Nootropics

Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote relaxation, particularly boosting mood, executive functions, attention, memory, creativity, or motivation in healthy individuals.

The use of cognition-enhancing supplements by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for non-medical uses. Nonetheless, the international sales of cognitive- or mood-enhancing supplements have continued to grow over time and in 2012 reached 0.69 billion. With sales supported by global health trends, the market is expected to reach US$33.85 billion by the year 2030, at a CAGR of 14.8%.

While most nootropics are not regulated, there are other nootropics like theanine, which the Food and Drug Administration (FDA) considers to be generally recognized as safe (GRAS) and allows its sale as a dietary supplement.

They are often found in supplement form as nutraceuticals, or in recent years, as functional food or drinks. Recently, some companies even began using nootropics in beer as an alcohol replacement.

History and definition

The term ''nootropic'' is derived . It was first introduced by Corneliu Giurgea in 1972 to describe a new classification of molecules that acted selectively towards the brain's higher-level integrative activity. In order for a product to qualify as a true nootropic, it must fulfill Giurgea's five criteria for the category.

# It should aid with improvement in working memory and learning.
# Supports brain function under hypoxic conditions or after electroconvulsive therapy.
# Protection of the brain from physical or chemical toxicity.
# Natural cognitive functions are enhanced.
# It requires to be non-toxic to humans, without depression or stimulation of the brain.

Marketing claims

Nootropics are often advertised with unproven claims of effectiveness at improving cognition. The FDA and FTC warned manufacturers and consumers in 2019 about possible advertising fraud and marketing scams concerning nootropic supplement products. The FDA and FTC stated that some nootropic products had not been approved as a drug effective for any medical purpose, were not proven to be safe, and were illegally marketed in the United States under violation of the Federal Food, Drug, and Cosmetic Act.

Having said that, there are some nootropics like Theanine, that the Food and Drug Administration (FDA) considered generally recognized as safe (GRAS) and allows its sale as a dietary supplement.

In 2018 in the United States, some nootropic supplements were identified as having misleading ingredients and illegal marketing. In 2019, the US Food and Drug Administration (FDA) and Federal Trade Commission (FTC) warned manufacturers and consumers about possible advertising fraud and marketing scams concerning nootropic supplements.

Over the years 2010 to 2019, the FDA warned numerous supplement manufacturers about the illegal status of their products as unapproved drugs with no proven safety or efficacy at the doses recommended, together with misleading marketing.

Availability and prevalence

In 2008, the most commonly used class of drug was stimulants, such as caffeine. Manufacturers' marketing claims for dietary supplements are usually not formally tested and verified by independent entities.

In 2016, the American Medical Association adopted a policy to discourage prescriptions of nootropics for healthy people, on the basis that the cognitive effects appear to be highly variable among individuals, are dose-dependent, and limited or modest at best.

Use by students

The use of prescription stimulants is especially prevalent among students. Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. Based upon studies of self-reported illicit stimulant use, of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.

Side effects

The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effect. Long-term safety evidence is typically unavailable for nootropics. Racetams, piracetam and other compounds that are structurally related to piracetam, have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.

In the United States, dietary supplements may be marketed if the manufacturer can show that the supplement is generally recognized as safe, and if the manufacturer does not make any claims about using the supplement to treat or prevent any disease or condition; supplements that contain drugs or advertise health claims are illegal under US law.

Types

Central nervous system stimulants

Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found that these drugs enhance cognition in healthy people. In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D₁, adrenoceptor A₂, or both types of receptor in the prefrontal cortex. Relatively high doses of stimulants cause cognitive deficits.

* Amphetamine systematic reviews and meta-analyses report that low-dose amphetamine improves cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people and in individuals with ADHD. A 2014 systematic review noted that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information in non-ADHD youth. It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.
* Methylphenidate a benzylpiperidine