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a three month schizophrenia trial with Raloxifene or placebo - Blood-tests results

raloxifene schizophrenia trial

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#1 YoungSchizo

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Posted 20 June 2018 - 10:09 PM


Sup guys, 

 

I have been in a double-blind schizophrenia trial where they test Raloxifene/placebo on schizophrenic patients. Well.. I am still in the trial but the next en last appointment is a half year from now but the medication/placebo trial was for 12 weeks and has ended. I was wondering if from the blood-test, taking from week 1 and week 12 can give any insight into weather I had Raloxifene or placebo? There are quite a few changes in my blood results but I have no idea if I can contribute and/or conclude from it if I had the real deal or if it's just coincidence because there was a 12 week period in between. I will post them if someone is willing to have a look into it.

 

The study is based on changes in positive, negative and cognitive symptoms and depression. I didn't notice any changes the first 4-5 weeks but the second 7 weeks I have noticed a significant decrease in depressive symptoms (each week it was getting better), while the other symptoms remain as they were/are. I have no idea if I can contribute this change to the medication or because in those weeks I had things to do to keep my mind of things (I was injecting myself with FORTNITE, guilty!  :laugh:  :happy:  :cool: ).

 

Anyways, over six months I will get to hear if I had Raloxifene or placebo but I'm not planning to wait for that and will run my own "trial" within 2 months.

 

Any input?

 

I have a list of pharmacy's that are reliable but most of the contacts do not ship to the Netherlands. If someone can share a cheap and reliable source please PM me! 

 

 



#2 Galaxyshock

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Posted 21 June 2018 - 08:28 AM

Hmm an estrogenic compound for schizo treatment? Does this have something to do with the fact that male gender is linked to worse outcome in schizophrenia and targeting hormones may help? I suppose it's taken in combination with anti-psychotic treatment.



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#3 Mind_Paralysis

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Posted 21 June 2018 - 02:35 PM

Hmm an estrogenic compound for schizo treatment? Does this have something to do with the fact that male gender is linked to worse outcome in schizophrenia and targeting hormones may help? I suppose it's taken in combination with anti-psychotic treatment.

 

If I understand it correctly, abnormalities in both estrogenic and androgenic hormones have been observed in both genders with the disease, and the idea is that this drug - a SERM, will modulate activity more to the beneficial side - one can also not say that the drug should be considered to have the same effects as estrogen as well, since it actually seems to DECREASE some of the effects of estrogen on the body, instead causing some androgenic effects.

 

(I believe the drug is used by bodybuilders already, in order to combat gynoid side-effects and for post-cycle health)

 

I must admit that the whole part with the hormonal disturbances in Schizophrenia is completely new territory for me - could one say that Schizophrenia then appears to be more of a metabolic, whole-body-wide disease than previously assumed? A bit like its mirror opposite in some ways, Autism. (which is NOT just a neurological disorder - there are metabolic abnormalities that are a trade-mark of the disease as well, like disruptions in tryptophan-metabolism, which could underlie the sleeping-problems seen in Autism)



#4 YoungSchizo

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Posted 21 June 2018 - 10:04 PM

Hmm an estrogenic compound for schizo treatment? Does this have something to do with the fact that male gender is linked to worse outcome in schizophrenia and targeting hormones may help? I suppose it's taken in combination with anti-psychotic treatment.

 

Yes, one of the inclusion criteria's was that one has to be at least 2 weeks on antipsychotics. But other than that, there was not really a limit (at least for men) to be excluded.

 

Another reason why they came with this hypothesis is because post-menopause women with low levels of Estrogen were more likely to get worse psychotic symptoms than healthy women and showed improvement when Raloxifene was added. The idea behind it came from doctor Cynthia Shannon Weickert whom's twin brother was schizophrenic and started to investigate the role of Estrogen and schizophrenia. 

 

Raloxifene and cognition

Raloxifene on positive, negative, cognitive and depression, here. (This is I guess a part of the study which I'm a participant of or a study/summary that was before me..? idk..)

The one on which I decided to participate was a summary of study's (till 2017) and it's outcome's but.. weird.. Can't find it anymore. What I do remember was there were 4 large study's done to date, 2 of them showed significant changes, 2 didn't.  

 

If I understand it correctly, abnormalities in both estrogenic and androgenic hormones have been observed in both genders with the disease, and the idea is that this drug - a SERM, will modulate activity more to the beneficial side - one can also not say that the drug should be considered to have the same effects as estrogen as well, since it actually seems to DECREASE some of the effects of estrogen on the body, instead causing some androgenic effects.

 

(I believe the drug is used by bodybuilders already, in order to combat gynoid side-effects and for post-cycle health)

 

I must admit that the whole part with the hormonal disturbances in Schizophrenia is completely new territory for me - could one say that Schizophrenia then appears to be more of a metabolic, whole-body-wide disease than previously assumed? A bit like its mirror opposite in some ways, Autism. (which is NOT just a neurological disorder - there are metabolic abnormalities that are a trade-mark of the disease as well, like disruptions in tryptophan-metabolism, which could underlie the sleeping-problems seen in Autism)

 

Yes, I've read, Raloxifene is also gaining attention in the bodybuilding community to combat gyno. 

 

I already knew many years ago about Estrogen (and other hormones like Testosterone) might play a role but because it is a mainly female hormone I didn't investigate. I tried Pregnenolone (which is already well documented of having a positive effect on some symptoms) in the past when off antipsychotic and did notice positive changes on mind and body. I've also tried Testosterone gel for a couple months but didn't notice any changes. 

In the past I was obsessed with the possible role of (high) Cortisol levels and symptom severity but I never could convince my docs to have a look at that. Besides I've read that Mirtazapine lowers Cortisol and Mirtazapine is one of the only drugs I react very positive to. 



#5 YoungSchizo

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Posted 21 June 2018 - 10:30 PM

Anyway, what catch my attention is what this article states:

 

Aside from its use in mitigating Estrogen, Raloxifene has demonstrated considerable use as an endogenous Testosterone stimulating compound, as studies have demonstrated an increase of serum Testosterone levels by 20% from 120mg of Raloxifene per day[4].

 

 

and my prolactin, testosterone and estrogen levels. (2 years ago my Testosterone levels was just 1 point above the acceptable value.)

 

Here a pic at week 1 of the study:

 

Attached File  Capture.PNG   11.43KB   0 downloads

 

Week 12:

 

Attached File  Capture1.PNG   25.72KB   1 downloads

 

I don't know if this (big?) change is possible when someone is on the same meds and diet but for me it's quite a difference, no?

 

Although I didn't notice a change in severity of positive, cognitive, negatives I do notice difference on depressive symptoms.


Edited by YoungSchizo, 21 June 2018 - 10:33 PM.


#6 Galaxyshock

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Posted 25 June 2018 - 01:49 PM

I must admit that the whole part with the hormonal disturbances in Schizophrenia is completely new territory for me - could one say that Schizophrenia then appears to be more of a metabolic, whole-body-wide disease than previously assumed?

 

I suspect it's glutamate dysfunction, induced by excess kynurenic acid production/release in response to trauma/stress/extreme experience, which then can pretty much affect every process in the body as glutamate is the main excitatory neurotransmitter. Fixing downstream processes like dopaminergic, serotonergic and hormonal with pharmaceuticals can be enough to "quiet it down" so the patient has minimal symptoms, but the kynurenic acid -response to intolerable stress remains there and the schizophrenic remains always vulnerable.

 

Kynurenic acid is antagonist of all ionotropic glutamate receptors (AMPA, kainate, NMDA) and nicotinic acetylcholine, so it's dissociative on steroids. Once released in sufficient amount say goodbye to reality.


Edited by Galaxyshock, 25 June 2018 - 02:01 PM.

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#7 Mind_Paralysis

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Posted 25 June 2018 - 05:14 PM

I suspect it's glutamate dysfunction, induced by excess kynurenic acid production/release in response to trauma/stress/extreme experience, which then can pretty much affect every process in the body as glutamate is the main excitatory neurotransmitter. Fixing downstream processes like dopaminergic, serotonergic and hormonal with pharmaceuticals can be enough to "quiet it down" so the patient has minimal symptoms, but the kynurenic acid -response to intolerable stress remains there and the schizophrenic remains always vulnerable.

 

Kynurenic acid is antagonist of all ionotropic glutamate receptors (AMPA, kainate, NMDA) and nicotinic acetylcholine, so it's dissociative on steroids. Once released in sufficient amount say goodbye to reality.

 

Interesting! I've been aware of this substance, even looked into its properties and metabolism to some extent, but I had no idea it was an antagonist of ALL ionotropic Glurs, as well as nAch-a7! : O

That would actually explain quite a bit... because if that's correct, then KYNA targets multiple of the various targets that several different types of Anti-schizophrenia drugs are currently being developed to treat!

 

A drug which hampers KYNA metabolism could then theoretically be useful even for the depressive symptoms of Schiz' then... Ampa-agonism triggers neurogenesis, which is why Ketamine, Tianeptine and Lamotrigine helps with depression.

 

 

Interesting side-note - I conversed a bit with an Italian Professor whom had worked with drugs that increased the body's own production of KYNA - in theory... he should probably have some ideas on how to LOWER KYNA-production as well... Hmm...


Edited by Mind_Paralysis, 25 June 2018 - 05:18 PM.

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#8 Galaxyshock

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Posted 26 June 2018 - 07:39 AM

Indeed targeting KYNA might just be treating the disorder at very roots. There of course could be another endogenous "master" chemical that controls KYNA levels, but right now a lot of evidence and reasoning point towards kynurenic acid being the major player in psychotic symptoms. Sure, KYNA isn't there only to do you harm as it has neuroprotective qualities too, and well, when facing extreme fear or something it's probably rather natural to dissociate to some extent. The issue is when the situation changes but the dissociation remains as if the mind is no longer capable to face reality as it remembers it being too painful or something. A gentle way to remove this dissociation and increase self-assurance would probably be the way to come out of that state.

 

Let us know if you find something to control KYNA levels.


Edited by Galaxyshock, 26 June 2018 - 07:41 AM.


#9 YoungSchizo

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Posted 06 December 2018 - 01:13 PM

 

The study is based on changes in positive, negative and cognitive symptoms and depression. I didn't notice any changes the first 4-5 weeks but the second 7 weeks I have noticed a significant decrease in depressive symptoms (each week it was getting better), while the other symptoms remain as they were/are.

 

I got the answer from the double-blind study yesterday to whether I had placebo or Raloxifene. As I suspected already, I had Raloxifene.

The improvement in depressive symptoms was not a coincidence, I've been running my own trial with Raloxifene and I've been pretty much stable with my depression and it especially really helps against unwanted suicidal ideation. Though, sadly it did not improve any schizo symptoms. At least not in me, according to other study already completed it can also improve schizo symptoms in a sub-group.

 

I don't know whether a increase in Estrogen can lift a depression? But what I do know my Testosterone has been low for years due to the use of antipsychotics and I'm sure there's a connection with the increase of testosterone and improvement of depression. I also do not know which mechanism of Raloxifene causes to lower Prolactin.. Could it be that it perhaps increases Dopamine in some parts of the brain or could that also be related to increase of Estrogen and/or Testosterone?



#10 John250

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Posted 06 December 2018 - 09:06 PM

I got the answer from the double-blind study yesterday to whether I had placebo or Raloxifene. As I suspected already, I had Raloxifene.
The improvement in depressive symptoms was not a coincidence, I've been running my own trial with Raloxifene and I've been pretty much stable with my depression and it especially really helps against unwanted suicidal ideation. Though, sadly it did not improve any schizo symptoms. At least not in me, according to other study already completed it can also improve schizo symptoms in a sub-group.

I don't know whether a increase in Estrogen can lift a depression? But what I do know my Testosterone has been low for years due to the use of antipsychotics and I'm sure there's a connection with the increase of testosterone and improvement of depression. I also do not know which mechanism of Raloxifene causes to lower Prolactin.. Could it be that it perhaps increases Dopamine in some parts of the brain or could that also be related to increase of Estrogen and/or Testosterone?


From what I read estrogen and prolactin work together. If estrogen is lowered(raloxifene) that I’m turn can lower prolactin.

#11 YoungSchizo

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Posted 06 December 2018 - 09:20 PM

From what I read estrogen and prolactin work together. If estrogen is lowered(raloxifene) that I’m turn can lower prolactin.


That's not the case. Look up at the blood-work screenshots, my estrogen doubled actually (up to 1 point under acceptable value) and prolactin almost decreased in half (almost back to acceptable value).

Edited by YoungSchizo, 06 December 2018 - 09:37 PM.


#12 mono

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Posted 07 December 2018 - 12:06 AM

Yes I also have schizoaffective disorder and was psychotic and unmedicated for a number of years. I only just started medication early this year and have had barely any positive symptoms since then, but the depression and negative symptoms are seemingly worse.

 

The only thing is there have been studies done on the KYNA hypothesis, such as this one with galantamine and memantine and was only for cognitive impairment.

https://www.scienced...21500131630004X

 

I am glad you found that raloxifene was of some help YS, but it doesn't sound like the silver bullet that I would be looking in order to motivate me to try something like that.

 

Right now I am trialling uridine, and plan to look into other dopaminergic drugs such as 9-ME-BC and BPC-157, as that is the only thing I have been finding effective.


Edited by mono, 07 December 2018 - 12:07 AM.


#13 YoungSchizo

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Posted 07 December 2018 - 12:43 AM

Yes I also have schizoaffective disorder and was psychotic and unmedicated for a number of years. I only just started medication early this year and have had barely any positive symptoms since then, but the depression and negative symptoms are seemingly worse.

The only thing is there have been studies done on the KYNA hypothesis, such as this one with galantamine and memantine and was only for cognitive impairment.
https://www.scienced...21500131630004X

I am glad you found that raloxifene was of some help YS, but it doesn't sound like the silver bullet that I would be looking in order to motivate me to try something like that.

Right now I am trialling uridine, and plan to look into other dopaminergic drugs such as 9-ME-BC and BPC-157, as that is the only thing I have been finding effective.



It's definitely not a silver bullet for psychotic symptoms, though I'll probably keep it in my stack as add-on to Parnate and it's effects on increasing testosterone. However, I think women are the sex that would mostly benefit from Raloxifene for mainly positive and cognitive symptoms.

If I recall correctly you PM'ed once in the past, I guess you weren't on medication yet because it totally didn't make sense at all what you all said

Edited by YoungSchizo, 07 December 2018 - 12:45 AM.


#14 YoungSchizo

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Posted 07 December 2018 - 12:47 AM

Wtf.. forum is bugged..

My full reply:

It's definitely not a silver bullet for psychotic symptoms, though I'll probably keep it in my stack as add-on to Parnate and it's effects on increasing testosterone. However, I think women are the sex that would mostly benefit from Raloxifene for mainly positive and cognitive symptoms.

If I recall correctly you PM'ed once in the past, I guess you weren't on medication yet because it totally didn't make sense at all what you all said :D so I'm glad for you your positives are under control! Which AP are you on?

I've practically gave up on trialing nootropics and supplements in order to counter negatives and cognitives but if you find something that helps, please share it with us.

I've been one week on Cariprazine 1.5mg, it's such a WEIRD drug! I have no idea what to think of it yet, maybe I'll review it soon and share.

Edited by YoungSchizo, 07 December 2018 - 12:51 AM.


#15 mono

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Posted 07 December 2018 - 12:50 AM

Fair enough. It is always good to hear about different treatments and what is working and what is not. If I do find anything helpful I'll be sure to share it with the boards.

 

Yes that's right I sent you a PM a while ago when I was psychotic, that is probably why it didn't make any sense, haha. Right now I am on Invega/paliperidone injection once every three months.


Edited by mono, 07 December 2018 - 12:52 AM.


#16 John250

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Posted 07 December 2018 - 05:45 PM

That's not the case. Look up at the blood-work screenshots, my estrogen doubled actually (up to 1 point under acceptable value) and prolactin almost decreased in half (almost back to acceptable value).

Wow estrogen doubled on ralox that’s bizzare. I might be reading this wrong as I’m driving but it seems ralox regulates estrogen and dopamine.

https://www.ncbi.nlm...cles/PMC149792/

Edited by John250, 07 December 2018 - 05:55 PM.

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#17 YoungSchizo

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Posted 07 December 2018 - 08:45 PM

Wow estrogen doubled on ralox that’s bizzare. I might be reading this wrong as I’m driving but it seems ralox regulates estrogen and dopamine.

https://www.ncbi.nlm...cles/PMC149792/

Wow.. thanks, interesting info! I already thought it might regulate dopamine and it sure does, even much more than that. Too bad it doesn't affect my schizo symptoms though..

I think/guess the increase in Estrogen is dose related, 120mg is the max. dosage. Bodybuilders only use 20/40mg to combat gyno.
From the 'study' on myself I have about a month left of Ralox, after I'm done I'm going to let my blood-work done again. If it gets above acceptable Estrogen values I will cut back on the dosage and see how that'll effect me.

Edited by YoungSchizo, 07 December 2018 - 08:46 PM.






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