4029 replies to this topic

[lostfalco]

Hey falco' you've certainly taken your fair share of interesting chemicals these days, What do you say is your 80/20 of getting results ( where as 20% of your activities or drugs are giving you 80% of the reward) so far? Excluding LLLT of course :D

 I know this is a stocktake type interview question, but I would be really... interested :D

 

 

This is a tough question because I've realized how interconnected everything is. 

 

I kept seeing study after study where 'below threshold' dosing of multiple substances showed non-linear improvements. 

 

My current method consists of low dosing multiple substances simultaneously. 

 

I usually either go with a subtherapeutic dose or the lowest effective dose currently measured. 

 

Remember, there are numerous ways to think of the 80/20 principle. You could think of it as 20% of the substances for 80% of the results or you could think of it as 20% of the dose. Make sense? (There are about a thousand other ways you could think of it as well)

 

I've been experimenting with using 20% of the dose while keeping the number of substances (ie. mechanisms that I target) the same. 

 

I look at potentially synergistic mechanisms and start very slowly while gradually working my way up in dose. 

 

This has paid huge dividends for me over the past year and has taken my experiments into entirely new territory. 

 

I'll talk about it more when I discuss The Genesis Protocol which is a somewhat modified God Stack/Happy Cil-TULIP. 

Edited by lostfalco, 15 June 2016 - 02:29 PM.

[lostfalco]

I did note the date of the original post but I'm guessing, the follow up article has something to do with Lostfalco's blog and renewed "chatter."  

 

I'd also bet that Lostfalco was unaware of the initial post, but he'd have to weight in on that.   It's really immaterial, and a good thing for all of us.  Seems like ibudilast has real potential, and that Lostfalco deserves credit for being an early populariser.

 

It also makes  me even more excited to try intranasal insulin, which I will be starting this week.

Give Metabolic Alchemy the credit! =)

 

I heard about ibudilast first from him (when someone referenced his blog on reddit) which caused me to look at all the research firsthand. 

 

Major props to him. 

 

Here's a link to his new post on it (the old one got deleted). http://www.metabolic...matory-disease/

Edited by lostfalco, 15 June 2016 - 06:49 PM.

[lostfalco]

considering were already talking about Mag L-theronate anybody know if the effects of Mag l-theronate on the body would be able to replicate/replace existing magnesium supplements in terms of DNA repairing, and all the 'physical' aspects people generally take mag for? - slightly vague question but im wondering if id be able to swap out my normal mag supplement for it .. or if im best off using something like Mag Tech via natural stack.

 

 

 

Does iHerb ship to Australia? 

 

They have a pretty good selection if Amazon doesn't work for you. 

 

Also, /u/mrhappyoz on reddit is from Australia if I remember correctly. 

 

I would drop him a message and see where he gets his supplements. 

 

He popularized the Uridine/Choline/DHA stack here on Longecity years ago. 

[thedarkbobo]

Hmm since I have some - how much is safe taken this way or what was your dose?

 

Two things of some possible pertinence:

 

I've been enjoying non-brain sites for LLLT to good effect. I've been using it alongside brain LLLT, but making sure my total time of exposure is not greater than it would be by my brain LLLT dosage alone? As the mechanism is hormetic I'm wary of overdoing it, but it would also make sense that if different mitochondria are being exposed at different sites, there's no problematic amount of stress being put on the body that would sacrifice hormesis. Does this make sense, or may there be some more global effects on the body such that we wouldn't want to double up even on non-overlapping/unrelated sites? 

Obviously some of the effect is on blood cells, so there is some overlap. At the right dosage the two feel at least similar, but I'm not probably going to do the math to figure out relative blood/tissue exposure at different sites.

 

Intranasal BPC-157 is effective and combines beautifully with I-insulin; antidepressant-feeling.

 

[LongLife]

 

Just wanted to add that it appears your blog is gaining some followers/copy cats.  Check out this article touting Ibudilast--

 

http://www.metabolic...matory-disease/

 

Good news is, it shouldn't be long before a Nootropics Company starts selling Ibudilast powder domestically!

 

Not quite sure if its a copy cat, as if you read the article you'll note the person brings up a article he previously wrote on Ibudilast a year ago!... (didn't mean to discredit your post)

All in all your right ibudilast powder should be coming soon :D

 

I wonder the best way to determine market interest in chemicals..


considering were already talking about Mag L-theronate anybody know if the effects of Mag l-theronate on the body would be able to replicate/replace existing magnesium supplements in terms of DNA repairing, and all the 'physical' aspects people generally take mag for? - slightly vague question but im wondering if id be able to swap out my normal mag supplement for it .. or if im best off using something like Mag Tech via natural stack.

BLUECHEER:

 

Cell receptors for magnesium, calcium and iron are shared. Overload with supplements is easily accomplished (>500mg). Absorption can be an issue with certain forms of magnesium too. Epson Salt (mag sulfate) is cheap and easily absorbed through the skin by topical application (spray it on) and soaking feet/body in water solution. Once the body is "saturated" via multiple applications, then a maintenance dose of magnesium can be used daily.

 

This is where the Mag-l-theronate would enter the picture. If considering this form for cognitive improvement; <gram a day (throughout the day) would provide the maximum magnesium required (likely), depending on weight/health factors. Supplements are food concentrates less the macro-nutrients (proteins, carbohydrates, fats). Many supplements are best taken at night, such as Magnesium+Glycine=Melatonin, etc., for their relaxing functions as well as the fact that between midnight and 4/5 a.m. is when the body repairs and maintains (DNA REPAIRING), requiring basics for their performance. While one is horizontal for numerous hours (sleeping), the metabolism is different and the supplements are utilized efficiently.

 

QUESTION: Swapping out? I would do chelated mag in the morning, spray magnesium sulfate during the day and Mag-l-theronate at night. you will know if you are over doing it if your bowels become prevalent, which means you also have overloaded your cells receptors and are blocking them up so only a tiny amount of calcium and/or iron is being used. Easy does it. More is not better.

 

 An alternative is to review your diet, swap out less nutrient food for higher nutrient food, so you might use something like:

 

http://www.whfoods.c...utrient&dbid=75

 

World's Healthiest Foods rich in
magnesium

Food Cals   DRI/DV

 Pumpkin Seeds18048%

 Spinach4139%

 Swiss Chard3538%

 Soybeans29837%

 Sesame Seeds20632%

 Quinoa22230%

 Black Beans22730%

 Cashews22129%

 Sunflower Seeds20428%

 Navy Beans25524%

 

For serving size for specific foods see the Nutrient Rating Chart.

 

This method of mineral intake (diet) may be the most economical since you would be receiving FOOD, multiple minerals, multiple vitamins, unknown factors and a tremendous list of other "good for you" substances. Your bowels would also be happy campers via this route of mineral administration too :-)

[lostfalco]

Well, I just became aware of Dr. Bredesen's work (thanks to SciLi on reddit)...but these are almost exactly the same (theoretical) conclusions I've come to after extensive experimentation. Here's the applicable thread. https://www.reddit.c...ws_reversal_of/

 

I'm aiming at supranormal cognition so I'm a bit more aggressive with pharmaceuticals than he is with his patients but I would strongly recommend reading his work!

 

Also, check out The God Stack which displays a very similar approach (note The Big Six (diet, exercise, sleep, meditation, fasting, and standing) mentioned at the bottom of the post). http://www.lostfalco.com/tgs/

 

The Genesis Protocol also employs a very similar strategy.  

 

Bredesen's approach is a (fairly) comprehensive one from a large number of angles simultaneously. I would change a few things (we could nitpick all day) and I'm not endorsing everything but this is pretty freaking cool!

 

Make sure you check out the table I attached below which summarizes (very nicely) the program followed by one of the patients. 

 

http://www.impactagi...ull/100690.html

 

Aging (Albany NY). 2014 Sep;6(9):707-17.

Reversal of cognitive decline: a novel therapeutic program.

Bredesen DE1.

Author information

Abstract

This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.

 

http://www.impactagi...ull/100690.html

 

"3) Just as for other chronic illnesses such as osteoporosis, cancer, and cardiovascular disease, the underlying network features a threshold effect, such that, once enough of the network components have been impacted, the pathogenetic process would be halted or reversed. Therefore, even though it is not expected that most patients will be able to follow every single step of the protocol, as long as enough steps are followed to exceed the threshold, that should be sufficient."

 

Patient one: therapeutic program

As noted above, and following an extended discussion of the components of the therapeutic program, the patient began on some but not all of the system: (1) she eliminated all simple carbohydrates, leading to a weight loss of 20 pounds; (2) she eliminated gluten and processed food from her diet, and increased vegetables, fruits, and non-farmed fish; (3) in order to reduce stress, she began yoga, and ultimately became a yoga instructor; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; [5] she took melatonin 0.5mg po qhs; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin 1mg each day; (8) she took vitamin D3 2000IU each day; (9) she took fish oil 2000mg each day; (10) she took CoQ₁₀ 200mg each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated HRT (hormone replacement therapy) that had been discontinued following the WHI report in 2002; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

 

 

Attached Files

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Edited by lostfalco, 16 June 2016 - 05:36 PM.

[88LS]

Definitely agree that is the way forward LF - my stack / lifestyle very much emulates the multi-pronged approach mentioned above, I find it MUCH more beneficial to overall brain health than any single nootropic.


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[normalizing]

to check if allowed to post here ive lost maybe about 10 posts or so quite a huge loss for me, but ill survive! so anyway, i had to ask, do you just walk to the pharmacy and ask for intranasal insulin or do you have to get it prescribed or what do you say to them, reason for need?

[lostfalco]

to check if allowed to post here ive lost maybe about 10 posts or so quite a huge loss for me, but ill survive! so anyway, i had to ask, do you just walk to the pharmacy and ask for intranasal insulin or do you have to get it prescribed or what do you say to them, reason for need?

Yep, just walk up and ask for Novolin R. It's completely legal to purchase without a prescription so you don't need to give them a reason. Just act like you know what you're doing and you should be good. ha

 

I've done it numerous times now and have never had a problem. It's only $25 at Walmart. That's the best price I've been able to find so far. 

 

I wrote a quick description of how to make it here. http://www.lostfalco...nasal-insulin/ 

 

You really just need a nasal spray bottle and then you should be good to go. 

 

Let us know how it goes if you try it out!

[lostfalco]

Definitely agree that is the way forward LF - my stack / lifestyle very much emulates the multi-pronged approach mentioned above, I find it MUCH more beneficial to overall brain health than any single nootropic.


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Totally agree! There is so much crosstalk within the body between multiple systems, transmitters, receptors, growth factors, hormones, etc. that it makes a lot of sense. 

 

I pretty much abandoned the search for 'a' nootropic a few years ago. LLLT is about as close as you can get because it affects a huge number of things simultaneously so it's a great place to start. Using it as a foundation can take us to some pretty cool places when combined with other powerful substances. 

 

Of course, we have to control the risk of polypharmacy and I think we can do this by going with low doses and building up piece by piece. That's how I was able to live through something as crazy as the god stack. ha

[Amorphous]

I've been taking Ibudilast and galantamine for about 2 weeks. Results has been excellent. This week, somehow, I was not able to take the second dose in the mid-day. I didn't see any diminishing effect. The effect seems to last the whole day (over 8+ hrs). I am going to start my next cycle of pinealon in the coming week. Let see how they are going to work together.
Lostfalco- Thanks for you suggestion of Nasal spay bottle; otherwise I'll still be using a nasal drop bottle.

[Lsdium]

I've been taking Ibudilast and galantamine for about 2 weeks. Results has been excellent. This week, somehow, I was not able to take the second dose in the mid-day. I didn't see any diminishing effect. The effect seems to last the whole day (over 8+ hrs). I am going to start my next cycle of pinealon in the coming week. Let see how they are going to work together.
Lostfalco- Thanks for you suggestion of Nasal spay bottle; otherwise I'll still be using a nasal drop bottle.

 

Amorphous, what kind of effect have you notice from this combination?

[lostfalco]

I've been taking Ibudilast and galantamine for about 2 weeks. Results has been excellent. This week, somehow, I was not able to take the second dose in the mid-day. I didn't see any diminishing effect. The effect seems to last the whole day (over 8+ hrs). I am going to start my next cycle of pinealon in the coming week. Let see how they are going to work together.
Lostfalco- Thanks for you suggestion of Nasal spay bottle; otherwise I'll still be using a nasal drop bottle.

Very cool, Amorphous! Glad the two-step is working for you. http://www.lostfalco...-fog-two-step/ 

 

Ibudilast has a pretty long half-life (12 to 19 hours) so it definitely makes sense that it could maintain effects throughout the day. 

 

Looking forward to hearing how it combines with pinealon. That was my favorite Russian peptide bioregulator. My guess is that they should mix quite nicely. 

 

No problem on the bottles. I'm pretty fond of them myself. My girlfriend, on the other hand, is not too happy with the fact that our refrigerator crisper drawer is now filled with like 30 of them. ha  She'll get over it. 

 

Thanks for the update!

 

http://www.ncbi.nlm....pubmed/19032723

 

Br J Clin Pharmacol. 2008 Dec;66(6):792-801. doi: 10.1111/j.1365-2125.2008.03270.x.

Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses.

Rolan P1, Gibbons JA, He L, Chang E, Jones D, Gross MI, Davidson JB, Sanftner LM, Johnson KW.

Author information

Abstract

AIMS: 

To investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single-dose and a multiple-dose regimen.

METHODS: 

Healthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17-day stay in a Phase 1 unit. Subjects were randomized 1 : 3 to either oral placebo or ibudilast at 30-mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite.

RESULTS: 

Ibudilast was generally well tolerated. No serious adverse events occurred. Treatment-related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half-life for ibudilast was 19 h and median T(max) was 4-6 h. Mean (SD) steady-state plasma C(max) and AUC(0-24) were 60 (25) ng ml(-1) and 1004 (303) ng h ml(-1), respectively. Plasma levels of 6,7- dihydrodiol-ibudilast were approximately 30% of the parent.

CONCLUSIONS: 

Ibudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day(-1)) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models.

 

Edited by lostfalco, 17 June 2016 - 05:41 PM.

[lostfalco]

Just a little reminder of why I take PDE5 inhibitors (tadalafil, sildenafil, vardenafil). =) 

 

They also mix amazingly well with PDE4 inhibitors (ibudilast, liposomal luteolin, etc.).

 

"There is mounting evidence from clinical and experimental trials that indicates that NO-cGMP-PKG is the central mechanism of a network of signaling pathways that interconnects neuroinflammation, neurodegeneration, and cognitive disorders, resulting in increased pharmaceutical interest in PDE5-Is as promising therapeutic targets for neurodiseases."

 

 

 

 

http://www.ncbi.nlm....les/PMC4681825/

 

Mediators Inflamm. 2015;2015:940207. doi: 10.1155/2015/940207. Epub 2015 Dec 3.

Phosphodiesterase-5 Inhibitors: Action on the Signaling Pathways of Neuroinflammation, Neurodegeneration, and Cognition.

Peixoto CA1, Nunes AK2, Garcia-Osta A3.

Author information

Abstract

Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and memory loss diseases. Mechanistically, PDE5-Is produce an anti-inflammatory and neuroprotection effect by increasing expression of nitric oxide synthases and accumulation of cGMP and activating protein kinase G (PKG), the signaling pathway of which is thought to play an important role in the development of several neurodiseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The aim of this paper was to review present knowledge of the signaling pathways that underlie the use of PDE5-Is in neuroinflammation, neurogenesis, learning, and memory.

 

Edited by lostfalco, 17 June 2016 - 06:02 PM.

[LongLife]

 

Just a little reminder of why I take PDE5 inhibitors (tadalafil, sildenafil, vardenafil). =) 

 

They also mix amazingly well with PDE4 inhibitors (ibudilast, liposomal luteolin, etc.).

 

"There is mounting evidence from clinical and experimental trials that indicates that NO-cGMP-PKG is the central mechanism of a network of signaling pathways that interconnects neuroinflammation, neurodegeneration, and cognitive disorders, resulting in increased pharmaceutical interest in PDE5-Is as promising therapeutic targets for neurodiseases."

 

 

 

 

http://www.ncbi.nlm....les/PMC4681825/

 

Mediators Inflamm. 2015;2015:940207. doi: 10.1155/2015/940207. Epub 2015 Dec 3.

Phosphodiesterase-5 Inhibitors: Action on the Signaling Pathways of Neuroinflammation, Neurodegeneration, and Cognition.

Peixoto CA1, Nunes AK2, Garcia-Osta A3.

Author information

Abstract

Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and memory loss diseases. Mechanistically, PDE5-Is produce an anti-inflammatory and neuroprotection effect by increasing expression of nitric oxide synthases and accumulation of cGMP and activating protein kinase G (PKG), the signaling pathway of which is thought to play an important role in the development of several neurodiseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The aim of this paper was to review present knowledge of the signaling pathways that underlie the use of PDE5-Is in neuroinflammation, neurogenesis, learning, and memory.

 

 

LOSTFALCO:  "Just a little reminder of why I take PDE5 inhibitors (tadalafil, sildenafil, vardenafil)." 

 

Which PDE5 inhibitors have you used or more inclined to? Tadalafil, Sildenafil or Vardenafil?

[normalizing]

lostfalco whats the reason for recommending this; https://www.amazon.c...ds=850nm led 48

[lostfalco]

 

 

Which PDE5 inhibitors have you used or more inclined to? Tadalafil, Sildenafil or Vardenafil?

 

I've used all three as well as icariin. 

 

I prefer tadalafil because of its long half life. Just dose in the morning and you're done.  

 

Sildenfil and vardenafil are great too. Here are links to where I get them. http://www.lostfalco...harmaceuticals/

[lostfalco]

lostfalco whats the reason for recommending this; https://www.amazon.c...ds=850nm led 48

I use that device for transcranial low level laser therapy. I recommend it because it's extremely affordable (most devices are hundreds or thousands of dollars), it's convenient to use on your forehead, and it matches fairly closely with devices used on humans in a few of the scientific studies. 

 

This article talks about the 96 LED but the 48 LED works as well. http://www.lostfalco...therapy-dosing/

 

This article explains a bit about how low level laser therapy works on mitochondria. The videos are especially helpful and there are links to a few of the scientific studies on humans. http://www.lostfalco...-laser-therapy/

Edited by lostfalco, 19 June 2016 - 12:48 PM.

[normalizing]

uh i thought snorting insulin was a bit off, but this is just too much. shoving lasers up my forehead... no thanks. i missunderstood i guess, i read somewhere that blue light and such help with insomnia.

 

about icariin, you better have some good high quality source my friend because i have been trying to get this gold for years, tried about several different companies with no success of getting the real deal and before i claim its all fraud, ive had good icariin one time and i know this shit is hard to get again!

 

edit: searched again with this reminder at hand, it seems it was chinese company with mixed herbs so im not even sure if icariin itself did this but im still quite curious if i ever get real good quality icariin to know cheers!

Edited by normalizing, 19 June 2016 - 04:18 PM.

[lostfalco]

uh i thought snorting insulin was a bit off, but this is just too much. shoving lasers up my forehead... no thanks. i missunderstood i guess, i read somewhere that blue light and such help with insomnia.

 

about icariin, you better have some good high quality source my friend because i have been trying to get this gold for years, tried about several different companies with no success of getting the real deal and before i claim its all fraud, ive had good icariin one time and i know this shit is hard to get again!

 

edit: searched again with this reminder at hand, it seems it was chinese company with mixed herbs so im not even sure if icariin itself did this but im still quite curious if i ever get real good quality icariin to know cheers!

It's really just shining certain wavelengths of light into your brain. Think of it more like placing a flashlight on your forehead. As always though, if it's too much for you then definitely don't do it. 

 

I've been using it for years and Nattzor did a quality self experiment that you can check out here. https://www.gwern.net/LLLT

 

Blue light (around 470nm) is good in the morning for waking you up but should be avoided at night (it will prevent you from falling asleep). It excites intrinsically photosensitive retinal ganglion cells. I use two different bright light devices for this listed here. http://www.lostfalco.com/devices/

 

I prefer the other PDE5 inhibitors over icariin. 

Edited by lostfalco, 19 June 2016 - 05:27 PM.

[normalizing]

well,i did use viagra for exams in college and it helped. and no, you cannot get erections on math tests

[lostfalco]

http://www.ncbi.nlm....pubmed/27286139

 

J Child Adolesc Psychopharmacol. 2016 Jun 10. [Epub ahead of print]

Agomelatine as a Treatment for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Double-Blind, Randomized Clinical Trial.

Salardini E1, Zeinoddini A1, Kohi A1, Mohammadi MR1, Mohammadinejad P1, Khiabany M1, Shahriari M1, Akhondzadeh S1.

Author information

Abstract

OBJECTIVE: 

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Due to lack of response to the medication and significant side effects of the treatment with stimulants, alternative medications should be considered. The aim of this study is to evaluate efficacy of agomelatine in treatment of ADHD.

METHODS: 

Fifty-four outpatients, children 6-15 years old, with diagnosis of ADHD according to DSM-IV-TR diagnostic criteria participated in a 6-week, parallel, double-blind, randomized clinical trial. Fifty patients completed 6 weeks of treatment with either ritalin (methylphenidate hydrochloride [MPH]) (20 mg/day in participants below 30 kg and 30 mg/day in patients with weight ≥30 kg) or agomelatine (15 mg/day in patients with weight ≥30 kg and 25 mg/day in patients with weight ≥45 kg). Participants were assessed using Parent and Teacher ADHD Rating Scale-IV at baseline and at weeks 3 and 6.

RESULTS: 

General linear model repeated measures showed no significant differences between the two groups on Parent and Teacher Rating Scale scores (F = 1.13, df = 1.26, p = 0.305, and F = 0.95, df = 1.25, p = 0.353, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the agomelatine group (9.28 ± 8.72 and 24.12 ± 7.04, respectively) and the MPH group (6.64 ± 11.04 and 25.76 ± 7.82, respectively) (p = 0.46 and p = 0.44, respectively). There was a trend for less insomnia in the agomelatine group versus MPH-treated group (4% vs. 24%, p = 0.09).

CONCLUSIONS: 

A treatment course of 6 weeks with agomelatine demonstrated a favorable safety and efficacy profile in children and adolescents with ADHD. Nonetheless, larger controlled studies with longer treatment periods are necessary.

 

[lostfalco]

I've been talking a lot lately about how I come across study after study that shows that combinations of substances often work better than one substance alone. 

 

So...I figured I'd post more of them when I see them (I've posted numerous studies before). 

 

Here's a study of fluoxetine and bright light therapy for nonseasonal major depressive disorder (MDD) which concluded, "Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects."

 

As many of you know, I've been using bright light therapy for 5+ years now and really like it. 

 

Here are the bright light devices I use. http://www.lostfalco.com/devices/

 

http://www.ncbi.nlm....pubmed/26580307

 

JAMA Psychiatry. 2016 Jan;73(1):56-63. doi: 10.1001/jamapsychiatry.2015.2235.

Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

Lam RW1, Levitt AJ2, Levitan RD3, Michalak EE1, Cheung AH2, Morehouse R4, Ramasubbu R5, Yatham LN1, Tam EM1.

Author information

Erratum in

• Omission in Byline and Errors in Affiliation and Table. [JAMA Psychiatry. 2016]

Abstract

IMPORTANCE: 

Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD).

OBJECTIVE: 

To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD.

DESIGN, SETTING, AND PARTICIPANTS: 

Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with ≥1 follow-up rating).

INTERVENTIONS: 

Patients were randomly assigned to (1) light monotherapy (active 10,000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill).

MAIN OUTCOMES AND MEASURES: 

Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point).

RESULTS: 

A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, -0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light, and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005) and remission (β = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events.

CONCLUSIONS AND RELEVANCE: 

Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects.

 

Edited by lostfalco, 20 June 2016 - 08:08 PM.

[LongLife]

LOSTFALCO:

"Blue light (around 470nm) is good in the morning for waking you up but should be avoided at night (it will prevent you from falling asleep)."

 

I have come across a variety of nm wavelengths which are purported to effect the human brain in one one manner or another. All of the research that you have posted on LLLT also sites various wavelengths; no consistent wavelength for brain improvement (very general term), such as 808, 850, 870, 633, 635, etc., nano-meter wavelengths.

 

Is brain, mitochondria, hair, improvements predicated on wavelength or the amount of joules of energy received by the cells/mitochondria? Or is it both?

 

I realize that the research information published are the results of experimentation, so maybe this is not a well defined area or conclusive; which wavelengths actually best effect which areas of the brain.

 

Have you come across a chart/list of wavelengths (in nano-meters) and what effects they have on humans? If you have, can you share that information please. 

 

[lostfalco]

LOSTFALCO:

"Blue light (around 470nm) is good in the morning for waking you up but should be avoided at night (it will prevent you from falling asleep)."

 

I have come across a variety of nm wavelengths which are purported to effect the human brain in one one manner or another. All of the research that you have posted on LLLT also sites various wavelengths; no consistent wavelength for brain improvement (very general term), such as 808, 850, 870, 633, 635, etc., nano-meter wavelengths.

 

Is brain, mitochondria, hair, improvements predicated on wavelength or the amount of joules of energy received by the cells/mitochondria? Or is it both?

 

I realize that the research information published are the results of experimentation, so maybe this is not a well defined area or conclusive; which wavelengths actually best effect which areas of the brain.

 

Have you come across a chart/list of wavelengths (in nano-meters) and what effects they have on humans? If you have, can you share that information please. 

Blue light affects intrinsically photosensitive retinal ganglion cells in your eyes which affect your suprachiasmatic nucleus which synchronizes all of your body's systems through CLOCK genes. It's an approved treatment for seasonal affective disorder. 

 

 

 

LLLT uses light that is placed on your skin, shines through your skull, and reaches mitochondria in your brain. I've written about it here. http://www.lostfalco...therapy-dosing/

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

 

Check out the TULIP Experiences Thread for other's experiences. http://www.longecity...uantified-self/

 

Here's the TULIP Research Thread. http://www.longecity...biophysics-etc/

 

Scott Roberts (zawy on Longecity) has a nice discussion of wavelengths here. http://heelspurs.com/led.html#opti

 

Joe Cohen describes his experiences here. https://selfhacked.c...review-of-lllt/

 

 

Edited by lostfalco, 20 June 2016 - 11:00 PM.

[lostfalco]

Some brief thoughts on LLLT as a treatment for Alzheimer's. 

 

1. 660nm light activates the body's natural ability to fight fungal infections. 

2. Fungal infections have recently been correlated (causation is not established at this point) with Alzheimer's disease. 

3. Therefore....the future data is worth keeping an eye on!

 

Quick discussion, device I use, and references here. http://www.lostfalco...eimers-disease/

Edited by lostfalco, 21 June 2016 - 06:16 PM.

[lostfalco]

A brief description of a recent (2012) human study on intranasal insulin as a treatment for Alzheimer's.  http://www.lostfalco...for-alzheimers/

 

Combine that with LLLT and we are off and running!

 

Edited by lostfalco, 22 June 2016 - 11:12 PM.

[Bluecheer]

 

Hey falco' you've certainly taken your fair share of interesting chemicals these days, What do you say is your 80/20 of getting results ( where as 20% of your activities or drugs are giving you 80% of the reward) so far? Excluding LLLT of course :D

 I know this is a stocktake type interview question, but I would be really... interested :D

 

 

This is a tough question because I've realized how interconnected everything is. 

 

I kept seeing study after study where 'below threshold' dosing of multiple substances showed non-linear improvements. 

 

My current method consists of low dosing multiple substances simultaneously. 

 

I usually either go with a subtherapeutic dose or the lowest effective dose currently measured. 

 

Remember, there are numerous ways to think of the 80/20 principle. You could think of it as 20% of the substances for 80% of the results or you could think of it as 20% of the dose. Make sense? (There are about a thousand other ways you could think of it as well)

 

I've been experimenting with using 20% of the dose while keeping the number of substances (ie. mechanisms that I target) the same. 

 

I look at potentially synergistic mechanisms and start very slowly while gradually working my way up in dose. 

 

This has paid huge dividends for me over the past year and has taken my experiments into entirely new territory. 

 

I'll talk about it more when I discuss The Genesis Protocol which is a somewhat modified God Stack/Happy Cil-TULIP. 

 

No thanks for even trying to answer it, I think that's a great answer. To be a pain, let me ask a different question... see if I can probe an answer out of this, 
What are the things you have done that have payed higher dividends the longer you have done them.. If you say everything then that is certainly fine.

But for example I have found some what of a compounding effect from certain things... Ie Meditating and & LLLT - and too an extent exercise. But defiantly i have felt after say 1-4 weeks as opposed to 1-4 sessions of both meditating and LLLT my overall cognition is abundantly positively shaped.

 

I must also ask, Is there a reason Coq 10 & Pqq powder has never been brought up on this thread, Does this process make them loose there flame? I would assume with such a interest in this thread that it would be one of the first go to things for price.

Edited by Bluecheer, 23 June 2016 - 10:44 AM.

[Bluecheer]

 

 

Just wanted to add that it appears your blog is gaining some followers/copy cats.  Check out this article touting Ibudilast--

 

http://www.metabolic...matory-disease/

 

Good news is, it shouldn't be long before a Nootropics Company starts selling Ibudilast powder domestically!

 

Not quite sure if its a copy cat, as if you read the article you'll note the person brings up a article he previously wrote on Ibudilast a year ago!... (didn't mean to discredit your post)

All in all your right ibudilast powder should be coming soon :D

 

I wonder the best way to determine market interest in chemicals..


considering were already talking about Mag L-theronate anybody know if the effects of Mag l-theronate on the body would be able to replicate/replace existing magnesium supplements in terms of DNA repairing, and all the 'physical' aspects people generally take mag for? - slightly vague question but im wondering if id be able to swap out my normal mag supplement for it .. or if im best off using something like Mag Tech via natural stack.

 

QUESTION: Swapping out? I would do chelated mag in the morning, spray magnesium sulfate during the day and Mag-l-theronate at night. you will know if you are over doing it if your bowels become prevalent, which means you also have overloaded your cells receptors and are blocking them up so only a tiny amount of calcium and/or iron is being used. Easy does it. More is not better.

 

Hey Thanks! I really appreciate it, And yeah i will continue to try and get a diverse high amount of magnesium from food.. But yeah i was wondering more in regards to supplementation as I generally supplement with zinc and magnesium regardless of diet (intermittently) - So in your opinion you don't feel there is one superior type of magnesium you should stick to supplementing with (excluding mgl Theronate)
- 
And I' am guessing you shouldn't opt out of normal mag supplementation just because your using (possibly) high amounts of Mag-L Theronate?
 

[lostfalco]

I have come across a variety of nm wavelengths which are purported to effect the human brain in one one manner or another. All of the research that you have posted on LLLT also sites various wavelengths; no consistent wavelength for brain improvement (very general term), such as 808, 850, 870, 633, 635, etc., nano-meter wavelengths.

 

Is brain, mitochondria, hair, improvements predicated on wavelength or the amount of joules of energy received by the cells/mitochondria? Or is it both?

 

I realize that the research information published are the results of experimentation, so maybe this is not a well defined area or conclusive; which wavelengths actually best effect which areas of the brain.

 

Have you come across a chart/list of wavelengths (in nano-meters) and what effects they have on humans? If you have, can you share that information please. 

Hey LongLife, I created a post that lists all of the wavelengths that have been tested on humans for brain enhancement. 

 

Here is the link.   http://www.lostfalco...in-enhancement/

 

I still need to add a few studies but it's a good start...I hope it helps clear things up a little!

 

Improvements are predicated upon BOTH wavelength AND Joules of energy delivered.

 

There is no difference related to which wavelength would enhance a specific 'area of the brain'. 

 

The important thing is that all neurons have mitochondria (thousands of them per neuron) and that is what we are targeting.

 

Only certain wavelengths are absorbed by cytochrome C oxidase in mitochondria due to quantum mechanics. 

 

That is why wavelength matters so much. 

 

 

Edited by lostfalco, 25 June 2016 - 09:15 PM.