6219 replies to this topic

[aperson444]

 

@twindaddy37: for me it's not so much a question of what i stack with it, rather what i don't. for example, i find an nsi-cycle is better without much of caffeine usage.

tianeptine and phenibut and stuff like that i dont take with the nsi...

on the other hand i use a lot of stuff for overall body health, but it does not have anything to do with the nsi... magnesium, zinc, vitamin d, iodine... i use up to 10 grams fishoil per day... i use gynostemme extract 2-3 times a day.  creatine daily...

occasional liposomal vitamin c, i use citrulline-malate a few times per week. fasoracetam a few times per month... niacin (the flush version, 500mg on empty stomach with orangejuice) 1-2 times per week.  MSM daily... ALCAR, NAC daily (!!)... chlorella... and guess what i also use MMS now...

 

maybe look into citrulline, fasoracetam and gynostemma extract... 1g of fish oil is not a lot.

 

why do you take the uridine ?

 

My mission is one of creating a highly resilient mental space so that my mind can heal from past damages (8 years of heavy narcotic abuse, and lots of them while living an extremely fast paced lifestyle that was filled with chronic stress that beat my body and mind into the ground). I have experimented for two years to find the perfect combination of substances that has made me most resilient to my life stressors- and i take the appropriate actions to grow both spiritually, emotionally and mentally. The damage left me with some pretty gnarly imbalances, namely alot of constant worrying, a flat mood and alot of negative self talk. I did manage to fix this and live in a pretty decent headspace for about 7 months, without anything. Then i was living on own and stress was little. Out of blue i was blessed with twin girls, and my life became VERY hectic again- so i needed fortification. My mission to fix the physical, nutritional and mental imbalances led me to finding an appropriate stack that works best with my chemistry, that gives me no side effects- and this is what i have settled on. I have used most of the adaptogenic herbs, gynostemma ect. I find that anything over 1 gram of fish oil hurts my libido and it is afterall a PUFA, which is why i limit my dosage of fish oil. Also like stinkornijor said, i found that fish oil in excess hurts mood. I also take MCT oil, which i think is healthier. I have not tried fasoracetam whats the benefit of this substance? Doesnt NSI have a niacin like component to it? The only niacin i get is in a multi. MSM did nothing for me. I do take mag citrate every three days before bedtime. I try not to overdo anything and strive for balance. My goal is to build stress resilience, which is why i also do some cold exposure therapy. I figure if i can create a headspace where i am simply (mostly) living in the present, my mind will have the optimum potential to grow and rewire where there was damage from the past. I cut out all media, social media, news, politics, groups of people with opinions, commercials and just INFORMATION in general, aside from this forum, so that i can learn to live through my intuition again, and i find there has been ALOT of growth in doing so.I also "minimized"- got rid of shit i didnt need or use basically to simplify.  Uridine i use for dopamine receptor modulation. I use phenibut on the weekend one day as a tool to be as social as possible, so i can flex the social muscles. 

 

 

NSI-189 does indeed have the niacin core structure (pyridine-3-carboxyl moiety) embedded in it, but I don't think that would confer any niacin-like activity to it because NSI-189 is so modified (i.e. the amine group in the 2-position, which is unlikely to come off metabolically). Out of curiosity, what brand of fish oil do you use? I too have noticed a decrease in libido, but I've always attributed that to my taking a relatively high dose of Cymbalta twice daily.

[Twindaddy37]

 

 

@twindaddy37: for me it's not so much a question of what i stack with it, rather what i don't. for example, i find an nsi-cycle is better without much of caffeine usage.

tianeptine and phenibut and stuff like that i dont take with the nsi...

on the other hand i use a lot of stuff for overall body health, but it does not have anything to do with the nsi... magnesium, zinc, vitamin d, iodine... i use up to 10 grams fishoil per day... i use gynostemme extract 2-3 times a day.  creatine daily...

occasional liposomal vitamin c, i use citrulline-malate a few times per week. fasoracetam a few times per month... niacin (the flush version, 500mg on empty stomach with orangejuice) 1-2 times per week.  MSM daily... ALCAR, NAC daily (!!)... chlorella... and guess what i also use MMS now...

 

maybe look into citrulline, fasoracetam and gynostemma extract... 1g of fish oil is not a lot.

 

why do you take the uridine ?

 

My mission is one of creating a highly resilient mental space so that my mind can heal from past damages (8 years of heavy narcotic abuse, and lots of them while living an extremely fast paced lifestyle that was filled with chronic stress that beat my body and mind into the ground). I have experimented for two years to find the perfect combination of substances that has made me most resilient to my life stressors- and i take the appropriate actions to grow both spiritually, emotionally and mentally. The damage left me with some pretty gnarly imbalances, namely alot of constant worrying, a flat mood and alot of negative self talk. I did manage to fix this and live in a pretty decent headspace for about 7 months, without anything. Then i was living on own and stress was little. Out of blue i was blessed with twin girls, and my life became VERY hectic again- so i needed fortification. My mission to fix the physical, nutritional and mental imbalances led me to finding an appropriate stack that works best with my chemistry, that gives me no side effects- and this is what i have settled on. I have used most of the adaptogenic herbs, gynostemma ect. I find that anything over 1 gram of fish oil hurts my libido and it is afterall a PUFA, which is why i limit my dosage of fish oil. Also like stinkornijor said, i found that fish oil in excess hurts mood. I also take MCT oil, which i think is healthier. I have not tried fasoracetam whats the benefit of this substance? Doesnt NSI have a niacin like component to it? The only niacin i get is in a multi. MSM did nothing for me. I do take mag citrate every three days before bedtime. I try not to overdo anything and strive for balance. My goal is to build stress resilience, which is why i also do some cold exposure therapy. I figure if i can create a headspace where i am simply (mostly) living in the present, my mind will have the optimum potential to grow and rewire where there was damage from the past. I cut out all media, social media, news, politics, groups of people with opinions, commercials and just INFORMATION in general, aside from this forum, so that i can learn to live through my intuition again, and i find there has been ALOT of growth in doing so.I also "minimized"- got rid of shit i didnt need or use basically to simplify.  Uridine i use for dopamine receptor modulation. I use phenibut on the weekend one day as a tool to be as social as possible, so i can flex the social muscles. 

 

 

NSI-189 does indeed have the niacin core structure (pyridine-3-carboxyl moiety) embedded in it, but I don't think that would confer any niacin-like activity to it because NSI-189 is so modified (i.e. the amine group in the 2-position, which is unlikely to come off metabolically). Out of curiosity, what brand of fish oil do you use? I too have noticed a decrease in libido, but I've always attributed that to my taking a relatively high dose of Cymbalta twice daily.

 

Thanks for the explanation, you sound you know your stuff. I use either NOW brand or this time its GNC brand. I don't really think it matters- i think it has something to do with how much EPA is in the fish oil, or how much EPA your taking that seems to decrease the libido. I don't know the mechanism by which it does so, I've seen various things thrown around like higher serotonin lowering libido, or prostaglandins being interfered with or decreased testosterone levels from the omegas. All i know is that when i take sustained doses of fish oil over 1 gram my libido takes a HUGE HIT- and this cant be good for me. 

[Fletch]

I think the doorway to psychedelics will remain shut for a very long time at least. It's a shame, I've read the works of Stanislav Grof and various other authors and believe they hold enormous potential for rapidly accelerating therapeutic progress when used properly.

 

Right now I just need more NSI-189 and hopefully my phenelzine source will come through. Found it from an unusual source ay a fair price. This could change everything if test results come back positive.

 

Ketamine is already being used here in the US by Dr.s for depression. Treatment is usually IV infusion once a week or so. It's highly effective.

 

 

Ketamine, DMT, Psylocibin can be useful but hold high risk of increasing damage instead of healing. Ketamine on regular basis will cause braindamage. This stuff is too unusual in the effect to fit in society and wont be what people are searching for because the picture of these drugs are transfigured. The trip to much of a challenge for the standard human. I would call it a 50/50 change of damage/healing ratio and personally I would advise against it.

 

I disagree. Ketamine has not been shown to cause brain damage. When used periodically for depression it is safe. The AD effect comes not from the acute hallucinogenic effect or the NMDA antagonism, but is an after-effect of the metabolite hydroxnorketamine. Hydroxinorketamine has no psychedelic properties AFIAK. Ketamine is not dangerous, outside of it's abuse potential.

[aperson444]

 

I think the doorway to psychedelics will remain shut for a very long time at least. It's a shame, I've read the works of Stanislav Grof and various other authors and believe they hold enormous potential for rapidly accelerating therapeutic progress when used properly.

 

Right now I just need more NSI-189 and hopefully my phenelzine source will come through. Found it from an unusual source ay a fair price. This could change everything if test results come back positive.

 

Ketamine is already being used here in the US by Dr.s for depression. Treatment is usually IV infusion once a week or so. It's highly effective.

 

 

Ketamine, DMT, Psylocibin can be useful but hold high risk of increasing damage instead of healing. Ketamine on regular basis will cause braindamage. This stuff is too unusual in the effect to fit in society and wont be what people are searching for because the picture of these drugs are transfigured. The trip to much of a challenge for the standard human. I would call it a 50/50 change of damage/healing ratio and personally I would advise against it.

 

I disagree. Ketamine has not been shown to cause brain damage. When used periodically for depression it is safe. The AD effect comes not from the acute hallucinogenic effect or the NMDA antagonism, but is an after-effect of the metabolite hydroxnorketamine. Hydroxinorketamine has no psychedelic properties AFIAK. Ketamine is not dangerous, outside of it's abuse potential.

 

 

Actually. ketamine's antidepressant effects are mediated directly by NMDA antagonism. According to (Vollenweider and Kometer, 2010), NMDA antagonists inhibit the firing of GABAergic interneurons which enhances the rate of glutamate release which subsequently upregulates or facilitates the activity AMPA receptors on cortical pyramidal neurons. If it were indeed ketamine's metabolite that were active instead of ketamine itself, then intravenous infusion would not be effective, as this route of administration bypasses first-pass metabolism. Nevertheless, ketamine is unlikely to cause brain damage when used at the doses used to treat TRD. Olney's lesions form in animals after very high doses of NMDA antagonists, especially PCP and MK801. Ketamine is not very potent so very large doses are required to create these lesions. Also, people using ketamine for depression are not taking ketamine daily. They typically take it maybe a few times each week and typically stop after several weeks. Psychedelics are perhaps even safer and do not cause visible damage to the brain (like chronic use of NMDA antagonists can) even after several uses. 

[Fletch]

 

 

I think the doorway to psychedelics will remain shut for a very long time at least. It's a shame, I've read the works of Stanislav Grof and various other authors and believe they hold enormous potential for rapidly accelerating therapeutic progress when used properly.

 

Right now I just need more NSI-189 and hopefully my phenelzine source will come through. Found it from an unusual source ay a fair price. This could change everything if test results come back positive.

 

Ketamine is already being used here in the US by Dr.s for depression. Treatment is usually IV infusion once a week or so. It's highly effective.

 

 

Ketamine, DMT, Psylocibin can be useful but hold high risk of increasing damage instead of healing. Ketamine on regular basis will cause braindamage. This stuff is too unusual in the effect to fit in society and wont be what people are searching for because the picture of these drugs are transfigured. The trip to much of a challenge for the standard human. I would call it a 50/50 change of damage/healing ratio and personally I would advise against it.

 

I disagree. Ketamine has not been shown to cause brain damage. When used periodically for depression it is safe. The AD effect comes not from the acute hallucinogenic effect or the NMDA antagonism, but is an after-effect of the metabolite hydroxnorketamine. Hydroxinorketamine has no psychedelic properties AFIAK. Ketamine is not dangerous, outside of it's abuse potential.

 

 

Actually. ketamine's antidepressant effects are mediated directly by NMDA antagonism. According to (Vollenweider and Kometer, 2010), NMDA antagonists inhibit the firing of GABAergic interneurons which enhances the rate of glutamate release which subsequently upregulates or facilitates the activity AMPA receptors on cortical pyramidal neurons. If it were indeed ketamine's metabolite that were active instead of ketamine itself, then intravenous infusion would not be effective, as this route of administration bypasses first-pass metabolism. Nevertheless, ketamine is unlikely to cause brain damage when used at the doses used to treat TRD. Olney's lesions form in animals after very high doses of NMDA antagonists, especially PCP and MK801. Ketamine is not very potent so very large doses are required to create these lesions. Also, people using ketamine for depression are not taking ketamine daily. They typically take it maybe a few times each week and typically stop after several weeks. Psychedelics are perhaps even safer and do not cause visible damage to the brain (like chronic use of NMDA antagonists can) even after several uses. 

 

 

From wiki on HNK:

 

"Moreover, (2S,6S)-HNK was tested and was found to increase the function of the mammalian target of rapamycin (mTOR), a marker of the antidepressant activity of ketamine, far more potently than ketamine itself (0.05 nM for (2S,6S)-HNK, 10 nM for (S)-norketamine, and 1,000 nM for (S)-ketamine (esketamine), respectively), an action that was observed to correlate closely with their ability to inhibit the α₇-nicotinic acetylcholine receptor.^[5][6][7] This finding has led to a call of reassessment of the understanding of the rapid antidepressant effects of ketamine and their mechanisms.^[8] However, subsequent research has found that dehydronorketamine, which is a potent and selective antagonist of the α₇-nicotinic acetylcholine receptor similarly to HNK, is inactive in the forced swim test at doses up to 50 mg/kg in mice, and this is in contrast to ketamine and norketamine, which are effective at doses of 10 mg/kg and 50 mg/kg, respectively.^[9]"
 

[FuzzMunky]

I am on day 23 of my NSI freebase trial - I take 20mg BID sublingual.

 

The very first day I had a placebo anti-anhedonia boost and lots of memories of how my brain used to work as a happy kid. Then for a couple of weeks I was pretty down. Then I had one more day of a positive experience, but it felt like quite a bland, lobotomised high. No desires or thoughts, but not really content either. Now I'm just really depressed, cannot even get off the couch, and I'm really fatigued for a couple of hours after I take it. 

 

Is Dr Strangelove's freebase still in-date? What else could be wrong? How long should I give this? Makes me feel really dumb as I cannot access my memory at all. I just feel like the guy who turned up to give a public speech without my notes, or like I have a big air bubble in my brain.

Edited by FuzzMunky, 08 March 2017 - 10:26 PM.

[focus83]

You might take too much NSI due to you taking it sublingually. Switch to taking it orally (as it is intended) 20mg a day. If that doesn't help decrease the dosage further.

[FuzzMunky]

You might take too much NSI due to you taking it sublingually. Switch to taking it orally (as it is intended) 20mg a day. If that doesn't help decrease the dosage further.

As I understand it, freebase doesn't work well orally. That is what I have been led to believe anyhow. Also, I started on a smaller dose (by half) and the effects didn't feel much different.

[bugsbunny]

" Psychedelics are perhaps even safer and do not cause visible damage to the brain (like chronic use of NMDA antagonists can) even after several uses. "

 

I dont think so. Psychadelics like LSD change the brainstructure in a very short time, while normally you need ages for these kind of changes to happen. It can turn you into a cripple or a guru in just one session for sure. Thats russian brain roulette, because you cant control whats happening while tripping. There is no way back or exit after taking them.

""Moreover, (2S,6S)-HNK was tested and was found to increase the function of the mammalian target of rapamycin (mTOR), a marker of the antidepressant activity of ketamine, far more potently than ketamine itself (0.05 nM for (2S,6S)-HNK, 10 nM for (S)-norketamine, and 1,000 nM for (S)-ketamine (esketamine), respectively), an action that was observed to correlate closely with their ability to inhibit the α₇-nicotinic acetylcholine receptor.^[5][6][7] This finding has led to a call of reassessment of the understanding of the rapid antidepressant effects of ketamine and their mechanisms.^[8] However, subsequent research has found that dehydronorketamine, which is a potent and selective antagonist of the α₇-nicotinic acetylcholine receptor similarly to HNK, is inactive in the forced swim test at doses up to 50 mg/kg in mice, and this is in contrast to ketamine and norketamine, which are effective at doses of 10 mg/kg and 50 mg/kg, respectively.^[9]""

 

Thats a nice collection of studies, but doesnt change the fact that it turns people into mushheads like MDMA does. This is the reason why ketamine isnt used as a anesthesia agent, people tripped to hard and some of them didnt recover. MDMA is used as a therapy helper too so nobody cares about risks anyways.

Edited by bugsbunny, 09 March 2017 - 05:17 PM.

[FuzzMunky]

" Psychedelics are perhaps even safer and do not cause visible damage to the brain (like chronic use of NMDA antagonists can) even after several uses. "

 

I dont think so. Psychadelics like LSD change the brainstructure in a very short time, while normally you need ages for these kind of changes to happen. It can turn you into a cripple or a guru in just one session for sure. Thats russian brain roulette, because you cant control whats happening while tripping. There is no way back or exit after taking them.

LSD, the chemical, doesn't inherently produce lasting changes in the structure of the brain (not that I am aware of anyway). It is the experience on the trip which produces psychological changes, which can show up as changes to the physical structure. So with proper guidance and in a therapeutic capacity, the dangers can be mitigated.

[aperson444]

" Psychedelics are perhaps even safer and do not cause visible damage to the brain (like chronic use of NMDA antagonists can) even after several uses. "

 

I dont think so. Psychadelics like LSD change the brainstructure in a very short time, while normally you need ages for these kind of changes to happen. It can turn you into a cripple or a guru in just one session for sure. Thats russian brain roulette, because you cant control whats happening while tripping. There is no way back or exit after taking them.

""Moreover, (2S,6S)-HNK was tested and was found to increase the function of the mammalian target of rapamycin (mTOR), a marker of the antidepressant activity of ketamine, far more potently than ketamine itself (0.05 nM for (2S,6S)-HNK, 10 nM for (S)-norketamine, and 1,000 nM for (S)-ketamine (esketamine), respectively), an action that was observed to correlate closely with their ability to inhibit the α₇-nicotinic acetylcholine receptor.^[5][6][7] This finding has led to a call of reassessment of the understanding of the rapid antidepressant effects of ketamine and their mechanisms.^[8] However, subsequent research has found that dehydronorketamine, which is a potent and selective antagonist of the α₇-nicotinic acetylcholine receptor similarly to HNK, is inactive in the forced swim test at doses up to 50 mg/kg in mice, and this is in contrast to ketamine and norketamine, which are effective at doses of 10 mg/kg and 50 mg/kg, respectively.^[9]""

 

Thats a nice collection of studies, but doesnt change the fact that it turns people into mushheads like MDMA does. This is the reason why ketamine isnt used as a anesthesia agent, people tripped to hard and some of them didnt recover. MDMA is used as a therapy helper too so nobody cares about risks anyways.

 

Well, ketamine is still used extensively as an anasthetic. It is especially common in emergency anasthesia and with pediatric patients. But the point of using HNK to treat depression is that it lacks any of the psychotomimetic effects of regular ketamine (which are still relatively mild at the doses used to treat depression). Ketamine is actually remarkably safe when used at the correct doses, though not as safe (physiologically) as psychedelics are. It is still physically possible to overdose on ketamine and there have been reports of bladder problems in chronic users of ketamine. Phencyclidine (PCP) is probably what you are thinking of. It was initially used as an anasthetic, but it had too many lasting psychotomimetic effects so it was taken off the market. As far as I know, psychedelics do not cause any physical abnormalities in brain structure. They might change the wiring of the brain, but these effects are far more difficult to track as current imaging techniques are largely based at the macroscopic level and look at anatomical and structural changes in the brain. Plus, individual factors are likely to interfere with results and results would vary too much from individual to individual.

[bugsbunny]

"Ketamine is actually remarkably safe when used at the correct doses"

 

What is the correct dosage? Since it doesnt cure depression in one session you'll need to take it regulary. If you take it too regulary braindamage will occure. Ketamine is only harmless in rare usage. Im not sure about deveriates of ketamine like Methoxetamine and the damage it makes to the body.

Edited by bugsbunny, 10 March 2017 - 07:41 AM.

[Sciencyst]

Some relevant studies to add to the ketamine discussion. The first study is only relevant to long-term use, but does prove Olney's lesions in humans. The second two studies seem to be more relevant, though the second is a neonatal brain. An anesthetic dose of ketamine in rodents is suggested to be 100-200mg/kg. In contrast, here's a human dose: A dose equivalent to 2 mg of ketamine per kg body-weight given intravenously over 60 seconds usually produces surgical anaesthesia within 30 seconds lasting for 5-10 minutes (dose may range from 1 to 4.5 mg/kg); an intramuscular dose equivalent to 10 mg per kg body-weight (range 6.5-13 mg/kg) usually produces surgical anaesthesia within 3 to 4 minutes lasting for 12 to 25 minutes (Reynolds et al., 1989). 

So the doses used in these studies are far below the recommended rodent anesthesia, yet cause harmful effects with a single administration. 

 

 

Brain damages in ketamine addicts as revealed by magnetic resonance imaging

 

https://doi.org/10.3...nana.2013.00023
 

Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5–12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2–4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine.

 

 

SINGLE-DOSE KETAMINE ADMINISTRATION INDUCES APOPTOSIS IN NEONATAL MOUSE BRAIN

https://doi.org/10.1...P.2005.16.4.231

 

See all › 43 Citations See all › 19 ReferencesShare Request full-text Single-dose ketamine administration induces apoptosis in neonatal mouse brain Article in Journal of basic and clinical physiology and pharmacology 16(4):231-43 · January 2005 with 60 Reads DOI: 10.1515/JBCPP.2005.16.4.231 · Source: PubMed 1st Michael Rudin 2nd Ron Ben-Abraham + 2 3rd Vered Gazit 27.06 · Washington University in St. Louis Last Yeshayahu Katz 37.54 · Unknown Show more authors Abstract Unlabelled: The activity of N-methyl-D-aspartate (NMDA) receptors is critical for neuronal survival in the immature brain. Studies have reported that chronic blockage of these receptors mediates apoptosis in neonatal animals. We investigated the apoptotic effect of a clinically relevant single dose of ketamine, an NMDA receptor antagonist, in the brain of neonatal mice. Seven-day-old ICR mice were injected with ketamine (1.25, 2.5, 5, 10, 20, and 40 mg/kg body weight, subcutaneously in 0.9% NaCl) or with 0.9% NaCl alone as control. Righting reflex testing was performed and mouse brains were examined at 24, 48, and 72 h and 7 days after injection. The number of degenerating neurons was measured using silver staining. Apoptosis was confirmed by DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). We observed in the sensorimotor cortex and cerebellum of ketamine-treated mice extensive apoptosis, which was clearly dose-dependent and present even after a low dose of ketamine (5 mg/kg). The most prominent apoptotic damage was detected 72 h post-injection (P < 0.001 vs control), at doses ranging from 10 to 40 mg/kg. After 7 d the number of neurodegenerative neurons, at doses ranging from 5 to 40 mg/kg, remained significantly high. The brain weight was comparable to that of untreated control mice and no gross neurobehavioral effects in the righting reflex test or alteration in the pattern of behavior was observed. The results indicate that the administration of ketamine in a clinically relevant single dose triggers long-lasting neuronal apoptosis in certain brain areas of neonatal mice. Implications: The administration of ketamine in a clinically relevant single dose to 7-d-old mice induced apoptosis in the sensorimotor cortex and cerebellum. This effect was dose-dependent and long lasting.

 

 

Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice

https://www.scienced...361923010001103

 

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20 mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.

 

And back to NSI-189... I did some preliminary docking research and compared it to WAY-100,635, a very selective D₄ agonist. The results were very similar, so I suspect it to have some activity there. But actual animal studies would need to confirm this. I have also been scouring chemical databases to find similar compounds and have come up with some very very speculative ideas. I suspect NSI-189 might bind to 5HT_1A as an antagonist, which could be partly responsible for the reported hyperalgesia and paresthesia. (Paradoxically, chronic administration of the very high efficacy 5-HT_1Aagonist befiradol results in potent analgesia following an initial period of hyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-HT_1A receptors (i.e. analogous to a 5-HT_1A antagonist-like effect). Or it could be neurogenic pruritus as others have mentioned. I think NSI-189 binds to several 5HT₂ receptors. I suspect it might act as a partial agonist, or mixed agonist/antagonist at different GPCRs. It's brightened colors A LOT, and I see some slight patterning in grass. Like StrangeLove mentioned it can re-activate previous psychedelic use. I've noticed that it's effects are much less noticeable in the 24 hours after consuming cannabis, but when I abstain I get the itchiness, a lot of tingling and enhanced empathy. Speaking of which, it makes my heart hurt similarly to MDA did the one time I tried it. I'm worried it could possibly have 5HT_2B activity, as the compound ST50300481 has a similar structure and is purported to bind to this receptor. So don't take this if you have heart issues. Some other possible targets of NSI-189 include: SERT, NET, DAT, Mineralocorticoid Receptor 1 modulation, and Metabotropic Glutamate Receptor 5 antagonism.

I've been searching for the supposedly novel target by which it causes neurogenesis by reading all Neural Stem publications, and even reading studies done by the authors of those publications, but I haven't found much interesting in that department.

Edited by UltraCitron, 10 March 2017 - 11:20 AM.

[linlin92]

Hmm, how did the NSI-189 thread turn into discussion about K?

 

I am still using NSI-189 (freebase) sublingual, worked up to 35mg per day once in the morning. I am now able to stack it with 10mg PRL-8-53, 15mg Tianeptine sulphate (love how this doesn't gunk up into a ball of goo!), and 25mg fasoracetam, every day except Sundays.

Its helped me in all areas of life. I am picking up lots of complex topics at uni and remembering it without too much effort - my study time has basically halved compared to last year, hardly any anxiety or stress at all which is amazing given my history of being a huge stresshead, and I just love learning new things - playing piano, DIY cosmetics and jewellry, fitness yoga feels amazing, and I have a huge desire to travel. I don't want to stop taking it, ever.

 

The downside, if you can manage it, is emotional response to situations can be a bit disproportional than what it normally be. For instance I could watch a TV commercial and if its even slightly sad tears start rolling down my face. And if someone tells me a funny joke I just cannot stop laughing

[aperson444]

Some relevant studies to add to the ketamine discussion. The first study is only relevant to long-term use, but does prove Olney's lesions in humans. The second two studies seem to be more relevant, though the second is a neonatal brain. An anesthetic dose of ketamine in rodents is suggested to be 100-200mg/kg. In contrast, here's a human dose: A dose equivalent to 2 mg of ketamine per kg body-weight given intravenously over 60 seconds usually produces surgical anaesthesia within 30 seconds lasting for 5-10 minutes (dose may range from 1 to 4.5 mg/kg); an intramuscular dose equivalent to 10 mg per kg body-weight (range 6.5-13 mg/kg) usually produces surgical anaesthesia within 3 to 4 minutes lasting for 12 to 25 minutes (Reynolds et al., 1989). 

So the doses used in these studies are far below the recommended rodent anesthesia, yet cause harmful effects with a single administration. 

 

 

Brain damages in ketamine addicts as revealed by magnetic resonance imaging

 

https://doi.org/10.3...nana.2013.00023
 

Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5–12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2–4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine.

 

 

SINGLE-DOSE KETAMINE ADMINISTRATION INDUCES APOPTOSIS IN NEONATAL MOUSE BRAIN

https://doi.org/10.1...P.2005.16.4.231

 

See all › 43 Citations See all › 19 ReferencesShare Request full-text Single-dose ketamine administration induces apoptosis in neonatal mouse brain Article in Journal of basic and clinical physiology and pharmacology 16(4):231-43 · January 2005 with 60 Reads DOI: 10.1515/JBCPP.2005.16.4.231 · Source: PubMed 1st Michael Rudin 2nd Ron Ben-Abraham + 2 3rd Vered Gazit 27.06 · Washington University in St. Louis Last Yeshayahu Katz 37.54 · Unknown Show more authors Abstract Unlabelled: The activity of N-methyl-D-aspartate (NMDA) receptors is critical for neuronal survival in the immature brain. Studies have reported that chronic blockage of these receptors mediates apoptosis in neonatal animals. We investigated the apoptotic effect of a clinically relevant single dose of ketamine, an NMDA receptor antagonist, in the brain of neonatal mice. Seven-day-old ICR mice were injected with ketamine (1.25, 2.5, 5, 10, 20, and 40 mg/kg body weight, subcutaneously in 0.9% NaCl) or with 0.9% NaCl alone as control. Righting reflex testing was performed and mouse brains were examined at 24, 48, and 72 h and 7 days after injection. The number of degenerating neurons was measured using silver staining. Apoptosis was confirmed by DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). We observed in the sensorimotor cortex and cerebellum of ketamine-treated mice extensive apoptosis, which was clearly dose-dependent and present even after a low dose of ketamine (5 mg/kg). The most prominent apoptotic damage was detected 72 h post-injection (P < 0.001 vs control), at doses ranging from 10 to 40 mg/kg. After 7 d the number of neurodegenerative neurons, at doses ranging from 5 to 40 mg/kg, remained significantly high. The brain weight was comparable to that of untreated control mice and no gross neurobehavioral effects in the righting reflex test or alteration in the pattern of behavior was observed. The results indicate that the administration of ketamine in a clinically relevant single dose triggers long-lasting neuronal apoptosis in certain brain areas of neonatal mice. Implications: The administration of ketamine in a clinically relevant single dose to 7-d-old mice induced apoptosis in the sensorimotor cortex and cerebellum. This effect was dose-dependent and long lasting.

 

 

Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice

https://www.scienced...361923010001103

 

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20 mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.

 

And back to NSI-189... I did some preliminary docking research and compared it to WAY-100,635, a very selective D₄ agonist. The results were very similar, so I suspect it to have some activity there. But actual animal studies would need to confirm this. I have also been scouring chemical databases to find similar compounds and have come up with some very very speculative ideas. I suspect NSI-189 might bind to 5HT_1A as an antagonist, which could be partly responsible for the reported hyperalgesia and paresthesia. (Paradoxically, chronic administration of the very high efficacy 5-HT_1Aagonist befiradol results in potent analgesia following an initial period of hyperalgesia, an effect most likely linked to desensitisation and/or downregulation of 5-HT_1A receptors (i.e. analogous to a 5-HT_1A antagonist-like effect). Or it could be neurogenic pruritus as others have mentioned. I think NSI-189 binds to several 5HT₂ receptors. I suspect it might act as a partial agonist, or mixed agonist/antagonist at different GPCRs. It's brightened colors A LOT, and I see some slight patterning in grass. Like StrangeLove mentioned it can re-activate previous psychedelic use. I've noticed that it's effects are much less noticeable in the 24 hours after consuming cannabis, but when I abstain I get the itchiness, a lot of tingling and enhanced empathy. Speaking of which, it makes my heart hurt similarly to MDA did the one time I tried it. I'm worried it could possibly have 5HT_2B activity, as the compound ST50300481 has a similar structure and is purported to bind to this receptor. So don't take this if you have heart issues. Some other possible targets of NSI-189 include: SERT, NET, DAT, Mineralocorticoid Receptor 1 modulation, and Metabotropic Glutamate Receptor 5 antagonism.

I've been searching for the supposedly novel target by which it causes neurogenesis by reading all Neural Stem publications, and even reading studies done by the authors of those publications, but I haven't found much interesting in that department.

 

Well, there are certainly going to be differences between the effects of ketamine administration on neonatal mice and on adult mice. There are conflicting results regarding the effect of ketamine on oxidative damage. These results seem to vary from species to species. For example, one study found that ketamine can actually reduce oxidative stress caused by maternal deprivation in adult rats (PMID: 25728399) and another study found that ketamine administration can reduce oxidative damage in cultured rat hippocampal neurons (PMID: 26935063). Another study found that ketamine administration to rats (4-30 mg/kg, corresponding to 0.65-4.9 mg/kg in humans according to the allometric dosing scale) produced oxidative damage, but the results seem to be contradictory. On some measures, the higher doses of ketamine actually produced less damage than the lower doses. The effect also varied by brain region. Another study found that ketamine increases oxidative stress, but this pathway is mediated by mTOR, the very pathway responsible for ketamine's antidepressant effects (PMID: 27590136). It looks like the oxidative damage caused by ketamine treatment can be prevented by concomitant administration of omega-3-fatty acids (PMID: 24316471). It can be argued that depression and chronic stress increase oxidative stress anyways, though. It looks like the apoptotic effect of ketamine is mediated by reactive oxygen species. In this case, this effect could be greatly attenuated by concomitant administration of an antioxidant (PMID: 23460563). The antidepressant dose of ketamine is well under the anesthetic dose (certainly below 2 mg/kg).

 

As far as NSI-189 goes, wasn't there a mention on the March, 2016 Corporate Presentation that NSI189's antidepressant effects were not mediated by any known GPCR's, kinases, or SERT/DAT/NET inhibition? I doubt they could have tested all possible protein targets of NSI-189, but I think that Neuralstem has not determined the target of NSI189 yet. It's possible that NSI-189 modulates the activity of some kinase pathways either by binding to a GPCR or by binding to the kinase specifically. There are so many interactions between various signalling pathways and there are still new proteins being discovered regularly. I think the most recent study (PMID: 28181668) on NSI-189 and its effects on rats with brain damage from stroke might shed some light on the potential mechanism of action: i) NSI-189 increases concentrations of BDNF, GDNF, VEGF, and SCF in hippocampal cells ii) NSI-189 increases Ki67 and MAP2 expression (responsible for cell proliferation and maintaining the structure of neurons, respectively, so NSI-189 is pro-proliferative) in the hippocampus and the cortex. 

 

Edited by aperson444, 10 March 2017 - 07:37 PM.

[Sciencyst]

Hmm, how did the NSI-189 thread turn into discussion about K?

 

I am still using NSI-189 (freebase) sublingual, worked up to 35mg per day once in the morning. I am now able to stack it with 10mg PRL-8-53, 15mg Tianeptine sulphate (love how this doesn't gunk up into a ball of goo!), and 25mg fasoracetam, every day except Sundays.

Its helped me in all areas of life. I am picking up lots of complex topics at uni and remembering it without too much effort - my study time has basically halved compared to last year, hardly any anxiety or stress at all which is amazing given my history of being a huge stresshead, and I just love learning new things - playing piano, DIY cosmetics and jewellry, fitness yoga feels amazing, and I have a huge desire to travel. I don't want to stop taking it, ever.

 

The downside, if you can manage it, is emotional response to situations can be a bit disproportional than what it normally be. For instance I could watch a TV commercial and if its even slightly sad tears start rolling down my face. And if someone tells me a funny joke I just cannot stop laughing

 

Something about antidepressant musings. I digress. That's awesome that your stack is working so great for you!  What's especially amazing is that you seem to be able to experience emotions to overwhelming degrees at times, yet aren't bothered by stress. When I tried tianeptine, it just dulled all emotions equally like SSRIs do. I guess that's the magic of this wonderful molecule, NSI-189. You have found the satori of nootropic use!! Do you feel like there's a change in thought process or verbal fluency? Those are always the two areas for me that respond wildly differently to noots. I've been taking NSI-189 and occasional piracetam and faso for the past two weeks, but I feel like thoughts don't come easily, and finding the right word is difficult. Though, that might be directly caused by cannabis, which I quit two days ago. I guess I'll have to wait and see.
 

 

***blah blah blah incoherent rambling***

 

Well, there are certainly going to be differences between the effects of ketamine administration on neonatal mice and on adult mice. There are conflicting results regarding the effect of ketamine on oxidative damage. These results seem to vary from species to species. For example, one study found that ketamine can actually reduce oxidative stress caused by maternal deprivation in adult rats (PMID: 25728399) and another study found that ketamine administration can reduce oxidative damage in cultured rat hippocampal neurons (PMID: 26935063). Another study found that ketamine administration to rats (4-30 mg/kg, corresponding to 0.65-4.9 mg/kg in humans according to the allometric dosing scale) produced oxidative damage, but the results seem to be contradictory. On some measures, the higher doses of ketamine actually produced less damage than the lower doses. The effect also varied by brain region. Another study found that ketamine increases oxidative stress, but this pathway is mediated by mTOR, the very pathway responsible for ketamine's antidepressant effects (PMID: 27590136). It looks like the oxidative damage caused by ketamine treatment can be prevented by concomitant administration of omega-3-fatty acids (PMID: 24316471). It can be argued that depression and chronic stress increase oxidative stress anyways, though. It looks like the apoptotic effect of ketamine is mediated by reactive oxygen species. In this case, this effect could be greatly attenuated by concomitant administration of an antioxidant (PMID: 23460563). The antidepressant dose of ketamine is well under the anesthetic dose (certainly below 2 mg/kg).

 

As far as NSI-189 goes, wasn't there a mention on the March, 2016 Corporate Presentation that NSI189's antidepressant effects were not mediated by any known GPCR's, kinases, or SERT/DAT/NET inhibition? I doubt they could have tested all possible protein targets of NSI-189, but I think that Neuralstem has not determined the target of NSI189 yet. It's possible that NSI-189 modulates the activity of some kinase pathways either by binding to a GPCR or by binding to the kinase specifically. There are so many interactions between various signalling pathways and there are still new proteins being discovered regularly. I think the most recent study (PMID: 28181668) on NSI-189 and its effects on rats with brain damage from stroke might shed some light on the potential mechanism of action: i) NSI-189 increases concentrations of BDNF, GDNF, VEGF, and SCF in hippocampal cells ii) NSI-189 increases Ki67 and MAP2 expression (responsible for cell proliferation and maintaining the structure of neurons, respectively, so NSI-189 is pro-proliferative) in the hippocampus and the cortex. 

 

Your response is so perfect, citations and everything!! You are a shiny golden god of this forum   Okay, so ketamine is a truly strange beast. I've always found it very odd that NMDA antagonists seem to be both neuorprotective and neurotoxic. So it depends greatly on the state of the brain to which it's administered. I've toyed with MXE holes a lot, and it's something I regret a lot. I certainly felt less depressed, but damn did I feel brain-damaged and paranoid for months afterwards. 

Yeah, they claimed it's effects are not mediated by any of those. But! That doesn't mean that it doesn't exert any effects at those targets, just that it's not the particular mechanism that made this compound attractive to NS in the first place. And from the rapidly-acting and very pronounced CNS effects, I feel strongly that it affects monoamines in one way or another. I've also realized that it feels extremely similar to guanfacine, complete with a drop in hypothermia and a particular relaxed-but-alert headspace. I'll need to do some more docking tests.. again of course they don't mean anything until actual studies prove it. Interesting, so we know it increases a lot of neurogenic 'brain-roids', but not how it does it. Thanks for the info!!

[Fletch]

 

I feel strongly that it affects monoamines in one way or another.

 

 

I thought they ruled out monamines?  I just ordered some and I'm taking Nardil(MAOI), so I'm greatly concerned by this- even though it's subjective opinion. Did they not rule out monoamines?  I'm considering replacing Nardil with it, but considering it doesn't act in any of the same ways (AFIK) I was going to stack it and maybe reduce my Nardil dose. I can't see how it would be a replacement, especially since Nardil works on GABA as well.
 

Edited by Fletch, 10 March 2017 - 10:06 PM.

[Sciencyst]

 

 

I feel strongly that it affects monoamines in one way or another.

 

 

I thought they ruled out monamines?  I just ordered some and I'm taking Nardil(MAOI), so I'm greatly concerned by this- even though it's subjective opinion. Did they not rule out monoamines?  I'm considering replacing Nardil with it, but considering it doesn't act in any of the same ways (AFIK) I was going to stack it and maybe reduce my Nardil dose. I can't see how it would be a replacement, especially since Nardil works on GABA as well.
 

 

It's speculative, but it subjectively feels that way - the hypothermia, color enhancement, and tingles all feel very monoaminergic. And the most similar compounds I can find to it with known bioactivity do affect monoamines. 

[Mind_Paralysis]

 

 

 

I feel strongly that it affects monoamines in one way or another.

 

 

I thought they ruled out monamines?  I just ordered some and I'm taking Nardil(MAOI), so I'm greatly concerned by this- even though it's subjective opinion. Did they not rule out monoamines?  I'm considering replacing Nardil with it, but considering it doesn't act in any of the same ways (AFIK) I was going to stack it and maybe reduce my Nardil dose. I can't see how it would be a replacement, especially since Nardil works on GABA as well.
 

 

It's speculative, but it subjectively feels that way - the hypothermia, color enhancement, and tingles all feel very monoaminergic. And the most similar compounds I can find to it with known bioactivity do affect monoamines. 

 

 

Your findings are similar to another poster on this forum, who ran NSI-189 through a program which analyses molecular structures and compares it to other known molecules, in order to deduce potential affinities and effects - however, there are a few differences between your findings...

 

He, through the program, concluded that NSI-189 does not actually affect monoamines DIRECTLY, but rather, it modulates the activity of some monoamine-receptors.

 

The receptors which the compound most likely have direct affinity for, are as follows, in order of magnitude:

 

5HT1a

D2

D3

 

http://www.longecity...nism-of-action/

 

The D-receptors are most likely the source of the stimulating properties of the compound, and we can therefore conclude that it's most likely a agonist or partial agonist of those receptors - initial potentiation of stimulants, but then followed by lessening of stimulant effects, also points towards this - receptor-downreglation, is most likely the effect.

 

The 5HT1a-affinity is harder to deduce though... In theory, if it was an agonist, it would help with anxiety, but many of us whom have trialled the compound actually reports a significant worsening of anxious behaviour - however, many of us also note strange bouts of sleepiness and fatigue - this could also imply 5HT1a-agonism, as the effects are actually similar to antihypertensive agents with 5HT1a-agonistic properties.

 

 

However, the program plots several other pathways as much more likely, and potent, as the source of the antidepressant effects:

 

Modulation of the JAK-STAT pathway!

 

He also notes how this is plausible, since other JAK-STAT modulators have shown some neurogenic activity - just nothing as potent as NSI-189.

 

 

After attempting to read up on it, I can't say I understand much at all - the only thing I can deduce is that most of the antidepressant effects would come from an altering of the body's metabolism of amino-acids, causing more neurogenic activity - if so, NSI-189 is the compound created which affects neurogenesis the furthest up in the chain of events which govern the process - extremely "upstream" if you like.

 

 

If this holds true... NSI-189 should be synergistic with nearly any and every antidepressant ever created! It should be possible to combine it with literally anything under the sun!

Well, except we know nothing about the metabolism of NSI-189, so we don't know if it interferes with enzymes or if it's hepatotoxic in any way...

 

 

NOTE: Of course, if any of your antidepressants depend on modulation of D2, D3 or 5HT1a, then you may run into trouble as well... Not many do, however.

Edited by Stinkorninjor, 11 March 2017 - 10:15 AM.

[rjfm]

I am on day 23 of my NSI freebase trial - I take 20mg BID sublingual.

 

The very first day I had a placebo anti-anhedonia boost and lots of memories of how my brain used to work as a happy kid. Then for a couple of weeks I was pretty down. Then I had one more day of a positive experience, but it felt like quite a bland, lobotomised high. No desires or thoughts, but not really content either. Now I'm just really depressed, cannot even get off the couch, and I'm really fatigued for a couple of hours after I take it. 

 

Is Dr Strangelove's freebase still in-date? What else could be wrong? How long should I give this? Makes me feel really dumb as I cannot access my memory at all. I just feel like the guy who turned up to give a public speech without my notes, or like I have a big air bubble in my brain.

 

My inner dialogue was turned off a fair chunk when i was trialing NSI-189 freebase from Ceretropic. Is this what you understand by lobotomised high?

 

Sublingual seems to be indeed the way to go with it by the way.

[bocor]

Problem locating legit nsi 189 to buy! A lot of the sites that were selling have cease and desist orders is the eBay stuff legit? Is it only a matter of time before we can't find it anymore? Much thanks for an ongoing reliable source! Jeffer

[Baten]

Problem locating legit nsi 189 to buy! A lot of the sites that were selling have cease and desist orders is the eBay stuff legit? Is it only a matter of time before we can't find it anymore? Much thanks for an ongoing reliable source! Jeffer

 

Look for Strangelove in this thread. Can source from him.

[linlin92]

 

Something about antidepressant musings. I digress. That's awesome that your stack is working so great for you!  What's especially amazing is that you seem to be able to experience emotions to overwhelming degrees at times, yet aren't bothered by stress. When I tried tianeptine, it just dulled all emotions equally like SSRIs do. I guess that's the magic of this wonderful molecule, NSI-189. You have found the satori of nootropic use!! Do you feel like there's a change in thought process or verbal fluency? Those are always the two areas for me that respond wildly differently to noots. I've been taking NSI-189 and occasional piracetam and faso for the past two weeks, but I feel like thoughts don't come easily, and finding the right word is difficult. Though, that might be directly caused by cannabis, which I quit two days ago. I guess I'll have to wait and see.
 

 

Hi UltraCitron, My thought process has changed to a much calmer one. I don't dwell on negative things as much because I can catch myself doing it as soon as it happens and brush it aside like it was an annoying fly. If you are anxious you will hold onto the negative thought for dear life and then feel so terrible as a result of ruminating about it!

 

The verbal fluency is a bit of a mxied bag for me. On one hand I am more outgoing and can chat to anyone unlike before, but sometimes I find it hard to get the right words out of my mouth if that makes any sense! There's a lot of mental blocks for random words that should just roll off my tongue.. but it doesn't! Its super satisfying though when I finally get the word out of my stubborn head after a few seconds of focussing.

[Strangelove]

FuzzMunky, NSI-189 does not work for everyone, but your side effects seem like a possible over dose. It does not matter if you are using a low dose already, some (like me) need a smaller dose than average.

 

How is your health otherwise? I do not remember if we discussed it in your PMs but sounds like NSI-189 is "pushing" your brain but there is some other limiting factor. Do you have any issues with brain fog at all, or any other symptoms apart from the low mood?

 

The positives that linilin92 described is from the same freebase batch.

 

Twindaddy, the increased motivation after discontinuation is a very common effect, it has been reported often in past discussions. This was a major reason why some used to cycle it.

 

Edited by Strangelove, 12 March 2017 - 10:55 PM.

[FuzzMunky]

 

 

My inner dialogue was turned off a fair chunk when i was trialing NSI-189 freebase from Ceretropic. Is this what you understand by lobotomised high?

 

Yes, sort of. Something was annulled yet nothing was added except a default placidness - felt like a loss of character almost. I get a similar feeling from high concentration EPA/DHA, - makes me feel bland.

Certainly wasn't the inspired awakening I get when a rare substance hits the mark and reminds me of how my brain used to work. Anhedonia, to me, coincides with a lack of creative spirit, a narrowed (virtually extinguished) sensory memory and generally passionless affect. But I guess some would call that the lack of hypomania also.

[FuzzMunky]

FuzzMunky, NSI-189 does not work for everyone, but your side effects seem like a possible over dose. It does not matter if you are using a low dose already, some (like me) need a smaller dose than average.

 

How is your health otherwise? I do not remember if we discussed it in your PMs but sounds like NSI-189 is "pushing" your brain but there is some other limiting factor. Do you have any issues with brain fog at all, or any other symptoms apart from the low mood?

 

My health is otherwise ok (touch wood), save for the deficits I am self-medicating for.

 

I get a lot of brain fog with almost every nootropic I have taken seriously, with or without choline - very few exceptions. Piracetam was the worst. It was like having a metaphorical mould grow across the cornea of my consciousness, whilst having my temples in a tightening vice. 

 

NSI brain fog isn't so bad, but it's there.

I also experience the infamous NSI pins and needles - though I find them quite pleasant, so far.

 

I have cut the dose in half. I will see how that goes.

Edited by FuzzMunky, 13 March 2017 - 07:32 AM.

[Hyperflux]

It's been 3 weeks on 10mg freebase, feeling good. The fatigue seems to be mostly gone, or I've adapted to it. 

[Fletch]

Has anyone experienced, super irrational, persistent psychotic rage from NSI 189? I recently had someone insult me and talk to me in a manner I didn't appreciate, in front of other people, and I proceeded to obsess over it in a fit of uncontrollable rage, I proceeded to devise several detailed plans for retribution against him, and even consulted with others on ideas for how to get back at him. Normally I'm numb, apathetic, and it's difficult for me to even feel anger from the depression. For the record I would never do anything violent, but I will say I managed to obtain his social security number within an hour of getting back home. It took me over 24 hours to really start coming down from the rage and thirst for vengeance but this is somewhat concerning and I cannot find anyone who has remotely shared this experience with the drug. I was only on piracetam and fish oil at the time aside from the NSI 189, not sure what happened. I completed 15 days at 80mg/day and have some more on the way, but I might have to AT LEAST lower the daily dose if I'm to continue.

Reports like this one concern me greatly. I've experienced similar to the above not on NSI. When I was in benzo cold-turkey withdrawal (day 5) a couple weeks ago, I went into the biggest rage experience of my life over childhood/current issues with my sister. When I'm "wronged" I get very vengeful and I can't risk anything I boosting my emotional anger response. I've read several people say NSI increases emotional magnitude. The positive ones would be awesome to increase, but at the cost of increased agitation and reactivity I'm going to have to be very careful and start low dose. Any tips or anecdotes?

Has anyone experienced, super irrational, persistent psychotic rage from NSI 189? I recently had someone insult me and talk to me in a manner I didn't appreciate, in front of other people, and I proceeded to obsess over it in a fit of uncontrollable rage, I proceeded to devise several detailed plans for retribution against him, and even consulted with others on ideas for how to get back at him. Normally I'm numb, apathetic, and it's difficult for me to even feel anger from the depression. For the record I would never do anything violent, but I will say I managed to obtain his social security number within an hour of getting back home. It took me over 24 hours to really start coming down from the rage and thirst for vengeance but this is somewhat concerning and I cannot find anyone who has remotely shared this experience with the drug. I was only on piracetam and fish oil at the time aside from the NSI 189, not sure what happened. I completed 15 days at 80mg/day and have some more on the way, but I might have to AT LEAST lower the daily dose if I'm to continue.

Reports like this one concern me greatly. I've experienced similar to the above not on NSI. When I was in benzo cold-turkey withdrawal (day 5) a couple weeks ago, I went into the biggest rage experience of my life over childhood/current issues with my sister. When I'm "wronged" I get very vengeful and I can't risk anything I boosting my emotional anger response. I've read several people say NSI increases emotional magnitude. The positive ones would be awesome to increase, but at the cost of increased agitation and reactivity I'm going to have to be very careful and start low dose. Any tips or anecdotes?

[magniloquentc0unt]

i think the cases of extreme emotionality (be it anger or anything else) are due to too high a dose. 40mg was too high for me, i went down to 20 and felt it was too bland, now im stuck at 30 and i find it optimal for me. I am way more empathic toward others, can address my attention clearly and i keep getting surprised how more easily i can remember something if i really wish to.

40mg + being dumped caused some severe depression which prevented me from going to work intermittingly for a couple of weeks as i could not think of anything else, too. but i picked up smoking weed again after long years of abstinence in that period so im pretty sure that can make me slightly psychotic too and it surely played a role. so yeah, muddy opinion.

 

in all honesty i think this stuff should be coupled with some sort of serotonergic substance. moclobemide works well for me and i have a script, but i think mirtazepine could be something even better. 

in any case. it is hands down the only thing that gets near to what i would describe as a medication for anhedonia.

 

and for the record, i tried a combo with 200mg modafinil and about 10gin and tonics and i felt extremely lucid the whole evening, which was an interesting experience and slightly disappointing aswell - so thats safe

Edited by magniloquentc0unt, 13 March 2017 - 08:28 PM.

[Hyperflux]

Any athletes or lifters here? I think that NSI negatively impacts my training, probably due to poorer sleep quality but I'm not too sure. I'm still sticking with it because this is the best I've felt in terms of mood and emotion in a while. It makes you remember all the good things you've experienced and lived through in life, really gives you perspective.