Sunifiram

Sunifiram, originally developed as DM-235 together with unifiram (DM-232) in 2000 at the University of Florence in Italy, is an experimental drug which has antiamnesic effects in animal studies and which is considered up to 10 000 times more potent than piracetam. Its creators, aiming to create a drug that would restore normal conditions in individuals with cognitive dysfunctions due to ageing or neurodegenerative diseases, consciously modified pyrrolidin-2-one nucleus shared by the racetam compounds to allow more efficient brain tissue penetration, and throughout a series of subsequent modulations have discovered that while retaining some racetam-like properties, their newly synthesized substances were positive allosteric modulators of AMPA receptor (ampakines).

In animal studies, it has been shown to antagonize memory impairment induced not only by scopolamine, but also by mecamylamine (nicotinic antagonist), baclofen (GABA agonist), clonidine (alpha-2 agonist), and NBQX (AMPA antagonist), sometimes at the dose as low as 0.001 mg/kg. When administered at 0.1 mg/kg, it had a precognitive effect for social learning in rats. Sunifiram also increased the release of acetylcholine from parietal cortex in freely moving rats, showing some analgesic activity as a consequence of cholinergic potentiation. Furthermore, more recent studies suggest that it is able to improve cognitive deficit and restore hippocampal LTP (long-term potentiation) related to hippocampus-dependent memory impairment, a promising finding give the nature of cognitive deficits observed in long-term depression.

While sunifiram may improve both short-term and long-term memory by modulating the release of neurotransmitters like acetylcholine and glutamate, much of its mechanisms of action remains unknown.

Sunifiram is often viewed as a highly controversial nootropic compound due to its highe potency, lack of human studies and the fact that some people claim to use it “recreationally”, for its mood-enhancing and energy-boosting properties. That said, none of the records from animals studies mention significant side effects, regardless of the dose, profound negative effects were not recorded none of the animal studies. Despite the aforementioned case of recreational use of sunifiram, evidence of its addictive properties can be found neither in scientific literature nor in anecdotal reports.

For many people, sunifiram feels similar to modafinil in that it enhances their focus and mental clarity, makes learning easier, improves their energy levels and self-confidence and has a subtle, positive effect on their mood. Some individuals with depression mention its capability to bring back long-forgotten, positive emotions in a way that feels almost childlike. Many of those who find considerable, consistent benefits with sunifiram use had previously tried numerous nootropics to no avail.

Benefits of taking sunifiram

• enhanced long-term and short term memory;
• improved learning skills;
• boost in energy;
• increased motivation;
• enhanced stamina;
• improved mood;
• anxiety relief;
• focus and attention;
• enhanced visual acuity;
• increased libido.

Side effects

• headaches;
• irritability;
• anxiety;
• insomnia.

Interactions

Anecdotal evidence from sunifiram users suggests that its concomitant use with alcohol, THC or stimulants (including caffeine) might produce unpleasant effects or induce short-lived states of emotional instability.

Contraindications

People with epilepsy or ASD should consult their doctor prior to trying sunifiram as it could potentially exacerbate their symptoms due its glutamatergic action.

Dosage

Due to lack of human studies, caution is advised when handling this compound. It is typically recommended to start with 5 – 10 mg dose per day. Depending on individual response, the dosage can be gradually increased, however, it is suggested not to exceed 25 mg daily.

Sunifiram is often taken orally, with or without food. Some people prefer its sublingual use in order to maximize its absorption, which is reasonable albeit unproven for this particular substance.

As a stimulating compound, it is best not to take it later in the day in order to avoid difficulties falling asleep.