Opioids Dyphenhydramine works as good as promethazine for potentiating opiates ?

[Chickens]

Speaking solely from personal experience, diphenhydramine feels horrible, both alone and as a potentiator. I could see how some people might think it increases the “nod", but for me, it just makes me so sleepy I can't function.

 

[Allylbenzene]

I have pointed out many times how just how badly animal models fail in modelling psychoactive compounds.

I know. I can't collate all the positive reports from people using agmatine for drug potentiation, reducing tolerance build-up & withdrawls and general theraputic purposes.

 

[Coffeeshroom]

Speaking solely from personal experience, diphenhydramine feels horrible, both alone and as a potentiator. I could see how some people might think it increases the “nod", but for me, it just makes me so sleepy I can't function.

No offense ND when you nod you can?

 

[Skorpio]

Agmatine is a good cheap OTC opiate potentiator thats also naturally occuring (sometimes considered a neurotransmitter).
It reduces tolerance build-up for most drugs and reduces withdrawals (reported for benzos, stimulants, opiates).
Agmatine shares similar MOA to ketamine (NMDA antagonist, AMPA, mTOR) with additional pro 5-HT2A, imidazoline, sigma-1 activity and alpha-2 adrenergic antagonism.

Agmatine synthesis in morphine dependence - Annals of General Psychiatry

annals-general-psychiatry.biomedcentral.com

Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system - PMC

Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the ...

pmc.ncbi.nlm.nih.gov

Agmatine Potentiates Morphine-Induced Conditioned Place Preference in Mice: Modulation by Alpha(2)-Adrenoceptors - Neuropsychopharmacology

The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1–7.5 mg/kg) significantly...

www.nature.com

General Agmatine overview:

https://www.sciencedirect.com/science/article/abs/pii/S0143417924000283

I’ve always understood agmatine to function through nitric oxide signaling systems primarily.

At what dose does agmatine inhibit NMDA channels? It’s use as a supplement implies that it either is not a non-competitive antagonist or is only at some absurdly high concentration.

 

[Allylbenzene]

I'm not sure. Doses range from 150mg to 6g depending on the intention. Recreational can be 2g+

I’ve always understood agmatine to function through nitric oxide signaling systems primarily.

Agmatine...is an endogenous ligand at alpha 2-adrenergic and imidazoline receptors, to which it binds with high affinity. Thus, agmatine -
(a) is locally synthesized in brain by a specific enzyme, arginine decarboxylase;
(b) is stored in a large number of neurons with selective distribution in the CNS;
(c) is associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells;
(d) is released from synaptosomes in a Ca(2+)-dependent manner;
(e) can be enzymatically degraded by agmatinase in synaptosomes;
(f) can be inactivated by selective reuptake;
(g) blocks the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites;
(h) has systemic actions when administered intraventricularly. Additionally -
(i) agmatine is a precursor of brain putrescine and, hence, of higher polyamines
(j) it competitively inhibits the activity of all isozymes of nitric oxide synthase.

Agmatine meets most criteria to establish it as a novel neurotransmitter/neuromodulator in the CNS

Agmatine: an endogenous ligand at imidazoline receptors is a novel neurotransmitter - PubMed

Agmatine, an amine and organic cation, is an endogenous ligand at alpha 2-adrenergic and imidazoline (I-) receptors, to which it binds with high affinity. In addition, agmatine has properties of an endogenous neurotransmitter. Thus, agmatine (a) is locally synthesized in brain by a specific...

pubmed.ncbi.nlm.nih.gov

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators​

https://journals.sagepub.com/doi/10.1177/2470547019858083

 

[Skorpio]

I'm not sure. Doses range from 150mg to 6g depending on the intention. Recreational can be 2g+

Agmatine: an endogenous ligand at imidazoline receptors is a novel neurotransmitter - PubMed

Agmatine, an amine and organic cation, is an endogenous ligand at alpha 2-adrenergic and imidazoline (I-) receptors, to which it binds with high affinity. In addition, agmatine has properties of an endogenous neurotransmitter. Thus, agmatine (a) is locally synthesized in brain by a specific...

pubmed.ncbi.nlm.nih.gov

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators​

https://journals.sagepub.com/doi/10.1177/2470547019858083

I have never heard of recreational effects of agmatine. What have you experienced?

 

[Allylbenzene]

Although I have some I don't use it for that purpose. Here's a report of frequent 2.6g use. I'd interpret this particular example as therapeutic use comparable to a psychedelic or ketamine (which is gaining popularity in America as a prescription anti-depressant).

In essence, I've been doing 2.6 grams of Agmatine once a week since the beginning of November/December.

It shares a similiar, primary, MOA (mTor & AMPA) as ketamine in terms of neurogenesis, and it has some pretty pleasant 5HT2-A agonistic actions making it as en excellent insight tool (no hallucinations though).

In depth information can be found in my previous posts. It is particularly interesting that it does not have any hallucinatory effects, such as OEVs and CEVs, despite its 5HT2 actions. Yet distinctly feels very much like a psychedelic in terms of time-dilatation, emotions, and insight. A topic discussed in one of the links below.

Considering how agmatine works, if someone is using it to potentiate another drug it might be best to pre-dose ~1hr beforehand. Otherwise agmatines NMDAi and alpha-2 adrenergic agonism could blunt the drugs effects.

Feels exactly like a long lasting ketamine for me. Very obvious it is a NMDA receptor antagonist. It’s supposed to effect calcium channels similarly to pregabalin and for me doses as low as 250mg absolutely increase the effects of pregabalin. I’d go as far to say agmatine is very strong in its own right, especially as an NMDA Antagonist.

reddit.com/r/gabagoodness/comments/o51plu/does_agmatine_have_any_recreational_properties_or/

So someone here recently recommended me to mix Agmatine Sulfate with Kanna extract and this truly changes the game in relation to the rush. As we all know, sometimes the rush can be a bit anxiety-inducing, unsettling, etc, but when adding Agmatine Sulfate (I use around a gram 1 hour before) not only makes the whole Kanna experience cleaner and more euphoric, but smoothens out the rush in a way that makes it extremely orgasmic, it feels so close to the comeup of a MDMA experience, a love-filled I euphoric I want to hug the world empathogenic type of experience, with little to no discomfort added in relation to it.

reddit.com/r/Kanna/comments/18qr34z/how_to_smoothen_the_rush_agmatine_sulfate/

I just started taking Agmatine to lower my tolerance to other substances, and I heard that it also effects the Cannabanoid Receptors, but i didnt think it would do THAT much. I took a single evening dose of 500mg, a little later took a few hits, then another hour an a half i smoked 2 more hits, and then all of a sudden I was SO HIGH i could barely walk or talk. It felt like I took a whole edible plus some. And mind you, I smoke everyday just about. This is one promising supplement it seems. There was nothing on this sub on the search of agmatine so figured I'd add something to it for others wondering the same.

reddit.com/r/Marijuana/comments/zt0afy/agmatine_sulphate_supplement_cannabis_wow/

Agmatine–cannabinoid interactions are supported by the close association between cannabinoid CB1 receptors and agmatine immunoreactive neurons and evidence that shared brain mechanisms underlie the pharmacological effects of agmatine and cannabinoid agonists.
...
These results demonstrate a synergistic interaction between agmatine and cannabinoid agonists and suggest that agmatine administration enhances cannabinoid action in vivo.

pubmed.ncbi.nlm.nih.gov/19538988

Shulgin reports on the synergistic value of rilmenidine (Imidazoline agonist) & clonidine (alpha-2 adrenergic agonist) when combined with psychedelics; agmatine is considered an endogenous ligand at both of those receptors.

Thread 'Recreating entactogenesis via psychedelics (2cbFly) plus blood presure meds plus THC'

Jun 26, 2017

Not sure yet if it´s a breakthrought or just plain bullshit, but we have a Shulgin report, a Medical paper and some anecdotal evidence.

The shulgin post:

8.0 mg 2C-B-fly and 2.0 mg of rilmenidine at 12:30 pm; cannabis vapor at 4:00: The result was spectacular. I got a +4 experience from a pure imidazoline blood pressure medication! It is probably the entactogenic core of MDMA. I tend to think of the effects of MDMA as sweeter and gentler than this, but this was much stronger than any MDMA I have previously experienced. It turns out that 2.0 mg of rilmenidine is a very high dose. This...

• Hexagon Sun

• 

Interestingly, Agmatine and DMT both interact with the sigma 1 receptor.

N,N-Dimethyltryptamine (DMT) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation.

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00330/full

 

[NY2soFlo]

Although I have some I don't use it for that purpose. Here's a report of frequent 2.6g use. I'd interpret this particular example as therapeutic use comparable to a psychedelic or ketamine (which is gaining popularity in America as a prescription anti-depressant).


Considering how agmatine works, if someone is using it to potentiate another drug it might be best to pre-dose ~1hr beforehand. Otherwise agmatines NMDAi and alpha-2 adrenergic agonism could blunt the drugs effects.


reddit.com/r/gabagoodness/comments/o51plu/does_agmatine_have_any_recreational_properties_or/


reddit.com/r/Kanna/comments/18qr34z/how_to_smoothen_the_rush_agmatine_sulfate/


reddit.com/r/Marijuana/comments/zt0afy/agmatine_sulphate_supplement_cannabis_wow/


pubmed.ncbi.nlm.nih.gov/19538988

Shulgin reports on the synergistic value of rilmenidine (Imidazoline agonist) & clonidine (alpha-2 adrenergic agonist) when combined with psychedelics; agmatine is considered an endogenous ligand at both of those receptors.

Thread 'Recreating entactogenesis via psychedelics (2cbFly) plus blood presure meds plus THC'

Jun 26, 2017

Not sure yet if it´s a breakthrought or just plain bullshit, but we have a Shulgin report, a Medical paper and some anecdotal evidence.

The shulgin post:

8.0 mg 2C-B-fly and 2.0 mg of rilmenidine at 12:30 pm; cannabis vapor at 4:00: The result was spectacular. I got a +4 experience from a pure imidazoline blood pressure medication! It is probably the entactogenic core of MDMA. I tend to think of the effects of MDMA as sweeter and gentler than this, but this was much stronger than any MDMA I have previously experienced. It turns out that 2.0 mg of rilmenidine is a very high dose. This...

• Hexagon Sun

• 

Interestingly, Agmatine and DMT both interact with the sigma 1 receptor.

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00330/full

Hello sir. Glad to see your still here dispensing the most up to date info that doctors and "experts" haven't a clue of.