Author Topic: Paper, Jun/21: Neuroenhancement: State of the Art and Future Perspectives  (Read 294 times)


"Neuroenhancement: State of the Art and Future Perspectives"


Pharmacological neuroenhancement refers to the non-medical use of prescription drugs, alcohol, illegal drugs, or the so-called soft enhancers for the purpose of improving cognition, mood, pro-social behavior, or work and academic performance. This phenomenon is undoubtedly more frequent than previously supposed especially amongst university students. The aim of the present paper was to carefully review and comment on the available literature on neuroenhancement, according to Prisma guidelines. The results showed a great use of all prescribed drugs (benzodiazepines, antidepressants, antipsychotics, nootropic compounds, and especially stimulants) as neuroenhancers amongst healthy subjects, although probably the real prevalence is underestimated. The use of illicit drugs and soft enhancers is similarly quite common. Data on the improvement of cognition by other compounds, such as oxytocin and pheromones, or non-pharmacological techniques, specifically deep brain stimulation and transcranial magnetic stimulation, are still limited. In any case, if it is true that human beings are embedded by the desire to overcome the limits of their intrinsic nature, neuroenhancement practices put into question the concept of authenticity. Therefore, the problem appears quite complex and requires to be deepened and analyzed with no prejudice, although within an ethical conceptual frame.

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Benzodiazepines are used as emotional enhancers thanks to their relaxant and anxiolytic activity. This class of drugs became extremely popular in the 1970s, since they represented a real advancement, as compared with barbiturates, given their relatively safety in overdose. In particular, diazepam (Valium) led to a so-called “Valium-mania”, as it was increasingly used not only for anxiety disorders, but also to deal with everyday life problems, so that it became the most prescribed drug of any types of the seventies (Calcaterra & Barrow, 2014). However, although their benefits remain unequivocal if correctly used, the popularity of BDZs slightly decreased after the mounting evidence of their adverse side effects, including severe seizures and withdrawal symptoms after abrupt discontinuation, or attention deficits, memory impairments, sleepiness and abuse/addiction in the longterm use (Panes et al., 2020; Pieters & Snelders, 2009).

In any case, different data indicate that BDZs are still quite used for their sedating properties for the purpose of neuroenhancement, as it is believed that a quieter and better sleep can improve cognitive performances, especially amongst students, as they are convinced that a relaxed brain is more efficient (Mache et al., 2012; Maier et al., 2013).

Antidepressants are a class of drugs indicated not only for depression, but also for several other psychiatric conditions, including anxiety disorders, obsessive-compulsive (OCD) spectrum disorders, eating disorders, premenstrual syndrome, or pain syndromes, and several other (Cascade et al., 2007; Hofmeister & Bodden, 2016; Kennedy et al., 2016; Pratt et al., 2017). Not surprisingly they are also abused by an increasing number of healthy individuals (Normann & Berger, 2008).

Fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI), was marketed in 1984 and, after a few years, it became known a sort of “miracle drug”, since it was thought as able to reduce negative feelings, induce a general state of psychic well-being and improve social performance even in non-depressed individuals. In 1994 Prozac was the second most-sold drug worldwide (“Prozac-mania”) (Elliott, 2000). According to the American psychiatrist Peter Kramer, Prozac was more than an AD, it was rather a drug that could help people to find their real self and, in other words and ultimately, authenticity (Kramer, 1993). However, Kramer himself underlined that the drug should be used only when necessary, that is to say in depressed patients, so that the ensuing mood increase was with no doubt useful in those individuals who could experience a real change in their life, as they were not suffering any more.

The evidence for the use of ADs in healthy control subjects is limited, even because this phenomenon is mainly hidden. Some studies indicate that ADs may influence emotional processing in healthy individuals by increasing recognition and recall of positive emotions and reducing salience of negative affects (Harmer et al., 2003a; Harmer et al., 2004). Indeed, ADs were found to attenuate the activity of subcortical limbic neural regions during exposition to negative emotional stimuli (Bigos et al., 2008; Del-Ben et al., 2005; Harmer et al., 2006; McKie et al., 2005; Takahashi et al., 2005). A study evaluated participants’ ability to correctly detect subtle expressions of sadness and the results showed that duloxetine (SNRI) might reduce accurate recognition of sadness (Bamford et al., 2015). In another study, volunteers who received a single dose (10 mg i.v) of citalopram (another SSRI) recognized more facial expressions of happiness and fear than those who had taken placebo, while no differences were observed in the recognition of other basic emotions (Harmer et al., 2003b). Subsequently, a 7-day double-blind trial carried out in healthy volunteers (n=42) treated with citalopram (20 mg/day), reboxetine (a norepinephrine-serotonin reuptake blocker) at a dose of 8 mg/day, SNRI), or placebo, highlighted that both citalopram and reboxetine decreased the identification of the negative facial expressions of anger and fear, while enhancing the relative recall of positive emotional material (Harmer et al., 2004). In any case, the available literature indicates that there is no evidence of any effect of ADs on the mood of healthy individuals (Normann & Berger, 2008). Furthermore, these compounds were found to cause emotional blunting, a syndrome which is totally different from apathy, in a significant percentages (30-40 %) of the cases in the long-term use (Marazziti, 2017; Price et al., 2009; Sansone & Sansone, 2010; Wongpakaran et al., 2007). Again, it is still an unresolved issue whether or not ADs, particularly SSRIs, may or may not impair or improve some cognitive domains (Marazziti et al., 2019). According to some authors, cognitive impairment would represent real side effects of SSRI (Fava et al., 2006; Popovic et al., 2015), although, a recent meta-analysis reported that all ADs would produce positive and significant effects on control and executive functions (Rosenblat et al., 2015). However, further and focused studies are necessary to disentangle some AD side effects from effective symptom improvement that might be positive for patients (table 1).
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