21 replies to this topic

[peakplasma]

I recently took 100mg Modafinil with CILTEP I had overwhelming nausea with no other positive effects.

After some research I found a study suggesting Modafinil may increase cAMP-dependent PKA similar to Forskolin. See below...

Modafinil inhibits K_Ca3.1 currents and muscle contraction via a cAMP-dependent mechanism

Abstract

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K_Ca3.1 channels and vascular smooth muscle contraction. K_Ca3.1 currents and channel activity were measured using a voltage-clamp technique and inside-out patches in mouse embryonic fibroblast cell line, NIH-3T3 fibroblasts. Intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) concentration was measured, and the phosphorylation of K_Ca3.1 channel protein was examined using western blotting in NIH-3T3 fibroblasts and/or primary cultured mouse aortic smooth muscle cells (SMCs). Muscle contractions were recorded from mouse aorta and rat pulmonary artery by using a myograph developed in-house. Modafinil was found to inhibit K_Ca3.1 currents in a concentration-dependent manner, and the half-maximal inhibition (IC₅₀) of modafinil for the current inhibition was 6.8 ± 0.7 nM. The protein kinase A (PKA) activator forskolin also inhibited K_Ca3.1 currents. The inhibitory effects of modafinil and forskolin on K_Ca3.1 currents were blocked by the PKA inhibitors PKI_14–22 or H-89. In addition, modafinil relaxed blood vessels (mouse aorta and rat pulmonary artery) in a concentration-dependent manner. Modafinil increased cAMP concentrations in NIH-3T3 fibroblasts or primary cultured mouse aortic SMCs and phosphorylated K_Ca3.1 channel protein in NIH-3T3 fibroblasts. However, open probability and single-channel current amplitudes of K_Ca3.1 channels were not changed by modafinil. From these results, we conclude that modafinil inhibits K_Ca3.1 channels and vascular smooth muscle contraction by cAMP-dependent phosphorylation, suggesting that modafinil can be used as a cAMP-dependent K_Ca3.1 channel blocker and vasodilator.

Unfortunately, i do not have access to the full article nor do I fully understand its implications... but I would be interested to know if Modafinil could be cycled with Forskolin in CILTEP.

Can anyone provide additional insight or their experiences?

For the record, I've taken daily Forskolin(10mg)+Artichoke(500mg) for over a month with very positive effects (along with l-Deprenyl (0.75mg) for over a year)

Thanks!

[peakplasma]

Sorry for posting twice but here is a fascinating study discussing Modafinil-induced LTP with comparison to Forskolin-induced LTP.

This article seems to suggest permanent negative effects from modafinil LTP.... is that right? It seems a bit mixed at least...

Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons

Sleep is a natural process that preserves energy, facilitates development, and restores the nervous system in higher animals. Sleep loss resulting from physiological and pathological conditions exerts tremendous pressure on neuronal circuitry responsible for sleep-wake regulation. It is not yet clear how acute and chronic sleep loss modify neuronal activities and lead to adaptive changes in animals. Here, we show that acute and chronic prolonged wakefulness in mice induced by modafinil treatment produced long-term potentiation (LTP) of glutamatergic synapses on hypocretin/orexin neurons in the lateral hypothalamus, a well-established arousal/wake-promoting center. A similar potentiation of synaptic strength at glutamatergic synapses on hypocretin/orexin neurons was also seen when mice were sleep deprived for 4 hours by gentle handling. Blockade of dopamine D1 receptors attenuated prolonged wakefulness and synaptic plasticity in these neurons, suggesting that modafinil functions through activation of the dopamine system. Also, activation of the cAMP pathway was not able to further induce LTP at glutamatergic synapses in brain slices from mice treated with modafinil. These results indicate that synaptic plasticity due to prolonged wakefulness occurs in circuits responsible for arousal and may contribute to changes in the brain and body of animals experiencing sleep loss.

In the above article, scroll down below Figure 4 to read about For-LTP (Forskolin dependent-LTP).

Activity-dependent synaptic plasticity occurs in hypocretin/orexin neurons.
We tested the ability of forskolin to induce LTP in hypocretin/orexin neurons to determine the mechanisms underlying the synaptic potentiation resulting from prolonged wakefulness. Bath application of forskolin, an activator of adenylyl cyclase, induces LTP at all synapses on neurons in the hippocampus (42–45). The forskolin-induced LTP (For-LTP) is PKA dependent, and the PKA cascade is right downstream to the activation of the D1 dopamine receptor (39, 43, 44). Bath application of forskolin for 10 minutes induced a long-lasting potentiation of spike firing in hypocretin/orexin neurons (Figure 5). This potentiation persisted for the duration of the experiment (more than 1 hour; n = 5; Figure 5A). For-LTP is dose dependent and can be observed at a concentration as low as 1 μM (Figure 5B). In slices pretreated with a membrane-permeable PKA inhibitor, KT5720 (20 μM), For-LTP of spike frequency was largely blocked (116.7% ± 15.4% of baseline; n = 7; P > 0.05; Figure 5C).

Forskolin (50 μM) also induced LTP of mEPSC frequency in hypocretin/orexin neurons

I'm not sure if this good or bad honestly... I am actually having a really difficult time navigating these results!

Edited by peakplasma, 25 November 2012 - 08:15 PM.

[alecnevsky]

Great finds! In regards to the latter, I think any effects (despite whatever modafinil-induced potentiation) of sleep deprivation are harmful in virtue of sleep deprivation alone. It seems like this study just says that hypothalamus is potentiated by modafinil in sleep-deprived conditions. At least that's how I interpreted the abstract.

EDIT: I actually checked out the article(thought it was only a pubmed abstract) and found some elucidation here :

Chronic administration of modafinil induced synaptic plasticity in hypocretin/orexin neurons, as measured by increased synaptic strength and increased number of synapses on hypocretin/orexin-containing perikarya (Figure 2), suggesting that prolonged wakefulness over several days leads to reorganization of excitatory synapses on hypocretin/orexin neurons. This type of synaptic reorganization has also been observed following food deprivation.

I think it's more interesting to see what modafinil does in non-sleep deprived brains though. (That is, to the point that the brain on modafinil is not yet sleep-deprived.)

I've been on CILTEP for 1.5 months and have both, modafinil and armodafinil coming as we speak so I'll keep these studies in mind and update within a week. Thanks for pointing this out!

Edited by alecnevsky, 25 November 2012 - 08:15 PM.

[peakplasma]

Chronic administration of modafinil induced synaptic plasticity in hypocretin/orexin neurons, as measured by increased synaptic strength and increased number of synapses on hypocretin/orexin-containing perikarya (Figure 2), suggesting that prolonged wakefulness over several days leads to reorganization of excitatory synapses on hypocretin/orexin neurons. This type of synaptic reorganization has also been observed following food deprivation.

This is very interesting since I have read that dietary restriction can contribute to neurogenesis (positive effect i don't know)...
Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mi1ce
Neuroprotective signaling and the aging brain: take away my food and let me run.
DR might also enhance neurogenesis, synaptic plasticity and self-repair mechanisms.

But I digress...

In the excerpt below am I misunderstanding the context of "occlusion"?

It is suggested in this study that LTP can be elicited following intensive activation of neuronal ensembles centered on hypocretin/orexin neurons (Figure 6). Occlusion of LTP has been observed following regimens that might be expected to result in experience-dependent synaptic plasticity, such as training in a novel task or administration of drugs of abuse (24, 25). The occlusion of For-LTP in hypocretin/orexin neurons by modafinil treatment indicates that the molecular and cellular machinery responsible for LTP (in particular the PKA-dependent pathways downstream to D1 receptor activation) contribute to experience-dependent synaptic plasticity following prolonged wakefulness (Figures 7 and 8).

I'm more confused now! This does not seem to be a positive finding!

Edited by peakplasma, 25 November 2012 - 09:02 PM.

[alecnevsky]

It seems their argument is essentially: this particular modafinil treatment causes experience-dependent synaptic plasticity via hypocretin/orexin neurons just like in food deprivation/drugs etc, but, administered with Forskolin, it [modafinil treatment] occludes the LTP machinery of Forskolin-LTP, therefore Forskolin LTP has, also, an (some) effect on state-dependent plasticity under conditions of sleep deprivation. I can only speculate though... this is like another language to me!


I think the point is: we know both For and Mod. affect synaptic plasticity. Mod. potentiates hypothalamus during prolong wakefullness. But what does For-LTP do? Well if we administer both, then one occludes the other. So then, For-LTP also affects plasticity under prolong wakefullness like Mod. otherwise Mod. would not have affected its potentiation machinery.

Edited by alecnevsky, 25 November 2012 - 09:46 PM.

[peakplasma]

It seems their argument is essentially: this particular modafinil treatment causes experience-dependent synaptic plasticity via hypocretin/orexin neurons just like in food deprivation/drugs etc, but, administered with Forskolin, it [modafinil treatment] occludes the LTP machinery of Forskolin-LTP, therefore Forskolin LTP has, also, an (some) effect on state-dependent plasticity under conditions of sleep deprivation. I can only speculate though... this is like another language to me!


I think the point is: we know both For and Mod. affect synaptic plasticity. Mod. potentiates hypothalamus during prolong wakefullness. But what does For-LTP do? Well if we administer both, then one occludes the other. So then, For-LTP also affects plasticity under prolong wakefullness like Mod. otherwise Mod. would not have affected its potentiation machinery.

It seems you are quite right!

From the Wikipedia article on LTP....

In 2006, Jonathan Whitlock and colleagues reported on a series of experiments that provided perhaps the strongest evidence of LTP's role in behavioral memory, arguing that to conclude that LTP underlies behavioral learning, the two processes must both mimic and occlude one another.

So it seems that Modafinil-LTP can substitute Forskolin-LTP, I am just wondering if this type of LTP is conducive to learning. I will keep searching for new articles...

[abelard lindsay]

But I digress...

In the excerpt below am I misunderstanding the context of "occlusion"?

It is suggested in this study that LTP can be elicited following intensive activation of neuronal ensembles centered on hypocretin/orexin neurons (Figure 6). Occlusion of LTP has been observed following regimens that might be expected to result in experience-dependent synaptic plasticity, such as training in a novel task or administration of drugs of abuse (24, 25). The occlusion of For-LTP in hypocretin/orexin neurons by modafinil treatment indicates that the molecular and cellular machinery responsible for LTP (in particular the PKA-dependent pathways downstream to D1 receptor activation) contribute to experience-dependent synaptic plasticity following prolonged wakefulness (Figures 7 and 8).

I'm more confused now! This does not seem to be a positive finding!

"occlude" means to block. Modafinil blocked Forskolin LTP in hypocretin/orexin neurons. It must be taken into account that cAMP signaling is very compartmentalized and that the LTP process was only blocked in these neurons and not more widely in the brain.

http://www.ncbi.nlm....pubmed/20800665

The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

So Modafinil is alterting cAMP metabolism in different areas of the brain, we know that from the previous study (http://www.ncbi.nlm....pubmed/22414869) and it is preventing LTP induction in the prefrontal cortex which is where most of the positive activity of PDE4 inhibition takes place, for example:

http://www.ncbi.nlm....pubmed/23003922

RNA interference-mediated phosphodiesterase-4D splice variants knockdown in the prefrontal cortex produces antidepressant-like and cognition-enhancing effects.

and http://www.ncbi.nlm....pubmed/21833500

Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA/DARPP-32 signaling cascade in frontal cortex.

The nausea inducing PDE4 receptors are in the solitary nucleus (http://en.wikipedia....olitary_nucleus)

http://www.ncbi.nlm....pubmed/16901513

These findings suggest that PDE4 inhibitors produce emesis by increasing NK(1) receptor activation in the AP/NTS (Solitary Nucleus)

So maybe CILTEP activity is being blocked in the prefrontal cortex by modafinil and being enhanced in other parts of the brain like the AP/NTS and that caused nausea in the OP? Anyway, doesn't seem like the two really go together all that well.

Edited by abelard lindsay, 26 November 2012 - 03:15 PM.

[peakplasma]

Thanks Abelard for the input.

My confusion regarding the context of occlusion was the comment in the study that suggested Modafinil occluded LTP in the same manner observed when "training in a novel task". I assumed "training a novel task" with CILTEP would enhance the Forskolin-induced LTP rather than blocking it.

These findings suggest that PDE4 inhibitors produce emesis by increasing NK(1) receptor activation in the AP/NTS (Solitary Nucleus)

So maybe CILTEP activity is being blocked in the prefrontal cortex by modafinil and being enhanced in other parts of the brain like the AP/NTS and that caused nausea in the OP? Anyway, doesn't seem like the two really go together all that well.

Sounds like a good thesis. Based on my nausea I would agree that it may be a sub-optimal combination.

[alecnevsky]

I am just going to paste the abstract of the study Aberald referenced that I find pretty critical here :

Chronic modafinil did not significantly modify working memory errors but decreased long-term memory errors on the Olton 4×4 maze, meaning that the drug may have a favourable profile on performance of visuo-spatial tasks (typically, a hippocampus-dependent task) when chronically administered. On the other hand, chronic modafinil resulted in a marked decrease of successful responses in a complex operant conditioning learning, which means that repeated administration of the drug influences negatively problem-solving abilities when confronting the rat to a sequencing task (typically, a prefrontal cortex-dependent task). In addition, in vivo electrophysiology showed that modafinil resulted in impaired capacity of the rat prefrontal cortex to develop LTP following tetanization. It is concluded that modafinil can improve the performance of spatial tasks that depend almost exclusively on hippocampal functioning, but not the performance in tasks including a temporal factor where the prefrontal cortex plays an important role. The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

I think that answers some of my question of modafinil's effects on a non-sleep-deprived brain. So a better mathematician but a but a terrible manager? Lol.

Edit: Which, actually, in terms of just studying and passing exams could not be at all bad...Although I am not sure how much of prefrontal cortex is involved in abstract manipulation and math that is not rote arithmetic. Is there much of prefrontal cortex "problem solving" in abstract manipulation of symbols? I wonder... Also, aren't visuospatial tasks a function of parietal lobe, no? So this could in fact, not make you better in abstract symbol manipulation and make you a worse problem solver, in long term... What's the deal?

I am going to link this before my "editing window" expires:

"Modafinil significantly reduced error rates in the long delay condition of
the visuo-spatial task and in the manipulation conditions,
but not in the maintenance condition of the numeric task.
Analyses of reaction times showed no speed-accuracy
trade-off. Attentional control tasks (letter cancellation,
trail-making, catch trials) were not affected by modafinil.
Conclusions: In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult
and monotonous working memory tasks, especially in
lower performing subjects. Overlapping attentional and
working memory processes have to be considered when
studying the noradrenergic modulation of the prefrontal
cortex."

http://www.gwern.net...004-mueller.pdf

Edited by alecnevsky, 26 November 2012 - 06:43 PM.

[alecnevsky]

Bump. I am still thinking about this:

"The fact that modafinil together with preventing operant conditioning learning was also able to block LTP induction in the prefrontal cortex, suggests that the drug could interfere some critical component required for LTP can be developed, thereby altering neuroplastic capabilities of the prefrontal cortex.

Versus this:

"In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks, especially in lower performing subjects."

And, I am tentatively concluding that, while modafinil improves working memory (esp. visuo-spacial) in the short term, its long term effects are a concern.

But, what about this then:

Our results demonstrate that spatial attention and choice decisions followed different strategies of probabilistic information selection on placebo, but that modafinil brought the pattern of spatial attention into alignment with that of predictive choices. Modafinil also enhanced learning of the probability distribution, evidenced by earlier learning of the probability distribution. Together, these results suggest that enhancing cognitive control mechanisms (e.g., through prefrontal cortical function) leads spatial attention to follow choice decisions in selecting information according to rule-based expectations.

http://www.ncbi.nlm....pubmed/23190326

Admittedly, I cannot understand what they're talking about... It seems like they're suggesting improvements in prefrontal cortex function via modafinil in the short term. But so then, why should it lead to conclusions of first quote, namely, that modafinil in the long term leads to "altering neuroplastic capabilities of the prefrontal cortex"

Could it be because of it alters the reward mechanism like other stimulants:

"The findings lead to the conclusion that protracted exposure to these cognitive enhancers [edit:modafinil included] can induce gene regulation effects in corticostriatal circuits that are qualitatively similar to those of cocaine and other amphetamines."

http://www.ncbi.nlm.nih.gov/pubmed/23085425


And, apparently, corticostriatal circuits are crucial for abstract learning:

"[font=arial, helvetica, 'Ｍ]Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning."[/font]

http://www.nature.co...ature10845.html

But, note that Mueller study says:

"Neither our study nor any other published study has observed impairment of cognitive performance by higher doses of modafinil. This supports clinical observations of relatively safe use and broad “therapeutic window” in patients with various neuropsychiatric diseases (Jasinski 2000; Taylor and Russo 2000; Rugino andCopley 2001; Högl et al. 2002; Rammohan et al. 2002;DeBattista et al. 2003; Talbot et al. 2003; Thorpy et al.2003).

Which doesn't really contradict the long term impairment of cognitive performance in the prefrontal cortex via occlusion of LTP of the first study or the one on addiction induced gene alteration. So, then could large doses taken less than chronically, could actually yield the noticeably enhancing effects in the short term, and no long term deficits if maintained by proper "wash out" periods. (I obviously want this conclusion to be true, so I am not sure how unbiased I am in reasoning thus.)

[fql]

Full article:
http://stimu.org/dow...t mechanism.pdf

[alecnevsky]

Nice. Going to try Armo + PDE tomorrow. Looks like my intuitions were right about not mixing Forskolin with Mod. People who do mix forskolin with Mod are probably experiencing either Modafinil or Forskolin insofar as LTP, not both separately and not both synergistically. Unless I gauged the article wrong.

[peakplasma]

Nice. Going to try Armo + PDE tomorrow. Looks like my intuitions were right about not mixing Forskolin with Mod. People who do mix forskolin with Mod are probably experiencing either Modafinil or Forskolin insofar as LTP, not both separately and not both synergistically. Unless I gauged the article wrong.

I've experimented in the months since this post with ModLTP....(mod-ell-tepp) or (mod-ell-tipp)??

Modafinil has a Forskolin-like cAMP increase so it blends poorly with Forskolin.... but Modafinil + PDE inhibitor is a winner!

What PDE-I are you using?

Edited by peakplasma, 26 March 2013 - 12:28 AM.

[chung_pao]

I've also concluded what peakplasma was suggesting.
Taking modafinil, forskolin and artichoke (PDE-4 inhibitor) is not synergistic. The synergism comes from either using modafinil OR forskolin along with a PDE-I.
Trying to isolate the variables I recently tried only adding artichoke to modafinil, and the effect was surprisingly potent and synergistic.
However, modafinil still has its flaws. It's like it shuts off all my verbal fluency while significantly improving spatial and math abilities. It actually makes reading less enjoyable, and slower...

Edited by chung_pao, 26 March 2013 - 01:18 AM.

[alecnevsky]

Nice. Going to try Armo + PDE tomorrow. Looks like my intuitions were right about not mixing Forskolin with Mod. People who do mix forskolin with Mod are probably experiencing either Modafinil or Forskolin insofar as LTP, not both separately and not both synergistically. Unless I gauged the article wrong.

I've experimented in the months since this post with ModLTP....(mod-ell-tepp) or (mod-ell-tipp)??

Modafinil has a Forskolin-like cAMP increase so it blends poorly with Forskolin.... but Modafinil + PDE inhibitor is a winner!

What PDE-I are you using?

I am just using the rest of my artichoke stash left over from CILTEP dosing (Jarrow 500).

It's like it shuts off all my verbal fluency while significantly improving spatial and math abilities. It actually makes reading less enjoyable, and slower...

There is definitely something to this. Symbols and notation is much easier to interpret, encode, and retrieve but reading text becomes somewhat cumbersome. But! In my case anyway, the reading bit doesn't apply to verbal thought processing as I can still produce fairly careful/comprehensive arguments to my professors etc. The thoughts are definitely more dry and categorical. I stack a few other things with Mod to avoid this zombying out.

[peakplasma]

There is definitely something to this. Symbols and notation is much easier to interpret, encode, and retrieve but reading text becomes somewhat cumbersome. But! In my case anyway, the reading bit doesn't apply to verbal thought processing as I can still produce fairly careful/comprehensive arguments to my professors etc. The thoughts are definitely more dry and categorical. I stack a few other things with Mod to avoid this zombying out.

Did you not get good results from regular CILTEP?

Also, how do you rate ModLTP for analytical thinking? As one study suggests, Modafinil is a great enhancer of "cold cognition" (vs. hot cognition).

[Kowalsteeze]

Modafinil direclty increases NE which will increase the activation of B-adrenergic receptors. B-adrenergic receptors increase cAMP as on of their primary functions. Mind that these effects should be acute until the b-adrenergic receptors downregulate. So modafinil would not be comparable to forskolin for the purpose of ativating PKA consistently.

[peakplasma]

Modafinil direclty increases NE which will increase the activation of B-adrenergic receptors. B-adrenergic receptors increase cAMP as on of their primary functions. Mind that these effects should be acute until the b-adrenergic receptors downregulate. So modafinil would not be comparable to forskolin for the purpose of ativating PKA consistently.

You are correct that Modafinil can increase cAMP indirectly via monoaminergic (NE) action.

However, the if you dig into the research, the OP study suggests that Modafinil may directly increase cAMP via PKA-dependent phosphorylation!!!

The mechanisms of the cAMP-induced decrease in KCa3.1 currents
or in VSM contraction might be PKA dependent. It has been
reported that PKA inhibits KCa3.1 channels by phosphorylation at
its calmodulin-binding domain [20,24]. In addition, it has been
suggested that MLCK is phosphorylated by PKA and that this phosphorylation
reduces the affinity of MLCK for the Ca2+/calmodulin
complex [23]. Therefore, PKA-dependent phosphorylation of these
proteins might inhibit KCa3.1 currents and muscle contraction, and
this might be the mechanism of action of modafinil.

→ source (external link)

PKA-dependent phosphorylation might explain at least in
part the mechanism underlying modafinil-induced wakefulness
and synaptic plasticity in hypocretin neurons. PKA activation by
forskolin-induced long-term potentiation (LTP), and this forskolininduced
LTP was inhibited by modafinil treatment in mice [50],
suggesting that synaptic plasticity induced by modafinil treatment
shares a common pathway, cAMP/PKA stimulation, with
LTP induced by forskolin.

→ source (external link)

You seem intelligent with good grasp of the subject. Can you help us analyze this?

[chziime]

Could someone please post an anecdotal experience about combining Modafinil and Artichoke Extract? What dose of Modafinil did you have to use, and how long does it last?

[xsiv1]

Could someone please post an anecdotal experience about combining Modafinil and Artichoke Extract? What dose of Modafinil did you have to use, and how long does it last?

I've used 100mgs of Moda with the entire CILTEP stack barring any dopamine precursor. I'm not sure what variables played a role in my negative experience with the combination but I've decided it was most likely a sleep deficit. I was yawning and feeling tired all afternoon the day I took the aforementioned first thing in the morning.

[machete234]

Out of my order only the artichoke extract came through so now Im interested what would happen if I combined armodafinil with artichcoke extract.

What will change regarding the effects and will anything change at all?

I've also concluded what peakplasma was suggesting.
Taking modafinil, forskolin and artichoke (PDE-4 inhibitor) is not synergistic. The synergism comes from either using modafinil OR forskolin along with a PDE-I.
Trying to isolate the variables I recently tried only adding artichoke to modafinil, and the effect was surprisingly potent and synergistic.

Could you describe the difference to modafinil solo?
I have no problems with modafinil and verbal fluency for example it could be that talking to people is improved.
Writing sentences down tends to become more of a problem because Im a bit overloaded with grammatical possibilities.

Edited by machete234, 06 December 2013 - 08:08 PM.

[leonidas]

Very interesting conversation topic - sounds like you guys could be on to something.

Its, a few months on - any positive / negative experiences to shed more light on Modifinil / Armodifinl combined with Artichoke Extract?