Pregnenolone Uses, Side Effects & Safety

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Pregnenolone is a hormone that the body produces from cholesterol. Despite a lack of effectiveness and safety data, pregnenolone made its way into some compounding pharmacies and bodybuilding products. However, many users are not told that pregnenolone is not a dietary supplement but an unapproved drug.

What is Pregnenolone?

Pregnenolone is a steroid hormone that the adrenal glands, brain, and gonads produce from cholesterol. In the body, it’s considered a precursor of other steroid hormones like testosterone, progesterone, cortisol, and estrogen. That’s why it’s sometimes referred to as a “prohormone” [1, 2, 3, 4].

There’s been some research on pregnenolone in the past decades, mostly in lab animals. Proper scientific evidence is lacking to determine the effectiveness and safety of pregnenolone.

Despite this, some companies advertise pregnenolone as an anti-aging and nootropic compound. It has been marketed for boosting the production of other hormones. Some claim it may make people feel more energetic and youthful. These claims are unsubstantiated.

The FDA issued a warning letter to New York-based company called American Hormones for illegally producing pregnenolone [5]. This is a serious violation.

In the letter, the FDA states that pregnenolone is a new unapproved drug since it is not generally recognized as safe and effective for the labeled uses among experts.

What’s more, the company in question purported to be a compounding pharmacy, although they were actually operating as a pharmaceutical manufacturer.

This poses a major risk to public health. Manufacturers that don’t follow laws and regulations sell potentially dangerous, adulterated, and misbranded compounds to consumers.

The same company also made numerous unsubstantiated claims about “bioidentical hormones” such as progesterone.

Pregnenolone is not explicitly listed on the World Anti-Doping Agency (WADA) Prohibited List.

However, all non-approved substances are on the prohibited list [6].

According to the FDA, unapproved drugs like pregnenolone are unsafe and should not be taken for any reason [7, 8].

If you are currently taking bodybuilding products that claim to contain steroids, prohormones, SARMs, or other unapproved substances, the FDA recommends that you stop taking them immediately due to the health risks linked with their use.

It’s also a good idea to check the label and quality certificate of any “natural” bodybuilding supplements you may be taking. The FDA considers bodybuilding products in general particularly risky, since they are often laced with illegal substances that have been linked with serious health risks [8].

The FDA also recommends talking with a doctor about the products you were taking (or considering), especially if you’re uncertain about the ingredients they contain. Immediately see a doctor if you experience side effects such as weakness, nausea, pain, or jaundice.

Some scientists describe pregnenolone and its sulfate (pregnenolone sulfate) as excitatory neurosteroids. In cell-based studies, pregnenolone seemed to shut off GABA receptors and activate glutamate’s NMDA receptors [9].

Thus, pregnenolone may have certain stimulatory effects on the brain. Some people use it for cognitive and mood issues. However, clinical trials are lacking to describe the effects of pregnenolone on brain health, mood, and neurotransmitter balance in humans [9].

Scientists are investigating whether pregnenolone affects the following pathways in animals or cells:

• Levels of other neurosteroids like pregnenolone sulfate and allopregnanolone. Allopregnanolone is hypothesized to increase the growth of neurons and decreases cell death and inflammation [10].

These mechanisms remain unproven.

Pregnenolone is a building block for steroid hormones in the body. It is being researched for its effects on the brain, but clinical evidence is lacking.

Proponents:

• Purported to support cognition and motivation
• Said to be both relaxing and stimulating
• Allegedly “boosts hormones”
• Marketed for libido and longevity

Skeptics:

• Unapproved new drug, not a dietary supplement
• Unknown safety
• Lack of effectiveness data
• Advertised for unapproved uses
• Illegally produced and likely misbranded
• May cause serious side effects
• Reported to increase anxiety and cause sleep issues

Pregnenolone blood tests are only ordered to test for rare types of genetic conditions that affect the production of steroid hormones such as congenital adrenal hyperplasia (CAH).

Genetics may affect how pregnenolone acts in the body. For example, a variation (rs6971) in the gene TSPO has been associated with poor internal production [14].

Pregnenolone is classified by the FDA as an unapproved new drug.

Evidence is lacking to support any of the uses listed below.

We strongly advise against taking pregnenolone until its safety and effectiveness have been determined in large clinical trials.

In a single study of 80 adults with bipolar disorder and depression, pregnenolone as add-on therapy for 12 weeks improved depressive symptoms compared to placebo. These findings have not yet been replicated [15].

Larger studies are needed to determine the safety and effectiveness of pregnenolone in people with bipolar disorder going through depressive episodes.

There is insufficient evidence to determine the effects of pregnenolone on autism.

In one study, pregnenolone added to standard therapy for 12 weeks seemed to improve symptoms such as irritability and lethargy in 12 adults with autism. However, this study was small, unblinded, and lacked a control group, which makes its findings unreliable [16].

Studies on the effects of pregnenolone as add-on therapy in people with schizophrenia had mixed results.

Pregnenolone was researched for affecting so-called negative symptoms in schizophrenia, which include blunted emotions, loss of motivation and social interest, inattention, and cognitive issues.

Several small studies had encouraging findings. In one study, adding pregnenolone to standard therapy improved attention, verbal, and working memory performance in schizophrenic patients [17, 18, 10].

However, in one study, pregnenolone did not improve negative symptoms in patients with schizophrenia and schizoaffective disorder [19].

In another randomized, double-blind study of 82 women hospitalized with an acute episode of schizophrenia, pregnenolone in combination with the antipsychotic medication risperidone did not reduce negative symptoms compared to risperidone plus placebo [20].

Some scientists have suggested that the interactions between pregnenolone and various antipsychotic, antidepressant, and mood-stabilizing medications may, in part, account for these conflicting results. Dosage regimens, therapy duration, and gender may also play a role.

Additionally, several clinical trials suggest that pregnenolone likely doesn’t affect the positive symptoms in people with schizophrenia, which include hallucinations, confusion, delusions, and disorganized speech [21, 22].

High-quality, large-scale studies are needed to clarify the effects of pregnenolone of symptoms in people with schizophrenia.

Researchers are also investigating the possible mechanisms by which pregnenolone sulfate may affect schizophrenia-like symptoms and cognitive deficits in mice [23].

So far, the effects of pregnenolone on schizophrenia symptoms appear conflicting. Further clinical trials are needed.

Some researchers believe that pregnenolone and pregnenolone sulfate may act as signaling molecules in the brain that stimulate neuronal activity. Most of the studies have been carried out in lab animals or cells and their findings can’t be applied to humans [17, 24].

In animals, pregnenolone and its sulfate salt (pregnenolone sulfate) were researched for:

• Increasing the growth of existing neurons and survival of new neurons [25, 26].
• Supporting myelination, the formation of the fatty layer that insulates nerves and helps them properly functioning [17].
• Stabilizing microtubules, affecting the ion flux into cells and dopamine release [29].
• Affecting neuronal development and plasticity of neurons during aging [25].
• Blocking chemical-induced amnesia and preventing drug-induced cognitive decline [25, 30, 32].

The effects of pregnenolone on cognitive function and brain development in humans remain unknown.

The effects of pregnenolone and pregnenolone sulfate on cognitive pathways in the brain were investigated in animals, but human trials are lacking.

The effects of pregnenolone on deep sleep in humans are unknown.

In one study published back in 1993, a single dose of pregnenolone increased time spent in deep (slow wave) sleep in male volunteers [13].

The authors of this study were interested in the effects of pregnenolone on various receptors in the brain, they didn’t test for safety and effectiveness. No research teams have since replicated their findings [13].

Pregnenolone and its derivative allopregnanolone seemed to stimulate deep sleep in animal studies [33].

In rats, low concentrations of pregnenolone sulfate increased the amount of REM sleep, while high concentrations increased both REM and slow-wave (deep) sleep [34].

According to some theories, deep sleep helps consolidate memories [35].

In lab animals, mood-stabilizers like lithium, clozapine, and olanzapine increase pregnenolone and allopregnanolone levels. Limited studies also suggest that allopregnanolone blood levels are lower during depressive episodes [36].

Thus, scientists have hypothesized that neurosteroids like pregnenolone and allopregnanolone play a role in mood balance and emotional stability. However, more large-scale human studies are needed to verify this theory [36, 37, 38].

A small trial comparing 8 men with anxiety disorder and 8 healthy people suggested a link between anxiety and lower levels of pregnenolone sulfate. However, this trial was very small and only measured potential associations. We still don’t know how pregnenolone might affect anxiety in humans [39].

In one small brain imaging study of 31 people, pregnenolone increased allopregnanolone levels, which reduced activity in brain regions associated with negative emotions. The authors concluded that the effects and mechanisms of pregnenolone should be further researched in patients with anxiety [38].

Pregnenolone was also researched for improving mood and cognition in patients who have several diagnoses, such as depression or bipolar and substance-use disorder. Larger trials are needed before we can draw any conclusions [40, 41]:

Additionally, some scientists are investigating whether pregnenolone might affect mood and cognition by increasing the birth of new brain cells, which is called neurogenesis, in animals and cells. These proposed mechanisms of pregnenolone remain unexplored in humans [25].

Pregnenolone has been implicated in mood and emotional balance, but its effects on mood disorders have yet to be determined in large clinical trials.

Synthetic pregnenolone derivatives are being researched as antiviral agents against the herpes simplex virus [42].

Scientists are investigating whether pregnenolone suppresses immune cells to restore immune balance (homeostasis) [3].

Additionally, acute but not chronic pregnenolone significantly reduced alcohol preference and intake in rats. The effects of pregnenolone on alcohol intake and addiction in humans are unknown [43, 44].

One group of researchers posits that pregnenolone might protect the brain from cannabis intoxication [45].

In rats and mice, THC, the main active component of marijuana, increased pregnenolone in rats and mice, but we have no way to know how pregnenolone affects brain health in marijuana users. Also, marijuana is illegal in most states and its medicinal use is controversial due to the high risk of side effects, addiction, and withdrawal syndrome [45].

Cell-based and animal studies are also exploring if pregnenolone has anti-arthritic, anti-aging, lipid-lowering, or anti-fatigue properties. Human studies haven’t been carried out [46].

Unfounded Weight Loss Claims

Pregnenolone has not been shown to affect weight loss.

Some people have argued that since pregnenolone can be used by the body to make testosterone and other steroid hormones, it may help with weight loss. However, research is lacking to back them up. Ongoing studies are exploring how pregnenolone interacts with other hormones, but clinical data are lacking. The effects of pregnenolone on weight loss are unknown [47, 48, 49].

Some pregnenolone advocates say that it may “boost” testosterone, which helps maintain and build muscle mass and affects metabolism. These claims are unfounded. Despite serious safety concerns and a lack of data, it has been marketed for weight loss, especially in testosterone-deficient men.

If you are struggling with weight loss or low testosterone, see a doctor to get an accurate diagnosis and to discuss your treatment options.

Remember that pregnenolone is an unapproved drug that carries many risks. Your doctor will recommend safe, approved therapies.

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

Pregnenolone Side Effects

The following side effects of pregnenolone have been reported [32]:

• Skin inflammation and acne
• Gastrointestinal issues
• Sleep problems
• Drowsiness/tiredness
• Restlessness and increased excitement
• Agitation
• Anorexia
• Sweating
• Tremor
• Heart palpitations
• Hair loss
• Muscle pain
• Cold extremities
• Blunted mood
• Sinusitis
• Increased appetite

The complete side effects profile of pregnenolone is unknown since it is an unapproved drug, which means that there aren’t enough clinical data about its safety and effectiveness.

Since pregnenolone may affect other steroid hormones, including sex hormones, there is a theoretical risk of hormone-dependent cancers.

Pregnenolone sulfate impaired memory acquisition and memory retention in rats [28, 50].

Allopregnanolone impaired learning in rats [51].

Pregnenolone sulfate promoted sleep and impaired wakefulness in animals [34].

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.

We highly recommend against purchasing pregnenolone, since it is an unapproved drug that can cause serious side effects. Talk to your doctor about approved therapies for your condition.

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.

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