Vitamin Pregnenolone - New Treatment for Schizophrenia - anyone trying it?

SzAdmin · September 22, 2014, 10:27pm

Please let me know if you have tried pregnenolone? What effects positive or negative have you noticed?
If you haven’t tried it - perhaps try it and report back.

I’ve read that it can be helpful in negative symptoms that are common in schizophrenia.

The dosing in the top study was 50 mg per day.

It can be purchased here (this link is a google shopping search:
https://www.google.com/?gws_rd=ssl#q=Pregnenolone&safe=off&tbm=shop

I found some clinical trials that had demonstrated effect…

Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.
Ritsner MS1, Bawakny H, Kreinin A.

ncbi.nlm.nih.gov

Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.

MS Ritsner, H Bawakny and A Kreinin, Psychiatry and clinical neurosciences, Jun 2014

Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents. This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA.Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011. Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications. The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores. Secondary outcomes included assessments of functioning, and side-effects.Analysis was by linear mixed model. Fifty-two participants (86.7%) completed the trial. Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79). Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.

Neuroscience. 2011 Sep 15;191:78-90. doi: 10.1016/j.neuroscience.2011.06.076. Epub 2011 Jul 1.
Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence.
Marx CE1, Bradford DW, Hamer RM, Naylor JC, Allen TB, Lieberman JA, Strauss JL, Kilts JD.

ncbi.nlm.nih.gov

Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence.

CE Marx, DW Bradford, RM Hamer, JC Naylor, TB Allen, JA Lieberman, JL Strauss and JD Kilts, Neuroscience, Sep 2011 15

Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). Additional evidence consistent with a therapeutic role for pregnenolone in schizophrenia includes neurosteroid changes following administration of certain antipsychotics in rodent models. For example, clozapine elevates pregnenolone levels in rat hippocampus, and these increases may potentially contribute to its superior antipsychotic efficacy [Marx et al. (2006a) Pharmacol Biochem Behav 84:598-608]. Further, pregnenolone levels appear to be altered in postmortem brain tissue from patients with schizophrenia compared to control subjects [Marx et al. (2006c) Neuropsychopharmacology 31:1249-1263], suggesting that neurosteroid changes may play a role in the neurobiology of this disorder and/or its treatment. Although clinical trial data utilizing pregnenolone as a therapeutic agent in schizophrenia are currently limited, initial findings are encouraging. Treatment with adjunctive pregnenolone significantly decreased negative symptoms in patients with schizophrenia or schizoaffective disorder in a pilot proof-of-concept randomized controlled trial, and elevations in pregnenolone and allopregnanolone post-treatment with this intervention were correlated with cognitive improvements [Marx et al. (2009) Neuropsychopharmacology 34:1885-1903]. Another pilot randomized controlled trial recently presented at a scientific meeting demonstrated significant improvements in negative symptoms, verbal memory, and attention following treatment with adjunctive pregnenolone, in addition to enduring effects in a small subset of patients receiving pregnenolone longer-term [Savitz (2010) Society of Biological Psychiatry Annual Meeting New Orleans, LA]. A third pilot clinical trial reported significantly decreased positive symptoms and extrapyramidal side effects following adjunctive pregnenolone, in addition to increased attention and working memory performance [Ritsner et al. (2010) J Clin Psychiatry 71:1351-1362]. Future efforts in larger cohorts will be required to investigate pregnenolone as a possible therapeutic candidate in schizophrenia, but early efforts are promising and merit further investigation. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.
Ritsner MS, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, Weizman A, Lerner V.
J Clin Psychiatry. 2010 Oct;71(10):1351-62. doi: 10.4088/JCP.09m05031yel. Epub 2010 Jun 15.
PMID: 20584515

Pregnenolone for cognition and mood in dual diagnosis patients.
Osuji IJ, Vera-Bolaños E, Carmody TJ, Brown ES.
Psychiatry Res. 2010 Jul 30;178(2):309-12. doi: 10.1016/j.psychres.2009.09.006. Epub 2010 May 21.
PMID: 20493557

Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia.
Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, Strauss JL, Naylor JC, Payne VM, Lieberman JA, Savitz AJ, Leimone LA, Dunn L, Porcu P, Morrow AL, Shampine LJ.
Neuropsychopharmacology. 2009 Jul;34(8):1885-903. doi: 10.1038/npp.2009.26. Epub 2009 Apr 1.
PMID: 19339966
Additionally, I also found these journal articles…
The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional N-methyl D-aspartate receptors to the cell surface via a noncanonical, G protein, and Ca2±dependent mechanism.
Kostakis E, Smith C, Jang MK, Martin SC, Richards KG, Russek SJ, Gibbs TT, Farb DH.
Mol Pharmacol. 2013 Aug;84(2):261-74. doi: 10.1124/mol.113.085696. Epub 2013 May 28.
PMID: 23716622

Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
Wong P, Chang CC, Marx CE, Caron MG, Wetsel WC, Zhang X.
PLoS One. 2012;7(12):e51455. doi: 10.1371/journal.pone.0051455. Epub 2012 Dec 11.
PMID: 23240026

A steroid modulatory domain in NR2A collaborates with NR1 exon-5 to control NMDAR modulation by pregnenolone sulfate and protons.
Kostakis E, Jang MK, Russek SJ, Gibbs TT, Farb DH.
J Neurochem. 2011 Nov;119(3):486-96. doi: 10.1111/j.1471-4159.2011.07442.x. Epub 2011 Sep 28.
PMID: 21883211

Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence.
Marx CE, Bradford DW, Hamer RM, Naylor JC, Allen TB, Lieberman JA, Strauss JL, Kilts JD.
Neuroscience. 2011 Sep 15;191:78-90. doi: 10.1016/j.neuroscience.2011.06.076. Epub 2011 Jul 1. Review.
PMID: 21756978

The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia.
Ritsner MS.
Neuroscience. 2011 Sep 15;191:91-100. doi: 10.1016/j.neuroscience.2011.04.017. Epub 2011 Apr 24. Review.
PMID: 21549182

Pregnenolone, dehydroepiandrosterone, and schizophrenia: alterations and clinical trials.
Ritsner MS.
CNS Neurosci Ther. 2010 Spring;16(1):32-44. doi: 10.1111/j.1755-5949.2009.00118.x. Review.
PMID: 20070787

Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum.
Whittaker MT, Gibbs TT, Farb DH.
J Neurochem. 2008 Oct;107(2):510-21. doi: 10.1111/j.1471-4159.2008.05627.x. Epub 2008 Aug 14.
PMID: 18710414

Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects.
Ritsner M, Maayan R, Gibel A, Weizman A.
Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65. Epub 2006 Nov 21.
PMID: 17123790

Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy?
Marx CE, Shampine LJ, Duncan GE, VanDoren MJ, Grobin AC, Massing MW, Madison RD, Bradford DW, Butterfield MI, Lieberman JA, Morrow AL.
Pharmacol Biochem Behav. 2006 Aug;84(4):598-608. Epub 2006 Sep 8.
PMID: 16962649

Hatty · September 22, 2014, 10:31pm

Thank you. That’s a very useful post.

SzAdmin · September 22, 2014, 10:51pm

Let us know if you try it - and what the effects were.

Jayster · September 23, 2014, 3:09am

Gee, I wonder about calling this hormone a vitamin. I gather Vitamin D is a hormone, however.

Well, I know who to ask about Pregnenolone. Specifically, I go to a specialist in OTC nutrients for schizophrenia, although his practice has been turned upside down by all the cancer patients who clearly demonstrated that his stuff saves lives; schizophrenics like myself have to deal with stuff like, “Well, you probably were misdiagnosed when they labeled you schizophrenic.” Yeah, and I was surely misdiagnosed when they locked me up against my will for nearly two years in mental hospitals; now I’ve lived independently for greater than 30 years.

I do well.

Jayster

pob · September 23, 2014, 4:58am

I wonder if any studies have been done on long term effects.

SzAdmin · September 23, 2014, 5:10am

Studies haven’t been done on the long term effects of pharmaceuticals, so I doubt that they’ve been done with nutritional supplements.

pob · September 23, 2014, 5:14am

I think this is a hormone that occurs naturally in the body. I would be wary of upping the amount because it is a hormone… Though the good effects would be tempting. I would probably not try it until it was tested by time.

SzAdmin · October 7, 2014, 4:59am

Great - Let us know how it goes.

shutterbug · October 7, 2014, 5:04am

Will order some and let you know.

10-96

SzAdmin · October 7, 2014, 11:26pm

Let us know of you’ve tried it - and if it does anything for you. Tell us us how long you’ve been using it - and what brand of product (where you purchased it). Thanks.

SzAdmin · October 8, 2014, 5:16pm

Thanks Pixel,

Let us know.

anon32099838 · October 18, 2014, 2:16pm

I read good things about Pregnenolone and decided to try it over a year ago. I took half of the pill, which was a total of 25 mg. I felt a bit lightheaded after it. The reason I didn’t take it anymore is because I couldn’t read after I took it, this effect went away luckily. I first got the side-effect of not being able to read after I took a high dose of Piracetam for some time. After that I have gotten it also from fish oil and Licorice root, with varying degrees of severity. I did like how it made me feel overall, it helped my akathisia a lot and negative symptoms were better. I think I still have it so I might try it again but I doubt I will have a different response, I know that’s just me and almost everybody else doesn’t get the effect on their ability to read.

Envisioneer · October 20, 2014, 7:03pm

I will try it. I researched about it before but never tried it yet. I will share my results on here too.

Hatty · October 21, 2014, 12:25am

How can one get this stuff? Does it have to be prescribed? What if you live in the UK? Anyone know?

SzAdmin · October 21, 2014, 5:03pm

Hi - you can just buy it online. I like to use the Google Shopping Search engine - here is the link/search - just click on it and you can see where you can buy the products. You need to take 50mg a day says the study.

locamotion · October 26, 2014, 10:25am

This drug is a steroid. I take steroids off and on to treat asthma and RA. They are horrible albeit lifesaving drugs. It is dangerous to take steroids long term. They negatively affect immunity and caused thinning of the skin as well as disrupt sleep and cause excessive weight gain. I am currently taking Medrol - a steroid for RA and am suffering from all its effects. I wonder if Medrol and Prednisone help negative symptoms. I know that steroids can cause psychosis. I have had problems with that when taking higher doses. I would want some of these questions answered before I would agree to take it.

Jayster · October 26, 2014, 6:05pm

Are steroids hormones? Are steroids vitamins?

Jayster

SzAdmin · October 26, 2014, 6:34pm

Its a Neurosteroid - which I think is different:

SzAdmin · October 27, 2014, 5:06pm

Interesting information on the neurosteroid action:

And - as was suggested - just for shorter term use right now until longer term studies come out: