Sunifiram is a relatively new racetam-like substance 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 offers 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 (sometimes referred to as DM-235) 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 and has somewhat similar effects, its chemical structure is different enough that it doesn't technically belong to the same class of substances, the racetams. And unlike piracetam which has been around since the 1960's, sunifiram was first synthesized by a team of researchers in Italy in 2000.
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 doses of sunifiram. 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
In 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
Sunifiram is an extremely potent nootropic, so a small amount can have a big effect. 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 idea of sunifiram's effective dosage range.
An effective starting 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.
There are a number of case reports of people using much-higher dosages of sunifiram. Many of them are in excess of 50 mg, some has high as 100 mg per dose. While most people who experience a nootropic effect from taking sunifiram do so at low doses, others may require a much higher dose.
If you decide to try sunifiram, as always it's a good idea to start toward the lower end (5 mg) and work your way up as needed. And as always, you should consult a licensed medical professional before starting or stopping any new drug, supplement, exercise program, or behavioral routine. Most doctors aren't taught about nootropics so you may have to educate yours a bit. The References section at the bottom of this page is a good place to start.
Sunifiram Safety
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 negative effects have 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 high doses (> 12 mg). This can likely be avoided by starting with a low dosage and working your way up as needed.
Two of the most common negative effects from sunifiram and other similar nootropics are headaches and upset stomach. Both of these potential negative 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 unwanted 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 effect of ampakines like sunifiram 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
Of all the nootropics discussed on this website, sunifiram can be one of the hardest to get your hands on. You won't find it in brick-and-mortar stores like Walmart, nor will you find it at common online retailers like Amazon. Since sunifiram is still relatively new and is a fairly novel substance, most nootropic vendors don't even carry it.
As of right now, there are only a couple of reputable places to order sunifiram from. If you're looking for sunifiram powder, Science.bio offers it in this form. Their products are of the highest quality and they have an amazing selection of nootropics and other substances. Science.bio also has reasonable prices, fast and discreet shipping, and excellent customer service.
Additionally, you can also find sunifiram at Pure Rawz. They offer this novel nootropic in two different forms: powder and tablets. This company also has an excellent reputation for providing high-quality products at reasonable prices. And like Science.bio, Pure Rawz has an astonishing selection of products – nootropic and otherwise. Be aware that their sunifiram tablets are dosed at 80 mg each, which is very high for most people.
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 brand new to the wonderful world of cognitive enhancers, an older and more-researched nootropic like piracetam or aniracetam might be a better place to start. But if you're an experienced biohacker or just want to try something new, sunifiram certainly seems to have a lot of potential as a nootropic.
Have you used sunifiram? If so, what has your experience with it been like? Please leave your answer in the comments section at the bottom of the page. And if you haven't already, sign up for the Nootropics Zone newsletter below to learn about dozens of brain-boosting substances.
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References
1Malykh, A., & Sadaie, M. (2010). Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs, 70(3):287-312.
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 July 5, 2024.]
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