Aspartame Potentiates Opiates?

[SpunkySkunk347]

A few times while on oxycodone, I happened to drink some diet mountain dew, and noticed that afterwards my oxycodone high had been significantly improved.

However, I can think of countless other junkie obsessive compulsive rituals regarding what may potentiate or ruin a high (I recall a few junkies who wouldn't drink coffee or take a shower while on opiates, under the belief that it would ruin their high - a big consequence being that a whole circle of junkies smelled like shit because they never took showers, all because the "druggy expert of the group put the idea in their head that taking a shower would somehow put some Bad JuJu on their high).

So I remained skeptical of my theory. Although I am perhaps more educated on drug affairs than your average junkie, I am not any less susceptible to the placebo effect than they are.

I told some of my friends my theory and they also reported intensified euphoria.

I wanted to know what some of your theories regarding this may be, perhaps some of you could even try this yourself and report back what you felt.

If aspartame does indeed potentiate opiates either directly or indirectly, does anyone have any speculations on the mechanism of this synergy?

Perhaps the mechanism has something to do with vascular dilation. I am under the belief that a fairly active portion of opiates effects and the overall physical qualia of opiates comes from vascular dilation. I also believe that the reason speedballing was so popular is because the vasoconstricting effects of cocaine and the vasodilating effects of heroin compliment each other. Perhaps aspartame somehow causes slight vascular constriction, causing the vascular dilating effects of opiates to be more pleasurable.

Or perhaps the mechanism has something to do with the enzymes involved of both aspartame's and oxycodone's metabolism

 

[sekio]

Aspartame is metabolized by esterases and peptidases (neother of which are involved in opioid metabolism), and moreover it doesn't cross the blood-brain barrier. I don't think it's vascularly active either.

There's nothing on PubMed or google. I would say this is placebo and nothing more.

 

[SpunkySkunk347]

Alright, thanks for your input. I'm wondering now if maybe caffeine or carbonation has something to do with my perceived potentiation of effects. Maybe carbonation in the digestive tract (which itself has been said to alleviate gastrointestinal discomfort) somehow synergizes with opiate euphoria (which anyways seems to heighten feelings of bodily comfort that would normally be experienced with things like a massage, a hot bath, etc.)

I don't know, placebo seems to be a perfectly reasonable conclusion (don't let the length of my posts cause you to think I'm more committed to my hypothesis than I actually am; when I'm high the length aspect of my posts tends to be quite a bit greater )

 

[sekio]

Whoops! Diet Mtn Dew, from what I recall, has one of the highest levels of caffeine among the non-"energy drink" market. That's probably the mechanism responsible for increasing euphoria, and is well documented; indeed heroin made for smoking is often prepared with caffeine base.

 

[SpunkySkunk347]

Ah, that would explain it. Since I read your post I've been looking up posts and articles about mixing caffeine with opiates for half an hour.
It also explains why on nights where I drank an energy drink I've been floored by my evening dose.

This thread has been concluded now I suppose lol, I'll be sure to recommend to my friends to drink some caffeine after taking their oxy; it'll add to the long strange list of rituals that users in this area of the world undergo when using opiates.

 

[kken]

caffeine is often pre mixed into opioid medications, does it really potentiate the euforia? its well documented it increases analgesic properties

by indirectly increasing dopamine thats released by secondary cascade from opioids? if so would it also increase addiction potential

 

[SpunkySkunk347]

I just read some other post in some other forum which said caffeine increases absorption rates of opiates from the GI tract, which would make sense since caffeine dilates blood vessels.
However, I don't know how reliable that information is, no references were given.

 

[jegarst]

Concerning your statement "perhaps aspartame somehow causes slight vascular constriction..."

Aspartame is metabolized to methanol and two amino acids. That methanol is oxidized to formaldehyde and that in turn is readily oxidized to formic acid. Formic acid is naturally metabolized (reduced; recycled) to methyl groups by the folate and B12 vitamin systems for many uses in biochemistry. [FYI, caffeine is N-demethylated twice each time producing formaldehyde and likewise formic acid]. One use of the methyl groups made via folate is conversion of relatively toxic homocysteine to less dangerous methionine for methylation reactions. If folate is deficient (likely with drug users, anyway) less methyl groups are made and this reaction is less effective. That allows more homocysteine to be produced. Homocysteine is a potent vasoconstrictor (http://www.ncbi.nlm.nih.gov/pubmed?term=vasculature constriction,homocysteine)and a risk factor for cancers and other disease. While aspartame is not even absorbed intact to make it to the blood-brain barrier, homocysteine produced consequent to a deficiency of folate whether from aspartame or from caffeine consumption would and could cause vasoconstriction.

John E. Garst, Ph.D. (Medicinal Chemistry, Pharmacology, Toxicology, and Nutrition)

 

[Droppersneck]

Whoops! Diet Mtn Dew, from what I recall, has one of the highest levels of caffeine among the non-"energy drink" market. That's probably the mechanism responsible for increasing euphoria, and is well documented; indeed heroin made for smoking is often prepared with caffeine base.

I dont know 42mg of caffeine is the standard amount for most cokes

 

[sekio]

@jegarst: Formaldehyde is readily sequestered in small amounts by your body's natural detoxification mechanisms (it is also generated by natural metabolic processes) and as a result I highly doubt the natural removal of methyl groups generates appreciable amounts of vasoconstriction at all.

@droppersneck: You may be right about that. However there is still an ap[preciable amount of caffeine in cola, and I'm sure it would synergize with opiates.

 

[jegarst]

@sekio, you misunderstand. When folate and its more active intermediate tetrahydrofolate (actually a multiply conjugated glutamate) is deficient then homocysteine cannot be remethylated. Folate issues are common and even more so in people with folate related polymorphisms (~40% of some populations); technically that raises the Km of the reaction, which is to say, it increases further the requirement for folate in the reaction. Homocysteine accrues and it is exceedingly toxic, amongst its actions being vasoconstriction.

You are correct that formaldehyde is sequestered (stored), but when made available it, along with formate, are both direct participants in the folate reaction. Ethanol is oxidized to acetaldehyde. Acetaldehyde is a known inhibitor of the folate reactions; that can be easily demonstrated by formate accrual in the blood and urine of rats given ethanol.

 

[mgmt&mdma]

im suprised no ones said this but (and correct me if im wrong)-

most diet drinks contain artificial sweeteners, and if you look on the bottle/can it'l say "phenlyketonurics: contain phenylanine" and phenylanine is an amino acid that helps reduce pain (d-phenylanine)

so maybe thats why?

 

[sekio]

Phenylalanine is a part of the aspartame dipeptide, it's released when your body breaks it down.

I really doubt that formaldehyde/homocystine generated from aspartame metabolism is the cause for any of this. I would expect fruit juices and other natural products to cause the same reaction...

 

[DJHENRU]

damn, was I always mistaken thinking it was lpa... so can I just go get some aspartame instead of paying out the ass for a dietary suppliment?
"L-phenylalanine is found in most foods that contain protein such as beef, poultry, pork, fish, milk, yogurt, eggs, cheese, soy products (including soy protein isolate, soybean flour, and tofu), and certain nuts and seeds. The artificial sweetener aspartame is also high in phenylalanine.

D-phenylalanine is made in the laboratory but is not found in food."
anyways http://www.arthritis-treatment-and-relief.com/aspartame-and-arthritis-pain.html some one has found relief while taking it.

 

[SpunkySkunk347]

In some other thread I believe we calculated out how much aspartame is ultimately metabolized into L-dopa, and we found that it was a negligible amount for any psychological effects.

 

[DJHENRU]

I just want pain relief though. =[

 

[SpunkySkunk347]

Can you describe your pain for me? I want to know if it's something similar I went through, because I might have some advice. Like, how would you say the pain affects you psychologically?

 

[Alcyone]

Homocysteine is a potent vasoconstrictor (http://www.ncbi.nlm.nih.gov/pubmed?term=vasculature constriction,homocysteine)and

That's very interesting, but could you please point me towards a specific source? None of the papers in that Pubmed query specifically state that homocysteine is a vasoconstrictor. I'm well aware of the fact that elevated levels of homocysteine are associated with arterial vasospasticity and increased vascular resistance, but I believe it has not been shown to be the causative factor. I'm not aware of any evidence supporting your claim that homocysteine has acute vasoconstrictive effects or that it's "exceedingly toxic".

Interestigly, homocysteine has been shown to counteract adrenergic vasoconstriction in-vitro:
Sensitivity to norepinephrine was diminished in HC arteries, which increased the median effective concentration (EC50) from 0.24 ± 0.06 μmol/L in control arteries to 0.65 ± 0.10 μmol/L in HC arteries (P < .01). Homocysteine also caused concentration-dependent vasodilation of arteries contracted with an intermediate concentration of norepinephrine that was greater in intact than denuded arteries, with the half-maximum responses occurring at 61 ± 6 μmol/L (intact) and 90 ± 11 μmol/L (denuded; P < .05). [...] An elevated homocysteine level in vitro diminishes adrenergic contraction, with a differential endothelial versus smooth muscle influence that appears unrelated to the generation of reactive oxygen species.
(Source: J Vasc Surg 2000;31:751-9.)

Anyhow, I agree that homocysteine is not good for you.

 

[DJHENRU]

Can you describe your pain for me? I want to know if it's something similar I went through, because I might have some advice. Like, how would you say the pain affects you psychologically?

Alright im prescribed gabapentin for it:I have a curved spine, where I maybe was to wear a backbrace but didnt, I duno how this contributes.
Then I had a horse, smash the shit out of my foot so it was like pancake flat. (was getting pain at this point, terrible cramping in my legs where I couldnt sleep) for a while I was better using alot of cannabis.

Then I stupidly used a needle to IV administer in my femoral vein, about 6 weeks after that I started to get similar cramping but much worse, pain in my feet as well, after that.

Now for a while on meds, I just get alot of feet and ankle pain, everyday mostly throught the day.
I had Poppyseed tea & some gabapentin yesterday, right now the thight opposite of the one I injured hurts, and the big toe of the smashed foot has arthritic pain. this is from the scared nerve contributing to it)
I was diagnosed with some sort of scarred nerv,e where It was smashed & may get surgury for it.
I dont how much the IV administration is apart of it as well or a curved(or previously injured) spine. The thigh hurts sometimes with inflamation.

NSAIDS dont help that much. Cannabis hadn't a while ago, when I was more dependant on it, but that maybe attributed to OD causing greter sensitivity.
Opiates are very good, gabapentin is subpar(pregabalin ok). I cannot get prescribed opiates sadly.
DPLA Kind of good, I once was in pain stated breakdancing and was getting the tingling almost painful nerve feelings but the pain would subside(I guess this is technically a DPLA od)

Like, how would you say the pain affects you psychologically?

Didint read, I dont really know how to explain.

 

[negrogesic]

Not to my knowledg. If so, any such effect is negligible and unlkely to be differentiated from placebo (as I've said before, placebo is a strong drug). There was once a patient who demanded holistic analgesia for post-op pain control. Guess how long his chanted turned into screaming for pain meds.......not very, but surprisingly long (30 monutes post op, the funny thing is, it was for a gastric bypass.......which is a rather painful recovery. From what I recall, I consented to a drip a little under an hour after said patient regained full consciousness (I was his anesthesiologist and defacto attending; residency sucks). Point is, while perhaps an intellectual curiosity, I see little merit in any clin sign "potentiation" opioids of d-asp, although we all can acknowledge the apparent MOR peptide ligand modulation of the amino.