• N&PD Moderators: Skorpio | thegreenhand

DL-phenylalanine as an opioid potentiator

infraredz

Greenlighter
Joined
Aug 30, 2012
Messages
45
I stumbled across this just now and figured I'd ask if anyone has tried it since I can't find any real personal experiences with it (especially with bluelight or other such forums)....

D-L Phenylalanine

Here is what wikipedia has to say about it:

DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its supposed analgesic and antidepressant activities. DL-Phenylalanine is a mixture of D-phenylalanine and L-phenylalanine. The reputed analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin (endorphin) degradation by the enzyme carboxypeptidase A.[6] The mechanism of DL-phenylalanine's supposed antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect. Also, as DL-phenylalanine inhibits endorphin degradation, this leads to an inhibition of GABA release in the ventral tegmental neurons (in the midbrain), which results in greater dopamine release. This can explain the analgesic effects following ingestion. D-Phenylalanine is absorbed from the small intestine and transported to the liver via the portal circulation. A small amount of D-phenylalanine appears to be converted to L-phenylalanine. D-Phenylalanine is distributed to the various tissues of the body via the systemic circulation. It appears to cross the blood–brain barrier less efficiently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is excreted in the urine without penetrating the central nervous system.

L-Phenylalanine is an antagonist at α2δ Ca2+ calcium channels with a Ki of 980 nM.[7] At higher doses, this may play a role in its analgesic and antidepressant properties.

In the brain, L-phenylalanine is a competitive antagonist at the glycine binding site of NMDA receptor[8] and at the glutamate binding site of AMPA receptor.[9] At the glycine binding site of NMDA receptor L-phenylalanine has an apparent equilibrium dissociation constant (KB) of 573 µM estimated by Schild regression[10] which is considerably lower than brain L-phenylalanine concentration observed in untreated human phenylketonuria.[11] L-Phenylalanine also inhibits neurotransmitter release at glutamatergic synapses in hippocampus and cortex with IC50 of 980 µM, a brain concentration seen in classical phenylketonuria, whereas D-phenylalanine has a significantly smaller effect.[12]

Anyone tried it? Is it worth a trip to a vitamin store for a pain patient who needs more analgesia with less opioid meds?

Thanks as always.

Mods: if this belongs in ADD please move it (i'm still not sure what qualifies for what...)
 
I don't know the answer to this one. :\ I'll leave it here for a while longer, and then bump it over to ADD tomorrow if it still isn't getting any replies by then.
 
Though I can't say I've ever given this combo a go-round, I do remember reading in one of the thousands of opioid potentiation guides that Diet Mountain Dew was a good potentiating agent for the expressed purpose that it is high in phenylalanine. I am very interested to hear the feedback on this thread though, will be keeping an eye on it!
 
I don't fully understand how this is supposed to be superior to L-Phenylalanine? Like it possibly slows the degredation of endogenous opioids?

That Wikipedia article is very poorly written and does not meet Wikipedia's criteria for proper sources. The 1989 article cited for the claim that there is a "possible blockage by D-phenylalanine of enkephalin (endorphin) degradation" does not in reality say that, all it says is that D-Phenylalanine was found to bind to carboxypeptidase A, in the same way that L-Phenylalanine does, only slightly stronger. The other relevant claims made in the article are completely unsourced.

I've tried L-Phenylalanine and I certainly did not find it to potentiate opioids at all, nor did I notice any pain relief. It's effects are pretty subtle, although unwanted side effects can be noticeable for certain people.

I don't fully understand what binding to caboxypeptidase A even does.

EDIT: There is an old thread in ADD about this, someone said that it probably doesn't do much and you'd have to take huge amounts of it, but that was just their educated opinion, not from personal experience.

EDIT 2: This article is better sourced than the Wikipedia article, and it does make D- And DL-Phenylalanine sound very promising. I might actually give D-Phenylalanine a try for pain (I have to say I don't honestly expect much though). Restoring the Natural Opioid System with D-Phenylalanine (DPA): A Novel Therapeutic Approach
 
Last edited:
I thought tonic waters potentiation power came from the quinine in it? Well - I know that diet coke which has aspartame in it poteniates my oxy to some degree. If I've drunk a good 1.5 litre bottle of the stuff (which I can do very easily and within 10 minutes, but I don't suggest anyone try this or attempt to as you could drown yourself internally, literally) I get a better high for either one of two, or both reasons - the aspart and caffeine or either or. I believe it's both, as coke zero doesn't have such a profound effect on potentiation.
 
I thought tonic waters potentiation power came from the quinine in it? Well - I know that diet coke which has aspartame in it poteniates my oxy to some degree. If I've drunk a good 1.5 litre bottle of the stuff (which I can do very easily and within 10 minutes, but I don't suggest anyone try this or attempt to as you could drown yourself internally, literally) I get a better high for either one of two, or both reasons - the aspart and caffeine or either or. I believe it's both, as coke zero doesn't have such a profound effect on potentiation.
Tbh I'm not sure.. All I know is that Tonic water helps.
 
Definitely belongs in ADD. There are some really brilliant people there such as Ebola, Sekio, epilson, ect...


They would be able to answer your question more in depth


I am really interested in this aswell....nice post OP(original poster)
 
Last edited:
^Their question was has anyone tried it. That is not really an ADD topic. ADD would generally just be discussing the theory of whether or not it could potentially work and the science behind it. (It also didn't get much response the last time someone posted about this in ADD, hopefully it gets more response this time). The OP seems more to be looking for personal experiences. I've only tried L-Phenylalanine myself and didn't experience any perceptible potentiation of opioids or lengthening of opioids' effects.

I do agree that it's more advanced than BDD, I was going to move it to OD and tweak the thread title in the hopes of generating more replies from anyone who has actually tried DL-Phenylalanine as a supplement (I don't think that the fact that foods/drinks that contain small quantities of Phenylalanine along with many other ingredients are sometimes used as potentiators really counts, as the (subjective) potentiation could be due to other factors, for example quinine in tonic water). But I see someone already moved it to ADD. I still think the title at least needs to be changed to reflect the content of the thread but I guess that's up the the ADD mods now (EDIT: Thanks ADD mods for changing the title :))
 
Last edited:
Phenylalanine is an amino acid, the "unnatural" form has been speculated to be an enkephalinase inhibitor, but IMO it is probably not active worth a damn at all in humans. If it is active, it's incredibly weak and has poor central bioavailibility.
D,L-phenylalanine is a mixture of 50% natural form (L-phenylalanine, found in protiens, used to make DOPA etc) and 50% unnatural form (D-phenylalanine, the speculated potentiator). As SwimmingDancer pointed out there is not a lot of precedence for D-phenylalanine being some sort of miracle potentiator...

The active "potentiator" in tonic water is quinine, but it's only presentas a flavouring, and you'd need to drink at least 2 litres of tonic water before you got a medicinal dose of quinine.

Is it worth a trip to a vitamin store for a pain patient who needs more analgesia with less opioid meds?

No.
 
I'm taking DL-Phe on a daily basis currently. And yes, it most definitely produces some moderate stimulating effects.
However these effects need about one week to build up - while single doses don't cause any noticeable effect to me.

Keep in mind that the body synthesizes Dopamine, Noradrenaline and Adrenaline from it.
So it is only logical that high intake of Phenylalanine makes the body produce these neurotransmitters more easily.

When it comes to pain reducing effects, I did not feel significantly less of my chronic back pains than usual while being on Buprenorphine patches for years.
 
Coming from someone who deals with chronic pain, and who used to take opoids to help and now takes aminos I'd have to say it's very unlikely.

I take DPA (d-phenylalanine) along with l-tyrosine (which the body converts from l-phenylalanine) and haven't noticed any remote enhancement of effects.

DPA however has been shown to increase our own natural endorphins naturally.

If you want to potentiate opiates, benadryl or white grapefruit juice an hour beforehand will do the job.
 
Phenylalanine is found in all food, it's a natural amino acid that is required to make protiens
 
L-dopa doesn't produce stimulation, I can't imagine that D or L-PhA would.

Inhibiting enkephalinase doesn't potentiate opiates.
 
All journal articles I can find about this subject are from the 1980s, and the only one of them that looked believable, claimed that D-phenylalanine wasn't actually found to inhibit enkephalinase even in vitro:

http://deepblue.lib.umich.edu/bitstream/handle/2027.42/23269/0000206.pdf?sequence=1
In light of the report by Ehrenpreis that systemically administered D-phenylalanine has analgesic properties, it was of interest to test whether decreased enkephalin breakdown could be the mechanism of this analgesia. In our in vitro system neither D-phenylalanine nor its L-isomer was able to inhibit either enzyme

All the articles that claim enkephalinase inhibition by D-Phe are from journals related to acupuncture and other 'alternative' medicine... Looks like a pseudo-scientific myth to me. :|
 
I enjoy the combo. Sober I cant really stand the feeling of DLPA, but when drinking some poppy tea, OMG I can eat a shitload of it.
Makes me feel pretty warm and gives me bellringers aka tinnitus.
 
Just found this article from 2000:

In the author's clinical experience, concurrent treatment with DL-phenylalanine (DLPA) often appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain. An analysis of this phenomenon suggests that it may be mediated, at least in part, by up-regulation of the 'endogenous analgesia system' (EAS), a neural pathway that projects caudally from medullary nuclei to the dorsal horn of the spinal column; when stimulated by chronic pain or therapeutic measures such as opiates or acupuncture, the EAS suppresses activation of second-order pain-receptive neurons in the dorsal horn, and thereby alleviates pain. Since serotonin and enkephalins are key neurotransmitters in the EAS, it is reasonable to predict that measures which promote serotonin activity (such as 5-hydroxytryptophan and serotonin-reuptake inhibitors) as well as enkephalin activity (such as D-phenylalanine, an enkephalinase inhibitor) should potentiate EAS-mediated analgesia - a view consistent with much previous medical research. Comprehensive support of the EAS with well-tolerated nutrients and pharmaceuticals may amplify the analgesic efficacy of chronic opiate therapy, while enabling dosage reductions that minimize opiate side-effects. Analogously, this approach may complement the efficacy of acupuncture and other analgesic measures that activate the EAS.

http://www.ncbi.nlm.nih.gov/pubmed/10998643
 
DPA however has been shown to increase our own natural endorphins naturally.

Just curious, do you have a source for this?

My understanding of endogenous opioids is that they're released by the pituitary gland and then destroyed almost immediately by enzymes. Due to that fact (the fact that their half-lives are literally only seconds) we're unable to measure brains levels of endogenous opioids - even after someone has died.
 
Where did you obtain that understanding? Just imagined? There are many studies that include measurements of various opio-peptides coming out of live humans.
 
Top