What is Sunifiram?
Sunifiram is a nootropic drug that was derived from Piracetam in 2000 with the hope of benefitting Alzheimer’s patients. Even though no country has approved its use as either a drug or supplement, neurohackers use it for nootropic purposes.
Sunifiram is structurally similar to Piracetam with actions much like those of Nefiracetam, however it’s not a racetam thanks to an alteration in chemical structure (the breaking of the pyrrolidone backbone). It is much more powerful than Piracetam; it may be 1,000 times as potent as this common nootropic. (3)
Neurohackers report benefits in concentration, learning, motivation, energy, memory, and depression relief. It is stimulating, so you will want to avoid taking it too late in the day.
This powerful boost in mood and energy from Sunifiram is largely thanks to how it works as a member of the AMPAkine family.
As there have been no human studies with this compound, animal research and user reviews are the best way to evaluate nootropic efficacy.
How Does it Work?
Sunifiram works through three main mechanisms:
- Increases glutamate levels in the brain
- Boosts acetylcholine release
- Impacts delivery of glucose to the brain
Glutamate is a neurotransmitter involved in synaptic plasticity and memory formation. It plays a critical role in communication between neurons, particularly in the hippocampus, where memory formation and long term-term potentiation occur. Low levels of glutamate have been tied to difficulties with attention, memory, and learning.
Once this drug crosses into the brain, it binds to AMPA and NMDA receptors – this leads to increased levels of glutamate. The powerful cognitive benefits of this nootropic are thought to be largely thanks to this ability to stimulate glutamate receptor activity.
This action also leads to mild stimulatory effects without the jitters and negative side effects that accompany traditional stimulants, such as caffeine.
Sunifiram is similar in mechanism of action to members of the racetam family when it comes to its effects on acetylcholine levels in the brain. Acetylcholine (ACh) is the primary neurotransmitter involved in concentration, learning, and memory.
This compound enhances ACh release, although the exact way in which it does so is unknown. This boost in ACh helps to benefit learning, memory, and focus.
Glucose is the main source of fuel, or energy, for your brain. Research suggests that low doses of Sunifiram increase glucose uptake in the brain, while high doses decrease glucose uptake in the brain. This study demonstrates that this drug may either increase or decrease cellular metabolism depending on dose. (6)
Potential Brain Benefits
Anecdotal reports suggest that Sunifiram can help make focusing easier, extending attention span for difficult mental tasks. These effects may be thanks to the increases in ACh and glutamate in the brain.
Improves Memory and Learning
Studies have found benefits of Sunifiram for working memory, short-term memory, and memory recall. It encourages long-term potentiation, leading to better memory storage and recall later on.
Animal studies have found the following effects:
- In mice, this drug was found to increase how quickly they learned to avoid shocks. (5)
- In rats, it was found to enhance their social learning skills, shortening the time it took to recognize other rats. (3)
- Induced amnesia in mice was ameliorated with Sunifiram. (4)
- Mice with surgically damaged memory and long-term potentiation experienced symptom reversal. (1)
One animal study supports the energizing effects of this nootropic. (4) Mice who were given a sleep-inducing drug slept less when also taking Sunifiram.
This effect may be partly thanks to its impact on glucose and cellular metabolism. An effective dose of Sunifiram for increased cellular metabolism is a lower dose; if too high of a dose is used, users may experience less mental energy rather than more. (6)
Increased glutamate levels have also been found to lead to increased energy levels and help fight off fatigue, which can help to clear brain fog. Users report feelings of motivation and clarity, which can be extremely helpful when studying or completing a tedious task.
Research on mice found that Sunifiram exhibits analgesic properties. (3) When mice were exposed to heat, supplementation led to a delayed response, suggesting reduced feelings of pain.
Anxiety, Depression, and Mood
Many neurohackers report improvements in mood when taking this compound, ranging from overall mood improvement to reduction in anxiety and depression symptoms.
There are no studies to confirm or deny these effects. One mouse model of depression found no impact, however this model examined depression associated with reduction of ERK activation, which Sunifiram does not impact. (1) There are numerous other models of depression that could potentially lead to different results.
This nootropic is very potent, so small doses can yield impressive results.
Typical dosage ranges from 3-10 mg/day early in the day. The more you take, the more stimulatory effects you will experience. Do not exceed 10 mg/day – studies suggest that certain beneficial mechanisms may reverse at higher doses. (6)
The exact half-life in humans is unknown, with estimates ranging from 45 minutes to two hours. With this short half-life, you may choose to split your dosage into 2-3 equal doses throughout the day. Do not take this nootropic late in the day or you may experience insomnia.
Users report noticing the effects roughly one hour post ingestion, with faster and more noticable effects following sublingual application, which is thought to boost absorption. Because of this, powder may be preferable to capsules. The powder does cause a slight tingling sensation.
Users who take large doses and supplement every day report building a tolerance. To avoid tolerance, you may choose to cycle Sunifiram, with a common schedule of supplementing during the week and taking the weekend off. Another common cycle is 2-3 weeks on, 1 week off.
When taken within recommended dosages, this drug appears to be well-tolerated. Keep in mind that it has not undergone human clinical trials, nor has it been on the market for very long.
Side effects that have been reported include:
- Difficulties sleeping
- Interactions with other nootropics
As its chemical structure is very similar to racetam drugs, the safety profile may be similar. These drugs are considered safe at recommended doses and have a low toxicology profile.
This nootropic stacks well with Noopept and choline. It is best to avoid stacking with stimulants as many users report negative experiences.
Sunifiram and Noopept Stack
One of the most common Sunifiram stacks is with Noopept. Combined, many users report impressive benefits for memory, focus, energy, and mood. For many, these effects reduce if used together for extended periods of time. You may be able to extend these benefits by cycling Sunifiram.
Recommended Dosage (split into 2-3 doses, early in the day):
- 5-10 mg Noopept
- 3-6 mg Sunifiram
Sunifiram and Choline Stack
Because this drug leads to an increase in ACh release, it is recommended to stack with a source of choline. When choline stores are low, this can lead to headaches, dizziness, and other side effects. Sufficient choline will also enhance the nootropic benefits.
Alpha GPC and Citicoline (CDP Choline) are two highly bioavailable sources of choline that are able to cross over the blood-brain barrier.
- 3-8 mg/day Sunifiram, split into 2-3 doses early in the day
- 300-600 mg Alpha GPC, split into 2 doses
Sunifiram vs Noopept: What is the Difference?
Both Sunifiram and Noopept are very potent nootropics. When neurohackers are looking for a smart drug to quickly enhance memory, focus, energy, and learning, these are two of the most effective.
Many users report similar effects, however there are some important differences.
Benefits of Noopept over Sunifiram:
- It does not appear to build a tolerance
- Studies have demonstrated neuroprotective effects
Benefits of Sunifiram over Noopept:
- Appears to have less intense side effects
- Kicks in slightly faster
- Produces a less edgy energy
So which is a better nootropic? There is no one-size-fits all answer to this question. With similar benefits, preference is very user-specific.
Sunifiram vs Unifiram
These two compounds are structurally similar ampakine nootropics. (2,7,8) Their effects on memory, learning, and concentration appear to be very similar.
These two compounds were both created in 2000. Sunifiram has been widely used in the nootropic community since 2013; Unifiram is newer and less popular. While they exhibit similar effects and work through the same mechanisms, Sunifiram is much less expensive than Unifiram.
This supplement is highly regarded according to user reviews. Experiences tend to be positive with very few side effects.
“From my experience sunifiram was insanely creative. Ideas jump out of my head. I also felt the need to draw while under the influence of it. Headaches after some time.” Reddit user review
Another Reddit user took this supplement for four months. In the first month they reported increased memory encoding, improved short-term memory, 5 hours of stimulation after dosing, improvements in concentration, and enhanced primitive experiences, including sex, taste, and sound. This user did report negative interactions with coffee, L-Theanine, and Phenylpiracetam.
Where to Buy Sunifiram
You will not find this supplement in local drug stores or through a doctor’s prescription. If you want to buy Sunifiram, you will need to turn to trusted online nootropic retailers.
It comes in both powder and capsule forms. Pure Nootropics and Nootropics Depot carry good quality, competitively priced nootropics. You can even find Liftmode Sunifiram through Amazon.
- Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice https://www.ncbi.nlm.nih.gov/pubmed/23295391
- Design, synthesis and nootropic activity of new analogues of sunifiram and sapunifiram, two potent cognition-enhancers https://www.ncbi.nlm.nih.gov/pubmed/19786353
- Molecular simplification of 1,4….gives piperazine derivatives that maintain high nootropic activity. https://www.ncbi.nlm.nih.gov/pubmed/11087574
- DM235 (sunifiram) a novel nootropic with potential as a cognitive enhancer https://www.ncbi.nlm.nih.gov/pubmed/12070754
- Design, synthesis and preliminary pharmacological evaluation of new analogues of unifiram and sunifiram as cognition modulators https://www.ncbi.nlm.nih.gov/pubmed/18954993
- Piracetam and TRH analogues antagonise inhibition by barbiturates… https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574967/
- Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings https://www.tandfonline.com/doi/full/10.3109/14756366.2015.1021252
- Pharmacological characterization of DM232 (Unifiram) and DM235 (Sunifiram), new potent cognition enhancers https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3458.2006.00039.x