The Neurosteroidogenic Enzyme 5α-Reductase Mediates Psychotic-Like Complications of Sleep Deprivation

Hi guys! I know there are a lot of guys that feel better after sleep deprivation (SSRI /Finasteride /Isotretinoin etc), or during night. There is a interesting study here.

"Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone. SD selectively enhanced 5αR expression and activity, as well as AP levels, in the prefrontal cortex; furthermore, finasteride (10-100 mg/kg, IP) dose-dependently ameliorated PPI deficits, hyperactivity, and risk-taking behaviors, in a fashion akin to the antipsychotic haloperidol and the mood stabilizer lithium carbonate. Finally, PPI deficits were exacerbated by allopregnanolone (10 mg/kg, IP) and attenuated by progesterone (30 mg/kg, IP) in SD-subjected, but not control rats. Collectively, these results provide the first-ever evidence that 5αR mediates a number of psychosis- and mania-like complications of SD through imbalances in cortical levels of neuroactive steroids. “”

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Before taking fin i was super anxious all the time stuck in fight or flight mode for no reason, could not sleep, had unexplained abnormal behaviour which i cannot document and was overly aggressive for no reason in all situations. After fin im MUCH more calmer, i can finally feel tired late at night (although too much now due to fatigue)

all my psychological problems prior to finasteride were related to extremely high 5ar activity due to not sleeping well for years, however this activity was my manhood, now im calm finally but turning into a hermaphrodite

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You pinpoint the problem. :rofl:

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BINGO.

Excellent find. Possibly one of the most enlightening studies I’ve come across. It demonstrates that Finasteride seems to have a similar effect to antipsychotics and mood stabilisers. Interestingly, it also points out that allopregnanolone seems to ‘‘exacerbate’’ the effects which finasteride impaired. Makes one wonder whether the Sage Pharmaceutical allopregnanolone analogue drugs in stage 3 trials may help remedy much or our problem.

Hi Orthogs, so you think that Sage 217 will be effective in helping pfs patients?.

I dearly hope it can help as I cannot hold on for much longer. Do we know a possible market date for the drug?

Nice find, iull1k.

Hang in there guys.

A quote from Wikipedia, which is taken from reputable sources:

“Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.[29][30][31] This appears to be because 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 luteal phaselevels) inhibit the activity of the receptor, while lower and higher concentration increases stimulate it.”

By having very low levels of allopregnanolone, our GABAA receptors are probably in a state of highly stimulated activity. This may well explain brain fog and loss of libido and sexual functioning. Think of it as taking a high level of Benzodiazapenes constantly.

If we were to increase the levels of allopregnanolone in our brains, we would enter the part of the U curve where the receptors would be inhibited, which may help alleviate brain fog and similar symptoms.

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These are interesting thoughts - thanks for this Orthogs.

There is a lot to keep us motivated here.

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There are insteresting conclusions here that we wrote on PSSD forum.
http://www.pssdforum.com/viewtopic.php?f=22&t=806&hilit=neurosteroids
http://www.pssdforum.com/viewtopic.php?f=10&t=2242&p=21602#p21602
http://www.pssdforum.com/viewtopic.php?f=22&t=806&hilit=neurosteroids&start=40#p9793
http://www.pssdforum.com/viewtopic.php?f=22&t=806&hilit=neurosteroids&start=60#p17103

Also if someone is interersted. There is a doc written by myself, 3 years ago.
http://www.pssdforum.com/viewtopic.php?f=5&t=523&p=4293#p4288

Now, after 3 years, i would like to write a new DOC, because a lot changed, we have more info and much more structurated. Maybe i will have time for this.

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Phase 3 ends November 2019 - release date end of 2020 if all goes well.

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Nice work @iull1k

https://drive.google.com/file/d/0B5GlVMx53zuIZFV0M1NBdW11REU/view

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Some info related to the aforementioned biphasic effect of allopregnanolone:

To determine why the system goes haywire during puberty, the team homed in on the CA1 region of the hippocampus, a curved slice in the center of the brain that regulates emotion. The CA1 has been implicated in controlling anxiety. The team was searching for a specific type of GABA receptor known as alpha4-beta2-delta, known to be particularly sensitive to steroids.