Anyone here supplementing with pregnenolone?

Is anyone here on the schizophrenia forum supplementing with pregnenolone? What effects have you noticed? I hear it can be very helpful in relieving negative cognitive symptoms, i.g. lifting brain fog, improving memory, attention, etc.

I found three clinical trials that had demonstrated effect...

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

Effects of a neurosteroid, pregnenolone, during the neonatal period on adenosine A1 receptor, dopamine metabolites in the fronto-parietal cortex and behavioral response in the open field.
Muneoka KT, Shirayama Y, Minabe Y, Takigawa M.
Brain Res. 2002 Nov 29;956(2):332-8.
PMID: 12445703

Never heard of it before. It's amazing how many supplements are available out there OTC.

Are you taking it?

I bought some of this stuff yesterday, brit. My son doesn't want to try it, but I'll try it and let you know if it helps me at all. Not the same as having someone with sz take it, but it's supposed to be generally useful for anyone, so ...

Maybe if it's helpful to me, my son will try it. I always hate to suggest things to him, because then he feels like he has to do what I'm asking, then he gets resentful.

I wish he were like you and willing to experiment some.

nbritton, are you still around? Do you know specifically how pregnenolone is supposed to help? I ask because I started taking this stuff regularly about a month ago, and I'm noticing an unexpected change. I'm not sure if it's this stuff that's causing it.

I've been in the doldrums for a number of years now. Totally lacking in motivation. I do the minimum I need to do to get by. My doctor said it was hormonal, and we experimented with some hormones for a while, but it made no difference at all.

Then a week or two after starting with this stuff, I found myself suddenly very productive at work. I think I've got more done in the last few weeks than in the previous few years. I feel like my old self again.

I'm also calmer.

I'm thinking about trying to convince my son to try this stuff, but I'm not sure exactly how it's supposed to help. According to wikipedia it's a potent anxolytic, and my son does have a lot of anxiety.

Anyway if you're still around, do you have any more info on this supplement? Thanks.

Not sure if nbritton is still around or not but after skimming some of the links he provided previously it looks like it addresses the NMDA hypofunction issue. So for sz there are 2 major theories one involves dopamine and one involves glutamate which binds to and activates the NMDA receptor. They are interlinked in a few ways for example dopamine signalling through the D2 receptor decreases baseline NMDA function so this may be one way the APs affect the NMDA pathway. NMDA fuctioning too low can be mimicked by the street drugs PCP and ketamine. So the way pregnenolone works is to increase the number of NMDA receptors on the cell surface so you end up getting more signal with the same amount of glutamate so theoretically it relieves the hypofunction. The one thing I would warn you about is that too much NMDA activity is actually neurotoxic so its a very delicate balance. This is one of the reasons we don't have any prescribed drugs targeting this protein yet. They are working on something that will regulate the glycine modulatory site as a treatment for sz rather than targeting the glutamate binding directly.

Also I just looked up what it is structurally and its a steroid in fact the precursor to all the steroid hormones so these are OK short term but in the long term there can be consequences. So when pro sports players are talking about the problems with steroid supplementation this is going to apply because it makes all of them once it goes into your body also its likely to result in a decrease in the levels of endogenous pregnenolone in your body which could make any sort of withdrawal well on the order of unhappy.

It looks like pregnenolone is a precursor to a bunch of hormones like estrogen and testosterone. My doctor thought I was low on estrogen. The compounding pharmacist she sent me to thought I was low on testosterone - based on my symptoms. I had all of the symptoms of low T, none for low estrogen. (My blood work came back in the normal range for everything except DHEA which I was way too high on.) The testosterone cream he gave me did nothing.

All I know is I feel better now. And I don't want to go back to feeling unmotivated again.

I wish I knew a doctor I really trusted.

Well there may be side effects but so far as I can tell most of them are not nearly so severe as an antipsychotic so I wonder why this is not being used more TBH. The only real problem I could see is if you ever had to get off of it. Further reading suggests it actually mitigates glutamate neurotoxicity so no worries about that just the steroid effects and I'm sure you would be taking a lower dose than some guy who wants to build muscle for pro sports...

Yes, I'm taking 50 mg daily, and apparently I could be taking a lot less than that. I've seen a variety of recommendations - from 5 mg to 25 mg per day to 300 mg one time a week. I just bought what I could find. I may start taking the 50 mg capsule 3 or 4 times per week and see if I get the same effect (assuming the effect I'm seeing is from the pregnenolone).

Very interesting. I might try it. I just gave up diet coke. I drank about 8 a day because I'm always so
tired but i have to change my habits because i have fibromyalgia and a sprained ankle from September that won't heal. My body is totally whacked. Costello, would be cool if your son would try it.

I mentioned it to him again this morning. He didn't seem interested.

I'm curious about this. Where did you find it to buy it? A healthfood store or regular store or does it come under another name? But, I wonder does it effect blood glucose like other steroids?

I found it at a local store which carries supplements and things. I check my blood sugar every morning, and I've seen no effect at all on it.

You mentioned you are always so tired. Have you had your thyroid checked?