Potential and Mechanisms of Sunifiram
Sunifiram is an experimental drug currently marketed as a brain enhancer. Those that sell and use the drug claim it improves mental focus, decreases depression, and even increases your sex drive, but is there any truth behind the hype? Read on for a rundown of the science behind 3 possible uses of sunifiram that are supported by evidence.
Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What is Sunifiram?
Sunifiram, or DM-235, is an experimental drug designed to improve cognitive function in Alzheimer’s disease [R].
Research on sunifiram was discontinued due to a lack of funding and the patent lapsed. Therefore, it was never tested on humans, and long-term toxicity is unknown. In addition, sunifiram hasn’t been approved for use in any country and is currently only being sold as a smart drug (nootropic) [R].
Sunifiram is similar in structure and function to piracetam. Piracetam-like drugs make the nervous system more sensitive to stimulation while having low toxicity and no serious side effects. However, sunifiram is about 1,000 times more potent than piracetam, making it effective at much lower doses [R].
Mechanism of Action
The full mechanism of sunifiram remains unknown. However, research indicates that like other drugs in the racetam class, it probably works on multiple targets within the body [R].
The drug scopolamine blocks the neurotransmitter acetylcholine, which transmits signals between cells in parts of the brain that deal with memory and learning. In mouse studies, sunifiram increased acetylcholine release in the brain [R, R].
Blocking AMPA receptors induced amnesia in mice. Sunifiram reversed the amnesia, indicating it activates AMPA receptors [R].
Sunifiram also stimulates the glutamate receptor, NMDA. It increases the rate at which glutamate (a neurotransmitter) is delivered between brain nerve cells. This can help restore memory function in damaged or surgically altered brains [R, R].
The brain uses glucose delivered by red blood cells for energy. The drug pentobarbital inhibits glucose movement across cell membranes. In low doses, sunifiram reversed this effect. However, at higher doses, it prevented glucose from existing red blood cells. Sunifiram increases glucose uptake in the brain at low doses and decreases uptake at higher doses [R].
Potential Uses of Sunifiram
1) May Improve Memory
Sunifiram supplementation (0.01 mg/1 kg) increased the rate at which mice learned to avoid shocks (passive-avoidance test). Also, at a higher sunifiram dose (0.1 mg/kg), rats recognized partners more quickly (social learning test) [R, R].
However, another study found that sunifiram had no effect on the learning ability of rats [R].
2) May Improve Learning
Long-term potentiation, which is when specific synapses are strengthened after frequent stimulation, is the underlying mechanism of learning [R].
When sunifiram was given to mice with surgically impaired memory and long-term potentiation, it restored both factors [R].
3) May Decrease Pain Sensitivity
Sunifiram supplementation delayed mice’s response to heat, indicating that sunifiram has pain relieving properties. The strongest pain-relieving effect was observed at middle doses (0.01 mg/kg), with higher and lower doses having less of an effect [R].
4) May Increase Energy
Mice were given a drug (pentobarbital) that induced sleep. Sunifiram supplementation reduced the amount of time they slept, suggesting it may have energizing effects. However, there are no other studies that address sunifiram’s potential energizing effects [R].
Sunifiram was never tested on humans, so long-term toxicity is unknown. However, it is structurally most similar to piracetam-like drugs, which generally show very low toxicity [R].
Users have reported a range of side effects, including:
Reports of unpleasant side effects appear to increase when users take large doses (10 mg or more) or mix sunifiram with stimulants.
Drug Interactions and Stacks
Sunifiram can be used in stacks, meaning that it can be combined with other supplements and drugs for greater cognitive benefits that can be achieved with sunifiram alone. It can be stacked with:
Stacking sunifiram with noopept has resulted in mixed reviews. Some report excellent focus, motivation, and improved mood while others have reported a drastic reduction in positive effects with continued use.
Users have also reported unpleasant and long-lasting side effects when mixing sunifiram with caffeine, modafinil, and other stimulants.
Based on effective doses found in animal studies and user experience, 4-8 mg is generally cited as a safe and effective dose.
Limitations and Caveats
Sunifiram has never undergone any clinical trials or been approved for human use. People have been using it without any verifiable reports of serious injury. However, users should be aware that its long-term effects are unknown [R].
There’s a lot of variability in the experiences of users, ranging from zero effect to laser-like focus or even uncomfortable levels of energy. Given this variability, sunifiram may or may not give you the desired effects.
Users taking larger doses (10 mg or more) or using sunifiram every day for extended periods of time report developing a tolerance, which reduces the effectiveness.
There is a lot of variability in the experiences reported by users of sunifiram. Some people experience no effects at all, while others report dramatic changes in cognitive function. Some additional effects reported by users include:
- Improved focus
- Reduced need for sleep
- Enhanced enjoyment of music
- Upbeat Mood
- Food tasting better
- Mental clarity
- ‘Sharp’ visuals
Although some users have reported that sunifiram alleviated their depression, mouse studies found that it didn’t have any antidepressant effects [R].
Other users claim that sunifiram increases sex drive and intensifies sexual experiences; however, this has never been studied in humans or animals.
Users have compared it to noopept, but with a quicker onset.