Histogram
8
7
6
Count
5
4
3
2
1
0
50
55
60
65
70
75
80
X! plus
85
90
95
100
Major Stimulants
.
Cocaine
Amphetamine
Cocaine

Coke, Dust, Snow,
Flake, Blow, Girl
Cocaine: Forms

Coca leaf ( from Erythroxylum coca ) – < 2% cocaine
Cocaine HCL – Powder; high cocaine content

Freebase/Paste- high cocaine content /smokable


Crack – Rock cocaine- high cocaine content/
smokable cheaper/safer to produce
The Psychological Effects of
Cocaine








Euphoria
Increased Vigilance
Reduced reaction time
Increased strength and endurance
Insomnia
Anorexia
Mood elevation
Increased endurance
High Dose & CNS

Higher doses


intense feeling of euphoria
described as “whole body
orgasm”
COCAINE- Sympathomimetic Effects






Increased heart rate
Increased blood pressure
Increased respiratory rate
Pupil dilation
Vasoconstriction
Increased sweating
History of stimulant use


Coca and the Inca
Archaeological evidence of coca use by
Incans – 5000 B.C.




Native tribes of the Andes have
chewed the coca leaf for centuries.
The coca plant was considered as
divine. (Leaves contain 1% cocaine).
Mountain natives chewed balls of
leaves almost continually, distances
were measured by the number of
stops required to maintain dose level.
Use of the Coca leaf has a long history and remains a
tradition even today amongst some Native South
Americans.
Habitual Coca-leaf chewing is not generally regarded as a drug
addiction. However it is known that this habit is associated with
minimum food consumption, which may in some cases adversely
affect intellectual and physical functions.
South American Issue
today: Smoking basuco:
http://www.youtube.com/watch?v=UclSEhNdUK8
( making cocaine)
Coca Paste: The paste is the
middle step between the leaf and
the powder cocaine. It is much
more likely to cause dependence. It
is generally very cheap in the
Andes countries. Coca paste is
much more popular in South
American countries then in the
United States. (but see “PACO.”
History of Cocaine.. cont’

Spanish explorers noticed the anti-fatigue effects of coca.
Encouraged its’ use by natives to increase their work efforts ….
used coca leaf as payment…
Around 1855 , Albert Neiman isolated
cocaine from the coca leaf and described the
anesthetic action of the drug when it was put
on his tongue.
The Rising Popularity of Cocaine -Late 1800’s
1870 Vin Mariani (Coca wine) was for sale
throughout France; containing 6 mg cocaine per
ounce of wine.
In the U.S.- Metcalf’s
Wine of Coca

Public speakers, singers, and actors have
found Wine of Coca to be a valuable tonic to
the vocal cords. Athletes, pedestrians and
base ball players have found by practical
experience that a steady course of coca
taken both before and after any trial of
strength or endurance will impart energy to
every movement and prevent fatigue. Elderly
people have found it a reliable aphrodisiac
superior to any other drug...
The Rising Popularity of Cocaine –
THE REAL THING!?
In 1886, John Pemberton developed Coca Cola, a drink
that contained cocaine and caffeine. Cocaine was
REMOVED from Coca Cola in 1901 (but it still has the
caffeine).
The Rising Popularity of Cocaine Sigmund Freud (1884)

..in 1884, recommended cocaine
for a variety of illnesses and for
alcohol and morphine addictions.
Changing Sentiments

Unfortunately, many of his
patients ( and his Friend “Ernst
Von-Fleischl) went on to become
addicted to cocaine and
experience “cocaine
Psychosis.” Freud Later
retracted his statements and
support of the substance.
Annie C. Meyers- Changing
Public Sentiment


A “well-balanced Christian women” before
becoming a “cocaine fiend”
“I deliberately took a pair shears and pried
loose a tooth that was filled with gold. I
then extracted the tooth, smashed it up,
and the gold went to the nearest
pawnshop, blood streaming down my face
and drenching my clothes, where I sold it
for 80 cents to buy cocaine.
Around this time ( late 1800s and early 1900 ) there were also many reports of cocaine-related
acts of violence. There was also a propaganda campaign aimed at associating cocaine use with
minorities and minority violence.
History of Cocaine

Harrison Narcotic Act of
1914
 Banned cocaine in the
U.S.
History of Cocaine
John Belushi


By 1930s, cocaine pretty
much disappeared, but
was replaced by
amphetamine.
By the late 1970s, coke
began a comeback and
use levels exploded
around 1985
In November of 1983 colorful
former Cowboys linebacker
Thomas “Hollywood” Henderson
was arrested for smoking crack
with two under-aged teenage girls.
In the
meantime…AMPHETAMINES

Developed in the
1920’s but not utilized
until the 1930’s
Amphetamines Effects..much like the
Effects of Cocaine but with longer
durations








Euphoria
Vigilance
Reduced reaction time
Increased strength and endurance
Insomnia
Anorexia
Mood elevation
Increased endurance
Amphetamines- effects
on endurance
Performance on bicycle machine after control
and 10 mg methamphetamine injections
3000
REVS/15 min
Drug
2800
2600
2400
Control
2200
2000
1
2
3
HOURS
4
5
Amphetamine: Forms




d-amphetamine
l-amphetamine
methamphetamine
Methamphetamine is
more potent than damphetamine, which is
more potent than lamphetamine
“Ice” or “Crank”


Meth Crystals….
Pure dmethylamphetamine
HCL
(pure methamphetamine will naturally
form crystals)




Is easier to vaporize ( smoke)
because of lower melting point.
Started in the West moved east
over time
Labs all over Duplin Co.
Very dangerous to synthesize
Amphetamines ( again..like cocaine
effects but longer) - Sympathomimetic
Effects







Increased heart rate
Increased blood pressure
Increased respiratory rate (dilation
of bronchial villi of the lungs)
Pupil dilation
Changes in blood flow
Increased sweating
body temperature
Amphetamine: A Brief History
•
1930s U.S. – benzedrine marketed for treatment of
asthma, narcolepsy, depression, appetite suppression
(bennies)
Amphetamine: A Brief History
cont’
•
Also used to keep soldiers alert during combat in WWII
•
After war, prescribed for fatigue and appetite
suppression
Amphetamine in the
1960’s

Early 1960’s - Unfortunately prescribed by physicians to
treat heroin addiction….
Dramatic explosion in the drug
using sub-culture of the 1960's and
very early 1970's.
“SPEED FREAKS.”
Many say that the introduction of
amphetamine ended the true “hippie
culture” of the 1960’s San Francisco
scene
Amphetamine use in the 1960’s
cont’


The typical Speed freak would display a
pattern of:
Massive doses, and re-dosing: RUNS- lasting
2-5 days.
All in pursuit of the “full body flush (orgasm)”
However, these runs were inevitably followed by the “CRASH”
CRASH: Sleep for 24 hours or more ..and other more
serious problems
Speed
Kills...
…was a slogan that emerged about this time..
Though O.D.s are fairly rare…amphetamine
toxicity syndrome ( amphetamine Psychosis..
often lead to acts of violence).
By Mid 60’s popular use was
significantly declining.
Amphetamine use diminished in the
1970’s and 1980’s…but…
•
now back up –primarily methamphetamine use.. smoked,
snorted, injected or taken orally – ice, crank, crystal,
speed, meth, chalk






Message from the Director on "Bath Salts" Emerging and Dangerous Products
"Bath Salts", the newest fad to hit the shelves (virtual and real), is the latest addition to a growing list of items that young people
can obtain to get high. The synthetic powder is sold legally online and in drug paraphernalia stores under a variety of names,
such as "Ivory Wave," "Purple Wave," "Red Dove," "Blue Silk," "Zoom," "Bloom," "Cloud Nine," "Ocean Snow," "Lunar Wave,"
"Vanilla Sky," "White Lightning," "Scarface," and "Hurricane Charlie." Because these products are relatively new to the drug
abuse scene, our knowledge about their precise chemical composition and short- and long-term effects is limited, yet the
information we do have is worrisome and warrants a proactive stance to understand and minimize any potential dangers to the
health of the public.
We know, for example, that these products often contain various amphetamine-like chemicals, such as
methylenedioxypyrovalerone (MPDV), mephedrone and pyrovalerone. These drugs are typically administered orally, by
inhalation, or by injection, with the worst outcomes apparently associated with snorting or intravenous administration.
Mephedrone is of particular concern because, according to the United Kingdom experience, it presents a high risk for overdose.
These chemicals act in the brain like stimulant drugs (indeed they are sometimes touted as cocaine substitutes); thus they
present a high abuse and addiction liability. Consistent with this notion, these products have been reported to trigger intense
cravings not unlike those experienced by methamphetamine users, and clinical reports from other countries appear to
corroborate their addictiveness. They can also confer a high risk for other medical adverse effects. Some of these may be linked
to the fact that, beyond their known psychoactive ingredients, the contents of "bath salts" are largely unknown, which makes the
practice of abusing them, by any route, that much more dangerous.
Unfortunately, "bath salts" have already been linked to an alarming number of ER visits across the country. Doctors and
clinicians at U.S. poison centers have indicated that ingesting or snorting "bath salts" containing synthetic stimulants can cause
chest pains, increased blood pressure, increased heart rate, agitation, hallucinations, extreme paranoia, and delusions. It is
noteworthy that, even though we are barely two months into 2011, there have been 251 calls related to "bath salts" to poison
control centers so far this year. This number already exceeds the 236 calls received by poison control centers for all of 2010. In
response to this emerging threat, several states, including Hawaii, Michigan, Louisiana, Kentucky, and North Dakota, have
introduced legislation to ban these products, which are incidentally labeled as "not fit for human consumption." In addition,
several counties, cities, and local municipalities have also taken action to ban these products.
We will continue to monitor the situation and promote research on the extent, pharmacology, and consequences of "bath salts"
abuse. In the meantime, I would like to urge parents, teachers, and the public at large to be aware of the potential dangers
associated with the use of these drugs and to exercise a judicious level of vigilance that will help us deal with this problem most
effectively.
Sincerely, Nora D. Volkow, M.D.
Director National Institute on Drug Abuse
Controversies in the 1970’s(While Amphetamine use declined Cocaine use
Resurfaced )The Cocaine Comeback:
14
Percent Using
High School Seniors reporting cocaine use
12
10
8
6
4
WHY??
2
0
75
80
85
90
95
00
05
Percentage of High School Seniors Reporting Use
of Cocaine During the Past Year
Factors contributing to the cocaine
comeback in the 19070’s and 80’s


Some otherwise respected scientists made quite
controversial claims….
“Cocaine is not an addictive or especially dangerous
drug. It should be legalized” (Ashley, 1976)
Maybe Ashleys’ Ideas are
somewhat accurate when
assessing cocaine use by
intranasal administration

However, it is now quite clear that
the abuse potential for cocaine
depends much on the form of
cocaine that is used, and the route
of administration…
Cultural association of cocaine, money
and glamour-Famous Cocaine users of the
1970’s and 80’s
Tim Allen
Robin Williams
Cocaine in the Nineties:
The Crack Phenomenon
Crack is the smokable form of
cocaine. Cocaine hydrochloride is
treated by mixing with baking soda
and water…the water is boiled
off..the process leads to audible
“cracking sounds,…the result is
“Crack cocaine.”
Cocaine in the Nineties:
The Crack Phenomenon
CRACK COCAINE
Less expensive
More intense effects (Shorter duration of action)
More risk of overdose
Much higher rate of addiction
Mechanisms of action- Cocaine


Cocaine blocks the reuptake of monoamine
neurotransmitters; DA, NE and 5-HT in the brain.
Therefore, these neurotransmitters stay in the synaptic
cleft for a longer time and repeatedly activate postsynaptic
receptors.
Mechanisms of action- Cocaine


cocaine can also cause the release of dopamine from
neurons in the brain.
The effects of this indirect monoamine agonist on the
PNS account for its’ sympathomimetic actions.
Amphetamines-Mechanism of
Action


amphetamine effects are very similar to those
of cocaine, but longer in duration…
Blocks reuptake of monoamines: dopamine,
serotonin and norepinephrine
COCAINE VS AMPHETAMINES?


Cocaine & amphetamine indistinguishable to IV
users
Oral or nasal route - local anesthetic properties
would set them apart
Cocaine and Amphetamine block reuptake of dopamine
Cocaine-Pharmacokinetics

Inhalation (smoking) & IV injection
 Onset:

< 2 min
For both routes
 Duration
of action – 5-10 min.
Cocaine -Pharmacokinetics

Oral -Essentially ineffective for
cocaine ( see first pass effects).
 effective
for amphetamine
analogs
 onset: 30 minutes / peak 2-3 hrs

Intranasal
 onset
3-4 minutes
 peak effects: 15-30 minutes ~
Amphetamines



Amphetamine
(6-8 hrs)
Dextroamphetamine
(8-10 hrs)
Methamphetamine
(12+ hrs)
In case you’re interested/Cocaine:
Local Anesthetic
 Inject

SC
Half-life: 1 hr
 Numbing
< 2 min
 Peak effects: 15-20 minutes

Pharmacodynamics
 Blocks
Na+ channels
 Constricts blood vessels ~

Cocaine
Pharmacokinetics:
Metabolism
 Broken
down by liver enzymes
 Half-life:  1 hr

Amphetamines
 In
liver,
 Half-life: 7-30 hrs ~
TOLERANCE

Tachyphylaxis- especially for the positive
effects of these drugs
 brief
& transient tolerance
 reuse within minutes - hours
SENSITIZATION / Reverse
Tolerance- (induced with lower doses)
Psychomotor stimulant induced stereotypy repetitive behaviors.
In rats, stereotypic behaviors may include head sways,
hyperactivity, avoidance
behaviors, and
automutilation (self-mutilation).
Punding – a repetitive and essentially useless complex
behavior. The human equivalent of drug-related stereotypy.
Psychomotor stimulant
sensitization

Stereotypy/ Punding
 Probably
associated with effects
on basal ganglia…initially a
kind of hyperactivity
 With repeated high dose use may
become Parkinson like (pill rolling
finger movements, ataxia or
unsteady gait).
ADVERSE Effects of the
Psychomotor Stimulants
Adverse effects of occasional
intranasal use of cocaine is
debatable.
However, repeated use, especially if high
doses are used has clear adverse
consequences- Stimulant Psychosis
Psychotomimetic Effects

Schizophrenia-like psychosis
 Paranoia
 Delusions
 Hallucinations:
parasitosis/Formication syndrome
Methamphetamine
 earlier
developing
 may persist for days, weeks ~
Additional Symptoms of
Psychomotor Stimulant
TOXICITY









Aggression/violence
Degeneration of nasal mucosa
(cocaine)
Rotting teeth
Dry, itchy skin
Numbness
Insomnia
Extreme body temperature
Depression
stroke
Video on Meth toxicity
Friendly Fire… you may have thought
that the military had learned for WWII,
but…(aggression)
 “Go
pills” in the US military
 April 2002 bombing of a Canadian
unit in Afghanistan killed 4 and
wounded 8
 Both US pilots were under the
influence of “go pills”
 June 2003 court martial for
“dereliction of duty” (dropped
manslaughter charge)
Lethality

Cocaine
 Oral:
500 mg
 Nasal: 150-300 mg

Amphetamine/Methamphetamine
 toxic
effects: 15 mg in novices
 lethal 500-1700 mg

Inhalation (smoked): much lower ~
Cocaine Overdose

John Belushi
Cocaine Overdose
Stimulant Overdose


Convulsions; seizures
Cardiac failure
DAWN COCAINE O.D.
Emergency Room Visits due to Cocaine and Heroin Image courtesy of the Office of National Drug Control
Policy
Cocaine/Methamphetamine
Dependence & Abstinence





Crash
Depression
Withdrawal
Extinction/cravings
Residual effects: Meth and
dopamine damage—cognitive
impairment (Chang, 2003)
Cocaine Abuse:
Animals


Self-administration
Will work hard to get
 progressive

FR6400
Continuous access:
 Weight
loss
 Self-mutilation
 parasitosis?
 Death
within 2 weeks ~
Cocaine Abstinence Syndrome
Phase 1: Crash
9 hrs - 4 days
Binge
Relapse
Phase 2: Withdrawal
1 - 10 weeks
Early
•Agitation
•Depression
•Anorexia
•High Craving
Early
•Normal sleep
•Normal mood
•Low anxiety
•Low craving
Middle
•Depression
•Fatigue
•Insomnia
•No craving
Middle & Late
•Anhedonia
•Anergia
•Anxiety
•High Craving &
conditioned cues
Phase 3: Extinction
indefinite
•Normal hedonic
response
•Normal mood
•Episodic craving
•Conditioned cues
trigger craving
Abstinence
Late
•Exhaustion
•Hypersomnolence
•Hyperphagia
•No Craving
Gawin & Kleber (1986)
Increase in Meth-lab
seizures 2000-2004




Washington—0
California—(-66%)
Illinois—730%
North Carolina—2171% (318
busts)
House Bill 248: Meth
Lab Prevention Act



Signed by Gov. Easley Sept. 28th
2005; Into effect Jan. 2006
All products containing ephedrine
and pseudoephedrine sold behind
the counter
Purchasers over 18 and must
show ID and sign log
Attention Deficit Disorder





Hyperactivity and the “paradox”
Amphetamine (Adderall)
Methylphenidate (Ritalin,Concerta)
10 million + prescriptions per year
700% increase between ’92 & ‘04
The ADHD Controversy





Is it a disease?
Do stimulants work?
ADHD in adults
Side effects: growth suppression
Abuse