I wonder what advantages this new CT38 peptide has over the abortion drug mifepristone (aka RU-486)?
Both CT38 and mifepristone act to temporarily inhibit the actions of the HPA-axis, and in both cases this is thought may lead to a HPA-axis reset. The idea is that the temporary inhibition of the HPA-axis resulting from taking these drugs for a few days or weeks facilities the axis reset.
From Cort's
excellent article:
If his hypothesis is correct, he believes CT38 will be able to reset the limbic system almost as quickly as it fell off the tracks in the first place; i.e., a couple of treatments might be enough to return the system to normal and begin the healing process.
The HPA-axis reset achieved by mifepristone works in a similar way, and has been shown effective for major depression,
1 and psychotic major depression.
1
A mifepristone HPA-axis reset was also trialed for Gulf War illness,
1 but did not seem to help the symptoms, except some improvement in verbal learning (but did not improve other cognitive measures).
In terms of how the HPA-axis reset is actioned, the difference between CT38 and mifepristone is where they inhibit the HPA-axis. Here is the HPA-axis (and how it activates as part of the fight-or-flight response):
Stress ➤ Hypothalamus releases CRH ➤ Pituitary releases ACTH ➤ Adrenal glands release cortisol ➤ Activates glucocorticoid receptors
CT38 inhibits the effect of CRH (corticotropin-releasing hormone) by down-regulating the corticotropin-releasing hormone receptor 2 in the pituitary (ref:
1), and this then inhibits the whole HPA-axis.
Whereas mifepristone acts further downstream in the HPA-axis, by blocking the glucocorticoid receptor 2 (a cortisol receptor), preventing cortisol from activating the glucocorticoid receptor.
So this is how both drugs achieve an axis reset in their own ways; presumably CT38 must offer some additional advantages by inhibiting the HPA-axis further up, otherwise why would Cortene be trialing CT38 for ME/CFS.
Or maybe with CT38 they are not aiming to reset the HPA-axis, but rather reset some more local feedback loop just within the limbic system.
I am planning to try a HPA-axis reset using mifepristone in the very near future. I guess from its failure to make any major improvements in Gulf War illness, I should not expect it to help ME/CFS much. Although since the mifepristone HPA-axis reset did prove effective in treating depression, I am keeping my fingers crossed that a mifepristone reset may permanently improve the comorbid depression I often have, and lead to a better mood.
www.ec21.com is a good source of inexpensive mifepristone powder.