27 replies to this topic

[FunkOdyssey]

Memantine: The Next Trend in Academic Performance Enhancement?
KEN S. OTA, OMS III; TINA GODWIN, OMS II

Western University of Health Sciences College of Osteopathic Medicine of the Pacific Pomona, Calif

To the Editor: Although memantine hydrochloride is currently known as the latest treatment for moderate-to-severe Alzheimer disease (AD),1 we entertain the idea that it might also come to be known as a memory enhancer among healthy high achievers.

The drug acts by noncompetitively binding to the N-methyl D-aspartate (NMDA) receptors of neurons in brain tissue to prevent overstimulation by glutamate.2 When this excitatory neurotransmitter overactivates NMDA receptors in a tonic manner, an excessive influx of neurotoxic calcium ions follows.2 The resultant excitotoxicity may play a role in the impairment of memory and cognition in AD.3 Because memantine has a low-to-moderate affinity for NMDA receptors, it does not seem to block normal glutamate transmission; rather, it reduces abnormal neurotransmitter-mediated activation of the receptors,4 thereby potentially reducing excitotoxic neuronal damage. This form of neuroprotection may explain the improved cognition in patients with AD reported in the literature.5–7

Can transient low-level, nonpathologic, glutamate-mediated neuronal damage occur in the brains of normal individuals? And, if so, could memantine's neuroprotective effect antagonize the damaging effects and enhance memory potential in these individuals? Future research should address these issues.

Memantine's suggested neuroprotective effect2,8 may also increase brain levels of the neuronal marker, N-acetyl aspartate (NAA). Because NAA is found primarily on neuronal axons in the brain,9 perhaps the neuroprotective effect of memantine can be measured by quantifying the change in NAA concentrations in brain tissue via magnetic resonance spectroscopy. Magnetic resonance spectroscopy has demonstrated that patients with AD show a decline in NAA relative to normal controls.10 The reduction in excitotoxicity via memantine's mechanism of action may allow affected neurons to regain some level of physiologic functioning, such as growth of neuronal processes and synaptogenesis, which is fundamental to learning and memory formation11—a process that is damaged in AD.2

Moreover, a direct relationship has been observed between NAA levels in the brain and intelligence. Healthy individuals with high levels of NAA appear to have higher scores on intelligence tests than healthy individuals with lower levels of this marker in brain tissue.12 It may be possible that the higher levels of NAA indicate an increased presence of neuronal processes and their synapses.

The effects of drugs that have cognitive-enhancing potential have been studied in healthy individuals. Acetylcholinesterase inhibitors (some of which are used to treat AD), such as donepezil, huperzine {alpha}, and physostigmine, have been shown to improve memory and cognitive tasks in normal subjects.13–15 Another medication that enhances cognitive performance is methylphenidate, a drug commonly prescribed for attention deficit hyperactivity disorder (ADHD) but increasingly used by healthy university students nationwide as an academic performance–enhancing agent.16 A recent national survey17 reported that ADHD medications have much higher rates of abuse in colleges with higher admission standards.

In light of all of the mentioned factors and the recent reports regarding the misuse of anabolic-androgenic steroids for the enhancement of athletic performance,18,19 the misuse of memory-enhancing drugs to improve academic performance by some ambitious students may not be a far-fetched conjecture. The purpose of this letter is to raise a medically and ethically relevant question: If transient low-level, nonpathologic, glutamate-mediated neuronal damage can occur in normal brain tissue, and neuroprotection against this occurrence could promote neuroplastic processes such as synaptogenesis, could memantine be misused by students for academic performance-enhancement in the near future?

References
1. Ellis JM. Cholinesterase inhibitors in the treatment of dementia [review]. J Am Osteopath Assoc. 2005;105: 145–158. Available at: http://www.jaoa.org/.../full/105/3/145. Accessed May 10, 2006.

2. Danysz W, Parsons CG. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry.2003; 18(suppl 1):S23 –S32.[Medline]

3. Ashford JW, Mattson M, Kumar V. Nerobiological systems disrupted by Alzheimer's disease and molecular biological theories of vulnerability. In: Kumar V, Eisdorer C, eds. Advances in the Diagnosis and Treatment of Alzheimer's Disease. New York, NY: Springer Publishing Co;1998: 53-89.

4. Lipton SA. Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx. 2004;1:101 –110.[Medline]

5. Rossom R, Adityanjee, Dysken M. Efficacy and tolerability of memantine in the treatment of dementia. Am J Geriatr Pharmacother. 2004;2:303 –312.[Medline]

6. Rogawski MA. What is the rationale for new treatment strategies in Alzheimer's disease? CNS Spectr.2004; 9(7 suppl 5):6 –12.[Medline]

7. Robles-Bayon A. The action of memantine on the cognitive disorders of patients with dementia: reflections following 2 years' experience in Spain [in Spanish]. Rev Neurol.2006; 42:288 –296.[Medline]

8. Rao VL, Dogan A, Todd KG, Bowen KK, Dempsey RJ. Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Brain Res.2001; 911:96 –100.[Medline]

9. Barker PB. N-acetyl aspartate—a neuronal marker? Ann Neurol.2001; 49:423 –424.[Medline]

10. Adalsteinsson E, Sullivan EV, Kleinhans N, Spielman DM, Pfefferbaum A. Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease. Lancet.2000; 355:1696 –1697.[Medline]

11. Waites CL, Craig AM, Garner CC. Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci.2005; 28:251 –274.[Medline]

12. Jung RE, Brooks WM, Yeo RA, Chiulli SJ, Weers DC, Sibbitt WL Jr. Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain. Proc Biol Sci.1999; 266:1375 –1379.[Medline]

13. Davis KL, Mohs RC, Tinklenberg JR, Pfefferbaum A, Hollister LE, Kopell BS. Physostigmine: improvement of long-term memory processes in normal humans. Science.1978; 201:272 –274.[Abstract/Free Full Text]

14. Zhang Z, Wang X, Chen Q, Shu L, Wang J, Shan G. Clinical efficacy and safety of huperzine alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial [in Chinese]. Zhonghua Yi Xue Za Zhi.2002; 82:941 –944.[Medline]

15. Mumenthaler MS, Yesavage JA, Taylor JL, O'Hara R, Friedman L, Lee H, et al. Psychoactive drugs and pilot performance: a comparison of nicotine, donepezil, and alcohol effects. Neuropsychopharmacology.2003; 28:1366 –73.[Medline]

16. Butcher J. Cognitive enhancement raises ethical concerns: academics urge pre-emptive debate on neurotechnologies. Lancet.2003; 362:132 –133.[Medline]

17. McCabe SE, Knight JR, Teter CJ, Wechsler H. Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey [published correction appears in Addiction. 2005;100:573]. Addiction.2005; 100:96 –106.[Medline]

18. Maravelias C, Dona A, Stefanidou N, Spiliopoulou C. Adverse effects of anabolic steroids in athletes: a constant threat. Toxicol Lett. 2005;158:167 –175.[Medline]

19. Calfee R, Fadale P. Popular ergogenic drugs and supplements in young athletes. Pediatrics. 2006;117:e577–589. Available at: http://pediatrics.aa...full/117/3/e577. Accessed April 20, 2006.

Edited by FunkOdyssey, 31 May 2008 - 03:41 PM.

[Lufega]

I know magnesium also works by inhibitin NMDA receptors to some degree. I haven't noticed that it does so strong enough to increase my level of intelligence or processing speed. How has memantine worked for you and how long have you been taking it? I'm very interested in this drug and pramipexole. I am a demotivated disaster right now and I think I could benefit from either one or both. Do you use a low dose like LDN? What's recommended?

[jackinbox]

I tried memantine for about a week but discontinued its use since I had some side effects (headache, if I remember correctly). I didn't feel any positive effect during that short period. I remember reading this article and the suggestion of using memantine to enhance memory of healthy adult is not well founded. I don't remember finding any report of personal experience with memantine on the internet either.

[FunkOdyssey]

I know magnesium also works by inhibitin NMDA receptors to some degree. I haven't noticed that it does so strong enough to increase my level of intelligence or processing speed. How has memantine worked for you and how long have you been taking it? I'm very interested in this drug and pramipexole. I am a demotivated disaster right now and I think I could benefit from either one or both. Do you use a low dose like LDN? What's recommended?

I've been taking the standard 20mg dose for maybe a couple of months now. Memantine is not particularly motivating by itself, however it seems to reduce brain fog and allow me to think more clearly. It may not work as well in the young and completely healthy, but for me it noticeably enhances cognition.

Where memantine can be useful for motivation is in combination with ADD medication, by preventing tolerance to the initial motivating effects that normally diminish with continued use.

[bgwithadd]

If anything, taking too much makes me feel kind of supid. It literally seems to make me start to drool. It does make the adderall hit harder, but I would not use it on its own. Good for anxiety and depression and irritability to a fair extent, though, I think.

Upping NAA doesn't mean upping intelligence, it could be like upping glutamate and cause damage. Hopefully now, though.

[FunkOdyssey]

If anything, taking too much makes me feel kind of supid. It literally seems to make me start to drool. It does make the adderall hit harder, but I would not use it on its own. Good for anxiety and depression and irritability to a fair extent, though, I think.

Have you ever taken the same dose for a week straight? Or are you describing acute effects of a random high dose? Because the "stupid" feeling you are describing is experienced by everyone when they first take the drug or when they increase the dose, and it disappears quickly with continued use. I'd say 3-4 days would be typical.

The drug is really not meant to be used on an occasional basis. There is some adaptation that needs to occur before this drug shows its good side. If you take it here and there, all you'll experience is the ugly. Pramipexole is the same way.

Edited by FunkOdyssey, 26 April 2009 - 07:08 AM.

[bgwithadd]

It seemed to increase for about a week as I took one 10mg tab each day then sort of held steady another week or maybe slightly increased. When I stopped taking it a while I slowly came back to normal. One time though I felt like I was leaving my body or something. Very odd. Of course, I take so many things it is hard to compare any experience I have to baseline.

The halflife is like 3 days so taking it every other day should be ok.

Edited by bgwithadd, 26 April 2009 - 08:29 AM.

[jackinbox]

I wonder if there is any risk of interaction with Wellbutrin.

[Lufega]

Is this safe to use with an acetylcholinesterase inhibitor like pyridostygmine?

[Rational Madman]

If anything, taking too much makes me feel kind of supid. It literally seems to make me start to drool. It does make the adderall hit harder, but I would not use it on its own. Good for anxiety and depression and irritability to a fair extent, though, I think.

Have you ever taken the same dose for a week straight? Or are you describing acute effects of a random high dose? Because the "stupid" feeling you are describing is experienced by everyone when they first take the drug or when they increase the dose, and it disappears quickly with continued use. I'd say 3-4 days would be typical.

The drug is really not meant to be used on an occasional basis. There is some adaptation that needs to occur before this drug shows its good side. If you take it here and there, all you'll experience is the ugly. Pramipexole is the same way.

As an adjunct therapy to other agents, I've been taking Memantine for its anti-depressant, mood stabilization, and anxiolytic properties. With my long trial coming to an end, though, I'm afraid I'm going to have to second the concerns of bgwithadd.

When introduced to Memantine, I noticed some positive benefits--such as enhanced verbal fluency and the reduced incidence of hypomania. However, over time, I've come to believe that Memantine has had a dreadfully adverse impact on the encoding of memories. To compound this problem, most of the positive benefits became considerably less pronounced. After I found some empirical evidence to validate my concerns, I had sufficient cause to convince my psychiatrist to allow me to taper off the drug.

Perhaps Memantine is an effective agent for Lyme Disease, or neurodegenerative diseases like Huntington's and Alzheimer's. But, for otherwise healthy individuals, or those suffering from a much slower rate of drug dependant-glutamate induced degeneration, I would highly advise against using Memantine for anything exceeding a short trial. For some individuals, like Shawn, it may work wonders, but for most others--like myself--it would be totally inappropriate.

To clarify the content of my entry, it was not my intention to equate any of the aforementioned conditions. The appropriateness of Memantine is dependent on the severity of the subject's condition, and his or her's cost benefit analysis. From what I've read, though, Memantine only becomes effective as a neuroprotective agent at 20 mg/d, and at that dose, it may have a definite impact on learning.

Edited by Rol82, 24 August 2009 - 02:45 AM.

[Rational Madman]

Is this safe to use with an acetylcholinesterase inhibitor like pyridostygmine?

Based on empirical evidence, the co-administration of Memantine and acetylcholinesterase inhibitors have been found to be more efficacious than the administration of either of these agents alone. But, from the studies that I've read, all of the subjects are suffering from some form of dementia.

[Rational Madman]

I wonder if there is any risk of interaction with Wellbutrin.

There are no known interactions, and I can't think of why the combination of Namenda and Wellbutrin would be problematic. Maybe if used concurrently, the bioavailability of Wellbutrin might be effected. In any case, exercise caution, and proceed carefully if directed by a physician.

[Galantamine]

Memantine blocks calcium channels (NMDA receptors), and therefore a crucial step in memory formation.

Agents like the racetams work in direct opposition to NMDA antagonists (memantine, huperzine, l-theanine).

The extent of channel blockaid will be a key indicator of decreased anterograde memory formation - and memantine is pretty potent. I would consider memantine to be an anti-nootropic.

[winston]

Replying to the post directly above, does anyone else have any input? I am interested in adding memantine to my daily vyvanse to reduce tolerance to some of it's effects. However I also take piracetam and am concerned about its NMDA interaction with memantine
If it is a problem, could the two simply be taken at different times of day?
I'll also occasionally be taking small benzodiazepine doses, or at least possibly. Is that a problem?

[AbolishtheState]

Memantine: The Next Trend in Academic Performance Enhancement?
KEN S. OTA, OMS III; TINA GODWIN, OMS II

Western University of Health Sciences College of Osteopathic Medicine of the Pacific Pomona, Calif

...

In light of all of the mentioned factors and the recent reports regarding the misuse of anabolic-androgenic steroids for the enhancement of athletic performance,18,19 the misuse of memory-enhancing drugs to improve academic performance by some ambitious students may not be a far-fetched conjecture. The purpose of this letter is to raise a medically and ethically relevant question: If transient low-level, nonpathologic, glutamate-mediated neuronal damage can occur in normal brain tissue, and neuroprotection against this occurrence could promote neuroplastic processes such as synaptogenesis, could memantine be misused by students for academic performance-enhancement in the near future?.

Setting aside the primary discussion of memantine's efficacy as a nootropic agent for a moment, I would like to posit a question of a more general nature, which this article raises. Why is it that the use of performance-enhancing substances by healthy individuals is so often characterized as abusive misuse? Is it not the right of each individual--as a self-owner--to decide which substances they will introduce to their own body? If a rational adult--in the sense of intellectual maturity, rather than arbitrary societal/legal definitions--has weighed the costs and benefits of a particular performance-enhancing substance and still wishes to use it, that is their business and theirs alone. I do not believe this is a question of ethics or morality, but rather one of personal preference. It is the frame of mind evident in the quoted paragraph which has stigmatized the transhumanist movement with the negative connotations of substance abuse, cheating of nature, and what have you. These memes must change, if we ever hope to transcend the many flaws with which nature has left us.

[sylent1]

My question would be why it would be considered misuse for any individual to use substances that have a neuroprotective nature. Isn't preventing oxidation by free radicals and excititoxicity from neurotransmitters the FIRST step in prolonging healthy mental function-whether this manifests as an increase in cognitive function for university students or not?
From what I understand memantine acts as an antagonist to the Alpha 7 nicotinic receptors which seem to play an important role in cognitive function. While this would make one feel a little foggy at first ands seem counterproductive once the receptors upregulate it should manifest as icreased clarity and cognitive function. Not sure if the Alpha 7's affect crystallized or fluid intelligence -maybe someone can help here but stacked with an acetacholine precursor, an ACHe inhibitor and perhaps, a very low dose of galantamine as a positive allosteric modulator the effects should be considerable. People should avoid looking for 'trippy' effects as at lower doses they will experience cognitive boosts while receiving neuroprotective benefits-but you aren't necessarily going to NOTICE it until you USE it.

[ocean.soul]

I have been taking 20mg of memantine for four months and I have not notice any decline in my memory or cognition. If you are going to take it, you have to start with 10mg for a week, the following week you add the other 10mg at least 12hs after you took the previous. But all this is describe in the prospect that comes with the pills when you buy it... The prospect (Akatinol prospect, at least) says that memantine is a nootropic.

And one last thing, memantine does blocks NMDA, but more precisely:
Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. And thats not quite the same...

Personally I'm not concern about the NMDA receptor, but
-Memantine acts as a non-competitive antagonist at the 5-HT3 receptor.
-Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs)
-Memantine acts as an agonist at the dopamine D₂ receptor.
I'm trying to understand all this but, it's difficult!

[AyshnCowboy]

If anything, taking too much makes me feel kind of supid. It literally seems to make me start to drool. It does make the adderall hit harder, but I would not use it on its own. Good for anxiety and depression and irritability to a fair extent, though, I think.

Have you ever taken the same dose for a week straight? Or are you describing acute effects of a random high dose? Because the "stupid" feeling you are describing is experienced by everyone when they first take the drug or when they increase the dose, and it disappears quickly with continued use. I'd say 3-4 days would be typical.

The drug is really not meant to be used on an occasional basis. There is some adaptation that needs to occur before this drug shows its good side. If you take it here and there, all you'll experience is the ugly. Pramipexole is the same way.

greetings: newbie onboard here. I have been taking memantine for a month straight out, the headaches seem not to subside very much I still have it for about ten minutes every time I dose my self... I am thinking of switching to Piracetam for better memory and attention span I hope I can get some advise about this move or if there is a better med that could be suggested that would be extremely welcome...

[Guacamolium]

Start with a lower dose I'd suggest. Going from 2.5mg (or lower) and ramping up slowly eliminates most of the the worst side effects in my experience. Somebody else said they titrated slowly to 30mg and it was workable with his ADD meds. Memantine is a patience oriented cognitive enhancer for sure.

[kadlec]

How long do you have to take a certain memantine dose to feel wether it works or not?

I started at 5mg and then increased by 5mg every 7 days. I didn't feel anything until I reached 20mg.
But I also experience memory issues. I don't know if going lower to 10mg would work or not. Maybe at 10mg
memantine doesn't work anymore and I still get the memory issues.

My doc also told me that usually people take 20mg. The leaflet also says 20mg is the normal dose but this is also for dementia.

[xks201]

It's misuse because we are supposed to be stupid apes crawling on our hands, right? I also found the naivete of the author shameful.

[andrea23]

28caps of 20mg costs more than 100$ :/

[kadlec]

It's misuse because we are supposed to be stupid apes crawling on our hands, right? I also found the naivete of the author shameful.

I couldn't care less about wether someone thinks that taking it as brain enhancement is bad. My concern is wether it really enhances the brain or wether it only dumbs you down by making the memory worse. I fear that memantine isn't very helpful. My memory definitely has been impacted since I started taking it.

[Lunast]

Can someone PM me a reliable/inexpensive source to purchase memantine? I'm interested in purchasing it to combat the cognitive effects of prolonged and chronic stress. Also, I'm hoping it will help to abate some anxiety, depression and possibly assist in adhd symptoms.

[gamesguru]

im thinking mematine is most popular with adderall users.

uh maybe it could be cycled, or combined w/ something like green tea, which has glutamate-releasing and memory-enhancing properties? it's not clear how much the glutamate release of green tea would offset the nmda antagonism of the memantine... this seems slightly redundant? unless im missing somefing, like men reduces Addy tolerance thru nmda-indepnt mechanism?

i would try the green tea maybe, pretty confident it could help offset the memory loss.

Edited by gamesguru, 20 June 2016 - 02:22 AM.

[John250]

Where is everyone getting their Memantine?

[truboy]

Where is everyone getting their Memantine?

 

alldaychemist com

[John250]

Ohh allday is still around nice. Thanks