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C10H12N20
03-09-2004, 16:10
Since it sounds like domestic L-Tryptophan (5HTP precursor) has been quietly allowed to be sold in the US, I wanted to examine the topic of 5HTP vs L-Tryptophan. Some books on 5HTP mention that L-Tryptophan is a better alternative to 5HTP (better absorption though BBB etc)... Has anybody heard more on this theory? I would imagine that 5HTP is better cause it's closer to serotonin in the process...

VelocideX
03-09-2004, 17:24
5-HTP is good in that it passes the blood-brain barrier much more rapidly than l-tryptophan, but is also suffers from a major drawback: the 5-HTP --> 5-HT (serotonin) occurs with the assistance of l-aromatic amino decarboxylase, which occurs pretty much everywhere in the body. Most cells in your body contain this enzyme, and the net effect is that <1% of 5-HTP actually makes it to your brain.

l-tryptophan is more efficient in making it to your brain, but 5-HTP is faster... ultimately l-tryptophan is probably a better supplement to postload with, but due to the long half-life for l-tryptophan --> serotonin conversion many people are unhappy with it -- they'd much rather take a pill that fixes them up a little bit within an hour than one which fixes them a lot more within 12 hours...

C10H12N20
03-09-2004, 17:42
So one could assume that 5HTP is better for postloading MDMA if you want quick results, and L-Tryptophan works better as an antidepressant?

AznHangukBoi
03-09-2004, 18:12
hmmm maybe i should get both 5-htp AND l-tryptophan...

C10H12N20
03-09-2004, 18:40
There is a theory that 5HTP can create Serotonin in the body and that can cause a heart attack, it's not proven but as a precaution i take 5HTP with magnesium. I wonder since L-Tryptophan is more efficient, maybe magensium is not necessary.

Adam X
03-09-2004, 20:40
5-HTP will cause serotonin production anywhere that L-AAAD is found. If you don't mind serotonin floating around parts of your brain where it's not necessarily supposed to be, then by all means take 5-HTP. I for one feel that the method which causes the least disruption for the brain/body is the best way to go, so I take L-tryptophan.

Also, the body uses L-tryptophan to make vitamin B3, not just serotonin.


X

C10H12N20
03-09-2004, 21:16
What about carcinogenic effects of L-Tryptophan that people talk about... Does L-Tryptophan have more carcinogenic properties than 5htp?

Adam X
03-09-2004, 21:44
Carcinogenic?

If someone wants to provide reliable references that orally administered L-trytophan is carcinogenic then by all means, please do.

Your body/brain need L-tryptophan, it's an essential amino acid. Most amino acids can be synthesized endogenously, L-tryptophan cannot. If L-tryptophan is carcinogenic it's news to me, and if it is, well that's the biggest catch-22 I've ever seen.


X

C10H12N20
03-09-2004, 21:54
You are right seems like a bunch of crap used for marketing 5htp:
http://www.bodyandfitness.com/Information/Health/Research/htp.htm

Here is the study that proves otherwise:
http://jeekim.com/~weight-loss/weight-loss-research-abs.5030.html

Adam X
03-09-2004, 22:37
(Picking apart http://www.bodyandfitness.com/Infor...esearch/htp.htm)


Compared with L-tryptophan, 5-HTP is one step closer to serotonin in the body's manufacturing process. In addition, far more 5-HTP is converted to serotonin (70% versus 1-3% ), because

Actually 100% of 5-HTP is converted to serotonin at some point. This isn't necessarily a good thing.


the body uses a large percentage of dietary L-tryptophan to make therapeutically irrelevant compounds (e.g., kynurenine, vitamin B3).

Vitamin B3 (niacin) is therapeutically irrelavent?

Nutr Cancer. 2003;45(1):124-31. (Chronic DNA damage and niacin deficiency enhance cell injury...)

Mutat Res. 2002 Oct 31;508 (1-2):83-97. ("...Niacin supplementation may help to protect the bone marrow cells of cancer patients...")

J Nutr. 2002 Jan;132(1):108-14. ("...niacin deficiency alters poly(ADP-ribose) metabolism in the bone marrow and increases the risk of nitrosourea-induced leukemias.")


In addition, consumption of L-tryptophan produces potentially toxic, carcinogenic compounds, especially under the very conditions (stress, anxiety) for which people have used L-tryptophan.

I've never seen something called "potentially toxic" and "carcinogenic" in the same sentence. Wouldn't something that is carcinogenic HAVE to be toxic? Furthermore, I see no evidence that L-tryptophan intake is associated with any sort of increased cancer risk.


And, 5-HTP is extracted from an African herb (Griffonia simplicifolia), making it inherently safer than a synthetically produced compound like L-tryptophan.

Cyanide can be extracted from peach pitts. Does this make it safer than the products of NaOH + HCl synthesis (water and table salt)?


X

AznHangukBoi
03-09-2004, 23:22
ahhh now this is getting me worried about which is best, or if taking either is worth while... lol

C10H12N20
03-09-2004, 23:31
Amazing what people will make up to sell shit... It sounds to me that L-Tryptophan is the way to go, at least for me. I found 5HTP short lasting, and when I take it, I get a mood swing on the downside five hours later. I will definitely try L-Tryptophan. Thanks for great input.

AznHangukBoi
03-09-2004, 23:43
tell me how it is when u get it, im interested

VelocideX
04-09-2004, 02:59
Thanks for your input Adam X... it is, as always, useful and substantiated.

Invalid Usename
04-09-2004, 10:46
Originally posted by C10H12N20
There is a theory that 5HTP can create Serotonin in the body and that can cause a heart attack, it's not proven...
And there isn't anything in the medical literature suggesting that this is the case, either.

Invalid Usename
04-09-2004, 10:51
Originally posted by Adam X
Actually 100% of 5-HTP is converted to serotonin at some point. This isn't necessarily a good thing.
Is that a personal opinion?

Pippin
04-09-2004, 12:44
(From VelocideX ) - I'd be inclined to agree that getting serotonin being produced in cells in which serotonin is not normally found is, a priori, probably not good. Cell membranes and other separative structures exist for a reason -- to keep some chemical reactions away from others. Whilst it might not have any effect, it might also have some as-of-yet unknown effect.

BlueMind
04-09-2004, 18:10
I have read that increased intake of 5-HTP leads to cardiovascular issues. Good for the head, but not the heart, apparently.

C10H12N20
04-09-2004, 18:27
BlueMind,

That's why you need to take 5HTP with magnesium. The theory goes that 5HT (serotonin) build acts as vasocontrictor... Magnesium on the other hand, helps to relax muscles, soft tissues and arteries... But look above, there might be no cardiovascular risk at all.

VelocideX
05-09-2004, 01:56
My problem with the 5-HTP --> serotonin = extra cardiovascular issues is that MAO is found quite prominently in the blood. I'm not sure of the exact concentrations, but would the serotonin simply not be oxidised by MAO-B in the blood? (I do realise that MAOA is the preferred substrate, but both are equally capable are they not?)

BilZ0r
05-09-2004, 04:59
hmmm....
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7619676

It seems possible then velocide... but I'm still notice convinced. That abstract doesn't say how high the initial dose was... and I suspect it was quite low, and that in higher doses you would get an increase in plasma 5-HT...

C10H12N20
05-09-2004, 18:29
So what does this mean? You do get 5HT produce outside your brain and if the dose was higher you would get it in the blood, hence the risk of heart problems is real?

BilZ0r
06-09-2004, 01:34
I would say that for a single dose, the effect on the heart would be minimal. Perhaps if you were taking 5-HTP everyday, it might be something to worry about.

BlueMind
06-09-2004, 17:44
For what it is worth, I have found websites now selling L-Tryptophan OTC, and labeling it for human consumption (as compared to the veterinary related stuff that is also available).

Adam X
07-09-2004, 18:15
I buy 1Kg of bulk USP L-tryptophan every few years for a few hundred dollars.


X

VelocideX
08-09-2004, 00:38
Yay for bulk amino acids :)

junglelove
08-09-2004, 00:51
magnesium as mentioned above is good, so is l-theanine and l-taurine which act as NMDA antagonists/blockers thus combating MDMA-induced neurotxicity and tolerance build-up. Many NMDA blockers have also been implicated in sparing effects upon 5-ht and serotonin when concominantly administered with MDMA and other alike substances.

VelocideX
08-09-2004, 01:47
I was not aware either l-theanine or l-taurine were NMDA antagonists. I've had a quick search around, but found nothing conclusive. Any references?

junglelove
08-09-2004, 02:12
Brain Res. 1978 Jul 28;151(1):215-9.

Theanine as a glutamate antagonist at a crayfish neuromuscular junction.

Shinozaki H, Ishida M.
--------
Toxicol Lett. 2001 Apr 30;121(2):89-96.

Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin.

Sugiyama T, Sadzuka Y, Tanaka K, Sonobe T.
-------
Biol Pharm Bull. 2002 Dec;25(12):1513-8.

Neuroprotective effects of the green tea components theanine and catechins.

Kakuda T.

Theanine is more efficient in blocking activation of AMPA/Kainate in glutamate receptors but also to a lessr degree blocks NMDA.

junglelove
08-09-2004, 02:13
Biosci Biotechnol Biochem. 2002 Dec;66(12):2683-6.


Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors.

Kakuda T, Nozawa A, Sugimoto A, Niino H.

BilZ0r
08-09-2004, 02:18
There isn't much good evidence that MDMA neurotoxicty is blocked by NMDA antagonists anyways... But there is some evidence (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12596867) that theanine binds very weakly to ionotropic glutamate receptors, but probably so weakly it doesn't matter

junglelove
08-09-2004, 02:21
JF Stover and AW Unterberg
Increased cerebrospinal fluid glutamate and taurine concentrations are associated with traumatic brain edema formation in rats.
Brain Res, September 1, 2000; 875(1-2): 51-5.
-----
N Menendez, O Herreras, JM Solis, AS Herranz, and R Martin del Rio
Extracellular taurine increase in rat hippocampus evoked by specific glutamate receptor activation is related to the excitatory potency of glutamate agonists.
Neurosci Lett, July 17, 1989; 102(1): 64-9.
----
SS Oja and P Saransaari
Modulation of taurine release by glutamate receptors and nitric oxide.
Prog Neurobiol, November 1, 2000; 62(4): 407-25.
----
A Dahchour and P De Witte
Taurine blocks the glutamate increase in the nucleus accumbens microdialysate of ethanol-dependent rats.
Pharmacol Biochem Behav, Feb 2000; 65(2): 345-50.


Endogenous taurine acts as a negative feedback loop upon most of the excitoxic actions at glutmate receptors; supplementing with exo-taurine makes good sense therefore

junglelove
08-09-2004, 02:24
Originally posted by BilZ0r
There isn't much good evidence that MDMA neurotoxicty is blocked by NMDA antagonists anyways... But there is some evidence (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12596867) that theanine binds very weakly to ionotropic glutamate receptors, but probably so weakly it doesn't matter

There isn't much evidence at all as far as how and what produces the 'alleged' MDMA neurotoxicity - just exploring possible pathways..

Adam X
08-09-2004, 02:40
I would say that the likelyhood that MDMA "neurotoxicity" is NDMA-receptor mediated is extremely unlikely. Significant excitotoxic insult results in actual neuronal destruction, not just "pruning" of the axons.


X

BilZ0r
08-09-2004, 05:08
Yeah, but that actaul binding paper junglelove, shows that theanine has a Ki for the NMDA receptor of 300ÁM, there no way you're gonna get that kinda concentration in the brain from recreational use.

VelocideX
08-09-2004, 13:11
Originally posted by Adam X
I would say that the likelyhood that MDMA "neurotoxicity" is NDMA-receptor mediated is extremely unlikely. Significant excitotoxic insult results in actual neuronal destruction, not just "pruning" of the axons.


X

I agree, though there is a larger question as to what effect NMDA antagonists have on methamphetamine/amphetamine. People report that they don't need to dose escalate when taking dexamphetamine and DXM concommitantly.

Adam X
08-09-2004, 23:45
I would wager that the same thing occurs when taking an SSRI like Prozac. DXM is also an SSRI. I would assume that post-synaptic serotonin levels probably mediate tolerance to dopamine increasing drugs by maintaining a homeostatic ratio of dopamine to serotonin. Even small increases in serotonin would likely have some effect on development of tolerance. I noticed that daily L-tryptophan also prevents tolerance to dextroamphetamine, and when some tolerance eventually does occur taking a break from Dexedrine and supplementing with high (2-3g/day) levels of L-tryptophan bring tolerance down to baseline within 21 days.


X

VelocideX
08-09-2004, 23:57
That's extremely interesting, I've never heard anything like that before (re dopamine-serotonin ratio). You're implying that tolerance isn't just due to some period of neurotransmitter excess but stems from an imbalance in the neurotransmitter ratio, which in theory could be altered by the appropriate drug from the opposite class?

Do you think this applies equally well to the noradrenic and cholinergic systems?

Do you have any references which might support this notion?

C10H12N20
09-09-2004, 00:04
has anybody proven that DXM is an SSRI? i had that suspicion, i always feel happy after taking cough medicine :)

VelocideX
09-09-2004, 00:07
DXM does indeed have serotonin-reuptake inhibiting properties. I found a whole bunch of references on this earlier I think...

VelocideX
09-09-2004, 00:12
From this thread (http://www.bluelight.ru/vb/showthread.php?s=&threadid=140425&highlight=DXM%2A)

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9232674
here is a paper which implies that 5-HT1 activation is a key component of dxm's antitussive (anticoughing) effect.

DXM appears to inhibit the uptake and metabolism of 5-HT in platelets:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=238000

Treatment with reserpine, a non-neurotoxic 5-HT depleter, inhibits the antitussive effect of DXM:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2965557

l-Tryptophan administration appears to increase the antitussive effects of DXM:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2384857

DXM appears to release 5-HT in the brainstem:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1636059

Adam X
09-09-2004, 00:22
That's extremely interesting, I've never heard anything like that before (re dopamine-serotonin ratio). You're implying that tolerance isn't just due to some period of neurotransmitter excess but stems from an imbalance in the neurotransmitter ratio, which in theory could be altered by the appropriate drug from the opposite class?

The brain constantly tries to maintain homeostasis. Serotonin-dopamine are fairly intimately linked, if the ratio of one to the other is disrupted the brain makes adaptive changes. Usually this change results in a dulling of the sites of action of amphetamine, instead of a boosting of the serotonin (which could create problems itself). Trick the brain into thinking that serotonin and dopamine levels are in proper proportion and you slow the process of tolerance. Look at MDMA tolerance/addiction compared to d-amp or d-meth... Which would you rather have to deal with?


Do you think this applies equally well to the noradrenic and cholinergic systems?

I don't know. I would guess no, since tolerance to the physiological stimulant effects of amp decreases more rapidly than tolerance to the behavioral.


Do you have any references which might support this notion?

Not at the moment, this is just a theory of mine. I might dig around though, but I don't see how I'd be able to find anything really conclusive either way. Plus I have a chem midterm coming up, maybe when that's done I'll have more time to poke around.


X

VelocideX
09-09-2004, 00:37
Nice theory in any repect :)

junglelove
09-09-2004, 02:58
That is a very viable pathway: usually serotonin acts as a negative feedback, check upon dopamine. excitation of 5-ht2a receptors by mdma is a trigger to dopamine release, while 5-ht2a antagonists preclude or delay DA release. Notably mdma also binds to 5-ht1a which inhibits serotonin firing and decreases tryptophan hydroxylase. given that mdma has a much higher binding affinity to 5-ht sites than DA it seems to be the case that via desensitization and inhibited production of 5-ht (inhibit tr hydroxylase) less DA is stimulated to be released because less 5-ht receptors are available for agonism. modulating 5-ht receptor sites might be an alternative pathway to combat tolerance buildup - that might be a reason why DXm works so well along with ssri's (via 5-ht inhibition and receptor upregulation)

BilZ0r
09-09-2004, 03:11
hang on, hang on, hang on.
Adam, correct me if I'm wrong you're saying, DXM could/does inhibit METH tolerance, by acting as an SSRI. Now you must be saying that by acting as an SSRI, its increasing 5-HT levels? See I just wonder. METH is going to be releasing some 5-HT anyways, not to much granted, but the SSRI action of DXM might cancel out the releasing abbility, and kinda equal things out.

MDMAs affinity for 5-HT1A has gotta be pretty tiny, but I don't get the rest of your explanation.