Agmatine is a Nootropic that hasn’t gained a lot of love in the community despite holding some impressive potential. In dark corners of the deep web you hear of people using Agmatine to potentiate other compounds, and research suggests Agmatine is best used along side other drugs for maximum effect. Smart and informed Kratom users rely on Agmatine to boost the power of the plant, reduce their dose requirements, reduce pain perception, and lower tolerance – All very important applications for the Kratom connoisseur. Agmatine reportedly lowers tolerance to not only Kratom but many other substances through various mechanisms.

Tolerance and Potentiation

Opioids – Agmatine appears to be a potent enhancer of opioid type compounds and also reduces tolerance. Some studies suggest NMDA antagonism is responsible for these actions while others point to the activation of imidazoline receptors. Notable NMDA antagonizers like Ketamine have proved efficacy in reducing tolerance to opioids, and Agmatine may work through similar mechanisms. Agmatine is thought to attenuate Morphine withdrawal and addiction by modulating a2A receptors.

Cannabinoids – Agmatine potentiates certain cannabinoids through the activation of imidazoline receptors and enhances their painkilling properties. Many users also self report combining Agmatine with various Cannabis products to enhance potency.

Agmatine is also widely used to potentiate other popular Nootropics and substances like Phenibut, Nicotine, Modafinil, and Adderall – presumably through NMDA antagonism.

Cognitive Effects

During the learning process Agmatine shows increased concentrations in the pre frontal cortex and hippocampus. This suggests Agmatine plays a role in memory formation and learning…but we’re talking rat brains here so your mileage may vary.

Alcohol Withdrawal

Of particular interest to me was Agmatines role in the attenuation of alcohol withdrawal symptoms. Interestingly, alcohols anxiolytic effects are prevented when Arginine is inhibited, suggesting that Agmatine (a product of Arginine) could play a role in managing alcohol dependence. A combination of Agmatine, Zinc, and Magnesium might prove to be a very effective DIY stack for managing mild to moderate alcohol withdrawals, although speaking from experience heavy drinkers should probably stick to more proven medications like Valium/Benzodiazepines and seek medical attention. Alcohol withdrawals can kill you.

Agmatine reduces glutamate excitotoxicity. During alcohol withdrawal, glutamate pathways are in a hyperexcitable state resulting in severe anxiety, seizures, and brain damage in serious cases. Agmatines role in modulating glutamate could prove useful in managing withdrawal symptoms.

Addiction

Agmatine may play a role in managing addictions and impulse control through a2A receptor modulation. a2A receptors are said to be central to addictive behaviors and impulses. a2A receptors for example are upregulated during Nicotine addiction, and Agmatine shows some promise in treating Nicotine related impulse behaviors in rats.  It appears more human studies are needed to prove Agmatines relationship to addiction.

Nitric Oxide

Agmatine is a popular supplement in the body building community due to its “pump” effect – essentially increasing Nitric Oxide and blood flow. While many studies point out that Agmatine reduces NOS, it appears to be a regulator rather than something that acutely lowers or increases concentrations. Anecdotally many athletes use it for enhanced physical performance.

Experience and Dosage

I’ve used Agmatine 3 nights in a row at 500mg. At such dose I find my ability to get into the zone much easier especially with writing. The Nitric Oxide effect feels pronounced – I’m extremely lean and easily notice small changes to my muscle pump and overall vascularity. The effect is here. Of particular interest, I have a small stash of Trazadone (anti depressant) I use as a sleep aid. While the medication is technically an anti depressant, the drowsiness side effects are so pronounced it’s often prescribed for sleep. I found the drowsiness effects of the Trazadone seemed to be non existent with 500mg of Agmatine. While I will need to experiment more, I think it does indeed modulate anti depressants to a large degree.

A blunting of emotions and general mood stabilizing effect is perceived.

I am most interested in whether or not Agmatine will reduce Phenibut rebound anxiety to any notable degree. This is something I will report back on.