Sunifiram is an experimental drug that some people claim may have “nootropic” (“cognitive-enhancing”) effects. Some very preliminary findings from animal research may suggest that sunifiram could have some interesting potential effects on learning, memory, pain sensitivity and more – however, it has never been scientifically or medically tested in humans, and therefore practically nothing is known for sure about its overall effectiveness or safety. So what does the current science have to say about this drug’s purported effects? Read on to learn more about the potential effects, mechanisms, and side-effects of this highly experimental drug.
Disclaimer: This post is not a recommendation or endorsement for the use of sunifiram. The FDA has not approved this drug for any specific medical or other use, and the available research on it is still in a very early stage, without adequate data to come to any conclusions about its general efficacy or safety in humans. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about sunifiram’s mechanisms, potential effects, and possible side-effects.
What is Sunifiram?
Sunifiram, or “DM-235”, is an experimental drug that was originally developed with the goal of treating the symptoms of cognitive decline in Alzheimer’s disease patients [1].
However, research on sunifiram was eventually discontinued due to a lack of research funding, and its patent expired. Therefore, sunifiram has never been tested on humans, and its potential long-term toxicity and general safety in healthy human users remains unknown [1].
In addition, sunifiram hasn’t been officially approved by any country for any medical or other use. It is currently only sold online – by unverified vendors – as a so-called “smart drug”, or “nootropic” [1].
Mechanism of Action
Sunifiram is believed to be somewhat similar in molecular structure to piracetam, which has led some researchers to speculate that it may have somewhat similar effects throughout the body and the brain [2].
However, this belief is entirely speculative – and drugs that are chemically and molecularly similar can still have dramatically different effects.
Additionally, some early evidence suggests that sunifiram may be up to 1,000 times more potent than piracetam [2] – which, if true, raises additional doubts about just how similar sunifiram might actually be to these other drugs.
Therefore, the precise mechanisms involved in the actions of sunifiram remain unknown. However, some preliminary research suggests that it probably acts on a wide variety of different targets within the body and brain [1].
Some of the possible mechanisms that have been proposed so far include:
- May stimulate the release of acetylcholine: According to a few early animal studies in mice, sunifiram was reported to counteract the effects of scopolamine, a drug that is known to block the release of the neurotransmitter acetylcholine. These findings have led some researchers to suggest that one of sunifiram’s main effects may be to increase the activity of acetylcholine throughout the brain [3, 2].
- May block AMPA receptors: Similarly, another animal study in mice reported that sunifiram counteracted the effects of other experimental drugs that are believed to suppress the activity of AMPA receptors, which play a major role in stimulating synaptic plasticity [4].
- May activate NMDA glutamate receptors: According to two studies in cells and living mice, sunifiram may also promote the release of the excitatory neurotransmitter glutamate. This, in turn, may increase the activity of NMDA receptors, which glutamate binds to in order to stimulate synaptic plasticity [5, 6].
- May affect cellular energy use: The brain relies heavily on glucose to help power its cells, which is delivered to neurons by red blood cells. According to one cell study, sunifiram was reported to counteract the inhibition of glucose transportation across cell membranes caused by another drug called phenobarbital. This may suggest that some of sunifiram’s potential effects could stem from an ability to affect how cells receive and use energy. However, this effect may be complex: for example, the authors of this study reported that sunifiram may increase glucose uptake at lower doses, but actually decreases it at higher doses [7].
However, it is important to note that all of the existing preliminary data about sunifiram’s potential mechanisms comes solely from studies in animals or cell cultures. Therefore, it isn’t yet known whether these same mechanisms might be involved in the actions of sunifiram in healthy human users – and much more research would be needed to verify these early findings.
Potential Uses of Sunifiram
Listed below are some of the potential effects of sunifiram that have been reported by preliminary studies so far.
However, the following potential uses of piracetam are based solely on animal- and cell-based studies, and are therefore “lacking evidence” from any appropriate human trials so far.
In other words, these are only potential “launching-points” for future clinical studies in humans: and no solid conclusions can be made about sunifiram’s effects in humans until much more additional research is done.
Therefore, while some of these early results might seem promising, it is important to keep in mind that the evidence as a whole is still too weak to come to any definitive conclusions about sunifiram’s effects in healthy human users.
LACKING EVIDENCE:
1) May Affect Memory
Although no appropriate studies have been done on human populations, some very preliminary findings from research in animals may suggest that sunifiram could have some potential effects on memory.
For example, in two animal studies on mice, sunifiram was reported to counteract some of the experimentally-induced memory impairments (amnesia) caused by other drugs, including scopolamine, clonidine, baclofen, and mecamylamine [2, 8].
Additionally, another animal study has reported that sunifiram may affect a process called long-term potentiation (LTP), which refers to the strengthening of individual synaptic connections between neurons. LTP is one of the main mechanisms involved in synaptic plasticity, and is believed to play a particularly important role in the ability to acquire, encode, and store new memories [9].
According to this animal study, surgically-induced impairments in memory and reduced long-term potentiation were partially reversed when mice were treated with sunifiram [5].
However, even aside from the fact that these effects have only been reported in animal models, there is also another major limitation to note about these studies: they only observed that memory was “improved” after it had already been impaired by other factors, such as other drugs or surgical interventions. In other words, these studies don’t provide any direct evidence that sunifiram actually affects memory in healthy animals with “normal” or “intact” cognitive abilities.
2) May Affect Learning
Similarly, some other very early research may suggest that sunifiram could potentially have some influence on learning – although once again, these effects have only been reported by animal studies, with no corresponding human trials.
Additionally, some follow-up studies even failed to replicate some of the earlier findings, which potentially raises questions about just how robust these initial reports might be.
According to one animal study, small doses of sunifiram (0.01mg per 1kg of body weight) were reported to slightly increase the rate at which mice learned how to avoid shocks (using a behavioral task called the passive avoidance test) [10].
In one other animal study, a significantly higher dose of sunifiram (0.1mg/kg) was reported to increase the rate at which rats learned to recognize social partners after brief interactions (using a behavioral task called the social learning test) [2].
However, the authors of a different animal study reported that they were unable to detect any effect of sunifiram on the learning ability of rats [8].
Given the conflicting results – as well as the lack of any corresponding research in human users – the purported effects of sunifiram on learning should be taken with a considerable grain of salt until much more scientific data is available.
3) May Affect Pain Sensitivity
Preliminary results from a single animal study may suggest that sunifiram could have some potential effects on pain sensitivity.
In this study, the authors tested the effect of sunifiram on how mice respond to heat-related pain. They tested multiple doses of sunifiram, and reported a mild pain-blocking effect of a “medium” dose of sunifiram (0.01mg/kg). They also tested lower and higher doses, which were reported to have much weaker effects [2].
4) May Affect Wakefulness and/or Sleep
Finally, some preliminary research in animals has reported that sunifiram may have some influence on sleep – and wakefulness-related behaviors.
According to this single animal study in mice, sunifiram was reported to partially counteract the sleep-promoting effects of another drug called pentobarbital. While the mice still experienced drug-induced sleep from the pentobarbital, the sunifiram group of mice reportedly showed a reduction in the overall amount of time they slept. The study’s authors propose that this might indicate a sort of “energizing” effect of sunifiram, although no other follow-up studies have been done to confirm these initial findings [8].
Additionally, this study suffers from a similar limitation as some of the other research already described above – namely, it only reported an effect in response to interference from another drug, which doesn’t necessarily mean it would have similar effects in “normal” or otherwise-healthy animals.
Side-Effects
Like any drug, sunifiram has the potential to cause adverse side-effects.
Some researchers have speculated that because sunifiram appears to be structurally similar to the “racetam” family of drugs on a chemical or molecular level, sunifiram’s overall safety and risk profile may be somewhat similar to these other drugs [1]. However, this speculation is entirely theoretical, and cannot be taken for granted – especially in light of the fact that drugs that are extremely similar on a molecular level can often still have very different effects.
Because this compound has not been studied in human populations, there is no clinical evidence about how safe it is for human users, or how frequently it might lead to negative side-effects [1].
For this reason, we would strongly advise against experimenting with this compound until more data about its safety is available.
If you do personally decide to “experiment” with unknown substances such as sunifiram, make sure you seek appropriate medical care immediately if you think you may be experiencing any noticeable side-effects.
Currently, the only information about sunifiram’s potential side-effects comes either from one or two small animal studies, or from online reports from people who have personally decided to experiment with this drug.
Two animal studies that used particularly large doses of sunifiram in mice noted no outwardly-obvious behavioral signs of side-effects [8, 2]. However, these preliminary findings are not remotely adequate to form any solid scientific conclusions about the potential toxicity or possible side-effects of sunifiram in healthy human users.
Some of the side-effects that users have reported include:
Somewhat unsurprisingly, the frequency of adverse side-effects appear to increase as users increase the size of the doses they take.
Many users have also reported mixing sunifiram with other drugs – particularly stimulants – which makes it even more difficult to form any conclusions about the potential risks or dangers involved in experimenting with this drug.
Drug Interactions
Just as data about sunifiram’s safety in humans is lacking, so too is any hard data about how it might interact with other drugs and substances – so caution is advised.
As always, it is extremely important to keep your doctor informed about any supplements or other substances you are taking in order to further minimize the risk of experiencing any adverse interactions.
Dosage
Note: The information in this section contains information about the dosages commonly used by some of the early animal studies that have been done on sunifiram so far, or the “typical” doses reportedly used by people who are experimenting with personal use of this compound. The information below is not intended as a guide for personal use of phenylpiracetam, as adequate data about its potency, safety, or overall effects in healthy human populations is not currently available.
Due to a lack of any appropriate clinical trials, official dosage information about sunifiram is unavailable.
While sunifiram has been used in a number of preliminary animal studies, the dosages used in this research vary considerably: some animal studies (typically in mice or rats) report using as little as 0.01mg per kg of body weight, while others have used 0.1mg/kg – which is ten times larger – or even more.
The only other available information about sunifiram’s dosage comes from online reports from people who have personally decided to “experiment” with this highly-unknown drug – and this information is obviously not scientifically reliable. With that in mind, these users typically claim to use somewhere between 4-8mg. However, the general effectiveness, overall safety, or potential long-term toxicity from these doses is entirely unknown.
Interestingly, some online users who report taking relatively large doses (10mg or more) – or who have reported using smaller doses of sunifiram every day for extended periods of time – often report developing a tolerance to sunifiram effects. This means that taking it regularly could reduce any effects it might have to begin with, and continued use could potentially lead to having to “escalate” the dose more and more just to experience the same effects.
Limitations and Caveats
Sunifiram has never undergone any clinical trials in humans – nor has it been officially approved for any medical or other use by governing bodies, such as the FDA. Therefore, anyone who personally decides to “experiment” with sunifiram needs to be aware that its long-term effects in humans are essentially entirely unknown [1].
Furthermore, the only scientific data about its effects and mechanisms comes exclusively from studies in either animals or cells. There is no guarantee that these mechanisms and effects would be the same in human users.
