4029 replies to this topic

[Adaptogen]

hey, i'm sure this has probably been discussed before, but I came across this:

"Although in the pre-clinical and clinical studies the 810 nm light was often used for nerve repairs [36], the effects of laser irradiation with different wavelengths on dendrite growth remain unclear. Studies had shown that the 633 nm laser had advantages over other wavelengths in treating neurological diseases [12, 22]. We found that compared with 810 nm laser treatment, irradiation with 633 nm light induced higher BDNF expression (data not shown). Previous studies from this lab, and others, have shown that cell death induced by Aβ25-35 is significantly diminished with 633 nm LLLT."   http://dx.doi.org/10.1117/12.2068980

 

 

how does the evidence of other studies reflect this? if it isnt idiosyncratic, would that mean that the CCTV LEDs that most people are using are not optimal for cognitive enhancement?

[Kinesis]

I couldn't get your link to work, but according to the research I've read wavelengths in the 600 nm range may work well in vitro and for small animals but wouldn't have enough penetrating power to have much effect on the human brain in transcranial use. Most of the studies cited in this review used wavelengths in the 810-870 mm range. In humans the radiation has to get through 1-2 cm of skin and bone before the question of brain tissue efficacy even becomes relevant.

http://neurophotonic...55&PDFSource=24

Edited by Kinesis, 17 April 2016 - 12:50 AM.

[Adaptogen]

I think you're right, I found this supporting statement in another article:

 

"The rationale for the optical parameters were as follows: The wavelength of 810-nm is optimum for light penetration of living tissue due to minimization of absorption by all three major tissue chromophores, hemoglobin, melanin and water. Moreover this wavelength has been shown to be effectively absorbed by mitochondria that are believed to be responsible for the biological effects of photobiomodulation." - Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety

[Kinesis]

This graphic helps put it in perspective.  It is from "Mechanisms Of Low Level Light Therapy" (http://photobiology.info/Hamblin.html), where Michael R. Hamblin explains that

 

The second important consideration involves the optical properties of tissue. Both the absorption and scattering of light in tissue are wavelength dependent (both much higher in the blue region of the spectrum than the red), and the principal tissue chromophore (hemoglobin) has high absorption bands at wavelengths shorter than 600 nm. For these reasons, there is a so-called "optical window". The second important consideration involves the optical properties of tissue. Both the absorption and scattering of light in tissue are wavelength dependent (both much higher in the blue region of the spectrum than the red), and the principal tissue chromophores (hemoglobin and melanin) have high absorption bands at wavelengths shorter than 600 nm. Water begins to absorb significantly at wavelengths greater than 1150 nm. For these reasons, there is a so-called "optical window" in tissue covering the red and NIR wavelengths, where the effective tissue penetration of light is maximized (Figure 2). Therefore, although blue, green and yellow light may have significant effects on cells growing in optically transparent culture medium, the use of LLLT in animals and patients almost exclusively involves red and NIR light (600 - 950 nm).

 

So in transcranial photobiomodulation, you're basically striking a compromise between the wavelength preferences of the target molecules (e.g. cytochromes) and the ability of the intervening tissue to transmit the radiation to it.  The chart shows how the most important intervening substances (melanin in the skin, hemoglobin in the blood, and water in all tissues) absorb light as a function of wavelength, forming a sort of "optical window" through which the light must pass.to reach the brain.  Notice the rapid falloff in absorbance of melanin and hemoglobin as the wavelength rises from about 600-800 nm, while the absorbance of water rises from around 800 nm and up.

 

 

 

 Figure 2. Optical window in tissue due to reduced absorption of red and NIR wavelengths (600-1200 nm) by tissue chromophores.

[Norcient]

LostFalco, almost done reading the whole thread here over the course of a weeks time. 

 

I gathered you dropped CoQ10 because of spending too much on all other interesting compounds and supplements. 

You should check out purebulk.com - http://purebulk.com/...0-coenzyme-q10/ they do cut the price very much compared to, say, LEF. At least 10 times cheaper if you buy it like this, possibly more. Granted what they have is ubiquinone. 

You then take the powder, and mix it with with coconut-oil (heating the coconut oil up, but not boiling it!). Put it in a container and put it in the fridge. Now you have a block of coconut-oil with CoQ10 in it. As always be careful of oxidation with CoQ10. 

Unfortunately they don't carry the better quality. 

Also look out for some deals, because they pretty regularly often do 20-25% off.

 

Bought all the things for TULIP and will start straight away when I get it. Will let you know how it goes.

 

 

 

Oh.. and just a funny thing, because it's old now but I just read most of the thread. Remember that some guys were selling a package of LED's and naming it TULIP package - without any reference to your protocol/stack. I can solve the mystery for you. It's because of key-words. Drop-ship sellers or online marketeres look up keywords - what has been queried together with LED 96 in a search on google or other websites. It makes sense that some would see that TULIP + LED 96 + LED 48 etc. was a often used search term - and thus they just put this "buy together with" package - not knowing anything about what your TULIP protocol actually is.

[lostfalco]

Hey lostfalco, can you give us an update as to the state of readiness of lostfalco.com? In particular, it would be quite convenient to be able to read a more tidy and condensed version of your current thinking based on all the conversation here. Ideally, there would be one "special" blog entry which you would periodically update to be a summary of exactly that, with links out to the detailed posts. (But I realize how frustrating blog interfaces can be, for that purpose, as they're all geared to chronological journalling.)

Hey resveratrol_guy, sadly it's still a bit of a mess. I totally agree with you about condensing and synthesizing everything in this labyrinthian thread! I'm feverishly working on it behind the scenes. With that said, the God Stack post and the TULIP post are pretty good places to start. They're pretty much place holders for the time being and need significant editing and revision but they're something. I'll definitely let you know when the site is ready for prime time! Should be pretty soon. 

 

TULIP  http://www.lostfalco...-laser-therapy/

The God Stack 1.0    http://www.lostfalco.com/tgs/ 

Edited by lostfalco, 17 April 2016 - 03:47 PM.

[lostfalco]

I've been having such good results with this little stack that I couldn't help but share. http://www.lostfalco...ch-to-the-head/

 

I have all the science in my head but I won't have it written down till Friday (frickin' school). 

 

Just wanted to get it out there in case people suspect they are suffering from neuroinflammation/brain fog and want a novel combo to experiment with. 

 

I hope it helps!  

 

Edited by lostfalco, 18 April 2016 - 01:49 AM.

[Bluecheer]

I've been having such good results with this little stack that I couldn't help but share. http://www.lostfalco...ch-to-the-head/

 

I have all the science in my head but I won't have it written down till Friday (frickin' school). 

 

Just wanted to get it out there in case people suspect they are suffering from neuroinflammation/brain fog and want a novel combo to experiment with. 

 

I hope it helps!  

 

Have you felt that you have clearer lungs aswell?

Got asthma so hm..

Also I was wondering,
I cant find any information to the contrary, but do you think Coq10 or PQQ would break a fast? I'm worried that it would... although I haven't found any evidence saying that it would.

[MindExplorer]

Lostfalco, should ibudilast be synergistic with any AChEI or specifically galantamine? Synergy with ibudilast aside, do you prefer galantamine to huperzine A or have you only tried the former? I haven't used either, but I'd like to understand theoretical and/or practical differences between them, and I very much plan to try out this stack.

[lostfalco]

Lostfalco, should ibudilast be synergistic with any AChEI or specifically galantamine? Synergy with ibudilast aside, do you prefer galantamine to huperzine A or have you only tried the former? I haven't used either, but I'd like to understand theoretical and/or practical differences between them, and I very much plan to try out this stack.

Hey MindExplorer, ibudilast should be synergistic with a number of AChEI. There are quite a few good options out there that activate the cholinergic anti-inflammatory pathway. (see study below)

 

I prefer galantamine over huperzine from pretty extensive personal testing with both. That's just me though. Other options are def worth a try if someone has a preferred acetylcholinsterase inhibitor. 

 

If you try the ibudilast + galantamine/huperzine combo let me know how it goes. I'm always curious to see how it affects others. 

 

https://www.ncbi.nlm...les/PMC4100123/

 

Int J Mol Sci. 2014 Jun 2;15(6):9809-25. doi: 10.3390/ijms15069809.

Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity.

Pohanka M1.

Author information

Abstract

Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer's disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a "cholinergic anti-inflammatory pathway" which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system.

 

https://www.ncbi.nlm...pubmed/19795377

 

J Neurosci Res. 2010 Mar;88(4):807-15. doi: 10.1002/jnr.22237.

Huperzine a improves chronic inflammation and cognitive decline in rats with cerebral hypoperfusion.

Wang J1, Zhang HY, Tang XC.

Author information

Abstract

Chronic cerebral hypoperfusion has been suggested to contribute to the progression of dementia. Inflammation and white matter lesion (WML) are involved in the pathologic process. This study investigated whether huperzine A, a natural acetylcholinesterase (AChE) inhibitor, has beneficial effects on long-lasting inflammation as well as cognitive impairment in a rat model of cerebral hypoperfusion and how it plays these roles. Chronic cerebral hypoperfusion was induced by occlusion of bilateral common carotid arteries (two-vessel occlusion; 2VO). Huperzine A was initially given 150 min after 2VO and daily for 3, 7, 14, and 28 days. Learning and memory dysfunction as tested by Morris water maze performance was observed in 2VO-operated rats and was significantly improved by huperzine A treatment. WML and activation staining of immune cells were evaluated by Klüver-Barrera (KB) and immunohistochemistry, respectively. Myelin damage and increased immunostains were found in optic tract at all indicated days. Huperzine A treatment significantly ameliorated all these phenomena. Moreover, huperzine A also suppressed overexpression of the inflammatory factor tumor necrosis factor-alpha (TNF-alpha) and overphosphorylation of JNK and p38 mitogen-activated protein kinases (MAPKs) in a cell model of chronic hypoxia. Preincubation with mecamylamine (MEC), a nicotinic acetylcholine receptor (nAChR) antagonist, for 30 min before hypoxia notably reversed the effects of huperzine A on TNF-alpha production and MAPKs phosphorylation. In conclusion, delayed and chronic administration of huperzine A could protect against 2VO-induced cognitive impairment, which might be related to its beneficial effects on WML, and the nAChR-dependent cholinergic anti-inflammation pathway plays an important role.

 

Edited by lostfalco, 18 April 2016 - 03:50 AM.

[lostfalco]

Have you felt that you have clearer lungs aswell?

Got asthma so hm..

Also I was wondering,
I cant find any information to the contrary, but do you think Coq10 or PQQ would break a fast? I'm worried that it would... although I haven't found any evidence saying that it would.

 

haha Good question, Bluecheer. Tbh, my breathing feels pretty darn good on ibudilast. It wasn't too bad before though so hard to say anything definitive. =)

 

Ubiquinol typically has about 5 calories (LEF, at least) and PQQ has virtually zero...I think you're pretty good. 

[Jochen]

Lostfalco,

 

I hope to get my intranasal bottles soon so I can make some intranasal galantamine (got some good points from MYASD on reddit).

Mainly making this from my stepfather (parkinson'), but will test it out on myself first to see all the GI negatives (and other side effects) are indeed bypassed this way

 

as always, thank you for your insights and keeping this thread going :-)

[De La Torre]

I've been having such good results with this little stack that I couldn't help but share. http://www.lostfalco...ch-to-the-head/

 

I have all the science in my head but I won't have it written down till Friday (frickin' school). 

 

Just wanted to get it out there in case people suspect they are suffering from neuroinflammation/brain fog and want a novel combo to experiment with. 

 

I hope it helps!  

 

Hey LF

 

Really keen to try this combo.

The galantamine was easy to source.

2 questions...

What's the protocol for adminstration for these two products...?

And do you have another viable source for the ibudilast,

as the site you linked, won't accept my credit card (don't usually have this issue).

 

Much love bro...

[cougar]

Thank you very much lostfalco for bringing up the neuroinflammation topic. I've been thinking about this possibility for quite a long time, but had never taken any action about it yet. Although I've never been diagnosed for Traumatic Brain Injury (TBI), I really suspect I had it. This is because I had a few accident of TBI throughout my life, with the most serious one happened about thirty years ago while I was still in university when I fell down from about 1.5 meters with the back of my head landing the ground. I didn't feel too much different after that, but thinking back, I believe some kind of damage must have formed since then, given my subjective perception of faster cognitive decline over the years, along with my frequent headache almost always coming from the back of my head. Given my possible TBI history, do you think I've probably had chronic inflammation in my brain for a long time?

I have Galantamine at hand, but I don't have Ibudilast. Because I can't wait to start doing something about my possible TBI, I've taken 200 mg Advil (Ibuprofen) and 4 mg Galantamine about an hour ago. Hard to say if it's placebo but at least I'm much less sleepy now than an hour ago. Is it possible to replace Ibudilast with Ibuprofen in your protocol? It would be great if Ibuprofen also works because Advil is easily available over the counter.

Here's a study about Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain: http://www.ncbi.nlm....pubmed/21696706

 

 

Thanks a lot!
 

 

Edited by cougar, 18 April 2016 - 12:50 PM.

[lostfalco]

1. Given my possible TBI history, do you think I've probably had chronic inflammation in my brain for a long time?

2. Is it possible to replace Ibudilast with Ibuprofen in your protocol?

Here's a study about Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain: http://www.ncbi.nlm....pubmed/21696706

 

 

Thanks a lot!
 

Hey cougar, I'm sorry to hear about your tbi. They can def have lasting effects on neuroimmune function. One major effect is called reactive gliosis which refers to post-tbi chronic microglial/astrocytic activation. 

 

1. This is definitely possible.  

 

2. I don't think ibuprofen could quite be called a 'replacement' (it has a different mechanism than ibudilast) but I do think it's worth a try with galantamine (or a cholinergic anti-inflammatory pathway activator of your choice). =)

 

 

http://www.ncbi.nlm....les/PMC3489473/

 

Neuroscience. 2012 Dec 6;225:65-75. doi: 10.1016/j.neuroscience.2012.08.058. Epub 2012 Sep 6.

Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat.

Cao T1, Thomas TC, Ziebell JM, Pauly JR, Lifshitz J.

Author information

 

Abstract

Traumatic brain injury (TBI) survivors experience long-term post-traumatic morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to whisker stimulation models the agitation of TBI survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate post-traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. Here we hypothesize that a temporal sequence of microglial activation states contributes to the circuit pathology responsible for post-traumatic morbidity, and test the hypothesis by examining microglial morphological activation and neuroinflammatory markers for activation states through gene expression and receptor-binding affinity. Adult male, Sprague-Dawley rats were subjected to a single moderate midline fluid percussion injury (FPI) or sham injury. Microglial activation was determined by immunohistochemistry, quantitative real-time PCR and receptor autoradiography in the primary somatosensory barrel field (S1BF) and ventral posterior medial nucleus (VPM) of the thalamus at 7 and 28 days following FPI. Morphological changes indicative of microglial activation, including swollen cell body with thicker, shrunken processes, were evident in S1BF and VPM at 7 and 28 days post-injury. Principally at 7 days post-injury in VPM, general inflammatory gene expression (major histocompatibility complex I, major histocompatibility complex II, translocator protein 18 kDa [TSPO]) is increased above sham level and TSPO gene expression confirmed by receptor autoradiography. Further, CD45, a marker of classical activation, and TGF-βI, an acquired deactivation marker, were elevated significantly above sham at 7 days post-injury. Daily administration of the anti-inflammatory ibuprofen (20mg/kg, i.p.) significantly reduced the expression of these genes. Evidence for alternative activation (arginase 1) was not observed. Thus, these data demonstrate concomitant classical activation and acquired deactivation phenotypes of microglia in diffuse TBI in the absence of overt contusion or cavitation. Anti-inflammatory treatment may further alleviate the neuropathological burden of post-traumatic inflammation.

 

 

http://www.ncbi.nlm....les/PMC3934516/

 

J Neurotrauma. 2014 Mar 1;31(5):487-97. doi: 10.1089/neu.2013.3090. Epub 2013 Nov 20.

Reversal of established traumatic brain injury-induced, anxiety-like behavior in rats after delayed, post-injury neuroimmune suppression.

Rodgers KM1, Deming YK, Bercum FM, Chumachenko SY, Wieseler JL, Johnson KW, Watkins LR, Barth DS.

Author information

Abstract

Abstract Traumatic brain injury (TBI) increases the risk of neuropsychiatric disorders, particularly anxiety disorders. Yet, there are presently no therapeutic interventions to prevent the development of post-traumatic anxiety or effective treatments once it has developed. This is because, in large part, of a lack of understanding of the underlying pathophysiology. Recent research suggests that chronic neuroinflammatory responses to injury may play a role in the development of post-traumatic anxiety in rodent models. Acute peri-injury administration of immunosuppressive compounds, such as Ibudilast (MN166), have been shown to prevent reactive gliosis associated with immune responses to injury and also prevent lateral fluid percussion injury (LFPI)-induced anxiety-like behavior in rats. There is evidence in both human and rodent studies that post-traumatic anxiety, once developed, is a chronic, persistent, and drug-refractory condition. In the present study, we sought to determine whether neuroinflammation is associated with the long-term maintenance of post-traumatic anxiety. We examined the efficacy of an anti-inflammatory treatment in decreasing anxiety-like behavior and reactive gliosis when introduced at 1 month after injury. Delayed treatment substantially reduced established LFPI-induced freezing behavior and reactive gliosis in brain regions associated with anxiety and continued neuroprotective effects were evidenced 6 months post-treatment. These results support the conclusion that neuroinflammation may be involved in the development and maintenance of anxiety-like behaviors after TBI.

 

http://www.ncbi.nlm....les/PMC3390983/

 

J Neurotrauma. 2012 Jul 1;29(10):1886-97. doi: 10.1089/neu.2011.2273. Epub 2012 Apr 26.

Acute neuroimmune modulation attenuates the development of anxiety-like freezing behavior in an animal model of traumatic brain injury.

Rodgers KM1, Bercum FM, McCallum DL, Rudy JW, Frey LC, Johnson KW, Watkins LR, Barth DS.

Author information

Abstract

Chronic anxiety is a common and debilitating result of traumatic brain injury (TBI) in humans. While little is known about the neural mechanisms of this disorder, inflammation resulting from activation of the brain's immune response to insult has been implicated in both human post-traumatic anxiety and in recently developed animal models. In this study, we used a lateral fluid percussion injury (LFPI) model of TBI in the rat and examined freezing behavior as a measure of post-traumatic anxiety. We found that LFPI produced anxiety-like freezing behavior accompanied by increased reactive gliosis (reflecting neuroimmune inflammatory responses) in key brain structures associated with anxiety: the amygdala, insula, and hippocampus. Acute peri-injury administration of ibudilast (MN166), a glial cell activation inhibitor, suppressed both reactive gliosis and freezing behavior, and continued neuroprotective effects were apparent several months post-injury. These results support the conclusion that inflammation produced by neuroimmune responses to TBI play a role in post-traumatic anxiety, and that acute suppression of injury-induced glial cell activation may have promise for the prevention of post-traumatic anxiety in humans.

 

Edited by lostfalco, 18 April 2016 - 03:45 PM.

[cougar]

Thanks a lot lostfalco for your quick response. I just completed my daily Lumosity training, and got some interesting results. I broke my own records in "Eagle Eye", "Disillusion", and "Color Match". Doing better in "Eagle Eye" and "Disillusion" might not be a big deal because I just started playing these two games. However, my improvement in "Color Match" might be more interesting because I struggled at it lately. In addition, I also made my third, forth and fifth best scores in "Highway Hazards", as well as my third and fifth best scores in "Train of Thought". Even though they are not my best scores, I still think it was pretty good because my records in these two games were made a few days ago while I was on Adderall.

The studies you refereed are very interesting. Not sure if I had post-traumatic anxiety, but I do have anxiety my entire life. It might be worth mentioning that Memantine literally killed my anxiety to zero, and dramatically reduced the frequency of my headache. The only downside is that it also made me ignoring more details, more specifically, now I'm more prone to make subtle mistakes. I use Memantine to reduce amphetamine tolerance which seemed to have worked because after taking low dose amphetamine for eight months', it's still working. By the way, here's a study of "Memantine protects against LPS-induced neuroinflammation": http://www.ncbi.nlm....pubmed/16989956.

Do you think Memantine will stack well with Galantamine and Ibudilast (or Advil)?


Thanks a lot!

[lostfalco]

Thanks a lot lostfalco for your quick response. I just completed my daily Lumosity training, and got some interesting results. I broke my own records in "Eagle Eye", "Disillusion", and "Color Match". Doing better in "Eagle Eye" and "Disillusion" might not be a big deal because I just started playing these two games. However, my improvement in "Color Match" might be more interesting because I struggled at it lately. In addition, I also made my third, forth and fifth best scores in "Highway Hazards", as well as my third and fifth best scores in "Train of Thought". Even though they are not my best scores, I still think it was pretty good because my records in these two games were made a few days ago while I was on Adderall.

The studies you refereed are very interesting. Not sure if I had post-traumatic anxiety, but I do have anxiety my entire life. It might be worth mentioning that Memantine literally killed my anxiety to zero, and dramatically reduced the frequency of my headache. The only downside is that it also made me ignoring more details, more specifically, now I'm more prone to make subtle mistakes. I use Memantine to reduce amphetamine tolerance which seemed to have worked because after taking low dose amphetamine for eight months', it's still working. By the way, here's a study of "Memantine protects against LPS-induced neuroinflammation": http://www.ncbi.nlm....pubmed/16989956.

Do you think Memantine will stack well with Galantamine and Ibudilast (or Advil)?


Thanks a lot!

No problem, cougar. I'm glad it's working so well for you! That's pretty damn cool. 

 

Here's the stack in case people are interested. http://www.lostfalco...h-to-the-head/ 

 

Yes, memantine should stack well with galantamine + ibudilast or advil. (see study below)

 

One thing to keep in mind is that microglia do great things for our cognition. It's excessive microglia activation that is the problem.

 

I think of it like turning the radio volume up and down. Since you're already doing so well with galantamine and advil, keep those doses the same and just add a tiny bit of memantine.

 

If it helps, then try adding a bit more. If it doesn't help, then drop it. You know the drill. =)

 

Awesome it's working for you! Keep us all updated and thanks for measuring your results!

 

https://www.ncbi.nlm...les/PMC4788730/

 

Am J Neurodegener Dis. 2016 Mar 1;5(1):29-51. eCollection 2016.

Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson's disease.

Lauterbach EC1.

Author information

Abstract

Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) and the pre-motor stages of Parkinson's disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD. The literature of common psychotropics used in treating psychiatric disorders was reviewed for preclinical and clinical findings regarding microglial activation. Findings potentially compatible with reduced microglial activation or reduced microglial inflammogen release were evident for: antipsychotics including neuroleptics (chlorpromazine, thioridazine, loxapine) and atypicals (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone); mood stabilizers (carbamazepine, valproate, lithium); antidepressants including tricyclics (amitriptyline, clomipramine, imipramine, nortriptyline), SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), venlafaxine, and bupropion; benzodiazepine anxiolytics (clonazepam, diazepam); cognitive enhancers (donepezil, galantamine, memantine); and other drugs (dextromethorphan, quinidine, amantadine). In contrast, pramipexole and methylphenidate might promote microglial activation. The most promising replicated findings of reduced microglial activation are for quetiapine, valproate, lithium, fluoxetine, donepezil, and memantine but further study is needed and translation of their microglial effects to human disease still requires investigation. In AD-relevant models, risperidone, valproate, lithium, fluoxetine, bupropion, donepezil, and memantine have therapeutic microglial effects in need of replication. Limited clinical data suggest some support for lithium and donepezil in reducing MCI progression, but other drugs have not been studied. In PD-relevant models, lamotrigine, valproate, fluoxetine, dextromethorphan, and amantadine have therapeutic microglial effects whereas methylphenidate induced microglial activation and pramipexole promoted NO release. Clinical data limited to pramipexole do not as of yet indicate faster progression of early PD while the other drugs remain to be investigated. These tantalizing psychotropic neuroprotective findings now invite replication and evidence in AD-and PD-specific models under chronic administration, followed by consideration for clinical trials in MCI and early stage PD. Psychiatric features in early disease may provide opportunities for clinical studies that also employ microglial PET biomarkers.

 

"Galantamine

In a model of HIV-associated dementia, galantamine and nicotine pretreatment each attenuated TNFa and NO release through a mechanism involving the alpha7 nicotinic cholinergic receptor and p44/42 MAPK system in microglia activated by exposure to both interferon-gamma and the HIV-1 coat glycoprotein gp120 [128]. Thus, a single study demonstrated that galantamine reduced NO and TNFa release in an HIV model.

Memantine

Memantine 10 mg/kg/day intraventricularly for 28 days (plasma levels similar to therapeutic doses in humans) reduced microglial activation and improved hippocampal-dependent spatial memory impairments in rats undergoing chronic intraventicular LPS infusions [129]. In a study of APPswe/PS1 transgenic mouse retina, memantine reduced activated microglia and ERK1/2 phosphorylation after 10 mg/kg/day for 8 days [130]. In single studies, memantine reduced microglial activation after acute administration in an AD transgenic mouse and after chronic administration in rats receiving intraventricular LPS infusions."

 

Edited by lostfalco, 18 April 2016 - 05:46 PM.

[cougar]

Interesting study, thanks lostfalco.

I didn't know the anti-anxiety and headache relief effects of Memantine was probably from it's microglial activation reduction mechanism. I thought they were related to it's NMDA antagonism. I took 5mg Memantine in the beginning. As I increased my dose to 10mg later, I noticed further reduction in the frequency of my headache. I thought it was a confirmation of my overactive glutamate system and too much Calcium influx. I will probably cut my dose down to 5 mg. Also, I think I will try 100mg instead of 200mg Advil taking chronically before I have a chance to try Ibudilast. What's your opinion?

By the way, do you have any concern regarding the possibility of over activating the NMDA and AMPA receptors (unrelated to your new stack, but in general)?

Edited by cougar, 18 April 2016 - 07:08 PM.

[Bluecheer]

Thank you very much lostfalco for bringing up the neuroinflammation topic. I've been thinking about this possibility for quite a long time, but had never taken any action about it yet. Although I've never been diagnosed for Traumatic Brain Injury (TBI), I really suspect I had it. This is because I had a few accident of TBI throughout my life, with the most serious one happened about thirty years ago while I was still in university when I fell down from about 1.5 meters with the back of my head landing the ground. I didn't feel too much different after that, but thinking back, I believe some kind of damage must have formed since then, given my subjective perception of faster cognitive decline over the years, along with my frequent headache almost always coming from the back of my head. Given my possible TBI history, do you think I've probably had chronic inflammation in my brain for a long time?

I have Galantamine at hand, but I don't have Ibudilast. Because I can't wait to start doing something about my possible TBI, I've taken 200 mg Advil (Ibuprofen) and 4 mg Galantamine about an hour ago. Hard to say if it's placebo but at least I'm much less sleepy now than an hour ago. Is it possible to replace Ibudilast with Ibuprofen in your protocol? It would be great if Ibuprofen also works because Advil is easily available over the counter.

Here's a study about Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain: http://www.ncbi.nlm....pubmed/21696706

 

 

Thanks a lot!
 

 

I know this is super obvious, but sometimes an over looked matter. Ibuprofen greatly increases the risk of Heart attack and stroke..

Were as I have not seen similar information stating Ibudilast does.

So I would be more conservative with ibuprofen.
 

Thank you very much lostfalco for bringing up the neuroinflammation topic. I've been thinking about this possibility for quite a long time, but had never taken any action about it yet. Although I've never been diagnosed for Traumatic Brain Injury (TBI), I really suspect I had it. This is because I had a few accident of TBI throughout my life, with the most serious one happened about thirty years ago while I was still in university when I fell down from about 1.5 meters with the back of my head landing the ground. I didn't feel too much different after that, but thinking back, I believe some kind of damage must have formed since then, given my subjective perception of faster cognitive decline over the years, along with my frequent headache almost always coming from the back of my head. Given my possible TBI history, do you think I've probably had chronic inflammation in my brain for a long time?

I have Galantamine at hand, but I don't have Ibudilast. Because I can't wait to start doing something about my possible TBI, I've taken 200 mg Advil (Ibuprofen) and 4 mg Galantamine about an hour ago. Hard to say if it's placebo but at least I'm much less sleepy now than an hour ago. Is it possible to replace Ibudilast with Ibuprofen in your protocol? It would be great if Ibuprofen also works because Advil is easily available over the counter.

Here's a study about Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain: http://www.ncbi.nlm....pubmed/21696706

 

 

Thanks a lot!
 

 

I know this is super obvious, but sometimes an over looked matter. Ibuprofen greatly increases the risk of Heart attack and stroke..

Were as I have not seen similar information stating Ibudilast does.

So I would be more conservative with ibuprofen.
 

[cougar]

I know this is super obvious, but sometimes an over looked matter. Ibuprofen greatly increases the risk of Heart attack and stroke..

 

 

Thanks for your info Bluecheer. Do you have a link to the study, or maybe a few studies?
 

[Bluecheer]

I am at work so cant pull up best sources atm,
But here’s one:
http://www.ncbi.nlm....pubmed/26841787
The large randomized trials of prolonged coxib treatment added importantly to information provided by epidemiological studies that had previously associated regular use of NSAIDs with increased blood pressure and enhanced risk of congestive heart failure, and identified an increased risk of myocardial infarction as a class effect of cyclooxygenase-2 inhibitors.
I thought it was quite common warning though, I heard Rhonda Patrick talking how it more than 3 fold increased the risk of stroke and heart attack in users.

I’m fairly sure the FDA released a official warning relating to it.
(if you search you’ll find much more valid information than this)
Sorry if this wasn’t that helpful.. I have high cholesterol so I worry about things of this nature

[MindExplorer]

Isn't "NSAID" just a label for OTC pain relievers, not a specific class of drugs with shared MOA? If so, that abstract doesn't really tell me anything.

 

Edit: Too tired to follow the references, but from Wikipedia:
 

Along with several other NSAIDs, chronic ibuprofen use has been found correlated with risk of hypertension^[18] and myocardial infarction (heart attack),^[19] particularly among those chronically using high doses. In older hypertensive patients treated with hydrochlorothiazide, ibuprofen at a high daily dose was found to significantly increase systolic blood pressure.^[20] On 9 July 2015 the US FDA toughened warnings of increased heart attack and stroke risk associated with ibuprofen and related NSAIDs; the NSAID aspirin is not included in this warning.^[21]

 

Edited by MindExplorer, 19 April 2016 - 07:14 AM.

[resveratrol_guy]

Hey resveratrol_guy, sadly it's still a bit of a mess. I totally agree with you about condensing and synthesizing everything in this labyrinthian thread! I'm feverishly working on it behind the scenes. With that said, the God Stack post and the TULIP post are pretty good places to start. They're pretty much place holders for the time being and need significant editing and revision but they're something. I'll definitely let you know when the site is ready for prime time! Should be pretty soon. 

 

TULIP  http://www.lostfalco...-laser-therapy/

The God Stack 1.0    http://www.lostfalco.com/tgs/ 

 

Thanks. This thread isn't getting any shorter, so the website is becoming more necessary by the day. It will help the majority of us who don't have a week to read everything here, and a decade to digest it!

[magta39]

Lostfalco is this MOA for aspirin the same as for ibudilast?   https://www.research...thology_in_Mice

[magta39]

Curcumin is a potent modulator of microglial gene expression and migration

• Marcus Karlstetter†,
• Elena Lippe†,
• Yana Walczak†,
• Christoph Moehle,
• Alexander Aslanidis,
• Myriam Mirza and
• Thomas LangmannEmail author

†Contributed equally

Journal of Neuroinflammation20118:125

DOI: 10.1186/1742-2094-8-125

©  Karlstetter et al; licensee BioMed Central Ltd. 2011

Received: 2 March 2011

Accepted: 29 September 2011

Published: 29 September 2011

Abstract

Background

Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin.

 

http://jneuroinflamm...1742-2094-8-125

 

[lostfalco]

What's up my friends?

 

I'm super sorry about not responding over the past few days but I've been working like crazy to finish the article I promised you for Friday. 

 

So far, I'm extremely happy with how it's turning out and can't wait to show it to you. 

 

I promise to answer every question I've missed on the thread on Saturday. Cool?

 

If you're reading this and wondering what the h$#% I'm talking about, the relevant post is here.  http://www.lostfalco...ch-to-the-head/

 

Talk to you soon!

 

-LF

Edited by lostfalco, 20 April 2016 - 04:41 AM.

[normalizing]

im curious now, did anyone else even bother trying this exclusive ibudilast?

[Bluecheer]

 

Isn't "NSAID" just a label for OTC pain relievers, not a specific class of drugs with shared MOA? If so, that abstract doesn't really tell me anything.

 

Edit: Too tired to follow the references, but from Wikipedia:
 

Along with several other NSAIDs, chronic ibuprofen use has been found correlated with risk of hypertension^[18] and myocardial infarction (heart attack),^[19] particularly among those chronically using high doses. In older hypertensive patients treated with hydrochlorothiazide, ibuprofen at a high daily dose was found to significantly increase systolic blood pressure.^[20] On 9 July 2015 the US FDA toughened warnings of increased heart attack and stroke risk associated with ibuprofen and related NSAIDs; the NSAID aspirin is not included in this warning.^[21]

 

 

Pretty much, Its Non steroidal anti inflammatory drugs. ( although apparently Aspirin does not increase your risk of heart attack ) .. I'm sorry I know that's not the best source but I don't have much computer access at the moment( and I cant copy and paste with these work computers )
But if it is a concern you will find plenty of studies citing this, or take the FDA's warning which they have restated (which is unusual for the FDA)

sorry I cant be of more help at the moment.

[MindExplorer]

 

 

Isn't "NSAID" just a label for OTC pain relievers, not a specific class of drugs with shared MOA? If so, that abstract doesn't really tell me anything.

 

Edit: Too tired to follow the references, but from Wikipedia:
 

Along with several other NSAIDs, chronic ibuprofen use has been found correlated with risk of hypertension^[18] and myocardial infarction (heart attack),^[19] particularly among those chronically using high doses. In older hypertensive patients treated with hydrochlorothiazide, ibuprofen at a high daily dose was found to significantly increase systolic blood pressure.^[20] On 9 July 2015 the US FDA toughened warnings of increased heart attack and stroke risk associated with ibuprofen and related NSAIDs; the NSAID aspirin is not included in this warning.^[21]

 

 

Pretty much, Its Non steroidal anti inflammatory drugs. ( although apparently Aspirin does not increase your risk of heart attack ) .. I'm sorry I know that's not the best source but I don't have much computer access at the moment( and I cant copy and paste with these work computers )
But if it is a concern you will find plenty of studies citing this, or take the FDA's warning which they have restated (which is unusual for the FDA)

sorry I cant be of more help at the moment.

 

 

No worries. It wouldn't make sense for all OTC pain relievers (i.e. those that we arbitrarily call NSAIDs) besides aspirin to share the same health concerns, but a bit of googling suggests that both ibuprofen and naproxen belong to the propionic acid class of NSAIDs, so they do share structural and presumably pharmacological properties. I imagine the FDA warning you and Wikipedia referenced resulted from that class of NSAIDs specifically, even if they used irrationally broad language in the warning.
 

[Groundhog Day]

With ibudilast, It's quoting me $16+ for shipping to the US! Is it available anywhere else or what else on the site is useful to get to $100 for free shipping?