Cognitive performance enhancement -
A total of chemically different substances were uniquely identified by NPSfinder ®. Only one CE was uniquely identified by the EMCDDA; no CE was uniquely identified by the UNODC. Conclusions: These results show that NPSfinder ® is helpful as part of an Early Warning System, which could update clinicians with the growing numbers and types of nootropics in the increasingly difficult-to-follow internet world.
Both non-pharmacological and pharmacological enhancers are sought by the general public in order to improve performance during studying and at work by increasing concentration, motivation and accuracy, via physical, behavioral and biochemical activities 2.
These phenomena commonly occur with aging 7 — 9. It was found that some CEs also improve cognitive functions in healthy subjects, such as memory, executive functions, creativity, and motivation Their use has become more and more prevalent among college, high school, and university students as well as in the military 11 — The world of CEs is multifaceted and complex, with different molecules acting with different modes of actions and on different and often multiple receptors in the central nervous system CNS.
Food-based antioxidants, herbal, and other food-derived nootropic agents have become increasingly popular in recent times after there have been suggestions of associations between cognition and diet Prescription drugs, such as modafinil, amphetamine, and methylphenidate are used off-label by healthy people who do not have specific deficits but want to improve their standards of intellectual and cognitive performance Cognitive enhancers also include many drugs which have never reached the market as they have been discontinued in Phase II or III clinical trials 7 — 9.
The many dimensions of cognitive enhancement are described and disentangled in a recent review 2. Dresler and colleagues 2 pointed out how cognitive enhancement is not a monolithic phenomenon and how there are a great variety of interventions that can be classified and clustered into biochemical, physical, and behavioural enhancement strategies.
While the benefits of medications, such as MPH or modafinil, in patients suffering from specific diagnosed conditions such as ADHD or narcolepsy have been studied and evaluated, the potential benefits of these substances in heathy individuals remain unclear.
The use of CEs in healthy individuals poses significant concerns due to the lack of clinical evidence regarding their safety, effectiveness, and social consequences, especially with long-term use.
Urban and Gao 24 emphasized that these newly misused drugs, i. In these cases, glutamate modulation may impair behavior flexibility, which may facilitate addictive behaviors.
Urban et al. Like many other NPS, nootropics have become increasingly easily available on the internet over the last 20 years.
According to the United Nations Office on Drugs and Crime UNODC Early Warning Advisory EWA on new psychoactive substances NPS , NPS have been reported from over countries and territories from all regions of the world 29 — The European Database on New Drugs EDND of the EMCDDA records the notifications of new substances and the detection of NPS in Europe Although many of these identified NPS might be used by healthy people as CEs, there are limited data on how many or which substance is, nor are CEs classified as a specific category.
Despite being a challenging task in view of the pharmacological differences of CEs, producing a formal classification of these substances is crucial in order to further develop scientific research on the topic as well as regulate and monitor their use and effects.
Scientific data regarding NPS used or misused as CEs are lacking. Recent research papers mostly focus on the misuse of specific and well-known CEs such as methylphenidate analogs 36 , 37 , designer benzodiazepines, phenmetrazine, modafinil, novel synthetic opioids 37 , and MPH More literature is available on CEs which are potentially able to address cognitive deficits in specific patient groups.
Froestl and Maitre 39 have classified these molecules into 19 categories based on their pharmacodynamics. Some of these molecules could not be classified based on their pharmacodynamics and hence were classified based on their chemical structure or their origin i.
as natural products or endogenous molecules Many of these drugs were clinically tested for their potential to improve cognitive function.
Although they all might have a potential for being misused by the general public looking to enhance their cognitive abilities, the vast majority of these molecules have never reached the market as most of them have been discontinued in Phase II or III clinical trials 7 — 9.
A comprehensive literature review completed by Froestl et al. Many CEs were described as groups or families i. beta-amyloid aggregation inhibitors. These CEs were not identified by either the EDND, EWA, or NPSfinder ® as this is not part of the remit of any of the NPS early identification systems.
In particular, many categories of CEs described by Froestl et al. Apart from the known families of CEs historically derivatives of MPH, modafinil, and racetams , psychonauts subjects who experience intentionally drug-induced altered states of consciousness 40 have been experimenting with a variety of commonly prescribed drugs as well as illicit substances, often finding subjective evidence of cognitive enhancement and sharing their knowledge within the dark web sites and surface internet fora.
At present, a comprehensive, up-to-date list of currently available CEs does not exist. Finally, some of these substances are not illegal i. prescribed medication, food supplements, natural remedies etc. For these reasons, it is difficult to create an early identification system which is able to keep professionals up-to-date with the CEs which are currently available to the general public via the online market.
At present, NPSfinder ® is a password protected proprietary software, which allows registered researchers only to screen and classify the substances that are identified by the software.
An open access part, which will allow the general public to have free access to the substances, is under development. Every time a new website is identified, all its items are scanned and compared with the online existing ones.
When a novel substance is found, this is added to the growing NPSfinder ® database. NPSfinder ® screening process is tailored to each website, and no specific keywords are used by the software. This list is continuously growing the current, full list of these sites is available upon request. NPSfinder ® has been already successfully used to identify other types of NPS, including synthetic cathinones 41 , novel psychedelics 42 , and novel opioids In each paper, the comparison with international or European NPS databases has shown that NPSfinder ® is able to identify substances which were not previously described by the existent early detection systems.
Raising awareness of novel substances has important implications from both a legislative and a clinical perspective. Although the language most typically used in these websites was English, further languages analyzed by NPSfinder ® included: Dutch, French, German, Italian, Russian, Spanish, Swedish, and Turkish.
FN, DA, CZ, and LG. In this way, a full assessment and editing of each NPSfinder ® data item were conducted, and the range of unique CEs presented here was identified.
The collection of further information was completed by consulting a range of open libraries and chemistry databases referring to the index item, if existing. Data were then screened for relevance and possible duplications.
Therefore, it is to be noted that these identified CEs are thought by psychonauts as having cognitive enhancing properties according to their subjective and anecdotical experience rather than due to any pharmacological analysis. When a substance that was identified by NPSfinder ® was not explicitly described as able to enhance cognitive abilities but was listed as a known CE within the comprehensive review by Froestl et al.
Using chemical structure identification and other published information i. published research papers and official databases , researchers assigned each molecule to its drug class, using the classification described by Schifano et al.
After about 18 months of operation, the number of substances identified by the web crawler activities was 5, By the time of writing January , 4, unique NPS substances were included in the database, and 1, out of 5, A total of unique CEs was identified by NPSfinder ® Table A1.
Of these, 35 were explicitly described as having nootropic properties by psychonauts; the remaining molecules were classified as CEs as also present in the comprehensive review on CEs written by Froestl et al.
Table 1 CEs identified by NPSfinder ® using Schifano et al. Current NPSfinder ® results were compared with the EMCDDA and the UNODC databases in order to ascertain which molecules were also detected and listed by the official European and United Nation early identification systems.
Only one CE was uniquely identified by the EDND MIQ, also called meta-IQ ; no CE was uniquely identified by the EWA database. Figure 1 shows the number of CEs identified by each source including NPSfinder ® , EDND and EWA database as well as the ones identified by more than one source.
A full list of the CEs is available upon request. In this paper, we aimed to evaluate whether the innovative crawling software NPSfinder ® can be employed as a helpful tool in the early identification and prediction of CEs.
To the best of our knowledge, this is an unprecedented list of drugs which are described as CEs and, therefore, with a potential for recreational misuse by healthy individuals. NPSfinder ® identified 35 molecules out of the total of 4, that were described by psychonauts as having cognitive enhancing effects, such as improved memory, alertness, attention, and concentration.
A further molecules were previously described as CE 7 — 9 , although psychonauts did not explicitly describe them as CE. Since psychonauts experiment with novel substances in order to intentionally experience altered states of consciousness, it is to be expected that their interest also extends to the world of CEs.
Among the CEs that they have been discussing online, there are mostly molecules that are known to have nootropic properties, are not illegal, and are likely to be easily available on the market such as racetam compounds, modafinil and its derivatives, methylphenidate and its derivatives and food supplements.
Our results showed that NPSfinder ® could be employed as an Early Warning System tool to help clinicians with keeping their knowledge up-to-date with the growing numbers and types of nootropics in the increasingly difficult-to-follow online market.
It is not surprising that the included sources i. NPSfinder ® , EDND, and EWA have identified mis-matching numbers and types of CEs, as they differ in their methodology and purposes of CE identification.
In fact, the EDND was created in order to allow the European Union to rapidly detect, assess, and respond to health and social threats caused by NPS The UNODC EWA on NPS provides access to basic information on new psychoactive substances, including trend data, chemical details on individual substances, supporting documentation on laboratory analysis and legislative responses Specifically, the EDND and EWA focus on illegal drugs and do not look at websites that contain patented medications, while NPSfinder ® looks at websites whose contributors might have accessed sources containing patent medications.
The large number of molecules that are both identified by NPSfinder ® and described by Froestl et al. Among the CEs that have been subjectively identified by psychonauts as able to improve certain aspects of their cognition, there are molecules whose objective cognitive enhancing properties have not been established by research studies, such as the selective serotonin re-uptake inhibitors SSRIs , melatonin and many others.
The large number of unique molecules that were uniquely identified by NPSfinder ® can be explained with the innovative methodology that NPSfinder ® used for the early identification of all NPS, including CEs 41 — Flavonoids such as quercetin and naringin, as well as vitamins A, B, and D are also part of this group.
Perry and Howes 51 completed an informative review on medicinal plants in dementia, pointing out the potential cognitive benefits of a significant variety of plants and herbs.
A recent systematic review has found that tyrosine and caffeine could enhance cognitive performance when healthy young adults are sleep-deprived in a military context The non-medical use of methylphenidate as a CE, which involves an attempt to improve memory, increase mental concentration, control anxiety, and stimulate motivation and creativity, is rising worldwide 38 , Research studies have often failed to demonstrate that SSRIs can have cognitive enhancing properties 54 , It was also suggested that any cognitive benefits of SSRIs were likely to be secondary to their effect on mood or behavioral disturbances.
Interestingly, both fluoxetine and methylphenidate potentiate gene regulation in the striatum, and their combination seems to mimic cocaine effects, with related increased risk for substance use disorder It is possible that many prescribed drugs are currently being misused by the general public but not picked up by the regulatory bodies because the vast majority of them are not classified as illegal.
It is important that more studies and cross-sectional surveys are conducted as well as that the current pharmacovigilance systems focus on determining current patterns and quantifying current usage of these drugs by healthy people. Racetam compounds, which are classically one of the major CE family 58 , are identified by NPSfinder ® and listed within the IPEDs sub-group Table 4.
Piracetam enhances cognitive function without causing sedation or stimulation 3. This drug is also being used in clinical practice for the treatment of several diseases 59 — 62 although its mechanism of action remains not fully understood. NPSfinder ® identified aniracetam, coluracetam, fasoracetam, nefiracetam, oxiracetam, phenylpiracetam, piracetam, and pramiracetam.
For example, recent studies failed in showing that aniracetam improves working memory in pigeons 63 , learning and memory in rats 64 , or cognitive and affective behavior in mice Moreover, nefiracetam did not prove to be more efficacious than placebo in ameliorating apathy in stroke 66 despite some positive pre-clinical results 67 , There are no available studies on coluracetam, fasoracetam , and phenylpiracetam.
Among the psychostimulant CEs are described many derivatives of methylphenidate and modafinil Table 5. These have been listed in this group when not licensed as prescribed drugs.
Methylphenidate is a prescription drug with medical restrictions in several countries, therefore, many illegal analogues have emerged on the internet and darknet drug markets during the last few years The derivatives of methylphenidate that have been identified by NPSfinder ® include: 3,4-dichloromethylphenidate, 4-fluoromethylphenidate, 4-methylmethylphenidate, dexmethylphenidate, ethylphenidate, methylmorphenate , and methylnaphthidate.
No research studies are available regarding the misuse of these molecules by healthy subjects in order to ameliorate their cognitive function Table 6. The phenethylamines-related compounds that have been identified by NPSfinder ® are listed in Table 7. These are stimulant, entactogenic, and hallucinogenic substances that share similar chemical structures with amphetamine, catecholamines, synthetic cathinones, and other molecules Phenethylamines are known to enhance mood and empathy in healthy subjects.
Substituted phenethylamines also include substituted amphetamines, which have been used as CEs to promote learning and memory but can ultimately lead to addiction Dolder et al. To the best of our knowledge, there are no research studies or case reports focusing on the misuse of specific phenethylamines as CEs by healthy subjects.
GABAergic drugs are chemicals that produce their effects via interactions with the GABA system, such as by stimulating or blocking neurotransmission f-phenibut , which is closely related to phenibut , is a central nervous system depressant 72 ; tolibut is a GABA analog that was developed in Russia 77 , similarly to picamilon , which is formed by a synthetic combination of niacin and γ -aminobutyric acid GABA.
Picamilon was developed in the Soviet Union in 78 and further studied in both Russia 79 and Japan 80 as a prodrug of GABA. Among Cannabimimetic drugs there are the synthetic cannabimimetics that are designer drugs that target the same receptors to which cannabinoids in cannabis plants, tetrahydrocannabinol THC and cannabidiol CBD bind 81 , dexanabinol , drinabant , Dronabinol , JZL , rimonabant , and URB were the six CEs belonging to this group that were identified by the NPSfinder ® Table 9.
The use of cannabimimetics as CEs seems counter-intuitive as both pre-clinical and human studies have found a link between consumption of cannabinoids and long-term deficits of cognitive functions, especially high-order cognitive functions 83 — However, recent pre-clinical studies have found that deltaTHC can improve cognitive performances in rats 89 and mice This is a tryptamine derivative closely related to both the serotonin and melatonin neurotransmitters To the best of our knowledge, there are no studies, surveys, or case reports that identified 5-MT as a drug used by healthy people in order to improve their cognitive abilities.
Jansen et al. Fipexide also known as attentil and vigilor Table 11 is the only substitute piperazine that has been identified by NPSfinder ® as a CE. This was initially developed in Italy in 94 and used as a CE in Italy and France for the treatment of dementia Fipexide is no longer in use due to the occurrence of rare side-effects 96 , Ethical issues raised by cognitive enhancement have been debated for over a decade 98 , and many experts have identified multiple ethical concerns including risks to mental and health safety On the other hand, it is of concern that the safety and efficacy of these drugs in healthy individuals in the long-term are still unclear.
While some CEs have been studied and research data on their mechanism of action and potential benefit are available, the action, the beneficial effects, and the potential side-effects of the majority of them have yet to be fully described and understood.
Some of these drugs can cause dependence and have a significant range of harmful effects; they can be particularly dangerous to young people as their brains are not fully developed.
Studies producing null results and some evidence of task-specific impairments should be also noted The limited evidence of effectiveness as well as the potential side-effects should be cautiously considered by relevant legislative and regulatory bodies.
In , the US Presidential Commission for the Study of Bioethical Issues released a report on CE, reporting up-to-date findings and providing recommendations for clinicians The Australian Alcohol and Drug Foundation has recently raised doubts about the actual cognitive benefits of most CEs, indicating that scientific studies showed only little to no benefits for cognitive enhancement in healthy individuals, while the associated side-effects do pose significant risks to health and safety of the general public NPSfinder ® could also be an important tool for analytical toxicologists to focus their efforts on the detection of the most recently misused substances , An official, up-to-date, comprehensive list of CEs is not currently available in the literature.
The Early Warning Systems fail in the early detection of these substances as they are mostly legal products such as food supplements or prescribed medication, which are misused by healthy individuals to improve their cognitive abilities. We based our classification on the one described by Schifano et al.
We noted that another type of classification, such as the one described by Froestl et al. In fact, many CEs do not have a fully understood mechanism of action, which makes it difficult to link them to a specific category; other CEs have multiple mechanisms of actions i.
Furthermore, it is important to note that a limited number of languages were used for the screening of molecules on the web, and although many substances were first identified in seizures in Asia, only European languages are used. For all these reasons, forming a comprehensive and definite classification of CEs remains a complex challenge.
CEs are a wide and diverse group of molecules, constantly growing in terms of numbers as well as availability among the general public and especially via online platforms.
CEs differ for pharmacological activity, time, and mode of action, targeted cognitive domain, pharmacodynamic and pharmacokinetic properties, as well as possible short- and long-term side-effects. The popularity of chemicals that are potentially able to augment brain functions is not surprising in a society which constantly demands for increasingly high cognitive performances.
For the current official Early Warning Systems, it is challenging to identify and monitor the use of CEs as they are often sold as legal food supplements or as prescribed medication for a number of medical conditions. For this reason, NPSfinder ® can be considered as a helpful systematic tool which could update clinicians with the growing numbers and types of nootropics in the increasingly difficult-to-follow internet world.
Previously, Arillotta and colleagues 43 have identified novel opioids which were not listed in either international or European NPS databases, such as EMCDDA or UNODC. This information is useful to stakeholders such as enforcement agents, emergency department, scientific community, prevention program setters, and other regulatory agencies.
The same applies to CEs; in particular, the early identification of substances that are misused as CEs and the discovery of novel CEs that were never reported or identified before are crucial to raise the awareness of regulatory bodies.
The identification of a drug is key to the treatment of its potential physical and psychiatric effects; if the drug is novel, its description may shed some light on its pharmacokinetics and toxicodynamics, which would in turn inform treatment decision-making in clinical settings. The early identification and better understanding of the distribution and effects of CEs could promote both more effective prevention and harm reduction measures in clinical settings, including emergency departments, mental health and general practice clinics.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. FS and AV have conceived the idea of the manuscript and have coordinated the whole project.
FN, CZ, DA, and LG have actually carried out the process of both data collection and systematization. FN performed the literature searching, the analysis of data and drafted the manuscript.
FS, JC, and AG supervised the manuscript and contributed to the final version of the manuscript. FS approved the final content of the manuscript. JC provided data from the EMCDDA and UNODC databases for the purposes of this research. FS, JC, and AG have provided relevant epidemiological data and have contributed as well to the drafting and checking of the paper itself.
None of the authors of this paper was directly involved with the website development. AV has conceived the idea of a new early detention software for NPS, which was developed by the professionals at Damicom srl, a small enterprise from Rome Italy.
FS and AV have coordinated the testing of the web crawler. FN, CZ, and DA have suggested minor changes to the software which have made the screening process more precise and efficient. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The reviewer, SC, declared a shared affiliation, though no collaboration, with several of the authors, FN, FS, JMC, AG, DA, CZ, and AV to the handling editor.
The authors are grateful to Damicom srl, a small enterprise from Rome Italy , whose professionals have developed the NPSfinder ® web crawler and so generously have allowed here the testing of its potential. The authors are also grateful to the EMCDDA and UNODC for being able to use their databases for the purposes of this research.
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Increased levels of norepinephrine and dopamine may be responsible for enhanced concentration and learning observed in the hours immediately after exercise. Increased levels of serotonin, endorphins and anandamide may be responsible for enhanced mood and reduce anxiety observed after exercise.
Many students and professionals have learned to position exercise before periods of cognitive demand to optimize their performance and may sprinkle additional brief walks or calisthenics throughout their day to maintain performance.
Many studies have documented the impact of aerobic exercise on brain health and performance. A growing line of evidence suggests that strength training has benefits for mental health and cognitive function as well that may be somewhat unique, and perhaps complimentary, to the effects of aerobic exercise.
There may be additional social and cognitive benefits from team sports and group activities or participating in an event such as a race. Implementing lifestyle changes can help to develop many aspects of our cognition.
Engaging in consistent and diverse stimulation is a powerful tool in developing our brain function. As our brains continue to mature during our lifetime, these techniques may help to positively enhance our performance:. Cognitively stimulating leisure activities, such as word games, puzzles, gardening or writing calligraphy, can produce similar results to cognitive training programs and have a significant effect on the delay and reduction of cognitive decline.
If we keep our furry friends engaged, and introduce new stimuli continuously, their knowledge can flourish. By implementing lifestyle changes that expose ourselves to a variety of cognitively stimulating activities and ideas as well as regular physical activity, our neural network will respond with new connections and increased function.
Neuroenhancement or cognitive enhancement Cognitive performance enhancement the experimental use of enhanxement Cognitive performance enhancement non-pharmacological methods intended to improve cognitive and affective pdrformance in Cognirive people who pergormance not have a mental Cognitive performance enhancement. Pharmacological Nutritious antioxidant vegetables agents may Glutathione supplements compounds thought to be nootropicsHunger suppression strategies as modafinil[1] [3] caffeine[4] [5] and other drugs used for treating people with neurological disorders. Non-pharmacological measures of cognitive enhancement may Covnitive behavioral methods activities, techniques, and changes[7] non-invasive brain Cogntiivewhich has been used with the intent to improve cognitive and affective functions, [8] and brain-machine interfaces. There are many supposed performancce, most having only small effect sizes in healthy individuals. The most common pharmacological agents in neuroenhancement include modafinil and methylphenidate Ritalin. Stimulants in general and various dementia treatments [10] or other neurological therapies [11] may affect cognition.Video
Alpha Waves Activate 100% of Your Brain After 10 Minutes, Improve Memory \u0026 Intelligence - 528HZ - Metrics details. Cognitive complaints in the absence performmance objective Cognitive performance enhancement impairment, observed performannce patients with subjective cognitive Cognitive performance enhancement Plant-powered pick-me-upare common in old age. Performajce first step to Cognitive performance enhancement cognitive decline is to use techniques known to improve cognition, i. We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training CMPTnon-invasive brain stimulations NIBSdrugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence. CMPT have clinically relevant effects on cognitive and non-cognitive outcomes.
Ich meine, dass Sie den Fehler zulassen. Geben Sie wir werden es besprechen. Schreiben Sie mir in PM, wir werden umgehen.
ist absolut einverstanden
Darin ist etwas auch mich ich denke, dass es die ausgezeichnete Idee ist.
Ja kann nicht sein!