Pregnenolone As A Treatment For Loneliness

Discussion in 'Scientific Studies' started by haidut, Dec 11, 2016.

  1. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    I touched upon this idea/topic in some of my other posts, and just like those other posts, I would like to emphasize here that I am not suggesting steroid supplementation as a substitute for social interaction. The purpose of this post if to provide some insight on the biochemical effects of loneliness and social isolation, which seem to be pervasive in modern society. Loneliness is apparently a very strong predictor of future development of depression and as such understanding its effects and potentially offsetting some of them can prevent bigger problems in mental health in the future.
    This study focuses on the role of the steroid allopregnanolone in mental health. It describes a number of studies, both human and animal, which discovered that allopregnanolone levels initially rise and then plummet as a result of chronic stress. This pattern matches quite well the one observed with the steroid DHEA/DHEA-S. Given that both DHEA and allopregnanolone are potent inhibitors of the HPA response, the loss of these steroids due to chronic stress would lead to HPA overactivation. HPA overactivation has been causally linked to pretty much every major mental health conditions such as depression, bipolar disorder, PTSD, schizophrenia, AD, PD, and of course suicidal ideation and behavior. In general, most mental disorders are characterized by reductions of 5-AR activity and levels (low allopregnanolone, DHT, androsterone), increases in 11b-HSD1 (high cortisol), and decrease in 11b-HSD2 (low deactivation of cortisol).
    Given the animal and human trials showing elevation of allopregnanolone levels leading to suppression of HPA overactivation, the study proposes suplementation with pregnenolone as a reliable method to raise the allopregnanolone levels. Supplementation with allopregnanolone or other precursor such as progesterone or 5a-DHP are also likely to lead to the same outcome, assuming the theory is correct.
    Finally, adding some emodin and niacinamide could help even more as emodin is a very potent 11b-HSD1 inhibitor, while niacinamide (through NAD conversion) enhances 11b-HSD2 activity.

    Why may allopregnanolone help alleviate loneliness? - PubMed - NCBI

    "...To the extent that the brain is the central organ for evaluating relationships with others, the neuroendocrine system becomes an important system through which perceived social isolation may operate, at least in part, to affect morbidity and mortality. Research suggests that loneliness and social threats are associated most consistently with activity of the HPA axis [8 for review]. Human and animal investigations of social isolation and the neuroendocrine system suggest that: (a) chronic social isolation increases the activation of the HPA axis, and (b) these effects are more dependent on the disruption of a social bond between a significant pair than objective isolation per se [8 for review]."

    "...ALLO has specific regulatory effects on the HPA axis functions [38, 47]. While acute stress increases ALLO levels, which negatively modulates the stress-induced HPA axis activation and facilitates the recovery post-stressful events, repeated or chronic [physical or emotional] stress leads to a significant reduction in serum concentration of ALLO [37-38 for reviews]. This suggests that chronic stress alters ALLO synthesis, which in turn leads to the hyperactivation of the HPA axis [38, 50]."

    "...Combined, these results in animals indicate that administration of exogenous ALLO (or ALLO precursors) either during or following a period of chronic stress can prevent or normalize HPA dysfunction and impairment of hippocampal neurogenesis respectively, precluding the establishment of depressive/anxiety-like behaviors. In line with this, clinical studies show that decreases in the serum, plasma, and cerebrospinal fluid content of ALLO are associated with several psychiatric disorders such as depression, anxiety spectrum disorders, posttraumatic stress disorders, premenstrual dysphoric disorder, schizophrenia, and impulsive aggression [37-38, 51-61]. Together, these findings provide a strong rationale for our ALLO hypothesis of loneliness."

    "...Our ALLO hypothesis of loneliness suggests that low corticolimbic ALLO levels and diminished ALLO regulation play a crucial role in loneliness. Even if it is of course clear that feeling lonely is not a prerequisite to de-activate the ALLO system, we postulate the existence of a shared mechanism for both loneliness and the ALLO system. If this hypothesis is correct, one would expect that the exogenous administration of ALLO (or ALLO precursors) in lonely individuals to increase cortico-limbic levels of ALLO and BDNF mRNA expression and to decrease subjective feelings of loneliness and the associated deleterious physiological effects (e.g., elevated HPA activation, impaired sleep salubrity) in comparison with a placebo. The subjective character of loneliness can make it difficult to assess definitively. The tools of social neuroscience make it possible to approach loneliness not only by the analysis of subjective self-reports (e.g., UCLA loneliness scale), but also by approaching the automatic (non-conscious) self-preservation mechanisms of loneliness, for instance, using high performance electrical neuroimaging and evoked microstate analyses [13-14]."

    "...Based on these neural findings, exogenous administration of ALLO (or an ALLO precursor that can cross the blood brain barrier i.e., pregnenolone), with event-related functional and/or electrical neuroimaging in a double-blind, placebo-controlled, crossover design in lonely individuals should make it possible to observe a modulation of this cascade of activation and deactivation in the amygdala region and temporo-parietal junction observed in response to social threat. Based on a recent fMRI study showing the modulation of the amygdala and the dorsal medial prefrontal cortex (two regions rich in GABAA receptors) two hours after a single dose of 400 mg pregnenolone in healthy subjects while they were performing an attention emotion appraisal task [63], we expect the exogenous administration of a single dose of 400 mg pregnenolone to reduce [and normalize] the amplitude response of the amygdala that is known to be increased in lonely individuals. In turns, the reduction of amygdala activity should lead to an increased response of (and an increased connectivity with) the dorsal medial prefrontal cortex and the temporo-parietal junction in the early stages of information processing."

    Cortisol metabolism in depressed patients and healthy controls. - PubMed - NCBI
    "...RESULTS:Depressed patients showed reduced 5alpha-reductase activity manifested as a significantly lower amount of 5alpha-THF (102.8 +/- 167.2 vs. 194.6 +/- 165.8 microg, p = 0.019). The increase in the UFF/UFE ratio (0.73 +/- 0.32 vs. 0.29 +/- 0.13, p < 0.0001) indicates reduced activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). During pharmacological treatment, 5alpha-reductase activity in patients returned to the level of the control group, while the decrease in 11beta-HSD2 activity persisted until day 28."
     
  2. bzmazu

    bzmazu Member

    Joined:
    Oct 29, 2015
    Messages:
    1,183
    Gender:
    Male
    Location:
    Corozal, Belize
    Interesting and timely information...thank you
     
  3. MistyH

    MistyH Member

    Joined:
    May 28, 2016
    Messages:
    26
    Gender:
    Female
    My Grand Mother was an isolated diagnosed schizophrenic. My Mother is a paranoid (not diagnosed by anyone) person with delusional thoughts. She raised us to constantly live on HPA over drive. I had ADHD, a Tic and OCD. I crashed at 49 with CFS. This is fascinating to me and sadly, yet excitingly, I feel like I have answers to questions of a generation of Women in my family.
     
  4. mujuro

    mujuro Member

    Joined:
    Nov 14, 2014
    Messages:
    658
    Adding in Pansterone and Lapodin with the regular Bs and aminos has made my bipolar symptoms disappear. Even on days I forget to take my medication. Previously if I forgot my SSRI I'd know about it by 3pm. Now I sometimes go days without it, completely unintentionally. I've also cut my antipsychotic down by half and haven't noticed a thing.
     
  5. Greg says

    Greg says Member

    Joined:
    Nov 6, 2014
    Messages:
    331
    Gender:
    Male
    Didn't Ray Peat have hamsters to combat loneliness?
     
  6. gp3690

    gp3690 Member

    Joined:
    Aug 28, 2015
    Messages:
    57
    I can say that being home alone after work for more than three days has a serious mental effect. You dont realize this until you see people during the week and realize how great it feels!
     
  7. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    Sorry to hear about this. Hopefully, this knowledge can be used to help those women. Are you using pregnenolone?
     
  8. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    Wow, this is amazing! How much are you using of each? Do you mind posting your experience in the Pansterone and Lapodin threads below? Obviously, feel free to post the negative as well as the positives.
    Pansterone - Liquid Dietary Supplement For Rejuvenation
    Lapodin - Dietary Supplement With Beta-lapachone And Emodin
     
  9. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    Do you know where he said that?
     
  10. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    The interaction with other people in a positive way has direct physiological effects such as raising dopamine. Dopamine keeps serotonin low and the HPA axis is primarily under the control of serotonin. However, I emphasize that the interaction has to be a positive one. Being surrounded by bitter (or sick) people has direct sickening effect. Stressed cells emit electromagnetic signals that can be picked up from a distance of up to 30 feet. People who work on hospitals wards focusing on specific patients (kidney disease, GI, neurological, oncology, etc) overwhelmingly tend to get the same condition (and even die from it) as the patients they see every day. Given the long-distance cross-organism cellular communication, this is not a coincidence.
     
  11. lollipop

    lollipop Guest

    30 ft?!?! What profoundly important fundamental understanding! A must know type of knowledge. Thank you @haidut for highlighting this.
     
  12. High_Prob

    High_Prob Member

    Joined:
    Mar 23, 2016
    Messages:
    207
    Gender:
    Male
    Haidut, do you have sources? I would like to read about this further (about stressed cells emitting electromagnetic signals that can be picked up from a distance of up to 30 feet...)...
     
  13. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
    I think the official position is that this is a very "controversial" subject. Which really stands for "Gosh, I hope people don't suddenly realize how much they are effected by their environment or they will revolt against the unhealthy conditions we create for them that directly cause disease". The 30 feet limit was mentioned by Montagnier in an interview where he was asked how far away a person should be from "sick" cells or bacteria so that the healthy person cells does not get affected. Keep in mind, this also implies you can get even bacterial infection from a distance. You can jump to Section D for discussion on human cells receiving EMS and incorporating the information.
    How Bacteria Could Generate Radio waves
    [1501.01620] Transduction of DNA information through water and electromagnetic waves
    "...The experimental conditions by which electromagnetic signals (EMS) of low frequency can be emitted by diluted aqueous solutions of some bacterial and viral DNAs are described. That the recorded EMS and nanostructures induced in water carry the DNA information (sequence) is shown by retrieval of that same DNA by classical PCR amplification using the TAQ polymerase, including both primers and nucleotides. Moreover, such a transduction process has also been observed in living human cells exposed to EMS irradiation. These experiments suggest that coherent long range molecular interaction must be at work in water so to allow the observed features. The quantum field theory analysis of the phenomenon is presented."
     
  14. Regina

    Regina Member

    Joined:
    Aug 17, 2016
    Messages:
    1,814
    Gender:
    Female
    Location:
    Chicago
    It makes sense.
     
  15. MistyH

    MistyH Member

    Joined:
    May 28, 2016
    Messages:
    26
    Gender:
    Female
    Thank you Haidut. I am using pregnenolone. Sadly, my Grand Mother died at 43 in 1973 and my Mother and I have a strained relationship. Something I forgot to add was my Mother's removal of her uterus in the early 80's. I remember her claiming it saved her life. (We still suffered)
     
  16. Jsaute21

    Jsaute21 Member

    Joined:
    Sep 3, 2016
    Messages:
    1,232
    Gender:
    Male
    @haidut - have you seen any studies on OCD symptoms? and what hormones might have a positive effect? I assume Pansterone would be one that would be very positive.
     
  17. OP
    haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,457
    Gender:
    Male
    Location:
    USA / Europe
  18. Jsaute21

    Jsaute21 Member

    Joined:
    Sep 3, 2016
    Messages:
    1,232
    Gender:
    Male
    Thanks @haidut. Since finding Peat and this forum, symptoms have far improved. When i was eating PUFA, high muscle meat protein, starches, high fiber with low meal frequency, my OCD was pretty out of control. It was never bad growing up, except at one point in my teens and then i completely abandoned it for a decade. Pretty interesting. Glycine is a pretty awesome tool.
     
  19. Makrosky

    Makrosky Member

    Joined:
    Oct 5, 2014
    Messages:
    2,385
    Gender:
    Male
    haidut,

    I have a flatmate that generates really strong bad vibes. It makes me depressed. I know she is, she has told me. And seeing what she eats... wow, I will skip the details. I'm starting to get worried because I never felt it so strongly with anyone except her. I'm a really sensitive person and tend to pick up other's emotions but, man, this is strong. Makes me wonder if it's in my head ? But I get a physical reaction like to not even be close to her. It's ridiculous.

    Besides the normal Peaty tools, anything specific to counteract this kind of problems ?

    I'll try to move ASAP but it's not that easy for me right now.

    Thanks!
     
  20. Drareg

    Drareg Member

    Joined:
    Feb 18, 2016
    Messages:
    1,865
    Gender:
    Male
    She could be picking up on your outlook also,if you have changed meanings and gone more forward thinking people currently disposed to certain low energy meanings will start disliking you,she could be trying to bring you down in her own particular way.
    Surface tensions,the context of the environment will effect meanings,all this effects energy,she is eating you,cannabilzing you spiritually,get out! Get out man!
     
Loading...