Pramiracetam: How Does it Work in the Brain?

Pramiracetam (N-[2-[di(propan-2-yl) amino] ethyl]-2-(2-oxopyrrolidin-1-yl) acetamide, CI-879, Pramistar, Neupramir, Remen) is a fat-soluble nootropic in the racetam-class of compounds.

Pramiracetam was first synthesized by scientists at Parke-Davis in the late 1970’s. It was first tested with Alzheimer’s patients. Seeing mixed results, the company tried it with major depressive disorder. And licensed Pramiracetam as an orphan drug to Menarini who continued research on using it for dementia.

In 1991, the company licensed Pramiracetam to Cambridge Neuroscience Inc. (CNI).[i] The nootropic was then tested for restoring cognitive function after stroke or traumatic brain injury.

Researchers found that Pramiracetam was up to 30-times more potent than the original Piracetam. In Europe this nootropic is prescribed for the treatment of dyslexia, ADHD, dementia and other memory problems. Brand names for prescription Pramiracetam include Pramistar, Neupramir and Remen.

Pramiracetam has gained a reputation in the nootropics community for optimizing cognition. It’s a favorite with students and executives for boosting cognition, focus, memory, and recall.

Pramiracetam helps:

• High Affinity Choline Uptake (HACU): Pramiracetam has been shown to significantly increase HACU in the hippocampus. This action boosts acetylcholine (ACh) use which accounts at least in part for Pramiracetam ability to enhance cognition and memory.[ii]
• Neurotransmitters: Pramiracetam has a profound effect on the synthesis of the neurotransmitter acetylcholine (ACh).[iii] ACh is critical for encoding new memories, concentration, cognition and neuroplasticity.
• Cerebral Blood Flow: Pramiracetam increases nitric oxide (NO) activity in your brain.[iv] NO acts as a vascular dilator which means it relaxes blood vessels allowing for the freer flow of blood. Increased blood flow delivers more oxygen and nutrients to brain cells promoting better learning and memory.

Pramiracetam was developed by Parke-Davis in the late 1970’s from Piracetam by substituting the amide group with a dipropan-2-ylaminoethyl group. Parke-Davis was once America’s largest and oldest drug maker. It has since been acquired by Pfizer as part of their acquisition of Warner-Lambert in 2000.

Parke-Davis has an interesting history and were pioneers in many areas including drugs that affect cognition. Even conducting some research with peyote in the early 1900’s.[v]

Pramiracetam shares a unique quality with Coluracetam in the racetam-class of nootropics. Its primary method of action is boosting high affinity choline uptake (HACU) in the hippocampus. It helps increase acetylcholine synthesis and function which helps overall cognition, improved memory and recall, learning, and focus.

Pramiracetam has been shown in the lab to not directly influence GABA, dopamine, norepinephrine, or serotonin in the brain.[vi] So don’t look to Pramiracetam to correct mood and anxiety issues.

Pramiracetam does increase nitric oxide activity in your brain. Helping to increase cerebral circulation which improves the efficiency of brain cells needed for motor function, learning and visual function.



How does Pramiracetam work in the Brain?

• Pramiracetam boosts brain health and function in several ways. But two in particular stand out.
• Pramiracetam improves memory. Several animal and human studies show that Pramiracetam has a significant impact on memory.

In this animal study researchers administered Pramiracetam to rats in a one-trial test. This is significant because it proves that Pramiracetam works right out of the gate. It doesn’t take multiple doses, or a couple of weeks to build up in your system. It works on the first day you use it.

The scientists found that rats had a significant improvement in retention by using Pramiracetam. And the effect lasted for 24 hours.[vii]

Pramiracetam increases high-affinity choline uptake (HACU). Studies have shown that Pramiracetam boosts HACU in the hippocampus. The increase in acetylcholine (ACh) makes more of this neurotransmitter available to neurons for cognitive processing. Increasing attention, mental clarity, memory and verbal skills.[viii]

High affinity choline uptake (HACU) is the uptake of choline in synapses needed for acetylcholine (ACh) synthesis. This is a critical link in the chain of events needed for your brain to make ACh.[ix] Studies with Pramiracetam and other racetam nootropics like Coluracetam show that boosting HACU increases memory. And even restores memory function in parts of the brain that have been damaged.[x]

How things go bad

As we get older, our brain chemistry and metabolism changes. And it seems these changes are affecting younger and younger people.

• ? Recall, reaction time and learning capacity declines
• ? Acetylcholine receptors decline
• ? Acetylcholine levels decline
• ? Cerebral blood flow declines
• ? Nitric Oxide levels decline

All of these changes are contributing factors to age-related cognitive decline. Early signs of these effects can be seen in poor decision-making, difficulty learning, and even recalling simple things like an important appointment.

But even if you’re not concerned with the signs of aging, Pramiracetam can help.

Pramiracetam benefits

• Pramiracetam helps boost acetylcholine (ACh) synthesis and use in your brain, and increases cerebral circulation.
• As a nootropic, Pramiracetam easily crosses the blood-brain barrier.[xi] And since it is fat-soluble, it must be taken with a healthy fat such as unrefined coconut oil or MCT Oil to ensure absorption.
• Pramiracetam increases the amount and efficiency of acetylcholine by influencing the high affinity choline uptake (HACU) system in your brain. This increase in ACh can have a profound effect on overall cognition and memory.
• With Pramiracetam, you’ll find it easier to focus and learning ability will improve. This increase in ACh in your hippocampus helps with logic and understanding complex mathematical and technical subjects if that’s your thing.
• Increased neuroplasticity from more acetylcholine and improved cerebral circulation affects long-term potentiation.[xii] So you may find it easier to recall long-forgotten memories.

How does Pramiracetam feel?

• Many neurohackers report that taking Pramiracetam quickly gets your brain firing on all cylinders. There is an intense increase in focus and possibly even a boost in confidence.
• But once you get accustomed to this laser-like focus, the novelty wears off and you become used to being able to focus at will.
• Pramiracetam is reported to be great for intense, long study sessions. Or when you face logical, attention-based tasks where you need sharp focus. Like when you’re doing a presentation before the Board, or a group of VC’s.
• This nootropic makes burning through tedious, arduous tasks that require a level of sustained focus easier, and that would otherwise seem difficult.
• Others report improved recall ability, fluidity of thought, and ease of verbal communication and numerical calculations.

Pramiracetam Clinical Research

Pramiracetam Normalizes Brain Waves

Researchers working with old Fisher-344 rats found that the aged rats had a consistently different EEG profile from young rats. They found slow brain waves were present in both the frontal cerebral cortex and hippocampus. Theta brain wave activity was missing altogether but was dominant in the brains of young rats.

Theta brain waves are associated with creativity, integrative experiences and relief from trauma. Theta waves are commonly experienced by meditators. An “ah-ha moment” is a burst of Theta waves in your brain.

This research team found that Pramiracetam normalized brain wave activity in the old rats. And even more interesting was that its older sibling Piracetam did not produce this effect on brain waves. And that tolerance to Piracetam was a problem.

While it hasn’t been proven in the lab, this study shows that Pramiracetam would be of benefit to the older generation looking to improve cognitive function.[xiii]

Pramiracetam Improves Memory

• Researchers in Italy investigated Pramiracetam effects on memory, and memory training by a therapist. Types of memory measured were objective memory and metamemory performance.
• Metamemory is both the inner-knowledge of one’s own memories combined with the processes for formulating new memories with no inner-knowledge.
• 35 healthy volunteers were chosen with an average age of 64.8 years. 10 subjects received memory training only, 8 received Pramiracetam, 10 received both memory training and Pramiracetam, and the control group received nothing.
• Results of the study showed that those receiving both memory training and Pramiracetam experienced a significant improvement in memory. Followed by the Pramiracetam group. The memory training-only group and control group scored the lowest.
• The research team concluded that Pramiracetam significantly improves memory. And the addition of memory training to Pramiracetam has an even more profound effect of both types of memory measured.[xiv]

Pramiracetam Enhances Cognition

• This double-blind placebo-controlled study worked with young males who suffered cognition problems due to brain injuries. The men had problems with memory and recall.
• One group received 400 mg of Pramiracetam daily for 18 months. And the other group a placebo. Memory was measured during the trial and for 1-month after Pramiracetam was discontinued.
• The researchers found that Pramiracetam produced a significant improvement in cognition, memory and recall.[xv]

Pramiracetam Dosage

• Recommended Pramiracetam dosage is 250 – 400 mg up to 3-times per day. One Pramiracetam dose in the morning, and one in the early afternoon, and if you’re doing a 3rd dose do it later in the afternoon.
• Pramiracetam is fat-soluble so for best results take it with a quality fat like a tablespoon of extra virgin, cold-pressed unrefined coconut oil, MCT oil or olive oil. If you don’t take Pramiracetam with supplemental fat, don’t expect much of an improvement in cognition.
• You should use Pramiracetam with a choline supplement like Alpha GPC or CDP-Choline. It helps boost neural acetylcholine, so demands the presence of more choline in your brain.
  
• You can safely boost daily intake of Pramiracetam to 1500 mg if needed. But most find that lower doses are more effective.
  

Pramiracetam Side Effects

• Pramiracetam is non-toxic. So is considered well-tolerated and safe.
• As with many of the racetams, Pramiracetam can cause headaches because it boosts the use of acetylcholine in your brain. Choline supplements like Alpha GPC or CDP-Choline can help you avoid this side effect.
• Many neurohackers also find that stacking Pramiracetam with a choline supplement boosts the effect with improved memory and cognition. And this is supported in several research studies.
• Some users report that Pramiracetam blunts their emotions. Decisions when it comes life and work issues are logic-based rather than emotional. This can be good or bad depending on the situation of course. You could call it “emotional objectivity”.