Sunifiram, also known as DM-235, is one of the most exciting new developments in nootropics, potentially providing a powerful cognitive boost along with mood and energy enhancement.
First synthesized in 2000, sunifiram is a very recent discovery, and there is only a limited body of research available to date, but preliminary animal studies indicate that it may be an effective nootropic.
It is also believed to be a potential treatment for a variety of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and amnesia.
No serious side effects have been identified, though research is ongoing. There have been no documented studies or clinical trials involving humans, but animal studies suggest that sunifiram is both safe and well-tolerated.
Sunifiram is a derivative of the racetam family of nootropics but has a different chemical structure and is classified as a piperazine alkaloid rather than a racetam. It delivers many of the same memory and learning enhancements as piracetam but is as much as 1000 times more potent.
Sunifiram is also an ampakine, a compound that interacts with the glutamatergic AMPA receptors to boost the activity of the neurotransmitter glutamine, and as such may deliver significant mood and energy improvement as well as cognitive benefits.
Benefits and Effects
- Learning and memory: Sunifiram has been proven to act as a powerful nootropic, delivering measurable improvements in learning speed, memory retention, and recall. Animal studies showed that sunifiram not only enhanced performance in learning tasks, it actually reversed chemically-induced amnesia.
- Improved focus and motivation: Sunifiram users frequently report that it gives them better focus and concentration and improves their motivation to both tackle and complete mental tasks, and animal studies tend to bear this out. The focus and motivation enhancement effects could be attributable in part to the fact that sunifiram facilitates the release of acetylcholine, the neurotransmitter most closely associated with cognitive ability.
- Anxiety and depression management: Though animal studies don’t suggest that sunifiram acts as an anti-depressant or anxiety reliever, some users report that it has these effects. These effects may be explained at least in part to its actions as an ampakine, or compound that interacts with the glutamatergic AMPA receptors and acts as a mild stimulant.
- Mood and energy booster: Many users report that sunifiram gives them more energy and a brighter, generally happier outlook.
- Visual/perceptual enhancement: While user reports of visual and perceptual improvements are far from universal, 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.
- Increased sex drive: A significant percentage of users report that sunifiram has distinct and noticeable aphrodisiac properties, increasing their interest in sex. 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. It is known to work in two ways, both as an ampakine that stimulates the activity of glutamine receptors and as a cholinergic that increases the production and release of acetylcholine.
Like many nootropics, sunifiram’s precise mechanisms of action are not entirely understood. However, it is believed that its primary action is that of an ampakine, which means that after crossing the blood-brain barrier it binds to AMPA-type glutamate receptors in the brain. This stimulates the production of glutamate, a vital neurotransmitter that plays the 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. 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.
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.
Sunifiram is also thought to act as a cholinergic, increasing the production and release of the neurotransmitter acetylcholine. Though the exact process by which this occurs 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.
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. Most nootropics work at least in part by increasing the availability of acetylcholine, either by stimulating acetylcholine receptors or by directly supplying its precursor choline which is then synthesized into acetylcholine.
To date, the only documented sunifiram studies involved animals rather than human subjects making it challenging to make clinically-backed recommendations on dosage. 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.
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 to 10 mg taken a maximum of three times per day is typically considered both safe and effective. Sunifiram is best taken sublingually for maximum absorption.
It is always wise to start with the smallest possible effective dosage of a new supplement and gradually increase as needed, and that advice is particularly pertinent to sunifiram. Not only is it a new drug on which no human trials have been documented, large doses could have unpleasant side effects including over-stimulation and brain fog.
Tolerance to sunifiram may build rapidly. Some users recommend cycling it with other nootropics to avoid this effect.
Sunifiram can be stacked with other nootropics, but users are cautioned to be both careful and conservative about sunifiram dosages in combination 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 production of dopamine, serotonin, and GABA and acts as 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.
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 proven toxic.
User-reported side effects are both minor and temporary and include an increase in 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.
Sunifiram is one of the most exciting and promising new nootropic supplements, delivering robust cognitive, mood, perceptual, and energy benefits in an ultra-concentrated and potent form.
While it isn’t as known as some of the more traditional nootropics, many users consider it a favorite and use it regularly, but it’s not a supplement to be taken lightly or consumed carelessly due to the lack of research. Though animal studies conducted over the past 15 years show it to be safe, well-tolerated, and non-toxic, it’s important to remember that no human studies have been documented and much remains to be known about this powerful supplement.
For users who bear in mind that this is a new and to some extent unknown supplement, taking it responsibly and carefully monitoring its effects, sunifiram can be an excellent addition to the nootropic routine.
References [ + ]
|1.||^||Moriguchi S, et al. Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor. (2013)|
|2.||^||Manetti D, et al. Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity. (2000)|
|3.||^||Ghelardini C, et al. DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer. (2002)|
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