Performance Enhancing Agents

Learning Objectives
- To recognize drugs that can enhance physical
performance and the mental condition
- To appreciate their limitations.
- To understand the ethics related to their use.

Introduction
The desire to take medicine is perhaps the greatest
feature that distinguishes man from the animals.
William Osler (1849 -1919)
Greek for a drug or medicine is pharmakon
Prefix pharma = related to drugs
Diversity of meanings:
- Cure (remedy)
Illusion that all drugs cure.
To cure sometimes, relieve often, comfort always.
- Poison
- Magical charm : magic bullet, wonder drug
2

Introduction
Legitimate place and role for medicines in

disease
Worrying when healthy persons used drugs to
improve performance (sports, cognition, Viagra),
improve looks (Botox), or to handle problems
that could be solved or accomodated by the
individual (shyness).
Pill for every ill

Drugs and Sports

-

Doping
World Anti-doping Association (WADA)
Why is doping wrong ?
What can be done to rid doping from sports ?
Anti-doping measures
Prohibited List
Testing
- State-sponsored Doping
- Blood doping
- Game Theory and Doping
4

Eric Liddell
And where does the power
come from, to see the race
to the end?
From within

Marion Jones
Lance Armstrong :
You can never win
the Tour de France
wiithout doping

I am against
performanceenhancing
drugs. I have
never taken
them and I will
never take
them.
6

Doping
Doping : Use of artificial substances or methods to
enhance sporting performance.
- First used in 1890s in connection with horse racing.
- Dutch word dop = alcoholic beverage made from
grape skins. Zulu warriors for battle.
Earliest performance enhancing agents were more
food - tonics (strychnine, coca), egg white,
mushrooms (stimulant) - than drugs.
Growth of pharmaceutical industry in 20th century
introduced drugs : amphetamines, steroids,
7

Doping
International efforts to control and eliminate doping
is spearheaded by the World Anti-Doping Agency
(WADA).
Set up in 1999 by the International Olympic Council
(IOC).
Rather late in coming - many cases of doping in
Olympic Games prior to 1999.
Formed in response to embarrassingly high incidence
of doping among competitors of the 1998 Tour de
France.
World Anti-doping Code: Core document defining
8
rules, regulations, policies,

World Anti-Doping Code

Square:
Green equal * sign
Black background

WADAs definition of a performance

enhancing agent
Substance that fulfills at least 2 of the following
criteria:
- Enhances performance
- Harms the athlete
- Against the spirit of sports

10

Why doping is wrong

It is cheating
The most important thing in the
Olympic Games is not to win, but
to take part, just as the most
important thing in life is not the
triumph but the struggle. The
essential thing is not to have
conquered but to have fought
well.
Olympic Creed
11

Why doping is wrong

It is not safe : Harms the athlete
- Many of the substances used are designer drugs:
unapproved substances that have not been tested in
humans.
- Of those that are known : Used wrongly and at
inappropriate doses (eg: growth hormone, steroids)
It is unfair to those athletes who want to compete
fairly.
It harms reputation of the sport and defrauds those
who support the game.
12

How to get rid of doping in sports

Test more and doping will end
Raise the cost of cheating
Legalize doping

13

Test more and doping will end

Testing is under the purview of WADA:
- Prohibited List of substances and methods.
- In-competition and out-of-competition testing
of athletes (blood or urine samples).
But over-testing may lead to false positives.
- Highly sensitive and complicated tests.
- Carried out in different laboratories.

14

Testing works !

15

Raise the cost of cheating

Athletes cheat because doping is a rational choice

Drugs are effective and payoffs are high.
If you stay clean, you will be uncompetitive.
Risk of detection is low
How to raise the cost of cheating ?
Increase substantially the penalty for getting caught
Extend punishment to other team members

16

Legalize doping
Because sports is inherently unfair
- Athletes have inherently different abilities
- Exposed to coaches, training methods and facilities
of differing standards.
Sports is intrinsically harmful
- Boxing, professional football

17

Anti-doping measures: Prohibited List

Substances prohibited at all times (in- and out- ofcompetition)
- Examples: Steroids, hormones (growth hormone,
erythropoietin, insulin), masking agents
Substances prohibited in-competition
- Examples : stimulants (amphetamines, strychnine),
narcotics (heroin, morphine)
Substances prohibited in certain sports. In competition
- Alcohol (archery, automobile, karate)
- Beta-blockers (shooting, archery, darts, golf)
18

To increase the oxygen

carrying capacity of blood :
Increase stamina +endurance

To ensure that processes for

collection of urine or blood
samples are robust.
To prevent introduction of
genes into cells that would lead
to production of performance
enhancing proteins.
19

Prohibited List of substances

An open list

AAS = Anabolic androgenic steroids

Loophole : Use (or make) something that is not listed.
Designer Drugs
20

Prohibited List of substances

Based on threshold values

Backhanded way of saying that if a drug is used

below threshold limits, it is permissible.
Does not take into account inter-individual variations
in breakdown and/or excretion of drug.
21

Anti-doping measures: Testing

Elaborate and strictly defined procedure.
- Provide samples on demand. (A and B samples)
These samples are kept for many years.
- Refusal to provide is admission of guilt.
- Results cannot be challenged.
- Follow strict liability guidelines : guilty regardless
of intent or negligence.
- Non-analytical positive evidence : Evidence of
purchase is sufficient to indicate guilt.
22

Not examinable
23

Not examinable
24

Anti-doping measures: Biological Passport

The biological passport looks for changes in the
individual physiology of an elite athlete that may be
indicative of doping.
Baseline is the athletes biological markers collected
from blood / urine tests in- and out-of-competition
over a period of years.
Passport would eventually have 3 components:
- Blood module to detect blood doping.
- Steroid module to detect steroid doping
- Endocrine module to detect doping with hormones
(eg: growth hormone)
25

Claudia Pechstein :
German speed skater
5-time Olympic Gold
Never failed a doping test
Irregularities were found in her blood passport.
Blood count and 8 blood variables (including % retics)
% retics = % of immature red blood cells.
During a competition (2007), her % retics were found to be
very high.
Returned to normal levels after competition.
Found guilty of blood doping in 2009.

26

Sports Greatest Cover-up

State Sponsored Doping
East Germany : German Democratic Republic
1968 : 25 medals
1972 : 66 medals
1976: 90 medals
1988 : 102 medals : ranked 2nd in medal tally
Doping program was initiated in early 1970s
State Plan 14.25
Involved scientists, doctors, coaches, government
ministries. Ministry of State Security (Stasi).
- 30% of GDP to sports
- Recruited promising athletes supplemented
training with drugs.

27

Anabolic androgenic steroids (AAS)

Substances related to testosterone (male sex
hormone).
- Anabolic : muscle building
- Androgenic : masculinizing
They were very strong women. They were very fast.
We thought they were machines. Here (we) were, four
of Americas best athletes ever put together on a team,
and every single day, the East German women were
winning every event.
Observation of member of US swim team in 1976
28
Olympics

Drips, injections, pills, It was all normal. Nothing

strange about it and I wouldnt have known what to
ask, because I wasnt sceptical at all. I didnt start to
look like a man overnight, it happened gradually. I
wasnt really aware of it myself but it was obvious to
everyone else. And whether I wore a dress or a skirt,
make-up or jewellery, it got worse and worse. They
called me a transvestite or a gay, and it shocked me.
Katharina Bullin, East German volleyball player
29

Heidi Krieger
1986 Gold Medalist
European Championships
in Athletics

Andreas
Krieger (1997)

30

Sports Greatest Coverup

You can listen to the Podcast on BBC Discovery,
Episodes 1 and 2.
There is a summary that accompanies these podcasts.
To take note of how Plan 14.25 came to an end.
- The fates of the victims and perpetrators
- Who do you think should take responsibility ?
-

31

Blood Doping
Blood doping refers to the expansion of erythrocyte
volume by artifical means.
Erythrocytes (red blood cells) transport oxygen.
More erythrocytes greater oxygen carrying
capacity
Translates to greater stamina and endurance.
Downside : blood becomes thick and viscous. Danger
of clot formation, stroke.
Blood doping is popular with endurance athletes :
cyclists, marathoners, triathletes, cross country
skiers.
How to increase erythrocyte volume ?
32

Natural Means
Training or living in high altitudes.
Low oxygen in atmosphere causes body to produce
more erythrocytes.
Sleeping in a low oxygen tent
Use of xenon gas
Rare gas
Used as an anesthetic gas in Russia
Increases level of erythropoietin (EPO) a hormone
that induces formation of erythrocytes.

33

Unnatural means

Transfusion of erythrocytes
Athlete receives from someone else (homologous
transfusion)
Athlete receives his/her own erythrocytes (autologous)
Complicated process, cannot be done just be one
person.
Athlete will receive erythrocytes 1-7 days before
competition.
Erythropoietin (EPO)
Naturally occurring substance (hormone) that
increases production of erythrocytes.
Given by injection.
34
Gene doping : introduce EPO gene into cells

2006

35

EPO
EPO is a drug for renal failure
Two main types of EPO: recombinant EPO and
biosimilars.
(i) Recombinant EPO
Earliest to enter the market
EPO gene is inserted into non-human cells EPO
protein.
-epoietin (Epogen by Amgen), -epoietin
Not identical to human EPO, but performs
same function.
Patents on these products have expired.
36

EPO
(ii) Biosimilars (follow-on biologics)
Equivalent to generics
Products of biotechnology
Same function as or -epoietin but structurally not
identical.
Significant impact on testing because tests were
designed to detect or -epoietin.

37

Game Theory and Doping

Game theory has been used to explain the
widespread abuse of drugs in sports.
Game theory deals with conflict of interests between
parties who know each others preferences but not
their actual decisions. Theory deduces the best course
of action for the rational player.

38

Game Theory and Doping

Prisoners Dilemma
You and your partner are arrested for a crime.
You are held in separate cells and are unable to
communicate with each other.
You are offered the following options:
If you confess but your partner does not, you go free and
he gets a 3 year jail term.
If he confesses but you dont, he goes free and you get a
3 year jail term.
If both of you confess, each will get a 2 year jail term
If both of you remain silent, each will a 1 year jail term.
39

Game Theory and Doping

Athletes Dilemma (Economist July 20th 2013)
Involves not only athletes but the testing organization as
well as the fans/sponsors.
Athletes : Rational choice is to cheat.
Testers: Test thoroughly or test heartedly?
Rational choice is to test heartedly.
Fans /sponsors : What is their rational choice ?
Solution according to Game Theory ?

40

Drugs and the Mental State

- Turbo-charging the brain : cognitive enhancing drugs
Do they work ?
Ethical issues
- Drugs and Emotion
Prozac and depression
Medicalization of mental conditions : Diagnostic and
Statistical Manual of Mental Disorders (DSM)

41

Limitless (2011)

42

Cognitive Enhancers : Smart Drugs

Drugs that improve memory, concentration, planning,
problem solving and decision making.
Also called nootropics (mind-bending or turning) or
Neuroenhancers
Do they exist ? Do they really work ?
By analog to doping in sports, is it ethical to use these
drugs?
43

Scientific American, Oct 2009, p 46

44

Amphetamines
Amphetamines are stimulants.
World War II : given to soldiers to keep them awake
and to booster courage.
Paradoxically, they are used to treat Attention
Deficit Hyperactivity Disorder (ADHD)
Anecdotal evidence that amphetamines are widely
used in campuses to improve grades, increase
capacity for learning, achieve greater focus.
Mood elevation and impulsivity mean that users
tend to over-rate themselves and their outputs.
45

Recently in a university hall somewhere in Singapore,

two students passed out at their desks while in the throes
of an exam. The chief invigilator ascertained that they
had been popping pills which purportedly boost ones
mental horsepower. The two said they were introduced
to this practice by some in the then graduating class, who
continue to use these pills at work to this very day.
Straits Times. Andy Ho Think before you pop brainboosting drugs.

46

The Always on Drug : Modafinil

Tradename : Provigil , 1998.
Treatment of excessive daytime sleepiness (narcolepsy)
Subsequently approved for shift work disorder
Rejected by FDA for ADHD
Off-label use: For fatigue related conditions among
military personnel, air traffic controllers and jet-lag.
Mode of action unknown.
Long term effects unknown
May have addictive potential.

47

48

Can too much memory power be a bad

thing ?
Solomon Shereshevki
Forgets nothing.
Incapable of analytical thought.
Selective forgetting of the
useless is as important as
selective remembering of the
useful.
49

Ethical Issues
Is it safe ?
- Affects the brain
- Deemed safe if used within guidelines of permissible
use, not unregulated off-label use.
- Risk of side effects : Consider trade-off .
Is it fair?
- Analogy to drug use in sports is incorrect.
Would it lead to a situation where everyone is force to
take it (coercion) ?
- Military : no choice
- Grey zones : Should a school compel all students to
50
take it to improve rankings ?

Is it ethical?
American Academy of Neurology declared that it is not
unethical for doctors to prescribe brain boosters to
normal persons.
- The mere fact that cognitive enhancers are drugs is no
reason to outlaw them
- New practice that will gain acceptance with time
- Means of controlling use and preventing abuse.

51

Drugs and Emotion

Prozac is possibly the most influential drug used in
mental illness.
Used to treat depression.
Introduced in 1988.
Through books and movies, it has helped fuel social
acceptance of antidepressant use
Shorthand for antidepressants
Prozac moment
2010: Antidepressant use:
1 in 10 people in Europe.
11% of people over age of 12
Prozac 3rd most common prescription drug in US

52

Drugs and Emotion

In 2012, new studies caused a re-thinking about the
clinical effectiveness of antidepressants.
No better than a sugar pill (placebo).
Wide usage due to smart marketing by Pharma Industry.
Mode of action still remains unclear.
Does not just increase serotonin levels in brain but may
actually cause re-wiring of certain parts of brain linked to
emotion. Or even induce growth of new brain cells in
those parts.

53

Diagnostic and Statistical Manual of

Mental Disorders (DSM)
Influential publication that lists
psychological disorders and symptoms used to
diagnose it.
American Psychiatric Association
Influence diagnosis, treatment and who pays for the
treatment.
- DSM-1 (1952) Mental illness as a response to
experience and environment.
- DSM-3 (1980) and DSM-3 (1994): Checklists of
symptoms as diagnostic criteria. Diagnostic silos
Increase in the number of mental conditions with
each revision.
106 (DSM 1 + 2) 265 (DSM 3) 297 (DSM-4)

54

Diagnostic and Statistical Manual of

Mental Disorders (DSM)
DSM-5 was published in May 2013.
By the Book Economist May 18 2013
Key features:
- Reduce diagnostic silos because of evidence from
genetic studies and brain imaging.
- Has not reduced the number of mental conditions
(diagnostic inflation).
A psychiatric diagnosis is an important turning point
in anyones life.
Done well Life improving treatment.
Done poorly Inaccurate label, harmful treatment
55

Diagnostic and Statistical Manual of

Mental Disorders (DSM)
DSM-5 was published in May 2013.
By the Book Economist May 18 2013
Key features:
- Reduce diagnostic silos because of evidence from
genetic studies and brain imaging.
- Has not reduced the number of mental conditions
(diagnostic inflation).
Mourning a death depression.
Binge eating : eating to excess at least once a week
over past 3 months.
Aspergers disorder (high functioning autism) :
classified as a learning disorder.

56

A psychiatric diagnosis is
an important turning
point in anyones life.
Done well
Life improving treatment.
Done poorly
Harmful treatment, lower
self-confidence and
reduce self expectations

57