Neurosteroid Biosynthesis Upregulation

Therapeutic Efforts Pharmaceutical
#1

Now that we have solid proof that finasteride and 5ar inhibitors can downregulate nuerosteroids even after discontinuation, perhaps we should look deeper into compounds that upregulate neurosteroid biosythesis. Hopefully a few of us will be able to get our hands on some of these to test out.

Ganaxolone
An allopregnenolone analogue. Just finished up human trials and proven to be safe.
marinuspharma.com/ganaxolone.html

Olanzapine and clozapine
Olanzapine and clozapine increase the GABAergic neuroactive steroid allopregnanolone in rodents.
mendeley.com/catalog/olanzap … e-rodents/

Selective Brain Steroidogenic Stimulants
A new class of drugs - whose mechanism of action involves the stimulation of neurosteroidogenesis with the goal of increasing brain allopregnenlone levels. Found to elecit potent neurosteroidogenesis activity selectively at a low dose.
…these include…

Flouxetine (Prozac) and Norfluoxetine (Seproxetine)
Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake.
ncbi.nlm.nih.gov/pubmed/16432684
Important point here are that these can be taken in low enough doses that it will not affect the Serotonin pathway…

Neurosteroid Biosynthesis Upregulation: A Novel Promising Therapy for Anxiety Disorders and PTSD
intechopen.com/books/anxiety … s-and-ptsd

#2

I’m really interested in this. I no longer have ED sides (but I do have smaller testicles) and no suicidal thoughts that I’ve seen people on here have. But I really can’t concentrate and physically focus on things, it almost hurts my eyes to do so. I think this could be a great discovery.

#3

I´m interested in this.

#4

Thanks for posting this. The paper about neurosteroid upregulation is gold. Connected a lot of dots for me.

#5

nice job!

#6

It is nice that you have listed possible treatments here, but except ganaxolone, which i haven’t heard about, all of these options seems to carry their own very serious risks.
On the other hand, even if some of the drugs listed here would work without any sides, 5ar, which caused low allopregnanolone and THDOC, would remain low, so problem would persist after stopping the drug intake.
But, like i said, this isn’t a worthless thread.

#7

Nice!

#8

hi, where is the article to proove that these neurosteroids are downregulated even AFTER discontinuation?
I’m currently reading on this problem and would like to read this article…

by the way, would it be safe to buy this product called celtic dreams mist spray, containing allopregnanolone?
i have bad insomnia… connected or not to pfs, i dont know

#9

onlinelibrary.wiley.com/doi/10.1 … 9/abstract

#10

So, this can be valid in this case:

  • Took finasteride
  • Felt mental side effects, quit.
  • After quitting mental side effects didn’t go away.

But is it valid in my case?

  • Took finasteride (4 weeks)
  • Didn’t feel mental side effects but got gynecomastia
  • Quit, gynecomastia reduced to almost non-existant
  • 1 year and half later, after quitting, developed terrible insomnia…

How could I distinguish between these two cases?
A - I have a prob because of neurosteroid impairment from propecia that resulted in this insomnia
B - I have developed insomnia for some other reason and that resulted in neurosteroid impairment

I’m just looking for answers but I guess you don’t have an answer for me…
This insomnia showed up and never disappeared

#11

did they do any studies to proove that these neurosteroids are impaired in the whole finasteride population?

#12

So what about GHB? A few people have mentioned it in their recoveries, this article (ncbi.nlm.nih.gov/pubmed/15158173) suggests it can increase serum allopregnanolone, but chronic use renders it ineffective.

I’ve tried it. The product itself is pretty useless as the spray seems to stop working after about 4 or 5 uses. I’ve stopped using it as introducing exogenous allopregnanolone will probably only downregulate enodogenous allopregnanolone further, and the benefits from administration aren’t that noticeable.

#13

Those articles posted are really interesting.

I’ve been reading a lot about the GABA/Glutamate balance lately, still don’t fully understand but have a basic grasp of it.

Don’t know about anyone else but I definitely feel it’s more a glutamatergic dysfunction than a GABAergic one. Inability to think on your feet, or react to spontaneous events or conversation. Alternatively, I don’t have much problem with anxiety, probably even less so than I did before starting finasteride.

In contrast, PTSD sufferers are over-reactive to stimulus. Like they’re being flooded with glutamate, constantly on edge and unpredictable.

#14

what about gabapentin or pregabalin?
they act on glutamate, has anyone tried it?

#15

I tried gabapentin.

It worked pretty solid.

#16

by pretty solid, you meant, it solved all your issues? Or which issues did it solve?
at what dosage and for how long? i want to try lyrica (pregabaline)

#17

So I’d just like to add something I read a study on, that increases ENDOGENOUS BIOSYNTHESIS of Allopregnanolone:

  • Glycine (there’s studies that 3g before bed is better than any sleep aid) + Gelsemium sempervirens…these work sinergistically to increase the biosynthesis of allopregnanolone

Other stuff:

  • Allopregnanolone in spray form - I’m not sure how dangerous this is though…
  • GHB
  • Maybe Gabapentin or Pregabalin?
#18

This is a very interesting topic. I feel very certain that my PFS is purely neurological.

I had a second crash a week ago- chronic anxiety which meant I could not sleep for THREE NIGHTS and it gave me sexual sides which I had not experienced until this second crash. My penis reduced in side and libido was wiped out. After being fine sexually for two years post-fin, it is interesting that my anxiety caused the sexual sides. Btw, when I have moments of calm, my libido rises.

#19

If that is the case you may want to consider investigating other avenues for your issues. Most guys with longterm side effects find they do not resolve upon discontinuing drug, or manifest within weeks of stopping.

#20

Wanted to chime in. Ive been off and on zoloft several times. I keep getting off due to the sexual side effects. But it is known to upregulate allopregnanolone. It relieves my brainfog. I was making straight A’s in my last year of college on zoloft (with pfs). It definately makes me feel normal mentally. Also when I take it my face begins to brighten up andy eyes look clearer and brighter. I dont look and feel dead. This I believe had to do with allopregnanolone. I am also looking to improve this mental side effect without further decreasing my sex drive. Also when I was hospitalized I was given ativan. I noticed feeling normal mentally and even my fatigue was better. I know these claims sound farfetched but I have connected these dots to increasing neurosteroids as a solution to my mental sides.