6219 replies to this topic

[Nick Kyz]

Has anyone stacked NSI with LDN? I have some naltrexone, could try it out...

I'm planning to do exactly this (great minds think alike?). I've used LDN before but I've been reading research about its effects on microglia which is making me consider trying it again. Ibudilast is another one with potent anti-inflammatory effects on microglia. (R)

Edited by Nick Kyz, 06 April 2016 - 08:54 PM.

[Omega 3 Snake Oil]

Has anyone stacked NSI with LDN? I have some naltrexone, could try it out...

I was on LDN for about four months prior to trying NSI. I came to learn LDN causes ACTH to spike, which I think was causing some problems for me, so I stopped. After two weeks off of LDN I tried NSI for the first time and had a bad experience. I'm not sure if they are related but I'm thinking there might be some connection

 

Has anyone stacked NSI with LDN? I have some naltrexone, could try it out...

 reading research about its effects on microglia which is making me consider trying it again.

 

Can you please elaborate on this?

[Nick Kyz]

Here you go: http://www.ncbi.nlm....les/PMC3962576/

 

 

 

Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

 

[StevesPetRat]

Nick, I suspect the microglial effect is due to TLR4 antagonism... this is one of the most powerful inflammatory signaling pathways in the body.

More here. https://en.wikipedia...ki/(+)-Naloxone

I would be very, very interested to obtain some dextro-naltrexone or naloxone to block only the potentially inflammatory action at the toll-like receptor while allowing the (probably) beneficial mu-opioid agonism to continue.

In one study, dextro naltrexone was as effective as naltrexone in reducing pain in fibromyalgia. I expect we will eventually find "endorphin rebound" to be a total red herring in the efficacy of LDN in treating autoimmune disease.

Sorry for the tangent. The point is, I want to try dextro naltrexone + NSI-189

[Autonomous]

Nick, I suspect the microglial effect is due to TLR4 antagonism... this is one of the most powerful inflammatory signaling pathways in the body.

More here. https://en.wikipedia...ki/(+)-Naloxone

I would be very, very interested to obtain some dextro-naltrexone or naloxone to block only the potentially inflammatory action at the toll-like receptor while allowing the (probably) beneficial mu-opioid agonism to continue.

In one study, dextro naltrexone was as effective as naltrexone in reducing pain in fibromyalgia. I expect we will eventually find "endorphin rebound" to be a total red herring in the efficacy of LDN in treating autoimmune disease.

Sorry for the tangent. The point is, I want to try dextro naltrexone + NSI-189

 

If you're concerned with inflammation or TLR4 antagonism, why not just take Turmeric (Curcumin C3 complex) with BioPerine (10-15mg)?

 

http://www.ncbi.nlm....pubmed/24669820

 

I've been able to completely remove any corticosteroids or other anti-inflammatories that were previously needed to control allergies by adopting a daily turmeric extract regimen. Turmeric should be in everyone's stack unless you must take steroids.

[Nick Kyz]

Tumeric, especially Longvida Curcumin is good. But it's palliative and with most palliatives relying on it too long has deleterious effects, at minimum your homeostasis changes.  Everything should be cycled.

 

Re: Bioperine

It has many pernicious effects, it works by inhibiting enzyme reactions, which obviously increases bioavailability but that's not something you really want to do, especially to your liver detoxification pathways:

 

Piperine, a natural bioenhancer, nullifies the antidiabetic and antioxidant activities of curcumin in streptozotocin-diabetic rats. Piperine, a natural bioenhancer, nullifies the antidiabetic and antioxidant activities of curcumin in streptozotocin-diabetic rats.

Arcaro CA1, Gutierres VO1, Assis RP1, Moreira TF1, Costa PI1, Baviera AM1, Brunetti IL1.

Author information

 

Abstract

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation.

 

http://www.ncbi.nlm....pubmed/25469699

Edited by Nick Kyz, 07 April 2016 - 01:02 AM.

[tolerant]

 

 

 

Yes, anxiety.

This is a common enough startup side effect. Those who've stuck with it say it passes in 1 - 3 weeks, and was generally worth it.

You may want to lower further your selegiline, as some are reporting increased sensitivity to stims on NSI.

 

Anyway, that's not really why I came back to post. I still propose that cortisol modulation is a primary means by which the effects of NSI-189 are realized. However, looking at its low affinity for every tested receptor type (there's a post somewhere within the past few pages), I wonder if the upstream cause of this modulation is in fact epigenetic. Of course, I don't have any very strong evidence for this proposal except anecdote. Two of the most powerful substances I've tried are epigenetic modulators:

Fisetin: inhibits the cFos gene, this was a sort of lightbulb-turning-on type substance for me

Vorinostat: HDACi, proven in animal models of fear extinction; a single dose eradicated my conditioned adrenaline response at the poker table (I didn't write about it in that thread, but someone else has a nice series of posts).

 

NSI and vorinostat in particular felt very similar, thought the vorinostat provided a far more situational and short term emotional modulation, whereas NSI-189 was more chronic and general.

 

Any thoughts?

 

 

I've just taken five daily doses of 40 mg NSI and decided I might be suffering from an increase in generalised anxiety, so I'm taking a break. With regards to cortisol, I guess you can turn the neurogenesis hypothesis on its head and propose that drugs which promote neurogenesis do so by inhibiting cortisol and other adrenal steroids. Although this may contravene some of the published research where neurogenesis is achieved in vitro.

 

But what I'm really interested in is your experience with fisetin, and in particular vorinostat. Besides tree's very excellent account which you reference in your post, I haven't been able to find any other account of the use of vorinostat for fear and anxiety on the Internet. Would you kindly post your experience here or in the relevant thread? When did you take the vorinostat, i.e. was it before the poker game? Did you do try to control your thinking in relation to the adrenaline response, i.e. confront it/suppress it in any way? Where did you source the vorinostat from, if that information is not confidential?

Edited by tolerant, 07 April 2016 - 02:31 AM.

[tolerant]

Also, forgot to ask the following additional questions StevesPetRat with respect to vorinostat:

 

1. What was the dosage of vorinostat you took?

2. Was the adrenaline rush abolished once and for all?

3. Was the adrenaline rush unpleasant, i.e. a feeling of unwanted anxiety?

 

And with respect to fisetin:

 

1. What was the brand and dosage?

2. How long did you take it for?

3. If you're no longer taking it, did the effect you describe stay with you after you discontinued it?

 

Thank you very much in advance for taking the time to answer my questions. Any info on the above, however brief, will be much appreciated.

Edited by tolerant, 07 April 2016 - 05:20 AM.

[Strelok]

Does anybody see a problem with the occasional (2-3 days/week) concomitant use of NSI-189 along with modafinil/armodafinil? 

[jaiho]

Nope. No interaction with Modafinil. Just took 200mg Moda today, along with 40MG NSI-189.

I would suggest though that you try NSI daily, it may not build up in your system enough with intermittent dosing for the benefits.

[Bukujutsu]

Intresting, one thing I have notice is that I don't feel the need to take NSI, as I did with tianeptine.  I remember that I would wake up in the mornings and the first thing in my mind was "hmmm, I need to take my tianeptine."  It was weird I felt like I needed to keep taking it.  That's something I didn't felt with any other stuff.  Personally I attribute this to Tianeptine effect on the opoid receptor.

 

The effects are supposed to be insignificant at recommended doses, but many people do seem to be using excessive doses (of course if you're using it in doses that have significant effects on the u-opiod receptor, that doesn't mean it makes it superior as a long-term antidepressant). I've seen comparisons, and it's a tiny fraction of traditional opiods.

 

If you are using pharmaceutically recommended doses, it's likely because tianeptine has a particularly acute mood boosting effect, whereas others take months for the effects to fully manifest and aren't particularly noticeable or pleasant acutely.

[Bukujutsu]

 

 

 

Has anyone stacked NSI with LDN? I have some naltrexone, could try it out...

I was on LDN for about four months prior to trying NSI. I came to learn LDN causes ACTH to spike, which I think was causing some problems for me, so I stopped. After two weeks off of LDN I tried NSI for the first time and had a bad experience. I'm not sure if they are related but I'm thinking there might be some connection

 

Has anyone stacked NSI with LDN? I have some naltrexone, could try it out...

 reading research about its effects on microglia which is making me consider trying it again.

 

Can you please elaborate on this?

 

 

Have you tried U(ultra)LDN ? It may be superior, and the doses are far lower.

 

[Huckfinn]

I notice that Ceretropic sells Tianeptine Sodium Powder 1gr for 12$ and Sulfate Powder 2gr for 30$.

Which one do you advise and how much per day?

 

Thanks.

[Adr1n]

Sulfate has a more smooth curve on the onset of effects and at the end of it. But you can try first the sodium version to conclude if it works for you and if it's worth the money go for the sulfate one.

About the dose I would start by 5mg to see how you respond to it... The standard dose is 12,5 mg

[irony]

Tried my first dose today.  20mg freebase.   After about an hour I am feeling dopey and lazy on it, also kinda depressed when before I wasn't.   Does this pass?    Better to take before bedtime?

Edited by irony, 08 April 2016 - 12:35 AM.

[Nick Kyz]

Tried my first dose today.  20mg freebase.   After about an hour I am feeling dopey and lazy on it, also kinda depressed when before I wasn't.   Does this pass?    Better to take before bedtime?

Happens to me if I dose low. I would try upping the dose. I would also do freebase sublingual if you aren't already.

[Strelok]

 

Tried my first dose today.  20mg freebase.   After about an hour I am feeling dopey and lazy on it, also kinda depressed when before I wasn't.   Does this pass?    Better to take before bedtime?

Happens to me if I dose low. I would try upping the dose. I would also do freebase sublingual if you aren't already.

 

 

The freebase that I got tastes pretty terrible.
 

[irony]

Do you take it before bedtime or in the morning?

 

Once a day, BID, etc ?

[Strangelove]

I am going to put together everything we know about NSI-189 in a "newbie's" thread.

 

Most use it in the morning/early evening, for me and others can disrupt sleep if taken late in the day.

[Kinesis]

That would be great, Strangelove. I've been through this whole thread and feel overwhelmed by the sheer amount of point and counterpoint ... a summary would help a lot!

[Heisenburger]

Shit—we were talking about that a few months back and I promised to help. Forgot all about it, what with moving and everything. If you want me to proofread some drafts, send them to me and I’ll work on it. Maybe it’s good that we never got around to it, because if we had, it would have had to have been rewritten or appended somehow in light of the new tidbits of info dribbling from the mouths of Neuralstem.

[jaybird10 2]

Does anybody have any idea how the Neuralstem clinical trials are going and in what phase they are in? I wonder when the target timeline for fda approval of nsi-189.

[Strangelove]

Shit—we were talking about that a few months back and I promised to help. Forgot all about it, what with moving and everything. If you want me to proofread some drafts, send them to me and I’ll work on it. Maybe it’s good that we never got around to it, because if we had, it would have had to have been rewritten or appended somehow in light of the new tidbits of info dribbling from the mouths of Neuralstem.

 

Hi Heisenburger,

 

No problem at all, I am reading again the whole thread keeping notes. I believe they were a few other members that wanted to get involved also.

 

I ll let everyone know when ready, if anyone want to contribute putting everything together can post here or in a pm. 

[whatittakes]

 

Shit—we were talking about that a few months back and I promised to help. Forgot all about it, what with moving and everything. If you want me to proofread some drafts, send them to me and I’ll work on it. Maybe it’s good that we never got around to it, because if we had, it would have had to have been rewritten or appended somehow in light of the new tidbits of info dribbling from the mouths of Neuralstem.

 

Hi Heisenburger,

 

No problem at all, I am reading again the whole thread keeping notes. I believe they were a few other members that wanted to get involved also.

 

I ll let everyone know when ready, if anyone want to contribute putting everything together can post here or in a pm. 

 

 

My brief notes, 40mg sul, nightly, ~2 weeks each run:

 

- Definite mood improvements. Not night and day, but better than any SSRI/SNRI I've tried, which have all been failures so take that for what it's worth

- while it interferes with sleep by causing vivid dreams, it actually prevents my normal 3-4am wakeups. I'm a terrible sleeper (insomnia, latency, fragmented), so that's notable and suggest potentially cortisol suppression. Took at night this cycle to prevent overanalyzing acute effects/bias during the day. This could have been better or worse for studying effects, but there you go. I have to take Klonopin to sleep anyway, so it could also have offset any anxiety or stimulation from bedtime administration. 

- Cognitive improvements mostly around drawing associations between things I hadn't seen before

- more, easier laughter

- positive effects on depersonalization; not "knock it out of the park", but as anyone with serious DP/DR knows, even a little reduction is very mood boosting on its own 

- hard to say what effects on dysthymia, anhedonia. I'd say "some", but not the level I'd like 

- seemingly random recall of older memories, unbidden

- each cycle around 2wks I get extremely moody/emotional/"sad" and have to stop; so hoping continued cycling will have cumulative benefits. I didn't feel confident enough to "push through" this, it was legitimately bad enough that it felt debilitating and I needed to function so I had to stop. 

- co administered only what has been mentioned before, low dose Lamictal, occasionally Semax Amidate, alcohol. 

- source: not here but strongly trusted to be legitimate; SL, I'd be interested in trying yours to compare. PM if that's still an option. 

[Heisenburger]

I ll let everyone know when ready, if anyone want to contribute putting everything together can post here or in a pm. 

 

I think I may have an unused GoDaddy account lying around somewhere. I tried to start a message board a while back and gave up on it because of spammers. If there’s any time left on the contract, we could use it for a wiki. Or we can edit the actual Wikipedia page, but that’s kind of risky because some chucklehead will inevitably come along and mangle it all up.

 

[bluecity]

40-60mg a day for a month.

 

increased appetite.

less anhedonia.

 

overall, mild benefits.

 

is is ever possible for someone to react very differently to freebase and phosphate? e.g. one works very well, the other not at all.

Edited by bluecity, 10 April 2016 - 12:36 AM.

[Nick Kyz]

40-60mg a day for a month.

 

increased appetite.

less anhedonia.

 

overall, mild benefits.

 

is is ever possible for someone to react very differently to freebase and phosphate? e.g. one works very well, the other not at all.

Yes. If the method of administration is the same you will have different results.

 

Phosphate is more bioavailable orally, freebase is more membrane bioavailable (sublingual, nasal). 

[Heisenburger]

I just started using it again the day before yesterday after about a three or four-month hiatus. The effects were noticeable almost immediately. Right now I have a pretty formidable task ahead of me. I just moved 1000 miles away from my home of 20 years and am starting over again in a city I’ve never even been to. I have to help my wife, who right now has a broken leg and mostly scoots around in a wheelchair, clean out a 4000-square foot home that has been suffering from several years of neglect. Everything in the house has to be sorted, and either packed to go to our new home, donated, or discarded. On top of that, I need to find employment soon and try to hopefully get back into the swing of school and finish a degree (my fifth) that I temporarily abandoned about a year and a half ago after completing a little over half of it. My tail has definitely been dragging, and I feel more overwhelmed by obligation right now than I have at any other point in my life. I was even neglecting eating and bathing because I just didn’t want to take the time to do it. The NSI-189 snapped me out of it in just a couple of days. I could almost immediately sense a surge of newfound determination and confidence. Even though I’m still faced with a fairly daunting task, I’m looking at it logically and analytically and realizing that I can get everything done if I just budget my time well and put in a little overtime. NSI-189 is like powdered optimism for me.

[Adr1n]

Do you think NSI-189 is helping you adapt to all those new circunstances ?.. I'm interested on your experience since I have to emigrate soon to live in a new country with different people, job, culture, house, etc.. I really need something to help me adapt since it's hard to do all of that beign depressed. Is NSI-189 what I'm looking for, based on your experience?

Great to hear you are getting through that situation. Regards.

Edited by Adr1n, 10 April 2016 - 03:28 AM.

[rena123]

 

Shit—we were talking about that a few months back and I promised to help. Forgot all about it, what with moving and everything. If you want me to proofread some drafts, send them to me and I’ll work on it. Maybe it’s good that we never got around to it, because if we had, it would have had to have been rewritten or appended somehow in light of the new tidbits of info dribbling from the mouths of Neuralstem.

 

Hi Heisenburger,

 

No problem at all, I am reading again the whole thread keeping notes. I believe they were a few other members that wanted to get involved also.

 

I ll let everyone know when ready, if anyone want to contribute putting everything together can post here or in a pm. 

 

I would be highly interested to purchase 10g of your NSI-189 phosphate for treament resistant MDD, if third party lab certificates could be provided beforehand