Thinking About Injecting Allopregnanolone

[Oligoelement]

Since inhibiting the 5a reductase will also reduce allopregnanolone levels, I will inject it. It was approved by the FDA for postpartum depression back in June 2019, and it's also available on tocris. What do you guys think?
I know the data is not very clear on this, but I haven't been able to find an accurate distribution of the 5a reductase isoenzymes, and as far as I know, the type 2 is found in the brain.
@hemingway_the_mercenary

 

[Ollie]

Pretty sure it has to be IV'd and drip administered over 24 hours.

 

[Oligoelement]

Pretty sure it has to be IV'd and drip administered over 24 hours.

Yes, you're right, but as far as I know, it's because it can cause dizziness and other side effects. Do you know anything else about this steroid? I mean, could you answer a couple questions?
1.I have read that, although serum allo level decreases while taking finasteride, production on the brain could remain largely unafected, due to isoenzyme distribution. That would mean that serum allo would be an indicator of 5a activity in other parts of the body. However, as far as I know, it crosses the blood-brain barrier pretty easily, and therefore, a reduction in serum allo could lead to decreased levels in the brain. What do you know about this?
2.What do you know about buying it as an experimental/ its use for postpartum depression?

 

[Oligoelement]

Forgot to mention that, the other day I talked to a pretty knowledgeable Nutrition scientist and he told me that steroids (including neurosteroids) are mediators between the enviroment and our body, which means that there are some steroids that, although necessary, would not be requiered to the extent we need them today if we fixed the cronic and ongoing inflamation that most of us sufer.

 

[Ollie]

Yes, you're right, but as far as I know, it's because it can cause dizziness and other side effects. Do you know anything else about this steroid? I mean, could you answer a couple questions?
1.I have read that, although serum allo level decreases while taking finasteride, production on the brain could remain largely unafected, due to isoenzyme distribution. That would mean that serum allo would be an indicator of 5a activity in other parts of the body. However, as far as I know, it crosses the blood-brain barrier pretty easily, and therefore, a reduction in serum allo could lead to decreased levels in the brain. What do you know about this?
2.What do you know about buying it as an experimental/ its use for postpartum depression?

My understanding is pretty similar to yours. It links back to the ‘myth’ that 5ar inhibitors have a super flat response curve and therefor inhibit almost the same amount of 5ar (and DHT) regardless of dose. However I’ve come across several studies that show a much more linear dose response when observing effects in localised tissues... skin, follicles, prostate, brain etc ..
this is presumably due to 5ar concentrations differing organ to organ and person to person.

With this in mind I think you’re certainly right that neurosteroids probably aren’t as affected in the brain as some studies depict - my understanding is that we can’t actually measure neurosteroids in the brain anyway but rather have to use serum measurements ideally in the form of cerebral spinal fluid which from what I’ve read aren’t accurate anyway because allo dissipates quite quickly across brain tissue.

Regarding your question I would imagine that the fall in allo in the brain would almost certainly drop however the effect wouldn’t be cumulative as 5ar would still be produced in brain tissue and finasteride obviously doesn’t inhibit all 3 forms of 5ar anyway. dutasteride however would be a different argument - yet still deemed safe by the likes of Japan and Korea.

Regarding injection I don’t know if it would make sense to even do it ?! The half life is very short however perhaps the effects of the injected neurosteroids carry active benefits beyond that ... week, month.. who knows ? Presumably if it’s a treatment for severe depression it just make sense.

If you do try it though it would be interesting to hear your experience.

 

[Oligoelement]

My understanding is pretty similar to yours. It links back to the ‘myth’ that 5ar inhibitors have a super flat response curve and therefor inhibit almost the same amount of 5ar (and DHT) regardless of dose. However I’ve come across several studies that show a much more linear dose response when observing effects in localised tissues... skin, follicles, prostate, brain etc ..
this is presumably due to 5ar concentrations differing organ to organ and person to person.

With this in mind I think you’re certainly right that neurosteroids probably aren’t as affected in the brain as some studies depict - my understanding is that we can’t actually measure neurosteroids in the brain anyway but rather have to use serum measurements ideally in the form of cerebral spinal fluid which from what I’ve read aren’t accurate anyway because allo dissipates quite quickly across brain tissue.

Regarding your question I would imagine that the fall in allo in the brain would almost certainly drop however the effect wouldn’t be cumulative as 5ar would still be produced in brain tissue and finasteride obviously doesn’t inhibit all 3 forms of 5ar anyway. dutasteride however would be a different argument - yet still deemed safe by the likes of Japan and Korea.

Regarding injection I don’t know if it would make sense to even do it ?! The half life is very short however perhaps the effects of the injected neurosteroids carry active benefits beyond that ... week, month.. who knows ? Presumably if it’s a treatment for severe depression it just make sense.

If you do try it though it would be interesting to hear your experience.

Thank you very much Ollie, such a great response. I would do it because of the concern about alzheimer's and other neurodegenerative diseases that have been observed at the time of giving 5a reductase to rats. However, I'm gathering more information, because:
1. I think that the studies done on rats can't be extrapolated to humans, either due differences in isoenzymatic inhibition, distribution or quantity.
2.I haven't been able to find rates of neurodegenerative disseases among pseudohemafrodites (people born with a defect in the enzyme 5a reductase, which renders it useless), which would make the relation (if there's any) appear. A good group to test it would be the ones in Cuba, since the prevalence of the condition is extremely high there.