What Are Cognitive Enhancement Drugs?
The most popular CE drugs belong to two groups: soft enhancers and PCE. Soft enhancers are popular, legally available substances which include food products, herbals substances and tonics, and products containing caffeine. Conversely, PCE use is often prohibited and includes synthetic pharmaceutical substances and some illegal drugs (Maier, Ferris, & Winstock, 2018). Both CE groups differ in the magnitude of their effect on cognitive performance and in mechanism of action, although variations also exist within each group. Differences between the various CE categories and individual substances are discussed below.
Soft Enhancement
Some soft enhancers are commonplace in society, particularly those products containing caffeine, which is the most widely consumed psychoactive substance in the world (Zhang, Jiang, Liu, & He, 2017). Caffeinated beverages are among the most popular caffeine-based products because they act as a minor stimulant and promote feelings of alertness and wakefulness, which often become integrated into a personâs daily routine. Consequently, it has been suggested that use of caffeine for CE is less explicit than other soft enhancers or PCE (Rosen & Weil, 2004). For example, nutraceuticals (such as ginseng, Ginkgo biloba and bacopa monnieri) are more explicitly marketed as CE drugs but are significantly less popular, owing to the fact that these drugs each have medicinal properties that are reported to act differently on cognitive performance and mood, each with varying degrees of success (Rai, Bhatia, Sen, & Palit, 2003; Tsai, Lin, Simon Pickard, Tsai, & Mahady, 2012). Moreover, these substances are often available only at speciality retailers, which suggests that they are purchased with a specific intention in mind. Of course, nutraceutical drugs are not just marketed as CE substances; they are also lauded for their various physical health benefits (Ward et al., 2019), meaning the reasons for their consumption are not always clear.
Caffeine, a psychostimulant, acts on the autonomic nervous system and shifts dominance from the sympathetic nervous system (SNS) to the parasympathetic nervous system (PNS). Unlike PCE, its effects are non-selective as it acts through blocking adenosine receptors (A1 and A2) in the prefrontal cortex, which in turn promotes monoamine release. As such, the neurotransmitters dopamine, serotonin and noradrenaline are released, which increase feelings of wakefulness and alertness (Fredholm, Yang, & Wang, 2017). Therefore, caffeine shares more similarities with pharmaceuticals used for PCE than nutraceuticals which operate through enzyme synthesis (Ahmed et al., 2016), although effects are less pronounced and the substance has a shorter half-life than PCE (Franke et al., 2017). Notable soft enhancers which contain caffeine include coffee, energy drinks, caffeine pills and guarana (Maier, Liakoni, Schildmann, Schaub, & Liechti, 2015).
Pharmacological Cognitive Enhancement
Distinct from soft enhancers, PCEs are typically synthetic pharmaceutical substances and sometimes illegal drugs, whose use is controlled or prohibited by law. Most studies on PCE effects focus on amphetamines, in particular dextroamphetamine (d-amphetamine), which is sold under the trade name âAdderallâ, and racetams like piracetam. However, evidence in support of these drugs as effective PCE is limited, with the studies that exist demonstrating only modest enhancements with single periods of use. Reports suggest that the effectiveness of these drugs often does not meet or exceed user expectations (Bagot & Kaminer, 2014; Battleday & Brem, 2016; Linssen, Sambeth, Vuurman, & Riedel, 2014). Research has also looked at use of illegal drugs as PCE in the UK such as psychedelics (Elsey, 2017) and cannabis (Franke, Roser, Lieb, Vollmann, & Schildmann, 2016), but as use of these substances as CE appears to be rare they will not be discussed further. Instead, the focus will be on substances which are most commonly self-reported by users for PCE, namely d-amphetamine, methylphenidate (MPH) and modafinil.
Amphetamine is a central nervous system (CNS) stimulant which is used to treat attention deficit hyperactivity disorder (ADHD). D-amphetamine in particular has been found to modulate neurotransmitter networks, predominantly dopamine, serotonin and noradrenaline (Darracq, Blanc, Glowinski, & Tassin, 1998). Alterations to monoamine neurotransmission are linked to feelings of increased wakefulness and alertness in humans, which has also made the substance useful for the treatment of narcolepsy syndrome in the past (Parkes & Fenton, 1973). Furthermore, in adolescents with ADHD, studies show improved learning outcomes during schooling, owing to a long half-life, which extends the overall effect of the drug throughout the school day (Pelham et al., 1999). Moreover, dopaminergic drugs like Adderall are shown to positively impact mood, which evidence suggests can increase creative thought processes (Farah, Haimm, Sankoorikal, Smith, & Chatterjee, 2009). Benefits to cognition in healthy people do not appear to be as extensive as with other PCE, although findings are comparatively limited (Bagot & Kaminer, 2014; Ilieva, Boland, & Farah, 2013). However, users regularly self-report pleasurable experiences with the drug which may contribute to the perception of enhanced cognition (Vargo & PetrĂłczi, 2016; Vrecko, 2013).
Similar to Adderall, MPH is prescribed for ADHD and sometimes narcolepsy. Furthermore, the pharmacology of both substances is similar, as MPH also modulates noradrenaline and dopamine in the prefrontal cortex which is linked to a reduction of symptoms associated with ADHD, as well as selective improvements in cognitive functioning (Linssen et al., 2014). In particular, MPH has been shown to benefit cognition in adolescent and adult ADHD sufferers, who exhibit improved reaction time, attention and executive and non-executive memory (Coghill et al., 2014; Storebø et al., 2015). Emerging evidence has also suggested that MPH can improve working memory deficits found in stimulant users, although more research must be conducted in the area to confirm these findings (Moeller et al., 2014). With healthy people, studies using MPH to improve cognitive functioning show less compelling results, though it can be beneficial to certain cognitive functions, including processing speed, inhibitory control, working memory and memory consolidation (Linssen et al., 2014). While ADHD sufferers gain the most benefits from MPH, self-administration by healthy adults has risen, possibly to achieve CE, although reasons behind use have not been fully explored...