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Vinpocetine -- Ditch It


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#1 luv2increase

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Posted 29 July 2008 - 07:03 PM


I have come to the conclusion that vinpocetine should be eradicated from our supplement stashes. This is due in light of evidence brought about by "dopamine" who is now posting more frequently on our boards.


This is taken from M & M, a thread started by dopamine.

Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the alkaloid vincamine (from the periwinkle plant vinca minor) and has cerebral blood-flow enhancing (1) and voltage sensitive Na+ channel inhibiting properties (2), leading to it's use as a drug in Hungary, Germany and Russia in the treatment of cerebrovascular dementia and Alzheimer's disease (3). Vinpocetine has also become popular supplement in the United States, and is often marketed to otherwise healthy individuals for improvement of memory and self-treatment of age-associated memory decline. Though the specific mechanism of action of vinpocetine has not been fully elucidated, effects on the dopaminergic system have been scarcely investigated.

Trejo F et al, 2001 reported on the "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings" and found that vinpocetine increases DOPAC release, while simultaneously decreasing vesicular dopamine storage in a similar fashion as reserpine - an indole alkaloid with antipsychotic and antihypertensive properties with some structural similarities to vinpocetine (4). The authors report in the results section that "vinpocetine at increasing concentrations progressively decreases internal DA and increases DOPAC release" and "markedly inhibits DAT-mediated release of endogenous DA." (5)

The effects of vinpocetine on DA and DOPAC levels are not believed to be related to the well-demonstrated inhibitory effects on voltage sensitive Na+ channels, as "vinpocetine increases DOPAC release independently of the state of presynaptic VSSC." A possible MAO-A enhancing mechanism is ruled out "as vinpocetine fails to modify the inhibition of DOPAC formation caused by clorgyline" - a potent inhibitor of MAO-A, "indicating that a reserpine-like mechanism is involved in the vinpocetine-induced increase in DOPAC formation." (6)

If vinpocetine does indeed act in a "reserpine-like" fashion in striatal dopaminergic neurons, one could legitimately raise concern over the use of vinpocetine in otherwise healthy individuals for "cognitive enhancement," as side effects may manifest consistent with reserpine-like side effects, including depression and cognitive dysfunction (7, 8). Because resperine inhibits VMAT-2, the protein primarily responsible for the transportation of monoamines from the cytosol to synaptic vesicles, the amount of dopamine, norepinephrine and serotonin stored in neurons may be substantially decreased pre-synaptically by vinpocetine, leading to a downregulation of monoaminergic tone.

In other words, while vinpocetine may be neuroprotective under some experimental and clinical conditions, it may also interfere with monoamine storage, and affect the way in which the brain responds to drugs acting through dopaminergic, adrenergic, or serotonergic pathways (e.g. amphetamine, modafinil, methylphenidate, cocaine, SSRIs, bupropion, etc). Serious consideration should be given before taking vinpocetine, as it is a highly active pharmacological agent that interacts and interferes with a wide array of brain systems and functions.

1. Szilágyi G, Nagy Z, Balkay L, Boros I, Emri M, Lehel S, Márián T, Molnár T, Szakáll S, Trón L, Bereczki D, Csiba L, Fekete I, Kerényi L, Galuska L, Varga J, Bönöczk P, Vas A, Gulyás B. "Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study." Journal of Neurological Sciences 2005 Mar 15;229-230:275-84. Epub 2005 Jan 8. PMID: 15760651. [abstract]

2. Sitges M, Galván E, Nekrassov V. "Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes." Neurochemistry International 2005 Jun;46(7):533-40. PMID: 15843047. [abstract]

3. "Vinpocetine. Monograph." Alternative Medicine Review 2002 Jun;7(3):240-3, pp. 240. PMID: 12126465. [full text]

4. Trejo F, Nekrassov V, Sitges M. "Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings." Brain Research 2001 Aug 3;909(1-2):59-67. PMID: 11478921. [abstract]

5. Ibid, pp. 61.

6. Ibid, pp. 64.

7. Huffman JC, Stern TA. "Neuropsychiatric consequences of cardiovascular medications." Dialogues in Clinical Neuroscience 2007;9(1):29-45. PMID: 17506224. [abstract]

8. Cai JX, Ma YY, Xu L, Hu XT. "Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine." Brain Research 1993 Jun 18;614(1-2):191-6. [abstract]


Then I noticed through researching studies that vinpocetine has a negative impact on the NMDA receptors and the AMPA receptors. These are two very important receptor systems that substances claimed of being nootropics should elicit a positive affect on or no affect at all. Here are two studies which show vinpocetine have a negative affect on them, I THINK!

Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding.
Kaneko S, Sugimura M, Inoue T, Satoh M.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

The effects of several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.

PMID: 1652446 [PubMed - indexed for MEDLINE]


AND THIS ONE FOR AMPA

Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies.
Kiss B, Cai NS, Erdö SL.

Pharmacological Research Centre, Gedeon Richter Ltd., Budapest, Hungary.

The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.

PMID: 1687679 [PubMed - indexed for MEDLINE]



What do you all think? Dopamine, what are your thoughts on the studies I brought up and vinpocetine as a whole for its use in healthy individuals?


edit: I would like to add that I am down to 25mg of tramadol twice daily now. I was doing this just for health (tapering down to get off completely) then yesterday I found out that tramadol is an NMDA antagonist!!!!! No wonder why my memory has been so screwy as of late! Within a few days, I will be off completely. I also got a script for adderall last week, yet I only took a couple pills and decided against taking them. I figure I'd get BETTER, HEALTHIER results by just going about it the NATURAL, HEALTHY way.... This is of course in regards to combating my diagnosed inattentive-type ADD without hyperactivity and most importantly having phenomenal cognitive capabilities indefinitely throughout my immortal lifetime... :)

Edited by luv2increase, 29 July 2008 - 07:25 PM.

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#2 brotherx

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Posted 30 July 2008 - 08:26 AM

Hi,

thanks for posting - good to know!

Cheers

Alex



This is taken from M & M, a thread started by dopamine.

Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the alkaloid vincamine (from the periwinkle plant vinca minor) and has cerebral blood-flow enhancing (1) and voltage sensitive Na+ channel inhibiting properties (2), leading to it's use as a drug in Hungary, Germany and Russia in the treatment of cerebrovascular dementia and Alzheimer's disease (3). Vinpocetine has also become popular supplement in the United States, and is often marketed to otherwise healthy individuals for improvement of memory and self-treatment of age-associated memory decline. Though the specific mechanism of action of vinpocetine has not been fully elucidated, effects on the dopaminergic system have been scarcely investigated.



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#3 hamishm00

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Posted 30 July 2008 - 10:36 AM

I ditched vinpo about 8 months ago, as I found it completely ineffective as a noot.
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#4 dopamine

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Posted 30 July 2008 - 05:52 PM

Vinpocetine isn't a very effective nootropic for otherwise "healthy" individuals, as the primary mechanism of action relates to an overall decrease in neuronal excitability. The effects of vinpocetine on the brain are useful in certain conditions, like alzheimer's or certain forms of epilepsy, but probably doesn't provide any extra benefit to those seeking "cognitive enhancement."

The reserpine link with vinpocetine provides, as far as I can find, the best evidence of the effects of vinpocetine on monoamine metabolism. Like most "nootropics," vinpocetine is woefully under-researched for the purposes of enhancing cognition, and the evidence for a beneficial effect in brain disorders is suggestive at best. Nevertheless some find it useful, and achieve a positive effect, which I don't discount. But this is a case in which we simply do not know enough to draw solid conclusions on the efficacy and safety of vinpocetine.
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#5 edward

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Posted 31 July 2008 - 05:17 AM

I've never liked vinpocetine, and have mentioned this on here many times.
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#6 russianBEAR

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Posted 26 August 2009 - 11:43 PM

Being on vinpocetine was like an all-day-long psychedelic trip with tons of surprises.

I could never get a stable effect out of it, taking large doses. Take some one time and you're alert and ready to go to work. After an hour or two you're compeltely fried, with brain fog, wanting to lie down and rest as if you just took huge amounts of serotonergic something or other.

Then you take some more and you get even more sleepy and incapable. Or you start off barely feeling anything then you feel super alert later.

Not to mention the nightmares I had on that stuff, still gives me shivers down my spine thinking about it now. 

So it never really worked well for me. My grandma was taking it for a while (she's 80+ and takes loads of noots, drinks coffee every day for 60 years or so) and it helped her a whole lot. She had to stop because it's interfering with her arrythmia medication though.



That's about all I know about this substance - I'll never touch it again, it's not your classic conventional noot, and it's way too unpredictable and has severe side effects which go way beyond what you get from any noot.

#7 Animal

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Posted 10 September 2009 - 05:13 PM

First post here, but anyway...

I'm glad I read this thread before resuming my usage of vinpocetine following a brief hiatus. I suffer from dysthymia, and while some days are better then others I definitely noticed an exacerbation of the symptoms during my usage of vinpocetine. My mood was utterly flat, and I couldn't enjoy anything, even the usual things that bring me a brief respite from the low mood, such as watching a good film.

It was a horrible state to be in, and since stopping the vinpocetine 4 days ago I definitely feel better, although the subdued state of mind is lingering. I was considering resuming my usage of it today, because I had almost convinced myself that another supplement I was taking was responsible for the negative effects. Now I've read this thread I'll just avoid it.

I do suffer from bad circulation though, my extremities are almost always cold and I figured this was partly responsible for the fatigue (mental and physical) I suffer from. If anyone can recommend any other supplements that improve circulation (apart from Gingko and Aspirin) I would really appreciate it, thanks!

#8 3VeRL0ng

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Posted 10 September 2009 - 05:34 PM

Vinpocetine -- Ditch It


Already did, I react(ed) horribly to it, as well as all other vasodilators.
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#9 tunt01

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Posted 10 September 2009 - 06:38 PM

I do suffer from bad circulation though, my extremities are almost always cold and I figured this was partly responsible for the fatigue (mental and physical) I suffer from. If anyone can recommend any other supplements that improve circulation (apart from Gingko and Aspirin) I would really appreciate it, thanks!


- maybe consider proanthocyanidins that are found in fruits like blueberries, grapes. horse chestnut also may be an option.
- green tea works wonders.


i looked at vinpocetine when i was playing with alpha-gpc, piracetam and a few other noots. i never found vinpocetine that appealing. "viagra for the brain" is not a good strategy for LT health.

#10 Algear Linebra

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Posted 10 September 2009 - 10:32 PM

No nootic effect on me, just physical "side" effects.. I've ditched it already because of my own conclusions. Haven't read anything negative about it until i found this thread..

Edited by Algear Linebra, 10 September 2009 - 10:34 PM.


#11 nito

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Posted 10 September 2009 - 11:05 PM

I do suffer from bad circulation though, my extremities are almost always cold and I figured this was partly responsible for the fatigue (mental and physical) I suffer from. If anyone can recommend any other supplements that improve circulation (apart from Gingko and Aspirin) I would really appreciate it, thanks!


- maybe consider proanthocyanidins that are found in fruits like blueberries, grapes. horse chestnut also may be an option.
- green tea works wonders.


i looked at vinpocetine when i was playing with alpha-gpc, piracetam and a few other noots. i never found vinpocetine that appealing. "viagra for the brain" is not a good strategy for LT health.




Hi! What wonderwork does green tea do? I'm thinking of buying it for depression and energy but not sure if its all that effective.

#12 Animal

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Posted 13 September 2009 - 03:31 AM

I do suffer from bad circulation though, my extremities are almost always cold and I figured this was partly responsible for the fatigue (mental and physical) I suffer from. If anyone can recommend any other supplements that improve circulation (apart from Gingko and Aspirin) I would really appreciate it, thanks!


- maybe consider proanthocyanidins that are found in fruits like blueberries, grapes. horse chestnut also may be an option.
- green tea works wonders.


i looked at vinpocetine when i was playing with alpha-gpc, piracetam and a few other noots. i never found vinpocetine that appealing. "viagra for the brain" is not a good strategy for LT health.




Hi! What wonderwork does green tea do? I'm thinking of buying it for depression and energy but not sure if its all that effective.


Well I intend to buy some on Monday to experiment with, I'll let you know how it goes. Oh and thanks Prophets for the recommendation.

#13 protoject

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Posted 17 September 2009 - 12:33 AM

I have no particular aversion to Vinpocetine's mental effects but did experience acute agranulocytosis due to taking it, which really SUCKS balls. Not sure if it's very common but it has been noted in medical literature as well.
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#14 kismet

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Posted 17 September 2009 - 10:38 PM

I have no particular aversion to Vinpocetine's mental effects but did experience acute agranulocytosis due to taking it, which really SUCKS balls.

I thought it is a pretty rare side-effect. Can you explain the diagnosis, treatment and prognosis? I'm not sure what exactly the implications of agranulocytosis are and how one makes a recovery, maybe you can share your experience. I'm very interested in the side-effects of vinpo.

Edited by kismet, 17 September 2009 - 10:38 PM.


#15 WMC

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Posted 24 October 2009 - 04:06 PM

I wanted to post my adverse reaction to vinpocetine because after thorough searching on the internet I came across very few stories of bad reactions to this supposed safe nootropic. I was attracted to it looking for something that would help my perimenopause brainfog and offer help for mild depression. After taking 2.5 mg for 6 days, I experienced an increasingly bad headache, dizziness, hot flashes and insomnia. I felt oddly wired and had trouble thinking clearly. I have stopped it for a day and a half now and am still coming down from it. I slept for 12 hours (extremely unusual for me), awoke dizzy with a throbbing migraine. I am occasionally sensitive to medication - I can't take any of the ssri's. Supposedly I am what's known as a "poor metabolizer."

Edited by WMC, 24 October 2009 - 04:10 PM.


#16 Animal

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Posted 27 October 2009 - 06:23 PM

I have no particular aversion to Vinpocetine's mental effects but did experience acute agranulocytosis due to taking it, which really SUCKS balls.

I thought it is a pretty rare side-effect. Can you explain the diagnosis, treatment and prognosis? I'm not sure what exactly the implications of agranulocytosis are and how one makes a recovery, maybe you can share your experience. I'm very interested in the side-effects of vinpo.


The implications are an extreme vulnerability to pathological disease. I'm interested in how exactly you were diagnosed with agranulocytosis, considering the primary symptoms are indistinguishable from influenza until it progresses to a more life threatening stage. Were you having a complete blood count for unrelated reasons?

I assume what you really mean is that you had a temporary reduction in immune function, since agranulocytosis is a fairly severe disease condition that would require monitoring in a hospital.

Edited by Animal, 27 October 2009 - 06:24 PM.

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#17 agwoodliffe

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Posted 12 May 2010 - 08:52 PM

Oh shit. I've been taking 10mg for 2 whole months! Is Vinpocetine's effect on VMAT reversible?

#18 Imagination

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Posted 12 May 2010 - 09:04 PM

I had such good results with it initially, no other nootropic quite compared, but now it just seems to make me knackered, with no real noticable cognitive benifits either. Using the same brand too, darn! Back to the drawing board...again.

#19 agwoodliffe

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Posted 13 May 2010 - 05:31 PM

I really think that 'luv2increase' and 'Dopamine' are spot on about this. Until 2 days ago, I had been taking 10mg Vinpocetine daily for about 2 months. Over those 2 months, my mood gradually started to deteriorate, and I couldn't understand why. I thought that maybe my antidepressant medication was simply losing its effectiveness. However, about 2 days ago, I read the information posted by 'Dopamine' and 'luv2increase' and decided to stop taking Vinpocetine. Already, 2 days later, my mood has returned completely to normal.
That suggests to me that Vinpocetine DOES behave like Reserpine in inducing depression, albeit with a weaker and more reversible effect.
I agree with 'luv2increase' - Vinpocetine ain't worth it.

#20 nito

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Posted 14 May 2010 - 06:50 AM

i seem to become more angry when i take it lol.

#21 Guacamolium

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Posted 14 May 2010 - 09:04 AM

Well I was one of the non-responders to it other than one batch out of maybe 4 or so, but as of last year I always wondered what potential vincamine would have had if vinpocetine wouldn't have stepped in and stolen the spotlight.

#22 medievil

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Posted 14 May 2010 - 10:10 AM

agranulocytosis due to taking it? Damn that could end lethal, this stuff is pretty nasty.

#23 Guacamolium

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Posted 15 May 2010 - 02:33 AM

But what about Vincamine, Dopamine and Luv2increase? Since Vinpocetine has stolen its availability, should we pursue vincamine in lieu of vinpocetine, or what?

Good topic.

#24 agwoodliffe

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Posted 27 May 2010 - 09:44 AM

To anyone that is interested, I've actually been able to get ahold of the FULL report of 'Vinpocetine and DA & DOPAC release' from sciencedirect.com (since all University students are allowed to view all scientific documents for free!).
I've attached a copy of the report with the extension '.rftd' If you're unable to open this type of file, just let me know in a reply & I'll convert it. Enjoy!

Attached Files



#25 Furbix

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Posted 06 June 2010 - 11:21 PM

Recently started taking it and noticed instances of depression cropping up. Also I have an old injury that is made worse by aspirin but vinpocetine does nothing to it, instead I get a dull ache in the right side of my right knee where I have sustained no injury.

Does it have any utility for anything or should I just throw it away? How about taking it with a pre-workout drink, I've noticed it in several supplements that's why I ask.

#26 AtomicMan

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Posted 25 June 2010 - 03:27 AM

First, I wish to thank luv2increase for bringing this information to our attention. Still, I respectfully disagree with the majority of what has been said about vinpocetine above. There are numerous studies on its effectiveness, and it is recommended by Terry Grossman, M.D. and Ray Kurzweil in both Fantastic Voyage (2004) and Transcend (2009). The changes to the DA/DOPAC axis discussed in the Francisco Trejo article do not seem to me to outweigh the supplement's advantages. I do not, however, understand the significance of the NMDA studies.
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#27 gcurrie

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Posted 10 September 2010 - 07:51 PM

I've been taking it pretty much non-stop for over six years, between 10-20 mg daily.

I notice a decrease in clarity when I temporarily stop.

Absolutely no negative side effects that I have noticed.

However, I may cycle off and re-evaluate based on this information.

This, 2.5 mg of deprenyl and piracetam and/or aniracetam have been my daily regimen since 2004.
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#28 KimberCT

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Posted 10 September 2010 - 09:29 PM

I can't believe I missed this thread for so long!

Vinpocetine seems like it may have potential use for folks with cognitive problems (brain fog) due to anxiety.



#29 Pike

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Posted 10 September 2010 - 10:06 PM

Vinpocetine seems like it may have potential use for folks with cognitive problems (brain fog) due to anxiety.


i'll throw my personal experience in and say that it has the exact opposite effect. if anything, the revamped metabolization of dopamine and pro-depressant qualities of it only go to make anxiety worse.

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#30 NR2(x)

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Posted 10 September 2010 - 10:08 PM

I worry that vinpocetine has a antagonist action on the dopamine-1 cascade which would decrease working memory in most people. The metabolic effects are quite pronounced and therefore there are nootropic effects




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