Drug Interactions, Kratom Guides

Kratom & Agmatine (AgmaSet): Is This a Safe Combo?

Does Kratom Interact With Agmatine (AgmaSet)?

Kratom can interact indirectly with agmatine by increasing its effects. While this might sound good, it can actually be dangerous and causes a greater risk of side effects, such as drowsiness, depression, and anxiety.

 This interaction is considered moderate but differs from person to person, especially if the two drugs are taken for long and in large quantities.

Always get proper consultation from your physician before taking kratom and agmatine together.

Increased Effects (Agonistic Interaction)

Kratom and agmatine can interact agonistically. While a milder form of interaction could help mitigate pain better, a more severe form could cause effects like excess drowsiness, a potentially dangerous side effect if you’re doing activities that require absolute concentration.

Agmatine can also increase the chances of experiencing anxiety and depression. Overuse of kratom can also cause these effects [12].

Agonistic interaction happens by mixing two substances that give similar effects. These substances might act on the same or different receptors but produce some effects in the same direction when taken together.

Agmatine has pain-relieving effects on the body [1]. It can also help reduce heart rate and blood pressure [2].

Kratom has agonistic actions on the alpha-2 receptors, which means it can decrease pain and may reduce blood pressure [3]. Its pain-relieving qualities are similar to that of opioids [4].

Both the drugs have similar actions, so taking them together can cause their pain-relieving abilities to increase, causing side effects like sedation. You can avoid this by using small quantities of both drugs for a short duration.

Because these two medications are metabolized in different ways, there are minimum chances of any metabolic competition occurring in the body between them.

Kratom & Agmatine (AgmaSet) Interactions

Agmatine is classified as a guanidine, which means it exerts modulatory action at multiple molecular targets, such as neurotransmitter systems, ion channels, nitric oxide (NO) synthesis, and polyamine metabolism. There are a few other aminoguanidine medications, all of which share a similar level of risk when used alongside kratom.

Other guanidines that kratom interacts with include:

  • Arginine
  • Creatine
  • Saxitoxin
  • Triazabicyclodecene

Is it Safe to Take Kratom With Agmatine (AgmaSet)?

Kratom and agmatine can have moderate levels of interaction when taken together. They may be safe to consume together in short amounts and for a short time. Agmatine can help to increase the relaxing and pain-relieving properties of kratom.

However, the long time consumption of both drugs with high dosages may cause the two drugs to have more powerful effects, leading to some unwanted effects. 

There are no studies on how these two interact. Since we don’t know the exact amounts or how long it takes to cause a dangerous interaction, don’t take these medications until after you consult your physician. Never start them of your own accord; if you encounter any unusual side effects, get medical aid immediately.

What is Agmatine (AgmaSet)?

Agmatine is an aminoguanidine and a metabolite of the amino acid arginine that occurs naturally.

Agmatine can regulate many critical molecular targets of essential systems in the body. It is being studied to treat depression, high blood pressure, and nerve pain and helps build up muscles in bodybuilding and improve athletic performance. It also has the properties of neuromodulators, helping to transmit information across neurons.

It is found in ragweed pollen, ergot fungi, octopus muscle, herring sperm, sponges, and mammalian brains when arginine is decarboxylated by the enzyme arginine decarboxylase.

Agmatine Details & Specifications:

Drug NameAgmatine
Trade NameAgmaSet, Transparent Labs RawSeries Agmatine, Nutricost Agmatine, BulkSupplements Pure Agmatine Sulfate Powder, Hard Rhino Agmatine Sulfate Powder  
ClassificationGuanidine
CYP MetabolismNot specified
Interaction With KratomAgonistic
Risk of InteractionModerate  

What is Agmatine (AgmaSet) Used For?

Agmatine is being studied for several indications. Some of these are:

Neuroprotective Effects

Research shows agmatine has neuroprotective effects against brain edema following transient cerebral ischemia [6]. The potential mechanisms for this include anti-oxidation, anti-apoptosis, and anti-inflammation properties of agmatine [11]. It may also be effective in stroke, severe CNS injuries, epilepsy, glaucoma, neuropathic pain, and psychiatric conditions such as depression, anxiety, schizophrenia, and cognition.

Cardioprotective Effects & Blood Pressure Control

Agmatine has a cardioprotective function and may help reduce the effects of ischemic heart disease [7]. Agmatine can act directly on endothelial cells and increase nitric oxide synthesis, a substance that can cause vasodilation. This property may also help to lower blood pressure.

Peripheral Neuropathy

It is being studied for use in patients with small fiber peripheral neuropathy [1]. It can reduce neuropathic pain caused by small fiber neuropathy (SFN), which is resistant to conventional neuropathic pain medications.

Effects on Opioid Addiction

It may also decrease dependence in people who use opioids [8]. Agmatine can block the physical dependence on morphine by acting on the cAMP signaling pathway. This means it can prevent or reduce opioid-induced tolerance and self-administration amongst opioid users.

Effect on Blood Glucose & Insulin Sensitivity

Agmatine can improve insulin sensitivity by stimulating the adrenal gland and enhancing beta-endorphin secretion [9]. It also activates peripheral I2-imidazoline receptors in tissues, which helps improve the actions of insulin. Thus, it can help to reduce high blood glucose levels as well.

Use in Bodybuilding

Agmatine can increase the luteinizing hormone (LH) levels, which, in turn, can increase testosterone levels and help build more muscles during training [10].

What’s the Dose of Agmatine (AgmaSet)?

The recommended dose of agmatine is 1.6 mg to 6.4 mg per kilogram of bodyweight.

Generic & Brand Name Versions

  • BulkSupplements Pure Agmatine Sulfate Powder
  • Hard Rhino Agmatine Sulfate Powder
  • Nutricost Agmatine
  • Transparent Labs RawSeries Agmatine

What Are the Side Effects of Agmatine (AgmaSet)?

  • Diarrhea
  • Gastrointestinal disturbances
  • Hypotension
  • Increased anxiety and depression
  • Increased appetite
  • Nausea
  • Upset stomach

What is Kratom?

Kratom is a herbal extract derived from the tree Mitragyna speciosa and is native to Southeast Asia. Mitragynine, a substance found in kratom leaves, has effects similar to opioids like morphine. 

It was traditionally used for medicine and was considered a household staple but only recently made its way to the Western world.

It’s a unique plant because, in low doses, it acts as a stimulant, but in high doses, it can act as a sedative. Large amounts are more likely to cause side effects and addiction.

What’s Kratom Used For?

There are many uses for kratom, but here are the most common.

What is the Dose of Kratom?

The kratom dose is based on what effects you want. If you’re seeking pain relief or struggle to sleep, you’ll want higher doses — 5-10 g. If energy, concentration, and improved mood are what you’re after, stick with smaller amounts — 2-5 g. You can even try microdosing if you want (less than 2 g).

The key is to only use as much as you need and when you really need it. Too much kratom too often leads to an increased risk of side effects and addiction. Take breaks from it now and then to avoid building a tolerance.

What Are the Side Effects of Kratom?

Kratom is relatively safe and has few side effects that are worth noting. Still, they exist, and it helps to know what to expect.

Common side effects include:

What Are the Different Types of Kratom?

You might become overwhelmed if you buy kratom and know nothing about it. Many strains are available, and it’s hard to know which one does what and why they’re different.

Don’t worry — it’s actually quite simple. Kratom is divided into strains based on the veins in the leaves. The alkaloid content determines the color and greatly affects the effects. There are three primary colors, and we’ll go over each one.

White Vein Kratom

White strains boost concentration power, energy, and mood and can even help raise cognition. People use white strains to help with depression, though they can cause anxiety in some people.

Red Vein Kratom

Red strains are calming, can decrease anxiety, and help with insomnia. They have strong pain-relieving action due to their interaction with the opioid system.

Green Vein Kratom

Green strains are a balance between red and white. They have both stimulant and sedative effects that can alter with the amount of dosing. All kratom has this ability, but it’s more pronounced with green. These are ideal for anyone new to kratom or who doesn’t want anything too extreme.

Yellow Vein Kratom

Yellow kratom strains are derived from a fermented form of the green vein kratom, making it smoother and more relaxing.

Key Takeaways: Is it Safe to Mix Kratom & Agmatine (AgmaSet)?

Kratom and agmatine can interact moderately with each other. Their interaction is agonistic since both drugs are pain relievers. Taking them together in small doses could help lighten the pain better.

However, this interaction can worsen with long-term medication or high doses, leading to sedation-like effects that could become dangerous.

Because of the potential for danger, it’s always best to talk to your prescribing physician before you begin. 

References

  1. Rosenberg, M. L., Tohidi, V., Sherwood, K., Gayen, S., Medel, R., & Gilad, G. M. (2020). Evidence for dietary agmatine sulfate effectiveness in neuropathies associated with painful small fiber neuropathy. a pilot open-label consecutive case series study. Nutrients, 12(2), 576.
  2. Raasch, W., Schäfer, U., Qadri, F., & Dominiak, P. (2002). Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine‐mediated blood pressure reaction. British journal of pharmacology, 135(3), 663-672.
  3. Foss, J. D., Nayak, S. U., Tallarida, C. S., Farkas, D. J., Ward, S. J., & Rawls, S. M. (2020). Mitragynine, a bioactive alkaloid of kratom, reduces chemotherapy-induced neuropathic pain in rats through the α-adrenoceptor mechanism. Drug and alcohol dependence, 209, 107946.
  4. Eastlack, S. C., Cornett, E. M., & Kaye, A. D. (2020). Kratom—Pharmacology, clinical implications, and outlook: a comprehensive review. Pain and Therapy, 9(1), 55-69.
  5. Haenisch, B., von Kügelgen, I., Bonisch, H., Göthert, M., Sauerbruch, T., Schepke, M., … & Molderings, G. J. (2008). Regulatory mechanisms underlying agmatine homeostasis in humans. American Journal of Physiology-Gastrointestinal and Liver Physiology, 295(5), G1104-G1110.
  6. Huang, Y. C., Tzeng, W. S., Wang, C. C., Cheng, B. C., Chang, Y. K., Chen, H. H., … & Chang, C. P. (2013). Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation. Magnetic Resonance Imaging, 31(7), 1174-1181.
  7. Greenberg, S., Finkelstein, A., Gurevich, J., Brazowski, E., Rosenfeld, F., Shapira, I., … & Keren, G. (1999). The effect of agmatine on ischemic and nonischemic isolated rat heart. Journal of Cardiovascular Pharmacology and Therapeutics, 4(3), 151-158.
  8. Aricioglu, F., Means, A., & Regunathan, S. (2004). Effect of agmatine on the development of morphine dependence in rats: potential role of the cAMP system. European journal of pharmacology, 504(3), 191-197.
  9. Su, C. H., Liu, I. M., Chung, H. H., & Cheng, J. T. (2009). Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neuroscience letters, 457(3), 125-128.
  10. Kalra, S. P., Pearson, E., Sahu, A., & Kalra, P. S. (1995). Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone release in vivo and hypothalamic luteinizing hormone-releasing hormone release in vitro. Neuroscience letters, 194(3), 165-168.
  11. Xu, W., Gao, L., Li, T., Shao, A., & Zhang, J. (2018). Neuroprotective role of agmatine in neurological diseases. Current neuropharmacology, 16(9), 1296-1305.
  12. Gawali, N. B., Bulani, V. D., Gursahani, M. S., Deshpande, P. S., Kothavade, P. S., & Juvekar, A. R. (2017). Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway. Brain research, 1663, 66-77.