20 replies to this topic

[gizmobrain]

Background

I suspect that many of my symptoms may be a result of a hypo-active NMDA system. I can fully flesh out the rationale behind this if necessary, but I don't think it's necessary for the sake of this thread.

Objective

I'm trying to find the best ways to directly target this system without causing too much brain damage if I'm wrong.

Potential Combination

A company is packaging a spray version of pregnenolone together with a powdered version of D-serine. Here is an excerpt from their product description:

D-Serine powder can be used to optimize the brain's ability to learn and recall complex functions and may be a valuable asset to students, workers, or anyone who may have to process or memorize difficult material. Coupled with Pr-Spray, which aides in a host of natural processes enhancing hormone and brain function, this stack is purported to have many memory enhancing, mood elevating, and energizing benefits. Read more about each product below:

D-Serine Powder (DS):

D-Serine is an amino acid that serves as a key regulator in the formation of memories. It is synthesized in types of brain cells called astrocytes, and its production is essential in the process of long term potentiation. Long term potentiation is a process wherein neurological pathways are enhanced in response to certain environmental stimuli – in other words it is the process by which long term memories are consolidated in the brain.

Administration of D-Serine leads to accumulation of the amino acid in the cerebral cortex and hippocampus. These are areas of the brain involved in memory consolidation, and D-Serine acts via NMDA receptors on neurons in these areas. Administration of D-Serine to animals has been demonstrated to enhance learning and working memory.

Pr Spray:

Pr Spray provides pregnenolone in a sustained release form, aiding in a host of natural processes enhancing hormone and brain function.

Pregnenolone is a hormone naturally produced in the body. It is synthesized in the adrenals and gonads where it serves as a precursor to all the steroid hormones – DHEA, testosterone, progesterone, estrogen, cortisol, aldosterone and others.

Pregnenolone is also synthesized in the brain and central nervous system, where it acts (directly and as the sulfate) as a neurosteroid. As a neurosteroid it serves a variety of functions – most notably as an enhancer of NMDA activity and suppressor of GABA activity. This may in part be responsible for its purported memory enhancement, mood elevating, and energizing activities.

Pr Spray provides pregnenolone in a sustained release form for maximum round the clock bioactivity.

Since D-Serine hasn't been on the market for that long, I should probably point out that it activates the same receptor as glycine. See the D-Serine thread for more information. As far as Pregnenolone, does anyone have any recommendations? Spray form, pill form, etc?

Concerns

1. NMDAr over-activation

• What are the symptoms?
• Do these symptoms appear before neuron damage would occur?
• What would be the most effective "antidote" if this were to occur?
  
• N-Acetyl-L-Cysteine, Dextromethorphan (OTC NMDA antagonist), etc.

2. Danger of long term usage

• While this is important, it's not my main concern right now. I'm currently trying to establish whether or not my symptoms can be traced to the NMDA system. On the other hand, I certainly would stop anyone from discussing the potential concerns of long term use.

3. Efficacy

• Anyone have any advice for Pregnenolone? Spray form, pill form, etc.

Edited by zrbarnes, 12 July 2012 - 11:08 PM.

[gizmobrain]

Relating to concern #1:

Drug Chem Toxicol. 2012 Apr 10. [Epub ahead of print]
Effects of non-steroidal antiinflammatory drugs on D-serine-induced oxidative stress in vitro.

Armagan G, Kanıt L, Yalcın A.

Source

Department of Biochemistry, Faculty of Pharmacy, Ege University , Bornova, Izmir , Turkey.

Abstract

Inflammation is deleterious for organs with reduced capacity of regeneration, such as the brain. Recently, studies have focused on investigating the therapeutic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Excitotoxicity is the pathological process when receptors for the excitatory neurotransmitter glutamate, such as the N-methyl-D-aspartate (NMDA), receptors are overactivated. This process may be involved in neurodegenerative diseases. D-serine is one of the coagonist of NMDA receptors, and increased levels of D-serine are associated with excitotoxicity. In our study, the potential neuroprotective effects of mefenamic acid, acetaminophen, and naproxen sodium were investigated against D-serine-induced oxidative stress in the rat brain in vitro. To show their potential neuroprotective properties, NSAIDs were incubated with D-serine and reactive oxygen species (ROS), malondialdehyde, and protein carbonyl content of the brain after different treatments were measured. Our results demostrate that NSAIDs used in the present study significantly reduced ROS production, lipid peroxidation, and protein oxidation against D-serine treatment. PMID:22486999

Neurosci Lett. 2000 Aug 11;289(3):201-4.
Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.

Casper D, Yaparpalvi U, Rempel N, Werner P.

Source

Department of Neurological Surgery, Neurosurgery Lab, Montefiore Medical Center, The Bronx, New York 10467, USA. casper@aecom.yu.edu

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Alzheimer's disease, although the underlying mechanisms are unknown. Glutamate excitotoxicity has been implicated in Alzheimer's disease, Parkinson's disease, and others. We examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons from mesencephalon, the area primarily affected in Parkinson's disease. We evaluated whether these drugs protect dopaminergic neurons against excitotoxicity. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity. One hundred micro-moles ibuprofen protected both dopaminergic neurons and neurons overall against glutamate toxicity. In addition, ibuprofen alone increased the relative number of dopaminergic neurons by 47%. Thus, NSAIDs protected neurons against glutamate excitotoxicity in vitro, and deserve further consideration as neuroprotective agents in Parkinson's disease. PMID:10961664

So possible damage can be reduced by NSAIDs (naproxen, ibuprofen, etc.). I don't know the pathway which it reduces it by, however. If it causes de-activation of NMDA, then it would be considered more an antidote. If it works by reducing glutamate or glycine/d-serine release, then it wouldn't be very useful for our purpose.

Edited by zrbarnes, 13 July 2012 - 02:53 AM.

[gizmobrain]

Unfortunately, I still don't have any information on whether this state could be "felt" in time to prevent damage. Anyone have any insight into this?

Next up is this acetylcholinesterase inhibitors study. Lately, AChE-I's have fallen into disuse because of the studies that have shown acetylcholinesterase's importantance. However, I still wonder if they can be put to good use for AChE neuroprotection and optimization with occasional usage.

It has been reported that AChE inhibitors have no effect on the baseline synaptic transmission or the magnitude of long-term potentiation induction (Barnes et al., 2000). In addition, α7 nAChR stimulation is reported to enhance glutamatergic transmission (Gray et al., 1996). Thus, α7 nAChRs might regulate the neuronal activity to prevent hyper-activity that leads to neuronal death without interfering with synaptic transmission. In other words, cholinergic stimulation does not appear to decrease basal transmission, even though NMDA receptors would be internalized by nAChR stimulation.

In the present study, we hypothesized that donepezil would internalize the functional NMDA receptors through α7 nAChR stimulation, which in turn would attenuate the neuronal death induced by excessive glutamate, although synaptic NMDA receptors would not be altered.

Anyone want to give some insight into what "internalize the NMDA receptors" means? Actually, it seems like there are a whole load of goodies in that study, so if anyone wants to give it a read, feel free to post some relevant information.

So potential harm prevention seems to lie in NSAID's and AChE-I's, while acute NMDAr overstimulation can be treated with NMDAr antagonists. I also have some Magnesium L-threonate and Dextromethorphan on hand. If things get too crazy, I suppose I could just take a couple shots or drink a beer. Good to see that we seem to have a few options for protecting against damage of an over-active NMDA state, if it comes to that.

Edited by zrbarnes, 13 July 2012 - 06:29 AM.

[medievil]

The glycine reuptake inhibitor and agonist sarcosine protects against excitoxiticy which is interesting.

[gizmobrain]

I currently have some Sarcosine, pregnagolone, and D- serine on its way. I will update this thread next week with results.

[medievil]

D aspartic acid would be a good adjunct too.

[gizmobrain]

Woke up this morning to the following orders sitting on my doorstep:

• Prototype Nutrition D-Serine
• E-Pharm TestForce2 (D-Aspartate Calcium Chelate with Sarcosine)
• Jarrow Formulas Pregnenolone
• Superior Nutraceuticals Uridine (UMP)

The D-Serine is interesting. Fairly good sized crystals, tastes sweet. If it looked more like sugar, I'm not sure I could tell the difference. It also readily dissolves in water. After taking one scoop (~1.5g), partially sublingual, I did not "feel" different (I didn't really expect to).

I picked up the Uridine just to trial it separate from this. However, can anyone tell me the significance of the following article:

Bull Exp Biol Med. 2008 Mar;145(3):320-2.
Effect of uridine of presynaptic NMDA and kainate receptor of rat brain cortex.

Petrova LN, Gabrelian AV.

Source

Laboratory of Neurochemistry of Physiologically Active Substances, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chemogolovka, Moscow Region. plv@icp.ac.ru

Abstract

It was demonstrated that uridine affects presynaptic NMDA and kainite receptors of rat brain cortex. Uridine considerably inhibited (45)Ca2+ uptake into synaptoneurosomes (IC50 = 7.1 x 10(-12) M) under conditions NMDA stimulation and increased it under conditions AMPA stimulation (157.8%). PMID:19039933

Inhibiting Ca2+ uptake into synaptoneurosomes under conditions of NMDA stimulation would be a bad or good thing for my purposes?

[gizmobrain]

Interesting... maybe Sarcosine would be preferable to D-Serine.

Arch Gen Psychiatry. 2005 Nov;62(11):1196-204.
Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study.

Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE.

Source

Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan.

Abstract

CONTEXT:

Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia.
OBJECTIVE:

To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia.
DESIGN:

Randomized, double-blind, placebo-controlled trial.
SETTING:

Inpatient units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic inpatients with acute exacerbation.
INTERVENTIONS:

Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy.
MAIN OUTCOME MEASURES:

Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores.
RESULTS:

The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains.
CONCLUSIONS:

This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.
Comment in

• Adding sarcosine, but not D-serine, to risperidone improves symptoms in people with acute phase schizophrenia. [Evid Based Ment Health. 2006]
• The glycine site of NMDA receptors--a target for treatment of schizophrenia. [Curr Psychiatry Rep. 2006]

PMID: 16275807

[hephaestus]

Woke up this morning to the following orders sitting on my doorstep:

• Prototype Nutrition D-Serine
• E-Pharm TestForce2 (D-Aspartate Calcium Chelate with Sarcosine)
• Jarrow Formulas Pregnenolone
• Superior Nutraceuticals Uridine (UMP)

The D-Serine is interesting. Fairly good sized crystals, tastes sweet. If it looked more like sugar, I'm not sure I could tell the difference. It also readily dissolves in water. After taking one scoop (~1.5g), partially sublingual, I did not "feel" different (I didn't really expect to).

I picked up the Uridine just to trial it separate from this. However, can anyone tell me the significance of the following article:

Bull Exp Biol Med. 2008 Mar;145(3):320-2.
Effect of uridine of presynaptic NMDA and kainate receptor of rat brain cortex.

Petrova LN, Gabrelian AV.

Source

Laboratory of Neurochemistry of Physiologically Active Substances, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chemogolovka, Moscow Region. plv@icp.ac.ru

Abstract

It was demonstrated that uridine affects presynaptic NMDA and kainite receptors of rat brain cortex. Uridine considerably inhibited (45)Ca2+ uptake into synaptoneurosomes (IC50 = 7.1 x 10(-12) M) under conditions NMDA stimulation and increased it under conditions AMPA stimulation (157.8%). PMID:19039933

Inhibiting Ca2+ uptake into synaptoneurosomes under conditions of NMDA stimulation would be a bad or good thing for my purposes?

According to this bluelight thread, it prevents amphetamine tolerance:

http://www.bluelight...-reduction-long

According to this other bluelight thread, nmda antagonists can prevent tolerance to all kinds of stuff:

http://www.bluelight... tolerance nmda

[gbpackers]

Is it dangerous to stack pregnenolone and D-serine for a a couple months with the oxiracetam, piracetam, bacopa, and rhodiola?

[gbpackers]

bump ... any updates on the d-serine and pregnenolone combo?

[gizmobrain]

Unfortunately, my physically demanding job has been going later into the night. Since this is a variable that messes with my energy, sleep schedule, and overall quality of life, I have been holding off on using the d-serine. I don't want to waste it without being able to discern its effects.

I'm on the look out for a new job though, so hopefully I can get back to this trial soon.

[gbpackers]

I see completely understandable - I might just go ahead and order it and check it out for myself. One of my friends already ordered it too actually. I took 150mg pramiracetam and 800mg piracetam today.. and feel focused and motivated when studying. Hoping the D-Serine adds to this effect.

[protoject]

D aspartic acid would be a good adjunct too.

Does that cross the BBB though????????

[Hebbeh]

D aspartic acid would be a good adjunct too.

Does that cross the BBB though????????

Yes

[gbpackers]

how do you dose the pregnenolone?

[medievil]

I allways used the 100mg time released version of nutricology. I suspect it would be synergetic with DHEA wich potentiates glutaminergic function.

L glutamic acid could perhaps be another helpfull addition.

[gizmobrain]

Because I noticed some pretty awesome results with Galantamine, I found this post very interesting:

I found an interesting hypothesis the other day on Memantine taken with adjunctive Galantamine. The research suggests that while Memantine indiscriminately acts as a partial-antagonist at extrasnyaptic and synaptic NMDA receptors, that Galantamine acts as a preferential NMDA agonist at synaptic receptors. The extrasynaptic NMDA receptors are the ones most commonly associated with excito-toxicity, so I take this to mean that Galantamine could theoretically contribute to restoring a more normal functionality to 'synaptic' NMDA receptors while leaving Memantine to suppress the more excito-toxic 'extra-synaptic' receptors.

Memantine is an Alpha-7 antagonist and Galantamine is an allosteric Alpha-7 modulator. And although there are no indications of how the various mechanisms affecting Nicotinic Alpha-7 receptors would interact with one another, I would posit that since Galantamine's actions on synaptic NMDA receptors is facilitated through Nicotinic Receptors (and since the glutaminergic affects are shown to be synergistic in the below studies), that the individual effects on Nicotinic receptors from the two compounds should retain some independance from one another (given that Galantamine's actions on NMDA are proposed to be an nAChR mediated response). I'm uncertain however (despite this) as to the degree that Memantine's Nicotinic Alpha-7 antagonism would continue to detrimentally affect cognition.. (?)

Nevertheless, the implications may be of interest given some of the feedback received here and in other threads with respect to Memantine.


http://www.ncbi.nlm....pubmed/17011596

Several drugs are in clinical use for symptomatic treatment of Alzheimer's disease patients. Since Alzheimer's disease is known to be associated with down-regulation of the cholinergic and N-methyl-D-aspartate (NMDA) systems, most of these drugs inhibit acetylcholinesterase, potentiate the activity of nicotinic acetylcholine receptors (nAChRs), or modulate NMDA receptors. Galantamine is an anticholinesterase and allosterically potentiates the activity of the nicotinic receptors. We have recently found that galantamine potentiates the activity of NMDA receptors as well. Memantine is unique in that it inhibits the NMDA receptors. We have developed a hypothesis that combining galantamine and memantine will be more effective for improving the patient's conditions than monotherapy with either drug. Patch clamp and intracellular Ca(2+) imaging experiments using rat cortical and hippocampal neurons clearly provided the in vitro bases for our hypothesis. Memantine blocked the extrasynaptic NMDA receptor 100 times more potently than the synaptic NMDA receptor at negative membrane potentials and the block of both types of NMDA receptors was attenuated with depolarization. However, galantamine potentiation of the NMDA receptors was not voltage dependent. Thus, co-application of memantine with galantamine prevented the galantamine potentiation and the activation of extrasynaptic NMDA receptors, but membrane depolarization revealed the galantamine potentiation. Therefore, cell death is expected to be prevented by memantine near the resting potential while the NMDA-mediated synaptic transmission, which is down-regulated in the patients, is maintained and potentiated by galantamine. These results provide in vitro bases for the beneficial actions of galantamine and memantine combinations.


http://www.life-enha...ate.asp?id=1732

…conclude that the effects of both agents, working together, should have net positive effects on both the cholinergic and glutamatergic systems in the brains of Alzheimer's patients.¹ This conclusion is not just theoretical but is supported by evidence obtained from preclinical studies (laboratory and animal) on the mechanisms of action of the two agents.²

Computer simulations of the biochemical interactions between galantamine and memantine in the human body predict that combination therapy with these two agents may enhance the neural signal-to-noise ratio even more than memantine does by itself. This should improve the patients' cognitive function, or at least retard its decay.


http://www.ncbi.nlm.nih.gov/pubmed/16809810

The search for effective treatments of Alzheimer's disease (AD) is one of the major challenges facing modern medicine. Acetylcholinesterase (AChE) inhibitors (AChEIs) are effective for the treatment of mild to moderate AD, and memantine, an N-methyl-D-aspartate (NMDA) inhibitor, has been approved for moderate to severe AD. Galantamine is of particular interest because it has a dual mechanism of action: it is postulated to be both an AChEI and an allosteric modulator of nicotinic receptors. Modulation of NMDA and nicotinic receptors by memantine and galantamine may provide an optimal combination therapy for AD. The cholinergic and glutamatergic neurotransmitter systems, which share a close functional relationship, may play a role in the pathogenesis of AD. Close examination of the pharmacology of the 2 compounds suggests that galantamine can augment memantine's glutamatergic noise suppression while simultaneously enhancing the physiologic glutamatergic signal. The link between these systems suggests that AD therapies, which capitalize on this relationship, may be more effective in improving cognition than approaches focusing on a single system.

I'll also point out the following potentially conflicting abstract as well, which states contradictory information about the combination and the efficacy of Memantine in a model of Ischemia in gerbils. I would have expected Memantine to shine here as Ischemia supposedly leads to excitotoxicity - So I'm not certain why Memantine wouldn't have worked?


http://www.ionchanne...p?pmid=19103181

Galantamine is an acetylcholinesterase inhibitor and memantine is a non competitive antagonist of NMDA receptors that are being used to treat Alzheimer's disease (AD) patients. The fact that drugs with different mechanisms of action are available to treat AD introduces the prospect of prescribing drug combinations to amplify drug efficacy. This study was planed to evaluate the potential neuroprotective effects of galantamine combined with memantine in a transient global cerebral ischemia model in gerbils. Animal groups included in the study were: sham, ischemia, and ischemia plus galantamine (1 mg/kg and 10 mg/kg), memantine (10 mg/kg and 20 mg/kg), 1 mg/kg galantamine plus 10 mg/kg memantine, and 10 mg/kg galantamine plus 10 mg/kg memantine, respectively. Surviving pyramidal neurons in the CA1 subfield of the hippocampus, TUNEL, caspase-3 and SOD-2 immunohistochemistries, and the object placement test were evaluated 72 h after reperfusion. Memantine did not exert a clear neuroprotective effect, nor did it prevent spatial memory loss. In a previous study using the same experimental model, galantamine was neuroprotective and improved spatial memory. In this study, the association of 10 mg/kg memantine with 10 mg/kg galantamine increased the number of living pyramidal neurons, reduced TUNEL, active caspase-3 and SOD-2 immunoreactivity, and preserved spatial memory after ischemia-reperfusion injury; however, the effects of the combination were not statistically different from those observed in animals treated with galantamine alone. We believe these results are of interest from a clinical point of view because the association of both drugs is being used in clinical practice and in clinical trials to treat Alzheimer's disease and vascular dementia.

Edited by zrbarnes, 09 August 2012 - 11:44 PM.

[gbpackers]

I tried 1.5g of d-serine and 10 sprays of the pregnenolone spray from prototype nutrition with 2.8 grams of piracetam. Not sure what I noticed... maybe some more focus then usual but I felt somewhat energized - not sure if that was just placebo. Anyone has advice on the dosages? I'm going to try adding in oxiracetam to the mix tomorrow

[metaprog]

D-Aspartic Acid definitely crosses the BBB. I recently started taking it for its heralded testosterone-enhancing properties. After a couple of days, I noticed increased mental clarity & memory along with other other cognitive benefits. I initiated the regimen along with gingko, ginseng & a couple other nootropics. After trying different combinations to isolate the primary molecule responsible for the enhanced cognitive abilities, I found the D-Aspartic to be responsible. I initially took 3 grams daily for the first 4 days.

In addition to the VERY noticeable enhanced memory, learning abilities & other cognitive benefits, I noticed the following benefits/symptoms/side-effects:

1. Laser-sharp focus coupled with inner calm while "peaking" on the molecule followed by racing thoughts & inability to focus well once the molecule was being metabolized/no-longer binding to the NMDA-glutamate circuitry.

2. Increased muscle stress/tension throughout the body that lasted up to 24 hours (albeit in a relatively rapidly decreasing magnitude) following the 3-5 hour "peak" positive effects.

3. Marked mental sluggishness & "gray" disposition with regards to both mood & overall general excitation level of the brain if I missed a dose. This is something I've noticed with nearly every nootropic or psychoactive chemical I've ever tried. Some form of internal regulation of the bio-feedback cycle (possibly leading to "dependence") seems to always occur to me. Whether this is an adaptive attempt by my brain to decrease endogenous production of a molecule that is being supplemented exogenously is something I cannot be certain of. But it is the primary unwanted side-effect I get...and the one that prevents me from confidently tinkering with my brain via the use of nootropics on a "long-term" basis.

@zrbarnes & @gbpackers: How has your experience been with D-Serine? I'm on the verge of ordering the bottle from ProtoType Nutrition. I've done a bit of research on D-Serine and, with the exception of temporary nephrotoxicity seen in daily users of more than ~10g, I don't find much evidence of negative side effects. I've yet to research comparative metrics on binding affinity, half-life, etc. between it & D-Aspartic, but the literature is clear that D-Serine is a more competitive & effective agonist at the NMDA-glutamate receptor.

[metaprog]

@ zrbarnes - I've had some pretty interesting results with Galantamine as well... a very potent acetylcholinesterase-inhibitor. Its been well-known for its lucid-dreaming enhancing properties. The cognitive benefits were immediately & drastically noticeable, as were the lucid-dreaming properties. Dreams were MUCH more vivid than usual as was my ability to recall them...much like when I was a teenager. As positive as the benefits were, so was the magnitude of the side-effects...severe muscle tension that would last up to 48 hours after ingesting the Galantamine, the usual gastrointestinal discomfort/agitation, mental sluggishness in the 48 hours after the peak positive effects of the molecule wore off, etc. To differing degrees & qualitative factors, there were nonetheless a lot of similarities in the negative effects of both galantamine & D-Aspartic. Given their action at the same receptor circuitry, I guess this is not too surprising.