Print Friendly, PDF & Email

Pregnenolone is a supplement that everyone should read about.

It has helped me by increasing mood, motivation, and brain function.  Pregnenolone feels like a steroid for the brain to me.

Our genetics can affect how pregnenolone works in our bodies. For example, a variation (rs6971) in the gene TSPO can influence internal production meaning you may need to take a supplement (R).

Go to SelfDecode to discover how you can have your genetic makeup investigated for such variations.

10153855_1563733560511823_7315609736208167559_n

Pregnenolone Intro

Pregnenolone and its sulfate (pregnenolone sulfate) are excitatory neurosteroids – they stimulate the brain (R).

Pregnenolone is the main steroid produced from cholesterol (R).

It is produced in three main organs: the brain, gonads and adrenal glands (R), but the salivary gland and white blood cells are also capable of producing pregnenolone (R, R).

Pregnenolone is neuroprotective and enhances learning and memory (R, R) and increases the amount of deep sleep (R).

Pregnenolone has a beneficial effect on mood (R, R).

Ever since the 1940s, pregnenolone was reported to have anti-stress and mood-elevating effects on factory workers, students, and pilots (R).

Pregnenolone has a beneficial effect in various neuropsychiatric disorders (R, R), and relieves anxiety and depression (R).

Pregnenolone is the main precursor of many other steroid hormones (R). For example, pregnenolone increases the level of other neurosteroids such as pregnenolone sulfate and allopregnanolone.

Allopregnanolone is another molecule that increases the growth of neurons, decreases cell death and inflammation (R).

Like most products that can’t be patented, pregnenolone doesn’t have large clinical trials for various conditions.  This is where Selfhacking comes in and testing out if pregnenolone works for you.

My Experience and What I Use

I’ve been taking pregnenolone for 3-4 years, on and off.  I really love it.  You need to find the right dosage.  Pregnenolone doesn’t work for a lot of my clients.  The most common issues with pregnenolone are that it gives people anxiety and they have more trouble sleeping.

For me, it will cause sleep issues if 1) I take too much and 2) I don’t exercise enough and 3) I don’t exercise enough earlier in the day.  Exercise makes pregnenolone convert to other hormones to produce cortisol.  If I exercise later in the day with pregnenolone, it makes me more wired than ordinarily (perhaps I have a larger cortisol spike).

I find when I was having chronic inflammation, I was deficient in pregnenolone.  I’m not deficient now, but since I have a very heavy workload, I use more up, so in these times it’s useful.

Pregnenolone

  • Longevity9.5/10
  • Inflammation9.0/10
  • Mood9.6/10
  • Cognition9.5/10
  • Energy9.0/10

        Pros

  • Great for cognitive enhancement
  • Is relaxing and stimulating at the same time
  • Increases motivation
  • Increases wakefulness
  • Increase hormones
  • Good for libido
  • Good for longevity

        Cons

  • May increase anxiety for some
  • Can cause some sleep issues

The Good

1) Pregnenolone is a Nootropic and Boosts Cognitive Function

shutterstock_247872679

Pregnenolone and pregnenolone sulfate act as signaling molecules in the brain where they stimulate neuronal activity (R, R).

Pregnenolone increases the growth of neurons (R).

Pregnenolone enhances myelination, enhances the formation of new synapses, and has neuroprotective properties.  Myelin is a fatty layer that electrically insulates nerves, and is essential for their proper functioning (R).

Pregnenolone sulfate enhances the survival of newborn neurons in adult mice (R).

Pregnenolone also improves neurological recovery (R).

Pregnenolone and pregnenolone sulfate protect neurons against cell toxicity and toxin-induced cell death (R, R).

Low blood levels of pregnenolone are found in the elderly, including those with dementia (R).

Nootropic Mechanism:

Pregnenolone regulates neuronal function by activating and deactivating GABAA, NMDA, sigma-1, cholinergic and dopamine receptors (R).

Pregnenolone sulfate decreases the activity of GABAA receptors, kainate, and AMPA receptors and increases the activity of NMDA receptors (R).  (This might be why pregnenolone increases anxiety in some.)

When bound to receptors, pregnenolone, and its metabolites cause a series of reactions, including the stabilization of microtubules, the increase of ion flux into cells, and dopamine release (R).

By regulating microtubules, pregnenolone may increase neuronal development and plasticity of neurons during aging (R).

Joe’s Experience: Pregnenolone boosts cognitive function for me and is one of my favorite nootropics.  It goes well with infrared therapy/LLLT.

2) Pregnenolone Improves Learning and Memory

brain_133874900

Pregnenolone/pregnenolone sulfate enhance learning and memory in mice and rats (R, R, R).

Pregnenolone/pregnenolone sulfate results in better performance of mice and rats in various mazes (R).

Pregnenolone sulfate blocks chemical-induced amnesia in rats (R, R).

Pregnenolone sulfate prevents learning and memory deficits induced by certain drugs (R).

Joe’s Experience: Pregnenolone boosts learning and memory for me.

3) Pregnenolone Stimulates Deep Sleep

Sleeping

Pregnenolone and its derivate allopregnanolone stimulate deep sleep in animal studies (R).

Low concentration of pregnenolone sulfate increased the amount of REM (paradoxical sleep), while high concentrations increased both REM and slow wave sleep (deep sleep) (R).

Pregnenolone increased the amount of time spent in deep sleep in human volunteers (R).

Deep sleep, in turn, helps consolidate memories.

Joe’s Experience: Pregnenolone is more likely to worsen your sleep than benefit it. I have found pregnenolone (at 50mg) delays sleep onset and results in less sleep for me.  Other people also report insomnia from these doses.

4) Pregnenolone Relieves Schizophrenia Symptoms

Pregnenolone can potentially be used to alleviate and treat certain symptoms of schizophrenia (R).

Pregnenolone levels are lowered in the brain of schizophrenic patients (R, R).

Elevations in pregnenolone and allopregnanolone after pregnenolone treatment in schizophrenia were correlated with cognitive improvements (R).

Treatment with pregnenolone sulfate reduced schizophrenia-like symptoms and rescued the cognitive deficits in mice (R).

Pregnenolone reduced symptoms in patients with schizophrenia and schizoaffective disorder (R).

Pregnenolone improved attention, verbal and working memory performance in schizophrenic patients (R, R).

Low dose pregnenolone together with antipsychotics reduced drug-induced side effects in schizophrenic patients (R).

5) Pregnenolone Boosts Mood and Relieves Depression

Sleeping

Decreased pregnenolone and allopregnanolone levels have been linked to depression (R).

Pregnenolone has significant mood-stabilizing effect (R).

Pregnenolone enhances the activation of neurocircuits that control emotion (R).

Blocking allopregnanolone impairs social and emotional functioning (R).

In response to emotional cues, allopregnanolone reduces the activity in brain regions associated with the generation of negative emotion (R).

Pregnenolone reduces depression in patients with bipolar disorder, recurrent major depressive disorder and history of substance abuse/dependence (R, R).

A synthetic pregnenolone derivative acts as an antidepressant in rats (R).

Depressive disorders are associated with neuronal abnormalities in brain microtubule function (R).

By increasing formation and stability of tubules, pregnenolone increases neurite growth (R) – and can combat depression.

Joe’s Experience: Pregnenolone boosts mood and motivation quite a bit.  In fact, it increases mood and motivation more than anything else I’ve tried.

6) Pregnenolone is Anti-Anxiety

Patients with general anxiety disorder have significantly lower levels of pregnenolone sulfate (R).

Allopregnanolone (measured after taking pregnenolone) reduces self-reported anxiety (R).  

Pregnenolone reduces irritability in adults with autism spectrum disorder (R).

Allopregnanolone is a potent activator of GABA (A) (R).

Joe’s Experience: Pregnenolone does have anti-anxiety effects, but I’ve had some clients tell me it increases their anxiety.  For me, it makes me more emotional and more passionate.  This includes good and bad emotions.  For example, a breakup would feel worse if I’m taking pregnenolone, but you are more likely to fall in love, in my experience.

7) Pregnenolone Balances the Immune System

immune_231473869

Synthetic pregnenolone derivatives act as antiviral agents against Herpes Simplex Virus (R).

Pregnenolone suppresses immune cells to restore immune balance (homeostasis) (R).

8) Pregnenolone Increases Libido (Anecdotal)

I haven’t seen any studies with libido and pregnenolone, but I notice a difference and my clients often do.

This could be from increasing ‘downstream’ hormones such as progesterone, DHEAtestosterone, etc…

9) Pregnenolone Reduces Alcohol Preference and Intake

Acute but not chronic pregnenolone significantly reduces alcohol preference and intake in rats (R).

Pregnenolone treatment significantly reduces alcohol self-administration in rats (R).

10) Pregnenolone Kills Brain Cancer cells

Cancer

Pregnenolone induces glioma cell death (R).

11) Pregnenolone Protects from Cannabis Intoxication

Pregnenolone protects the brain from cannabis intoxication (R).

The administration of THC, the main active component of marijuana, substantially increases the production of pregnenolone (R).

Other

Pregnenolone has Anti-Arthritic, Anti-Ageing, and Anti-Fatigue properties.  It also lowers cholesterol (R).

The Bad

1) Pregnenolone Can Impair Memory

Pregnenolone sulfate impairs memory acquisition (R) and memory retention (R) in rats.

Allopregnanolone impaired learning in rats (R).

2) Pregnenolone Can Reduce Wakefulness

Pregnenolone sulfate promotes sleep and can impair wakefulness (R).

3) Pregnenolone Can Cause Anxiety

I haven’t seen this in studies, but in some clients, pregnenolone can increase anxiety, even though it also has anti-anxiety actions.

Safety of Pregnenolone

Studies conducted in the 1940s and 1950s showed that pregnenolone at 25–500 mg/day was safe and well tolerated in humans, with minimal side effects, and did not affect weight, heart rate, blood pressure, menstrual cycle, or glucose levels (R).

Pregnenolone Dosage

Pregnenolone is very safe as far as toxicity.

Generally, if you do get a side effect from pregnenolone, you can stop taking it and it will go away.  I’ve never heard of permanent negative effects.

I recommend starting out with 5mg if you’re healthy and make sure to pay attention to your sleep.

If you have schizophrenia or chronic inflammation, you will want to take 25mg a day (if your doctor thinks it’s a good idea).

What Else Increases Pregnenolone?

Other:

  • THC, the main active component of marijuana, substantially increases the production of pregnenolone (R)
  • Stress (R)
  • SSRIs and Antipsychotic drugs used for treating depression and bipolar disorder: clozapine, olanzapine and fluoxetine (Prozac) elevate pregnenolone levels in the brain and blood of rats (R).

Pregnenolone Goes Well With

Pregnenolone goes well with aromatase inhibitors so that it doesn’t convert to estradiol.

My favorite aromatase inhibitors include:

Inhibiting cortisol production may also help.

This way pregnenolone will go more to making progesterone, DHEA and testosterone instead of estradiol and cortisol.

images

When to Take Pregnenolone

I recommend taking it right upon awakening and exercising in the morning and an empty stomach – so that it gets absorbed quicker.

Pregnenolone on SelfDecode

Buying Pregnenolone

There are many dosages of pregnenolone you can buy.  You can either buy a smaller amount or larger amount and break up the capsule.

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

HOW WOULD YOU RATE THIS ARTICLE?

1 Star2 Stars3 Stars4 Stars5 Stars (70 votes, average: 4.21 out of 5)
Loading...
TWEET
0

49 COMMENTS

  • Pat

    Whisper, thanks for your reply. We are of the same age and problems, so your story helped me decide to try the supplement. I wanted you to know the difference between thyroid and TSH though. TSH is thyroid stimulating hormone. When TSH is high it means your body is trying overly hard to produce enough thyroid, possibly without results. Taking thyroid medications will hopefully increase your T3 thyroid level and decrease your TSH level.

  • dean

    I have read that it can cause hair loss however it’s not listed in here so is this only in very high doses.

  • farzaneh

    I have fibrocyctic breast and I am 39,I was wondering if I want to take prognenolone,my breast cycts increase or maybe I willbe under risk of cancer with taking it.by the way I suffer from pms for ages.

  • Whisper

    Is Pregnenlone hard on the liver? And do pregnenlone that dissolve under your tongue “Work Best”. I have heard they might absorb faster. I take Pure Formula, started with 5 mg. Then went to 10 mg.
    I have sipuffered Low Adrenals almist all my life off and on. Stress has been a huge factor…I am a type A personally and care deeply about everything and everyone. I am getting better just try to relax more. My Thyroid Levels TSH was far to high near 10.00 with the understanding I needed more Thyroid small amount. The issue was Uterus Polyps …Estrogen was to high and I am past menopause. Not a good thing! Thankfully Polyps all gone Estrogen dropped faitprly swift…it did effect my Adrenals being to high in Estrogen now lower as my TSH is Much better , same dose of Thyroid meds now. I started Pregnenlone, made a huge difference for me at 10 mg. I might drop it to 5 mg. Most times I sleep 5 or 6 hours, I do feel rested. Sometimes maybe once a week or do I take a 2 hour nap. Best sleep ever. I think the Progesterone is helping, I have no doubts, but think taking a lower dose it needed. I will lower and see if I will sleep longer at night times. I might be taking the Pregnenlone to late in evening also. Also are the Rub in Creams good or drops? Dr. Ray Peat makes Progesterone in drops… with pure Vitamin E. Safest drops I ever used years ago. 3 drops is all you need daily. I spoke with him years ago, extremely kind gentleman…he told me my Thyroid was not working well he was right took a long time to find that out. I like reading intelligent conversations, but am careful to use my own judgement and not believe everything I read. We have to remain wise. Wisdom is imperative and of great importance. Thanks for sharing each of you and Joe I read your page daily your extremely knowledgeable. Thank you for everything you share. You have a Gift! A huge blessing…sorry if and misspelling, my iPad loves to spell for me. Likes adding A to my messages. *:-)

  • Gilbert

    The flow chart diagram illustrating the pregnenolone conversion to cortisol is very instructive but very misleading. It shows all the steps going in only one direction. Reality is that most of the reaction can and do go both ways. For example,

  • Karen

    Thanks Kelly the reason why I am taking it is to help lower cortisol. For some reason when I bumped up to 30mg my period was very late. I stopped taking it and what do you know a few hours later my period came on. Naturopathic doc had me lower to 20mg for the time being. I do have adrenal fatigue. Appreciate your reply! I’ve taken 30 mg previously but never had cycle issues. I guess the pregnenolone is doing its job?

  • Kelly

    Sounds like the pregnenolone was lowering cortisol, so when you stopped taking it, your body started producing more cortisol. I’d suggest doing a saliva cortisol rhythm test so you know for sure if you have adrenal fatigue.

  • Karen F

    I worked my way up to 30mg/day of Pregnenolone and now I’m 33 days late for my period. No chance of pregnancy. Do I need to lower my dose in order to get a regular cycle again? This didn’t happen the last time I took it, not sure why it’s happening now. Any advice is appreciated!

  • Jeneba

    Please read the work of Dr. Rachel Yehuda. PTSD lowers cortisol levels.

  • Michael (NW)

    Hi, I was taking 10mg of Pregnenolone for some time for adrenal fatigue. 5mg in the morning and 5mg in the evening. I’ve been feeling much better, sleeping better, no stress, etc…. So, I recently decided to stop taking it, and a couple of days after I started having insomnia. I don’t feel sleepy any more. I just lay there alert although my mind and body are exhausted. Is this a symptom of discontinuing Pregnenolone?

  • John

    Wanting to use pregnenolone for its mental benefits that I have read on the net, but I dont want to mess with my fertility (after all pregnenolone is a pro-hormone from what I understand??).

    Could not find anything on the internet about it, theoratically it could be supressive of the endocrine system.

    What would be a good dose to start with

  • Claire

    Is this recommended for someone with c-ptsd? Cortisol levels are higher with this and although the benefits of mood stabilizers and lowering anxiety and deep sleep sound amazing, I’m checking whether it would cause more harm than good with this disorder?

  • Kelly Ward

    Joe, would DIM be a good AI as well? Thanks!

  • Pat

    Ditto to your experience…after bioidenticals in my late forties dosing 100mgs of pregnenolone…it is been consistently in my life….I am 66 and definitely feel the old age after my week ” break” every two months…it is miraculous in memory, mood and reducing arthritic pain…which comes on gang busters when I am off it…I take it in the morning, empty stomach…and I use Allergy Research micronized brand.

  • Bruce

    Your T is very high in my book, but if you like it so, perhaps you might respond differently to preg than others described here because of it. Sleep is extremely complex and can be effected even by your elevated expectations for the effects of preg, so be patient with your trial. In my personal experience, 5-15mg preg will never render you permanently insomniac, so relax, stop your trial for a while until your sleep returns to normal. The placebo effect on trials such as yours can be huge, so I’d suggest before trying any new supplement that’s supposed to create a noticeable effect (i.e., not taken on faith like a multiple vitamin that isn’t supposed to be noticeable) that you program your mind to be utterly neutral, doubting the very effects which prompted you to trial it in the first place. Only then will you likely be close to perceiving your body’s or mind’s response. This is good policy as individual response differences to supplements can be huge.

  • Bruce

    I used preg-10mg at night before bed with great success for years from VRP.com, one of the first advanced research based supplement suppliers. Then, after joining LEF.ORG, switched to their 100mg version with similar success and deepening of sleep for years. Then, after taking their male hormone blood test and speaking with their august doctor phone consultant experimented with larger amounts, as much as 200 or 300mg. In just a short time I became somnolent sensitized to preg, like I’ve always been with melatonin and had to stop taking it completely. After about 5 years I’ve come back to it carefully but find it’s very tricky to find a sustainable dose that’s both effective and doesn’t build up over a few days into an overdose and somnolence. There are a couple lessons here (don’t trust doctors:) first listen carefully to your body and experiment slowly with both dose and timing. Stay at a dose that works for you rather than dose for a blood test result. Third, don’t accept overly broad statements viven both here and over the web. This supplement obviously has very complex interactions that haven’t been captured by science nor in general practice but can be very effective for a number of reasons. You will find Sahiel’s idiosyncratic conclusions based mostly on self observations repeated all over the internet claiming that even 10mg preg could be dangerous. And then you find doctors on the advice lines at Life Extension Foundation unleashing hundreds of mg dosages onto members. It’s the Wild West of nutrition science, but the rewards can be worth the risk.

  • Christian

    So have a question. I’m 41 (technically) and have self-hacked for many years and am pretty darn healthy actually. Recently have been reading Lessons from the Miracle Doctors and your site and the one thing I started to try was the Pregnenolone…started at 5gm, then 10, then 15mg…after three days really didn’t feel much different but my sleep SUCKED. So I brought it back down to 5mg…and my sleep still stinks (which it never has before) and I’m exhausted during the day and my head is “heavy” and tired. So I read your portion about how it affected your sleep but seeing all the benefits this offers, what am I missing or not doing correctly? I take it in the morning on an empty stomach and to be clear for years I have also been on the Sotto pellet therapy for low T that started about five years ago so my current T is about 800. My energy levels during the day are usually pretty darn good, I don’t do caffeine as my genetics do not tolerate it, eat really good, and workout almost every day…except for the last three actually while taking the preg.

    Any thoughts or advice?

  • Chris

    This may help, in regards to your age and dosage and other things you might want to consider

  • Karen F

    If stress increases pregnenolone and I suffer from anxiety/panic disorder, wouldn’t I have plenty of it already??

  • Samson

    Nevermind Felicia. I don’t who or what you’re referring to. I thought you were referring to the SelfHacked author. The format of this thread is confusing.

  • Felicia L. Jones

    Do you notice the difference when you take turmeric, CoQ10, multi-vitamins? Probably not, as they are taken as a profilactical, not a cure. Is it imperative that you be snotty and arrogant? Am thinking that your intelligence is not as superior as you think it is nor is your soul in good shape. Small, withered and blackened I am assuming. Cheers!

  • Demetra J Mills

    I like LifePro topic pregnenolone with liver bypass.

  • Walter J Crook

    She said, “Maybe it is working.” She is open-minded and willing to consider various possibilities. You immediately come to the conclusion, “They just want to be nice,” without any evidence whatsoever to back up your claim. You are a closed-minded, arrogant, conceited idiot. And, btw, people are allowed to do what they want without your approval, something you are probably not able to comprehend.

  • putting "putting people in their place", in his place

    Turnerschick didn’t say she didn’t notice ANYTHING, just not cognitive improvements or bursts of energy. She could be getting any number of benefits from less stress to reduction of schizophrenia symptoms. Maybe you should try it and see if it improves your reading comprehension

  • Tim

    hi i was wondering, is there a specific form people take to notice a difference as i recall, orally its not very bioavailable if any at all.

    1. Nattha Wannissorn

      Yes Joe uses one from Pure Encapsulations and Biomatrix (links in the article). The one from Biomatrix you can put the drops under your tongue or just rub it in through your skin. I put it under my tongue.

  • turnerschick

    Been taking it for 5 years. No cognitive improvements or bursts of energy to speak of. However, people guess my age range to be late thirties and I’m 60 this year, so maybe it is working.

    1. putting people in their place

      they just wanna be nice. dont know why you been taking something for 5 years and you havent even noticed anything . stupid and waste of money if you ask me.

  • Gretchen Grieser

    Joe – I am a 51 year old female. I recently had my labs done. After reading your article I looked at my results. My Pregnenolone level is 9 ng/dL. My doctor gave me a bottle of 10 mg Pregnenolone tablets to take and said, “follow the instructions on the bottle”. The suggested use is 1 or more tablets a day as directed by your health care professional. I have been taken one tablet a day for a couple weeks but have not noticed any type of change. Any thoughts?

  • peter aris

    increased my libido through increasing my testosterone and went as high as 50mg per day but had to lower as affected my sleep.now take 12 1/2mg 3 times per week,much better

    1. Ken

      Agree totally

  • Isa

    Hi joe
    I have been taking pregnenolone for 24 years
    First recommended by a life extension employee
    I was 46 years old and having menopause symptoms . I started with 50mg and in the last five years I increased it to 100 mg
    I find that the 50 mg tablets by life extension are better for me then the 100mg. So I take 2 of the 50 mg
    Next week I will turn 70 years and I feel great
    I have tried to quit a few times to make sure it’s not psychological, and after 3 weeks I start noticing the lack of it.
    Old age starts creeping on me. I’m slower, more fatigued lacking energy
    I start again and I feel like 40 again
    This is my honest experience ! Not many people not even doctors know about pregnenolone!!
    I must note that the brain alertness is incredible
    I need it! I run two businesses and trade the stock market.
    Best of luck to all. It’s the first time I have the opportunity to share my experience with pregnenolone

    Isa

    1. Maureen

      Wow! That’s really amazing! I just recently started supplementing with Pregnenolone and take 10 mg in the morning when I get up. Do you recommend I supplement it with Resveratrol?

  • michelle frankie

    for me im still completely confused on this one..I for one have too high cortisol which u dont want and consequently when I take this supplement i feel really really bitchy like is that spiking cortisol ive been told i need adrenal support n all i knew were this and dhea…but actually im freagin luving this Relora ..and a tiny bit of dhea…I think I need to niix the preg even though it sounds good..i never feel anything good

  • Paul Smith

    Hi Joe,

    Firstly good article I’m also a fan of Pregnenolone.

    As you mention “you need to find the right dosage.”
    I wonder what if any dosages you recommend.

    I currently have 30mg every other day. Is that about right as I have not been taking it for long so my levels are already probably too low. Once your levels are higher do you generally stick with 10mg?

    Thanks,

    Paul

    1. Joseph M. Cohen

      It depends on too many factors to recommend a dosage. It needs selfhacking.

  • dollartlover

    Is taking progesterone as good as taking pregnenolone for fibrocystic breasts?

  • Santino

    I guess you are confusing something. The pregnenolone steal means that it is converted into progesterone to make cortisol. So there is not enough left to make DHEA.

  • Don

    i cant believe it was not mentioned that pregnenolone is not bioactive orally. it has a lot of research showing this but yet it is completely absent in this article.

    1. Joseph M. Cohen

      Reference? Something is causing similar benefits as is mentioned when ingested.

      What about sublingual?

  • Dimoff

    Each time I take pregnenolone (And I’ve taken it hundreds of times) I can feel my liver afterwards. Similar to testosterone feeling.
    Plus, is my hair going to fall out from it in case I have the rest of the balding genes? Probably yes.

  • Santino

    Hello Joseph,

    thanks for that article.

    I wonder why you think it is negative if pregnenolone get converted to cortisol. You know that cortisol is a very important hormone (you wrote yourself in another post).

    If your body takes the pregnenolone to make cortisol, he does it for a reason (for example because of a stress response). And I don’t see any negative point here.

    Actually, people often get sick because at some point, their adrenals are no longer able to give a strong enough cortisol response. Yes, high cortisol is associated with a lot of negative things (depression, impaired memory etc. etc.) However correlation is not causation and imagine you had the same stress but low cortisol levels. You more likely would get pretty sick (inflammatory diseases, fatigue, exhaustion).

    So I don’t feel there is a reason to worry that the body makes too much cortisol out of it. The body will make what he needs the most, and if that is cortisol, that other environmental factors should be changed (for example lowering stress).

    Also I don´t think that cortisol impairs immunity (only excess would do so). In fact if you have too low cortisol, your immunity is impaired. Dr. Jeffries had a lot of experience with patients and cortisol replacement and wrote the book “safe uses of cortisol”. His observation was that physiologic doses of cortisol increase the peoples ability to overcome infections.

    So why do you think that it bad if the body takes the extra pregnenolone to make cortisol?

    Another question I have for you, which would be cool to have a review about it progesterone.

    I think that progesterone can have many of the positive effects of pregnenolone and is an underestimated hormone in males. The body also can make cortisol if he needs it and the body also could make testosterone. It seems to help to balance the oestrogen/estradiol ratio and promotes an anti-inflammatory TH2-profile.
    It doesn’t have the possible negative side effects of pregnenolone (anxiety, irritability etc.). The only disadvantage for me would be that the body could not make DHEA (which could be supplemented as well, again without causing anxiety like pregnenolone does for many).

    What you think about hacking the system with progesterone in patients that have too low cortisol or have TH1 dominant inflammatory diseases?

    1. Anthony

      100% agree with you on cortisol! I have seen the MOST profound improvements with my clients on physiologic use of hydrocortisone. Faster healing, better glucose metabolism and skyrocketing energy and sense of well being!

  • Dylan Monahan

    I wonder if, in cases where memory appears to be negatively affected, if its potential GABA modulation is in play: I mean excessive neural inhibition could negatively impact on perception. On the other hand, a person who is for whatever reason, GABAergically dysfunctional, would likely become more capable of concentrating percepatory efforts, leading to results indiciative of improved memory. Or I might be parading my ignorance 😀

  • Tony Llabres

    Never been hot on the STEAL issue. Looks to me that once converted to DHEA, the preference is to STEAL (if I must use that word) from DHEA. Most men I see have tanked DHEA levels from a stress response the body cannot manage anymore. Very interesting topic and it dovetails into LOW T.

  • Tania L

    What time of day should pregnenolone be taking and is it best taken with food or on an empty stomach?

    Interesting article. It seems odd that it appears to both help and impair memory. What’s up with that?

    1. Joseph M. Cohen

      Morning, empty stomach.

      Ya, I don’t know.

  • MachineGhost

    I think you’re missing the biggest negative of all: the Pregnenolone Steal.

    1. Joseph M. Cohen

      Pregnenolone steal is incorporated by the idea that it can get converted to cortisol.

  • Leave a Reply

    Your email address will not be published. Required fields are marked *