Agmatine: Miracle Potentiator?

[mickeyaye6989 (OP)]

Stumbled onto a wikipedia article about a drug called Agmatine that I found quite interesting. I initially found this while reading random shit about neurotransmitters, as agmatine is an analogue of the amino acid arginine and is naturally created in the body in small quantities. There's a section claiming that it somehow not only potentiates opioids, but also help prevent tolerance buildup, making it seem like a miracle drug. While I'm skeptical it works to a full extent, it's worth checking out the following article: 




I've always kinda wondered how our bodies produce and use endogenous opioids, but don't become tolerant to the substances we produce naturally, while easily becoming tolerant to the substances we consume - maybe this could be a reason?




Not sure how to get access to this shit, but it looks like some body building supplements contain it in large quantities, as it's supposed to also release nitric oxide which would dilate blood vessels, thus increasing blood flow to muscles during training. Anywho, anyone ever tried this shit?

[Jega]

That was interesting absolutely, so credit for finding that PDF. But Agmatine is not going to modulate the Mu receptor.

Quote: "Analgesia Agmatine had no analgesia in severe nociceptive experimental models, such as hot radiation tail flick test, under the dosage range from 0.1 to 62.5 mg/kg administered subcutaneously. It, however, showed obvious analgesic actions in a dose-dependent manner in some weak nociceptive experimental models such as acetic acid writhing test in mice or 4 % saline writhing test in rat. The ED50 obtained in the two experiments were 10.1 (6.8-15.4) and 14.1 (8.4-23. mg/ kg, respectively. These results indicated that agmatine had weak analgesic effects."

Now we're not entirely sure how opiates work so it's entirely possible that it did provide week analgesic relief while not modulating the Mu receptor.

But as a drug to be studied as something that keeps tolerance down it is certainly worthy of further study. Good find.

[mickeyaye6989 (OP)]

Yeah, I agree that the potentiation of analgesia wouldn't necessarily come from direct modulation of the mu-opioid receptor. I'm thinking it has more to do with the effects that the drug has on the NMDA-receptor class, or something of that sort: "So far a widely received concept is that agmatine is a neurotransmitter and/or modulator, the biological and pharmacological actions of which are closely associated with imidazoline and NMDA receptors." We all know that methadone affects NMDA's, as well as DXM and other related morphinan-type substances.

The tolerance aspect may have something to do with our cAMP signaling pathways, as upregulation of cAMP often results in an excitatory response. This is often a problem during WD's because the lack of opioids causes our bodies to release much more cAMP than usual in response, making us feel everything that much more. Thats part of the reason that even a small scratch feels like someone dragging a knife across your skin during WD's. Here's an excerpt showing that it lowers the body's massive release of cAMP during precipitated WD's from a shot of naloxone: "Agmatine inhibited the cAMP overshooting of
morphine-dependent cells precipitated by naloxone." Here's another article describing cAMP's effects on our increased pain sensitivity during WD's: https://www.ncbi.nlm.nih.gov/pubmed/15829634

Additionally, the inhibition of monoamine neurotransmitters also would have an effect, as the increased heart rate and restlessness can partly be due to our body releasing a lot more norepinepherine and other stimulating substances because WD's cause inihibition of the a2-adrenergic receptors (these kinda work in reverse to logic - activiation of a2-adrenergic receptors causes DEREGULATION of neurotransmitters, not upreg). This is why drugs like clonidine that are a2-adrenergic agonists help out with the tachycardia and restlessness during a cold turkey kick.

Sounds like a pretty great drug to me. Can't be too expensive in bulk either.

[Mr.pooper]

I actually use it with kratom. I've found DXM def potentiates kratom. Agmatine was an interesting one. Although I've had some issues with it, I think. Been actually experimenting again with it as of this morning.

Took my usual dose of kratom and felt a decent amount of euphoria and it lasted longer than usual. Took 500mg of agmatine 20 mins prior to the kratom.

When I used it before, after 3 days it seemed to really shine through for tolerance reduction/euphoria. Lowered my dose and was getting better legs. It's pretty widely used amongst the kratom community. I'm pretty sure it has to do with the nmda receptor from what I remember.

The difficulty I had was after taking 1000mg before my doses. By day 3 I had to stop using the agmatine. I was starting to have these really uncomfortable sensations. Like the feeling one gets after standing up too fast sometimes, that weird black out feeling. Combined with a weird heart beating flutter, accompanied by a zapping shock feeling through out my body.

Tried it again a few weeks later with 1000mg only once in the day and had the start of the same issues.

Today 500mg once, seems to be much better results thus far. Maybe I'm sensitive to the drug.

The reason I have doubts as to the agmatine being the sole culprit, I was dosing 30-60mg of DXM before each of my kratom doses (4-5 times a day) for a few months. After learning about agmatine I tried using that instead of the DXM. So my issues could be kratom/DXM related and not actually agmatine. Just figured I'd put this info out there in case anyone else notices the same thing.

I'll see how all goes in the next few days. Recently did a 2 month kratom kick. So my tolerance is very low.

[Dopeless Hopefiend]

What's the kick from kratom like compared to other opiate kicks? Like intensity/duration etc?

[Mr.pooper]

What's the kick from kratom like compared to other opiate kicks? Like intensity/duration etc?

Kicks are similar to oxycodone, however the kicks are much shorter. Less PAWS IMO too. However my last kick was off some sketchy "kratom extract tinctures", and that was worse than/on par with heroin withdrawal. Not sure what the fuck was really in those tinctures. Definitely not just kratom. Stay the fuck away from extracts, especially tinctures.

[Opi-ette]

I have a big bag of it in my closet. It never did anything for me.

[theSWPK]

I have a big bag of it in my closet. It never did anything for me.

Oh but how wrong you are! It did do something for you, it took up closet space.

[Mr.pooper]

I have a big bag of it in my closet. It never did anything for me.

Powdercity? What doses were you taking, and how often? Some people need higher doses, and let it build up in their systems before noticing effects.

For example my bottle dosage reccomends 500mgx2 once a day at meal time. However I've read users of kratom taking 2gs before each of their doses(3-5 times a day).

[Opi-ette]

I have a big bag of it in my closet. It never did anything for me.

Powdercity? What doses were you taking, and how often? Some people need higher doses, and let it build up in their systems before noticing effects.

For example my bottle dosage reccomends 500mgx2 once a day at meal time. However I've read users of kratom taking 2gs before each of their doses(3-5 times a day).

TBH I don't remember, it was a while back. There was a thread somewhere I'd have to find where we were talking about it. I tried twice and nothing happened so I gave up. I didn't know it had to build up in the system. If thats the case, I'd definitely give it another go. Might as well since I have a boat load of it just taking up space in my closet lol

[Opi-ette]

I have a big bag of it in my closet. It never did anything for me.

Oh but how wrong you are! It did do something for you, it took up closet space.

Haha! True, I'll give ya that!  Precious closet space.

[SapphireBlue]

I've been using both agmatine and DLPA for several years now, along with ranitidine and they definitely potentiate.  I started with DLPA first and then added the agmatine a few years later, when i had maxed out my dose of DLPA. 

I haven't had any issues with either of them and I might as well flush my oxy down the toilet if I don't take my supplements before dosing. Tolerance has still gone up for sure, but the supplements are worth taking IMO.