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DL Phenylalanine: How does it work?

sweethome

Bluelighter
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Oct 2, 2008
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Can anyone provide some insight into DL Phenylalanine? Specifically how it works on the body?
I've found it to be quite helpful for seasonal depression. It is also quite good for a mood lift. On days when I feel quite down, I have taken it and noticed that it seems to help.
I can completely rule out placebo. I originally took the stuff based on advice of a friend who said she takes it as a supplement to help her function. I originally had no idea it helped with depression but I noticed that it certainly does help after I took it on a day when I was really down and out. Shortly after, I felt like my normal self again.... even perhaps in a better mood.
I read many reports online from people who echo my sentiments about this drug.

Does it work on the brain? Specifically on serotonin or dopamine? After I take it, what is actually occurring in my body with it?
 
DL-phenylalanine is a mix of D-phenylalanine and L-phenylalanine.

L-phenylalanine is converted by the body into dopamine and noradrenaline, and so is useful for boosting levels of these if you are deficienct for some reason.

D-phenylalanine increases the activity of endogenous opioid peptides like endorphin, enkephalin etc, think it inhibits their breakdown?

So the racemic mix is quite a good supplement for general mood lift and so on.
 
I've also heard that DL increases the effects of opiods. Any truth to this? I know there are a million threads on increasing the effects of opiods already. (Just a quick shift.... not trying to change topic)

Could you explain further about your comment "D-phenylalanine increases the activity of endogenous opioid peptides like endorphin, enkephalin etc, think it inhibits their breakdown? "
What specific feelings would this produce in the body?
 
Yes, it inhibits metabolism.

Budd, Keith, "Use of D-Phenylalanine, an Enkephalinase Inhibitor, in the Treatment of Intractable Pain, Adv. In Pain Research and Therapy.
 
I posted a response here but it flew away. OP asked what "feelings" D-phenylalanine's inhibition of enkephalinase will produce. I've seen nothing convincing in the scientific literature that confirms D-Phe's efficacy in CNS enkephalinase inhibition. It is, however, somewhat more active (significantly so?) peripherally, and thus has intestinal antisecretory effects, leading to firmer, drier stools. But the data suggest that D-Phe's psychotropic and analgesic effects are, at best, negligible (although some D-Phe is possibly converted to L-Phe). Experiantially, the opioid potentiation some DLPA users report is better explained as placebic (if that's a word).
 
L-phen is mainly a precursor to all endogenous phethylamines which include PEA, dopamine, norepinephrine, and epinephrine.

D-phen inhibits enkephalinase which breaks down enkephalins. Enkephalins stimulate the delta and mu opioid receptors, which in turn release even more dopamine.
 
phenylalanine is a precursor to dopamine and epinephrine as it is an amino acid tyrosine works in a similar way with vitamins and enzymes to produce chemical reactions that you keep your body operating at homeostasis

as an opiod potentiator i beelieve it to bee worthless although including it in your diet is prob a good idea seeing as us BL-ers like to deplete our natural neuro-makeup
 
People swear these drugstore amino acids are effective. Don't waste your money. "The rate-limiting enzymatic step in the synthesis of any of the catecholamines is catalyzed by tyrosine hydroxylase. Dietary changes in tyrosine levels, therefore, do not influence the synthesis of catecholamines." Synopsis of Psychiatry, Kaplan and Saddock 2007, page 100.

Even if you get past the rate limiting step by taking levodopa, you still need to lasso the aromatic amino acid decarboxylase effectively; so unless you raid the cabinets of a Parkinson's patient (not as easy as it sounds), you're better off acquiring some buproprion (once your DLPA placebo honeymoon is over.)

As for enkephilase inhibition, I'm all but convinced that you'll get no more of a high that way, even with a novel, exotic inhibitor:

Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have discriminative stimulus properties. European journal of pharmacology 2000, vol. 401, no2, pp. 197-204 (1 p.1/4)

The systemically active mixed inhibitor of enkephalin metabolism, N-((S)-2-benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB 120), alone or in combination with 4-{[2-[[3-(1 H-indol-3-yl))-2-methyl-1-oxo-2-[[(tricyclo-[3.3.1.1.]dec-2-yloxy) carbonyl]amino}propyl]amino]-1-phenylethyl]amino}-4-oxo-[R-(R*,R*)]-butanoate N-methyl-D-glucamine (CI 988; CCK1 receptor antagonist) was investigated for discriminative and morphine generalisation effects using an operant drug discrimination paradigm in rats. Animals dosed with RB 120 (10 mg/kg) failed to develop a discriminative response. Combined CI 988 (0.3 mg/kg) and RB 120 (10 mg/kg) also failed to elicit a discriminative response. Morphine-trained animals (3.0 mg/kg) did not generalise to RB 120 (10 and 20 mg/kg). Similarly, subsequent retraining of the same animals with 1.5 mg/kg of morphine did not elicit generalisation to RB 120 (10 or 20 mg/kg). Combined RB 120 (10 or 20 mg/kg) and Cl 988 (0.3 or 3.0 mg/kg) treatment produced no notable drug lever selection in rats able to discriminate morphine (1.5 mg/kg) from saline. These results suggest that RB 120 may have low abuse potential at analgesic doses.​

I want a morphine lever.
 
Can someone explain the above comment for people who aren't knowledgeable about biochemistry? I'm interested because I recently started a phenylalanine regimen. What does seep mean by "unless you raid the cabinets of a Parkinson's patient"? Selegiline is a Parkinson's drug which has been used in combination with phenylalanine in at least one study. Is seep referring to this combination? I actually have a left over selegiline Rx (transdrmal patches).
 
He's talking abiout using carbidopa to stop amino acid decarboxylase from destroying the L-DOPA before it makes it into your brain. If you don't use drugs like carbidopa alongside L-dopa all you get are peripheral effects.
 
Thanks.

So, for clarification...

What do you think of taking phenylalanine?

What do you think of taking phenylalanine along with selegiline? "Another study showed significant improvements in those with depression when 250 mg of L-phenylalanine was combined with 5 to 10 mg of Eldepryl [selegeline]"*

What do you think of taking phenylalanine in combination with carbidopa?

Not for getting high, but as a well rounded antidepressant.


*Encyclopedia of Mind Enhancing Foods, Drugs and Nutritional Substances (David W. Group, 2000) | http://www.bluelight.ru/vb/threads/...EGA-THREAD?p=11409348&viewfull=1#post11409348
 
1. It's useless in healthy humans. (not malnourished)
2. It's not a smart idea. The Segelegine would do more than the phenylalanine would.
3. It's even less of a smart idea than #2, and likely to be ridden with side effects.

I think you should consider a regime of exercise, sun, and a healthy balanced diet before considering a Phe treatment.
 
1. It's useless in healthy humans. (not malnourished)
2. It's not a smart idea. The Segelegine would do more than the phenylalanine would.
3. It's even less of a smart idea than #2, and likely to be ridden with side effects.

I've never noticed any kind of side effects from DL-phenylalanine in dosages of around 1 gram. I use it some times for come downs and hang overs or as a mild (placebo?) booster. Never noticed any dangerous interaction with DL-phenylalanine even with strong stimulants unlike with Selegiline. Anyways I hardly use it because it tastes awful. I rather consume L-tyrosine, which also fills up the dopamine reservoirs and is totally tasteless.

1. It's useless in healthy humans. (not malnourished)
2. It's not a smart idea. The Segelegine would do more than the phenylalanine would.
3. It's even less of a smart idea than #2, and likely to be ridden with side effects.

I think you should consider a regime of exercise, sun, and a healthy balanced diet before considering a Phe treatment.

what's a healthy human? how do you know if you're malnourished or not?
everyone in the world should exercise and eat a 'healthy diet.' that being said, who can keep up with the billions of things going on in their bodies and know whether or not they are low on certain chemicals?
do you really think all of the people benefiting from l-phen are having a placebo effect? i think it's just as likely that all the people saying it doesn't work were taking it to get high/change their lives incredibly with a 5 cent pill or didn't take it correctly.
and i think a lot of these scientists studying things like this have trouble focusing on the big picture, since there are so many variables in our health, and since they want to find this magic single chemical that does amazing things so they can get rich. they want things to be simple, like everyone else. complexity is scary. not to say that we should disregard scientific studies on these drugs, but generally if there are 1000s of people swearing that something works - that speaks louder to me than a scientific study saying it doesn't.
...
can we have some respect for the complexity of the brain and humble ourselves? it's kind of insulting to tell all these people who feel positive effects from something that they are just stupid. i've taken tons of drugs and am certain that i have little to no placebo effect, and l-phen works for me. at the very least it gives me an energy boost, and i'm pretty it has helped stabilize my mood as well, but i can't be sure since i'm taking other 'snake oil' supplements.
 
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Seems to have a typo in the ligand name "D-phenyalinine", but it's apparently a full agonist of Niacin receptor 2. Not sure that's particularly useful though.

http://www.drugbank.ca/drugs/DB02556#targets - D-Phe might have activity at these targets, it's inconclusive based upon the annotation (ignore the transporters).

Whatever L-phenylalanine isn't turned into tyrosine is probably going to end up as phenethylamine, though phenylalanine has several breakdown paths as well.

In any event, phenylalanine ultimately makes a lot more than just catecholamines.

"Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004)." - quote from https://www.ncbi.nlm.nih.gov/pubmed/19948186
 
student said:
what's a healthy human? how do you know if you're malnourished or not?

Here, this means a person eating a diet including at least a barely adequate amount of protein. Under such conditions, dietary phenylalanine and tyrosine are opulent to the point of saturating the enzymes involved in conversion to dopamine (at least in the case of tyrosine hydroxylase), so supplementation with either is of little worth. Now, if you're a tweaker who never eats or a vegan who bases each meal around rice, supplementation should prove more worthwhile. ;)

do you really think all of the people benefiting from l-phen are having a placebo effect?

Yes.

and i think a lot of these scientists studying things like this have trouble focusing on the big picture, since there are so many variables in our health, and since they want to find this magic single chemical that does amazing things so they can get rich.

1. This is not how scientists work in current institutional settings.
2. I don't see how this would invalidate specific metabolic research.

complexity is scary.

Right, so that's why these issues deserve careful, rigorous study, not compounded lore.

i've taken tons of drugs and am certain that i have little to no placebo effect

This is not how the placebo-effect functions. Rather, every time you take a drug, legitimately psychoactive or not, expectations color the experience you undergo. Thus, from singular personal bioassays, one cannot cleanly discern placebo from direct pharmacological effects (in part because the two shape each other in interaction).

it's kind of insulting to tell all these people who feel positive effects from something that they are just stupid.

Claiming that someone is experiencing placebo effects does not imply that the person is stupid or even that the effects are nonexistent.

seppi said:
Whatever L-phenylalanine isn't turned into tyrosine is probably going to end up as phenethylamine

Do we have anything quantifying the rate of such conversion? This is pretty flimsy evidence, but I have taken racemic and l-phenylalanine while on selegiline at doses up to multiple grams without noticing a thing, while 100 mg of PEA would induce a briefly lasting high equivalent to roughly 20 mg / dexedrine.

ebola
 
Do we have anything quantifying the rate of such conversion? This is pretty flimsy evidence, but I have taken racemic and l-phenylalanine while on selegiline at doses up to multiple grams without noticing a thing, while 100 mg of PEA would induce a briefly lasting high equivalent to roughly 20 mg / dexedrine.

ebola

Do you have access to institutional research tools, such as university journal access?
 
The reason I ask is that reviews (which I almost always cite) don't typically restate data from primary sources, but they're vetted in peer review far more thoroughly than primary sources because they're lit reviews.
If you have institutional access, you can just follow the citation trail until you find the data.
Reviews, in general, are very high quality evidence so long as it's published in a decent (i.e., not sketchy) peer reviewed journal - I typically don't question them unless I can't find a similar statement in another paper.


In any event, http://www.ncbi.nlm.nih.gov/pubmed/1651528 states the accumulation rate is the same between DA/PEA - it's 4x norepinephrine accumulation as well.

Also, per this paper, http://www.ncbi.nlm.nih.gov/pubmed/361043 (quote follows)
Using gas chromatography of the isothiocyanatederivative of PEA, we found+ that control subjects
excrete in 24hr 61.2 4-12.8#g of free PEA and
53.2 4- 12.0ng of conjugated PEA/g of creatinine.
Third, antidepressant effect of the amine or its amino
acid precursor: phenylalanine (particularly the D
isomer) has been shown to exert antidepressant effects
[32, 34~36]. D-Phenylalanine increases the brain content
of PEA [20], but it is not known whether it
is decarboxylated to PEA or if it acts indirectly.
 
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Very useful, thanks. Yeah, I've been happy with the evidence you've been contributing thus far. :)

ebola
 
Ye I've been using Ciltep which is a nootropic stack that contains 500 mg of L-phenylalanine as well as acetyl-L-carnitine, vitamin b6, artichoke extract, and coleus forskohlii root extract. I usually take two of them right when I wake up and in around 30 minutes I start to feel more awake and kind of have a better outlook on the day. I've also taken a few during the day as well and have found that it works as a good mood lifter as well. I haven't tested it for placebo yet, but I'm almost positive it isn't placebo. I've tried at least 20 different nootropics before and awaited the results but with no avail, not even any placebo. Being a previous amphetamine abuser looking for anything that helps with motivation and whatnot, phenylalanine does the trick for me.
 
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