Allopregnanolone May Soon Be Approved As A Fast-acting Antidepressant

[koky]

I'm curious as to experiences substituting 5A-dhp for progesterone

 

[Robert Williams]

You can bet there will be a oral version coming soon also... this is also in development and moving on to stage 3 trials
SAGE-217 - Wikipedia

 

[broozer]

You can bet there will be a oral version coming soon also... this is also in development and moving on to stage 3 trials
SAGE-217 - Wikipedia

but not until 2021 id think...watch the interview with sages' CEO on bloomberg

 

[Robert Williams]

but not until 2021 id think...watch the interview with sages' CEO on bloomberg

Yes that's the date I also have seen posted on numerous sites,

 

[broozer]

any news on the release for SAGE217 ? on their website it says they're in phase 3 now

 

[limitless77]

Low doses of SSRI's are known to raise allopregnanolone levels, by inhibiting the enzymes that convert it back into 5a-dhp:

"Scientists from the University of Bristol, UCL and the University of Sao Paolo-Ribeirao Preto in Brazil have shown in rats that the anti-depressant (fluoxetine) can inhibit a specific enzyme in the brain and could be used to alleviate symptoms of progesterone withdrawal such as PMS and possibly also postnatal depression.
The new research shows that the antidepressants such as fluoxetine inhibit the enzyme, which deactivates allopregnanolone, therefore maintaining the chemical balance of this in-built tranquilizer in the brain.

...Short term treatment with a low dose of fluoxetine immediately prior to the rat's premenstrual period not only raised brain allopregnanolone and prevented the development of PMS-like symptoms but also blocked the increase in excitability of brain circuits involved in mediating the stress and fear responses that normally occur during this phase of the cycle.
Surprisingly, in the case of rats, the effective dose of fluoxetine was well below that needed to produce anti-depressant effects. The effects of the drug were seen within hours of administration, unlike the two to three weeks of treatment normally needed when fluoxetine used to treat depression."

They are basing these new drugs on the mechanisms of the SSRI's at extremely low doses.

any idea what are these doses?

 

[NewACC]

do you think the antidepressant effect we feel after ejaculation is a result of increased Allopregnanolone ?

I don't know how ejaculation can cause antidepressant activity, because I feel A LOT DEPRESSED after ejaculation

 

[tommyg130]

The patents on most SSRI drugs have either expired or are close to expiration. Lately, there have also been a number of high profile cases obtaining favorable court outcomes by blaming SSRI drugs for a host of human criminal behaviors or adverse health events. As such, Big Pharma is desperate to find the "next big thing" in depression treatment, and preferably without the terrible side effects of SSRI drugs. Back in the 1960s it was discovered that GABA agonists had not only anti-anxiety but also rapid antidepressant effects. At the time, a number of GABA agonist steroids were in use as general anesthetics and it was discovered that these steroids also had antidepressant effects. Further research revealed that the progesterone (and 5a-DHP) metabolite allopregnanolone is one of the most potent endogenous antidepressant steroids. Since then, a number of companies have been quietly working on bringing synthetic versions of allopregnanolone to the market. It looks like one of them is now very close to being approved as a "novel", fast-acting antidepressant and Scientific American is running a story on that steroid. If Brexanolone gets approved, I would not be surprised if allopregnanolone, 5a-DHP, and even progesterone get pulled from the market as competing drugs that erode Brexanolone's profits. I guess the good news is that Big Pharma is finally going full-Peat in most of its drug development efforts

PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone measured in... - PubMed - NCBI
An Entirely New Type of Antidepressant Targets Postpartum Depression
"...Based on Mody’s research, a company called Sage Therapeutics has developed a new drug to treat postpartum depression. Administered intravenously, the medication elevates allopregnanolone. It does not target the GABA receptors directly but has a similar effect: Higher levels of the steroid help activate the receptors, keeping GABA at a healthy level. Two phase II clinical trials led by Meltzer-Brody at U.N.C. tested the new drug in severely depressed postpartum women and had successful outcomes, resulting in a significant improvement in the self-reported mood of 70 percent of the new mothers. Most striking, the effect occurred immediately after the drug was administered, and the benefits persisted for 30 days. The first two trials included a total of only 25 women but Sage has since conducted two phase III trials with a combined 246 postpartum women, and preliminary reports are promising. The drug, called Brexanolone, is now under review by the U.S. Food and Drug Administration. If approved, it would be one of the first antidepressants with a new mechanism of action developed in recent years. Beyond postpartum depression, Mody hopes these drugs could treat other types of hormonal depression such as premenstrual dysphoric disorder—an extreme version of premenstrual syndrome (PMS)—and depression around the time of menopause. Mody is also looking into whether nonhormonal depression in women is influenced by this system. Women are twice as likely to suffer from generalized depression than men, so it is possible there is a hormonal component to their depression outside the established periods of extreme hormone fluctuation."

Hi! Would using your allo-p supplement raise progesterone or preg levels via blood work? Both? Neither? If my progesterone is bottomed out via blood work would it be safe to say I have low allopreg? I’m looking to raise both. Is there one supplement that could raise both ?