Allopregnanolone levels and their correlation to symptoms of PFS sufferers would be useful

Allopregnanolone has been shown to be a positive allosteric modulator of GABA action on the GABAA receptors. Allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor – moderate level increases (in the range of 1.5–2 nM/L total allopregnanolone, which are approximately equivalent to inhibit the activity of the receptor, while lower and higher concentration increases stimulate it.

It would be interesting to match the symptoms of the participants of the study who were largely shown to have low levels of allopregnanolone with their actual readings.

I theorise that PFS mental symptoms manifest themselves as having three possible cases.

  1. The person experiences high levels of anxiety and emotional intensity which would likely indicate low levels of GABA activity. This would be because allo would be pushed into a region where it would be inhibitory of GABA activity.

  2. The person experiences low levels of anxiety and low levels of emotional intensity (flatness) and anhedonia which would likely indicate high levels of GABA activity. This would be due, in the case of PFS due to moving allo levels to a region which is very stimulatory of GABA activity.

  3. The person experiences no changes. This may well be because their allopregnanolone levels are within a normal range on the U-shaped curve.

It’s possible that depending on the level of impact PFS has had on the person’s allopregnanolone levels, it affects their state in this regard.

Sage-217, a allopregnanolone analogue would have to be dosed in such a way to make the PFS sufferer’s effective allopregnanolone level be such which pushes them into the ‘normal’ zone.

Data correlating allo levels and symptoms would appear to be useful in deciding on dosages of allo analogues such as Sage-217.


Great idea, I read the melcangi study where they had N=14 and the mean allopreg was lower than control.

But did every person have lower than control allopreg levels?

Lets say you have Case 2, low anxiety, suggesting higher than normal allopregnanolone, you’d need a different approach for this phenotype of the disease. It would be about lowering Allopregnanolone to normal then…

I agree this would be very interesting to see, allopregnanolone levels correlated to the patients symptoms. Also with PSSD.

Did the study specify whether any were high?

No, I just read the paper quickly, maybe i did not see it though. Would be really important to know, if they were ALL below mean or if there were ones with normal allo or even high. Also, N=14 is pretty low. But good for PFS standards, I guess.

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