Jump to content

Pregnenolone


Recommended Posts

rapunzel2

Some information about pregnenolone:

 

A role for Pregnenolone (Sulfate) in synaptic activity-dependent Ca2+ signaling and cAMP response

 

The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years

 

PREG and its metabolites pregnenolone sulfate (PregS) and allopregnanolone in serum are inversely associated with cognitive improvements after oral PREG therapy, raising the possibility that brain neurosteroid levels may be modulated therapeutically.

 

We have regularly advocated both its research exploration and (till then) it’s usefulness as a supplement in enhancing various Hippocampal related processes, and, in particular, as an adjunct in dealing with “some” of those stigmatized as evidencing ADHD symptoms.

 

It is also not inconsistent to assume, as some have reported that pregnenonolone sulfate, while acting on the Hippocampus in improving the pattern and nature of memory retrieval as well as consolidtion, also serves to help coping with ‘so-called “ depression symptoms, as well.

 

Pregnenolone is known to modulate at least two key nerve receptor systems in the brain: NMDA receptors and GABA receptors. NMDA receptors, which weaken with age, are involved in learning, memory, and alertness. Pregnenolone enhances NMDA receptor function. GABA receptors promote relaxation, mental slowing, sedation and sleep. Benzodiazepine drugs (Valium, Librium, Xanax, etc.) activate GABA receptors, while pregnenolone inhibits GABA receptors.

 

Thus, too little NMDA activity combined with excessive GABA activity would tend to promote mental sluggishness and depression. Since pregnenolone raises NMDA activity and lowers excessive GABA activity, pregnenolone seems to be a natural antidepressant.

 

Indeed a recent study of 27 depressed patients found that their cerebrospinal fluid (which circulates through the brain and spinal cord) was significantly lower in pregnenolone than in 10 non-depressed volunteers. .

 

Fast excitatory synaptic transmission that is contingent upon N-methyl d-aspartate receptor (NMDAR) function contributes to core information flow in the central nervous system and to the plasticity of neural circuits that underlie cognition.

 

Hypoactivity of excitatory NMDAR-mediated neurotransmission is hypothesized to underlie the pathophysiology of schizophrenia, including the associated cognitive deficits.

 

PregS is derived from PREG, the precursor of all neurosteroids, via a single sulfation step and is present at low nanomolar concentrations in the central nervous system. PregS, but not PREG, augments long-term potentiation and cognitive performance in animal models of learning and memory.

 

In this report, we communicate the first observation that PregS, but not PREG, is a potent (EC50 2 pM) enhancer of intracellular Ca(2+) that is contingent upon neuronal activity, NMDAR-mediated synaptic activity, and L-type Ca(2+) channel activity.

 

Low picomolar PregS similarly activates cAMP response element-binding protein (CREB) phosphorylation (within 10 minutes), an essential memory molecule, via an extracellular-signal-regulated kinase/mitogen-activated protein kinase signal transduction pathway.

 

This action of PregS upon CREB (cAMP response element-binding protein) is especially interesting as the role of cAMP action in excitatory Hippocampal cells is being further understood (and we have just a moment ago posted research on the role of consolidation in the Hippocampus and cAMP action in those cells.

 

Taken together, the results are consistent with a novel biologic role for the neurosteroid PregS that acts at picomolar concentrations to intensify the intracellular response to glutamatergic signaling at synaptic but not extrasynaptic, NMDARs by differentially augmenting CREB activation.

 

The discovery of a high potency (nanomolar) signal transduction pathway for PregS-induced NMDAR trafficking to the cell surface via a Ca(2+)- and G protein-coupled receptor (GPCR)-dependent mechanism and a potent (EC50 ~ 2 pM) direct enhancement of intracellular Ca(2+) levels is discussed in terms of its agonist effects on long-term potentiation (LTP) and memory.

 

Lastly, preclinical and clinical studies assessing the promnestic effects of PregS and pregnenolone toward cognitive dysfunction in schizophrenia, and altered serum levels in epilepsy and alcohol dependence, are reviewed in this link

 

http://www.ncbi.nlm.nih.gov/pubmed/24997854

 

Here we have an insight into a genomic signal transduction mechanism by which PregS could participate in memory consolidation of relevance to cognitive function.

 

PregS is present in human and rodent brain at physiologically relevant concentrations and meets most of the criteria for an endogenous neurotransmitter/neuromodulator.

 

PregS likely plays a significant role in modulation of glutamatergic excitatory synaptic transmission underlying learning and memory, yet the molecular target(s) for its action awaits identification.

 

Pregenenolone (in oral form) is readily available inexpensively from all health food outlets and on the internet.

 

http://www.ncbi.nlm.nih.gov/pubmed/25057049

 

 

in 2002- 0,5 tablet cipramil for half a year, ended it uneventfully. in 2006 - citalopram for half a year, ended in horrific state, ditched the drugs CT. 2007-2008 not feeling well but drug free. in 2008 prozac 20mg + quetiapine 25mg. 2009 tried to stop, ended up in hole after couple of months, started zoloft. 2009-2011 zoloft 50mg. went to 25mg in 2011 summer, it resulted in half a year horrible suffering. reinstated, changed drugs, nothing happened. by 2012 beginning suddenly felt great and CT meds. after 4 months came suddenly most horrible human suffering that's possible. was started on prozac and questiapine. started tapering slowly, GFCF diet and Hardy Nutritionals vitamins in 2013 summer. 

current medications: 1) fluoxetine and quetiapine since Aug 2012; 2) Daily Essential Nutrients by Hardy Nutritionals 7 capsules / since May 2013 + omega3; 3) Gluten-free-casein-free diet since june 2013

 

Started withdrawing slowly since april 2013. Mostly around 10% cuts. 

April'13 - March'14: fluoxetine 40mg -> 19,5mg; quetiapine 50mg -> 40mg
April'14-March'15: fluoxetine 19,5mg -> 14,4mg; quetiapine 40mg -> 22mg

April'15-March'16: fluoxetine 14,4mg -> 7,4mg; quetiapine 22mg -> 15mg

April'16-March'17: fluoxetine 7,4mg -> 5,0mg; quetiapine 15mg -> 7,25mg

April'17-March'18: fluoxetine 5,0mg -> 4,0mg; quetiapine 7,25mg -> 0 (as of 1st Feb 2018)!!!!

April´18-March´19: fluoxetine 4,0mg - > 2,3mg. Jumped off fluoxetine 1,4mg due to pregnancy in July 2019. Oct 2019 severe withdrawal syndrome started.

Took mistakenly a complex for hormonal support that included pregnenolone dec2019-april2020. Stopped it april 2020 and immediately severe akathisia started. Have had life threatening akathisia since, 100% disabled, suicidal, very hard to hold on. 

 

Link to post
Share on other sites
  • 5 months later...

I know this is an older post, but I just wanted to share my own experience with Pregnenolone. It's been a game changer for me. I had a bunch of lab work done, and it showed that my natural pregnenolone levels were on the lower end. Supplementing with preg helped big time. 

 

My taper from Haldol/Zoloft was going horribly. Every step down (3-5% per month) I felt like I was on the verge of a psychotic breakdown. Severe PSSD. Severe panic attacks. severe insomnia. Took a year long break from tapering. Added in pregnenolone. My taper was MUCH easier when I started again. No sexual side effects. No anxiety.  Sleep like a baby. I've added in other things too, such as HRT, so I can't prove that it was the preg. But the time frame matches up. And every time I've stopped taking preg, my withdrawal symptoms get much more difficult to manage.

 

I don't disagree that it can make things much worse if you don't need it. Definitely tread carefully here. Preg is more of a men's hormone from my understanding, so women should definitely be wary. In addition, our natural preg levels tend to dip as we get into our 40s, so younger people likely wouldn't need it or benefit from it. But in my personal opinion, it's worth having your preg levels checked via lab work and then - if they're low - starting with a low dose of preg supplementation to see if it helps. And of course using the lowest dose that helps and remembering not to stop taking it suddenly - you'll need to taper preg as well, although from my understanding, the taper can be done over a matter of days or weeks. 

As always, not medical advice and I'm not an admin. Just my N=1 experience. 

-SSRIs starting at age 16 - around 1996. Tried just about every one available for a period of a few years. Stabilized on Zoloft. Have been on it since about 2003.
 
-Added .5mg Haldol for Tourette's and OCD in 2005

 

 

-Tapered in fall/winter of 2012, got off of Zoloft completely. Think I went too fast. Long term withdrawal symptoms persisted for months, to the point that I went back to a 100mg dose.

 

 

-Found this site, tapered using the 10% plan in 2015. It was really rough. Went back on Zoloft at 100mg.

 

 

-Found a great therapist in 2017, learned new self care skills. Started tapering again. Got down to 50mg Zoloft, .4mg Haldol by late 2017 (? - memories a little fuzzy these days)

- Taper got rough again. Held dose at 50mg Zoloft, .4mg Haldol through early 2018. Wife had a baby. Was putting in a lot of hours at work. Had a "poop out". Brain fog, debilitating fatigue, and the works.

- Consulted with a health coach who specializes in mental health and psychiatric drug withdrawal. Developed a plan that involved hormones and supplements. Did a fairly rapid taper on Zoloft and Haldol over the course of 1 year. Felt awful, but it was manageable with the help of the hormones/supplements and frequent visits to my therapist. Psychiatric drug free as of 4/2020. I have about 10 months off of Haldol now, and 6 months off of Zoloft. Battling long term, protracted withdrawal symptoms, and going through h*ll, but so far I've managed to (just barely) keep my high paying job and maintain my relationship with my wife. (Updated 10/2020)

 

Link to post
Share on other sites
  • Administrator

How did you decide to take pregnenolone?

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

Link to post
Share on other sites
16 hours ago, Altostrata said:

How did you decide to take pregnenolone?

 

In the anti-aging/biohacking world, it's fairly common. My HRT doc first had me get labs for it and then based on my numbers, he recommended it. I started taking it. Felt an immediate improvement. Lol, which basically means that I went from barely being able to function to still feeling pretty awful, but at least being able to work and function and go about life like a normal human being.

Anyway, I ended up discussing it with my health coach too. He said that he has all of his guys who are getting off from psychotropic medications get labs for preg and then supplement if warranted, even if they're not doing HRT or anything. In the anti-aging forums that I've researched this stuff in, it seems like half the guys in there are either supplementing with preg or have at least tried it.

I was really surprised to see references in the SA forum here alluding to it being more of a women's hormone. I had no idea. Men definitely make preg naturally in their bodies, and in my experience it's been mostly men whom I've come across who supplement with it.

Self-Hacked has an interesting article on preg that's pretty balanced as far as talking about the possible benefits versus the very real risks and just the fact that there's so much that we don't know yet about pregnenolone as a supplement.

They have some interesting links to research studies on it as well https://selfhacked.com/blog/top-11-scientific-health-benefits-pregnenolone-including-drawbacks/

(Scroll down to #4 Cognitive Function)

Obviously the studies wrere only conducted on animals and are far from conclusive. But (just copying and pasting) preg is being investigated for:

  • Increasing the growth of existing neurons and survival of new neurons [2526].
  • Supporting myelination, the formation of the fatty layer that insulates nerves and helps them properly functioning [17].
  • Protecting neurons against toxicity [12, 27].
  • Deactivating GABAA, kainate, and AMPA receptors and activating NMDA, sigma-1, cholinergic, and dopamine receptors [1728].
  • Stabilizing microtubules, affecting the ion flux into cells and dopamine release [29].
  • Affecting neuronal development and plasticity of neurons during aging [25].
  • Impacting learning and memory [30, 28, 3132]
  • Blocking chemical-induced amnesia and preventing drug-induced cognitive decline [25, 3032].

Happy to discuss further!

My bottom line is just that it seems to help quite a bit, and I've had a medical professional and a health coach who is experienced in psychotropic drug withdrawal recommend it to me, so if it helps me to keep working and supporting my family, I'll keep taking it as long as I don't experience any negative side affects or come across any new information that shows that it's likely to be harmful long term. 

-SSRIs starting at age 16 - around 1996. Tried just about every one available for a period of a few years. Stabilized on Zoloft. Have been on it since about 2003.
 
-Added .5mg Haldol for Tourette's and OCD in 2005

 

 

-Tapered in fall/winter of 2012, got off of Zoloft completely. Think I went too fast. Long term withdrawal symptoms persisted for months, to the point that I went back to a 100mg dose.

 

 

-Found this site, tapered using the 10% plan in 2015. It was really rough. Went back on Zoloft at 100mg.

 

 

-Found a great therapist in 2017, learned new self care skills. Started tapering again. Got down to 50mg Zoloft, .4mg Haldol by late 2017 (? - memories a little fuzzy these days)

- Taper got rough again. Held dose at 50mg Zoloft, .4mg Haldol through early 2018. Wife had a baby. Was putting in a lot of hours at work. Had a "poop out". Brain fog, debilitating fatigue, and the works.

- Consulted with a health coach who specializes in mental health and psychiatric drug withdrawal. Developed a plan that involved hormones and supplements. Did a fairly rapid taper on Zoloft and Haldol over the course of 1 year. Felt awful, but it was manageable with the help of the hormones/supplements and frequent visits to my therapist. Psychiatric drug free as of 4/2020. I have about 10 months off of Haldol now, and 6 months off of Zoloft. Battling long term, protracted withdrawal symptoms, and going through h*ll, but so far I've managed to (just barely) keep my high paying job and maintain my relationship with my wife. (Updated 10/2020)

 

Link to post
Share on other sites
  • Administrator

We're very wary here of steroids in general. People get strange reactions, they can take a long time to go away.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

All postings © copyrighted.

Link to post
Share on other sites
  • 4 months later...
rapunzel2

Michigan, please be extremely careful. I didnt have any issues on taking pregnenolone but developed acute akathisia immediately when I tried to stop it. 10 months later Im still suicidal. akathisia has lessened but depression and anhedonia are indescribable and Im suicidal most of the days. 100 per cent dysfunctional, my boyfriend is taking care of me. very scared will I ever recover. 

in 2002- 0,5 tablet cipramil for half a year, ended it uneventfully. in 2006 - citalopram for half a year, ended in horrific state, ditched the drugs CT. 2007-2008 not feeling well but drug free. in 2008 prozac 20mg + quetiapine 25mg. 2009 tried to stop, ended up in hole after couple of months, started zoloft. 2009-2011 zoloft 50mg. went to 25mg in 2011 summer, it resulted in half a year horrible suffering. reinstated, changed drugs, nothing happened. by 2012 beginning suddenly felt great and CT meds. after 4 months came suddenly most horrible human suffering that's possible. was started on prozac and questiapine. started tapering slowly, GFCF diet and Hardy Nutritionals vitamins in 2013 summer. 

current medications: 1) fluoxetine and quetiapine since Aug 2012; 2) Daily Essential Nutrients by Hardy Nutritionals 7 capsules / since May 2013 + omega3; 3) Gluten-free-casein-free diet since june 2013

 

Started withdrawing slowly since april 2013. Mostly around 10% cuts. 

April'13 - March'14: fluoxetine 40mg -> 19,5mg; quetiapine 50mg -> 40mg
April'14-March'15: fluoxetine 19,5mg -> 14,4mg; quetiapine 40mg -> 22mg

April'15-March'16: fluoxetine 14,4mg -> 7,4mg; quetiapine 22mg -> 15mg

April'16-March'17: fluoxetine 7,4mg -> 5,0mg; quetiapine 15mg -> 7,25mg

April'17-March'18: fluoxetine 5,0mg -> 4,0mg; quetiapine 7,25mg -> 0 (as of 1st Feb 2018)!!!!

April´18-March´19: fluoxetine 4,0mg - > 2,3mg. Jumped off fluoxetine 1,4mg due to pregnancy in July 2019. Oct 2019 severe withdrawal syndrome started.

Took mistakenly a complex for hormonal support that included pregnenolone dec2019-april2020. Stopped it april 2020 and immediately severe akathisia started. Have had life threatening akathisia since, 100% disabled, suicidal, very hard to hold on. 

 

Link to post
Share on other sites
Michigan

Thanks for the note @rapunzel2Yes, I had seen your posts when I was researching Pregnenolone in this forum. Really sorry that you're still struggling. The body has an amazing capacity to heal, and you'll get there if you give it time. I'm finally working on getting off from all of my supplements and meds and whatnot (100% free from psych meds for a year now). I actually tried reducing my pregnenolone dose a couple of times and found that it was pretty difficult. I've managed to reduce the dose by about 1/3, and I'll likely stay there for quite awhile. It's defininitely something that needs to be tapered slowly, just like an A/D. Unfortunately I had a doctor put me on it and I didn't give it as much thought as I should have. When I'm ready to decrease my dose further, unfortunately I think I'm going to have to go the 10% per month route, just like I would do with a psychiatric medication. Again, hope you get some relief soon. Please keep us posted on your progress. 

-SSRIs starting at age 16 - around 1996. Tried just about every one available for a period of a few years. Stabilized on Zoloft. Have been on it since about 2003.
 
-Added .5mg Haldol for Tourette's and OCD in 2005

 

 

-Tapered in fall/winter of 2012, got off of Zoloft completely. Think I went too fast. Long term withdrawal symptoms persisted for months, to the point that I went back to a 100mg dose.

 

 

-Found this site, tapered using the 10% plan in 2015. It was really rough. Went back on Zoloft at 100mg.

 

 

-Found a great therapist in 2017, learned new self care skills. Started tapering again. Got down to 50mg Zoloft, .4mg Haldol by late 2017 (? - memories a little fuzzy these days)

- Taper got rough again. Held dose at 50mg Zoloft, .4mg Haldol through early 2018. Wife had a baby. Was putting in a lot of hours at work. Had a "poop out". Brain fog, debilitating fatigue, and the works.

- Consulted with a health coach who specializes in mental health and psychiatric drug withdrawal. Developed a plan that involved hormones and supplements. Did a fairly rapid taper on Zoloft and Haldol over the course of 1 year. Felt awful, but it was manageable with the help of the hormones/supplements and frequent visits to my therapist. Psychiatric drug free as of 4/2020. I have about 10 months off of Haldol now, and 6 months off of Zoloft. Battling long term, protracted withdrawal symptoms, and going through h*ll, but so far I've managed to (just barely) keep my high paying job and maintain my relationship with my wife. (Updated 10/2020)

 

Link to post
Share on other sites
Michigan

With that being said, I do think that pregnenolone has been instrumental in helping me to continue working and semi-functioning (so far at least, as of 1 year into being med free - knock on wood) after doing a fairly rapid taper from two psych drugs that I had been on for 15 years+. Preg seems like a mixed bag. Powerful and helpful in certain situations related to psych med withdrawal. But to be used with extreme caution due to the fact that we're discovering that it needs to be tapered slowly when you're ready to come off from it. 

-SSRIs starting at age 16 - around 1996. Tried just about every one available for a period of a few years. Stabilized on Zoloft. Have been on it since about 2003.
 
-Added .5mg Haldol for Tourette's and OCD in 2005

 

 

-Tapered in fall/winter of 2012, got off of Zoloft completely. Think I went too fast. Long term withdrawal symptoms persisted for months, to the point that I went back to a 100mg dose.

 

 

-Found this site, tapered using the 10% plan in 2015. It was really rough. Went back on Zoloft at 100mg.

 

 

-Found a great therapist in 2017, learned new self care skills. Started tapering again. Got down to 50mg Zoloft, .4mg Haldol by late 2017 (? - memories a little fuzzy these days)

- Taper got rough again. Held dose at 50mg Zoloft, .4mg Haldol through early 2018. Wife had a baby. Was putting in a lot of hours at work. Had a "poop out". Brain fog, debilitating fatigue, and the works.

- Consulted with a health coach who specializes in mental health and psychiatric drug withdrawal. Developed a plan that involved hormones and supplements. Did a fairly rapid taper on Zoloft and Haldol over the course of 1 year. Felt awful, but it was manageable with the help of the hormones/supplements and frequent visits to my therapist. Psychiatric drug free as of 4/2020. I have about 10 months off of Haldol now, and 6 months off of Zoloft. Battling long term, protracted withdrawal symptoms, and going through h*ll, but so far I've managed to (just barely) keep my high paying job and maintain my relationship with my wife. (Updated 10/2020)

 

Link to post
Share on other sites
  • 1 month later...

Interesting. I was wondering how this would affect WD. My nutritionist put me on it post-partum after he tested all my hormones & nuero-transmitters & most were low. He said it would help me make what I needed & my body would turn it into whatever was needed most. It did help some. I’ve been on 30mg for almost 3 yrs, & didn’t plan to go off since I knew there was a chance it would affect my AD taper. (I took the Dutch urine test, & my progesterone, estrogen, serotonin, epinephrine, norepinephrine, dopamine, & cortisol were low. Which makes sense as my symptoms PP were ExTREME. I assume most of those have corrected much since then, but I want to get off AD before testing again.)

 

Glad I read this about not stopping it CT! 

May 2019 started lexapro 2.5 mg

2020 went to every other day

2021 beginning of Mar, tried to stop but had insomnia

Mar 30, 2021 reinstated 1.25 ev other day, WD symptoms, not enough

April 19, 2021 started liquid, .85 mg/day

May 1, 2021 .8 mg/day

 

Link to post
Share on other sites
×
×
  • Create New...

Important Information

Terms of Use Privacy Policy