2626 replies to this topic

[fenra]

Lately I don't get a lot of focus or motivation from this stack... it does however put a big smile on my face all morning long. I wonder what causes this effect?

Edited by fenra, 06 February 2013 - 11:27 AM.

[jadamgo]

Update: Currently on 6mg forskolin + 2 artichoke caps + 2 CarnitAll caps every morning, with another 1 artichoke cap and 2 CarnitAll caps in the afternoon when I go to work.

This dosage works well, and I'll wait a while before messing with it. No significant peaks and valleys, unlike my earlier trials with 3 artichoke + 12mg forskolin in the morning. That schedule led to crashes in the afternoon, and if I took more forskolin, it started to feel like a vyvanse binge. Completely unacceptable.

I haven't tried adding racetams yet. I have noticed that caffeine, bright light therapy, and MPH aren't potentiated very much by the artichoke extract, but they're greatly potentiated by the forskolin. That's another reason I cut the forskolin dose -- the last thing I need is to have to break my MPH tablets into even smaller pieces.

[hephaestus]

I found concerta to be a lot more convenient than taking small doses of IR all day long.

[jadamgo]

I found concerta to be a lot more convenient than taking small doses of IR all day long.

God yes. I hate this 2.5mg bi-hourly microdosing crap. But it costs one twentieth of what Concerta costs...

[norepinephrine]

Just a quick update.

Received the 95% forskolin in the post the other day. For some reason, my scale is evidently not sensitive enough to weigh anything <30mg, so the first day I split the weighed 30mg in half to get approximately 15mg, and on the subsequent days I just went with 30mg.

Effects so far are cleaner - i.e., whereas I'd occasionally get an afternoon headache from Solaray 1% forskolin, I haven't noticed the same from 95% extract. Given I paid <$25 for 2g, it appears that going for a more pure extract actually makes better economical sense than the alternative of buying a name brand at the supplement store.

[peakplasma]

Just a quick update.

Received the 95% forskolin in the post the other day. For some reason, my scale is evidently not sensitive enough to weigh anything <30mg, so the first day I split the weighed 30mg in half to get approximately 15mg, and on the subsequent days I just went with 30mg.

Effects so far are cleaner - i.e., whereas I'd occasionally get an afternoon headache from Solaray 1% forskolin, I haven't noticed the same from 95% extract. Given I paid <$25 for 2g, it appears that going for a more pure extract actually makes better economical sense than the alternative of buying a name brand at the supplement store.

Could you show what kind of mg scale you have?

Edited by peakplasma, 08 February 2013 - 06:53 PM.

[medievil]

Does anyone find this stack effective with ginseng instead of artichoke/quercetine? as thats what i got and its supposed to be a PDE4 inhibitor, those ampoules also have ginger in it wich is one too.

[medievil]

Since they are available, im making a thread about selective 5HT4 agonists, 5HT4 is the serotonin receptors wich stimulates cyclic amp.

Naunyn Schmiedebergs Arch Pharmacol. 2012 Jun;385(6):565-77. doi: 10.1007/s00210-012-0746-y. Epub 2012 Mar 17.
Study of the regulation of the inotropic response to 5-HT4 receptor activation via phosphodiesterases and its cross-talk with C-type natriuretic peptide in porcine left atrium.

Weninger S, De Maeyer JH, Lefebvre RA.

Source

Heymans Institute of Pharmacology, UG, Gent 9000, Belgium. sabine.weninger@ugent.be

Abstract

We studied how 5-HT(4) receptor-mediated inotropic responses are regulated at the level of cAMP in porcine left atrium. We used selective phosphodiesterase (PDE) inhibitors to assess which PDE subtypes are responsible for the fade with time of inotropic responses to 5-HT(4) receptor activation with 5-HT and the 5-HT(4) receptor agonist prucalopride. A possible cross-talk via PDEs between cGMP and 5-HT(4) receptor-induced cAMP signalling was evaluated. Electrically paced left atrial pectinate muscles from young male pigs (15-25 kg) were studied in vitro. Simultaneous inhibition of PDE3 plus PDE4 subtypes was necessary to increase the amplitude and completely prevent the fade of the inotropic response to 5-HT and prucalopride. When responses to 5-HT or prucalopride had faded 1 h after addition, the nonspecific PDE-inhibitor IBMX still fully recovered inotropic responses. Stimulation of particulate guanylyl cyclase, together with PDE2 and PDE4 inhibition, delayed the fade of the response to 5-HT, while stimulation of soluble guanylyl cyclase independently of PDEs accelerated the fade of the response to 5-HT. In conclusion, both PDE3 and PDE4 subtypes are responsible for the suppression and the fade of the inotropic response to 5-HT and prucalopride. Signalling through the 5-HT(4) receptor remains fully active for at least 90 min with PDEs continuously regulating the response. cGMP levels, elevated by activation of particulate guanylyl cyclase under PDE2 inhibition, can indirectly enhance 5-HT(4) receptor-mediated signalling, at least when also PDE4 is inhibited, presumably through inhibition of PDE3. Elevation of cGMP generated by soluble guanylyl cyclase attenuates responses to 5-HT independently of PDEs.

Potential interesting synergy with this stack.

[norepinephrine]

Peakplasma - very similar to this one: http://www.amazon.co...=digital scale.

Medieval - why don't you try experimenting yourself? The only downside I can think of for ginseng is that it has a variety of other effects and not all of them may be desirable. IIRC, isn't ginseng a mild phytoestrogen?

Peakplasma - very similar to this one: http://www.amazon.co...=digital scale.

Medieval - why don't you try experimenting yourself? The only downside I can think of for ginseng is that it has a variety of other effects and not all of them may be desirable. IIRC, isn't ginseng a mild phytoestrogen?

[medievil]

I am using the combo but im very bad at noticing effects, ive used with quercetin before but i also took benzo's and phenibut wich inhibit cyclic amp so ive got no clue wheter the combo even worked then, things like amphetamine i can feel for the rest im extremely bad at testing stuff.

[kassem23]

I tried forskolin + artichoke extract today, one pill of each of the brands frequently mentioned in this thread.

I combined it with Monster Energy Absolutely Zero, which has a ginseng blend. I also smoked cigarettes.

At the first three hours it was quite great. Good mental energy and focus, but after that it was a disaster. Anxiety, hyperstimulation, and extreme rumination. Even now 10 hours post-dosing I am still trying to calm down and feel better. Even one beer didnt help significantly.

Best of luck to the rest.

[medievil]

I started feeling anxious and overstimulated after adding nefiracetam, first time i try the combo with amphetamine wich releases glutamate, d serine and other things that potentiate ltp compared to the reuptake inhibitors i normally take, i took 2mg clonazepam extra to calm down, also letting coluracetam disolve atm.

I tried forskolin + artichoke extract today, one pill of each of the brands frequently mentioned in this thread.

I combined it with Monster Energy Absolutely Zero, which has a ginseng blend. I also smoked cigarettes.

At the first three hours it was quite great. Good mental energy and focus, but after that it was a disaster. Anxiety, hyperstimulation, and extreme rumination. Even now 10 hours post-dosing I am still trying to calm down and feel better. Even one beer didnt help significantly.

Best of luck to the rest.

Have you got anything gabaergic? it works if you overdose on the cilltep. i suppose the ginseng added was too much for you.

[kassem23]

Yeah, it feels that way.

I am drinking beer at the moment. Dont have any GABAergic substances at my availaibility.

[medievil]

So now i know this stack works haha, its not fun the anxiety and overstimulation, still wondering why im the only one here stacking with nefiracetam much better option.

Is it possible this stack potentiates getting over the death of a family member? A close family member died yesterday and from feeling hopeless and extremely sad im progressing to acceptance extremely quick still feel very sad tough the forum takes my mind off.

[kassem23]

Very sad to hear that my mate.

[norepinephrine]

I've found a big difference in the stack between days I'm sleep-deprived and stressed (e.g., exam days) vs. days when I'm well-rested and relaxed. Basically, when my cortisol is already high, I'm a lot more senstive to CILTEP as well as more likely to meet overstimulation if I ingest too much caffeine. If I add ginkgo to the mix, the effect is further amplified. On days where I'm well-rested, though, CILTEP doesn't seem to have nearly the same effect, and I can ingest up to twice the amount of caffeine without noticeable overstimulation.

Another thing I've noticed, and have seen mentioned in another thread - my ability to perform after a lack of sleep is enhanced from CILTEP (barring I keep caffeine levels in check). I believe that's a product of PDE4 inhibition: http://www.longecity...ep-deprivation/ The problem, though, is despite an ability to perform, the combination of CILTEP and less-than-adequate sleep does produce a noticeable spike in exam anxiety, and I've been looking for appropriate means to counteract that. In order of effectiveness, aerobic exercise, swapping coffee for green tea, and taking ashwagandha have all seemed to help a bit. Actually, ashwagandha in general may be a good counterbalance to the rest of the ingredients, though someone with a better background in neurochemistry may want to chime in on whether the combination is counterproductive. It's definitely one of the only GABAergic supplements I'm willing to take.

[genagena]

Topic Starter: I'm not sure if you're still taking quercetin, but you might want to read this...


Quercetin impairs learning and memory in normal mice via suppression of hippocampal phosphorylated cyclic AMP response element-binding protein expression.

Jung WY, Park SJ, Park DH, Kim JM, Kim DH, Ryu JH.

Source

Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.

Abstract


Quercetin is a naturally occurring dietary flavonol and several reports have shown that quercetin substantially affects cognitive function in disease models, which suggests that quercetin might be a useful agent for treatment of memory dysfunction. However, only one report has examined the effects of quercetin on normal cognitive function. In the present study, we investigated the potential deleterious effects of quercetin on normal cognitive function using Western blot assays and the following behavioral tasks: passive avoidance, Y-maze, and Morris water maze. In the passive avoidance task, pre-acquisition administration of quercetin (10, 20, or 40 mg/kg, p.o.) caused significant cognitive impairments in mice (P < 0.05 or P < 0.01). Quercetin-treated groups (10, 20, or 40 mg/kg, p.o.) also showed significant memory impairments compared with the control group in the Y-maze task (P < 0.05). In the Morris water maze task, there were no significant differences among the groups during training trial sessions, but at the probe trial session, the quercetin-treated group (40 mg/kg, p.o.) spent significantly less time in the target quadrant than did the control group (P < 0.05). In Western blot assays of hippocampal tissue, we found that quercetin-treated groups showed decreased expression of phosphorylated Akt (pAkt), phosphorylated calcium-calmodulin kinase II (pCaMKII), and phosphorylated cyclic AMP response element-binding protein (pCREB). These results suggest that acute administration of quercetin impairs cognitive function by suppression of pAkt and pCaMKII, which, in turn, decreases pCREB expression in the hippocampus.

[abelard lindsay]

Topic Starter: I'm not sure if you're still taking quercetin, but you might want to read this...


Quercetin impairs learning and memory in normal mice via suppression of hippocampal phosphorylated cyclic AMP response element-binding protein expression.

We dumped quercetin about half way through the thread. Artichoke extract or luteolin are the preferred PDE4 inhibitors to use with this stack. The quercetin study you cited was referenced on the thread back in August 2012: (http://www.longecity...690#entry530580).

Edited by abelard lindsay, 10 February 2013 - 12:29 AM.

[abelard lindsay]

Lately I don't get a lot of focus or motivation from this stack... it does however put a big smile on my face all morning long. I wonder what causes this effect?

PDE4 inhibitors have shown anti-depressant activity in mice:

http://www.ncbi.nlm....pubmed/23384434

Etazolate, a Phosphodiesterase 4 Inhibitor Reverses Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior and Brain Oxidative Damage.

...
. Additionally, in the present study, the efficacy of etazolate (1mg/kg., p.o.) on the behavioral and biochemical paradigms was found comparable to that of fluoxetine, used as standard antidepressant.
...

There's also this review of PDE4 inhibition as a target for anti-depressant drug development:

http://www.ncbi.nlm....pubmed/19442182

PDE4 inhibitors produce antidepressant actions in both animals and humans via enhancement of cAMP signaling in the brain.

[OpaqueMind]

Is long term potentiation also involved in habit-formation? If so, that would be very interesting as one could take the ciltep stack when trying to implement new behavioural or mental habits.

Interestingly, my meditations are deepened on this stack, and meditation is known to induce synaptic plasticity and specific changes in interbrain communication pathways. My thinking is that the depths reached might correspond to the degree of neural change occurring. I think this because cerebrolysin, a potent neurotrophin promoter, has a similar but more pronounced effect and so points to the same possibility. I might try the two together at some point.

[medievil]

Phosphodiesterases

Recent studies have found that phosphodiesterase 4 (PDE4) inhibitors, such as Rolipram, cause emesis as one of their side effects.^[7] It has been found that these PDE4 inhibitors are numerous in the CTZ and in the brainstem in general.^[7] The mRNA products from genes that code for these PDE4 inhibitors are plentiful in the CTZ, and not only located in CTZneurons, but also in glial cells and blood vessles associated with with the CTZ neurons.^[7] Also, the hydridization signals from the PDE4 mRNAs are stronger in the area postrema and the CTZ than anywhere in the brainstem.^[7] The PDE4 degrades the phosphodiester bonds in the second messenger molecule cyclic adenosine monophosphate (cAMP), which is one of the ways the brain relays information. By modifying cAMP signaling in the CTZ, it is thought that this could mediate the emetic effects of PDE4 inhibitors in the CTZ.^[7]

Meclizine is neuroprotective and otc

Hum Mol Genet. 2011 Jan 15;20(2):294-300. doi: 10.1093/hmg/ddq464. Epub 2010 Oct 25.
Meclizine is neuroprotective in models of Huntington's disease.

Gohil VM, Offner N, Walker JA, Sheth SA, Fossale E, Gusella JF, MacDonald ME, Neri C, Mootha VK.

Source

Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA. vgohil@chgr.mgh.harvard.edu

Abstract

Defects in cellular energy metabolism represent an early feature in a variety of human neurodegenerative diseases. Recent studies have shown that targeting energy metabolism can protect against neuronal cell death in such diseases. Here, we show that meclizine, a clinically used drug that we have recently shown to silence oxidative metabolism, suppresses apoptotic cell death in a murine cellular model of polyglutamine (polyQ) toxicity. We further show that this protective effect extends to neuronal dystrophy and cell death in Caenorhabditis elegans and Drosophila melanogaster models of polyQ toxicity. Meclizine's mechanism of action is not attributable to its anti-histaminergic or anti-muscarinic activity, but rather, strongly correlates with its ability to suppress mitochondrial respiration. Since meclizine is an approved drug that crosses the blood-brain barrier, it may hold therapeutic potential in the treatment of polyQ toxicity disorders, such as Huntington's disease.

[abelard lindsay]

...
Meclizine is neuroprotective and otc
...

Meclizine is an anti-histamine and anti-emetic H1 receptor antagonist. It has very little, if anything, to do with cAMP, PDE4 inhibition or LTP.

Edited by abelard lindsay, 10 February 2013 - 02:49 PM.

[medievil]

Its just able to stop the gastro side effects, thats why i posted it so you can take the level of PD4 inhibition higher.

[peakplasma]

Its just able to stop the gastro side effects, thats why i posted it so you can take the level of PD4 inhibition higher.

Agreed but the anticholinergic + H1 antagonism is troubling. The study is interesting but the demyelination risk kills it for me.

[medievil]

<p>Demyelination risk? must have missed something better avoid that as the plague too.</p>

[dreth7]

Its just able to stop the gastro side effects, thats why i posted it so you can take the level of PD4 inhibition higher.

Agreed but the anticholinergic + H1 antagonism is troubling. The study is interesting but the demyelination risk kills it for me.

What would pose a risk for demyelination?

[abelard lindsay]

Its just able to stop the gastro side effects, thats why i posted it so you can take the level of PD4 inhibition higher.

Agreed but the anticholinergic + H1 antagonism is troubling. The study is interesting but the demyelination risk kills it for me.

What would pose a risk for demyelination?

Meclazine, because it reduces H1 receptor signaling could theoretically have a risk of demyleination. Luckily, Meclazine has nothing to do with the stack except theoretically preventing vomiting side effects from research chemicals (Rolipram) that no one on the thread is taking. A promising synthetic PDE4 inhibitor without vomiting side effects is GERB-7b. Less exotic and far cheaper PDE4 inhibitors that have not been explored yet are Biochanin-A and Mesembrine (from Kanna). Artichoke extract (mainly Luteolin) is the one people have had the most success with so far.

Edited by abelard lindsay, 11 February 2013 - 02:01 AM.

[abelard lindsay]

I tried forskolin + artichoke extract today, one pill of each of the brands frequently mentioned in this thread.

I combined it with Monster Energy Absolutely Zero, which has a ginseng blend. I also smoked cigarettes.

At the first three hours it was quite great. Good mental energy and focus, but after that it was a disaster. Anxiety, hyperstimulation, and extreme rumination. Even now 10 hours post-dosing I am still trying to calm down and feel better. Even one beer didnt help significantly.

Best of luck to the rest.

My best guess for why the stack didn't work out for you would be the nicotine. We've had a lot of reports about the stack potentiating stimulants so the cigarettes might have had a much stronger effect than you usually experience.

[peakplasma]

<p>Demyelination risk? must have missed something better avoid that as the plague too.</p>

What would pose a risk for demyelination?

Sorry I was referring to the link between H1 antagonism and demyelination (see Abelard's response).

Reducing the nausea to use stronger PDE4 inhibitors seems a worthy path to explore... I have had good results with ginger.

[fenra]

I tried forskolin + artichoke extract today, one pill of each of the brands frequently mentioned in this thread.

I combined it with Monster Energy Absolutely Zero, which has a ginseng blend. I also smoked cigarettes.

At the first three hours it was quite great. Good mental energy and focus, but after that it was a disaster. Anxiety, hyperstimulation, and extreme rumination. Even now 10 hours post-dosing I am still trying to calm down and feel better. Even one beer didnt help significantly.

Best of luck to the rest.

My best guess for why the stack didn't work out for you would be the nicotine. We've had a lot of reports about the stack potentiating stimulants so the cigarettes might have had a much stronger effect than you usually experience.

Didn't nicotine nullify the effects of LTP? Oh, and you did not add a dopamine precursor to the stack...

Edited by fenra, 11 February 2013 - 02:42 PM.