Pregnenolone is a supplement that everyone should read about.

It can help by increasing mood, motivation, and brain function. Pregnenolone feels like a steroid for the brain.

What is Pregnenolone?

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, but the salivary gland and white blood cells are also capable of producing pregnenolone [R, R, R].

Pregnenolone is neuroprotective and enhances learning and memory, and increases the amount of deep sleep [R, RR].

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.

Pregnenolone has a beneficial effect in various neuropsychiatric disorders and relieves anxiety and depression [R, R, 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 and 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 self-hacking comes in – testing out if pregnenolone works for you.

My Experience and What I Use

I’ve been taking pregnenolone for 3 to 4 years, on and off and I really love it. However, it can take some time to figure out 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, 2) I don’t exercise enough, or 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 usual (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 Snapshot

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

Pregnenolone Benefits

1) Is a Nootropic and Boosts Cognitive Function

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 enhanced 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) Improves Learning and Memory

Pregnenolone/pregnenolone sulfate enhanced learning and memory in mice and rats [R, R, R].

Pregnenolone/pregnenolone sulfate resulted in better performance of mice and rats in various mazes [R].

Pregnenolone sulfate blocked chemical-induced amnesia in rats [R, R].

Pregnenolone sulfate prevented learning and memory deficits induced by certain drugs [R].

Joe’s Experience:

Pregnenolone boosts learning and memory for me.

3) Stimulates Deep Sleep

Pregnenolone and its derivative allopregnanolone stimulated 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 50 mg) delays sleep onset and results in less sleep for me. Other people also report insomnia from these doses.

4) 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) Boosts Mood and Relieves Depression

Decreased pregnenolone and allopregnanolone levels have been linked to depression [R].

Pregnenolone has significant mood-stabilizing effects [R].

It also enhanced the activation of neurocircuits that control emotion [R].

Blocking allopregnanolone impaired social and emotional functioning [R].

In response to emotional cues, allopregnanolone reduced 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 the formation and stability of tubules, pregnenolone increases neurite growth and can combat depression [R].

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) Is Anti-anxiety

Patients with 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) Balances the Immune System

Synthetic pregnenolone derivatives act as antiviral agents against the herpes simplex virus [R].

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

8) Reduces Alcohol Preference and Intake

Acute but not chronic pregnenolone significantly reduced alcohol preference and intake in rats [R].

Also, pregnenolone treatment significantly reduced alcohol self-administration in rats [R].

9) Kills Brain Cancer Cells

Pregnenolone induced glioma cell death [R].

10) 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].

11) Other Benefits

Pregnenolone has anti-arthritic, anti-aging, and anti-fatigue properties. It also lowers cholesterol [R].

Measuring Pregnenolone in the Blood

You can take a blood test to measure pregnenolone levels. High or low pregnenolone numbers can indicate that certain processes in the body aren’t optimal.

Pregnenolone Side Effects

1) Can Impair Memory

Pregnenolone sulfate impaired memory acquisition and memory retention in rats [R,R].

Allopregnanolone impaired learning in rats [R].

2) Can Reduce Wakefulness

Pregnenolone sulfate promotes sleep and can impair wakefulness [R].

3) 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 to 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 5 mg 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 25 mg a day (if your doctor thinks it’s a good idea).

Pregnenolone and Weight Loss

Pregnenolone can be used by the body to make testosterone and other steroid hormones. Testosterone helps maintain and build muscle mass and boosts metabolism. This may help with weight loss, especially in men who are testosterone deficient [R, R, R].

What Else Increases Pregnenolone?

Other:

  • THC, the main active component of marijuana, substantially increased the production of pregnenolone [R]
  • Stress [R]
  • SSRIs and antipsychotic drugs used for treating depression and bipolar disorder: Clozapine, olanzapine, and fluoxetine (Prozac) elevated 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.

When to Take Pregnenolone

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

Pregnenolone on SelfDecode

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].

Buy Pregnenolone Capsules

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

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About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PHD (ECOLOGICAL GENETICS)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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