Pregnenolone part B :

Pregnenolone has a huge role in treatment of Psychiatry illness. But yes we require a skilled practitioner on how to use it.

Pregnenolone’s role in Tardive dyskinesia :

Pregnenolone, a neurosteroid, has shown promise in animal studies as a potential treatment for tardive dyskinesia (TD), a movement disorder caused by long-term use of certain antipsychotic medications. Neurosteroids are substances that occur naturally in the brain and help regulate and modulate the activity of brain cells.

Haloperidol-induced dyskinesia :

Research in rat models of TD induced by haloperidol (a common antipsychotic) has shown that pregnenolone and its metabolite allopregnanolone may help attenuate or reduce the symptoms of orofacial dyskinesia. Pregnenolone exhibits neuroprotective properties, which could be beneficial in managing the long-term effects of antipsychotics that can lead to tardive dyskinesia.

Pregnenolone may exert its effects by influencing neurotransmitter systems, including dopamine and GABA, which are known to be involved in TD. Specifically, pregnenolone may modulate GABA receptors. GABA hypofunction is a proposed mechanism in TD. Pregnenolone through its metabolites like Allopregnanolone , may help attenuate or reduce the symptoms of orofacial dyskinesia. Allopregnanolone, increases GABAergic activity, which can help regulate neuronal excitability .It also promotes neurogenesis, decreases apoptosis (cell death), and has neuroprotective effects.

L-DOPA-induced dyskinesia in Parkinson's disease model : Studies in rats with 6-OHDA-lesions (a model of Parkinson's disease) have shown that pregnenolone can counter L-DOPA-induced dyskinesia without affecting the beneficial motor improvements caused by L-DOPA. This suggests pregnenolone may have a specific antidyskinetic effect. Pregnenolone may have antidyskinetic properties, potentially by influencing dopamine receptors and other neurochemical pathways involved in movement control.

In previous studies, the investigators demonstrated that inhibiting an enzyme involved in the synthesis of a neurosteroid called 5 alpha reductase (5AR) dampens involuntary movement, or dyskinesia, in models of Parkinson’s that only affects one side of the body. The researchers are now trying to understand which specific neurosteroid(s) is responsible for the observed protection from dyskinesia. They found that inhibiting this enzyme results in a specific accumulation of the neurosteroid pregnenolone, which has been shown to have therapeutic properties in dopamine-related diseases.

Thus pregnenolone may play a role in mitigating abnormal movements associated with both of these conditions.

Pregnenolone for OCD : Pregnenolone has been explored as a potential adjunct therapy for Obsessive-Compulsive Disorder (OCD).

Studies suggest that pregnenolone by modulating GABA and NMDA receptors may enhance exposure therapy outcomes in OCD patients, particularly for those who are initially reluctant to expose themselves to anxiety-evoking stimuli.

Pregnenolone as a novel therapeutic candidate in schizophrenia and mental disorders : https://pubmed.ncbi.nlm.nih.gov/21756978/

Pregnenolone, shows promise as a potential therapeutic agent for schizophrenia, particularly for reducing negative symptoms and cognitive deficits.

Research published in 2018 adds that taking pregnenolone for one month appears to provide benefits for individuals experiencing their first schizophrenic episode who have not yet started antipsychotic treatment. Studies suggest that pregnenolone may work by modulating NMDA receptors and GABA systems, which are implicated in the pathophysiology of schizophrenia. NMDA receptor hypofunction is a key feature in the neurobiology of schizophrenia. Allopregnanolone, modulate NMDA receptor activity by affecting glutamate release. Allopregnanolone enhances GABAergic neurotransmission. GABA dysregulation is also implicated in schizophrenia.

https://trial.medpath.com/clinical-trial/b245c5eaecf65f60/addition-pregnenolone-l-theanine-antipsychotic-treatment-schizophrenia

Allopregnanolone has neuroprotective effects, increasing neurogenesis, decreasing apoptosis and inflammation, and modulating the hypothalamic-pituitary-adrenal axis. Allopregnanolone enhances the function of GABA receptors, specifically the GABAA receptor, in the brain. It acts as a positive allosteric modulator, meaning it binds to the receptor at a site other than the GABA binding site and increases the receptor's sensitivity to GABA. This enhancement of GABA-mediated signaling leads to anxiolytic, anti-stress, and antidepressant effects. This means GABA can more easily bind to the receptor, leading to a greater influx of chloride ions and a stronger inhibitory effect.

Anxiolytic effects: By reducing neuronal excitability, allopregnanolone can help to relieve anxiety.

Anti-stress effects: Allopregnanolone can modulate the hypothalamic-pituitary-adrenal (HPA) axis, a key stress response system, and help to regulate stress responses.

Antidepressant effects: The enhancement of GABAergic signaling has been linked to mood regulation, and allopregnanolone deficiency has been implicated in the development of mood disorders.

Allopregnanolone has also been known to decrease hippocampal volume loss

It Promotes myelination, increases neuron fiber density and increases brain connectivity. Pregnenolone and its derivative allopregnanolone have been linked to improved sleep, potentially by modulating GABA receptors and influencing sleep cycles. Pregnenolone directly suppresses the hypothalamus’ initiation of the stress cascade, and even lowers the amygdala’s emotional stress response.

Pregnenolone directly affects other substances in the human body, such as MT-associated proteins (MAPs). MAP defects have been linked with major depressive disorder (MDD) and taking pregnenolone may positively affect MAP levels, potentially helping to ease depressive symptoms.

A recent study of 27 depressed patients found that their cerebrospinal fluid (which circulates through the brain and spinal cord) was significantly lower in pregnenolone than in 10 non-depressed volunteers. Cerebrospinal fluid levels are generally believed to accurately reflect levels of various biochemicals in the brain.

Pregnenolone dosing is very important. Large doses can hyper stimulate HPA axis and can trigger mania.

It can cause confusion , anxiety, euphoria, irregular heart rythm, irritability, headache, increased appetite, sometimes paradoxically insomnia and upset stomach . Dosing is very very important . I expirenced euphoria at a dose of 50 mg / day. So I reduced the dose to 50 mg per week and found it beneficial.

Also it's important if you have history of seizures or epilepsy, I would recommend to avoid taking supplements.

Pregnenolone in smaller doses has shown to have anti convulsant effects but large doses can have pro convulsant effects.

Pregnenolone, specifically pregnenolone sulfate (PS), can have proconvulsant (seizure-inducing) effects in high concentrations, particularly in the hippocampus. While PS is an endogenous neurosteroid, it's unlikely that its normal levels trigger seizures on their own. Conversely, allopregnanolone, another neurosteroid derived from progesterone, generally has anticonvulsant properties.

Progesterone, through its conversion to neurosteroids like allopregnanolone, can reduce seizure susceptibility.

Allopregnanolone is a neurosteroid derived from progesterone that enhances GABA-A receptor function, leading to inhibition of neuronal excitability. It is generally considered anticonvulsant and may help to reduce seizure susceptibility.

It's always best to talk to your mental health practitioner when you are taking this supplement because he/ she may give you appropriate dose so that it doesn't harm you and benefit you.

Chemo-protective action of Pregnenolone :

A major determinant of the body’s ability to detoxify poisonous chemicals, such as pesticides, medical drugs, industrial contaminants and auto exhaust, is the health and effectiveness of the Cytochrome P450 enzyme system in the liver. This is one of the most broad-spectrum, universal detoxifying enzyme systems possessed by all mammals, including humans.

Moderate levels of cortisol (the state­of-siege anti-stress hormone) promote the activity of this detox system. However, larger amounts of cortisol (which is all-too-often over-produced by our adrenal glands due to aging or prolonged stress) degrade the P450 system’s anti-toxin effects. Although pregnenolone does not affect the rate of synthesis of the enzymes in the P450 system, it does stabilise these enzymes against the digestive activity of liver proteolytic enzymes, which would tend to break down the P450 enzymes. Pregnenolone thus increases overall P450 detox enzyme power by promoting conservation of existing P450 enzymes.

Pregnenolone derivatives also possess anticancer activity against lung cancer, cervical cancer and breast cancer :

https://onlinelibrary.wiley.com/doi/abs/10.1002/jccs.202200040#:~:text=Pregnenolone%20derivatives%20also%20possess%20anticancer,%2C%205%5D%20and%20breast%20cancer.&text=In%20continuation%20of%20our%20research,of%20Heck%20and%20Steglich%20reaction.

Low pregnenolone can also be associated with fatigue, reduced mobility, joint and muscle pain, and dry skin.

Pregnenolone in skin disorders : It is also is used for skin disorders including psoriasis and scleroderma. Pregnenolone opposes skin-aging stress hormones and regulates the immune system.

Low pregnenolone levels can contribute to dry skin :

Progesterone, which is synthesized from pregnenolone, stimulates the production of sebum (oil) in the skin. When pregnenolone levels are low, this can lead to reduced sebum production and consequently, drier skin.

Pregnenolone is involved in the production of skin cells and can help maintain skin hydration and elasticity thus giving you young looks .

Pregnenolone acetate has been reported to reduce wrinkles in elderly women when applied in the form of a 0.5% topical cream, effects which were suggested to be due to improved hydration of the skin.

Anti-arthritis effects : In the past, pregnenolone was explored as a potential treatment for rheumatoid arthritis and other inflammatory conditions, including ankylosing spondylitis. Some studies suggested it could reduce pain, muscle spasms, and improve joint movement and induce remission.

During the 1940’s, pregnenolone was used successfully as a treatment for rheumatoid arthritis. A 1950 review article on pregnenolone reported on a study by Henderson and colleagues which found that 300mg pregnenolone/day for 40 days resulted in a significant decrease in joint pain, tenderness and spasticity, with improved strength and range of motion. Another study by Freeman and colleagues, with 64 patients, used 500mg of pregnenolone daily for periods of 2 to 30 weeks. Twenty-four patients showed striking improvements and 20 showed minor improvements.

Unfortunately, the advent of the wonder drug cortisone (Cortisol) in the 1950’s caused pregnenolone to be passed by for arthritis treatment, since pregnenolone’s results were much slower to manifest. Coincidentally, pregnenolone couldn’t be patented by the drug companies whereas synthetic variants of cortisone could be (and were) patented. By the time the nightmarish side-effects of excessive cortisone were widely known by the medical community in the 1960’s (these side effects could include psychotic breakdown, adrenal failure and even death), pregnenolone had been completely forgotten.

Word of caution: I believe that pregnenolone supplementation, like DHEA, should be undertaken under the supervision of a health practitioner acquainted with its use as in high doses it may cause undesirable side effects like irritability, anxiety and confusion as I previously discussed.

While I generally don't treat patients of arthritis as it is not my subject topic ,I strongly recommend my good friend Dr. Ahmad Malik. He is an expert in dealing with patients of arthritis.

The Antimicrobial potential of Pregnenolone :

Pregnenolone known for its hormone balancing benefits may also provide a new layer of protection by keeping bacteria at bay.

pregnenolone could be a natural Antimicrobial agent with potential to help fight bacterial infections especially when Antibiotics don't work. We need more research to explore new ways to boost protection from harmful bacteria, especially for those with weakened immune system or antibiotic resistance concerns .

https://www.sciencedirect.com/science/article/abs/pii/S0166354215001886

Pregnenolone acetate has been reported to have some success in treating nocardiosis, a bacterial form of mycetoma, according to a report in the Archives of Dermatology in 1953.

https://jamanetwork.com/journals/jamadermatology/article-abstract/523484

Low levels of pregnenolone may increase the risk of fungal as well as bacterial infections by weakening the immune system's ability to fight off infections. Studies suggest that cutaneous warts, including genital warts, are more prevalent and severe when pregnenolone levels are low.

Research suggests that pregnenolone can lower C-reactive protein (CRP) levels, a marker of inflammation. In studies, pregnenolone has been shown to decrease inflammation and improve various aspects of immune function.

Low levels of pregnenolone may increase the risk of autoimmune diseases

Several studies suggest a link between low pregnenolone levels and increased susceptibility or exacerbation of autoimmune diseases. For example, neuroinflammatory diseases, where inflammation in the nervous system is a key feature, are often associated with reduced pregnenolone levels, highlighting its role in neuroprotection.

Pregnenolone can influence the immune system by promoting the degradation of molecules involved in inflammation, such as TIRAP and TLR2/4. It also has anti-inflammatory effects by suppressing the production of pro-inflammatory cytokines like tumor necrosis factor α and interleukin-6.

Disclaimer : This article is not medical advice . This article is only meant for information purposes only.