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?

Brain-Friendly Steroid

Pregnenolone and its sulfate (pregnenolone sulfate) are excitatory neurosteroids – they stimulate the brain [1].

Pregnenolone is the main precursor of other steroid hormones, produced from cholesterol in three main organs: the brain, gonads, and adrenal glands [22, 3, 45].

It 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 [6].

Pregnenolone protects the nerves, enhances learning and memory, and increases the amount of deep sleep [7, 89].

Pregnenolone is popular for its cognition-boosting antidepressant effects, but it lacks large clinical trials for various conditions. This is where self-hacking comes in – testing out if pregnenolone works for you.

Pregnenolone is a building block for steroid hormones in the body. It also enhances learning and memory and  improves sleep quality.

Snapshot

PROs

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

CONs

  • May increase anxiety in some users
  • Can cause sleep issues

Measuring Blood Levels

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

Genetics

Our genetics can affect how pregnenolone works in our bodies. For example, a variation (rs6971) in the gene TSPO can hinder internal production, meaning you may need to take a supplement [10].

  • Pregnenolone
  • Pregnenolone Sulfate

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 [11, 12].

Pregnenolone increases the growth of neurons [13].

Pregnenolone enhances myelination and has neuroprotective properties. Myelin is a fatty layer that electrically insulates nerves, and is essential for their proper functioning [11].

Pregnenolone sulfate enhanced the survival of newborn neurons in adult mice [14].

Pregnenolone also improves neurological recovery [15].

Pregnenolone and pregnenolone sulfate protect neurons against cell toxicity and death [8, 16].

Low blood levels of pregnenolone are found in the elderly, including those with dementia [11].

Pregnenolone and pregnenolone sulfate enhance brain activity and protect against brain cell damage.

Nootropic Mechanism:

Pregnenolone regulates neuronal function by activating and deactivating GABAA, NMDA, sigma-1, cholinergic, and dopamine receptors [11].

Pregnenolone sulfate decreases the activity of GABAA receptors, kainate, and AMPA receptors, and increases the activity of NMDA receptors [17].

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 [18].

By regulating microtubules, pregnenolone may increase neuronal development and plasticity of neurons during aging [13].

Joe’s Experience:

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

The nootropic effects of pregnenolone stem from its ability to boost cholinergic transmission and control GABA, glutamate, and dopamine secretion.

2) Improves Learning and Memory

In animal studies, pregnenolone and pregnenolone sulfate:

  • Enhanced learning and memory [19, 17, 20]
  • Resulted in better performance in various mazes [21]
  • Blocked chemical-induced amnesia [13, 19]
  • Prevented drug-induced cognitive decline [21].

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 [22].

Low concentration of pregnenolone sulfate increased the amount of REM sleep, while high concentrations increased both REM and slow-wave (deep) sleep [23].

Pregnenolone boosted deep sleep in human volunteers [9].

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.

A couple of studies found that pregnenolone improves sleep quality, but Joe’s experience suggests otherwise.

4) Relieves Schizophrenia Symptoms

Pregnenolone can potentially be used to alleviate and treat certain symptoms of schizophrenia. Pregnenolone levels are lower in the brain of schizophrenic patients [112424, 11].

Pregnenolone improved attention, verbal, and working memory performance in schizophrenic patients. Low-dose pregnenolone together with antipsychotics reduced drug side effects in schizophrenic patients [11, 611].

Elevations in pregnenolone and allopregnanolone after pregnenolone treatment in schizophrenia correlated with cognitive improvements [6].

Treatment with pregnenolone sulfate reduced schizophrenia-like symptoms and rescued cognitive deficits in mice [25].

In patients with schizophrenia, pregnenolone can improve cognitive and other symptoms while reducing the side effects of antipsychotics.

5) Boosts Mood and Relieves Depression

Decreased pregnenolone and allopregnanolone levels have been linked to depression [26].

Pregnenolone and allopregnanolone can balance mood and emotions [262728].

Blocking allopregnanolone impaired social and emotional functioning [28].

Pregnenolone reduces depression in patients with [29, 30]:

  • Bipolar disorder disorder
  • Major depressive disorder
  • History of substance abuse/dependence

Pregnenolone combats depression by boosting neural growth in the brain [13].

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.

Pregnenolone boosts mood, balances emotions, and stimulates the birth of new brain cells in people with bipolar disorder, major depression, and substance abuse.

6) Combats Anxiety

Patients with anxiety disorder have significantly lower levels of pregnenolone sulfate [31].

Allopregnanolone (measured after taking pregnenolone) reduces self-reported anxiety [28].

Pregnenolone reduces irritability in adults with autism spectrum disorder [27].

Allopregnanolone is a potent activator of GABA-A receptors, which have calming effects [32].

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.

Pregnenolone may reduce anxiety in some patients, but some of Joe’s clients experience the opposite effect.

7) Balances the Immune System

Synthetic pregnenolone derivatives act as antiviral agents against the herpes simplex virus [33].

Pregnenolone suppresses immune cells to restore immune balance (homeostasis) [4].

8) Reduces Alcohol Preference and Intake

Acute but not chronic pregnenolone significantly reduced alcohol preference and intake in rats [3435].

9) Kills Brain Cancer Cells

Pregnenolone induced glioma cell death in a cell-based study [36].

10) Protects from Cannabis Intoxication

Pregnenolone protects the brain from cannabis intoxication [37].

The administration of THC, the main active component of marijuana, substantially increases the production of pregnenolone in rats and mice [37].

11) Other Benefits

Pregnenolone has anti-arthritic, anti-aging, and anti-fatigue properties. It also lowers cholesterol [38].

According to very limited evidence, pregnenolone may reduce alcohol dependence, protect from cannabis intoxication, kill cancer cells, combat fatigue, and lower cholesterol.

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 testosterone-deficient men [39, 40, 41].

Pregnenolone might support weight loss and muscle-building by increasing testosterone, especially in testosterone-deficient men.

Pregnenolone Side Effects

Studies conducted in the 1940s and 1950s showed that pregnenolone (25 to 500 mg/day) was safe and well-tolerated in humans, with minimal side effects. It did not affect weight, heart rate, blood pressure, menstrual cycle, or glucose levels [21].

1) May Impair Memory

Pregnenolone sulfate impaired memory acquisition and memory retention in rats [17, 42].

Allopregnanolone impaired learning in rats [43].

2) May Reduce Wakefulness

Pregnenolone sulfate promotes sleep and can impair wakefulness [23].

3) May 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.

Pregnenolone was safe and well-tolerated in clinical trials. According to animal studies and user experiences, it may impair memory and cause anxiety and sleep issues.

Joe’s Experience

I’ve been taking pregnenolone for 3-4 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 anxiety and sleep issues.

For me, it will cause sleep issues if I take too much or don’t exercise enough. 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).

While I was having chronic inflammation, I was deficient in pregnenolone. I’m not deficient now, but I use up more of it given my heavy workload.

Pregnenolone is quite safe. 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’ve been using pregnenolone with great results, but it doesn’t work for a lot of my clients. To prevent sleep issues, I suggest finding the right dosage and exercising regularly.

Pregnenolone Dosage & Supplements

Dosage

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).

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

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

You may want to start with 5 mg of pregnenolone in the morning and track your response. It goes well with aromatase inhibitors such as ursolic acid and resveratrol.

Factors That Increase Pregnenolone

  • Lithium increased blood levels of allopregnanolone and pregnenolone in mice [26].
  • THC, the main active component of marijuana, substantially increased the production of pregnenolone [37]
  • Stress [44]
  • 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 [26]

Buy

Want More Targeted Ways to Enhance Brain Function?

If you’re interested in improving your cognitive function, we recommend checking out SelfDecode’s Limitless Mind DNA Protocol. It gives genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. This section contains sponsored links, which means that we may receive a small percentage of profit from your purchase, while the price remains the same to you. The proceeds from your purchase are reinvested into our research and development, in order to serve you better. Thanks for your support!

Takeaway

Pregnenolone is a brain-stimulating steroid people use to boost sleep quality, mood, and cognition. It acts as a nootropic by protecting brain cells, stimulating their growth, and increasing the neurotransmitters GABA and acetylcholine.

Solid science suggests pregnenolone may help with sleep issues, depression, anxiety, and schizophrenia. However, its benefits for weight loss, immunity, and substance dependence are not backed up by strong evidence.

Pregnenolone was safe and well-tolerated in clinical trials, but some users complain about anxiety and impaired sleep. To get optimal results, you may want to start with 5 mg in the morning and make sure to exercise regularly while you’re taking it.

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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