10 replies to this topic

[Strangelove]

I have been providing NSI-189 from the same third party tested lab for more than three years now, its very benign compared to traditional antidepressants, and among the more than one thousand private messages I have received there are some "life changing" (the same term that has been used in the NSI-189 poll) experiences.  

 

Unfortunatelly there are very few cases (I ll say less than five to a thousand) that some get serious side effects for weeks if not months from only a few doses. It seems the correlation to all these cases is previous damage in the nervous system from an accident, an infection (neuro-lyme) or a toxic reaction to a drug (isotretinoin). I have been contacted by the member Sdanhedonic that had a number of persistent side effects from isotretinoin that got worst when he used NSI-189. The side effects he got from oral isotretinoin are.

 

Severe anhedonia.

Depersonalisation.

Excessive sweating. 

Hair loss.

Loss of erections.

He looks very pale.

Lack of inner talk and memory problems.

 

As the last of his symptoms is something that NSI-189 can help with, I suggested to try NSI-189, unfortunatelly after only two oral doses his symptoms worsened, and got more side effects.

 

Copy pasting his past response.

 

- Worsening of depersonalization and dissociation

- My head feel numbs 

- Numb feelings in my hands

- Worsening of tinnitus

- Hearing loss and hearing difference (I don't hear any bass)

- Nausea

 

The numb feeling and tinnitus is two of the rare side effects of NSI-189 but they dissapear after discontinuation, something that is not the case with Sdanhedonic. He may need more time, but could we brainstorm to see what he may possibly do, to feel better soon?

 

What I now look at are isotretinoin overdose treatments.

Nervous system depressants.

Possibly a combo for inflammation that might be involved?

 

Any initial thoughts on this? I ll get into it, in more detail in my next posts.

 

 

 

 

 

 

 

[Mind_Paralysis]

The initial thought I'm having, is that he needs to check out what kind of inflammation-markers he's got, and do some testing for infections as well - we need a bit more data on him before we start suggesting any further treatment.

 

Looking through the wiki-info on Isotretinoin's effects on the brain... well, it's no wonder this stuff can cause issues! Damn.. it's one dirty f***ing drug!

 

https://en.wikipedia...#CNS_activities

 

Considering Isotretinoin's effects on serotonin and dopamine-receptors, then perhaps an SSRI + low dose Antipsychotic (something which specifically targets 5ht1a -receptors, for instance) should be considered?

[Galaxyshock]

Yeah accutane is heavy drug originally created for chemotherapy, causing pretty awful side effects, some of which are lasting, to many. I was lucky to only get some joint issues from it, then again it didn't really heal my skin - only dried it. There's a thread with over 600 pages about long-term isotretinoin damage @ acne.org: 

https://www.acne.org...-from-accutane/

I don't think they've found anything conclusive, things like CBD oil helped some I guess.

[magniloquentc0unt]

I am myself currently looking for a way to counteract accutane side effects

I have been taking it on an off for years and honestly i cant live without. i get acne everywhere on my body , although not harsh

so i take 5mg every other day and it keeps me decent looking

 

anyway, what he mentioned are typical isotretoinoin side effect, i believe the hair loss is especially symptomatic

 

on a cns side it increases 5ht1a transporters levels up to about 200% after 2 days or so. this can cause serotonin depletion. this is probably its main mechanism of action and what i would aim to counter

 

it also causes apoptosis in the hippocampus and other brain structures. nsi causes neurogenesis in those structures, which is probably the exact contrary of apoptosis, so thumbs up for the suggestion strangelove, i had tought of it myself and its actually how i landed here i would have done that suggestion, too

 

last year i took some nsi for a month and it made blasted me out of anhedonia (but made me super sad and paranoid, but i got dumped so its kinda understandable). interestingly in that period i wasnt taking accutane.

 

so sadly i dont have any answers but i am interested on ideas to counter the nasty effects of isotretinoin on the cns. i would saya anything that causes neurogenesis / increases neurotrophic factor

[MJ82]

Following

[Strangelove]

Thank you for the replies appreciated.

 

it also causes apoptosis in the hippocampus and other brain structures. nsi causes neurogenesis in those structures, which is probably the exact contrary of apoptosis, so thumbs up for the suggestion strangelove, i had tought of it myself and its actually how i landed here i would have done that suggestion, too.

 

This is what I thought, the symptoms that Sdanhedonic described seemed exactly the kind of symptoms that NSI-189 helps with, unfortunatelly it had the opposite effect, getting him stuck I believe into a negative loop. Possibly the kind of excitation that NSI-189 gives to the nervous system agitated his past isotretinoin issues. His main issue right now is numbness in all his body, similar have been described from NSI-189, but it was localized in areas that had a past physical damage and got away in some weeks, although in one case took months. 

 

The initial thought I'm having, is that he needs to check out what kind of inflammation-markers he's got, and do some testing for infections as well - we need a bit more data on him before we start suggesting any further treatment.

 

What I first thought is Lostfalco's brain fog treatment.

http://www.lostfalco...n-fog-two-step/

 

I have ibudilast on hand to send him, and is not that difficult to find galantamine. He already has brain fog, and I believe this combo can help with more of the symptoms.

 

This is what I thought, the symptoms that Sdanhedonic described seemed exactly the kind of symptoms that NSI-189 helps with, unfortunatelly it had the opposite effect, getting him stuck I believe into a negative loop. Possibly the kind of excitation that NSI-189 gives to the nervous system agitated his past isotretinoin issues. His main issue right now is numbness in all his body, similar have been described from NSI-189, but it was localized in areas that had a past physical damage and got away in some weeks, although in one case took months. 

Edited by Strangelove, 05 April 2018 - 10:34 PM.

[StevesPetRat]

A possible biological basis for the case reports of depression involves decreased metabolism in the orbitofrontal cortex (OFC) of the frontal lobe. It has also been found that decreased OFC metabolism was correlated with headaches.

(from Wikipedia on isotretinoin)

Interestingly, isotretinoin antagonizes, or at least opposes the activity of, the PPAR receptors, critical for longevity and metabolism (whoops, lost the link, but it's out there).

Yeah, that's a drug I wish I hadn't taken. Who knows what long term effects it had? Certainly wasn't worth the risk for the relatively small benefit of turning moderate acne into mild acne.

 

On to the topic at hand:

 

I had bad side effects, after over a year of successful use, from a single large (300-400 mg) dose of NSI-189 in November 2017. It wasn't until last month that I successfully reversed (really -- am in the process of reversing) the effects. I intend still to write up a longer post, with stronger justification for these points, but here are some thoughts that may help.

 

My primary side effect of relevance was a severe emotional flatlining. Nothing felt like anything any more, to the point where I seriously contemplated permanently dismembering myself (cutting off a finger) just to see if it was an "interesting" experience. I eventually realized that my emotions were "paralyzed" or "locked in" (have you seen the movie "Get Out"?) by a sort of low-grade anxiety. Other relevant effects:

• Pallor
• Poor cognition
• Loss of libido
• Worsened tinnitus
• Deadened senses
• Partial numbness

Hypothesis: NSI-189 works via hormetic mechanisms. In therapeutic doses, this activates neurogenesis. In overdose, this increases ROS, damages cell membranes, and impairs cerebral metabolism and communication. It also improves communication between the amygdala and the PFC, resulting in improved emotional self-regulation. This ability to emotionally self-regulate was the most profound of NSI-189's effects for me. However, in overdose, it shorts out this communication.

 

Three complementary methods exist to complement / repair / reverse the effects:

1. Repair and protect from further damage
2. Increase brain metabolism
3. Increase dopamine levels for better neural communication

Here's just a quick list of things that seemed to help the most:

Fasting

Glycine (needed for neurogenesis)

Tyrosine (+ methylation support if needed)

Caffeine / other dopaminergics as a stopgap

alpha Lipoic acid (activates PPAR, mitogenic, antioxidant)

ALCAR (may increase acetylcholine and thus lower dopamine. Excessive sweating could be due to higher ACH, especially if accompanied by salivation)

Pantethine

Creatine

Thiamine (500 mg, used to use allithiamine, but actually getting better results from standard thiamine lately)

Biotin (10 mg)

PQQ (PPAR activator)

Flax oil + Cod liver/fish oil (may increase ACH)

Potassium (critical for nerve conduction, hard to maintain adequate levels under stress)

Tocotrienols

 

That might be enough to get started. Get the brain burning brightly, the anxiety subsides as the communication fires back up, and emotions return. There should be a quick improvement in symptoms, but true healing will take longer.

 

ETA: Also anything that improves insulin sensitivity may be helpful. Gotta feed the brain.

Edited by StevesPetRat, 11 April 2018 - 07:28 AM.

[Strangelove]

Hypothesis: NSI-189 works via hormetic mechanisms. In therapeutic doses, this activates neurogenesis. In overdose, this increases ROS, damages cell membranes, and impairs cerebral metabolism and communication.

 

My exact thinking too. Unfortunatelly in some cases with nervous system damage, you do not get to hormetic zone, but you get directly to "over dose" and side effects, even with very small doses. You got very similar side effects, but you used 15X - 20X the dose, thankfully you are better now (I guess after you got interested in NSI-189 again) and hopefully Sdanhedonic will feel better soon too. I ll see how things are going for him, and post some of my research in isotretinoin.

[silversprings]

Just to offer some additional data, I too suffer from similar serious symptoms following an isotretinoin course (mostly depression, exhaustion, brain fog and effort intolerance) and have been taking 40 mg of NSI-189 daily for about a month. My symptoms did not worsen nor did new symptoms appear except for some increased fatigue during the first two weeks. However, I don't think they've improved at all either. Maybe some very very slight improvement with the depression, but it's hard to say.

 

Strangelove, would you advise me to stop taking the drug?

 

Also, I've had a lot of blood tests done for my issues, including testing for inflammation markers, but everything always comes back normal unfortunately. :( I'll be following this thread...

Edited by silversprings, 11 April 2018 - 07:35 PM.

[magniloquentc0unt]

i just decided i am going to trial selegiline to counteract accutane.

 

(Selegiline) was found to exert an anti-apoptotic effect in a variety of tissues and cells which was independent of MAO inhibition (Tatton and Chalmers-Redman, 1996)

 

this hopefully counteracts the aptoptosis caused by isotretinoin

 

besides, the anhedonia, lack of erection, brainfog etc is fundamentally the default """lack of dopamine""" effects list

 

the cleanest antidepressant effect ive ever had was from moclobemide, so i guess its worth investigating that area

 

my simptoms arent as bad as the ones in OPs report, but some overlap. 

ill let you guys know how it goes

 

 

[paolo x]

I have tinnitus since 7 months ago i took nsi freebase low doses for few days only.