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.
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.
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.
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.