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Chemically induced LTP?

ciltep pde4 forskolin ltp

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#1261 str1k3r

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Posted 14 March 2013 - 08:57 AM

Would be awesome if this forum had a wikipedia style cliffnotes page for monster threads like these...

I read your stack on pages 1-5, but I'm wondering what your current stack is (I haven't read all 40+ pages)? And also where you buy them. If you don't mind repeating. Or you can just link me to the latest post?

#1262 abelard lindsay

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Posted 14 March 2013 - 12:39 PM

Would be awesome if this forum had a wikipedia style cliffnotes page for monster threads like these...

I read your stack on pages 1-5, but I'm wondering what your current stack is (I haven't read all 40+ pages)? And also where you buy them. If you don't mind repeating. Or you can just link me to the latest post?


I updated the first post with my current stack and a brief summary of the thread.
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#1263 xsiv1

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Posted 14 March 2013 - 01:23 PM

I need a pick me up at 2-2:30 that doesn't involve caffeine, ephedrine or disturb my sleep heh. Sulbutiamine used to do the trick but I refuse to go over 400mgs. It's the reason I asked if anyone has ever used the CILTEP stack more than once in a day. I know I should address the root cause, but for the sake of someone whose pressed for time as it is (on recumbent now). Anyone get benefit from those green food shakes around lunch? (12pm). Tried Maca.. It's not doing anything discernible. ALCAR, multi - vitamins, EFAs, antioxidants are all used in modest amounts and I don't use alcar everyday.


Galaxy: You could try Rhodiola, it seems to go well with this stack. It'll raise your catecholamines and serotonin without burning you out. It can even improve sleep quality despite its stimulative nature: http://www.ncbi.nlm....pubmed/12423559

Green superfoods can work atleast spirulina/chlorella based tend to give very natural feeling energy.

AL:
I've been taking a Jarrow 350mg N-Acetyl-L-Tyrosine to get through the afternoon. It takes about 45 minutes to kick in. I am still working on perfecting the timing of when I take it. So far, taking it at about 1pm seems to work pretty well.


Thank you both. I have Rhodiola as a matter of fact and suppose I could try it around 1-2. My only concern is whether it's serotonergic enough to mix poorly with my smallish dose of an SSRI at bedtime. I've been on it for over a decade with no discernible effects (positive or negative anymore) and really have to find the mental fortitude to just wean off if properly. If anything, it may help me sleep some.

Also, AL, thanks for that suggestion. That's the very brand I use in my CILTEP stack on some days. Other days I'll use L-Phenylalanine and typically avoid 500mgs of L-Tyrosine only because it seemed to make me irritable in the past. Weird. Thanks again fellas.

Edited by xsiv1, 14 March 2013 - 01:32 PM.


#1264 Reformed-Redan

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Posted 14 March 2013 - 09:45 PM

This looks interesting:http://www.ncbi.nlm.nih.gov/pubmed/15790999

N-coumaroyldopamine and N-caffeoyldopamine increase cAMP via beta 2-adrenoceptors in myelocytic U937 cells.

Park JB.

Source

Phytonutrients Laboratory, BHNRC, ARS, USDA, 307C, Rm. 131, Beltsville, Maryland 20705, USA. parkj@ars.usda.gov

Abstract


N-caffeoyldopamine is a phytochemical found in various plants, including cocoa (Theobroma cacao L.). N-caffeoyldopamine and its natural analogs (N-cinnamoyldopamine, N-coumaroyldopamine, N-feruloyldopamine, and N-sinapoyldopamine) were synthesized and investigated to determine their potency as beta-adrenoceptor agonists, because they have chemical structural moieties found in beta-adrenoceptor agonists. Among the compounds tested in this study, N-coumaroyldopamine and N-caffeoyldopamine were the two most potent compounds, able to increase cAMP at the concentrations < 0.05 microM in U937 cells. The decreasing order of potency was N-coumaroyldopamine > N-caffeoyldopamine > N-feruloyldopamine > N-sinapoyldopamine > N-cinnamoyldopamine. Using beta2-specific antagonists (butoxamine and ICI 118551), N-coumaroyldopamine and N-caffeoyldopamine were found to increase cAMP via beta2-adrenoceptors in U937 cells. In producing cAMP in U937 cells, N-coumaroyldopamine and N-caffeoyldopamine were as potent as several well-known beta2-adrenoceptor agonists (salbutamol, procaterol, and fenoterol). These results indicate that N-coumaroyldopamine and N-caffeoyldopamine are potent compounds able to increase cAMP via beta2-adrenoceptors in U937 cells, and may have potential effects on human health.


This is just cool food for knowledge:
http://www.pnas.org/...6/2366.full.pdf

ABSTRACT Using primary olfactory neuronal cultures,
we have demonstrated rapid, potent increases in cAMP levels
and adenylate cyclase [AC; ATP pyrophosphate-lyase (cyclizing),
EC 4.6.1.1] activity in response to odorants. Isobutylmethoxypyrazine
is active at 1 nM. Odorant enhancement is
dependent on Ca22 concentration with maximal effects at
10-100 pzM. Biphasic temporal and concentration-related effects
occur with all odorants. All odorants examined elicit
desensitization with AC responses abolished when odorants are
reapplied immediately after removal. When reapplied 1 min
after removal, odorants elicit an AC response greater than on
first exposure, implying a cellular "memory" for odorants.



#1265 johnj88

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Posted 15 March 2013 - 01:16 AM

I had previously stated that 10 mg BID Coluracetam had synergized well with the CILTEP stack. I'm going to have to retract this statement.
A few days ago, I had taken CILTEP + Coluracetam + 15 mg Adderall sublingual (5 mg in the morning, 10 mg at night). I had a gut feeling that day that I wasn't feeling the Adderall as much as I should have been, especially as CILTEP enhances the subjective dopaminergic effect. I had to chug coffee along with the Adderall.

Today, I took CILTEP and 5 mg Adderall IR sublingual, and no Coluracetam, with even less sleep than the other day. Completely different feeling, the 5 mg Adderall IR felt much stronger.

All conjecture, but I'm going to go out on a limb and say that Coluracetam facilitates dopamine and decreases dopamine, much like Bacopa, antagonizing the stack. The somnolence from Coluracetam mimics that of Bacopa's as well. Finally, on days with just CILTEP + Coluracetam + L-phe + coffee, again I felt like Coluracetam diminished the effects of dopaminergic effects of CILTEP, as compared to just CILTEP + L-phe + coffee.

Edited by johnj88, 15 March 2013 - 01:16 AM.


#1266 xsiv1

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Posted 15 March 2013 - 02:21 AM

I had previously stated that 10 mg BID Coluracetam had synergized well with the CILTEP stack. I'm going to have to retract this statement.
A few days ago, I had taken CILTEP + Coluracetam + 15 mg Adderall sublingual (5 mg in the morning, 10 mg at night). I had a gut feeling that day that I wasn't feeling the Adderall as much as I should have been, especially as CILTEP enhances the subjective dopaminergic effect. I had to chug coffee along with the Adderall.

Today, I took CILTEP and 5 mg Adderall IR sublingual, and no Coluracetam, with even less sleep than the other day. Completely different feeling, the 5 mg Adderall IR felt much stronger.

All conjecture, but I'm going to go out on a limb and say that Coluracetam facilitates dopamine and decreases dopamine, much like Bacopa, antagonizing the stack. The somnolence from Coluracetam mimics that of Bacopa's as well. Finally, on days with just CILTEP + Coluracetam + L-phe + coffee, again I felt like Coluracetam diminished the effects of dopaminergic effects of CILTEP, as compared to just CILTEP + L-phe + coffee.


Did you feel wired for sound on that first day a few days ago? Sounds quite 'activating' to say the least.

#1267 elsargente

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Posted 15 March 2013 - 06:54 PM

So I took the following stack in the AM for about two weeks:

10mg Life Extension Forskolin
400mg NOW Foods Quercetin
1000mg NOW Foods L-Phenylalanine
100-200mg Caffeine

I noticed some pretty profound effects at first, and then it seems like the effects diminished somewhat. I stopped taking the stack for about a week and my grades started slipping so I decided to start taking the stack again on Monday and all week I have seen better motivation, concentration, clarity, reaction time, reasoning, ability to handle stress, ability to multi-task, organization... basically just about everything has improved, except my short-term memory seems to be about the same. I was wondering if you guys knew of anything I could take with this stack that would improve my short-term memory, and specifically help with a College Algebra course. Thanks. I also have some NOW Foods Artichoke Extract on the way, hopefully that works even better than the Quercetin, which I have read may affect memory negatively.

#1268 Reformed-Redan

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Posted 15 March 2013 - 07:42 PM

So I took the following stack in the AM for about two weeks:

10mg Life Extension Forskolin
400mg NOW Foods Quercetin
1000mg NOW Foods L-Phenylalanine
100-200mg Caffeine

I noticed some pretty profound effects at first, and then it seems like the effects diminished somewhat. I stopped taking the stack for about a week and my grades started slipping so I decided to start taking the stack again on Monday and all week I have seen better motivation, concentration, clarity, reaction time, reasoning, ability to handle stress, ability to multi-task, organization... basically just about everything has improved, except my short-term memory seems to be about the same. I was wondering if you guys knew of anything I could take with this stack that would improve my short-term memory, and specifically help with a College Algebra course. Thanks. I also have some NOW Foods Artichoke Extract on the way, hopefully that works even better than the Quercetin, which I have read may affect memory negatively.

Caffeine reduces cAMP. Might want to cut down on it if it weakens the CILEP stack. Still thinking Kanna is a better PDE4 inhibitor

Edited by redan, 15 March 2013 - 08:11 PM.

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#1269 peakplasma

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Posted 15 March 2013 - 07:58 PM

Caffeine reduces cAMP. Might want to cut down on it if it weakens the CILEP stack. Still thinking Kanna is a better PDE4 inhibitor

Do you have more information to support this claim?

Isn't caffeine a non-selective PDE inhibitor?

"[caffeine] blocks the Enzyme phosphodiesterase from removing the secondary messenger cAMP, so the excitory signals from adrenaline etc. persist much longer"


Also,

The stuffs dirt cheap also.


In a previous post you mentioned a selective PDE4 inhibitor RS-82856 was cheaply available. Do you have more information? Where would obtain this?

#1270 Reformed-Redan

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Posted 15 March 2013 - 08:10 PM

Caffeine reduces cAMP. Might want to cut down on it if it weakens the CILEP stack. Still thinking Kanna is a better PDE4 inhibitor

Do you have more information to support this claim?

Isn't caffeine a non-selective PDE inhibitor?

"[caffeine] blocks the Enzyme phosphodiesterase from removing the secondary messenger cAMP, so the excitory signals from adrenaline etc. persist much longer"


Also,

The stuffs dirt cheap also.


In a previous post you mentioned a selective PDE4 inhibitor RS-82856 was cheaply available. Do you have more information? Where would obtain this?

On both accounts I was mistaken. Sorry.

#1271 peakplasma

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Posted 15 March 2013 - 08:12 PM

On both accounts I was mistaken. Sorry.


We all make mistakes. It's very honourable to own to it like that. :~

#1272 Reformed-Redan

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Posted 15 March 2013 - 09:37 PM

Has anyone looked at reelin for facilitating LTP?

The NMDA receptor is modulated by a number of endogenous and exogenous compounds:[25]

Reelin modulates NMDA function through Src family kinases and DAB1.[29] significantly enhancing LTP in the hippocampus.



#1273 sparkk51

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Posted 16 March 2013 - 02:35 AM

Abelard, dont you think you should list reduced working-memory as a possible side effect on the first post?

#1274 abelard lindsay

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Posted 16 March 2013 - 02:52 AM

Abelard, dont you think you should list reduced working-memory as a possible side effect on the first post?


Added that. Hopefully, with the first post edits, people reading the thread from the beginning will get the more up-to-date stack instead of the earlier versions from the first few pages of the thread.

I took 100mg kanna with my regular 2 artichoke pills stack yesterday and was able to break out of my usual score range on odd-one-out. I also did well on paired associates, though not my high score. I've played these games 100s of times so getting these new high scores is pretty significant. I did not take the kanna stack today and played odd-one-out a few times and could not break out of my usual score range. I got the same score on Paired associates as when I was taking the artichoke/kanna stack yesterday.

Remember, Kanna is strong stuff and an SSRI, so it is not advisable to take with St John's Wort or prescription SSRIs or by people who react negatively to SSRIs.

Edited by abelard lindsay, 16 March 2013 - 03:37 AM.


#1275 Q did it!

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Posted 16 March 2013 - 06:48 PM

Started on the CILTEP stack last week and must say is has some great affects. Keeps me motivated and throughout the day. Have not taken it long enough to gauge memory effect to much but recall for numerical data has defiantly increased.

Here is my currant stack below. Might there be anything you guys can think of that might need to be taken away or added?

Attached Files


Edited by Q did it!, 16 March 2013 - 07:19 PM.


#1276 abelard lindsay

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Posted 16 March 2013 - 07:39 PM

I took 150mg of kanna today along with 10mg forskolin. I figure that since the PDE effects are more specific, I could up the forskolin dose without ill effects.

I just scored in the 97th percentile on the polygons concentration test on cambridgebrainsciences.com. This is a HUGE improvement over my usual score which is usually below the 50th percentile. *edit*: Meh, maybe I just got lucky. The next score about an hour later was in the normal range or maybe the effect is short-lived.. In fact, the concentration tests are my worst area by far. There's a definite effect I can feel, like my sub-conscious knows the answer to problems before my conscious brain does and subtly signals the answer to my conscious brain. Enough raving :). Probably just a placebo. On the downside, I have a very mild headache.

Edited by abelard lindsay, 16 March 2013 - 08:42 PM.


#1277 peakplasma

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Posted 16 March 2013 - 08:15 PM

Okay.. so it looks like Kanna is in the mix.

What brand do you take? Is 150mg the appropriate dose? Is that an extract?

At what dose is there euphoria? At what dose does it become "too psychoactive"? There seem to be an abundance of Erowid reports and I'm not looking to get high.

Also, should it be fermented? Or raw?

Edited by peakplasma, 16 March 2013 - 08:35 PM.


#1278 health_nutty

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Posted 16 March 2013 - 08:26 PM

Where do you buy your Kanna?

Sent from my SCH-I510 using Tapatalk 2



#1279 abelard lindsay

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Posted 16 March 2013 - 08:44 PM

I got mine on Amazon from mood and mind. The effect seems to be short lived if they are there (see my edit to the above post). Maybe an hour or two? 150mg is pleasant but certainly doesn't get me high. It doesn't say that it's fermented, so I guess it's not.

http://informahealth...i.36.3.173.6350

J Ethnopharmacol. 2009 Jan 12;121(1):86-91. doi: 10.1016/j.jep.2008.10.008. Epub 2008 Oct 17.
Investigations of the phytochemical content of Sceletium tortuosum following the preparation of "Kougoed" by fermentation of plant material.
Patnala S, Kanfer I.
Source
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Artillery Road, Grahamstown, East Cape, South Africa.
Abstract
AIM OF THE STUDY:
Sceletium plant species that contain alkaloids are claimed to have mood elevation and anti-anxiety properties, especially after the plant material has been fermented. The fermented preparation is locally known as "kougoed" or "channa" and has been emphasized and advertised for its increased potency when incorporated in commercial products. The aim of the study was to investigate quantitative and qualitative changes in alkaloidal content following fermentation of plant samples carried out under controlled conditions and also on pure mesembrinehydrochloride (MHCl).MATERIALS AND METHODS:
Samples were prepared from the aerial parts of Sceletium tortuosum. Studies were also conducted on mesembrinehydrochloride (MHCl) in aqueous and methanolic solutions under similar conditions of exposure to sunlight as well as under ambient and elevated temperature (40+/-2 degrees C). Quantitative and qualitative changes in alkaloidal content were monitored by HPLC and LC-MS, respectively.RESULTS AND CONCLUSIONS:
The initial fermentation study showed transformation of mesembrine to Delta(7)mesembrenone, where the content of the former decreased from a concentration of 1.33% to 0.05% whilst the latter increased from below its limit of quantitation (LoQ) to 0.11% on the 10th day. The experiments on pure MHCl revealed similar transformations in aqueous solutions whereas no change was seen in methanolic solutions. Sunlight and aqueous conditions appear necessary to facilitate the transformation, which was confirmed by the absence of such a transformation when solutions of MHCl were kept in the dark.



So the unfermented has mesembrine which has been shown to have pde4 activity in the earlier study. On the downside unfermented has more oxalate content (kidney stones, etc) so don't take too much (according to website below).

http://kanna-sceleti...ts-of-kana.html

Dried unfermented Kanna has a high oxalate content, up to 5.1 % has been recorded. Oxalates are associated with kidney stones, kidney damage, and even kidney failure. One study estimates the normal average daily intake of oxalates per person to be around 150 mg. On a high dose of Kanna of 200 mg twice daily (higher then normal usage), and assuming maximum oxalate content of 5.1% , the amount of daily oxalate intake from Kanna would be 20.4 mg. This in itself is perhaps unlikely to cause harm , but if combined with other high oxalate foods and with an added sensitivity towards oxalates, could perhaps be problematic.Normally though, I would not expect oxalates from dried Sceletium to be nephrotoxic if the user adheres to the recommended dosage. Calcium rich foods diminish the absorpsion of oxylates. Avoid using fresh undried Kanna. Oxalates can cause irritation to the mouth. If this occurs it may be better to take Kanna with meals. Milk or ice cream can be taken to help sooth symptoms of the mouth.


Before you get too worried, for comparison:
http://www.whfoods.c...=george&dbid=48

One cup of raw spinach in leaf form (not chopped) weighs about one ounce, and contains about 200 milligrams of oxalate, so 50 milligrams for the day would permit a person to consume only 1/4 cup of raw spinach (and no other oxalate sources could be eaten during the day).



http://www.ncbi.nlm....pubmed/21798331

Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s<1 μM).



So fermented has higher Delta(7)mesembrenone vs mesembrine in unfermented. Whether Delta-7-Mesembrone inhibits PDE4 is not something I was able to find out.


...... Oh cool, some south african site has the full studies online. (Note, while browsing around the main site I got some funny java applet warning)

http://www.def-sa.co...-food-plant.pdf


Seems that Zembrin is the purified PDE4 inhibitor they are talking about in this study.

http://www.def-sa.co...-food-plant.pdf

The extract Sceletium tortuosum Zembrin® was tested at
750g/ml on activity of a panel of phosphodiesterases (Fig. 4).
PDE4 activity was completely inhibited, and that of PDE3 was
reduced by 88% (range 87–89%).The other enzymes were less inhibited: PDE1 by 27% (range 23–32%), PDE2 by 33% (range 30–36%), PDE5 by 29% (range 28–30%), PDE6 by 29% (range 27–31%), PDE7A
by 34%(range 31–37%), PDE8A by 4%(range 2–6%), PDE10A by 49%
(range 48–50%), and PDE11A by 50% (range 46–54%). I


Zembrin is available for purchase here:

http://www.vitasprin...CFQxxQgodxGYA-Q


Yet another supplement I have to buy.

Edited by abelard lindsay, 16 March 2013 - 09:37 PM.


#1280 Killword

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Posted 16 March 2013 - 08:49 PM

I got mine on Amazon from mood and mind. The effect seems to be short lived if they are there (see my edit to the above post). Maybe an hour or two? 150mg is pleasant but certainly doesn't get me high.


I have had Kanna before and it is indeed very short-lived. Any idea of how much mesembrine is in the dried plant? I have some 25x extract around that I have been considering trying with this stack.

Also: as far as psychoactivity, I have only ever noticed a slight stimulation and mood boost. Did not feel high at all... maybe a little manic with high doses, though. I used to use it for writing papers in college when I was out of ADD meds for which it worked quite well. I did need to redose every hour, though.

Edited by Killword, 16 March 2013 - 08:55 PM.


#1281 Reformed-Redan

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Posted 17 March 2013 - 12:12 AM

I got mine on Amazon from mood and mind. The effect seems to be short lived if they are there (see my edit to the above post). Maybe an hour or two? 150mg is pleasant but certainly doesn't get me high. It doesn't say that it's fermented, so I guess it's not.

http://informahealth...i.36.3.173.6350


J Ethnopharmacol. 2009 Jan 12;121(1):86-91. doi: 10.1016/j.jep.2008.10.008. Epub 2008 Oct 17.
Investigations of the phytochemical content of Sceletium tortuosum following the preparation of "Kougoed" by fermentation of plant material.
Patnala S, Kanfer I.
Source
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Artillery Road, Grahamstown, East Cape, South Africa.
Abstract
AIM OF THE STUDY:
Sceletium plant species that contain alkaloids are claimed to have mood elevation and anti-anxiety properties, especially after the plant material has been fermented. The fermented preparation is locally known as "kougoed" or "channa" and has been emphasized and advertised for its increased potency when incorporated in commercial products. The aim of the study was to investigate quantitative and qualitative changes in alkaloidal content following fermentation of plant samples carried out under controlled conditions and also on pure mesembrinehydrochloride (MHCl).MATERIALS AND METHODS:
Samples were prepared from the aerial parts of Sceletium tortuosum. Studies were also conducted on mesembrinehydrochloride (MHCl) in aqueous and methanolic solutions under similar conditions of exposure to sunlight as well as under ambient and elevated temperature (40+/-2 degrees C). Quantitative and qualitative changes in alkaloidal content were monitored by HPLC and LC-MS, respectively.RESULTS AND CONCLUSIONS:
The initial fermentation study showed transformation of mesembrine to Delta(7)mesembrenone, where the content of the former decreased from a concentration of 1.33% to 0.05% whilst the latter increased from below its limit of quantitation (LoQ) to 0.11% on the 10th day. The experiments on pure MHCl revealed similar transformations in aqueous solutions whereas no change was seen in methanolic solutions. Sunlight and aqueous conditions appear necessary to facilitate the transformation, which was confirmed by the absence of such a transformation when solutions of MHCl were kept in the dark.



So the unfermented has mesembrine which has been shown to have pde4 activity in the earlier study. On the downside unfermented has more oxalate content (kidney stones, etc) so don't take too much (according to website below).

http://kanna-sceleti...ts-of-kana.html

Dried unfermented Kanna has a high oxalate content, up to 5.1 % has been recorded. Oxalates are associated with kidney stones, kidney damage, and even kidney failure. One study estimates the normal average daily intake of oxalates per person to be around 150 mg. On a high dose of Kanna of 200 mg twice daily (higher then normal usage), and assuming maximum oxalate content of 5.1% , the amount of daily oxalate intake from Kanna would be 20.4 mg. This in itself is perhaps unlikely to cause harm , but if combined with other high oxalate foods and with an added sensitivity towards oxalates, could perhaps be problematic.Normally though, I would not expect oxalates from dried Sceletium to be nephrotoxic if the user adheres to the recommended dosage. Calcium rich foods diminish the absorpsion of oxylates. Avoid using fresh undried Kanna. Oxalates can cause irritation to the mouth. If this occurs it may be better to take Kanna with meals. Milk or ice cream can be taken to help sooth symptoms of the mouth.


Before you get too worried, for comparison:
http://www.whfoods.c...=george&dbid=48

One cup of raw spinach in leaf form (not chopped) weighs about one ounce, and contains about 200 milligrams of oxalate, so 50 milligrams for the day would permit a person to consume only 1/4 cup of raw spinach (and no other oxalate sources could be eaten during the day).



http://www.ncbi.nlm....pubmed/21798331

Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s<1 μM).



So fermented has higher Delta(7)mesembrenone vs mesembrine in unfermented. Whether Delta-7-Mesembrone inhibits PDE4 is not something I was able to find out.


...... Oh cool, some south african site has the full studies online. (Note, while browsing around the main site I got some funny java applet warning)

http://www.def-sa.co...-food-plant.pdf


Seems that Zembrin is the purified PDE4 inhibitor they are talking about in this study.

http://www.def-sa.co...-food-plant.pdf

The extract Sceletium tortuosum Zembrin® was tested at
750g/ml on activity of a panel of phosphodiesterases (Fig. 4).
PDE4 activity was completely inhibited, and that of PDE3 was
reduced by 88% (range 87–89%).The other enzymes were less inhibited: PDE1 by 27% (range 23–32%), PDE2 by 33% (range 30–36%), PDE5 by 29% (range 28–30%), PDE6 by 29% (range 27–31%), PDE7A
by 34%(range 31–37%), PDE8A by 4%(range 2–6%), PDE10A by 49%
(range 48–50%), and PDE11A by 50% (range 46–54%). I


Zembrin is available for purchase here:

http://www.vitasprin...CFQxxQgodxGYA-Q


Yet another supplement I have to buy.

Nice research work. Looks like you found what made the PDE4 activity. Here's a short and interesting read on Zembrin:
http://www.foodnavig...e-a-blockbuster
cant find a study supporting these claims:

Symposium S2 – 2: Translational study of standardized zembrin extract and mesembrenone targeting pde-4
(phosphodiesterase subtype 4) for regulation of mood and cognition
*Hana Raheb B. A Honors; ;*Yves Bureau PhD Michael Woodbury-Farina MD, Vladimir Badmaev MD PhD
Nigel Gericke MBBS *Kristen Terpstra B. A Honors ; *Simon Chiu MD PhD; *Zack Cernovsky PhD;*Yves Bureau
PhD *J Houicin PhD;.
Department Psychiatry University of Puerto Rico PR USA ## CEO P l Thomas Inc. NJ USA: CEO HGHinc. South
Africa; *Lawson Health Research Institute London, Ont. ;Dept Psychiatry , University of Western Ontario
London Ont. Canada
Joint presentation: *Hana Raheb B. A Honors (Preclinical) * Yves Bureau PhD Michael Woodbury-Farina MD
(clinical)
Background: . There is increased evidence that PDE-4 (Phosphodiesterase subtype-4) plays a crucial role in
regulating memory and affective processes. We identify . Zembrin® ,an extract of Sceletium tortuosum
standardized to mesembrenone and related alkaloids content to behave as PDE-4 modulator..
Objective:: 1)to screen for cognitive effect of, mesembrenone in Fisher-344 rats in Morris Water maze test;;
2)to examine whether Zembrin® extract enhances cognition and regulates mood symptoms ; 3) to evaluate
the safety and tolerability in normal controls.
Method / Results: 1)Preclinical: Fischer rats were administered mesmebrenone 0.1 mg/kg sc,1 mg/kg sc and
saline for 6 days. Primary efficacy outcome was water-maze cell latency with constant platform
arrangement.2)Clinical: Randomized placebo-controlled parallel group cross-over design for 3 weeks: 25 mg
capsule Zembrin and placebo capsule group. VitalSign (neurocognitive battery of test) and HAM-D were
administered. We recruited normal community sample
Results: 1)Preclinical results favoured Mesembrenone at 1 mg/kg and 0.1 mg/kg over the placebo regarding
latency scores.2) Clinical: 21 subjects :male/female ratio 9/12;mean age 54.6 + 6.0 yrs. participated in the
study and well tolerated Zembrin® with no nausea or vomiting. Zembrin extract selectively and significantly
improved cognitive set flexibility and executive function Sleep quality was noted to improve in Zembintreated group. No serious adverse events were noted..
Significance: Our study demonstrated for the first time provide evidence of PDE-4 modulation as a promising
therapeutic target for neurodegenerative disorders:

From: http://naturalbioact...acts_Part11.pdf

I'm wondering about the statistical significance. Is it 1 one-hundredth or one one thousandth?

#1282 xsiv1

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Posted 17 March 2013 - 02:03 AM

http://www.vitasprin...CFQxxQgodxGYA-Q

That's the exact one I bought and I ended up throwing it out as I did notice it interacting negatively with the SSRI I'm on. It's effects are said to closely mimic Clomipramine from what I remember which I was on years ago and was one of the first successful AD's that worked after trying nearly every SSRI. So, yes, I can attest to the restlessness and agitation I felt when combined with an SSRI. I found out the interaction a bit late. My mistake.

#1283 chung_pao

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Posted 18 March 2013 - 12:11 PM

I added EGCG (1g) for COMT-inhibition and wow... The dopamine surge was immense.
Since COMT-inhibitors increase the activity of dopamine in certain areas, such as the PFC, shouldn't that greatly facilitate LTP and synergize with the rest of the stack? I believe this ingredient has the effect of potentiating the effect of dopamine on LTP.
My short term memory and attention was through the roof after adding it.
This was easy to gauge; I studied some math and reading, which I routinely do, which was much more effortless.

After experimenting with the stack, my most potent version looks like this:

Acetyl-l-tyrosine (any tyrosine works though...)
Piracetam 1.2g (piracetam works better than noopept, it seems)
Forskolin (20 mg active)
Artichoke extract (1-2 pills, Jarrow)
Tea (for theophylline and the mixed xanthines and substances providing PDE-inhibition and cAMP/cGMP release) which I use as my only caffeine source
EGCG 0.5-1g (for COMT-inhibition)

I respond really well to the added comt-inhibition, I might have a high baseline of it, making the inhibition very effective.
If anyone isn't having success with the stack, I advice you to try adding EGCG.
Tea also synergizes excellently with it; the vasodilation, bronchodilation and subsequent calm is profound. Might be due to cGMP induced NO.

And for the junkies, there's also room for a dopamine-release agent
.

Edited by chung_pao, 18 March 2013 - 12:25 PM.

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#1284 norepinephrine

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Posted 18 March 2013 - 02:43 PM

I've also had the best results consuming both green tea and espresso on the same day during CILTEP dosing, as well as ginkgo.

#1285 alecnevsky

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Posted 18 March 2013 - 04:55 PM

Has anyone gotten burnt out on this? I was taking this for ~5 months (you can check thread history for my first posts) with minimal cycling (at most once or twice a week.) I stopped drinking coffee but continued drinking black tea., and, in conjunction with CILTEP, it seemed as if I was getting tired prematurely. I could not go 9-10pm without feeling burnt out by 6pm. I am now cycling CILTEP and feel much better. Some suggested adrenal fatigue but I am not even sure whether that's empirically relevant. I do feel better now that I am off it. It seems like my CNS is less stressed and I am in a clear-thinking state. I will cycle off for a week and update on redose next week.

#1286 Reformed-Redan

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Posted 18 March 2013 - 09:07 PM

I added EGCG (1g) for COMT-inhibition and wow... The dopamine surge was immense.
Since COMT-inhibitors increase the activity of dopamine in certain areas, such as the PFC, shouldn't that greatly facilitate LTP and synergize with the rest of the stack? I believe this ingredient has the effect of potentiating the effect of dopamine on LTP.
My short term memory and attention was through the roof after adding it.
This was easy to gauge; I studied some math and reading, which I routinely do, which was much more effortless.

After experimenting with the stack, my most potent version looks like this:

Acetyl-l-tyrosine (any tyrosine works though...)
Piracetam 1.2g (piracetam works better than noopept, it seems)
Forskolin (20 mg active)
Artichoke extract (1-2 pills, Jarrow)
Tea (for theophylline and the mixed xanthines and substances providing PDE-inhibition and cAMP/cGMP release) which I use as my only caffeine source
EGCG 0.5-1g (for COMT-inhibition)

I respond really well to the added comt-inhibition, I might have a high baseline of it, making the inhibition very effective.
If anyone isn't having success with the stack, I advice you to try adding EGCG.
Tea also synergizes excellently with it; the vasodilation, bronchodilation and subsequent calm is profound. Might be due to cGMP induced NO.

And for the junkies, there's also room for a dopamine-release agent
.


I'd be careful with adding a DRI or even nicotine for the matter. Burnout as the next post indicated could occur very fast. I think a crash or bad headache could be expected after this stack.

Edited by redan, 18 March 2013 - 09:09 PM.


#1287 Reformed-Redan

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Posted 18 March 2013 - 09:24 PM

Also check this thread on COMT inhibition:
www.longecity.org/forum/topic/50102-comt-inhibitor-synergy

#1288 Reformed-Redan

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Posted 18 March 2013 - 09:47 PM

This doesn't look to good:

COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and S-adenosylmethionine (SAM) against L-dopa toxicity in vitro.

Werner P, Di Rocco A, Prikhojan A, Rempel N, Bottiglieri T, Bressman S, Yahr MD.

Source

Department of Neurology, Albert Einstein College of Medicine and Beth Israel Medical Center, F-121N, 1300 Morris Park Ave., Bronx, New York, NY, USA. pwerner@aecom.yu.edu

Abstract


L-dopa may be toxic to dopamine neurons, possibly due to catechol-autoxidation. Catechols are O-methylated by catechol-O-methyltransferase (COMT) in a SAM consuming reaction, preventing the initiation of catechol autoxidation. We hypothesized that SAM or SAM-precursors ameliorate L-dopa neurotoxicity, in a COMT-dependent fashion. We tested this hypothesis in primary mesencephalic cultures by adding 200 microM L-dopa with 2 mM methionine or 1 mM dimethionine or 0.5 mM SAM with or without 0.2 microM of the COMT-inhibitor 2', 5'-dinitrocatechol (OR 486). L-dopa was found to be neurotoxic as the surviving neurons had fewer and shorter processes. Methionine, dimethionine and SAM all protected DA neurons against damaged induced by L-dopa. The COMT inhibitor dinitrocatechol (DNC) completely abolished the protective effect against L-dopa toxicity. We conclude that supplementation with methionine, dimethionine or SAM ameliorates L-dopa neurotoxicity to dopamine neurons, while inhibition of COMT may aggravate or unmask L-dopa neurotoxicity.

http://www.ncbi.nlm.nih.gov/pubmed/11223018

Wondering if combing a COMT inhibitor with a MAO-B inhibitor like selegiline would ameriolate the neurotoxic effects of DOPAC buildup... You'd take selegiline then a COMT inhibitor; but, the COMT can also induce DNA damage. Don't think it's worth it.

This paper supporting the claim that certain COMT inhibitors cause DNA damage:
http://toxsci.oxford.../2/316.full.pdf
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#1289 xsiv1

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Posted 19 March 2013 - 01:21 PM

I thought the reason many people avoid L-Dopa is because of it's actions in the body as well. Don't people take EGCG to counteract some of these effects? Regardless, I normally avoid L-Dopa and if I do include a dopamine precursor, it's L-Phenylalanine or L-Tyrosine/Acetyl L-tyrosine depending on how I feel that morning.

Edited by xsiv1, 19 March 2013 - 02:09 PM.


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#1290 MikeMMK1990@gmail.com

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Posted 19 March 2013 - 01:42 PM

Also check this thread on COMT inhibition:
www.longecity.org/forum/topic/50102-comt-inhibitor-synergy


How about Echinacea or Bilberry extract (cichoric acid)? Those seem like the safest COMT inhibitors according to this thread and his other.





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