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Chemically induced LTP?

ciltep pde4 forskolin ltp

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#2611 Reformed-Redan

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Posted 27 June 2016 - 08:10 PM

Hi abelard lindsay,

 

I'm wondering about your thoughts on using grandaxin as a PDE10 and PDE4 inhibitor? Have you heard of such experiments? 

 

Thanks.


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#2612 bzyb

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Posted 28 June 2016 - 08:31 AM

 

 

 

Nice to see you all around.    Exciting stuff is in the works with regards to further developing the science of CILTEP.  We should have some announcement about that later this year.  

 

Meanwhile, at the summit of Mt. Everest (not photoshopped!):

 

attachicon.gifmteverest.jpg

 

Wow nice new developments.  Happy stack and ibudilast can help with the anti-social aspects of CILTEP and hopefully lower slight agitation?  Where to buy ibudilast, (not on amazon) seems like an all-round healthy supplement?

Nice picture, is it you or a friend (I can see have long hair)? Everest seems too tough to do, maybe better to just fly to the top.

 

 

A very adventurous and fit Natural Stacks customer sent that photo in.  I went for a 4 mile run yesterday if that counts for anything.  :-D

 


Ah, I see. I commend her for making it to the summit with all that extra luggage!  Four mile run, that's a longer distance than most Americans run in a year!  It's also in the same category of healthy activities as climbing mountains, with much less risk. I too shall choose the latter! But not today.


Edited by bzyb, 28 June 2016 - 08:32 AM.


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#2613 lostfalco

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Posted 30 June 2016 - 06:25 PM

Where to buy ibudilast, (not on amazon) seems like an all-round healthy supplement?

 

It's actually a prescription med in Japan.

 

I talk about where to get it (and some possible replacement substances) here. http://www.lostfalco...n-fog-two-step/
 



#2614 Droplet33

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Posted 10 July 2016 - 04:36 PM

 

 

Hey,

 

Is anyone here experimenting on how to combine this stack with the Uridine stack, or are you guys content with the CILTEP stack alone?  

Yeah, I've been doing this for the past few months or so with extremely good results. 

 

I've basically created my own ultra-effective version of CILTEP. 

 

I use low level laser therapy (LLLT) to increase cAMP.

 

I use ibudilast (a PDE4 inhibitor) to inhibit the breakdown of cAMP (luteolin has low absorption and is quickly metabolized, although a liposomal or intranasal version might work well).

 

I've patterned my uridine stack after Souvenaid (I buy my own ingredients). Here are all the ingredients and dosages. https://www.souvenai...ormation-Sheet/

 

 

LostFalco:  How does ibudilast compare to Zembrin?  The Zembrin CILTEP stack works great for studying, but I don't take it regularly since it makes me dislike talking to people.  

 

I have combined the happy stack with CILTEP and gotten good results.  The only caveat is that I have to take it with a gram or so of tryptophan or I feel unusually depressed the next day.

 

Cheers,

 

Abelard.

 

 

Out of curiosity, what is the timing of the tryptophan intake? Do you take it all at the beginning of the day or late before bed?
 



#2615 abelard lindsay

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Posted 14 October 2016 - 05:43 PM

So I'm going to try the ibduilast/forskolin CILTEP stack.  

 

One thing I've found with some of the more esoteric PDE inhibitors is that weird stuff can happen, and it's good to keep a big bottle of GABA around for if things start to get unpleasant.  Quercetin and Hesperidin at high dosages were pretty rough.  It looks to me like the IC50 on ibudilast is comparable to rolipram, so conceivably I could get my long term memory encoding stuck in the on position.  

 


Edited by abelard lindsay, 14 October 2016 - 11:12 PM.


#2616 lostfalco

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Posted 15 October 2016 - 07:07 PM

So I'm going to try the ibduilast/forskolin CILTEP stack.  

 

One thing I've found with some of the more esoteric PDE inhibitors is that weird stuff can happen, and it's good to keep a big bottle of GABA around for if things start to get unpleasant.  Quercetin and Hesperidin at high dosages were pretty rough.  It looks to me like the IC50 on ibudilast is comparable to rolipram, so conceivably I could get my long term memory encoding stuck in the on position.  

Very cool, Abelard. Looking forward to hearing how it works for you. 

 

Def interested in how ibudilast by itself compares to the ibudilast/forskolin combo for you since you have so much experience with PDE4 inhibition + cAMP increase. Keep us updated!



#2617 abelard lindsay

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Posted 15 October 2016 - 07:34 PM

 

So I'm going to try the ibduilast/forskolin CILTEP stack.  

 

One thing I've found with some of the more esoteric PDE inhibitors is that weird stuff can happen, and it's good to keep a big bottle of GABA around for if things start to get unpleasant.  Quercetin and Hesperidin at high dosages were pretty rough.  It looks to me like the IC50 on ibudilast is comparable to rolipram, so conceivably I could get my long term memory encoding stuck in the on position.  

Very cool, Abelard. Looking forward to hearing how it works for you. 

 

Def interested in how ibudilast by itself compares to the ibudilast/forskolin combo for you since you have so much experience with PDE4 inhibition + cAMP increase. Keep us updated!

 

 

My general impression of it is it's a bit like the Zembrin/CILTEP stack but without the negative social interaction problems that Zembrin causes.  I definitely felt a very clear cognition feeling where I had increased mental endurance.  Unlike Zembrin however, I had deep positive social interactions with two people yesterday that were relatively new friends.  I took some Nexus mid-day and that made things feel very intense.  I didn't get the perfect brain record thing that I did on some of the more, imho, dangerous CILTEP stacks, but I suspect I might if I took more forskolin.  I'll have to titrate up a little and see what happens.  One thing I've found is that besides being a strong PDE4 inhibitor, ibduilast is a strong PDE5 inhibitor too!

 

 

Ibudilast data:

http://ponderapharma...1.tb00066.x.pdf

 

PDE isoenzymes Enzyme source (reference) IC50, ìM

PDE1 Pig coronary SMC (17) 55

PDE2 Bovine aortic EC (16) 0.11

PDE3 Human platelets (15) 31

PDE4 Bovine aortic EC 0.08

PDE5 Human platelets 2.2 

 

 

 

Other PDE5 inhibitor data:

 

http://www.nature.co...lication_detail

 

IC50 (nM) PDE5A PDE1 PDE2A PDE3B PDE4B PDE6a PDE7B PDE8 PDE9A PDE10A PDE11A

Vardenafil 0.89 121 410 000 2400 2055 11 4600 410 000 3370 1000 308

RatioX/5 1 136 410 000 2696 2308 15 5168 410 000 3786 1123 346

Sildenafil 8.5 350 410 000 410 000 3190 49 410 000 4100 000 410 000 3800 1725

RatioX/5 1 41 41000 41000 375 7.4 41000 41000 41000 447 203

Tadalafil 9.4 410000 410 000 410 000 410 000 n.d. 410 000 410 000 410 000 410 000 67

RatioX/5 1 41000 41000 41000 41000 41000 41000 41000 41000 7.1 a

 

 

So if I'm reading this right, Ibudilast is even stronger than Tadalafil(Cialis) and Sildenafil(Viagra) and it has a half life of 19 hours!  This is the PDE5A subtype, so ibudilast might be selective for another subtype of PDE5, but probably close enough.  I can say that the effect was certainly comparable to Cialis in terms of countering erectile dysfunction, almost to an annoying extent while trying to get some sleep last night!

 

It's a shame this drug is so difficult to get these days.  I could see it becoming a real mainstay of the brain hacker/nootropics community, especially when potentiated with forskolin.  

 

One caveat is that the long half life means that it shouldn't be taken every day.  I'd say once every other day.  Cialis has a 17.5 hour half life and based on my experience, I wouldn't take it more than once every 48 hours maximum!



#2618 abelard lindsay

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Posted 20 October 2016 - 12:27 AM

I think Ibudilast has a long term impact.  I took it with forskolin last week and it was super strong.  I think it's making me feel more clear headed and perceptive even a week later.  I get that hi-def vision feeling very easily now and my mood is improved.  I am seriously intrigued by it as its PDE4 IC50 is stronger than Rolipram.

 

 


Edited by abelard lindsay, 20 October 2016 - 12:50 AM.


#2619 gizmobrain

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Posted 20 October 2016 - 03:26 PM

Abelard, what dosage have you been using when combining with Forskolin? 

 

I've been using 10mg Ibudilast twice daily (most days by itself) for a couple months with pretty substantial improvement of brain fog and midday sleepiness. I also went on a road trip where I was driving 12 hours a day and it was the perfect balance of alertness, good mood, and calm. 

 

When I add 10mg Ibudilast + my normal stack (artichoke+forskolin+3mg DA), I notice that ibudilast seems to cancel any motivating effects of the DA. I feel great, but I'm back to square one on motivation. Intranasal Insulin does the same thing. Probably great for people with anxiety, but not so great for me.

 

Ibudliast has been added to my short list of things that actually seem to help me without being borderline dangerous. The only things that have ever helped with motivation have been more questionable: Ciltep+DA, Nefiracetam, and 9-Methyl-BetaCarboline.



#2620 lostfalco

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Posted 20 October 2016 - 08:54 PM

I think Ibudilast has a long term impact.  I took it with forskolin last week and it was super strong.  I think it's making me feel more clear headed and perceptive even a week later.  I get that hi-def vision feeling very easily now and my mood is improved.  I am seriously intrigued by it as its PDE4 IC50 is stronger than Rolipram.

Very cool, Abelard. Thanks for reporting back!

 

I'm with you, it's effects on PDE4 subtypes are very interesting...and thankfully they don't include emesis. 

 

"Ibudilast inhibits PDE4A, 4B, 4C and 4D with IC50 values 54, 65, 239 and 166 nM." https://www.ncbi.nlm...pubmed/16313925

 

Sorry if I missed this...what doses are you testing with your ibudilast/forskolin combo?



#2621 abelard lindsay

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Posted 23 October 2016 - 03:25 AM

 

 

Sorry if I missed this...what doses are you testing with your ibudilast/forskolin combo?

 

 

I was taking 3.85 mg of forskolin with 10mg Ibudilast.   I might not experiment with higher doses.  In my experience, things get a bit weird on higher forskolin dosages and ibudilast is a very strong PDE4 inhibitor.  In my opinion, the long-term effects seem highly beneficial though.



#2622 Junk Master

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Posted 23 October 2016 - 11:53 PM

I didn't know if this has been brought up already, so my apologies if it has--

 

http://mymsaa.org/ne...-fast-track-fda

 

I find it particularly fascinating that one of it's uses is treatment of methamphetamine dependent patients!

 

So, both MS and Meth...

 

 



#2623 Droplet33

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Posted 24 October 2016 - 12:10 AM

I tried Ibudilast with just 1-2 Now artichoke pills a couple of months ago, without forskolin, and felt like having a laser as far focus goes. Can't say if it improved LTP thought, i only tried it  a few times this way.

It was great with forskolin (when i didn't had trouble with dosing galantamine, my scale isn't precise enough so i had to eyeball it), with similar dosing than abelard aks 10mg ibudilast with 4mg of forskolin (Tried with 10mg twice daily as well, but didn't notice a big difference).

But i'd like to extend a word of caution about ibudilast : It has anti inflammatory propriety for the body and inflammation is necessary to heal back some tear and wear if you have a active lifestyle (like weight lifting) or a daily job that is. If you do, keep a eye out about how you feel like when most the effects wear off.


Edited by Droplet33, 24 October 2016 - 12:19 AM.


#2624 Алиса Дементьева

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Posted 25 May 2017 - 08:08 PM

Hi, I have some notes I would like to share.
debugging:
took a simplified stack: 10mg adderall, 500mg artichoke, 100mgForskolin@20%, 1gram of l-tyrosine, small cup of coffee about twoone hour ago.
(I noticed today that I was taking below the bottle-recommended 1g dose of l-tyrosine.)

subjective:
My mind does feel quicker and not { hung up/negative limited mental options/distracting cognitive tasks/gallows humour/difficult social interaction-feeling(larrydavid_syndrome) } that I normally feel. But dont feel the motivation/executive function, ie the stay on track dont get distracted that I sorely lack. Affects are minimal; clear headed but not fully motivated; this write up/re-edit has distracted me now for 2 hours. This is better than baseline but not the CILTP that I felt; did I build tolerance in one day ?

objective:
On first/best dose of CILTP my dual-n-back increased to 4 for the first time. Today, I had no trouble maintaining n=3, and can move through it quickly, but not well enough to get back up to n=4. Motivation/energy right now is only at a level where I was able to play a few rounds for about 10 minutes at the n=3 level.

throwing darts:
I checked out 23andme, test is now at $300. Is there some motivation/MAOI/gene variants that can be tested for? Maybe I will get it done if there are some relevant genes I should be interested in. camKII gene ?

Modafinil, ritalin, and adderall all by themselves do not work for me. Only tried Modafinil + ritalin in combination and that got me going, in a certain way. My lack of response to adderall and ritalin, taken by themselves, has me believing COMT is fine. My lack of response to Modafinil by itself, also makes me believe MAOI is fundamentally ok. Selegiline seems good in that it combines MAOI/amphetamine, in trying to unlock the 'psycho-energic' effect.

However, I think I need to target executive functioning. I feel there is overlap between executive function and motivation. For improved executive function, modafinil has shown efficacy. I have read weight training provides benefit (vs aerobic training which improves mood and fluid intelligence). Bilingualism improves it as well. A good test for executive function is d-kefs. Top soccer players do very well on d-kefs.
https://en.wikipedia...utive_functions
http://www.plosone.o...al.pone.0034731


(***warning the following is speculation***)
I believe the weight training/executive functioning link may be based at the microtubule/camKII level:
http://www.sciguru.c...ry-Code-Cracked
So to target executive functioning maybe we need to go beyond LTP. The above link says memories are encoded in the microtubule lattice, as 6-bit protein-camKII-bytes. Modafinil's electrotonic coupling is determined to be CamKII-dependent. There are two types of camKII- specialized microtubule acting, and NT/receptor/LTP acting.
chemical-induced executive function:
1. l-carnosine, a-lino-acid, phosp-serine; stuff that helps build up neuronal microtubules
2. nerve growth factor. Maybe Ill try lions mane/ resveratrol / curcumin. Which is the best one for camKII ?
behavioral-induced executive function:
a) weight training. highRep-lowWeight

b) language training http://livemocha.com/

recap:
What is a good ngf for camKII ?

livemocha is not available, try https://www.lingq.com/



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#2625 stephen_b

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Posted 14 June 2019 - 04:26 AM

Wow, tune out a few years and ... where has this thread gone?

 

Anyway, I have used and liked the protocol for years now, though the benefits have sometimes been subtle and other times less so. I usually just artichoke, forskolin, and ALCAR (which I've taken for many additional years prior). I usually take a lower than normal dose, with just half a NOW artichoke extract capsule.

 

I have recently noticed that the results I get are very nicely enhanced by pycnogenol. For me, the CILTEP effects are not subtle at all with pycnogenol first thing on an empty stomach. I only add 30 mg.

 

I would be interested to hear if anyone else responds to this addition too.

 







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