Designer and
Performance-Enhancing Drugs
BBH 143: Drugs, Behavior, and Health
Week 15 (December 3-9, 2023)
Dr. Jeffrey W. Brown
Getty Images
Today’s Learning Objectives
• Define the term “designer drug” and describe the
interplay between how these drugs are regulated and
how those regulations are bypassed.
• Cultivate a basic understanding of synthetic
cathinones, synthetic cannabinoids, and several other
designer drugs, contrasting their effects to their
“parents” drugs.
• List major performance-enhancing drugs, and provide a
brief history of their use in both international and
American sporting events.
• Characterize the performance-enhancing potentials of
anabolic steroids, human growth hormone, and
erythropoietin, while exploring their side effects.
2
What is a “Designer Drug”?
• Designer drug: a synthetic drug that is a structural or
functional analog (_____________________________
_______________________________) of another drug
– Generally designed to evade legal restrictions, while
maintaining or enhancing potency relative to the “parent”
drug
• Selected examples
–
–
–
–
–
Synthetic cathinones
Synthetic cannabinoids
25I-NBOMe (25I)
MPTP and MPPP
Drugs we’ve covered?
• Thousands of designer drugs exist
3
Wikipedia
History and Regulation of
Designer Drugs
• Earliest examples were analogs of morphine and heroin in the
1920s
• Synthetic hallucinogens (e.g., DOM, LSD and PCP analogs) became
popular in the 1960s and 1970s
• The term “designer drug” was coined in the 1980s and gained
traction due to the recreational use of MDMA and synthetic opioids
– Laws were passed to enable 1-year emergency scheduling by the DEA
pending permanent scheduling
• Federal Analog Act of 1986: drugs structurally or pharmacologically
similar to listed Schedule I or II drugs can be automatically placed in
Schedule I
– Synthetic Drug Abuse Prevention Act of 2012
added 26 more widely used designer drugs to
Schedule I
– Black-market drug chemists are still finding
ways to circumvent these laws:
•
•
DEA
4
Today’s Learning Objectives
• Define the term “designer drug” and describe the
interplay between how these drugs are regulated and
how those regulations are bypassed.
• Cultivate a basic understanding of synthetic
cathinones, synthetic cannabinoids, and several other
designer drugs, contrasting their effects to their
“parents” drugs.
• List major performance-enhancing drugs, and provide a
brief history of their use in both international and
American sporting events.
• Characterize the performance-enhancing potentials of
anabolic steroids, human growth hormone, and
erythropoietin, while exploring their side effects.
5
Synthetic Cathinones
• Aka “bath salts”
– Sometimes labeled as “plant food,” “jewelry cleaner,” or “phonescreen
cleaner”
• A cathinone is a stimulant found in the
khat plant (East Africa and Arabian peninsula)
– Pharmacology similar to the amphetamines
– Synthetic cathinones are typically far
more potent than natural cathinones
• First synthesized in the 1920s, but began emerging for recreational
use in the United States around 2010
– Poison control centers received over 6,100 calls related to synthetic
cathinones in 2011 (peak use)
– Many made illicit via the Synthetic Drug Abuse Prevention Act of 2012
• Examples: MDPV, mephedrone, alpha-PVP* (aka flakka, gravel)
– Many available bath salts contain one or more of these
• Lifetime prevalence was ~1% among high school seniors in 2015
Goldberg and Mitchell, Drugs Across the Spectrum (8th ed.)
*Sometimes treated as distinct from bath salts
6
Effects of Synthetic Cathinones
• Similar to effects of cocaine and amphetamines,
but more potent
– Usually snorted
• Possible acute effects: tachycardia, hypertension,
euphoria, paranoia & hallucinations, panic
attacks, increased sociability and sex drive,
extreme agitation and aggression
– Documented overdose deaths (e.g.,
heart attack, liver/kidney failure) and
suicides
– Few data on chronic effects
Alpha-PVP (Flakka)
“Zombie Drug”-The Truth About Flakka (VICE News)
7
Synthetic Cannabinoids
• Most synthetic cannabinoids are designed with the
same pharmacology as THC (________________
_________________________), but with higher
potency
• Typically sold as liquid-infused plant matter to be
smoked or liquid to be vaped
–
–
–
–
Common street names include Spice and K2
Consists of a mix of synthetic cannabinoids
~700 available blends
Many constituents of Spice banned
by the Synthetic Drug Abuse Prevention
Act of 2012
• Use thought to have peaked in 2015
with 7,800 calls to poison control centers
Goldberg and Mitchell, Drugs Across the Spectrum (8th ed.)
8
Effects of Synthetic Cannabinoids
• Physiological and psychological effects similar to natural marijuana,
but with higher risks of toxicity and withdrawal
• The most severe signs/symptoms include:
– Severe agitation, tachycardia, hypertension, nausea and vomiting,
tremors/seizures, intense hallucinations and/or psychotic episodes,
suicide or suicidal ideation
Prevalence of Psychiatric Symptoms, Synthetic Cannabinoid & Cathinone Use (FYI) 9
Castaneto et al., 2014 (via Psychiatric Times)
MPPP (FYI)
• Derived from the fully synthetic opioid pethidine
(Demerol)
• MPPP was first synthesized in 1947 in an effort to
create a painkiller less addictive than morphine
• 23-y.o. graduate student Barry Kidston re-synthesizes the
drug in 1976 as a legal recreational alterative to pethidine
and self-injects
– Develops Parkinson’s disease-like signs within three days
– MPTP is a toxic byproduct of improper MPPP synthesis that
irreversibly kills dopamine neurons in the brainstem
– As many as 120 additional people using MPPP were diagnosed
with parkinsonism in the 1980s
• No present documentation of recreational MPPP use, but
currently used in Parkinson’s research
MPPP=Desmethylprodine (FYI)
10
25I-NBOMe (25I)
• Synthetic psychedelic, aka “N-bomb”
– Pharmacodynamics: ___________________________________
• First synthesized in 2003 for research purposes
– Enters into recreational use in 2010
– Common modes of administration include buccal, sublingual,
and intranasal
• Similar effects to LSD, but with greater potential for toxicity
– Cardiotoxicity (e.g., hypertension, tachycardia), delirium,
aggression, seizures, organ failure
• How does this compare to classic psychedelics?
– Linked to at least 19 overdose deaths
in the US as of 2023
• Placed in temporary Schedule I on an
emergency basis in 2013  since made permanent
11
WTSP
Today’s Learning Objectives
• Define the term “designer drug” and describe the
interplay between how these drugs are regulated and
how those regulations are bypassed.
• Cultivate a basic understanding of synthetic
cathinones, synthetic cannabinoids, and several other
designer drugs, contrasting their effects to their
“parents” drugs.
• List major performance-enhancing drugs, and provide
a brief history of their use in both international and
American sporting events.
• Characterize the performance-enhancing potentials of
anabolic steroids, human growth hormone, and
erythropoietin, while exploring their side effects.
12
Introduction to
Performance-Enhancing Drugs (PEDs)
• Aka ergogenic drugs
• Can be used to enhance athletic, combat, or academic
performance
– Use of such drugs in sports=“doping” or “juicing”
• Variety of PEDs
–
–
–
–
Anabolic steroids
Human growth hormone (hGH)
Erythropoietin (EPO)
Nutritional supplements
• Creatine
• Androstenidione
– Stimulants (e.g., cocaine, amphetamines, ephedrine, caffeine)
– Depressants (e.g., barbiturates, benzodiazepines, opioids,
alcohol)
– Marijuana
EM Resident
13
Early History of PEDs in Athletics
• Precedents in Ancient Greece, Roman, and the
Aztec Empire
• Strychnine (__________________________),
cocaine (e.g., Coca Wine), and caffeine all
used in 19th Century and early 20th Century
Aztec Game Ulama
Manzanillo Sun
Tom Hicks at the 1904 Olympics
14
PEDs in International Sporting
• First-documented use of amphetamines was at the
1952 Winter Olympics
– Safer than strychnine, more potent than caffeine,
longer-lasting than cocaine and legal
• Anabolic steroid use became the norm by 1956
Olympics, out in the open by 1968
• Regulation
– International Olympic Committee establishes rules
for drug testing (1968)
Kornelia Ender
– World Anti-Doping Agency (WADA) updates prohibited (1976 Olympics)
PEDs, testing requirements, and penalties across all sports;
200 countries ratify (2009)
• Recent Incidents of Note
– US Anti-Doping Agency bans cyclist Lance Armstrong
for life in 2012 for using EPO, testosterone,
corticosteroids, and masking agents
– 2014 Winter Olympics: state-sponsored Russian
scheme involving tainted urine samples
Getty Images
Lance Armstrong Documentary
Lance Armstrong
15
(2004 Tour de France)
PEDs in American Professional Sports
• Amphetamine use in the NFL (American football) was common in
the 1960 and early 1970s
– Frequently supplied by trainers, prescribed by doctors
– Banned by NFL in 1971 after player lawsuits
• It is thought that 50-90% of NFL players were on anabolic steroids
before it was banned in 1983
• Congress passes the Anabolic Steroid Control Act (1990), moving
anabolic steroids to Schedule III
– Effectively bans anabolic steroid use in professional sports
• Despite 1991 ban by MLB (baseball),
no regular testing was done until 2005
– Scandals plagued the MLB during
the late 1990s and early 2000s based
on unprecedented record breaking
– Culminated in BALCO Scandal
(2002-2011)
Baseball’s Steroid Era Explained
Major League Baseball (via Stamford Crimson)
16
Former MLB Players Known to Use PEDs
Statistics on PED Use in Sports (FYI)
WADA, 2019
WADA, 2016
*ADRV=anti-doping rule violation
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Today’s Learning Objectives
• Define the term “designer drug” and describe the
interplay between how these drugs are regulated and
how those regulations are bypassed.
• Cultivate a basic understanding of synthetic
cathinones, synthetic cannabinoids, and several other
designer drugs, contrasting their effects to their
“parents” drugs.
• List major performance-enhancing drugs, and provide a
brief history of their use in both international and
American sporting events.
• Characterize the performance-enhancing potentials of
anabolic steroids, human growth hormone, and
erythropoietin, while exploring their side effects.
18
Anabolic Steroids and Testosterone
• All structurally and pharmacologically related to the
androgen (_________________) testosterone
• Testosterone has
– Androgenic effects: development of primary and secondary
sexual characteristics during puberty
– Anabolic effects: increasing muscle mass, bone density, protein
synthesis, controlling body fat distribution
• Synthetic steroids have
fewer androgenic effects and
greater anabolic effects
• Therapeutic uses: bone
marrow stimulation, treatment
for growth failure, osteoporosis,
induction of puberty,
masculinizing hormone therapy
Effects of Testosterone in Puberty
19
Bouvattier and Young, 2020
Anabolic Steroids as PEDs
• Doses of anabolic steroids as PEDs are at least 5-29X
recommended therapeutic dose
– May be administered orally, intramuscularly, or topically
• Vigorous exercise causes microtrauma in muscles,
which the body naturally repairs
– Repair generates larger, strong muscles
– Anabolic steroids accelerate this process by 2X
• Average user is 30-y.o.,
educated, not-particularlyathletic White male (explanation?)
– About 1% of undergraduates
report using anabolic steroids
Craig Davidson’s Story
20
Possible Physiological Side Effects of
Anabolic Steroids
• Effects on all users: acne, immunosuppression,
hypertension, liver tumors, cardiovascular disease,
dysregulated cholesterol levels
• Effects on men: gynecomastia
(_________________), priapism
(_______________), atrophied
testicles, infertility, baldness
• Effects on women: decreased
breast size, deepened voice,
menstrual irregularities,
increased facial hair,
enlarged clitoris, baldness
• Effects on pubescent adolescents: stunted height,
increased penis size (male), delayed puberty (female)
Bond et al., 2022
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Possible Psychological Side Effects of
Anabolic Steroids
• Elevated self-esteem, feelings of power, irritability
• “Roid Rage”: an apparent form of mania marked by
uncontrolled violent outbursts
– Is this an actual phenomenon?
– Controlled studies correlate anabolic
steroid use to aggression and
hypomania in some individuals
– Actual correlation might be stronger (why?)
• Muscle dysmorphia: a type of body dysmorphic
disorder in which steroid users perceive their bodies to
be weak and small, contrary to objective reality
• >20% of users of anabolic steroid users might deal with
psychological dependence
22
Image
Human Growth Hormone (hGH)
• Hormone released by the pituitary gland
– Stimulates growth, cell reproduction and regeneration
• Originally harvested from cadavers for use as a PED
– Now genetically engineered
• Increases lean muscle mass but not strength or
endurance in younger athletes
– Some evidence of increased muscle strength in men over
50
• Possible side effects include
acromegaly
– Increase in size of head, hands and
feet, damage to internal organs
hGH-Induced Acromegaly
Slater et al., 2023
23
Erythropoietin (EPO)
• Naturally produced in the kidneys to increase
production of red blood cells
(function: ___________________________)
• Recombinant human erythropoietin (rhEPO) has
been used as a PED
– Mechanism:
– This is called blood doping
• Possible side effects:
blood clots (leading to heart
attack or stroke), anemia,
increased risk of autoimmune
diseases
iStock (ttsz)
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Next Time…
• The final exam 
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