• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 27 votes

Chemically induced LTP?

ciltep pde4 forskolin ltp

  • Please log in to reply
2626 replies to this topic

#841 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 10 October 2012 - 07:35 PM

First of all, hats of to you sir for making such a thorough reply. Now, as you seem to have a mathematical approach for definition of terms, let us clear things up.


It would be a large understatement to say that the term 'nootropics' is loosely defined, and so it certainly cannot be said that anything anyone considers a 'nootropic' should be avoided if you have an 'addictive personality' (another pseudo-clinical term with a very loose definition). I would be okay with the term 'nootropic' being thrown out, along with 'addictive personality', as they are both terms that are sourced from bro-science in my opinion.


The term nootropic, as you state, is a scientifically undefined term without basis which may mean diffrent things to diffrent people. Addictive personaly on the other hand, while it is an undefined medical term, has its root in genetic D2A1 molymorphism which results in increased addiction susceptibility and mental desire. This is often refered to as an "addictive personality" although it is not actually a personality trait. This is anything but bro-science.


What is a nootropic? An AMPA modulator? Something that improves LTP? Something that corrects an imbalance, temporary or permanent? Something that acts as a prophylactic against a large amount of predictable future neurophysical or emotional stress? A stimulant? Something that causes neurogenisis? Something that subjectively just makes you think better, or remember better without a clear explanation as to how it is accomplished? Something that specifically counteracts an addiction that was creating a loss in cognitive ability?

The general consensus, after reading quite alot on these forums, seems to be that a nootropic is something that increases mental clearity, cognition and memory retention to a certain unquantifiable degree. As people respond diffrently to diffrent kinds of substances which may, in their opinion, fall under the category of being a nootropic, it is not possible to define what a nootropic is and is not as it is not medically defined. Now, since my statement was completely relative, this may be disregarded.

Substances that do work for a certain individual, who has a fear of falling into an addictive pattern due to past experiences, should stay away from anything mind-altering that may increase well being.

A nootropic will be something different for everyone, especially those with a specific pathology, like many/most on this board have, addiction included. Many substances here, that subectively/objectively act as nootropics for an individual, do so specifically by lessening addiction to, sub-optimal self medication with, or damage caused by other substances.



It's not fair to lump "everyone" in to your admonishment in regard to a comment made by one person. Many people here are exceptionally reasonable, educated, and careful, even more so than most MDs (careful). I don't know of too many MDs, and I know more than a few personally, who take the time to read the full research regarding everything that they prescribe, especially in the context of other regulated or non-regulated options out there. Of course, there are exceptions and a select few fringe individuals on this board tend toward the reckless, choose to chase a nootropic buzz, or choose the shotgun approach without being aware of the science or the consequences. After all, the board itself is not password protected and is free to all to read who can use google. However, especially when the recklessness of modern commonly prescribed medications is taken into account, an example being long term adderall use amongst many others, then the approach by most here, who are attempting to find more sustainable and less long-term damaging solutions through a largely careful and responsible methodology, should escape your finger pointing.


The term "people" is plural refering to a group of people, in this case the community of longecity.org. As it is unlikely and illogical of me to adress every single person for a statement directed at a majority, there are no logical flaws. Yes there are plenty of smart people here, yes there are many who learn and actually put effort to state the correct facts, but the vast majority are one time casual people who come here and spread hearsay they heard on the streets or somewhere else without actually caring to confirm it.
Shit contains a fair amount of healthy chemicals, yet it is refered as unhealthy. Get my point?


Addressed above, but also patently untrue (especially with the lazy accusation of "zero research being behind them"): the term 'random shit' being wholly non-specific. Again, "people" on these forums covers a lot of "people", most of whom don't deserve your rush to judgment or other wise blind categorization based on relative unfamiliarity with specific personalities here and your skimming the forum.

Persoanlly, I'd be a heck of a lot more sick/damaged/less functional than I am if it weren't for this forum. I'm able to live my life becasue of it.


Are you stating that the majority of the consumed substances discussed on these forums have sufficient research to confirm their efficiecy for their health claims?
While results from animal and in vitro studies are transferable to real life results to a certain degree, its far from sufficient data to confirm health benefits. This applies to a large spectrum of substances, not to mention those who only have a nomenclature based name.

And to my defense, random shit is the only appropriate term when you consume something you believe is a nootropic supplied by a shady chinese company. Since you dont know for certain what it is you are consuming, it may be anything. Thus "random".


You seem to react mostly to my generalization, sorry to break it to you buddy but even if you were robert oppenheimer, in a crowd you are a nobody. Just like taking a piss in the pacific ocean wont dilute it.
  • dislike x 1

#842 golden1

  • Guest
  • 681 posts
  • 141
  • Location:US

Posted 10 October 2012 - 07:47 PM

Im sorry but if you have an addictive personality i would advise you to refrain from using any nootropics, because those who actually work and make you feel enlightened in any sense will get you hooked. And once you stop you will develop psychological withdrawal


Wat. So if a nootropic works for you and you keep taking it you are now addicted? And this only applies to people who have some genetic difference? okayyyyyy.
  • dislike x 1
  • like x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#843 stablemind

  • Guest
  • 520 posts
  • 33

Posted 10 October 2012 - 08:22 PM

You guys keep everything in this thread on topic. If you guys want to argue start another thread but don't ramble and turn this into a war zone. This thread is for CILTEP/LTP discussions and people aren't clicking this thread so they can see a bunch of people arguing with each other.
  • like x 1

#844 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 10 October 2012 - 08:32 PM

You guys keep everything in this thread on topic. If you guys want to argue start another thread but don't ramble and turn this into a war zone. This thread is for CILTEP/LTP discussions and people aren't clicking this thread so they can see a bunch of people arguing with each other.


Good luck with that. Not too many people actually seem to be interested in keeping on topic.

I pop in every now and again to answer questions that have already been addressed earlier in the thread, but other than that, I've about given up.

On the other hand, I still get awesome results with this stack. I have 10 grams of 98% forskolin extract being delivered tomorrow. 10 grams at 5mg a day * 5 times a week will last almost 8 years. I don't know the shelf life nor the advancements that will come in the next 8 years, so I will probably try to sell at least half of it.

Feel free to PM me if anyone is interested in any amount.

Edited by zrbarnes, 10 October 2012 - 08:42 PM.

  • like x 1

#845 stablemind

  • Guest
  • 520 posts
  • 33

Posted 10 October 2012 - 08:38 PM

You guys keep everything in this thread on topic. If you guys want to argue start another thread but don't ramble and turn this into a war zone. This thread is for CILTEP/LTP discussions and people aren't clicking this thread so they can see a bunch of people arguing with each other.


Good luck with that. Not too many people actually seem to be interested in keeping on topic.

I pop in every now and again to answer questions that have already been addressed earlier in the thread, but other than that, I've about given up.

On the other hand, I still get awesome results with this stack. I have 10 grams of 98% forskolin extract being delivered tomorrow. 10 grams at 5mg a day * 5 times a week will last almost 8 years. I don't know the shelf life nor the advancements that will come in the next 8 years, so I will probably try to sell at least half of it.

Feel free to PM me if anyone is interested.



Has the effects leveled off? I'm wondering how long I will be seeing an improvement for before I don't notice the effects anymore. My stack should be here on Friday, I'll update here with the results.

#846 Nootr

  • Guest
  • 180 posts
  • -9
  • Location:Spain

Posted 10 October 2012 - 08:43 PM

You'd think people on these forums had more sense but no, "nicotine is 3 times more toxic than potassium cyanide" LOL

Nicotine is a powerful poison. The lethal dose for humans starts at 50 mg, making it more toxic than arsenic or potassium cyanide. Nicotine is rapidly absorbed...
Just googled "nicotine toxic potassium cianide"
http://books.google....ABA&redir_esc=y
Which means that your claims are groundless and you seem to be a fool who tries to spoil this wonderful forum.
  • dislike x 1
  • like x 1

#847 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 10 October 2012 - 10:00 PM

Sorry but your statement carries no weight. The only thing that can be concluded is that nicotine is potent.

I think you need to reconsider your definition of "poison"
  • dislike x 4
  • like x 3

#848 Nootr

  • Guest
  • 180 posts
  • -9
  • Location:Spain

Posted 10 October 2012 - 11:34 PM

Nicotine destroys collagen making skin thin and age more quickly. its lethal dose is 50 mg. It is bad for health, skin, heart, memory, .i.e. toxic and is poison. If it's not a poison for you, ok take it, but I will avoid it and advise everyone doing the same. I am not going to argue with you anymore because it seems senseless since you even have not checked the data i provided.
  • dislike x 2

#849 moomoo

  • Guest
  • 73 posts
  • 14
  • Location:UK

Posted 11 October 2012 - 07:28 AM

Nicotine destroys collagen making skin thin and age more quickly. its lethal dose is 50 mg. It is bad for health, skin, heart, memory, .i.e. toxic and is poison. If it's not a poison for you, ok take it, but I will avoid it and advise everyone doing the same. I am not going to argue with you anymore because it seems senseless since you even have not checked the data i provided.


Dude. I checked the data and much more besides. Your argument isn't about the data (nearly everything has a lethal dose, even water) it's about what you believe the data says. You need to take some more nootropics. Your arguments are a collection of platitudes as if you are a child repeating something you've overheard the adults saying. Really.

You've made your point that you don't think nicotine is worth taking.

#850 Mr. Pink

  • Guest
  • 226 posts
  • 28
  • Location:USA

Posted 11 October 2012 - 08:49 AM

i started taking artichoke a few days ago. one 500mg capsule with 5% extract. it made me feel incredibly spacey and i couldn't concentrate. kind of like when i first started taking a higher dose of wellbutrin; it made me feel really spacey at first before i got used to it and found it has an amazing memory enhancing side effect for me.

after taking the artichoke for a few days, i've now added 20% forskolin extract. i took net 4 mg of forskolin in the moring, then 4 more in the afternoon. to my surprise, when mixing the artichoke with the forskolin, i did not have that weird spacey feeling. i don't know if i felt an increase in memory, but concentration and working memory were back to normal, unlike when i was just taking the artichoke without forskolin. anyway, i've got l-phenylalanine on the way and will add it soon.

wanted to add, i took them with the diet supplement i've been taking in the mornings for a while now which contains caffeine, and mucana pruriens (pro dopeamine), and bunch of other interesting things, probably in small quantities though. also took my noopept, choline bitartrate and l-theanine an hour or so later. i feel like i've baselined all the other things and today was just the addition of the forskolin.

Edited by Mr. Pink, 11 October 2012 - 08:52 AM.


#851 Nootr

  • Guest
  • 180 posts
  • -9
  • Location:Spain

Posted 11 October 2012 - 09:54 AM

Dude. I checked the data and much more besides. Your argument isn't about the data (nearly everything has a lethal dose, even water) it's about what you believe the data says. You need to take some more nootropics. Your arguments are a collection of platitudes as if you are a child repeating something you've overheard the adults saying. Really.

You've made your point that you don't think nicotine is worth taking.

Hey, adult. Such topics are based on facts (on collection of facts and experiments), not on argumentation. This is not a philosophical forum. You must move to philosophical forum and argument there.
Everyone here repeats something told by others, or do you claim that anyone here has made inventions in the the field of psycho-phamacy? And of course you don't need to take more nootropics cause you are a genius.

#852 Pirate

  • Guest
  • 147 posts
  • 13
  • Location:aus

Posted 11 October 2012 - 11:05 PM

Just finished reading this entire thread. Was a cause for the tiredness some people experienced ever identified?

#853 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 11 October 2012 - 11:39 PM

Just finished reading this entire thread. Was a cause for the tiredness some people experienced ever identified?


' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/2420646']
A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor. A study with forskolin and its analogs.

Abstract

Forskolin, an activator of adenylate cyclase, and its analogs were studied on the nicotinic acetylcholine receptor-ion channel complex (AChR) of rat and frog skeletal muscles. At nanomolar concentrations, forskolin caused desensitization of the AChR located at the junctional region of innervated and the extrajunctional region of chronically denervated rat soleus muscles. The desensitization of the AChR occurred without alteration of the conducting state (channel lifetime, conductance or bursting) as shown by single channel currents. Accordingly, forskolin decreased the peak amplitude of the repetitive evoked endplate currents in frog sartorius muscles. These findings taken together with the good correlation found between the effects of forskolin and its analogs on the desensitization of the nicotinic AChR and their ability to activate adenylate cyclase suggested a possible involvement of phosphorylation of AChR via cyclic AMP on the desensitization process.
PMID: 2420646

→ source (external link)


Essentially: desensitized nAChR's.

A couple days break with a dose of Galantamine seems to be enough to undo the desensitization (SmartPowders Galantamine works great for this, and is much cheaper than most sources). Also, keeping your dosage of Forskolin low (~5mg) can nearly prevent it from happening, while maintaining most of the positive effects and eliminating most of the negatives.

Today was my first day with the 98% Forskolin extract. Feels much cleaner and had no effect on my digestive tract what so ever. I think we have a winner!

Edited by zrbarnes, 11 October 2012 - 11:42 PM.


#854 Pirate

  • Guest
  • 147 posts
  • 13
  • Location:aus

Posted 12 October 2012 - 12:23 AM

Thanks zrbarnes. Ive appreciated all your work in this thread/stack.

So, what is your current daily stack/s? Did you ever find a replacement for adderall?



#855 abelard lindsay

  • Topic Starter
  • Guest
  • 873 posts
  • 227
  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 12 October 2012 - 05:24 AM

One thing I've noticed on the stack is that I can actually function and get work done even when I'm very drowsy. I can still fall asleep easily when I want to but when I'm drowsy I can still do most of what I need to get done where before I'd be mostly useless. This has tempted me into voluntarily filling up my schedule to the point where I've basically run out of time to do more stuff.

I toy around with small doses of quercetin every now and then but it's annoying that nobody, AFAIK, makes pills less than 250mg so I got bulk and weight out small amounts to stack with artichoke. It gives me this extra assertive edge that I like when dealing with people.

Edited by abelard lindsay, 12 October 2012 - 05:31 AM.


#856 Pirate

  • Guest
  • 147 posts
  • 13
  • Location:aus

Posted 12 October 2012 - 06:32 AM

One thing I've noticed on the stack is that I can actually function and get work done even when I'm very drowsy. I can still fall asleep easily when I want to but when I'm drowsy I can still do most of what I need to get done where before I'd be mostly useless. This has tempted me into voluntarily filling up my schedule to the point where I've basically run out of time to do more stuff.


How was your tiredness before this stack?

#857 abelard lindsay

  • Topic Starter
  • Guest
  • 873 posts
  • 227
  • Location:Mare Serenitatis Circumlunar Corporate Republic

Posted 12 October 2012 - 09:02 AM

Before the stack I had bad procrastination and reading concentration problems. i was awake but was not getting all the things I wanted to do done. Now I go through the day a bit sleepy but am a lot more productive. Phenylalanine seems to help with the sleepiness somewhat.

#858 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 12 October 2012 - 10:12 AM

I believe the lethargy from forskolin is related to low blood sugar. Considering adenylyl cyclase uses ATP to form cAMP, it puts strain on the glycolytic process to maintain homeostasis. This could be checked if anyone has an insulin monitor or something. Or eat some fruit and see if it helps.
I use 50mg forskolin daily, not sure how you guys feel anything from 5mg. The conducted studies have reached 10µM concentrations. 5mg doesnt get anywhere near that

nAChR desentisization has absolutely nothing to do with overall lethargy

Edited by nidhogg, 12 October 2012 - 10:13 AM.


#859 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 12 October 2012 - 01:55 PM

I believe the lethargy from forskolin is related to low blood sugar. Considering adenylyl cyclase uses ATP to form cAMP, it puts strain on the glycolytic process to maintain homeostasis. This could be checked if anyone has an insulin monitor or something. Or eat some fruit and see if it helps.


If you feel any of the common symptoms of lowered blood sugar, then you should definitely keep an eye on that. Forskolin does have large effects on glucose transport, especially when taking larger doses.

Have fun with that 50mg a day; I tried that for a while. Make sure you keep an eye on your intraocular pressure (Hypotony Maculopathy), and your kidneys if you are taking it long term.

nAChR desentisization has absolutely nothing to do with overall lethargy

On what basis have you formed said opinion?

Edited by zrbarnes, 12 October 2012 - 02:00 PM.


#860 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 12 October 2012 - 03:12 PM

I believe the lethargy from forskolin is related to low blood sugar. Considering adenylyl cyclase uses ATP to form cAMP, it puts strain on the glycolytic process to maintain homeostasis. This could be checked if anyone has an insulin monitor or something. Or eat some fruit and see if it helps.


If you feel any of the common symptoms of lowered blood sugar, then you should definitely keep an eye on that. Forskolin does have large effects on glucose transport, especially when taking larger doses.

Have fun with that 50mg a day; I tried that for a while. Make sure you keep an eye on your intraocular pressure (Hypotony Maculopathy), and your kidneys if you are taking it long term.

nAChR desentisization has absolutely nothing to do with overall lethargy

On what basis have you formed said opinion?


nAChR desentisization is induced by receptor phosphorylation from increased cAMP levels. Since this most often occurs by powerful agonist ligands, such as nicotine, its fair to draw parallels. Nicotine has shown to induce desentisization and receptor upregulation, or in plain english this means that the response from receptor binding decreases while the frequency of firing increases.
So in a slightly more macroscopic scale, this makes zero difference in terms of receptor activity and serves only to block the overstimuli from high potency ligands.

May i ask what you experienced using 50mg a day? I have primaforce brand. I have never read on any forum people suggesting 5mg a day. The standard seems to be 250mg of forskolii standardized to 20% forskolin. In vitro human studies for lipolysis have suggested 25mg twice a day.

Then again, cycling your supplements seem to be the most preferable approach, biochemically speaking.

#861 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 12 October 2012 - 03:24 PM

I would think that a system that has highly been implicated in wakefulness might be involved with why one might feel sleepy.

Multiple arousal systems maintain waking through the actions of chemical neurotransmitters that are released from broadly distributed nerve terminals when the neurons fire. Among these, noradrenaline-, histamine- and orexin-containing neurons fire during waking with behavioral arousal, decrease firing during slow-wave sleep (SWS) and cease firing during paradoxical sleep (PS), which is also known as rapid-eye-movement sleep. By contrast, acetylcholine (ACh)-containing neurons discharge during waking, decrease firing during SWS and fire at high rates during PS in association with fast cortical activity. Neurons that do not contain ACh, including GABA-containing neurons in the basal forebrain and preoptic area, are active in a reciprocal manner to the neurons of the arousal systems: one group discharges with slow cortical activity during SWS, and another discharges with behavioral quiescence and loss of postural muscle tone during SWS and PS. The reciprocal activities and interactions of these wake-active and sleep-active cell groups determine the alternation between waking and sleeping. Selective enhancement and attenuation of their discharge, transmitter release and postsynaptic actions comprise the substrates for the major stimulant and hypnotic drugs.

→ source (external link)


According to multiple lines of evidence, neurons in the ventrolateral preoptic area (VLPO) that contain GABA promote sleep by inhibiting neurons of the arousal systems. Reciprocally, transmitters used by these systems, including acetylcholine (ACh) and noradrenaline (NA), exert an inhibitory action on the VLPO neurons. Because nicotine, an agonist of ACh, acts as a potent stimulant, we queried whether it might participate in the cholinergic inhibition of these sleep-promoting cells. Indeed, we found that ACh inhibits the VLPO neurons through a nicotinic, as well as a muscarinic, action. As evident in the presence of atropine, the non-muscarinic component was mimicked by epibatidine, a nonselective nicotinic ACh receptor (nAChR) agonist and was blocked by dihydro-b-erythroidine, a nonselective nAChR antagonist. It was not, however, blocked by methyllycaconitine, a selective antagonist of the a7 subtype, indicating that the action was mediated by non-a7 nAChRs. The nicotinic inhibition was attributed to a presynaptic facilitation of NA release because it persisted in the presence of tetrodotoxin and was blocked by yohimbine and RS 79948, which are both selective antagonists of a2 adrenergic receptors. Sleep-promoting VLPO neurons are thus dually inhibited by ACh through a muscarinic postsynaptic action and a nicotinic presynaptic action on noradrenergic terminals. Such dual complementary actions allow ACh and nicotine to enhance wakefulness by inhibiting sleep-promoting systems while facilitating other wake-promoting systems.

→ source (external link)


Histaminergic tuberomammillary ™ neurons of the posterior hypothalamus have been implicated in cognition, alertness and sleep-wakefulness cycles. Spontaneous firing of TM neurons has been associated with histamine release and wakefulness. The exp<b></b>ression of alpha7 nicotinic acetylcholine receptors (nAChRs) in TM neurons suggests a role for endogenous choline and for nicotinic drugs in the regulation of intracellular Ca(2+) metabolism, normal TM neuronal activity and histamine release. First, we established the link between TM neuronal spontaneous firing frequency and cytosolic free Ca(2+) concentration ([Ca(2+)](i)). A strong correlation was observed: an onset of spontaneous firing (3-4Hz) was accompanied by a 20-fold increase in [Ca(2+)](i) from 56+/-18 nM to 1.0+/-0.6 microM. The same range of firing frequencies has been observed in TM neurons in vivo and is associated with wakefulness. Secondly, choline-induced activation of alpha7 nAChRs did not elevate [Ca(2+)](i) directly, i.e. in the absence of high-threshold voltage-gated Ca(2+) channel (HVGCC) activation. Cd(2+) (200 microM) completely blocked all Ca(2+) signals, but inhibited only 37+/-16% of alpha7 nAChR-mediated currents. Thirdly, the responsiveness of [Ca(2+)](i) to choline-mediated excitation was inhibited by hyperpolarization and enhanced by depolarization, sensitizing [Ca(2+)](i) at membrane voltages associated with normal TM neuronal activity. These properties of [Ca(2+)](i) define the ability of TM neurons to translate cholinergic stimuli of identical strengths into different cytosolic Ca(2+) effects, providing the physiological substrate for state-specific modulation of incoming cholinergic information and would be expected to play a very important role in determining activity profiles of TM neurons exposed to elevated concentrations of cholinergic agents, such as choline and nicotine.

→ source (external link)


Anecdotally speaking, after a wash out period, Galantamine has a much less significant effect then when I have been taking forskolin for many days straight. Given Galantamine's method of action, it seems to fit.

It could be by a related mechanism, since desensitization of nAChR's causes change in mAChR activity, and Galantamine also effects mAChR activity.

Acetylcholine has long been implicated in nocturnal phase adjustment of circadian rhythms, yet the subject remains controversial. Although the suprachiasmatic nucleus (SCN), site of the circadian clock, contains no intrinsic cholinergic somata, it receives choline acetyltransferase-immunopositive projections from basal forebrain and mesopontine tegmental nuclei that contribute to sleep and wakefulness. We have demonstrated that the SCN of inbred rats in a hypothalamic brain slice is sensitive to cholinergic phase adjustment via muscarinic receptors (mAChRs) only at night. We used this paradigm to probe the muscarinic signal transduction mechanism and the site(s) gating nocturnal responsiveness. The cholinergic agonist carbachol altered the circadian rhythm of SCN neuronal activity in a pattern closely resembling that for analogs of cGMP; nocturnal gating of clock sensitivity of each is preserved in vitro. Specific inhibitors of guanylyl cyclase (GC) and cGMP-dependent protein kinase (PKG), key elements in the cGMP signal transduction cascade, blocked phase shifts induced by carbachol. Further, carbachol administration to the SCN at night increased cGMP production and PKG activity. The carbachol-induced increase in cGMP was blocked both by atropine, an mAChR antagonist, and by LY83583, a GC inhibitor. We conclude that (1) mAChR regulation of the SCN is mediated via GC-->cGMP-->PKG, (2) nocturnal gating of this pathway is controlled by the circadian clock, and (3) a gating site is positioned downstream from cGMP. This study is among the first to identify a functional context for mAChR-cGMP coupling in the CNS.

→ source (external link)

Edited by zrbarnes, 12 October 2012 - 04:04 PM.


#862 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 12 October 2012 - 03:47 PM

May i ask what you experienced using 50mg a day? I have primaforce brand. I have never read on any forum people suggesting 5mg a day. The standard seems to be 250mg of forskolii standardized to 20% forskolin. In vitro human studies for lipolysis have suggested 25mg twice a day.


At 50mg a day, I had headaches, changes in blood pressure, chronic sleepiness after taking for more than a week straight, loose stools, and vision changes.

At 20mg, these all lessened, but chronic sleepiness persisted.

At 5-10mg, I don't have any issues, but I still distinctly feel it's effects. I've done some very informal placebo trials and I've yet to misjudge which dose contains forskolin, and which dose was artichoke only.

I've not trialed higher doses of the 98% extract to see if they exert the same side effects profile. I will probably do so (in the name of science, of course) at some point.

Edited by zrbarnes, 12 October 2012 - 04:31 PM.


#863 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 12 October 2012 - 04:20 PM

Just to make it clear, the full mechanism for how all these things work is theoretical.

We have empirical evidence (on n=1 experiment groups) that we are trying to match up with medical studies.

For instance, did you know that forskolin induced cAMP stimulation doesn't start working until a certain concentration? Did you know that it is an inhibitor of cAMP production at a certain concentration?

Forskolin, at 10(-11) M, stimulates guanylate cyclase activity in primary human thyroid cell cultures, but does not modify cAMP accumulation. At a 10-fold higher concentration it still stimulates guanylate cyclase activity and becomes an inhibitor of cAMP production. Above 10(-9) M, forskolin stimulation of cGMP decreases, while it also becomes a stimulator of cAMP production. There is an additive effect of TSH and forskolin on cAMP production at concentrations of the diterpene which are stimulatory. Concentrations of forskolin which are inhibitory for cAMP, but stimulatory for cGMP, are inhibitory for TSH stimulation of cAMP. The addition of 8-bromo-cGMP duplicates the forskolin effect at low concentrations.

→ source (external link)


However, does anyone have any data on how much of an oral dosage it takes in order to stimulate cAMP production in the human brain? I think you would have to do some very fatal tests to be sure (or at least some expensive tests to have a decent guess).

What if the 5mg dose is stimulating cGMP production, but not cAMP? Fortunately, cGMP has been implicated in LTP as well.

At the end of the day, it is far too complex to actually know every thing that is happening in between your ears. We are throwing a dart at a dart board in a dark room.

All we really have is our experience... our empirical data. Thank God it's not susceptible to the placebo effect, or anything :)

Edited by zrbarnes, 12 October 2012 - 04:26 PM.


#864 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 12 October 2012 - 06:45 PM

What the above states is that the cholinergic system is powerfully excitatotory so i guess its only logical to assume its involved. But this we knew already.
The problem is the inconsistancy. Assuming a potent downregulation occurs from forskolin, one should expect to feel the lethargy upon discontinuation and not during administration.
Personally I have felt lethargic consuming adrenergics, caffeine, nicotine and other stimulants working through various pathways. All which are supposed to be strongly excitatory.

Galantamine appears to be an acetylcholinesterase inhibitor, so it raises acetylcholine levels by inhibiting breakdown mechanism. Assuming the self-regulatory system of cholinergic neurons persists, there should be insignificant differences in cholinergic activity pre and post nAChR desensitiziation from endogenous ligands. Sensitivity does not equal receptor density, they are inversely proportional.

But as you said, its strictly theoretical until proven otherwise. There are way too many variables to consider to be able to draw a conclusion and that is the reason why i fail to correlate one mechanism to a largely systematic symptom, generally speaking.

If only an approximation of the oral bioavailability was given the rest could be calculated

#865 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 12 October 2012 - 08:38 PM

This is interesting:

Adenosine modulation of nicotinic ACh receptor (nAChR) function was studied in primary cultures of rat skeletal muscle. Activation of the nAChR by carbachol increased extracellular adenosine concentration in a dose-dependent manner. Furthermore, carbachol activation of the nicotinic receptor resulted in a twofold increase in cAMP levels in the muscle cells. The carbachol-dependent increase in CAMP levels was inhibited by adenosine receptor antagonists as well as by nicotinic receptor antagonists. These results suggest that the increased cAMP levels were due to adenosine receptor activation by the extracellular adenosine accumulated on nAChR activation. Others have shown that desensitization of the nAChR by agonist is mediated, in part, by phosphorylation. Since we found that nicotinic cholinergic agonists also cause adenosine accumulation with concomitant CAMP increases, we determined whether the accumulated adenosine has a role in desensitization. We found that the adenosine receptor antagonist, BW 143411, significantly inhibited carbachol-induced nAChR desensitization, indicating that extracellular adenosine is involved in nAChR desensitization. Our data suggest that nAChR function is regulated via a feedback mechanism mediated by adenosine released from muscle on activation of the nACh.

→ source (external link)


Also, Forskolin increases aChE:


We investigated an alternative bioscavenger approach using forskolin, an inducer of intracellular cyclic AMP (cAMP), which activates AChE promoter and up-regulates its expression. A mouse neuronal cell line, Neuro 2A, was treated with various doses of forskolin and analysis of the expressed enzyme indicates that the AChE activity was significantly increased in cells exposed to repeated administration of the drug every other day for 7-10 days. Cholinesterase enzyme assays showed that the enzyme activity was increased approximately 2-fold for the extracellular enzyme and 3-fold for the intracellular enzyme. The optimal dose found for extracellular enzyme production was 12-24 microM forskolin, while the optimal dose for intracellular was 12 microM. In parallel with the rise in the AChE level, the morphology of forskolin-treated cells showed neurite growth with increasing doses. Forskolin treatment protects Neuro 2A cells from diisopropylflurophophate (DFP), a surrogate of the organophosphate chemical warfare agents soman and sarin, induced toxicity in Neuro 2A cells. These results indicate that transcriptional inducers, such as forskolin, can sufficiently up-regulate cellular AChE production and protect cells against organophosphate toxicity.

→ source (external link)



Galantamine is not merely an aChE inhibitor, but also a allosteric positive modulator of nAChRs. It has been studied for its effects on nicotine withdrawal:


There are at least two possible mechanisms, operating alone or in combination, through which galantamine may reverse cognitive deficits from nicotine withdrawal. First, galantamine enhances cholinergic transmission by inhibiting acetylcholinesterase [23]. The importance of acetylcholine in cognition has been well documented [20, 21] and changes in cholinergic activity often correspond to changes in cognitive function [27, 39]. For example, microdialysis studies have shown an increase in extracellular levels of acetylcholine during many cognitive functions including attention [40], exposure to novelty [41], working memory [42], and spatial memory [43]. Pharmacological inhibition of acetylcholine and lesions of the cholinergic system often produce deficits in learning and memory (see [32] for a review). Alterations in endogenous cholinergic transmission is postulated to be one biochemical mechanism underlying nicotine withdrawal [6] and therefore galantamine might reverse nicotine withdrawal cognitive deficits by restoring cholinergic activity to pre-withdrawal levels.

Second, galantamine acts as an allosteric potentiating ligand at nAChRs [24, 25, 44]. Allosteric potentiating ligands of nAChRs bind to sites that are distinct from those of acetylcholine and nicotinic agonists and potentiation or enhance nAChR responsivity to acetylcholine and other nicotinic agonists [24, 25, 44, 45]. The binding sites for nicotinic agonists on nAChRs lie at the interface of alpha and B subunits except in the case of homomeric receptors where binding sites are formed at the interface between alpha subunits [46-48]. Galantamine on the other hand binds to alpha subunits of nAChRs allowing it to modulate nAChR responsivity to nicotinic agonists without interfering with agonist binding [44]. Hippocampal nAChRs containing a4B2 subunits, possibly a4B2* nAChRs (the * indicates other subunits may be incorporated into this receptor) mediate nicotine withdrawal-deficits in contextual conditioning [34, 35, 49] and agonists of this receptor such as nicotine [15] and the partial agonist varenicline [19] are able to reverse these deficits. Evidence indicates that galantamine binds to a4B2* nAChRs [25, 50, 51] and therefore may enhance hippocampal a4B2* nAChR responsivity to endogenous acetylcholine. This would compensate for reduced cholinergic function during nicotine withdrawal and therefore lead to an alleviation of the cognitive withdrawal symptoms.

In conclusion, galantamine is able to reduce nicotine withdrawal-deficits in contextual conditioning. This may be due to galantamine potentiating a4B2* nAChR responsiveness to endogenous acetylcholine, enhancing cholinergic transmission, or both.

→ source (external link)

Edited by zrbarnes, 12 October 2012 - 08:50 PM.


#866 Mr. Pink

  • Guest
  • 226 posts
  • 28
  • Location:USA

Posted 13 October 2012 - 05:02 AM

i've been taking artichoke/4mg of forskolin version for a couple days now, and i can't tell if there's positive effects, but i've noticed increased irritability. i was expecting that when i started noopept last month, but i didn't get that (10mgx3 times a day). i also take 100mg of l-theanine 3 times a day, and that hasn't really chilled that irritibility out. the irritibility, and i have to admit, depression, goes away after the 1st hour or so of dosing.

Edited by Mr. Pink, 13 October 2012 - 05:02 AM.


#867 nootropicthunder

  • Guest
  • 10 posts
  • 0
  • Location:Australia

Posted 13 October 2012 - 09:12 AM

So whats the go with this stack? It does reduce short term memory?

#868 nidhogg

  • Guest
  • 66 posts
  • 6
  • Location:Cold North

Posted 13 October 2012 - 11:33 AM

This is interesting:


Well sir, you certainly got me interested. I havent heard of galantamine prior to this but it does seem to beat huperzine in terms of overall effects. I assume its a regulated Rx drug but how hard is it to get a hold of in EU?

#869 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 13 October 2012 - 07:26 PM

So whats the go with this stack? It does reduce short term memory?


The idea of this stack is not really to push your brain into ungodly capabilities, but to take those days where everything just "clicks" and you feel at your best... and make those days happen more frequently. For me, there is a huge gap between my average everyday (without supps) performance and me at my best, so this works awesomely.

It seems that, like most supplements, there are a few that have reported issues such as irritability and temporary reduction of working memory. I don't remember anyone testing to verify that it was actually working memory; it was more of an anecdotal "I keep locking my keys in my car and rereading stuff". It may be that these folks already happen to have quite a bit of cAMP floating around in their PFC and adding to it causes the issues that are commonly reported by ADHD folks, or it could be a completely different mechanism.

Working' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/23040817']Working memory arises from recurrent excitation within layer III PFC pyramidal cell NMDA circuits, which are afflicted in aging and schizophrenia. Neuromodulators rapidly and flexibly alter the efficacy of these synaptic connections, while leaving the synaptic architecture unchanged, a process called dynamic network connectivity (DNC). Increases in calcium-cAMP signaling open ion channels in long, thin spines, gating network connections. Inhibition of calcium-cAMP signaling by stimulating alpha2A-adrenoceptors on spines strengthens synaptic efficacy and increases network firing, whereas optimal stimulation of dopamine D1 receptors sculpts network inputs to refine mental representation. Generalized increases in calcium-cAMP signaling during fatigue or stress disengage dlPFC recurrent circuits, reduce firing and impair top-down cognition. Impaired DNC regulation contributes to age-related cognitive decline

→ source (external link)


Earlier in this thread, unbeatableking argued with me that a this problem had nothing to do with NMDA receptors, yet he reported fantastic results in the glycine agonist thread.

This is weird.

The stuff has definitely stabilized my behavior and my thought processes. I don't feel like a raging asshole anymore.

The need to run out and jump around every so often has also dissipated.

Which has me thinking: do I suffer from an NMDA-receptor rooted dysfunction? For once in a long time I actually feel normal.


Glycine agonists (glycine, sarcosine, TMG, d-serine) increase the probability of NMDA firing, and LTP:

In' class='bbc_url' title='External link' rel='nofollow external'>http://jn.physiology.org/content/99/5/2719.full']In addition to forskolin, a number of other techniques have used biochemical manipulations to induce cLTP, including, manipulating postsynaptic calcium (Neveu and Zucker 1996), raising cAMP levels (Frey et al. 1993; Nguyen et al. 1994), adding glycine (Lu et al. 2001; Yudowski et al. 2007)

→ source (external link)


Irritability is probably induced by the increased probability of glutamate release by Forskolin. This can lead to irritability, depression, anxiety, aggressive behavior, and apathy if it is imbalanced with dopamine and gaba synthesis caused by some other reason. This could be from a lack of precursors (eat healthy food or take l-phenylalanine), genetic issues, or other supplements.

Both of these side effects are more likely to happen with overdosing.

Edited by zrbarnes, 13 October 2012 - 07:55 PM.

  • like x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#870 gizmobrain

  • Guest
  • 548 posts
  • 105
  • Location:USA

Posted 13 October 2012 - 07:36 PM

Well sir, you certainly got me interested. I havent heard of galantamine prior to this but it does seem to beat huperzine in terms of overall effects. I assume its a regulated Rx drug but how hard is it to get a hold of in EU?


Galantamine is one of those drugs that was actually discovered in nature and then replicated in the lab. Because of that, there are several "plant sourced" versions on the market. It may or may not actually come from the plant, but it allows them to skirt the issues with the FDA here in the US. I'm in no way educated on EU drug laws, but SmartPowders carries it, and ships internationally.





Also tagged with one or more of these keywords: ciltep, pde4, forskolin, ltp

4 user(s) are reading this topic

0 members, 4 guests, 0 anonymous users

Topic Led By