Pregnenolone Supplementation in Men: Experiences and Dosage Considerations

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Users on ExcelMale.com shared their experience with pregnenolone supplementation, providing insights into dosage and effects. Here's a summary of the key points:

Dosage and Effects​

  • Optimal Dose: The user found benefits at 100mg, including higher libido, more pronounced nighttime erections, and better sleep1.
  • Inconsistent Results: While 100mg seemed effective, the results were not consistent over time1.
  • Diminishing Effects: Continuous daily use of 100mg led to waning effects by the second day1.
  • Lower Doses: Experiments with 10mg, 25mg, and 50mg doses were less effective, with extended use leading to negative effects1.

Pregnenolone.webp

Observations and Theories​

  • Progesterone Levels: The user theorized that the diminishing effects might be due to elevated progesterone levels1.
  • Pregnenolone vs. Progesterone: Direct progesterone supplementation was found to be less beneficial and more likely to cause negative effects compared to pregnenolone1.

Questions for Further Research​

The user sought clarification on:

  1. The half-life of pregnenolone
  2. The half-life of pregnenolone's sulfate derivative
  3. The conversion rate of pregnenolone to progesterone
  4. Optimal dosing frequency1
This summary highlights the complexity of pregnenolone supplementation and the need for individualized approaches. More research is needed to fully understand the optimal use of pregnenolone in men.

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Citations:​

  1. Help determining proper pregnenolone dosage and frequency
  2. Help determining proper pregnenolone dosage and frequency
 
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Nelson Vergel
Nelson Vergel

Nelson Vergel

Taking pregnenolone at 100mg daily may offer several potential benefits:

Cognitive Function​

  • Improves memory and learning12
  • Enhances cognitive function and brain plasticity18
  • Increases growth of neurons in the brain2
  • Boosts production of myelin, improving nerve function2

Mood and Mental Health​

  • May help alleviate symptoms of depression and anxiety23
  • Improves emotional regulation and reduces negative emotional responses23
  • Potentially beneficial for individuals with schizophrenia or bipolar disorder45

Sleep​

  • Can stimulate deep sleep, potentially helping with sleep disturbances or insomnia23

Other Potential Benefits​

  • May aid in weight loss by inhibiting cortisol production23
  • Has anti-inflammatory effects and helps maintain immune balance5
  • Could help reduce chronic pain in some individuals5
It's important to note that while 100mg is within the range often recommended (50-100mg daily for the average person)1, individual responses can vary. Some studies have used higher doses up to 500mg daily46, but these were under medical supervision. Always consult with a healthcare provider before starting any new supplement regimen, as pregnenolone can interact with hormones and may have side effects in some individuals78.

Citations:​

  1. Pregnenolone: A Precursor Hormone with Potential Memory and Brain Benefits
  2. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  3. Pregnenolone – The Miracle Product of Cholesterol - Levitas Clinic Guildford
  4. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC
  5. Pregnenolone Benefits and Considerations: Is the Pregnenolone Steal Real?
  6. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial - PMC
  7. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  8. https://www.lifeextension.com/vitamins-supplements/item00700/pregnenolone
  9. Pregnenolone SR 100 mg
  10. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  11. How Taking Pregnenolone Might Boost Brain Health
  12. Pregnenolone (100 mg)
 
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Defy Medical TRT clinic doctor
Pregnenolone dosage can significantly impact both libido and sleep, with effects varying based on the amount taken. Here's how different dosages may affect these aspects:

Libido​

  • 100mg dosage: At this level, some men report experiencing higher libido and more pronounced nighttime erections1. However, these effects may not be consistent and can diminish over time with continuous daily use.
  • Lower dosages: Doses of 10mg, 25mg, and 50mg seem less effective for libido enhancement compared to the 100mg dose1.

Sleep​

  • General effects: Pregnenolone can stimulate deep sleep, making it beneficial for those with sleep disturbances or insomnia37.
  • 100mg dosage: This dose has been reported to improve sleep quality1.
  • Timing: Taking pregnenolone at night, before bed, is recommended due to its potential to cause drowsiness3.

Dosage Considerations​

  • Typical range: The general dosage range for pregnenolone is 50 to 200 mg per day, usually taken in the morning on an empty stomach2.
  • Individual variation: Responses to pregnenolone can vary significantly between individuals. What works for one person may not work for another18.
  • Consistency: Some users report that the effects of pregnenolone, particularly at higher doses like 100mg, may diminish over time with daily use1.
  • Professional guidance: It's crucial to consult with a healthcare provider before starting pregnenolone supplementation, as they can recommend an appropriate dosage based on individual needs and health status28.

Safety and Side Effects​

  • Drowsiness: Higher doses may cause drowsiness, which is why evening administration is often recommended3.
  • Hormonal effects: Pregnenolone is a precursor to other hormones, so its supplementation can affect overall hormonal balance6.
  • Long-term use: The effects of long-term pregnenolone supplementation are not well-studied, emphasizing the importance of medical supervision8.
In conclusion, while pregnenolone at higher doses (around 100mg) may positively affect libido and sleep for some individuals, responses can vary widely. It's essential to start with lower doses, monitor effects carefully, and work with a healthcare professional to find the optimal dosage for individual needs.

Citations:​

  1. Help determining proper pregnenolone dosage and frequency
  2. Pregnenolone for Men: What You Need to Know - Discounted Labs
  3. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  4. A 'Prohormone' that May Help Relieve Depression
  5. Pregnenolone | Rupa Health
  6. Pregnenolone For Men | Side Effects, Results, & Where To Find It
  7. Pregnenolone – The Miracle Product of Cholesterol - Levitas Clinic Guildford
  8. Understanding Pregnenolone: A Comprehensive Guide for Men on Benefits, Dosage, and Safety
  9. Improved sleep, better thought processes, and more energy
  10. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation - PubMed
  11. How Taking Pregnenolone Might Boost Brain Health
  12. Why does 100mg oral pregnenolone spike my libido beyond belief?
  13. Pregnenolone
  14. To view this content we will need your consent to set third party cookies.
    For more detailed information, see our cookies page.
  15. What is Pregnenolone? | CLNQ
  16. Pregnenolone: A Precursor Hormone with Potential Memory and Brain Benefits
  17. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  18. Pregnenolone 25 mg/Progesterone 60 mg/Testosterone 0.5 mg/0.5 mL Topical Cream | Formulas | Bayview Pharmacy
  19. https://onlinelibrary.wiley.com/doi/full/10.2164/jandrol.108.005660
  20. Pregnenolone Benefits: What Is It & Why You Should Take It
  21. DHEA & Pregnenolone | Gurnee Andropause
  22. Why sleep is more difficult for women - The Functional Neurology Center
  23. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  24. Have you heard about Pregnenolone? - Medical Specialty Clinic
  25. Increasing women’s sexual desire: The comparative effectiveness of estrogens and androgens - PMC
  26. Source Naturals Pregnenolone
  27. Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder - PMC
  28. https://www.maximustribe.com/resources/does-pregnenolone-increase-testosterone
  29. Neurobehavioral complications of sleep deprivation: shedding light on the emerging role of neuroactive steroids - PMC
 
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Progesterone and pregnenolone are both important hormones with distinct roles and effects in the body. Here's a comparison of their benefits and side effects:

Benefits​

Pregnenolone​

  • Cognitive Function: Improves memory, learning, and concentration2
  • Mood Regulation: May help alleviate depression and anxiety2
  • Sleep: Can stimulate deep sleep, beneficial for those with sleep disturbances2
  • Hormonal Precursor: Serves as a precursor for many other hormones, including progesterone, estrogen, and testosterone15
  • Neuroprotection: Enhances neuron growth and myelin production2
  • Weight Management: May aid in weight loss by inhibiting cortisol production2

Progesterone​

  • Reproductive Health: Regulates menstruation and supports pregnancy1
  • Mood Stabilization: Has calming effects and interacts with GABA receptors5
  • Sleep Support: Offers relaxing, sedative-like properties5
  • Bone Health: Plays a role in bone formation and density5
  • Skin Health: Helps regulate skin elasticity5

Side Effects​

Pregnenolone​

  • Common: Acne, agitation, diarrhea, drowsiness, excitement, hair loss, skin rashes, sweating, and tremor3
  • Hormonal Effects: May cause steroid-like side effects including overstimulation, insomnia, irritability, anger, anxiety, and mood changes4

Progesterone​

  • Common: Headache, breast tenderness, fatigue, nausea, diarrhea, constipation, and muscle/joint pain6
  • Serious: Dizziness, swelling, changes in heart rate, depression, difficulty breathing, and vision changes6

Key Differences​

  1. Hormonal Precursor: Pregnenolone is a precursor to many hormones, including progesterone, while progesterone has more specific effects15.
  2. Cognitive Effects: Pregnenolone has more pronounced effects on cognitive function and memory2.
  3. Reproductive Health: Progesterone plays a more direct role in menstrual regulation and pregnancy support1.
  4. Safety Profile: Pregnenolone is considered possibly safe for up to 12 weeks, while progesterone has more established long-term use in medical settings36.
  5. Mood Effects: Both can affect mood, but pregnenolone is more associated with anti-anxiety effects, while progesterone has more general calming properties5.
It's crucial to consult with a healthcare provider before using either hormone, as they can interact with other medications and may not be suitable for everyone, especially those with hormone-sensitive conditions or certain health risks346.

Citations:​

  1. Is Pregnenolone The Same As Progesterone - Walkin Lab
  2. Pregnenolone – The Miracle Product of Cholesterol - Levitas Clinic Guildford
  3. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  4. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  5. How Pregnenolone Benefits Your Hormones | Dr Anna Cabeca
  6. Progesterone: Uses and Risks
  7. Exploring the Differences: Progesterone vs Pregnenolone
  8. Pregnenolone-progesterone-allopregnanolone pathway as a potential therapeutic target in first-episode antipsychotic-naïve patients with schizophrenia - PMC
  9. Proper Use of Hormone Precursors by Dr. Joseph J Collins, RN, ND | Your Hormones
  10. How Taking Pregnenolone Might Boost Brain Health
  11. Pregnenolone: What You Need to Know | USADA
  12. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  13. Progesterone (oral route)
  14. Pregnenolone Benefits and Considerations: Is the Pregnenolone Steal Real?
  15. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration - PMC
  16. Pregnenolone – Health Information Library | PeaceHealth
  17. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  18. https://downloads.regulations.gov/FDA-2017-N-2562-0017/attachment_1.pdf
  19. What is Pregnenolone? | CLNQ
  20. Association of endogenous pregnenolone, progesterone, and related metabolites with risk of endometrial and ovarian cancers in postmenopausal women: the B~FIT cohort - PMC
 
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The half-life of pregnenolone and its sulfate derivative varies based on different studies:

Pregnenolone​

  • Half-life: 3.7 hours (95% CI: 3.4 to 4.0 hours)7

Pregnenolone Sulfate​

  • Half-life: Approximately 2.2 hours8
  • In pregnant women, the mean half-life was 2.22 ± 0.70 hours5
It's important to note that pregnenolone is cleared about three times more quickly than pregnenolone sulfate in both humans and rabbits13. The slower clearance rate of pregnenolone sulfate contributes to its higher circulating concentrations in the serum compared to pregnenolone4.

These half-life values suggest that both pregnenolone and its sulfate derivative are metabolized relatively quickly in the body. However, studies have shown that twice-daily oral administration of pregnenolone (300 mg/day or 500 mg/day) can achieve stable and elevated plasma levels over an extended period6, indicating that appropriate dosing can overcome the short half-life for therapeutic purposes.

Citations:​

  1. METABOLIC CLEARANCE RATES OF PREGNENOLONE, 17-ACETOXYPREGNENOLONE AND THEIR SULPHATE ESTERS IN MAN AND IN RABBIT
  2. Pregnenolone - Wikipedia
  3. METABOLIC CLEARANCE RATES OF PREGNENOLONE, 17-ACETOXYPREGNENOLONE AND THEIR SULPHATE ESTERS IN MAN AND IN RABBIT
  4. Pregnenolone sulfate induces transcriptional and immunoregulatory effects on T cells - Scientific Reports
  5. https://academic.oup.com/jcem/article-abstract/38/6/1038/2685426
  6. Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings - PMC
  7. https://onlinelibrary.wiley.com/doi/10.1111/jvim.15618
  8. https://www.lifeextension.com/magazine/2004/6/report_preg
  9. https://go.drugbank.com/drugs/DB02789
  10. Pregnenolone (medication) - Wikipedia
  11. Metabolic clearance rates of pregnenolone, 17-acetoxypregnenolone and their sulphate esters in man and in rabbit - PubMed
  12. https://academic.oup.com/jcem/article-abstract/39/1/27/2685422
  13. https://academic.oup.com/jcem/article-pdf/39/1/27/10521357/jcem0027.pdf
  14. Origin of deoxycorticosterone sulfate (DOC-SO4) in plasma of pregnant women: pregnenolone-3,21-disulfate is a placental precursor of DOC-SO4 - PubMed
  15. Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand
  16. Pregnenolone sulfate - Wikipedia
  17. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  18. Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand - PMC
  19. https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.839887/pdf
 
Based on the available search results, there is no clear evidence of significant differences in the half-life of pregnenolone between men and women. The studies provided do not specifically address gender differences in pregnenolone's half-life. However, some relevant information can be extracted:

  1. The half-life of pregnenolone is reported to be approximately 3.7 hours (95% CI: 3.4 to 4.0 hours)4.
  2. In pregnant women, the mean half-life of pregnenolone sulfate was found to be 2.22 ± 0.70 hours4.
While these studies don't directly compare men and women, they do reveal some general information about pregnenolone metabolism:

Gender Differences in Pregnenolone Levels​

  • Men generally have higher serum levels of pregnenolone compared to women2.
  • The age-related decline in pregnenolone levels is more pronounced in men (78% decrease) compared to women (45% decrease)5.

Age-Related Changes​

  • Pregnenolone levels peak around age 16-17 in both sexes, with a second, statistically insignificant peak around age 47-4813.
  • Pregnenolone sulfate levels peak around age 27-32, remain stable until about age 52, and then decline5.
While these findings suggest some gender-related differences in pregnenolone metabolism, they do not specifically indicate a difference in half-life between men and women. Further research would be needed to determine if there are any significant gender-based variations in pregnenolone's half-life.

Citations:​

  1. Age relationships and sex differences in serum levels of pregnenolone and 17-hydroxypregnenolone in healthy subjects - PubMed
  2. Gender differences in the relationships among neurosteroid serum levels, cognitive function, and quality of life - PMC
  3. Age Relationships and Sex Differences in Serum Levels of Pregnenolone and 17-Hydroxypregnenolone in Normal Subjects
  4. https://onlinelibrary.wiley.com/doi/10.1111/jvim.15618
  5. Pregnenolone | Rupa Health
  6. https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.839887/pdf
  7. https://academic.oup.com/jcem/article-abstract/38/3/480/2685384
  8. Pregnenolone - Wikipedia
  9. https://www.researchgate.net/figure...erum-of-230-women-aged-10-70-yr_fig8_11376895
  10. https://www.researchgate.net/public...and_17-Hydroxypregnenolone_in_Normal_Subjects
  11. https://denverhormonehealth.com/hormones/pregnenolone/
  12. https://www.lifeextension.com/magazine/2004/6/report_preg
  13. https://academic.oup.com/jcem/article/103/1/320/4590236
  14. Allopregnanolone - Wikipedia
  15. Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand
  16. https://academic.oup.com/jcem/article/87/5/2225/2847192
  17. Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings - PMC
 
Human studies have investigated pregnenolone for various conditions:

Cognitive Function and Memory​

  • Pregnenolone supplementation improved learning and memory in some studies.
  • It increased the growth of neurons in the brain and enhanced the production of myelin, leading to improved cognitive function.

Mood and Mental Health​

  • Low levels of pregnenolone were linked to depression and anxiety.
  • Supplementation showed mood-boosting effects and helped control emotions.
  • In schizophrenia patients, pregnenolone (500 mg/day) significantly improved negative symptoms compared to placebo3.

Sleep​

  • Human studies demonstrated that pregnenolone increased time spent in deep sleep (slow wave sleep)1.
  • This improvement in sleep quality positively impacted mood, anxiety, and memory consolidation.

Schizophrenia​

  • A proof-of-concept trial used pregnenolone doses up to 500 mg/day for 8 weeks3.
  • Patients showed significant improvements in negative symptoms (SANS scores) compared to placebo.
  • Serum pregnenolone increases predicted cognitive improvements (BACS scores).

Safety and Tolerability​

  • Studies from the 1940s and 1950s showed pregnenolone (25-500 mg/day) was safe and well-tolerated3.
  • It did not affect weight, heart rate, blood pressure, menstrual cycle, or glucose levels.
  • A recent study using low doses (15-30 mg/day) in healthy volunteers reported no significant side effects compared to placebo3.

Social Isolation​

  • A study investigated pregnenolone (400 mg single dose) for perceived social isolation, but results were not provided in the search results5.
While these studies show promise, it's important to note that a human study mentioned in one source found no significant effects on mood, memory, sleep quality, or subjective well-being6. More research is needed to fully understand pregnenolone's effects and optimal dosing in various conditions.

Citations:​

  1. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  2. Pregnenolone – The Miracle Product of Cholesterol - Levitas Clinic Guildford
  3. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC
  4. https://www.lifeextension.com/magazine/2007/11/report_pregnenolone
  5. https://cdn.clinicaltrials.gov/large-docs/77/NCT02826577/Prot_SAP_002.pdf
  6. What Is Pregnenolone? Other Names: Pregnenolona, Pregnénolone - Consensus: AI Search Engine for Research
  7. https://www.lifeextension.com/wellness/supplements/pregnenolone-for-brain-health
  8. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression - PMC
  9. New Research Study: Pregnenolone Neurosteroid for the Treatment of Menopausal Depression - MGH Psychiatry News
  10. Pregnenolone Randomized Controlled Trial
  11. How Taking Pregnenolone Might Boost Brain Health
  12. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. - International Association for the Study of Pain (IASP)
  13. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  14. New USC Mann Study Unlocks the Potential of Neurosteroids
  15. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  16. Pregnenolone – Health Information Library | PeaceHealth
  17. https://academic.oup.com/jcem/article-abstract/10/4/455/2719879
 
Pregnenolone improves cognitive function through several mechanisms:

Neuronal Growth and Protection​

  • Enhances the growth of neurons in the brain
  • Stimulates the formation of new synapses
  • Acts as a neuroprotector, safeguarding brain cells

Myelin Production​

  • Boosts the production of myelin, a fatty layer that insulates nerves
  • Improved myelin leads to better nerve function and cognitive performance

Neurotransmitter Regulation​

  • Increases acetylcholine levels, a key neurotransmitter for memory and learning
  • Blocks GABA, allowing neurons to fire more rapidly

Memory Enhancement​

  • Improves learning and memory processes
  • Enhances post-training memory when administered to specific brain regions
  • Reverses memory deficits in older, memory-impaired animals

Sleep Improvement​

  • Stimulates deep sleep (slow wave sleep), which is crucial for memory consolidation
  • Positively impacts overall cognitive function through better sleep quality

Mood Regulation​

  • Helps control emotions and reduce negative emotional responses
  • May alleviate symptoms of depression and anxiety

Neuroprotection​

  • Protects against inflammation in the nervous system
  • May help prevent age-related cognitive decline
Pregnenolone's effects on cognitive function are particularly notable in older individuals or those with cognitive impairments, as it may help compensate for age-related declines in hormone levels and neurotransmitter function1345.

Citations:​

  1. https://www.lifeextension.com/magazine/2007/11/report_pregnenolone
  2. https://www.pnas.org/doi/10.1073/pnas.92.23.10806
  3. https://www.lifeextension.com/wellness/supplements/pregnenolone-for-brain-health
  4. https://www.pnas.org/doi/10.1073/pnas.94.26.14865
  5. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  6. Pregnenolone: Your Brain's Hidden Superpower for Cognitive Clarity
  7. Pregnenolone: A Precursor Hormone with Potential Memory and Brain Benefits
  8. Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive - PMC
  9. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration - PMC
  10. How Taking Pregnenolone Might Boost Brain Health
  11. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  12. What Is Pregnenolone? Other Names: Pregnenolona, Pregnénolone - Consensus: AI Search Engine for Research
  13. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00169/full
  14. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - Neuropsychopharmacology
 
The optimal dosage of pregnenolone for cognitive benefits varies based on different studies and recommendations:

Lower Dosages​

  • 5-15 mg per day for enhancing memory and cognitive functions1
  • 10-20 mg per day for general well-being and overall health1
  • 2.5-25 mg per day, with recommendations to keep it at or below 10 mg3

Moderate Dosages​

  • 50-100 mg daily for the average person5
  • 25-50 mg twice a day for medication-sensitive individuals5

Higher Dosages (Clinical Studies)​

  • Up to 500 mg/day in divided doses used in studies on schizophrenia patients, showing improvements in cognitive symptoms4
  • 30 mg/day for 8 weeks improved attention and working memory in schizophrenia patients6

Considerations​

  • Start with lower doses and gradually increase as needed1
  • Age-based recommendations: 10 mg for people over 40, 25 mg for over 50, and 50 mg for over 602
  • Higher doses may be recommended for specific conditions like chronic fatigue or inflammatory arthritis5
  • Dosage should be personalized based on individual needs and health status12
It's crucial to consult with a healthcare provider before starting pregnenolone supplementation, as they can recommend an appropriate dosage based on individual needs and monitor blood levels for optimal hormone balance.

Citations:​

  1. Understanding Pregnenolone: A Comprehensive Guide for Men on Benefits, Dosage, and Safety
  2. https://www.eurohealthproject.com/pub/media/factsheets/pregnenolone-FS-EN.pdf
  3. Proper Use of Hormone Precursors by Dr. Joseph J Collins, RN, ND | Your Hormones
  4. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC
  5. Pregnenolone: A Precursor Hormone with Potential Memory and Brain Benefits
  6. A 'Prohormone' that May Help Relieve Depression
  7. Pregnenolone Testing 101: When To Test And How To Understand Results
  8. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder - PMC
  9. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  10. https://www.lifeextension.com/vitamins-supplements/item00302/pregnenolone
  11. Pregnenolone Supplement for Mood and Memory Support
  12. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  13. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  14. How Taking Pregnenolone Might Boost Brain Health
  15. Pregnenolone
 
Pregnenolone interacts with several important neurotransmitter systems in the brain, particularly GABA and NMDA receptors. Here's an overview of these interactions:

Interactions with GABA Receptors​

  • Pregnenolone sulfate (PS), a metabolite of pregnenolone, inhibits GABA A receptor function37.
  • PS reduces the duration of GABA-induced channel openings and increases the time receptors spend in closed conformations3.
  • It enhances GABA A receptor desensitization and stabilizes desensitized states7.
  • PS depresses peak responses and accelerates the decay of GABA-mediated inhibitory synaptic currents7.

Interactions with NMDA Receptors​

  • Pregnenolone sulfate acts as a positive allosteric modulator of NMDA receptors19.
  • PS binds to the transmembrane domain of NMDA receptors, specifically at residues on the GluN2B and GluN1 subunits11.
  • It stabilizes the open-state position of the GluN1 M3 helices, enhancing NMDA receptor function11.
  • PS can stimulate dopamine release via an NMDA receptor-dependent mechanism at very low concentrations (as low as 25 pM)8.

Differential Effects Based on Receptor Subtypes​

  • PS potentiates NMDA-induced currents in NR1/NR2A and NR1/NR2B receptor subtypes but inhibits NR1/NR2C and NR1/NR2D subtypes5.
  • The modulatory effects of PS on NMDA receptors are consistent with a two-state model where PS either stabilizes or destabilizes the active state of the receptor, depending on which NR2 subunit is present5.

Potential Therapeutic Implications​

  • The ability of pregnenolone to increase levels of its sulfated derivative (PS) and other neurosteroids like allopregnanolone may contribute to its potential therapeutic effects in conditions like schizophrenia9.
  • Pregnenolone administration can lead to significant increases in serum levels of pregnenolone sulfate, which may help ameliorate hypothesized NMDA receptor hypofunction in schizophrenia9.
These complex interactions with GABA and NMDA systems suggest that pregnenolone and its metabolites play important roles in modulating neuronal excitability and synaptic plasticity. The balance between its inhibitory effects on GABA receptors and excitatory effects on NMDA receptors may contribute to its overall impact on brain function and potential therapeutic applications.

Citations:​

  1. Structural insights into opposing actions of neurosteroids on GABAA receptors - Nature Communications
  2. Divergent mechanisms of steroid inhibition in the human Ï1 GABAA receptor - Nature Communications
  3. Pregnenolone sulfate block of GABAA receptors: mechanism and involvement of a residue in the M2 region of the α subunit - PMC
  4. Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway - Translational Psychiatry
  5. Inhibition of the NMDA response by pregnenolone sulphate reveals subtype selective modulation of NMDA receptors by sulphated steroids - PMC
  6. Pregnanolone Sulfate Promotes Desensitization of Activated NMDA Receptors
  7. Pregnenolone Sulfate Modulates Inhibitory Synaptic Transmission by Enhancing GABAA Receptor Desensitization
  8. Pregnenolone sulfate induces NMDA receptor dependent release of dopamIne from synaptIc termInals in the striatum - PMC
  9. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - Neuropsychopharmacology
  10. US6083941A - Inhibition of NMDA receptor activity by pregnenolone sulfate derivatives - Google Patents
  11. Site of Action of Brain Neurosteroid Pregnenolone Sulfate at the N-Methyl-D-Aspartate Receptor - PubMed
  12. Anxiety disorders and GABA neurotransmission: a disturbance of modulat | NDT
  13. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16143
  14. http://umu.diva-portal.org/smash/record.jsf?pid=diva2:152268
  15. https://www.researchgate.net/public...lone_Sulfate_Activates_NMDA_Receptor_Channels
  16. https://bpspubs.onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0704543
  17. https://academic.oup.com/endo/article/147/6/2737/2878871
  18. Site of Action of Brain Neurosteroid Pregnenolone Sulfate at the N-Methyl-D-Aspartate Receptor
  19. Scholars@Duke publication: Pregnenolone-sulfate: an endogenous antagonist of the gamma-aminobutyric acid receptor complex in brain?
  20. Neurosteroids and GABA-A Receptor Function - PMC
  21. Frontiers | Neuroactive Steroids: Receptor Interactions and Responses
 
Pregnenolone can interact with various supplements and medications, so caution is advised when combining it with other substances. Here are some key considerations:

​

Interactions with Other Medications​

  • Sedatives: Pregnenolone may decrease the effects of benzodiazepines and other sedative medications2.
  • Hormone-sensitive medications: Caution is advised when taking pregnenolone with medications for hormone-sensitive conditions3.
  • GABA-affecting drugs: Pregnenolone might interfere with medications that increase GABA activity, such as those used for epilepsy and depression5.

General Precautions​

  • Consult a healthcare provider before combining pregnenolone with any medications or supplements, especially those affecting hormonal levels15.
  • Monitor for potential side effects or changes in medication efficacy when using pregnenolone alongside other substances13.
  • Consider hormone level testing before and during pregnenolone supplementation to ensure proper balance5.
It's crucial to work closely with a healthcare professional when considering pregnenolone supplementation, particularly if you are taking other medications or supplements. They can provide personalized advice based on your specific health needs and current medication regimen.

Citations:​

  1. What is Pregnenolone? | CLNQ
  2. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  3. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  4. Proper Use of Hormone Precursors by Dr. Joseph J Collins, RN, ND | Your Hormones
  5. Pregnenolone
  6. https://go.drugbank.com/drugs/DB02789
  7. Pregnenolone: What You Need to Know | USADA
  8. Alcohol and pregnenolone interaction on cerebral arteries through targeting of vascular smooth muscle Ca2+- and voltage-gated K+ channels of big conductance - PMC
  9. Pregnenolone – Health Information Library | PeaceHealth
  10. https://www.pureencapsulationspro.com/media/Pregnenolone.pdf
  11. How Taking Pregnenolone Might Boost Brain Health
  12. How Pregnenolone Interacts with Weight Loss Medications | Curex
  13. Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital - PubMed
  14. https://go.drugbank.com/drugs/DB02789/biointeractions
  15. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
 
Last edited:
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Based on the available information, there are some important considerations regarding taking pregnenolone with antidepressants:

Potential Interactions​

  • Pregnenolone may interact with certain antidepressants, particularly those that affect serotonin levels like selective serotonin reuptake inhibitors (SSRIs)6.
  • Some antidepressants, including fluoxetine, norfluoxetine, fluvoxamine, and paroxetine, have been shown to elevate allopregnanolone (ALLO) levels in the brain4. Pregnenolone is a precursor to ALLO, so combining them could potentially lead to excessive ALLO levels.

Possible Benefits​

  • There is some evidence that pregnenolone may have antidepressant-like effects on its own6. This suggests it could potentially enhance the effects of antidepressants, though more research is needed to confirm this.
  • Pregnenolone has shown promise in improving depressive symptoms in bipolar disorder when used as an add-on therapy15.

Safety Considerations​

  • The safety of long-term pregnenolone use (beyond 12 weeks) is not well established7.
  • Pregnenolone can cause steroid-like side effects, including mood changes, which could potentially interact with the effects of antidepressants2.

Recommendations​

  • It is crucial to consult with a healthcare provider before combining pregnenolone with antidepressants or any other medications.
  • A healthcare professional can provide personalized advice based on your specific health needs, current medication regimen, and potential risks.
  • Monitoring for side effects and changes in mood or medication efficacy is important if pregnenolone is added to an antidepressant regimen.
In conclusion, while there may be potential benefits to combining pregnenolone with antidepressants, there are also risks and uncertainties. Professional medical guidance is essential to ensure safe and effective treatment.

Citations:​

  1. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression - PMC
  2. Pregnenolone: Health Benefits, Side Effects, Uses, Dose & Precautions
  3. https://womensmentalhealth.org/posts/pregnenolone-menopause-study-2-2/
  4. https://cdn.clinicaltrials.gov/large-docs/77/NCT02826577/Prot_SAP_002.pdf
  5. What Is Pregnenolone? Other Names: Pregnenolona, Pregnénolone - Consensus: AI Search Engine for Research
  6. Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting - PMC
  7. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  8. The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation - PMC
  9. Pregnenolone: What You Need to Know | USADA
  10. Pregnenolone – Health Information Library | PeaceHealth
  11. https://womensmentalhealth.org/post...euroactive-steroids-and-gaba-may-play-a-role/
  12. https://go.drugbank.com/drugs/DB02789
  13. How Taking Pregnenolone Might Boost Brain Health
 
Based on the available information, there are no specific dietary restrictions mentioned when taking pregnenolone. However, some general dietary considerations may be beneficial:

  1. Healthy Fats: Consuming 20-30 grams of healthy fats daily (e.g., avocados, coconut oil, olive oil, walnuts, fish, chia seeds, and flax seeds) is recommended to support hormone health, including pregnenolone production3.
  2. Balanced Diet: A balanced diet is important to enhance the benefits of pregnenolone supplementation7.
  3. Morning Intake: It's suggested to take pregnenolone in the morning on an empty stomach14.
While there are no strict dietary restrictions, it's important to note that pregnenolone interacts with various hormones in the body. Therefore, it's advisable to consult with a healthcare provider before starting pregnenolone supplementation, especially if you have any existing health conditions or are taking other medications47.

Citations:​

  1. Pregnenolone
  2. https://downloads.regulations.gov/FDA-2012-S-1178-0077/attachment_1.pdf
  3. How to Regulate Your Hormones with Three Steps for a Natural Hormone Balance | CentreSpring MD
  4. https://www.eurohealthproject.com/pub/media/factsheets/pregnenolone-FS-EN.pdf
  5. Pregnenolone
  6. Pregnenolone: What You Need to Know | USADA
  7. Understanding Pregnenolone: A Comprehensive Guide for Men on Benefits, Dosage, and Safety
  8. Pregnenolone | Healthmatters.io
  9. Benefits of Pregnenolone: What Is It & Why You Should Be Taking It - Marion Gluck
  10. Boost Pregnenolone for More Hormone Energy | Healthy Keto™ Dr. Berg
  11. The Pregnenolone Steal: A Closer Look at this Popular Concept - Dr Fiona ND
  12. PREGNENOLONE: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews
  13. https://www.pureencapsulationspro.com/media/Pregnenolone.pdf
  14. Pregnenolone Benefits and Considerations: Is the Pregnenolone Steal Real?
  15. Proper Use of Hormone Precursors by Dr. Joseph J Collins, RN, ND | Your Hormones
  16. How Taking Pregnenolone Might Boost Brain Health
  17. https://downloads.regulations.gov/FDA-2017-N-2562-0017/attachment_1.pdf
  18. http://www.ndhealthfacts.org/wiki/Pregnenolone
  19. https://pmc.ncbi.nlm.nih.gov/articles/PMC4194260/
 

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