Aniracetam - Educational material

Aniracetam's Many Benefits: "Clearer Mind, Better Memory, Calmer Sleep and Focused Attention". All based on Evidence and Controlled Human Studies

 

Aniracetam is used to improve cognitive function and enhance memory and learning ability. As part of the racetam family, it is distinguished by its pyrrolidone base structure and is derived from the first cognitive enhancer, piracetam [1]. In clinical settings in Japan and Europe, aniracetam has been used to treat conditions such as stroke and Alzheimer's disease. Initially, doctors in Japan prescribed it for eight years mainly to help with emotional problems such as depression and anxiety that can occur after a stroke, rather than to improve memory. However, due to limited human studies on aniracetam, the Japanese market no longer offers aniracetam.

Aniracetam contains an anisoyl group at position 1 on the 2-pyrrolidone ring in its molecular structure [1]. The synthesis of aniracetam involves the acylation of gamma-aminobutyric acid (GABA) with anisoyl chloride, followed by cyclization to form a pyrrolidone structure. This structural arrangement contributes to its dual role as an allosteric modulator of AMPA receptors, increasing synaptic transmission and neuroplasticity, indicating a complex mechanism of action.

In the body, aniracetam is rapidly converted into several metabolites, including 2-pyrrolidone and p-anisic acid in rats, and N-anisoyl-γ-aminobutyric acid (N-anisoylGABA) in humans [1]. Interestingly, the metabolite N-anisoyl-GABA, found in the brain, further contributes to its effects on improving neuronal function. These metabolites, along with the original compound, can be detected in both the brain and cerebrospinal fluid of rats and humans. Therefore, the unique structure allows aniracetam to help improve communication between brain cells, enhancing learning and memory in a way that involves more than just normal brain pathways.

The researchers found that aniracetam works mainly through a cholinergic mechanism, which is one way the nervous system sends messages. In addition, it can modulate AMPA receptors, which are important for fast synaptic transmission in the brain, and glutamate metabotropic receptors, but in different ways. Despite its minimal side effects, aniracetam is significantly reported for its cognitive benefits. Studies have shown its effectiveness in enhancing various aspects of cognitive performance in humans, such as visual recognition, motor performance and general intellectual function. It also helps to improve memory in people with cognitive difficulties and reduce anxiety in animal studies.

Aniracetam for cognitive performance and memory

Based on a controlled human clinical trial, administration of aniracetam significantly attenuated hypoxia-induced damage and improved brain health and mental performance. During the trial, healthy volunteers breathed in air with less oxygen to create a low-oxygen state (hypoxia). They were then given either aniracetam or a placebo pill while in this state, leading to clear signs of difficulty staying alert and a decline in motor coordination and memory. Interestingly, those who took aniracetam showed significant improvements in brain function, performing significantly better in the low-oxygen condition. This indicates the potential of aniracetam to protect cognitive function and mental performance in low-oxygen conditions [2]. In another study, an investigator revealed the cognitive benefits of aniracetam in people with mild to moderate brain pathology. At a daily oral dose of 1,500 mg, aniracetam showed noticeable improvements in cognitive function, as evidenced by a variety of psychometric tests. The results were significantly more noticeable in the patient group than in the placebo group. These results highlight the efficacy of aniracetam in improving cognitive function in elderly patients and those suffering from brain pathology [3].

In addition, a study in elderly people with mild cognitive impairment (MCI) also reported positive effects of aniracetam administration [4]. Aniracetam was found to improve memory performance and reduce levels of inflammatory mediators compared to untreated patients. However, in the same study, aniracetam showed lower efficacy compared to Huannao Yicong capsules against mild cognitive impairment in the elderly. Another study investigated the effect of aniracetam on people with mild cognitive impairment caused by clogged orifices syndrome due to cloudy phlegm. It was revealed that aniracetam significantly improved Mini-Mental State Examination scores and biochemical markers such as Acetylcholine, Superoxide Dysmutase and Malondialdehyde levels before and after treatment. They found that aniracetam was effective in improving symptoms and cognitive abilities in patients with MCI [5]. Similarly, another study investigated the potential of aniracetam (0.2g twice daily) in combination with traditional acupuncture therapy for the treatment of vascular dementia (VD). Results showed that the combination therapy improved cognitive and behavioural abilities, achieving a success rate of 90.3%. The researcher suggested that this integrated therapeutic approach was more effective than using aniracetam alone for VD [6]. In another study, 166 patients with mild cognitive impairment at Dongzhimen Hospital were randomly allocated to two groups: one received Shenwu gelatin capsule, a mixture of Chinese ginseng and chasteberry root, while the other was treated with aniracetam along with placebo capsules, for a three-month period. The treatments, administered three times a day, were assessed using the Mini-Mental State Examination score and the clinical memory scale. The results showed significant memory improvements in both groups, with no statistical difference in efficacy between aniracetam and the Shenwu gelatine capsule, highlighting the potential of aniracetam as a competitive treatment option for MCI [7]. Additionally, a six-month study involving 109 elderly patients with mild to moderate cognitive impairment (probable dementia of the Alzheimer's type) examined the efficacy of aniracetam (Ro 13-5057). The results revealed that the aniracetam group significantly improved psychobehavioural parameters compared to the placebo group. On the contrary, the condition of the placebo group worsened over time. It is noteworthy that aniracetam was exceptionally well tolerated by patients, highlighting its potential as an effective and safe treatment for cognitive impairment in older adults [8]. Furthermore, dementia treatment studies have highlighted the significant role of aniracetam in 276 older people with cognitive deficits. Both as a stand-alone therapy and in combination with cholinesterase inhibitors (ChEIs), it improved cognitive and emotional impairments. Aniracetam appeared to be particularly beneficial compared to cholinesterase inhibitors in improving cognitive and functional outcomes in mild dementia. Furthermore, when aniracetam was used alone compared to its combination with cholinesterase inhibitors, it showed improved cognitive performance and positive effects on mood and function [9]. Further, another study involving 622 people with mild senile forgetfulness (BSF), vascular dementia and Alzheimer's disease investigated the therapeutic potential of aniracetam. Administered three times a day for 1-2 months, aniracetam significantly increased cognitive function in these conditions. It significantly improved the memory quotient in BSF patients, with an efficacy of 75.36%, and showed significant improvements in central nervous system function, as seen in reduced reaction times. For those with vascular dementia, aniracetam achieved an 83% response rate, significantly higher than the 60% in the control group. Patients with Alzheimer's disease also saw visible improvements, with an efficacy of 68%, highlighting aniracetam's potential to double the response rate compared to controls. Importantly, the treatment was well tolerated, with no significant side effects, confirming the safety and efficacy of aniracetam in the treatment of cognitive and memory impairment in older adults [10]. In addition, to prevent the progression from mild cognitive impairment with amnesia (aMCI) to Alzheimer's disease (AD), a study comparing the traditional formulation Di-Huang-Yi-Zhi (DHYZ) with aniracetam was conducted. In this study, aniracetam was used as a standard to directly compare its efficacy with the traditional DHYZ blend. After treatment, the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognitive Component (ADAS-Cog), Barthel Index for Activities of Daily Living (ADL) and Traditional Chinese Medicine (TCM) symptoms, showed significant improvements in both groups. Together with the positive results of the DHYZ mixture, aniracetam showed beneficial effects and was well tolerated, highlighting its safety and utility in the treatment of cognitive impairment [11].

Aniracetam for insomnia

Interestingly, a study of nine elderly patients suffering from insomnia who were treated with a combination therapy with Zopiclone, a sleep-inducing drug, and aniracetam. The results were significant, with 78% participants, or seven out of nine patients, showing noticeable improvements, confirmed by over 50% increases in sleep duration. This study highlights a potential synergistic mechanism of action between aniracetam and Zopiclone in improving sleep quality among older people with insomnia [12]. Additionally, during an animal study, aniracetam significantly improved sleep patterns in some stroke-prone rats. These rats typically have problems with their sleep cycles, experiencing too little REM sleep (dream sleep phase) during the day and too much nREM sleep (deep sleep phase) at night. However, when given aniracetam at a dose of 30 mg/kg per day for five days, these rats saw a noticeable increase in REM sleep when it is light outside, suggesting that aniracetam may help humans with similar sleep problems often seen in vascular dementia [19].

 

Beneficial effects in animal studies

During an extensive rodent study, results revealed a significant role for aniracetam in improving cognitive function. Administered orally at doses ranging from 10-100 mg/kg, aniracetam provided a wide range of cognitive benefits, effectively overcoming learning difficulties and alleviating both mild and severe scopolamine-induced memory impairment. It provided protection against post-shock memory loss and prevented problems with recall or retention of information immediately after learning. Moreover, aniracetam was able to reverse memory problems and promote learning of tasks requiring active engagement [13]. Although the exact mechanisms of action of aniracetam are still under investigation, favourable results suggest that it works by modulating the release of neurotransmitters, chemicals that help with brain signalling, and by improving the brain's ability to make and maintain connections, particularly in situations that challenge brain function, including cognitive function [13]. Furthermore, aniracetam actively modulates neurotransmitters in the brain, which is particularly evident in stroke-prone rats, highlighting its ability to improve thinking and decision-making functions without affecting the areas responsible for emotional processing. It significantly raised extracellular glutamate levels in the prefrontal cortex, essential for executive function, without altering the amygdala. This targeted effect on glutamate activity in cognitive areas suggests that aniracetam may effectively counteract neuronal disorders associated with neurocognitive impairment [14]. Further studies have revealed aniracetam's ability to repair disruptions in the natural activity patterns of older rats, highlighting its potential to correct their daily rhythms of activity and rest. It appears to achieve this by affecting brain signalling pathways associated with acetylcholine and dopamine, important brain chemicals. This suggests that aniracetam may modulate neurotransmitter release to improve daily rhythm-related behaviour in older adults [15].

 

In addition, aniracetam showed noticeable benefits in studies on older rats and those affected by conditions that impair brain function. It helped older rats regain their sense of routine around meals, a behaviour that declines with age. This suggests that aniracetam may help maintain daily routines in humans facing similar age-related challenges. At doses around 100 mg/kg, it not only improves behaviour without side effects on appetite or movement; it appears to modulate the brain's cholinergic systems, responsible for memory and learning, to help keep the internal biological clock running [16]. Moreover, aniracetam has been tested for its effects on attention deficits caused by imbalances in the brain's serotonin system, important for regulating mood, sleep and cognition. Even when certain drugs induced attention problems in rats, aniracetam, together with its metabolites, helped reverse these issues, suggesting its potential for treating attention-related disorders in humans [17].

Does Aniracetam really work for social anxiety?

Although there are no human studies in this area, an animal study showed the potential of aniracetam to alleviate social anxiety. In rats with anxiety resulting from social interactions to fear-inducing environments, aniracetam at doses ranging from 10 to 100 mg/kg increased social behaviour and showed efficacy in reducing anxiety in both the elevated cross maze model and the fear-conditioned stress model. These results indicate the potential of aniracetam to manage anxiety through interactions with multiple types of brain receptors, including those associated with acetylcholine, dopamine and serotonin. This broad spectrum of activity suggests the use of aniracetam to treat a variety of anxiety-related conditions and improve social behaviour without causing significant side effects [21]. Furthermore, aniracetam has shown potential in reversing learning and memory problems in a rat model of Fetal Alcohol Spectrum Disorder (FASD), a condition that has no specific therapies. When administered to affected rats, aniracetam significantly improved cognitive performance and reduced anxiety, highlighting its role in enhancing the function of brain receptors affected by prenatal alcohol exposure [18].

 

Aniracetam for depression

The ability of aniracetam to reduce feelings of depression, particularly in older rats, was investigated in an animal model. While typical antidepressants reduced inactivity in both young and old rats, aniracetam (at doses ranging from 10 to 100 mg/kg) specifically reduced inactivity in older rats at the highest dose tested. This improvement was associated with aniracetam metabolites and suggests that its antidepressant effects may be due to an increase in the activity of dopamine, a neurotransmitter involved in mood regulation, by stimulating nicotinic acetylcholine receptors [20].

 

Aniracetam for neurogenic bladder dysfunction

Another animal study showed that aniracetam, at doses of 100 and 300 mg/kg, significantly increased bladder capacity in rats with cerebrovascular damage, but not in unaffected rats. This effect was also observed with direct injections of aniracetam into the brain, indicating that its effect on bladder capacity is related to its ability to activate cholinergic neurons in the brain, particularly through the muscarinic acetylcholine receptor pathway. This suggests that aniracetam may be an effective treatment for the bladder hyperresponsiveness seen in patients with cerebrovascular disease, offering a new approach to managing the symptoms of such conditions [23].

 

Aniracetam for memory and attention impairment

In other experiments, aniracetam administered to rats, particularly at a dose of 50 mg/kg, showed significant improvements in learning and memory. This included improved performance in active avoidance tasks and alleviation of scopolamine-induced memory deficits, with no effect on the rats' locomotion. Importantly, biochemical analysis indicated a role for aniracetam in increasing the activity of enzymes associated with neurotransmitter responses in the prefrontal cortex and hippocampus of the brain, areas involved in cognition. In addition, aniracetam was found to affect the production of inositol phosphate and increase calcium levels within nerve endings in the hippocampus, suggesting that its effects include modulation of intracellular signalling pathways important for cognitive function [22]. Aniracetam also counteracted the decline in cognitive performance observed in older rats after periods of unrestricted feeding, which tended to lead to a decrease in correct responses and an increase in omissions and reaction times during the choice response task. Administration of aniracetam improved their accuracy and reactivity, indicating its potential to restore motivation and ability to perform tasks by improving attention and alertness without affecting body weight [24]. Additionally, in a one-year study, aniracetam significantly counteracted scopolamine-induced memory loss in rats. At a dose of 50 mg/kg, aniracetam improved memory behaviour, demonstrating its potential as a memory-enhancing drug [26].

Aniracetam for stroke and brain injury

In a study on rats with induced stroke, aniracetam and another compound were tested for their effects on recovery. When administered at various intervals after stroke, aniracetam significantly protected brain tissue, improved motor skills and reduced the area of brain damage. Importantly, combining aniracetam with another therapeutic option further reduced inflammation and increased protective markers in the brain. These results suggest the potential of aniracetam in combination with other options for post-stroke recovery by modulating specific brain receptors [25]. In another study on the role of aniracetam in cognitive recovery after brain injury, it was found to be effective in improving cognitive performance when administered shortly after injury. Even when treatment was started 11 days after injury, aniracetam led to results comparable to those of intact rats in cognitive tests. This suggests the potential of aniracetam as a therapeutic option for chronic cognitive impairment after brain injury [27]. Similarly, aniracetam has shown efficacy in improving cognitive performance after brain injury. When administered at doses of 25 to 50 mg/kg after injury, aniracetam was found to significantly improve performance in cognitive tasks such as the Morris water maze. Therapeutic effects were seen even when treatment was delayed for up to 11 days after injury, highlighting the drug's ability to promote recovery through continuous treatment [30].

 

Aniracetam for Fetal Alcohol Spectrum Disorders (FASD)

Aniracetam has been investigated as a possible method to help with learning and memory problems caused by exposure to alcohol before birth, a condition known as Fetal Alcohol Spectrum Disorder (FASD). This problem is partly caused by changes in the way certain signals work in the brain (AMPAR-mediated synaptic transmission), especially in the part of the brain important for learning and memory. In a study on rats given alcohol before birth, the administration of aniracetam significantly improved communication between brain cells. This improvement was observed at a dose of 50 mg/kg administered from day 18 to 27 after birth. Aniracetam also made positive changes at a very detailed level in how brain cells send signals, showing that it can help repair learning and memory problems caused by pre-birth alcohol exposure by targeting and adjusting the way specific brain cell receptors work [31].

 

Aniracetam for Alzheimer's disease

Furthermore, in a model of Alzheimer's disease, aniracetam's effects at the cellular level were observed in studies involving older mice and young mice exposed to amyloid-beta protein. Aniracetam treatment improved cell membrane fluidity and corrected abnormal intracellular calcium ([Ca(2+)]i) levels in the prefrontal cortex and hippocampus. These results suggest that aniracetam may reverse deleterious cellular changes by restoring cell membrane fluidity and regulating calcium levels important for cell signalling and function [28]. In addition, studies on aniracetam's effects on learning have highlighted its ability to activate protein kinase C (PKC) in the brain, particularly the γ PKC isoform (γ-PKC). It significantly improved learning performance in mouse models known for poor contextual learning. When administered at a dose of 100 mg/kg, aniracetam not only improved learning ability, but also significantly increased hippocampal γ-PKC activity shortly after training, indicating a key mechanism by which aniracetam may facilitate learning and memory [29]. Furthermore, aniracetam was tested for its ability to mitigate satiety-induced performance decline in cognitive tasks in aged rats. Initially stable with food restriction, the rats' task engagement decreased significantly after they were allowed to eat freely, resulting in fewer correct responses and delayed reaction times. Aniracetam, administered orally at 30 mg/kg for 14 days, improved accuracy and speed of response, suggesting that it may renew motivation probably impaired by satiety by increasing attention and vigilance [32].

Aniracetam dosage

The dosage of aniracetam varies depending on the condition being treated. The following doses have been found to produce beneficial results in various scientific studies.

- Aniracetam was administered intravenously at doses of 10 mg and 100 mg under hypoxia to study its effects on brain function and mental performance [2].

- A daily oral dose of 1,500 mg aniracetam has been reported showing significant improvements in cognitive function in older patients with mild to moderate brain pathology [3].

- Patients with Mild Senile Cognitive Impairment received aniracetam at a dose of 0.2 g three times daily, reduced to 0.1 g for those over 70 years of age, as part of a three-month treatment period [5].

- Aniracetam tablets were administered orally at a dose of 0.2 g twice daily to patients with vascular dementia as part of a study comparing them with acupuncture therapies [6].

In view of the above doses used in human studies, it is suggested to take aniracetam orally in daily amounts of 1000 to 1500 mg. Even doses as small as 400 mg have shown some efficacy, and it is typical to divide the total daily dose of 1,000 to 1,500 mg into two doses of 500 to 750 mg, taken twice daily with meals. Due to the very bitter taste, people who prefer to avoid this experience may find capsules a more suitable option for taking aniracetam [34].

 

Summary

Aniracetam is considered a powerful nootropic compound capable of improving cognitive function and mental performance under a variety of conditions, including hypoxia. It is beneficial for people with age-related cognitive impairment, dementia and Alzheimer's disease. Clinical studies have shown its efficacy in improving brain function in healthy volunteers exposed to low-oxygen environments and in patients with mild to moderate brain pathology. In addition, studies indicate aniracetam's potential to address depression, anxiety and sleep disorders, further highlighting its broad therapeutic applications. Despite ongoing research into its exact mechanism of action, aniracetam's ability to modulate neurotransmitter activity and increase synaptic plasticity suggests its key role in improving cognitive function. In addition, studies have shown its efficacy in conditions such as mild senile cognitive impairment and vascular dementia, with improvements in cognitive function and biochemical markers. Its use in combination with traditional therapies such as acupuncture for vascular dementia has also been studied, indicating better results with integrative approaches. Animal studies further support aniracetam's ability to improve learning and memory, modulate neurotransmitter valence and address specific behavioural and physiological dysfunctions, including neurogenic bladder dysfunction and recovery from stroke or brain injury. Together, these findings point to aniracetam's potential as an effective nootropic, with significant benefits for cognitive health and mental performance, with its safety profile and regulatory status varying by region. However, further human studies are needed to fully explore its use in cognitive and mental health therapies.

Disclaimer

This article is written to educate and raise awareness of the substance discussed. It is important to note that the substance discussed is a substance and not a specific product. The information contained in the text is based on available scientific studies and is not intended as medical advice or to promote self-medication. The reader is advised to consult a qualified health professional for all health and treatment decisions.

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