The Case of Pharmacological Neuroenhancement: Medical, Judicial and Ethical Aspects from a German Perspective.

Pharmacological neuroenhancement (PN) describes the use of psychoactive drugs for the purpose of enhancing cognition (e. g., fatigue, concentration, memory etc.) by healthy subjects without medical need. Drugs used for this purpose can be divided into freely available, over-the-counter drugs (e. g., methylxanthines such as caffeine), prescription drugs (e. g., antidementia drugs, methylphenidate) and illicit drugs (e. g., illicit amphetamines). Clinical studies have shown that the aforementioned substances only have limited pro-cognitive effects and have considerable safety risks and side effects.The German judicial perspective shows legal differences between substances (drugs, food, food supplements, fortified food) that can be bought in a supermarket, drugs that can be bought in a pharmacy as over-the-counter- (OTC-) drugs, drugs with or without the need for a prescription and illicit drugs. Supermarket drugs and fortified food can be sold freely and follow the general rules of civil and penal law; regarding acquisition, parents are responsible for their children. OTC drugs require special information about therapy. Regarding prescription drugs, there are legal problems caused by an off-label use and the non-medical purposes of PN drugs. Furthermore, prescription stimulants for PN are governed by the specialized law for narcotics, and their use might be punished. Beyond the general lack of rules for regulation for PN drug use there are specific needs for prevention (e. g., control of the black market, etc.).Possible future policy will depend, among others, on the probability with which effective PN drugs with an acceptable risk-benefit ratio will be available, on individual and societal implications, and on public opinion towards PN. While 4 different general policy scenarios can be identified, it is important to advance a broad societal debate on PN to collect relevant empirical data and to address enhancement-related conceptual issues.

[Pharmacological cognitive enhancement from a perspective of misuse and addiction]. / Pharmakologisches Neuroenhancement aus Sicht der Suchtmedizin.

Pharmacological "cognitive enhancement" (CE) and "pharmacological neuroenhancement" (PN) are different terms to describe the use of diverse substances by healthy individuals aiming at an increase of individual cognitive skills. Targets of CE are an increase of vigilance, attention, concentration, memory and motivation. Substances used for pharmacological CE can be divided into two categories: stimulants and non-stimulants. The sub-group of methylxanthines like caffeine as well as the sub-group of amphetamines like prescription and illicit amphetamine as well as methylphenidate and modafinil belongs to the group of stimulants; antidementives, antidepressants, phytopharmaceutical products like Ginkgo biloba etc. belong to the group of non-stimulants. Prevalence rates depend on the (type of) study and (group of) substances used for CE. And they range from a 1 % lifetime prevalence rate up to 20 % one-year prevalence rate. This review presents stimulant and non-stimulant substances, their limited clinical effects on cognitive skills as well as their prevalence rates and the aspect of misuse and addiction of the above-mentioned substances which belongs to their respective category.

[Stimulant and non-stimulant medication in current and future therapy for ADHD]. / Psychostimulantien und Nicht-Stimulantien in der heutigen und zukünftigen ADHS-Therapie.

The current pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) is mainly based on the stimulant methylphenidate and to a small extent on amphetamines which are not approved in Germany. The only approved non-stimulant so far is atomoxetin (Strattera®), a norepinephrine reuptake inhibitor. There is no approved pharmacotherapy for adults. The aim of the available medication is a reduction of impulsivity, hyperactivity, and attention deficits. Neurobiological correlates of these effects are still not fully understood, however, a functional implication of dopaminergic and noradrenergic systems is known. To date there is no disease-modifying therapy. The currently available substances have limitations due to the short half-life of stimulants, the unknown pathomechanisms, and the use of stimulants in developing brains with possible long-term side-effects. Moreover, the abuse potential of stimulants is still controversially discussed. The recently developed Lisdexamfetamin and SPD-465 have stimulant effects, too. A number of different developmental substances in preclinical and clinical phases show other mechanisms: SPD-503 represents an α(2)A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the α(4)ß(2)-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor agonists and PF-3 654 746 exhibits antagonistic properties to histaminergic H(3)-receptors. The α(2)A-adrenoceptor-agonist Guanfacine (Intuniv®) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse®) are yet approved for ADHD treatment in the USA. The aim of this review is to summarise established pharmacological treatment options and the stage of development of upcoming symptomatic stimulant and non-stimulant substances in ADHD therapy.

Non-medical use of prescription stimulants and illicit use of stimulants for cognitive enhancement in pupils and students in Germany.

INTRODUCTION: The aim of this study was to assess for the first time the prevalence and factors associated with stimulant use exclusively for cognitive enhancement among pupils and university students in Germany. METHODS: A sample of 1 035 pupils (vocational and grammar schools) in small and big cities and 512 university students of 3 Departments (Medicine, Pharmacy, Economics) completed a questionnaire regarding knowledge and use of stimulants for cognitive enhancement and factors associated with their use. RESULTS: Lifetime prevalence for use of prescription stimulants (methylphenidate, amphetamines) for cognitive enhancement in pupils was 1.55% and in students 0.78%. Last-year and last-month prevalence rates were significantly lower. 2.42% of pupils and 2.93% of students reported lifetime illicit use of stimulants (amphetamines, cocaine, ecstasy) for cognitive enhancement with lower last-year and last-month rates. Prevalence was higher in male pupils, pupils from vocational schools and pupils with bad marks. DISCUSSION: The illicit use of stimulants for cognitive enhancement is significantly higher than non-medical use of prescription stimulants among pupils and students. Stimulant use is determined by gender, school type, and school marks. The potential risks associated with stimulant use require early awareness and intervention strategies.

Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany.

INTRODUCTION: Substance use for cognitive enhancement (CE) is a topic of increasing importance. There are only few data about substances, prevalence rates and factors associated with CE. The aim of this study was to assess first data about the use of coffee, caffeinated drinks and caffeine tablets for CE at school and university. METHODS: A self-report questionnaire was developed to analyze 1 547 pupils and students about their use of coffee, caffeine tablets, and caffeinated drinks for CE and factors associated with this use. RESULTS: Lifetime, past-year, and past-month prevalence for the use of coffee for CE was 53.2%, 8.5%, and 6.3%, for the use of caffeinated drinks 39%, 10.7%, and 6.3%, and for the use of caffeine tablets 10.5%, 3.8%, and 0.8%. Use of caffeinated substances for CE was influenced by gender and school grades. DISCUSSION: The use of coffee and caffeinated drinks for CE was found to be widespread in the surveyed population. Although the use of caffeine tablets was found to be smaller than the above-mentioned means, it still indicates a relatively high disposition for using tablets for purposes of CE.

[Pharmacological neuroenhancement and brain doping : Chances and risks]. / Pharmakologisches Neuroenhancement und "Hirndoping" : Chancen und Risiken.

Pharmacological neuroenhancement refers to the use of psychoactive substances by healthy subjects with the purpose of cognitive enhancement, e.g., vigilance, concentration, memory, or mood. "Brain doping", however, refers to the illicit use of a subcategory of these substances such as prescription drugs. This subcategory includes psychostimulants (e.g., amphetamines, methylphenidate), modafinil, antidementia drugs (acetylcholine-esterase inhibitors, memantine), and antidepressants (selective serotonin reuptake inhibitors) which are being prescribed for the treatment of ADHD (attention deficit/hyperactivity disorder), Alzheimer's disease, and depression. Only psychostimulants and modafinil show significant effects on concentration, attentiveness, and vigilance in healthy subjects. However, a general use by healthy persons can not be justified because of relevant side effects and safety risks. Caffeine for pharmacological neuroenhancement can be seen as an equally effective alternative. "Brain doping" raises numerous ethical and social concerns that require a continued discussion. Demands of liberalization should be critically questioned.

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. / Von der symptomatischen zur kausalen Therapie? Neue Entwicklungen in der Pharmakotherapie der Alzheimer-Demenz.

Until today the pharmacological therapy of Alzheimer's disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are presently studied in different phases of preclinical and clinical trials. Against earlier expectations which derived from promising preclinical immunization studies the breakthrough of disease-modification in AD is not in sight yet. Aim of this review is to summarize established pharmacological treatment options and the stage of development of upcoming symptomatic and disease-modifying substances of AD.