Research: Finasteride, GABA-A and mental/anxiety problems

[cdnuts]

No. I always felt better the day after drinking, but it would not last and ultimately I would end up feeling worse. It is a nice respite once in awhile.

[kirrabeachbum]

Agreed as well. My speech actually becomes close to perfect with alcohol (ethanol), at least while it’s in me…

[flguy23]

I have sometimes when I drink the alcohol doesnt get me drunk like it used to. I can get drunk sometimes and other times its like im fine

[way]

@peres

@ithappens

anything that directly affects GABA alcohol, marijuana, and GHB etc

Alcohol also? That could explain why I had 2 days of recovery to pre-fin state after I drunk a lot at the party

this is exactly what i also experienced

[frk]

I just stumbled upon this: benzobuddies.org/forum/index … ic=18353.0 . I thought it might be of interest to you. When reading this thread, I was asking myself how many guys there actually used benzos to treat anxiety and depression that was actually caused by their finasteride usage…

I am so happy I was lucky enough to discover this site after one week of fin before I did permanent damage to my body. I can’t thank you enough for this. I’m trying to help whenever I can.

Good luck.

[Mew]

[Size=4]It’s official:[/size]

[Size=4]December 2010 – Depression has been added by Merck USA as an officially reported post-marketing side effect from Propecia (Finasteride) use.

Read Details: viewtopic.php?f=24&t=4666[/size]

[Mew]

Researchers now suspect low levels of Allopregnanolone (a neurosteroid) could be a factor in Multiple Sclerosis, as noted below.

Finasteride inhibits Allopregnanolone production as noted here:
viewtopic.php?f=8&t=202
viewtopic.php?f=8&t=38

Interesting to note that loss of hydroxysteroid dehydrogenase enzyme function (ie, 3a-HSD) was identified as a key culprit in the below. Allopregnanolone synthesis requires functional 3a-HSD enzymes.

3a-diol G (metabolite of DHT, via DHT -> 3a-HSD enzyme -> 3a-diol G pathway) has been documented to be surpressed by Finasteride in the FDA clinical trials at similar amounts as DHT, and many men on Propeciahelp.com have documented below range 3a-diol G levels post-drug: viewtopic.php?f=4&t=2763

It would be interesting to test 3a-HSD enzyme activity, somehow. The below info is more related to the cognitive effects that can arise by inhibiting Allopregnanolone, however.

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[Size=4]Genetic abnormality found in MS patients [/size]
theglobeandmail.com/life/health/new-health/paul-taylor/genetic-abnormality-found-in-ms-patients/article2176500/

"Multiple sclerosis patients enrolled in a study were found to have a genetic abnormality that leads to reduce brain levels of a specific neurosteroid called allopregnanolone, according to an international research team.

Previous studies have shown that neurosteroids play a key role in some brain functions as well as repair. The discovery, published in the journal Brain, could lead to new treatments for MS, which is characterized by inflammation and damage to myelin, the protective covering of nerve cells. As the disease progresses, it can affect vision, hearing, memory and movement."

[Size=4]Brain Steroids Found Lacking in MS[/size]
medpagetoday.com/clinical-context/MultipleSclerosis/28655

Individuals with multiple sclerosis (MS) may have impaired production of important neurosteroid molecules in their brains, so replacement therapy could be helpful, researchers said.

Autopsy findings from 16 MS patients showed high expression of micro-RNA molecules in white matter that suppress enzymes responsible for neurosteroid synthesis, particularly allopregnanolone, according to Christopher Power, MD, of the University of Alberta in Edmonton, and colleagues.

The researchers also confirmed that levels of allopregnanolone and other steroids were depressed in the MS patients’ white matter, they reported online in Brain.

Similar findings emerged from analyses of mice with experimental autoimmune encephalitis (EAE), a standard model of MS.

Most strikingly, treating the animals with allopregnanolone partly normalized their behavioral deficits and reduced levels of neuroinflammation and injury to nerve fibers, Power and colleagues indicated.

“These studies are the first report of perturbed neurosteroidogenesis in multiple sclerosis and the related model, EAE, which also showed improved outcomes in terms of neurobehavioural deficits, neuropathology and neuromolecular changes with neurosteroid (allopregnanolone) replacement,” they wrote.

“The neurosteroid allopregnanolone, or perhaps closely related compounds, might represent unique therapeutic options for people with multiple sclerosis.”

Micro-RNA molecules help regulate gene expression throughout the body. Power and colleagues guessed that up- or downregulation of these molecules could play a role in the MS disease process.

Although the broad outline of MS pathology is well established – an autoimmune attack on the myelin sheaths that surround and protect nerve fibers – how and why it arises and other details remain uncertain.

As Power and colleagues explained in the Brain paper, “the working hypothesis was that specific changes in micro-RNA profiles in the white matter of patients with multiple sclerosis point to disordered homeostatic mechanisms in the central nervous system, leading to new perspectives on multiple sclerosis pathogenesis.”

They analyzed samples of white matter from the 26 individuals with high-throughput microarray techniques. Individual micro-RNA species showing more than 1.5-fold differences between MS patients and controls were flagged for closer examination.

Some two dozen micro-RNAs were differentially expressed to that degree, with about half upregulated and half downregulated.

Checking the biological pathways affected by these molecules led the researchers to hone in on just three – dubbed miR-338, miR-155, and miR-491 – as most likely involved in the MS disease process. All three were upregulated in the MS patients.

In vitro experiments showed that these species inhibited expression of hydroxysteroid dehydrogenase enzymes necessary for steroid synthesis in the brain. The steroid most affected was allopregnanolone, although dehydroepiandrosterone synthesis also was suppressed.

Studies in EAE mice also showed reduced neurosteroid levels in their brains. Intraperitoneal injections of allopregnanolone in mice shortly after induction of EAE led to improvements in several markers of disease, relative to sham-treated animals.

These included:

Preserved myelin in the spinal cord
Reduced reactivity in immune cells
Lower immunoreactive cell counts in the spinal cord
Reduced axonal injury
75% reduction in clinical disease severity scores

Although neurosteroids had not previously attracted much attention in MS research, their involvement should not be a surprise, Power and colleagues argued.

These substances "exert diverse effects on neural cell function and survival in the brain," they wrote. In particular, allopregnanolone is recognized as a regulator of GABAergic function, which in turn affects behavior and survival of glial cells and neurons.

Allopregnanolone also appears to diminish proinflammatory activity of at least some immune cells, the researchers indicated. But unlike glucocorticoids, it lacks broad immunosuppressive effects – “hence, this and related molecules might provide new therapeutic options, devoid of the side-effects of common immunosuppressive therapies,” Power and colleagues wrote.

[golf]

When is the medicinal version of allopregnanalone getting approved again?

Im also curious how injections of allopregnanelone (or 3ahsd) would effect 3adiolg

[bluecloud87]

Mew, that MS article was a great find. Very scary, however.

Doesn’t progesterone convert to allopregnanolone?

Maybe it would be worth posting about progesterone/ alloregnanolone on the bodybuilding forums?

[moonman1]

Allopregnanelone and Alzheimer’s.

pnas.org/content/107/14/6498.full.pdf

[Sim882]

@bluecloud87

Mew, that MS article was a great find. Very scary, however.

Doesn’t progesterone convert to allopregnanolone?

Maybe it would be worth posting about progesterone/ alloregnanolone on the bodybuilding forums?

My dr gave me 20mg of daily progesterone - disast er

[Oitspitw]

Why sim? I’m on 25mg of daily oral pregnenolone for past couple weeks. No improvement. How is progesterone messing u up and how long you taking it?

I’m gonna try to get all my mineral and amino acids checked to make sure my precursors are all ok.

[Sim882]

@Oitspitw

Why sim? I’m on 25mg of daily oral pregnenolone for past couple weeks. No improvement. How is progesterone messing u up and how long you taking it?

I’m gonna try to get all my mineral and amino acids checked to make sure my precursors are all ok.

took it for 2 weeks and became extremely fatigued.

My fatigue has got significantly worse past 12 months, following all of which contributed:

-pnemonia

• trying to swtich from HGH to GHR-6
• progesterone
• trying to get off HGH
• trying DHEA and pregenolone

[anon70124568]

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