Clonidine works on adrenergic receptors, known for their role in the ‘fight or flight’ response and consolidating traumatic memories. While clonidine has shown some promise in treating PTSD, its sister drug, guanfacine, which activates the same receptors, has not shown similar promise.
A retrospective study in 2021 involving 79 veterans with PTSD found that clonidine was linked to improvements in 72% of patients and ‘much improvement in 49% with few side effects. Meanwhile, studies have found that guanfacine does not relieve PTSD symptoms.
For the present study, researchers examined the effects of clonidine and guanfacine on genetically modified mice and neurons from human stem cells. They found that clonidine interferes with the binding protein cofilin, known to control protrusions on dendritic spines where memories are consolidated and stored. By interacting with cofilin, clonidine prevents dendritic spines from growing into a 'mushroom-like shape', ultimately reducing the ability of memories to consolidate.
Meanwhile, they found that while guanfacine also binds to adrenergic receptors, it did not interact with cofilin. This, noted the researchers, may explain the disparate results in clinical trials between the two drugs.
The researchers next observed how the drugs work in vivo. To do so, they gave mice a mild shock and then observed their behavior after taking clonidine and guanfacine when placed back where the shock occurred.
While they did not know for certain how much mice remembered the incident, they found that clonidine-treated mice displayed fewer trauma-linked behaviors- such as freezing in their tracks- compared to untreated mice. Those on guanfacine, however, behaved similarly to untreated mice.
The researchers wrote that their findings suggest clonidine may provide immediate treatment for PTSD symptoms related to the pandemic and military combat. They also noted that their findings confirm clinical observations of clonidine's positive effects, and thus warrant large-scale, placebo-controlled trials for clonidine to treat PTSD.
Sources: Science Daily, Nature
