DL-phenylalanine as an opioid potentiator

[sekio]

Opioid peptides are quite measurable, the problem is they are shitty drugs and we can't effectively get them past the BBB.

They are quite detectable in cell culture & in brain homogenate.

 

[magellan13]

In response to someone suggesting the old white grapefruit juice and benadryl as opiate potentiators, I have used heroin for close to 10 years and grapefruit juice and benadryl don't do it for me. Additionally I've tried using prilosec prior to opiate use and didn't notice much of an effect, I'd say it was negligible.
I should preface I do have a decent opiate tolerance (haha) so maybe that had something to do with it.

I'm not sure how well known this is, but an opiate potentiator that is extremely noticeable in its action is MXE (methoxetamine). I did not notice a tolerance to the potentiation effect developing over a 2 week period of daily use. I consider white grapefruit juice/benadryl/prilosec to be theoretical potentiators, with little practical effect, but mxe has a definite potentiation effect, even with a significant tolerance to opiates.

 

[Lightning-Nl]

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.

This isn't an effect of increased opioid activity - this is due to the fact that Phenylalanine gets metabolized into L-Tyrosine, then from L-Tyrosine into L-DOPA, then gets deactylated into Dopamine then Dopamine Beta Hydroxylase converts it into Norepinephrine.

Phenylalanine also gets cleaved into Phenethylamine. Phenethylamine is actually a more potent stimulant than Amphetamine, but lacks significant peak plasma time.

Anyways, the effects your feeling (sensation of heat, ringing ears) is quite typical of alpha-adrenergic action, and DAr agonism.

 

[ebola?]

This isn't an effect of increased opioid activity - this is due to the fact that Phenylalanine gets metabolized into L-Tyrosine, then from L-Tyrosine into L-DOPA, then gets deactylated into Dopamine then Dopamine Beta Hydroxylase converts it into Norepinephrine.

As a friendly reminder from this broken record, l-tyrosine is saturated under normal dietary conditions, so it follows that DLPA's psychoactivity should be roughly nil. Yes, there is auxiliary metabolism to phenethylamine, but that will get chopped to shit by MAO right-quick.

Phenethylamine is actually a more potent stimulant than Amphetamine

No, it's quite a bit less potent, even when potentiated via inhibition of mao. This is borne out by binding affinity data and anecdotal reports of recreational use.

ebola

 

[Lightning-Nl]

As a friendly reminder from this broken record, l-tyrosine is saturated under normal dietary conditions, so it follows that DLPA's psychoactivity should be roughly nil. Yes, there is auxiliary metabolism to phenethylamine, but that will get chopped to shit by MAO right-quick.

Hey ebola,

I don't appreciate the insults and I find it highly inappropriate. Stop please. If you read my post more closely, you'll see that I said that L-Phenylalanine gets converted into PEA. Not Tyrosine.

No, it's quite a bit less potent, even when potentiated via inhibition of mao. This is borne out by binding affinity data and anecdotal reports of recreational use.

ebola

Well that's funny because I recently read a study that claimed that PEA was vastly more potent in functional efficacy than Amphetamine.

But since you didn't read my post, you wouldn't have realized that I said that the reason why it's effects are negligible is due to the fact that it's half-life is only 15 minutes at best.

I'll admit that I haven't looked at PEA's Ki or EC50 values in a very long time. However, I went by a stud I read. In fact, I'll go back through my history to find it for you.

Not amused by your hostility, ebola. An admin, especially, should know better.

 

[h3lp]

One can't make assumptions upon the effectiveness of any opiate enhancer without prior experience from the test subject at least in terms of enhancement in using other substances.

 

[Lightning-Nl]

One can't make assumptions upon the effectiveness of any opiate enhancer without prior experience from the test subject at least in terms of enhancement in using other substances.

I disagree. Anyone can make educated assumptions based on many factors - but the problem is; people like to assert these assumptions as fact.

In reality, assumptions are just that - assumptions. Without a shred of proof to back it up - you can't consider anything fact.

 

[h3lp]

I think that each individuals response to drug combinations will be greatly unique making it difficult to identify facts that educated assumptions would be based on.

 

[ebola?]

I don't appreciate the insults and I find it highly inappropriate.

What insults? I merely noted that I have posted this fact numerous times before, and I wasn't talking specifically about conversations with you. In the future, if you think a mod has committed an offense, you can either try to resolve it via PM to any NPD mod you'd like or report the offending post, for review among smods and admins as well.

Well that's funny because I recently read a study that claimed that PEA was vastly more potent in functional efficacy than Amphetamine.

This runs counter to the evidence found by Schmitt et al. (2010) and every anecdote detailing use combined with an MAOI I've seen.
But I'd love to see the study you're talking about. The evidence here is in vitro binding affinity assay, and thus controls for rapid breakdown by MAO.

But since you didn't read my post. . .

We discourage ad-hominem 'arguments' in this sub-forum and several others.

you wouldn't have realized that I said that the reason why it's effects are negligible is due to the fact that it's half-life is only 15 minutes at best.

I read it and understood what you said but disagreed. That happens sometimes.

I'll go back through my history to find it for you.

I'd be much obliged, sir.

Not amused by your hostility, ebola. An admin, especially, should know better.

My apologies--I didn't mean to express any hostility. Also, I'm not an admin.

ebola

 

[vortech]

My experience taking DL-phenylalanine for the past 3 weeks with a consistent dose of suboxone daily is that it most certainly potentiates it. There is a significant difference compared to the days when I have taken the suboxone without it. I take 450mg 1 or 2 times a day.

 

[MartinFn]

DLPA potentiates opiods...

Well Vortech,
that's very good, and you give me the hope i need so much, to ease my fuckin pain, my friend.... So as you say, you use the DLPA, at doses 450mg 1 or 2 times daily..
I wanna know, (if you don't mind and have the time to answer my questions of course..), if it starts working straight away when you take it, or after some time, (maybe after a week, like somebody above posted..)..Also, i've hear that the DPA, without the L-phenylalanine, works much better..If you've tried it, i would like to know your opinion..
And my last question, if you can give us an idea of how much it helped you, (for example, if it made the suboxone 50% stronger, smth like that, you know..).
That's all, i hope you, and all the Bl community, be as fine as it gets, %)..:D, and i would be very happy if you can answer my questions, cause i'm in fuckin terrible pain, and it gets me in a bad mood, so i'm searching for smth that could potentiates the opiods i take, i'm sure you know about pain, and you can guess of what i'm going through..
In the end, it can't kill me, but...yeah, fuckin fucked situation my friend...
Well, any-fuckin-way..

Hey to everybody..%)



MartinFn

 

[vortech]

It has an effect within 30 minutes. It may also have additional effect after a week of taking it consistently but I can't say for sure. I don't think it makes it 50% stronger, at least not in every aspect. It does seem to significantly potentiate the 'nod' (like a calm tranced-out sleepy feeling) that comes in waves those first couple hours after the suboxone starts working. It also has a general anesthesia effect and helps the chronic pain in my legs more than suboxone alone (suboxone isn't a very good pain medication).

Best of luck finding the relief you seek!

 

[h3lp]

This topic will be very subjective because as with most/all opioid potentiation the results are anecdotal and will have minimal conclusive evidence as far as credibility.

Further dealing with any type phenylalanline increases the anecdotal nature of the subject at hand. When dealing with neuroscience, to simply analyze the chemical structure of a chemical and attempt to draw a hypothesis is not sufficient to give any type of medical advise especially with a topic as crucial as pain relief.

With that being said one of the most common opioid potentiator is Clonidine which is sold under names such as Apvay and Nexiclon for a variety of conditions including ADHD, High Blood Pressure, Anxiety/Panic disorders, and certain pain conditions.



It is classified as an Alpha-2 adrenergic receptor and as such effects various parts of the brain and body including the Brainstem, Hippocampus, and Cerebellum through adrenergic receptors located in subsequent regions.

It has been proven as effective in veterinarian anaesthesia practices by producing effects such as sedation, muscle relaxation and analgesia through the central nervous system, which is probably why, anecdotally speaking, it has presented itself as an opiod potentiator through the similar effects opiates have on the body. This of course has no medical backing and can only be assumed from word of mouth.

Personally I am perscribed metoprolol for high blood pressure (which is a condition that Clonodine also provides relief from). I also have found that metoprolol produces its own unique "high" when used medically. But that is a personal opinion. I am also a frequent IV heroin/morphine user and have noticed that when used in combination with therapeutic doses of metoprolol, is effectively potentiated.

I DO NOT suggest anyone make the assumption that high blood pressure medications are effective or safe opioid potentiators but am simply presenting anecdotal evidence for further research.

 

[TriputoryHeadicine]

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.



No.

My buddy insisted drinking smaller bottle of tonic water had an additive effect; I was doubtful after reading how much you need. Maybe he's built forit, or placeboed.

 

[MartinFn]

Best of luck finding the relief you seek!

Thank you very much Vortech, my best wishes for the ease of your pain too, friend..and with suboxone, i can guess the things are difficult..but anyway..

With that being said one of the most common opioid potentiator is Clonidine

Yeah, and as a matter of fact i've and i still use it, from time to time, (The more rare you use it, the better it works.., as i've found from personal experience..It has a bad side-effect, though, it makes you VERY sleepy...
I also use orphenadrine citrate as a potentiator, it's better (but nothin to write home about..) than clonidine, and it also makes you VERY sleepy..
Well, the searching never ends, i guess..i would like to try, (except phenylalanine), nigella sativa, i've hear a lot of good things about it...%)...



MartinFn

 

[dharmabum22]

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

I've researched DL- phenylalanine and human's experience with it, on forums and sites such as this. What I've found is that experience of any "buzz" does depend on the individual. Some people swear that when insufflating (snorting) they definitely feel something akin to an amphetamine. One person wrote he uses DL-phenylalanine as a substitute to Adderall. The reason that insufflating makes the most sense to me is that more DL-phenylalanine crosses the BBB when administered through the mucous membrane because it does not compete with other proteins (amino acids) when taken orally. Other proteins have more of an affinity than DL-phenylalanine and that is why it is suggested to take on an empty stomach. "As individuals vary, so do the results" : one can read that on almost any medication bottle and that is definitely the case with DL-phenylalanine. Just like the forums about loperamide: some people swear it works, as I am one of them-it works wonders for opiate withdrawals and if I take enough, it does cross the BBB. Anyways, I have snorted DL-phenylalanine and when I take over 1000 mg, I get a mild euphoric and somewhat "speedy" feeling. As far as opiate potentiation, I empty the capsules right in my methadone "take home" bottles before I drink the methadone. I do that first thing in the morning on an empty stomach and it DOES potentiate it. That is my personal experience.

 

[dharmabum22]

h3lp is right about Clonidine. I have used it to potentiate my methadone and I also found it really increase "benzos". Clonidine is very popular at this Chicago methadone clinic. So popular that people on the streets ask for it.

 

[Syco(r)a(x)]

An older thread, not sure if this link had been added for viewing but it seemed directly relevant and not so pseudo science-y ?

http://www.ncbi.nlm.nih.gov/pubmed/10998643

 

[jambabomba]

DLPA worked for me and I definately felt opioid effect from it. I've history with opioids and currently use LDN so its pretty familiar feeling to me. Its different from its L-form pure L-Dopa and noradrenaline's raising effects and it slightly boosted codeine's effects.

I used it 3g/day.

 

[Whendawhipcomesdwn]

Definitely works for me. Potentiates adderrall too. Top 10 experience was phenibut, adderall, opioid,DLPA.

Im going to buy some right now since I just landed some adderall. 2 day washout, then Saturday is going to be bliss. 750 mg adds roughly 40% to both.

Thing is Phenibut basically resets your tolerance to stims. It also will completely block most of the effects of cocaine and all of the negative ones. There is a sweetspot dose. Cocaine is a once in a blue moon type thing for me but lets just say I had female companionship, a very low tolerance to phenibut plus cocaine. I experienced most of the good with none of the vasoconstriction or anxiety. Another top 10.

DLPA effects seemed to subside a bit with daily use and it may have potentiated and smoothed out the Adderall more than the opiod but Im going to go with top 2 for solo experiences. That was actually the kickoff to an awesome night. Cant believe I let myself run out.