Our evidence-based analysis of Sunifiram features unique references to scientific papers and anecdotal reports.
What Is Sunifiram?
Sunifiram, also known as DM-235, is an exciting recent development in nootropics. It’s structurally similar to racetam nootropics but about 1,000 times stronger than piracetam.[1]
Research suggests that sunifiram may boost brainpower, mood, and energy even when taken in low doses.
Sunifiram was first synthesized in 2000 by scientists at the University of Firenze in Italy.[2]
Very little research is currently available, but preliminary animal studies indicate that it may be a highly effective nootropic and a potential treatment for various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and amnesia.[3]
No toxicity threshold or serious side effects have been identified, but there have been no documented studies or clinical trials involving humans to date. Animal studies indicated no toxicity, even at high doses.[4]
Sunifiram is currently considered an experimental drug, which means it has not been approved for any use in human or veterinary medicine.
It is unregulated in the US, where it can be legally purchased, possessed, and used.
Benefits and Effects of Sunifiram
Sunifiram is so new and untested that little is known about how it actually works or the effects it might have on humans.
Initial animal studies indicate that it may have powerful nootropic benefits, and anecdotal evidence from users suggest it may have other benefits as well.
Enhances Learning and Memory
Animal studies show that sunifiram can act as a powerful nootropic, delivering measurable improvements in learning speed, memory retention, and recall.
Research on rats showed that sunifiram not only enhanced performance in learning tasks, it actually reversed chemically-induced amnesia.[5]
In a study on healthy adult rats, sunifiram significantly enhanced learning and memory even at very small doses.[6]
Many users say that sunifiram has a positive effect on their ability to learn and understand.[7]
One user said his IQ increased by 15 points over a four-month period, during which he took 25 mg of sunifiram four times weekly.[8]
May Improve Focus, Motivation, and Mental Clarity
Sunifiram users frequently report that it gives them better focus, mental clarity, and concentration.[9][10]
Others report that it improves their motivation to both tackle and complete mental tasks.[11]
These effects may be attributable in part to the fact that sunifiram facilitates the release of acetylcholine, the neurotransmitter most closely associated with cognitive ability.
Mood and Energy Booster
Many users report that sunifiram gives them more energy and a happier, more positive outlook.[12][13][14][15]
Visual and Perceptual Enhancement
Many people say that taking sunifiram gives them a brighter outlook in a very literal sense, making light and shadow more pronounced and colors more vibrant.
For some people, it also makes music more mentally engaging and emotionally meaningful.[16][17]
Increased sex drive
A significant percentage of users report that sunifiram has distinct and noticeable aphrodisiac properties, increasing their interest in sex.[18][19]
This effect doesn’t appear to be universal and has not been replicated in animal studies.
How It Works
Though sunifiram is a piracetam derivative, it has a different chemical structure from the racetams and is chemically classed as a piperazine alkaloid.
Its precise mechanisms of action are not entirely understood, but it is known to work by stimulating the activity of glutamate receptors and by increasing the production and release of the “learning neurotransmitter” acetylcholine.
It is believed that sunifiram’s primary action is that of an ampakine, which means that it binds to AMPA-type glutamate receptors in the brain after crossing the blood-brain barrier.[20] This stimulates the production of glutamate, a vital neurotransmitter that plays a pivotal role in neural activation.
Glutamate is an excitatory neurotransmitter that is crucial to synaptic plasticity, or the ability of nerve synapses to respond to increases or decreases in activity.
Adequate levels of glutamate are essential to long-term potentiation, or lasting improvement in signal strength between neurons.[21]
Glutamate levels are of particular importance in the hippocampus, the part of the brain that plays the primary role in both spatial navigation and the formation and storage of memory, and it is believed that much of sunifiram’s cognitive enhancement ability is ultimately accomplished by improving neural signal strength in this part of the brain.[22]
In addition to enhancing memory formation and recall, ampakines also generally act as mild stimulants that increase alertness and energy but without the restlessness and other adverse side effects associated with caffeine, methylphenidate (Ritalin), and amphetamines.[23]
Sunifiram is also thought to act as a cholinergic, increasing the production and release of the neurotransmitter acetylcholine.
Acetylcholine is closely associated with most aspects of cognition, including memory, learning speed and ability, and fluid intelligence or capacity to solve unique problems without relying on learned behaviors.
Though the exact process by which sunifiram modulates acetylcholine production has not been identified, an Italian animal study showed that tests using piperazine compounds such as sunifiram had a cholinergic effect similar to that of piracetam.[24]
Dosage
The only documented sunifiram studies available to date involved animals rather than human subjects, making clinically-backed recommendations on dosage impossible.
However, it is known that sunifiram is much more potent than other racetams, with one study showing that sunifiram is about 1000 times more potent than piracetam.[25]
It is widely accepted that sunifiram requires a much smaller dose than racetams for effectiveness. Based on a combination of user reports and information gained from animal studies, a dosage of 5-10 mg taken a maximum of three times per day is typically considered both safe and effective.[26]
Some users say sunifiram is best taken sublingually for maximum absorption and that it should be cycled rather than taken continuously to prevent tolerance, but there is no scientific documentation on human dosing.
It is always wise to start with the smallest possible effective dosage of a new supplement and gradually increase as needed. That advice is particularly pertinent to sunifiram because it is an experimental drug about which little is known.
Stacking
Sunifiram can be stacked with other nootropics, but users are cautioned to be careful and conservative about sunifiram dosages combined with other potent supplements, particularly until they’re sure how they react to sunifiram.
Stacking for enhanced cognitive effects: This is possibly the most common type of sunifiram stack and is best accomplished by pairing sunifiram with one or more of the racetams like piracetam, oxiracetam, or Noopept. Because racetams make a powerful draw on the brain’s choline stores, it is recommended to add a good choline source like CDP choline, Alpha GPC, or centrophenoxine to this type of stack.
Stacking for mood enhancement: Aniracetam is known to stack well with sunifiram for mood enhancement. L-theanine, which enhances dopamine production, serotonin, and GABA and acts as a glutamine reuptake inhibitor, also stacks well with sunifiram. Sulbutiamine, which potentiates cholinergic, dopaminergic, and glutamatergic transmission, is another excellent addition to this type of stack. As always, when a racetam supplement is used, a good choline source is important both as a potentiator and to prevent headaches and other unwanted side effects.
Side Effects
To date, no serious side effects of sunifiram have been documented, but it’s important to remember that no human studies or clinical trials have been conducted.
Information from animal studies indicates that it is both safe and well tolerated, and even doses many times higher than the effective dosage range have not been found to be toxic.[27]
User-reported side effects are both minor and temporary and include increased body temperature, increased perspiration and salivation, headache, nasal stuffiness, increased sensitivity to visual and audio stimulation, and insomnia.
Where to Buy
Sunifiram is not widely available and can only be purchased from a select few vendors. We do not have any suppliers to recommend at this time.
Closing Thoughts
Sunifiram is an exciting development among nootropic supplements. Though there is very little documented research on its effects or mechanisms of action, it appears to have the potential to deliver robust cognitive, mood, perceptual, and energy benefits in an ultra-concentrated and potent form.
Many nootropics users consider it a favorite and regularly add it to their stacks, but it’s not a supplement to be taken lightly or consumed carelessly. Animal studies suggest that it’s safe, well-tolerated, and non-toxic, but it’s important to remember that its effects on humans have not been fully explored.
If you prefer supplements that are well-researched and thoroughly understood, sunifiram isn’t your best choice. But if you’re willing to experiment with a new and to some extent unknown supplement, sunifiram could be worth your consideration.
References
Planning to start a new supplementation regimen? See our medical disclaimer.
This page was last updated on July 16, 2021.