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Brain Talks Vancouver, British Columbia
May 10th, 2012
Dr. Der ryck Smith, C linical Professor Department of Psychiatry
University of British Columbia
Cognitive Enhancement Practical & E thical
Considerations
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Learning Objectives
1. To be aware of the controversies surrounding neuroenhancement
2. To review the efficacy and evidence of cognitive enhancement.
3. To address the ethical issues of cognitive enhancement using medications.
4. To be aware of the resources available for further learning.
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Why a Public Discussion on Cognitive Enhancement
1. Have been prescribing ADHD medications for 30 years. We know these medications improve
2. There are ongoing controversies in the science and
ethical journals.1
3. Debate has not yet reached mainstream, clinical psychiatry
1. Bostrom, N. Cognitive Enhancement, Sci Eng E thics 2009; 15: Pp 311-341
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A New Cognitive Enhancer
Antagonist of adenosine receptors Leads to increases in:
1. Dopamine 2. Acetylcholine 3. Serotonin 4. Glutamate
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Positive Effects
1. Improves motor functioning during fatigued states1.
2. Improves cognitive functioning. 3. Increased feelings of well being,
relaxation, alertness and concentration. 4. Improved information processing and
memory. 5. Neuroprotective effects from long-term
use in both animal and human subjects2. Slide 1 of 3
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Positive Effects
6. Increased muscarinic and nicotinic receptors in animal brain.
7.of between 30 60%.8
8. Reduced risk of depression.3
9. No negative health outcomes. 10. 100-mg. dose reduced omission errors,
false alarms, reaction times and increased vigilance.4
Slide 2 of 3
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Positive Effects
11. Improves passing accuracy and jump performance in football (soccer).5
12. Robust improvement on NART and WTAR in the elderly.6
13. Improves brain functioning, by conditioning, even in the absence of the drug.7
Slide 3 of 3
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1. Should this medication be available for general use?
2. Who would be interested in
participating in a clinical trial or trying this medication?
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Caffeine
Methylxanthine Antagonist of adenosine receptors Adenosine ubiquitous nucloside that is a homostatic regulator Caffeine blocks A1 receptors in brain that are inhibitory and A2A receptors in the basal ganglion that are excitatory.
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References
1. van Duineu, H. The effect of caffeine on cognitive task performance and motor fatigue. Psychopharm 2005 180: 539-542
2. Rosso, A, Caffeine, Neuroprotective functionings in cognition and Am. J. Alz. Disease 2008 23: 417-422
3. Smith, A, Caffeine, cognitive failures and health in a non-working community sample, Human Psychopharm 2009 24:29-34
4. Maridakis, V., Sensitivity to change in cognition and mood in response to differing doses of caffeine, International J Neuroscience 2009 119:975-994
5. Fosket, A. Caffeine enhances cognitive functioning and skill performance during simulated soccer activity, Int J Sports Nutrition 2009 19:410-423
6. Corley, J. Caffeine, consumption and cognitive function at age 70, Psychosomatic Med. 2010 72:206-214
7. Attwood, A. Conditional effects of caffeine in performance in humans, Physio and Behav 2010 99:286-293
8. Lindsay, J. Am J Epidem; 2002 156: Pp 445-453
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Definitions
Cogniceuticals (Russo 2007) Pharmaceuticals that effect cognition
Nootropics Products including drugs, supplements and nutraceuticals that improve cognition, memory, intelligence and attention
Nutraceuticals A food or food product that provides health or medical benefits, example - brahmi
Neuroenhancement Prescribing medications to normal adults for purposes of augmenting their normal cognitive or affective function
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Cognitive Enhancers
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Cognitive Enhancement
beyond normal Restoration returns diminished function to the normal range
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Cognitive Enhancers
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Cognitive Enhancers
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Other Types of Cognitive Enhancers
1. Reading 2. Writing 3. Private Schools 4. Telescopes 5. Personal Computing Devices 6. ? Brain Chips1
7. ? Brain Training 8. ? Transcranial direct current stimulation2
9. ? Transcranial magnetic stimulation3
1Sandhana, L., Chips Coming to a Brain Near You, www.wired.com/print/medtech/news/2004/10/65422 2Sparing, R. Enhancing Language Performance, Neuropsychologia, 2008; 46: Pp 261-268 3Synder, A. Concept formation, J. Integ Neuro Science, 2004; 3(1) : Pp 31-46
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Transcranial Direct Current Stimulation
Sparing, R. Enhancing Language Performance, Neuropsychologia, 2008; 46: Pp 261-268
Weak current tDCS was applied to 15 healthy subjects Target posterior perisylvian region (ppr) Included sham conditions Visual picture naming task was faster in all subjects following stimulation of the left ppr
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Why Are People Interested In Cognitive Enhancement?
millions of years before evolution offers him
Cornelieu Giurgea
Romanian Neuroscientist 1960
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Why Are People Interested In Cognitive Enhancement?
Aging
1
Cognitive abilities decline with age Experiments with adults age 21 and age 72
Memory declines with age Susceptibility to misinformation increases with age
Cognitive speed Inhibitory function
Memory Brain volume
Brain activity Prefrontal white matter most susceptible4
1Saunders, J. The effects of age on remembering and knowing misinformation, Memory, 2010 18(1) Pp 1 11 2Ebmeier, K. Normal cognitive decline or dementia? The Practitioner 2010; 254: Pp 23-27 3Grady, C, Cognitive Neuroscience of Aging; Ann. N.Y. Acad. Sci. 2008; 1124 Pp 127-144 4Gunning-Dixon, F. Aging of cerebral white matter: a review of MRI findings Inter. J. Geriatric Psychiatry 2009; 24: Pp 109-117
Decreases with age3
Decline with age2
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AAMI Prevalence Estimated From Standard Clinical Memory Tests
0 50 - 59 80 plus
Perc
ent M
eetin
g O
bjec
tive
AAM
I Pe
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man
ce C
riter
ia o
n Tr
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Crook, T.H. The Memory Advantage 2006; Figure 7 Pp 30
70 - 79 60 - 69 Age Ranges
100 90
80
70
60
50
40
30 20
10
AAMI = Age Associated Memory Impairment
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Why Are People Interested In Cognitive Enhancement?
Competitive Environment We are in an environment that is becoming increasingly competitive cognitively.
best university best job best lecture best research proposal
Success in life can depend upon superior cognitive functioning.
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Methods of Enhancing Cognition
1. Mental exercises 2. Diet 3. Exercise 4. Medication
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Training In Working Memory
Strategies elaborate encoding using mental stories imagery relationship between new and currently memorized material rehearsing out loud
Questions
1. Does this generalize to daily life? 2. How long do the effects last?
Morrison, A.B., Does Memory Training Work?, Psychon Bulletin Rev 2011: 18 p 46-60
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Effects of Diet and Exercise
Omega 3 fatty acids Curcumin (tumeric) Vigorous exercise BDN F
Modulates efficacy of synaptic transmission Stimulates synaptic and cognitive plasticity
Gomez-Pinilla, F. Collaborative effects of diet and exercise on cognitive enhancement, Nutr Health 2011: 20 (3-4), 165-169
All increase brain-derived neurotropic factor (BDNF)
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1. Cholinergic Agents 2. Nicotine Agents 3. Glutamatergic Agents memory, attention 4. Stimulants (dopamine enhancers)1
5. Mirtazapine attention Public Demand
Nutritional supplements that promise improved memory > $1B in the U.S.
Agents That Could Be Considered Cognitive Enhancers
1Backman, L. Linking cognitive aging to dopamine; Neurosci. Biobehav. Reviews 2010; 34: Pp 670-677
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Attention
ADHD or related medications Amphetamine Atomoxetine Methylphenidate Modafinil
- improve working memory, processing speed, declarative memory, ? executive memory, cognitive control
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Current Use of Pharmaceutical Enhancers
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Stimulant Use in U.S. Colleges
Esteban, S Non-medical use of prescription stimulants among U.S. college students: prevalence and correlates from a national survey; Addiction, 99 Pp 96-106
Sample of 10,904 college students in 2001 self administered mail survey response rate 52%
Results Non-medical stimulant use (Ritalin, Dexedrine, Adderall)
Life time 6.9% Past year 4.1% in one site 25% Past month 2.1% White, male, lower grade point average Highest rates
1. North eastern U.S 2. More competitive admission standards More likely to use other substances Obtained from peers and friends
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Why Do Students Use ADHD Meds? Web Survey 3,400 under graduate students1
6 month prevalence of non medical ADHD use 5.4% 1. Concentrate for studying 3.6 2. Study longer 3.4 3. Less restless when studying 2.8 4. Concentrate in class 1.9 5. Less restless in class 1.6 6. Keep track of assignments 1.6 7. Feel better 1.5 8. Get high 1.4 9. To prolong effects of alcohol 1.4 10. Prevent other student from having an academic edge 1.3
A positive screening for ADHD was associated with non medical use of stimulants in 12,000 Canadian students grade 7 12.2
1Rabiner, D, Motives and Perceived Consequences of Nonmedical ADHD Medication Use by College Students, J of Att. Disorders, 2009 Pp 259 270 2Poulin, C From attention-deficit/hyperactivity disorder to medical stimulant use to the diversion of prescribed stimulants to nonmedical stimulant use ,Addiction, 2007; 102: Pp 740-751
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Non Medical Use of Stimulants
Psychological Bulletin 2011: 137 p 717-741
National Survey on Drug Use and Health (2008) Non-medical use of stimulants
Life time prevalence > 12 8.5% Ages 21 25 12.3%
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Obtaining Neuro Enhancers All medications referenced in this workshop can be purchased on line using credit cards, with no prescription or no medical examination! To Buy Adderall On L ine, C lick H ere
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Use By Scientists and Researchers
1. Internet poll from Nature1 2. 1,400 scientists, 60 different countries 3. 20% had used cognitive enhancers
62% Methylphenidate 44% Modafinil
Why? a) Improve concentration b) For a specific task c) Jet lag
4. Recent meeting in Hong Kong informal poll confirmed significant use in neuroscience researchers2
1 Nature (2008) 452 Pp 674-5 2 Congress of Neuropsychopharmacology, 2010
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Sleep Deprived Emergency Physicians1
1. Double blind, random crossover 2. Modafinil improved:
a. Sustained attention b. Cognitive control c. Working memory d. Self reported ability to attend lectures and learn
3. Equivocal results in non sleep deprived normals2
1 Gill, M. Cognitive Performance Following Modafinil versus Placebo in Sleep-deprived Emergency Physicians: A Double-blind Randomized Crossover Study, Acad Emerg Med, 20006, Vol 13 No. 2 2 Randall, D, The cognitive enhancing properties of modafinil are limited in non sleep deprived middle aged volunteers, Pharmacology, Biochemistry and Behavior, 2004 77 Pp 547-555
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Review of Effectiveness
Medications for: 1. 2. ADHD 3. Narcolepsy
Cognitive enhancement in healthy subjects . Modest improvement in:
1. Working memory 2. Executive functions 3. Sustained attention 4. Episodic memory
de Jongh, R. Boxtox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories; Neuroscience and Biobehavioral Reviews 32 (2008) Pp 760-776
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What Is Being Enhanced?
Lanni, C, Cognitive enhancers between treating and doping the mind; Pharmacological Research, 2008 57; Pp 196-213
1. Memory 2. Attention 3. Creativity
Memory - Neurogenesis can take place in hippocampus - Drugs acting on neurotransmitters
1. Acetylcholine 2. Nicotine
Cognitive functions contributing to mental performance are distinct but heavily intermingled.
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Ampakines
Are not agonists or antagonist of neurotransmitters Modify receptor biophysics by modifying synaptic current
2Lynch, G. Memory Enhancement, Nature Neuroscience, 2002; 5:1035-1038 Slide 1 of 2
Memory enhancement: the search for mechanism-‐based drugs
Effects of a positive modulator on the recall of nonsense syllables by aged subjects. ut prompting 5 minutes later .
Three of the groups were given the ampakine C X516 at the indicated dosages. Retention scores (mean s.e.m.) are shown; the differences were significant (A N O V A). Right, the drugs did not detectably affect heart rate; blood values in the low micromolar range were associated with improved memory scores
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Ampakines
Enhance attention, alertness, learning, memory Interest with glutamatergic AMPA receptors Being developed by Cortex, Shire, Servier One compound CX717 in Phase II trials Phase II completed March 3, 20081
Ampalex C X516 can be purchased on line from China
1ClinicalTrials.gov Slide 2 of 2
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The Future
As of 2008, 32 compounds in clinical trials for treatment of cognitive impairment. 1. Acetylcholinesterase Inhibitors 2. Nicotinic Acetylcholine Receptor Agonists 3. Serotonin Receptor Antagonists 4. GABA Agonists 5. Multi Functional Drugs
These new compounds are the most likely candidates for cognitive enhancement.
Buccafusco, J. J. Emerging cognitive enhancing drugs; Expert Opinion 2009; 14: Pp 577-589
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The Future
1. Purposeful development of drugs for enhancement of normal functioning unlikely
2. Expansion of: a) b)
3. example 90% of prescriptions for 1
Apnea and Shift Work Sleep Disorder 4. More development for disease specific states, dementia,
ADHD etc.
1Vastab, B. Wakefulness enhancer raises concerns; JAMA 2004 291: Pp 167-70
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Ethics
A branch of philosophy that addresses questions about morality that is, concepts such as good and bad.
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Neuroethics
The examination of what is right and wrong, good and bad about the treatment of, perfection of or unwelcome invasion of and worrisome manipulation of the human brain
William Safire
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Ethical Issues
1. Liberal viewpoint Everyone should do what they want as long as it does not cause others harm
2. Distributive justice Everyone should have equal access to beneficial treatments Our society tolerates inequality of resources, e.g. private MRIs, cosmetic surgery, private schools
3.developed
4. Expansion of existing medical diagnoses and emergence of new categories
Slide 1 of 2
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Ethical Issues
5. Coercion Could individuals be forced by their employers, peers or other to take cognitive enhancers? School attendance is current mandatory for children.
6. Use of language can define the debate ? Prescription Drug Diversion1
? Prescription Drug Abuse ? Cognitive Enhancement ? Life Style Choice
7. A waste of scarce medical resources Compare with plastic surgery
8. Treatment for unhealthy labor practices Long hours Shift work
Slide 2 of 2 1Racine E., Cognitive Enhancement Neuroethics 2010 3: Pp 1-4
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Neuroethics
1. Neuroethics Society - To promote the development and responsible application of
neuroscience through research, education and public engagement
- Can join for $60/year - www.neuroethicssociety.org 2. Neuroethics (Journal)
- New journal with international focus - Published since 2008 http://www.springer.com/content/120989/
Recent Article Racine, E. Cognitive Enhancement, Lifestyle Choice or Misuse of Prescription Drugs, Neuroethics 2010 3 Pp 1-4
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Position Paper of the American Academy of Neurology
1. Prescription of medication for neuroenhancement is:
Not legally obligatory Not legally prohibited Legally permissible (in the U.S.)
2. Neuroenhancement would be prescribed for improving the wellbeing of the patient
3. - 4.
populations.
Larrivierre, D., Responding to Requests from Adult Patients for neuroenhancements; Neurology 2009; 73: Pp 140-6-1412
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My (Tentative) Position
The Facts 1. Informed healthy adults are obtaining cognitive enhancers
from: a) Internet b) Friends
2. The market for cognitive enhancement is expanding: a) ? Increased demands b) Graying population with intellectual decline c) Awareness in popular media
3.prescribing
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My (Tentative) Position
Healthy, informed adults seeking cognitive enhancers should have these medications prescribed by doctors: Why? 1. Better regulation than informal market 2. Screening for health issues 3. Medical monitoring