Pharmakologisches Neuroenhancement aus Sicht der Suchtmedizin

Zusammenfassung

Pharmakologisches „Cognitive Enhancement“ (CE) oder auch „pharmakologisches Neuroenhancement“ (PN) beschreibt die Einnahme diverser Substanzen durch Gesunde mit dem Ziel, die eigene geistige Leistungsfähigkeit vor allem bezüglich Vigilanz, Aufmerksamkeit, Konzentration, Gedächtnis und Motivation zu verbessern. Die eingenommenen Substanzen lassen sich in Stimulanzien (Methylxanthintyp wie Koffein, Amphetamintyp wie Methylphenidat, Amphetamine und Modafinil) und Nicht-Stimulanzien (verschreibungspflichtige Medikamente wie Antidementiva, Antidepressiva und frei verkäufliche Präparate wie Phytopharmaka, z. B. Ginkgo biloba) unterteilen. Die Einnahmeprävalenzen weisen je nach Studie und Substanz große Unterschiede auf und liegen zwischen 1 % Lebenszeitprävalenz und 20 % Ein-Jahres-Prävalenz. Das Missbrauchs- und Abhängigkeitsrisiko ist sehr unterschiedlich und scheint bei Nicht-Stimulanzien zu vernachlässigen zu sein, während es bei Stimulanzien vom Methylxanthintyp, v. a. aber vom Amphetamintyp nicht zu unterschätzen ist. Diese Übersichtsarbeit stellt die o. g. Substanzen mit ihren größtenteils auf einfache kognitive Teilleistungen begrenzten klinischen Effekten sowie suchtmedizinische Aspekte der zum PN eingesetzten Substanzen dar.

Abstract

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.

Schlüsselwörter

Pharmakologisches Neuroenhancement - Suchtmedizin - Stimulanzien - Missbrauch - Abhängigkeit

Key words

cognitive enhancement - substance misuse/addiction - stimulants - misuse - addiction

• Literatur

• 1 World Anti-Doping Agency (WADA). Homepage of the WADA containing pdf file with prohibited substances. 2013 http://www.wada-ama.org/en/World-Anti-Doping-Program/Sports-and-Anti-Doping-Organizations/International-Standards/Prohibited-List/ Accessed Nov. 2014
• 2 Forstl H. Neuro-enhancement. Brain doping. Nervenarzt 2009; 80: 840-846
• 3 Franke AG, Lieb K. Pharmacological neuroenhancement and brain doping: Chances and risks. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2010; 53: 853-859
• 4 Simon P, Striegel H, Aust F et al. Doping in fitness sports: estimated number of unreported cases and individual probability of doping. Addiction 2006; 101: 1640-1644
• 5 Striegel H, Ulrich R, Simon P. Randomized response estimates for doping and illicit drug use in elite athletes. Drug Alcohol Depend 2010; 106: 230-232
• 6 Franke AG, Lieb K. Pharmacological Neuroenhancement: Substances and Epidemiology. In: Hildt E, Franke AG, , Hrsg. Cognitive Enhancement – An Interdisciplinary Perspective. Heidelberg: Springer Verlag; 2013: 17-27
• 7 Maher B. Poll results: look who’s doping. Nature 2008; 452: 674-675
• 8 Soyka M. Neuro-enhancement from an addiction specialist’s viewpoint. Nervenarzt 2009; 80: 837-839
• 9 Mehlman MJ. Cognition-enhancing drugs. Milbank Q 2004; 82: 483-506 , table of contents
• 10 de Jongh R, Bolt I, Schermer M et al. Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories. Neurosci Biobehav Rev 2008; 32: 760-776
• 11 Middendorf E, Poskowsky J, Isserstedt W. Formen der Stresskompensation und Leistungssteigerung bei Studierenden. HISBUS-Befragung zur Verbreitung und zu Mustern von Hirndoping und Medikamentenmissbrauch. Hannover: HIS Hochschul-Informations-System GmbH; 2012
• 12 Kramer PD. Listening to Prozac. New York: Viking Press; 1993
• 13 Normann C, Boldt J, Maio G et al. Options, limits and ethics of pharmacological neuroenhancement. Nervenarzt 2010; 81: 66-74
• 14 Deutsche Angestelltenkrankenkasse (DAK). Gesundheitsreport 2009. Analyse der Arbeitsunfähigkeitsdaten. Schwerpunktthema Doping am Arbeitsplatz. Berlin/Hamburg: DAK Forschung, IGES Institut GmbH; 2009
• 15 Franke AG, Lieb K. Missbrauch von Psychopharmaka zum „Cognitive Enhancement. InFo Neur Psych 2009; 11 (07) 42-50
• 16 Arzneimittelfachinformation. Coffeinum N 0,2g. Berlin: MERCK dura; 2008
• 17 McLellan TM, Lieberman HR. Do energy drinks contain active components other than caffeine?. Nutr Rev 2012; 70: 730-744
• 18 Giles GE, Mahoney CR, Brunye TT et al. Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose. Pharmacol Biochem Behav 2012; 102: 569-577
• 19 Nehlig A, Daval JL, Debry G. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev 1992; 17: 139-170
• 20 Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci 2004; 61: 857-872
• 21 Ferre S, Ciruela F, Borycz J et al. Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain. Front Biosci 2008; 13: 2391-2399
• 22 Lin FJ, Pierce MM, Sehgal A et al. Effect of taurine and caffeine on sleep-wake activity in Drosophila melanogaster. Nat Sci Sleep 2010; 2: 221-231
• 23 Ker K, Edwards PJ, Felix LM et al. Caffeine for the prevention of injuries and errors in shift workers. Cochrane Database Syst Rev 2010;
• 24 Foskett A, Ali A, Gant N. Caffeine enhances cognitive function and skill performance during simulated soccer activity. Int J Sport Nutr Exerc Metab 2009; 19: 410-423
• 25 Wesnes KA, Barrett ML, Udani JK. An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study. Appetite 2013; 67: 105-113
• 26 Ishak WW, Ugochukwu C, Bagot K et al. Energy drinks: psychological effects and impact on well-being and quality of life-a literature review. Innov Clin Neurosci 2012; 9: 25-34
• 27 Aggarwal R, Mishra A, Crochet P et al. Effect of caffeine and taurine on simulated laparoscopy performed following sleep deprivation. Br J Surg 2011; 98: 1666-1672
• 28 Wesensten NJ. Legitimacy of concerns about caffeine and energy drink consumption. Nutr Rev 2014; 72 (Suppl. 01) 78-86
• 29 Mariotti KC, Rossato LG, Froehlich PE et al. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects. Curr Clin Pharmacol 2013; 8: 350-357
• 30 Repantis D, Schlattmann P, Laisney O et al. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacol Res 2010; 62: 187-206
• 31 Spencer RC, Klein RM, Berridge CW. Psychostimulants act within the prefrontal cortex to improve cognitive function. Biol Psychiatry 2012; 72: 221-227
• 32 Linssen AM, Sambeth A, Vuurman EF et al. Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies. Int J Neuropsychopharmacol 2014; 17: 961-977
• 33 Bagot KS, Kaminer Y. Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review. Addiction 2014; 109: 547-557
• 34 Wood S, Sage JR, Shuman T et al. Psychostimulants and cognition: a continuum of behavioral and cognitive activation. Pharmacol Rev 2014; 66: 193-221
• 35 Minzenberg MJ, Carter CS. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 2008; 33: 1477-1502
• 36 Sugden C, Housden CR, Aggarwal R et al. Effect of pharmacological enhancement on the cognitive and clinical psychomotor performance of sleep-deprived doctors: a randomized controlled trial. Ann Surg 2012; 255: 222-227
• 37 Franke AG, Heinrich I, Lieb K et al. The use of Ginkgo biloba in healthy elderly. Age (Dordr) 2014; 36: 435-444
• 38 Arzneimittelfachinformation. Tebonin. Karlsruhe: Schwabe; 2008
• 39 Diamond BJ, Bailey MR. Ginkgo biloba: indications, mechanisms, and safety. Psychiatr Clin North Am 2013; 36: 73-83
• 40 Birks J, Grimley EV, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2002;
• 41 Birks J, Grimley EvansJ. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007;
• 42 Birks J, Grimley EvansJ. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2009;
• 43 Tan MS, Yu JT, Tan CC et al. Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. J Alzheimers Dis 2015; 43: 589-603
• 44 Solomon PR, Adams F, Silver A et al. Ginkgo for memory enhancement: a randomized controlled trial. JAMA 2002; 288: 835-840
• 45 Repantis D, Laisney O, Heuser I. Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 2010; 61: 473-481
• 46 Yesavage JA, Mumenthaler MS, Taylor JL et al. Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 2002; 59: 123-125
• 47 DGPPN, BÄK, KBV, AWMF, AkdÄ, BPtK, BApK, DAGSHG, DEGAM, DGPM, DGPs, DGRW (Hrsg) für die Leitliniengruppe Unipolare Depression*. S3-Leitlinie/Nationale Versorgungs-Leitlinie Unipolare Depression – Kurzfassung, 1. Auflage 2009. Berlin, Düsseldorf: DGPPN, ÄZQ, AWMF; 2009
• 48 Holsboer-Trachsler E, Holsboer F. Antidepressiva. In: Gründer G, Benkert O, Hrsg Handbuch der psychiatrischen Pharmakotherapie. Berlin Heidelberg: Springer-Verlag; 2012: 589-628
• 49 Repantis D, Schlattmann P, Laisney O et al. Antidepressants for neuroenhancement in healthy individuals: a systematic review. Poiesis Prax 2009; 6: 139-174
• 50 Wilens TE, Adler LA, Adams J et al. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008; 47: 21-31
• 51 Franke AG, Bonertz C, Christmann M et al. Non-medical use of prescription stimulants and illicit use of stimulants for cognitive enhancement in pupils and students in Germany. Pharmacopsychiatry 2011; 44: 60-66
• 52 Franke AG, Christmann M, Bonertz C et al. Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany. Pharmacopsychiatry 2011; 44: 331-338
• 53 Franke AG, Lieb K, Hildt E. What users think about the differences between caffeine and illicit/prescription stimulants for cognitive enhancement. PLoS One 2012; 7: e40047
• 54 Franke AG, Schwarze CE, Christmann M et al. [Characteristics of university students using stimulants for cognitive enhancement: a pilot study]. Psychiatr Prax 2012; 39: 174-180
• 55 Dietz P, Striegel H, Franke AG et al. Randomized response estimates for the 12-month prevalence of cognitive-enhancing drug use in university students. Pharmacotherapy 2013; 33: 44-50
• 56 Deline S, Baggio S, Studer J et al. Use of neuroenhancement drugs: prevalence, frequency and use expectations in Switzerland. Int J Environ Res Public Health 2014; 11: 3032-3045
• 57 Maier LJ, Liechti ME, Herzig F et al. To dope or not to dope: neuroenhancement with prescription drugs and drugs of abuse among Swiss university students. PLoS One 2013; 8: e77967
• 58 Ott R, Biller-Andorno N. Neuroenhancement among Swiss students – a comparison of users and non-users. Pharmacopsychiatry 2014; 47: 22-28
• 59 Burgard DA, Fuller R, Becker B et al. Potential trends in Attention Deficit Hyperactivity Disorder (ADHD) drug use on a college campus: wastewater analysis of amphetamine and ritalinic acid. Sci Total Environ 2013; 450-451: 242-249
• 60 Franke AG, Bagusat C, Dietz P et al. Use of illicit and prescription drugs for cognitive or mood enhancement among surgeons. BMC Med 2013; 11: 102
• 61 Franke AG, Bagusat C, McFarlane C et al. The Use of Caffeinated Substances by Surgeons for Cognitive Enhancement. Ann Surg 2014;
• 62 Hughes JR, Oliveto AH, Helzer JE et al. Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?. Am J Psychiatry 1992; 149: 33-40
• 63 Satel S. Is caffeine addictive? – a review of the literature. Am J Drug Alcohol Abuse 2006; 32: 493-502
• 64 Kaminer Y. Problematic use of energy drinks by adolescents. Child Adolesc Psychiatr Clin N Am 2010; 19: 643-650
• 65 Iversen L. Speed, Ecstasy, Ritalin. Amphetamine – Theorie und Praxis. Bern: Verlag Hans Huber; 2009
• 66 Tossmann P, Boldt S, Tensil MD. The use of drugs within the techno party scene in European metropolitan cities. Eur Addict Res 2001; 7: 2-23
• 67 Gahr M, Freudenmann RW, Hiemke C et al. Abuse of methylphenidate in Germany: data from spontaneous reports of adverse drug reactions. Psychiatry Res 2014; 215: 252-254
• 68 Clemow DB, Walker DJ. The potential for misuse and abuse of medications in ADHD: a review. Postgrad Med 2014; 126: 64-81
• 69 Stempel K. Rauschgiftlage. In: DHS Hrsg Jahrbuch Sucht 2014. 2014. Lengerich: Pabst; 2012: 141-153
• 70 Fleckenstein AE, Volz TJ, Riddle EL et al. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 2007; 47: 681-698
• 71 Gouzoulis-Mayfrank E, Daumann J. Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines. Dialogues Clin Neurosci 2009; 11: 305-317
• 72 Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P. Treatment for amphetamine dependence and abuse. Cochrane Database Syst Rev 2001;
• 73 Vocci F, Ling W. Medications development: successes and challenges. Pharmacol Ther 2005; 108: 94-108
• 74 Shoptaw SJ, Kao U, Heinzerling K et al. Treatment for amphetamine withdrawal. Cochrane Database Syst Rev 2009;
• 75 Ling W, Rawson R, Shoptaw S et al. Management of methamphetamine abuse and dependence. Curr Psychiatry Rep 2006; 8: 345-354
• 76 Lingford-Hughes AR, Welch S, Nutt DJ et al. Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2004; 18: 293-335
• 77 Shearer J, Wodak A, Mattick RP et al. Pilot randomized controlled study of dexamphetamine substitution for amphetamine dependence. Addiction 2001; 96: 1289-1296