10 replies to this topic

[playground]

I have started this thread to explore the whole issue of Galantamine as a neurotrophic agent.

 

An effective, herbal, neurotrophic agent. 

A european equivalent of Lion's Mane, perhaps.

 

My interest in this subject comes from the recent findings that IGF-2 induces neurogenesis

in the infant and *adult* brain.

 

This thread is suggesting that you can get IGF-2 expression in the hippocampus by taking

Galantamine (which is actually a herbal abstract of Caucausian Snowdrop - a flower).

The medicinal use of Snowdrop goes back hundreds of years in eastern Europe.

Galantamine has been used pharmaceutically since the 1960s in Russia.

 

 

Some interesting papers are presented below:

 

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Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice.

Abstract

Galantamine, a drug for the treatment of Alzheimer's disease, has neuroprotection in several experimental models and stimulates adult neurogenesis in the rodent brain, but the exact mechanism remains unclear. This study examined whether galantamine affects the expression of neurotrophic/growth factors in the mouse hippocampus and prefrontal cortex.

METHODS:

Nine-week-old male ddY mice were used. The mRNA levels of neurotrophic/growth factors were analyzed by a real-time quantitative PCR. The protein levels of insulin-like growth factor 2 (IGF2) were analyzed by Western blotting.

RESULTS:

Acute administration of galantamine (0.3-3 mg/kg, i.p.) increased IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex, in time- and dose-dependent manner. Galantamine (3 mg/kg, i.p.) caused a transient increase in fibroblast growth factor 2 mRNA levels and a decrease in brain-derived neurotrophic factor mRNA levels in the hippocampus, while it did not affect the mRNA levels of other neurotrophic/growth factors. The galantamine-induced increase in the hippocampal IGF2 mRNA levels was blocked by mecamylamine, a nonselective nicotinic acetylcholine (ACh) receptor (nAChR) antagonist, and methyllycaconitine, a selective α7 nAChR antagonist, but not by telenzepine, a preferential M(1) muscarinic ACh receptor antagonist. Moreover, the selective α7 nAChR agonist PHA-543613 increased the IGF2 mRNA levels, while donepezil, an acetylcholinesterase inhibitor, did not. Galantamine also increased hippocampal IGF2 protein, which was blocked by methyllycaconitine.

CONCLUSIONS:

These findings suggest that galantamine increases hippocampal IGF2 levels via α7 nAChR activation in mice and imply that the effect may contribute to its neuroprotection or neurogenesis.

 

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Galantamine promotes adult hippocampal neurogenesis via M₁ muscarinic and α7 nicotinic receptors in mice.

Abstract

Galantamine, an inhibitor of acetylcholinesterase, promotes hippocampal neurogenesis, but the exact mechanism for this is not known. In the present study, we examined the mechanisms underlying the effects of acute galantamine on neurogenesis in the mouse hippocampus. Galantamine (3 mg/kg) increased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the subgranular zone of the dentate gyrus. This effect was blocked by the muscarinic receptor antagonist scopolamine and the preferential M1 muscarinic receptor antagonist telenzepine, but not by the nicotinic receptor antagonists mecamylamine and methyllycaconitine. Galantamine did not alter the ratio of neuronal nuclei (NeuN)- or glial fibrillary acidic protein (GFAP)-positive cells to BrdU-labeled cells in the subgranular zone and granule cell layer. Galantamine (1, 3 mg/kg) promoted the survival of 2-wk-old newly divided cells in mice in the granule cell layer of the dentate gyrus, whereas it did not affect the survival of newly divided cells at 1 and 4 wk. Galantamine-induced increases in cell survival were blocked by the α7 nicotinic receptor antagonist methyllycaconitine, but not by scopolamine. Bilateral injection of recombinant IGF2 into the dentate gyrus of the hippocampus mimicked the effects of galantamine. The effects of galantamine were blocked by direct injection of the IGF1 receptor antagonist JB1. These findings suggest that galantamine promotes neurogenesis via activation of the M1 muscarinic and α7 nicotinic acetylcholine receptors. The present study also suggests that IGF2 is involved in the effects of galantamine on the survival of 2-wk-old immature cells in the granule cell layer.

 

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[playground]

There are supplement manufacturers selling this stuff for $2 per 4mg pill.

Try searching on ebay for it.  You'll see what i mean.

 

I don't recommend you buy this stuff from ebay.

 

The cheapest source of galantamine, that i have found so far, is powdercity.com.

 

http://www.powdercit...t&q=galantamine

 

They sell 0.25 gram of pure galantamine for less than $10.

A standard dose is 4mg to  8mg for normal people. 

12mg is a standard dose for people with dementia.

 

4 to 8mg is very difficult to measure out accurately (even with accurate scales).

Powder city also sell 7mg galantamine capsules.... 30 capsules for $13

 

 

Edited by playground, 28 February 2016 - 11:12 AM.

[playground]

Galantamine, along with other acetylcholinesterase drugs, helps people (and rats) stop smoking.

 

Just the article title and authors are shown below:

 

Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers.
Ashare RL1, Kimmey BA2, Rupprecht LE3, Bowers ME1, Hayes MR3,4, Schmidt HD2,4.

 

Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats.

Hopkins TJ, Rupprecht LE, Hayes MR, Blendy JA, Schmidt HD. Neuropsychopharmacology. 2012 Sep; 37(10):2310-21. Epub 2012 Jun

 

Donepezil, an acetylcholinesterase inhibitor, attenuates nicotine self-administration and reinstatement of nicotine seeking in rats.

Kimmey BA, Rupprecht LE, Hayes MR, Schmidt HD.

 

Edited by playground, 28 February 2016 - 02:01 PM.

[medievil]

I think alldaychemist sells it cheaper, i ordered from there myself before, i would check if i wasnt using my phone hotspot for my internet as its slow sometimes.

[playground]

It seems that Galantamine is actively sought out by lucid dreamers.

 

Here's what nootriment has to say about it:

 

Using Galantamine For Lucid Dreams:

 

Galantamine Hydrobromide is effective as a lucid dreaming supplement because it boosts acetylcholine activity. It does this because it is an acetylcholinesterase (AChE) inhibitor. Once acetylcholine is released from a neuron, it is broken down by an enzyme called acetylcholinesterase and recycled into various components. Galantamine prevents this break-down from occurring so that there is more acetylcholine available to interact with neural receptors. Galantamine will be even more effective at promoting lucid dreams with choline which is a precursor to acetylcholine. By pairing these two together, you can increase the stimulation of cholinergic neurons from two directions at once.

 

In order to use Galantamine for lucid dreaming, it is recommended that you follow a Wake-Back-To-Bed (WBTB) strategy. This is a very common lucid dreaming practice in which you will allow yourself to sleep deeply at first for about four or five hours, wake up for a short period of time, and then fall back to bed. Not only does this method make it more likely that you will induce a lucid dreaming state, it can also counteract a side effect of taking Galantamine before your normal sleep schedule. If you take this nootropic one or two hours before you would normally fall asleep, you may find that you experience intense nightmares or very restless sleep. It is not recommended to use it in this way as you may find your sleep is disrupted and the experience will not be very pleasant.

 

Rather than taking Galantamine before you fall asleep at night, it is suggested that you take it approximately 4 or 5 hours into your normal sleep cycle. Set an alarm to wake yourself after 5 hours and then take a 4 to 16 mg dosage immediately. Most individuals will see results with 4 or 8 mg so you should start at these lower dosages. Depending on the Galantamine pill that you buy, this will usually consist of one or two tablets. You may decide to stack it with a choline supplement like Alpha GPC or Citicoline at a 250 mg to 500 mg dosage (or Lecithin). (Some individuals find it is better to consume the choline evenly throughout the day rather than at night since it can lead to increased alertness and make it difficult to fall asleep again.)

After taking the Galantamine, it will reach full concentration in your brain within 60 minutes. This should allow you enough time to fall back to sleep and enter a REM dreaming stage. You may not experience lucidity on your first time using it, but many find that after a week they are consistently able to become lucid during their dreams. Some reviewers recommend not taking Galantamine two days in a row as it takes approximately 48 hours for the effects to wear off. Only use this supplement on days when you can afford to devote more time to sleep as it may lead to sleep disruptions on occasion.

 

 

Edited by playground, 28 February 2016 - 09:40 PM.

[playground]

More on Galantamine and Lucid dreaming here:

http://dreamstudies....-dreaming-pill/

 

I'm going to be setting my alarm clock for 5 hours after i fall alseep so that i can take

the 4mg dose of Galantamine that's waiting for me, on my desk.

 

Probably...  nothing will happen... but we'll see.

 

 

[William Sterog]

More on Galantamine and Lucid dreaming here:

http://dreamstudies....-dreaming-pill/

 

I'm going to be setting my alarm clock for 5 hours after i fall alseep so that i can take

the 4mg dose of Galantamine that's waiting for me, on my desk.

 

Probably...  nothing will happen... but we'll see.

 

I ALWAYS have lucid dreams if a take a suplement made by Uncaria Rhynchophylla, Ziziphus Jujuba and Albizia Julibrisin right before going to sleep. I don't know the reason why.

[playground]

The 4mg Galantamine definitely did something.

 

It put more flesh on the bones of my usual skeleton dreams.

 

I would say my dream was clear-er, but not lucid.

But, i remembered it perfectly well, which isn't usual for me.

 

So i would say that there's something

to this 'galantamine' and lucid dreaming connection

(but admittedly, one observation isn't much of a basis).

 

 

[playground]

However, one explanation for Galantamine's effectiveness with Lucid dreaming

is based on Galantamine's anti-acetylcholineesterase activity.

 

That presumably means that Huperzine A would also work as a pro-lucid dreaming agent.

(Since it's also an anti-acetylcholineesterase agent)

 

In fact that would be a good test:

 

If Huperzine A works to enhance dream lucidity, then it suggests the anti-acetylcholinessterase

aspect of Galantamine is what give it it's 'pro-lucid-dreaming' feature.

 

If huperzine A doesn't enhance dream lucidity, then it suggests that there's some other feature

of Galantamine which enhances lucid dreaming.

 

For example, It's possible that there's something about agents that induce neurogenesis

that they also prone to enhancing lucid dreaming (perhaps in ways we cant current imagine.

We know, for example, that beta-NGF enhances dreaming and enhancing visualisation skills)

 

I happen to have a supply of huperzine A  (how convenient). 

I might put this hypothesis to the test.

 

Edited by playground, 08 March 2016 - 12:25 AM.

[normalizing]

playground; http://www.ergo-log....am-vitamin.html add this one too and also a small dose of melatonin and report.

 

personally i tried the b6 trial but i dosed way too high at 100mg and i couldnt sleep at all! but i think much lower dose and melatonin works well. i remember doing the combo years ago and it seemed to work back then

[William Sterog]

 

More on Galantamine and Lucid dreaming here:

http://dreamstudies....-dreaming-pill/

 

I'm going to be setting my alarm clock for 5 hours after i fall alseep so that i can take

the 4mg dose of Galantamine that's waiting for me, on my desk.

 

Probably...  nothing will happen... but we'll see.

 

I ALWAYS have lucid dreams if a take a suplement made by Uncaria Rhynchophylla, Ziziphus Jujuba and Albizia Julibrisin right before going to sleep. I don't know the reason why.

 

 

Ok, you say that I need references so I did a little research.

 

First of all, we are going to try to understand some of the basics mechanics of dreaming.

 

During a full eight-hour night sleep, most dreams occur in the typical two hours of REM.

http://science.howst...rain/dream2.htm

 

The release from aminergic inhibition stimulates cholinergic reticular neurons in the brainstem and switches the sleeping brain into the highly active REM state, in which acetylcholine levels are as high as in the waking state. 5-HT and NE, on the other hand, are virtually absent during REM.

http://www.ncbi.nlm....cles/PMC534695/

 

 

So ok, you dream during the REM phase, when your brain is loaded with high levels of acetylcholine and low levels of serotonin and norepinephrine.

 

 

Inhibition of 5HT reuptake occurs with SSRIs, SNRIs, tricyclic antidepressants, and the antidepressant trazodone and would be expected to promote wakefulness by increasing the binding to 5HT1 and 5HT2 receptors. By increasing binding to 5HT1 receptors, an increase in wakefulness may occur in association with suppression of REM sleep.

 

http://www.ncbi.nlm....les/PMC3076958/

 

Dopamine reuptake inhibition would be expected to have wake promoting effects.

http://www.ncbi.nlm....les/PMC3076958/

 

 

As a result, medications which inhibit this enzyme, monoamine oxidase inhibitors (MAOI), increase the available amount of NE, 5HT, epinephrine, and DA, and, much like agents which inhibit the reuptake of these neurotransmitters, MAOI may have some degree of wake promoting effects.

http://www.ncbi.nlm....les/PMC3076958/

 

Among antidepressant and antipsychotic agents, suppression of REM sleep appears to primarily derive from blockade of Ach receptors (occurs primarily with TCAs and a number of the antipsychotic agents) and increasing 5HT binding to 5HT1A receptors, which occurs with TCAs, MAOIs, SSRIs, and SNRIs.

http://www.ncbi.nlm....les/PMC3076958/

 

So, high levels of serotonin and dopamine seems to promote wakefulness and supress REM sleep. 

 

Well, now we should look again at the compounds that I mentioned in my first post:

 

- Uncaria Rhynchophylla

 

Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla.

http://www.ncbi.nlm....pubmed/15890481

 

Geissoschizine methyl ether, an alkaloid from the Uncaria hook has third-generation antipsychotic-like actions at the dopamine and serotonin receptors.

http://www.ncbi.nlm....pubmed/21951966

 

Rhynchophylline and isorhynchophylline inhibit NMDA receptors expressed in Xenopus oocytes.

https://www.ncbi.nlm...pubmed/12433591

 

 

 

- Ziziphus Jujuba

 

Dopamine and serotonin activity:

Interactions were demonstrated with the adenosine A(1) receptor, dopamine transporter and dopamine D(5) receptor (antagonist activity), serotonin receptors (5-HT(1B) and 5-HT(6) antagonist activity) and the GABA benzodiazepine receptor at a concentration of 100 microg/ml or lower. these results suggested that the hypnotic effect of jujubosides on normal rats may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujubosides. Jujubosides may be good source of lead compounds for novel hypnotics.

 

NMDA inhibition.

http://www.ncbi.nlm....pt=AbstractPlus

 

- Albizia Julibrisin

 

The present study was undertaken to investigate the antidepressant-like effects of the methylene chloride fraction of Albizzia julibrissin (MCAJ) using a tail suspension test in mice. MCAJ was orally administered at 50, 100, or 200 mg/kg to mice, 1 h before the tail suspension test. Acute treatment with MCAJ at 200 mg/kg significantly reduced the immobility time compared with the control group, and thus showed an antidepressant-like effect. This effect was comparable to that of imipramine at 10 mg/kg. This antidepressant-like effect was reversed by treatment with WAY-100635 (a 5-HT1A receptor antagonist) or pindolol (a 5-HT1A/1B receptor antagonist). However, the antidepressant effect of MCAJ was not effected by treatment with GR55562 (a 5-HT1B receptor antagonist) or ketanserin (a 5-HT2A receptor antagonist). Therefore, our findings suggest that MCAJ exerts its antidepressant-like effect via the 5-HT1A receptor system.

 

 

So, we know that dopamine and serotonin plays a mayor role in wakefulness, and they supress REM phase in some way. Also, our three herbs interact with this sistems. 

 

Uncaria works like the antipsychotic medication Aripiprazole.

 

 

When looking at the level of the receptors, geissoschizine methyl ether is a potent agonist of the 5-HT1A receptors while it is inhibitory at the 5-HT2A, 5-HT2C, and 5-HT7 receptors at the same concentration range, with the possibility of being a partial agonist at higher doses. This profile is very similar to the anti-psychotic drug Aripiprazole.

 http://www.ncbi.nlm....pubmed/21951966 .

 

Does Aripiprazole interfere with dreaming?

 

105 reported cases of abnormal dreams while using Aripiprazole.

https://www.druginfo...mal dreams.html

 

Some anecdotal testimonies of antipsychotics causing lucid dreaming.

https://drugs-forum....ad.php?t=240904

 

Uncaria and Jujuba shows NMDA inhibition like we show before.

 

Does NDMA inhibitor interfere with dreaming?

 

Ketamine acts primarily as an antagonist of the NMDA receptor, and this action accounts for most of its effects.

http://journals.lww...._Tricks.39.aspx

 

Ketamine's other measurable effects on the body include rapid-eye movements, salivation, and the production of brainwave activity mimicking that of a dream state. So. if you look at the facts, you'll see what we have here is a safe, highly effective, and extremely repeatable means of inducing a lucid dream state at will. When administered in the correct dose, Ketamine is a lucid dream enabler (LDE). 

 

How I think this suplement works on inducing lucind dreaming?

 

I think the main responsable is Uncaria Rhynchophylla because of:

 

-His MAO-B inhibition. 

(+)-catechin and (-)-epicatechin inhibit the degradation of dopamine during the REM phase.

 

-His 5-HT regulation.
Geissoschizine methyl ether modulates the amount of serotonin in the brain during the REM phase.

 

-His NMDA inhibition.

I don't know why yet, but it seems to be a link between NMDA and lucid dreaming.

 

My hypothesis is that the brain shut down the consciousness lowering the levels of dopamine and serotonin during the dreaming phase. Uncaria doesn't alow to do that, keeping your mind awake even when you are sleeping, and causing lucid dreaming.

 

On topic: Would galantamine work as well? 

 

-Galantamine enhances dopaminergic neurotransmission in vivo via allosteric potentiation of nicotinic acetylcholine receptors.

http://www.ncbi.nlm....pubmed/16641937

 

-On the basis of the studies reviewed, galantamine does not appear to affect serotonin (5-HT) release in the brain.

http://www.life-enha...nsmitter-spiral

 

-Noradrenaline is the brain’s version of adrenaline. In another in vivo microdialysis study, it was shown that galantamine with nicotine given at ineffective doses increased noradrenaline release, although galantamine (3 mg/kg) alone did not affect the release in the hippocampus of rats.

http://www.life-enha...nsmitter-spiral

 

-Galantamine seems to potentiate of NMDA receptors.

http://www.ncbi.nlm....pubmed/15121761

 

In conclusion, if our hypothesis is right, galantamine doesn't see like the best way to induce lucid dreaming. Galantamine increases the acetylcholine, which is already elevated during dreaming, but Uncaria also acts increasing the acetylcholine in the brain:

 

Geissoschizine methyl ether, a corynanthean-type indole alkaloid from Uncaria rhynchophylla as a potential acetylcholinesterase inhibitor.

http://www.ncbi.nlm....pubmed/21714741

 

So, while Galantamine acts on dopamine an acetylcholine, Uncaria acts on Acetylcholine, Serotonin, Dopamine and MNDA inhibition, all of them seems related with lucid dreaming. Uncaria seems to be a superior option for lucid dreaming and maybe even for brain health proposes:

 

Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation.

http://www.ncbi.nlm....pubmed/24164737

 

Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways.

http://www.ncbi.nlm....pubmed/25079660

 

Geissoschizine methyl ether, an alkaloid from the Uncaria hook, improves remyelination after cuprizone-induced demyelination in medial prefrontal cortex of adult mice.

http://www.ncbi.nlm....pubmed/24190599

 

Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease.

http://www.ncbi.nlm....pubmed/21714741

 

Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack. in rats with kainic acid-induced epileptic seizure.

http://www.ncbi.nlm....pubmed/10467459

 

Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer's beta-amyloid proteins.

http://www.ncbi.nlm....pubmed/16676329

 

 

And for overall health:

 

Uncarinic Acid C Isolated from Uncaria rhynchophylla Induces Differentiation of Th1-Promoting Dendritic Cells Through TLR4 Signaling.

http://www.ncbi.nlm....pubmed/21499439

 

Inhibition of phospholipase cgamma1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla.

http://www.ncbi.nlm....pubmed/10869194

 

Please, let me know if I need some more references. Thanks. Also, excuse my english, is not my main language.

 

PD: I do not sell Uncaria or any other thing. I just get pissed off with the votes. And yes, Uncaria is one of my favorites herbs, extremely underrated though.