapy is generally considered the most effective treatment for PTSD. Some medications, such as antidepressants, can also be used, although there are limited pharmacotherapy options. This lack of FDA-approved drugs has led to off-label uses of drugs like clonidine, according to the study authors.
Study results for clonidine in PTSD have been conflicting. Although clonidine has shown some promise, guanfacine has not, according to researchers.
Building on this evidence, researchers at the Medical College of Georgia at Augusta University presented new laboratory evidence that although the 2 drugs bind to the same receptors, they do different things there. The results suggest that clonidine could provide immediate treatment to the significant number of individuals with PTSD.
The new studies looked at genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types. In the hippocampus, the center of learning and memory, investigators found that a novel axis on an adrenergic receptor called a2A is essential to maintaining fear memories in which individuals associate a place or situation with fear or other distressing emotions that are a hallmark of PTSD.
In this axis, the researchers found that the protein spinophilin interacts with cofilin, which controls protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored. A single neuron can have hundreds of these spines, which change shape based on brain activity and whose changing impacts the strength of the synapse.
“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,” said neuropharmacologist Qin Wang, MD, PhD, in a press release. “The mushroom spine is very important for your memory formation.”
For these mushroom shapes to form, levels of cofilin must be significantly reduced in the synapse where the spines reside. This is where clonidine may be able to play a role, according to the study.
The investigators found that clonidine interferes with cofilin’s exit by encouraging it to interact with the receptor, which consequently interferes with the dendritic spine’s ability to resume a mushroom shape and retain the memory. Guanfacine, notably, had no apparent effect on cofilin.
The findings help clarify the disparate results in the clinical trials of these 2 drugs, according to the study authors. When mice received both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating a traumatic memory, suggesting that they have opposite impacts, at least on this biological function.
The researchers also found living evidence. In their studies mimicking how PTSD happens, mice were given a mild shock and were treated with clonidine right after being returned to the place where the shock happened.
Clonidine-treated mice had a significantly reduced response, such as freezing, compared to untreated mice. In fact, mice who received clonidine reacted similarly to mice who were never shocked at all.
Wang noted that they cannot know for certain how much the mice remember of what previously happened, although clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.
When a memory is recalled, the synapses that hold the memory of what happened there become temporarily unstable before the memory restabilizes, or reconsolidates. This natural process provides an opportunity to intervene in reconsolidation, potentially diminishing the strength of the negative memory. Clonidine appears to be one way to do that, Wang concluded.
Blood pressure drug holds promise for treating PTSD. News release. EurekAlert; January 5, 2023. Accessed January 11, 2023. https://www.eurekalert.org/news-releases/975630