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All You Need To Know About Pregnenolone

All You Need To Know About Pregnenolone


Pregnenolone is a steroid hormone created in the adrenal gland. It was later discovered that the Central Nervous System CNS which is the brain and the Spinal Cord also synthesis this hormone, it is made from cholesterol.

It is the critical building block for the production of dehydroepiandrosterone (DHEA), progesterone, testosterone, cortisol, and estrogen. And because of this (its biochemical use as a starting point for other hormones) pregnenolone is sometimes referred to as a “precursor” or “pro-hormone”.

On its own however pregnenolone acts as a neurosteroid. Neurosteroids are synthesized in the brain and are used to rapidly stimulate neuronal activity.

Normalized levels of neurosteroids in the brain is also found to promote processes like neurogenesis (production of new nerve cells), myelination (insulation to protect the nerve fibers), neuronal survival, increased memory, and reduced neurotoxicity.


Steroid hormones are derivatives of cholesterol that are synthesized by a variety of tissues, most prominently the adrenal gland and gonads. The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from the uptake of cholesterol-containing low-density lipoproteins. Lipoproteins taken up from plasma are most important when steroid genic cells are chronically stimulated.

Oxidative enzymes located in both mitochondria and endoplasmic reticulum. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. Within mitochondria, cholesterol is converted to pregnenolone by an enzyme in the inner membrane called CYP11A1.


Scientists using data collected from animal studies believe that neurosteroids including pregnenolone diminish with age these declining levels may leave the brain vulnerable to damage and neurodegenerative diseases such as Alzheimer and Dementia. Scientists have proposed that neurosteroid levels of hormones such as pregnenolone can be used as markers for cognitive aging in laboratory animals.

Some tests have also concurred this argument by showing a correlation between neurosteroid levels especially DHEA and cognitive function among human beings.

Some people use pregnenolone for a wide number of reasons. And while not much research has been conducted to understand pregnenolone and its complexity. It has shown increased cognitive and behavioral advantages when used as a cure or a supplement for certain conditions. Some of these conditions are:


The disease is caused by a decrease in neurosteroid levels. It is caused by the build-up of amyloid-beta plaques in the brain which blocks communication between nerve cells and disrupts key activities in the brain cells which lead them to die.

Researchers found that the production of steroid hormones such as pregnenolone declines steeply with age which could be directly linked to the onset of neurodegenerative diseases. French researchers have paved the way in linking the effects of pregnenolone on cognitive aging.

In their research, they found that pregnenolone can directly influence acetylcholine, a key neurotransmitter required for optimal brain function, release in several key regions in the brain. They also found that pregnenolone was able to facilitate new nerve growth.

In their research, they found that pregnenolone sulfate found in the brain completely reversed memory deficit in older and impaired rats.

Furthermore, pregnenolone is the building agent for Dehydroepiandrosterone DHEA, which was found to be deficient in people with Alzheimer that in those without it can be therefore be theorized that the introduction of pregnenolone can be used in the production of DHEA which would, in turn, slow down or alleviate the symptoms attributed to Alzheimer.


Anxiety can often be caused by the overstimulation of brain cells for memory enhancement. Memory stimulants often have anxiety as their listed side effects, whilst medicine that curbs anxiety has shown to impair memory and learning skills. Pregnenolone, however, is able to stimulate memory and neuron pathways and as a building block for other hormones provide the hormones that off-balance any side effects caused by increased activities.

According to life-extension magazine “pregnenolone itself acts at excitatory receptors in the brain to stimulate nerve cell activity and enhance learning, other neurohormones produced from pregnenolone (such as allopregnanolone) act on inhibitory brain receptors, called gamma amino-butyric acid (A) (GABA(A)) receptors, which suppress brain cell activity to produce a calming, anti-anxiety, and even sleep-inducing effect.”

Researchers from University of California San Francisco in an attempt to see the efficiency and interaction of using pregnenolone with anxiety medication to elevate side effects found that pregnenolone is taken alongside anxiety medication was able to reduce side effects from the medication such as sedation and memory impairment.

Bipolar Depression

Bipolar disorder (BDP) formerly known as manic depression is a disorder that is characterized by extreme mood swings. That include emotional highs (hypomania) and extreme lows depression. These moods can severely affect sleep, energy, behavior and cognitive functions.

Based on the research conducted and published by the Proceedings of the National Academy of Sciences of the United States of America in 2012. Pregnenolone has shown that it can cure or alleviate depressive episode by curing certain brain cells. These tests were however done and tested on rats and no human trials had been done and conducted at the time.

It was however concluded in a study done and compiled by several psychologists and psychiatrists in 2014 that pregnenolone may improve depressive symptoms in patients with Bipolar disorder (BPD) and can be safely administered.


Schizophrenia is a mental disorder that causes positive and negative mood swings, hallucinations and delusions and causes one to lose touch with reality. Recent studies show that schizophrenia can be caused by several neurobiological alterations in the brain structure, physiology, and neurochemistry. Intervention methods include pharmacotherapy with antipsychotic and psychosocial intervention. And more recently the use of pregnenolone.

In recent studies, it showed the use of pregnenolone, as well as DHEA, played a significant role in the expressions of the stress response, anxiety, and cognitive functioning in people in schizophrenia.


Memory creation occurs as a result of the stimulation of the nerve cells. Stimulation leads to the creation of nerve cells knows as dendrites which connect to other neurons.  These structures are formed by activating special “switches” in the brain. While there are a variety of such excitatory switches, the category called NMDA (N-methyl-D-aspartate) channels (or receptors) comprises the most important group.

Now for learning to take place, the brain must activate memory-enhancing receptors which is done by the chemical amino acid glutamate which is present in all the areas of the brain. The overstimulation of the neurons by glutamate can be quite corrosive and causes damage to the neurons. This overstimulation of the neurons and damage has been considered as one of the key factors that lead to neurodegenerative disorders such as Alzheimer.

The special thing about pregnenolone, however, is that it is able to activate these channels without the activation of the glutamate and in turn set up a protective layer in the nerve networks in which the information is stored. I

n short, pregnenolone not only allows for the creation of memories but also plays an active role in their retention as well this sheds a light on the neuroprotective effect of pregnenolone on the brain cells.

Pregnenolone is showing considerable improvements in the acquisition of information as well. A team of French researchers found that pregnenolone stimulated the creation of ultra-microscopic structures called microtubules in brain cells. The microtubules are what nerve cells use to rearrange their structure making the new connections that form the structure of memory.

In other words, pregnenolone was important in creating new “data-storage” areas in the brain.

Overcoming Chemical Dependency

Most addictive substances such as nicotine and alcohol have adverse and severe effects on memory and learning which can get worse with aging. Research has shown that pregnenolone sulfate overcome any memory impairment caused by nicotine and alcohol. Pregnenolone has also been found to counteract some withdrawal symptoms associated with nicotine such as anxiety.

Further research showed the potent effect pregnenolone has on the sigma-receptors which have for a long time been associated with addictive behaviors.


Since pregnenolone is a precursor hormone used in the production of other key hormones some studies have shown that after our 20 and 30’s the production of pregnenolone slinks off by 5% each year after that. Hormone Replacement Therapy (HRP) is a common treatment protocol used in managing symptoms associated with menopause.

Pregnenolone is used to facilitate and supplement the creation of estrogen and progesterone. It is also used by women to lessen the incoming symptoms of menopause previously maintained by estrogen and progesterone such as fatigue, hot flashes, reduced sex drive, and weight gain.


There are several risks to using pregnenolone in the body some such as:


Physicians and health experts continue to express concern over the use of hormone inducing medication especially later in life, this is due to the increased risk of hormone-dependent malignancies such as breast and prostate cancers.

This has however been an area of contention between scientists as Harvard urologist Abraham Morgentaler cited that low testosterone levels increase prostate cancer risk and not higher levels as stated earlier.

To date, there has been no comparative study that has effectively found a correlation on the increase in human hormone-dependent cancer risk as a result of pregnenolone hormone usage.

However, it has been argued that because the use of pregnenolone is the same as hormone replacement therapy it runs the same cancer risk as well.

It has however been used by FDA and California law to restrict the use of pregnenolone to prescription-only use.


As pregnenolone boosts the productions of hormones including testosterone it has been a concern that it can in women give them more masculine traits such s facial hair and male pattern baldness. These effects happen infrequently and mildly they are also reversible if they do indeed occur.

Epileptic History

Increased brain activity from the neurosteroid caused by taking pregnenolone may reduce the seizure threshold and make seizures more likely. It is therefore imperative that the user makes sure they consult their physician before and (in case of) after before continued use.


The use of hormone enhancer can cause the body to be overwhelmed and may lead to fatigue in some cases. If this occurs one should consult their physician for further extrapolation on the cause.


The overstimulation of the brain might bring about insomnia for some.


Even with its anti-anxiety properties pregnenolone may cause anxiety due to overstimulation of the brain cells and increased neuron activity. If this occurs one should reduce the dosage and contact their physician.


Before taking pregnenolone it is important to be upfront and honest about other medications including hormones inducing supplements that you may be taking. The reason for this is because as pregnenolone is a precursor hormone the user risks replication of the hormone already being used as a supplement and that risks the overproduction of one hormone and that would have severe effects on the user. It would also create an imbalance in the bodies system.


The dosage of pregnenolone depends on several factors such as the person’s age, health, the reason for usage and mental history, this is due to the neurosteroid aspect of the medication. As a natural supplement dosage is important and therefore should be used based on the recommendation of a trained physician and specialist. It is however recommended that one uses the lowest possible dosage before increasing to a higher dosage in order to see how it interacts with the body and to monitor any significant changes that occur out of the expected outcome.


Although there is still a lot of room for the research of pregnenolone and a large number of comprehensive human trials to be done it is important to note that pregnenolone had a profound effect on vital brain structures and affects how we think, how we learn and how we retain information. The study of pregnenolone and other neurosteroids is changing the way we think out the actions of hormones in our bodies. Initial research shows great potential and promising results in the use of pregnenolone as a versatile natural supplement.

It is important to note however that the powerful nature of this supplement may have adverse side effects if used recreationally or without consulting a physician or health expert.

Upcoming research and new trials will help shed more light in the future on the other numerous ways that pregnenolone can be used and how the different ways it may be able to further help brain function

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Hi, I'm Pankaj Sinha, Co-founder of which discusses everything related to health and fitness and sometimes things related to science. I am from NE, India. I hold a bachelor's degree in Chemistry and these days I am pursuing my masters in Nutrition and Dietetics. I am also pursuing my personal trainer certification. Learn more about me in the about us section.

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