European Review for Medical and Pharmacological Sciences 2020; 24: 2129-2139 Nootropics use in the workplace: psychiatric and ethical aftermath towards the new frontier of bioengineering S. ZAAMI1, R. RINALDI1, G. BERSANI2, A. DEL RIO1, C. CIALLELLA1, E. MARINELLI1 1Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Departmental Section of Legal Medicine, “Sapienza” University of Rome, Rome, Italy 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Rome, Italy Abstract. – OBJECTIVE: The authors have Key Words: sought to expound upon and shed a light on the Nootropics, Human Enhancement, Productivity, rise of nootropics, which have gradually taken Workplace, Bioengineering, Ethics. on a more and more relevant role in workplaces and academic settings. MATERIALS AND METHODS: Multidisciplinary Introduction databases have been delved into by entering the following keys: “nootropics”, “cognitive enhance- ment”, “workplace”, “productivity”, “ethics”, “bio- The use of therapeutic drugs for non-medical engineering”. In addition, a broad-ranging search reasons as cognitive enhancers has been spreading has been undertaken on institutional websites in and its risks seem to have become at least in part order to identify relevant analysis and recommen- acceptable among students and certain groups of dations issued by international institutions and workers. Considering the ever more competitive agencies. Papers and reports have been inde- pendently pored over by each author. This search nature of modern societies, which reverberates on strategy has led to the identification of 988 sourc- workplaces as well, enhancers are reasonably ex- es but only 64 were considered appropriate for the pected to spread even more over time; nonetheless, purposes of the paper after being selected by at long-term consequences arising from their becom- least 3 of the authors, independently. ing mainstream “supplements”, for the purpose of RESULTS: The notion of an artificially en- boosting performance, are as yet unknown. Cog- hanced work performance – carried out by the ‘superworker’ – is particularly noteworthy and nitive enhancers, used by healthy individuals, are resonates with the conception of contempo- widely known as nootropics: drugs, supplements, rary work on so many different levels: the rising and other substances that may improve cogni- need and demands for higher degrees of flex- tive function, particularly executive functions, ibility and productivity on the job, the implica- strengthening memory, creativity or even moti- tions of a ‘24/7’ society, where more and more vation in healthy individuals who choose to use services are available at any time, the ever great- them in an effort to take their performances “to the er emphasis on entrepreneurial spirit, individu- al self-reliance and self-improvement, and last next level”. The word “nootropic” was coined in but not least, the impact of an ageing society on 1972 by a Romanian scientist, Corneliu Giurgea, economic standards and performance. who combined the Greek words for “mind” and CONCLUSIONS: Moreover, it is worth men- “bending”1-3. The pharmaceutical substances and tioning that human enhancement technologies compounds known as ‘cognitive-enhancers’ can will predictably and increasingly go hand in hand allegedly boost mental performance, the ability to with gene editing, bioengineering, cybernetics 4 and nanotechnology. Applications are virtually focus and keep concentration . In broader terms, boundless, and may ultimately affect all human such drugs are often claimed to heighten and foster traits (physical strength, endurance, vision, in- motor capabilities, affective skills, (i.e., one’s abili- telligence and even personality and mood). ty to deal with anxiety stemming from performing Corresponding Authors: Raffaella Rinaldi, MD; e-mail: [email protected] 2129 S. Zaami, R. Rinaldi, G. Bersani, A. Del Rio, C. Ciallella, E. Marinelli certain work tasks or eliciting feelings of trust and levels11. Adderall (trade name) is a mixture of am- affiliation) and are available for clinical and thera- phetamine salts. It is reportedly used off-label for peutic reasons5. the purpose of increasing focus (among workers Furthermore, stagnant economic conditions and students, in particular) or to get a “high” (a certainly play a role in incentivizing worker com- strong, pleasing feeling of euphoria, typical of petition, within which some may feel compelled to recreational drugs)12. Users have shown a tenden- consider substances to enhance their productivity. cy towards polydrug use and at times, adulter- In fact, the key factor accounting for nootropics ants such as caffeine and phentermine have been use in the workplace is productivity, as measu- found added to the amphetamines13,14. Polydrug red by the amount of work produced per working use, which involves countless substances that are hour, i.e., one of the main drivers of long-term eco- extremely hard to identify and regulate, is a seri- nomic growth and higher living standards6. As a ous threat that is bound to grow as online illicit matter of fact, since the crippling 2008 economic market avenues become ever more accessible. For crisis, productivity has lagged behind pre-crisis that reason, some have called for more invest- levels, with little or no significant steady growth7. ments in toxicological and forensic analytical data Productivity growth goes hand in hand with eco- facilities and better international coordination in nomic growth and development; hence the recent order to tackle that issue15. As for the enhancing slowdown in aggregate labour productivity in le- capabilities of amphetamines, a 2014 systematic ading economies has been widely characterized review has found that low doses of amphetamine as a puzzle, even paradox. Still, viewing pharma- could potentially foster memory consolidation cological enhancers as a relatively easy shortcut and retention of information in healthy youth, as towards greater productivity entails significant well as enhance task saliency (motivation to per- medical and ethical challenges8. form a task) and execution of tedious tasks requir- ing substantial effort16,17. Cognitive Enhancers Used Off-Label: What About Safety and Effectiveness? A Widely Used Central Nervous System It is worth noting, however, that no drugs are Stimulant: Methylphenidate licensed by medical authorities to be recommend- Methylphenidate (marketed und er the brand ed and prescribed as ‘cognitive enhancers’ as names Ritalin, Equasym, Concerta, Rubifenis such. Thus, the definition ‘performance-enhanc- and Medikinet) acts as a stimulant of the central ing drug’ is usually linked to the off-label use of nervous system (CNS)18; its main application is drugs prescribed for specific medical conditions treating ADHD and narcolepsy. It raises levels of by healthy individuals, for the purposes of per- the neurotransmitters dopamine and norepineph- formance enhancement; modafinil9, used for the rine19. At above optimal doses, methylphenidate treatment of narcolepsy, or methylphenidate10, reportedly causes off-target effects negatively af- for Attention Deficit Hyperactivity Disorder fecting learning skills20. Adverse side-effects are (ADHD), fall within that category. Users acquire a cause for concern: the dopaminergic activity of such medicines on the internet, or through some- methylphenidate may lead to euphoria and addic- one who does have a prescription. Such dynamics tion (its mode of dopaminergic action is similar to mark a cultural shift in drug abuse dynamics: they that of cocaine). Methylphenidate can reportedly are in fact free of the stigma usually associated exacerbate existing behavioral problems and cen- with street drugs while also appearing safer, al- tral nervous system disorders such as bipolar dis- though there can be no certainty as to their actual ease and psychosis; its peripheral effects should composition and nature; potential dangers are not not be overlooked: higher adrenaline concentra- as clearly perceived, since the term “medicine” is tions in plasma may in fact cause or worsen heart associated with treatment and cure. problems. Hence, methylphenidate is contraindi- cated for patients with high blood pressure, heart A Broad-Ranging (and Growing) Array of defects or a family history of heart problems21. Substances: Amphetamines Several pharmaceutical drugs which are com- Atomoxetine Hydrochloride Greater monly associated with cognitive enhancing (Ta- Alertness and Focus at What Cost? ble I): ≤ Atomoxetine hydrochloride is licensed for Amphetamines, which are stimulants used to the treatment of ADHD in children of six years treat ADHD or narcolepsy, heighten dopamine and older, in children over the age of six and in 2130 Nootropics use in the workplace Table I. Principal pharmacological active substances used as nootropics and performance enhancers, their mechanism of action, therapeutic indications and side effects. Chemical Brand Mechanism Therapeutic Drug Class Side effects name name of action indications Agitation, Dopamine reuptake ADHD*, anxiety, bladder Amphetamine Stimulant Adderall inhibitor; dopamine Narcolepsy pain, depression, releaser nervousness Dopamine and Ritalin, Anxiety/ noradrenaline Equasym, nervousness, reuptake inhibitor, ADHD*, Methylphenidate Stimulant Concerta, insomnia , appetite dopaminergic and Narcolepsy Rubifenis loss, dry mouth, noradrenergic Medikinet nausea, activity stimulant Nausea, vomiting, insomnia,