A Look at a 2021 Review and Other Available Research

Disclaimer: The information in this article is for informational purposes only. Consult your health care professional before taking any kind of supplement. Yes, dear reader, that includes you.

In the realms of psychiatry and mental health, depression, anxiety, and PTSD have long remained challenging conditions. Many conditions and subset of conditions have been called “treatment resistant,” and many of the main medications, like SSRIs, come with risks and downsides.

This is partially why ‘psychedelic’ drugs like psilocybin, LSD, MDMA, and ketamine have had a huge renaissance in the research; they have the potential to be a field-changing tool for some of these conditions.

However, when looking for ways to possibly improve anxiety and depression, there may also be lower-risk, inexpensive options in the realm of supplements. Unlike these serious psychedelics and current medications for depression and anxiety, none of which should be taken lightly, supplements available over the counter generally carry less downside.

One such supplement is agmatine.

What Is Agmatine?

Agmatine is a metabolite, like a chemical cousin, of the amino acid arginine. While it’s not an amino acid, its structure is similar. It has shown promise for an array of uses, from relieving pain, to curbing drug addiction, to supporting blood-flow related health markers, and even improving cognitive health.

The latter is what we’re focusing on today, because recent research has called agmatine ‘a novel candidate’ for ‘rapid-onset antidepressant response.’ In other words, it has shown some promise to support depression.

What is Agmatine Typically Used For?

Because of agmatine’s relation to arginine, one of its most common uses is as a bodybuilding supplement. Like arginine it has also shown to increase muscle pumps, and we compare the two in this article on agmatine vs arginine.

Secondary to its bodybuilding uses, it’s also commonly used to combat addiction, which we investigate here.

Its role as a cognitive enhancer is less common, but increasingly more popular thanks to recent research.

Using Agmatine For Anxiety and Depression: The Initial Research

We can’t talk about agmatine as a potential treatment for depression, without mentioning a much more promising, yet much more serious and potentially risky substance: ketamine.

This is the comparison used in the World Journal of Psychiatry’s 2021 review on agmatine for depression. One of the potential upsides of ketamine for treatment of depression is that its fast-acting (within a few hours), compared to other interventions which take days.

Agmatine, interestingly, acts on a similar mechanism, and the original hypothesis for how agmatine may support depression through the same mechanisms as ketamine. The authors of the review write, “Agmatine, an endogenous neuromodulator, shares some common molecular mechanisms with ketamine and the ability to elicit fast antidepressant-like effects in preclinical studies. Therefore, agmatine could be a novel candidate to elicit fast antidepressant responses.”

Effective in Mice

One of the first studies that showed this theory may have validity is the early research in mice. This 2002 study concluded, “Agmatine elicited a significant antidepressant-like effect through a mechanism that seems to involve an interaction with NMDA receptors.”

Effective in a Pilot Study

Now, case studies on humans have even shown some promise. For example, a 2017 review demonstrated some therapeutic potential.

More Human Research Is Needed for Agmatine and Anxiety/Depression, But It’s a Low-Risk Option

In the grand scheme, all we have are a few decent mice studies, a proposed theory, and a few case studies. This is very far from solid evidence that simply supplementing with agmatine will improve depression.

As is often the case with early promise, it may not live up to the hype, or it may only be for certain people in specific situations. We should not get our hopes up that agmatine is a miracle supplement for depression. It almost certainly isn’t. It’s not going to make your anxiety disappear.

However, it’s very low-risk as far as options go. One long-term study (5 years) showed that taking 2.67 grams of agmatine every day for 4-5 years showed no adverse effects. Those assessments included physical examinations, urine tests, and blood tests.

Based on what we know about agmatine, it’s unsurprising to find out that it’s safe. It’s also inexpensive. Bulk agmatine sulfate powder from third-party tested, reputable supplement companies will only cost you a few bucks and last you months.

It’s a flavorless supplement that’s easy to put in smoothies or add to pre or post-workout supplement stacks.

In the realms of science, there tends to be excessive caution about trying new stuff until there is definitive, nearly incontrovertible evidence. The problem is that if you always wait for this evidence, you’ll often wind up decades behind best practices.

More often, you can run self-experiments that are safe, and allow you to test and see if something supports you. That’s the case with agmatine. Its upside for anxiety and depression is likely limited, but because of its safety, even at relatively high doses, try it out and see if it helps you.

Side effects of agmatine

Just because it’s proven safe, doesn’t mean there aren’t a few side effects to be aware of.

GI Distress

Agmatine users have reported some gastrointestinal distress. So if gut health is a problem for you, start with a small dose and assess how it makes you feel.

This isn’t anything to worry about, but nonetheless it’s a consideration.

Pain Relief

Lots of people use agmatine for pain relief. In some cases, this can be a positive, as we’ve talked about in other articles. However, it may merely be an odd side effect for you.

Agmatine as a Nootropic?

Because of similar mechanisms and proposed benefits on cognitive health, agmatine has also been proposed as a nootropic, or “smart drug.” The idea with this category of supplements is to boost how your brain functions, which is very vague and often not well-defined.

However, this idea has much less research than its other uses. Again, you can test it out and see if it helps, but if you’re looking for a nootropic, there are lots of other ingredients and formulas that have shown much more promise.