Sunifiram is a relatively new nootropic racetam that has been getting some attention in the nootropics community over the past few years. Although there hasn't been much research done on it yet, preliminary studies are very promising.

Users from around the world have reported that sunifiram has a number of potent nootropic and mood-boosting properties. In this article, we're going to take a look at some of these benefits, the science behind them, and more. But first, let's take a look at what sunifiram is.

What Is Sunifiram?

Sunifiram is a synthetic derivative of piracetam, which was the first nootropic ever created and one of the most well-studied.1 Although sunifiram was created from piracetam, it's different enough that it isn't technically in the same class of substances, the racetams.

Sunifiram has been shown to be many times more potent than piracetam. In fact, it is estimated to be about 1,000 times higher.2 Unsurprisingly, many users have reported amazing results from very small sunifiram dosages. While piracetam doses are measured in grams, sunifiram doses are measured in single-digit milligrams. This means you have to take much less to experience a similar nootropic effect.

Users of sunifiram have reported a variety of nootropic benefits from it. Here are some of the nootropic benefits of sunifiram that users have reported:

  • Improved memory
  • Increased focus
  • Improved mood
  • Improved decision making
  • Increased alertness
  • Increased sense of well-being
  • Overall cognitive enhancement

Now that we've taken a look at what sunifiram is and its potential nootropic benefits, let's dive into the science of how it works.

How Sunifiram Works (a bit science heavy)

Sunifiram is known as an ampakine (sometimes written AMPAkine) because its main mechanism of action seems to be via the AMPA receptor.3 AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) is one of the three main subsets of glutamate receptors along with NDMA and kainate.4 Sunifiram seems to be a positive allosteric modulator of AMPA. It activates AMPA-mediated neurotransmission.5

Brain bulbIn addition to its ability to affect glutamate receptors, sunifiram has also been shown to aid in the release of acetylcholine in the cerebral cortex.6 Acetylcholine is a much-studied neurotransmitter known to play a vital role in learning, memory, decision making, and other cognitive processes. Many nootropics are known to affect acetylcholine levels in the brain.

While animal research shows sunifiram to affect glutamate and acetylcholine indirectly, it does not seem to bind to any of the neurotransmitter sites that nootropics often do directly. Researchers found that sunifiram did not significantly bind to GABA, serotonin, dopamine, opioid, glutamate, acetylcholine, histamine, or adrenergic receptors.7

While sunifiram is a derivative of the racetamic nootropic piracetam, it is not technically a racetam itself. This is because sunifiram does not have the same chemical (pyrrolidone) backbone that piracetam and the other racetams do.8 Sunifiram is chemically similar to other piperazine alkaloids such as unifiram and sapunifiram.9

Animal studies have shown sunifiram to have nootropic activity comparable to piracetam and other racetams. In rats, sunifiram has been shown to have an anti-amnesic (memory-enhancing) effect and can reverse cognitive impairment caused by several different drugs.10 While these results are promising, especially combined with positive reports from people who have used sunifiram, more (human) research needs to be done before its nootropic effects can be conclusively stated.

Sunifiram Dosage

The Nootropic Potential of Sunifiram 1Sunifiram is an extremely potent nootropic, so you only need a small amount to experience its effects. While there have not been studies done to figure out the optimal dosage for humans, we can look at animal research and the dozens (if not hundreds) of case reports published online to come up with a general dosage range.

An effective sunifiram dosage for most people seems to be somewhere between 5 and 10 milligrams (mg). At the lower end of that range, users have reported an increase in focus, improved memory, and overall cognitive enhancement. At the higher end and beyond, users have reported more of a stimulating effect in addition to the effects felt at lower dosages.

If you decide to try sunifiram, as always it's recommended that you start toward the lower end (5 mg) and work your way up as needed. And of course, you should always consult a licensed medical professional before starting or stopping any new drug, supplement, exercise routine, etc.

Sunifiram Safety and Side Effects

There have not been any human studies done on the long-term safety of sunifiram. However, between animal studies, case reports, and sunifiram's structural and functional similarity to other well-researched nootropics, it's reasonable to assume it has at least a fairly good safety profile.

No serious side effects have ever been reported from sunifiram use and there is no known toxicity associated with it.11 Some users have reported over-stimulation, insomnia, and anxiety when using extremely high doses (> 12 mg). This can easily be avoided by staying within the dosage range mentioned above.

The Nootropic Potential of Sunifiram 2Two of the most common side effects from sunifiram and other similar nootropics are headaches and upset stomach. Both of these potential side effects can usually be reduced or eliminated. If you experience upset stomach from sunifiram, taking it with a small meal should help. Most users who experience nausea and gastrointestinal discomfort from taking sunifiram on an empty stomach report that these side effects are lessened or eliminated when it's taken with food.

Sunifiram is often stacked with a choline source like alpha-GPC. Stacking simply means taking more than one nootropic at a time for increased effectiveness. Some users of sunifiram and similar nootropics report getting headaches. This is a known side effect of ampakines and may be due to changes in acetylcholine levels in certain parts of the brain.12 By taking a choline source like alpha-GPC, you ensure you that you have adequate levels of acetylcholine, thus reducing the likelihood of headaches.

Taking a choline source with sunifiram and other similar nootropics isn't just a good idea because it can reduce the likelihood of headaches. Several sunifiram users report that taking it with a choline source increases its effectiveness. This is also the case with many racetams and other similar nootropics. While there are others, the two most common choline sources taken with sunifiram are alpha-GPC and CDP-choline.

Where To Buy Sunifiram

The Nootropic Potential of Sunifiram 3As of right now, there aren't very many reputable places to buy sunifiram. Since it's relatively new and hasn't been studied nearly as much as many other nootropics, not many vendors carry it. However, if you want to try this potent nootropic, there is one trustworthy online store that sells it: Science.bio.

Science.bio offers sunifiram in powder form. Their products are of the highest quality and they have an amazing selection of nootropics and other substances. Additionally, their prices are reasonable, shipping is fast, and they have excellent customer service.

Conclusion

More research is needed to fully understand how sunifiram works and to conclusively state all of its nootropic benefits. However, the research that has been done is very encouraging. And reports from users all over the world show that sunifiram can have a powerful nootropic effect.

If you're new to the wonderful world of cognitive enhancement, you might want to try one of the older and better-researched nootropics like piracetam or aniracetam. But if you're an experienced biohacker and want to try something new, sunifiram might be just what you're looking for.

Have you used sunifiram? If so, feel free to share your experience in the comments section at the bottom of the page. And if you haven't already, please sign up for the Nootropics Zone newsletter below.

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References

2Ghelardini, C., Galeotti, N., Gualtieri, F., et al. (2002). DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer. Naunyn-Schmiedeberg's Archives of Pharmacology, 365:419-26.

3Scapecchi, S., Martini, E., Manetti, D., et al. (2004). Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs. Bioorganic & Medicinal Chemistry, 12(1):71-85.

4Froestl, W., Muhs, A., & Pfeifer, A. (2012). Cognitive enhancers (nootropics). Part 1: drugs interacting with receptors. Journal of Alzheimer's Disease, 32(4):793-887.

5Romanelli, M., Galeotti, N., Ghelardini, C., et al. (2006). Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers. CNS Drug Reviews, 12(1):39-52.

6Manetti, D., Ghelardini, C., Bartolini, A., et al. (2000). Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity. Journal of Medicinal Chemistry, 43(23):4499-507.

7Gualtieri, F. (2016). Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(2):187-94.

8Moriguchi, S., Tanaka, T., Tagashira, H., et al. (2013). Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice. Behavioral Brain Research, 242:150-7.

9Martini, E., Salvicchi, A., Ghelardini, C., et al. (2009). Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers. Bioorganic & Medicinal Chemistry, 17(21):7606-14.

10Manetti, D., Martini, E., Ghelardini, C., et al. (2003). 4-aminopiperidine derivatives as a new class of potent cognition enhancing drugs. Bioorganic & Medicinal Chemistry Letters, 13(14):2303-6.

11Sunifiram. (2018, June 14). Examine.com. Retrieved April 16, 2021 from https://examine.com/supplements/sunifiram/

12Wezenberg, E., Verkes, R., Ruigt, G. (2007). Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology, 32(6):1272-83.

[This article was originally published January 9, 2016. Updated April 16, 2021.]

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