Transcript Exercise, Ethanol, and Disease

Cocaine and Stuff
by
C. Murray Ardies, Ph.D.
Cocaine
A white powder purified from the leaves of the
Erythroxylon coca plant native to the Andes Mountains;
especially in Peru.
Cocaine has been used for probably thousands of years
while the first written of cocaine use was written by
Amerigo Vespucci in 1499 about the early South
American civilizations.
Early use was by chewing the leaves of the plant and
even today many of the natives in the mountain regions
use the leaf on a daily (continuous) basis without
significant social problems.
The drug cocaine was purified around 1860 by the
French chemist Angelo Mariani and it subsequently
was added to a variety of products including the one
which introduced cocaine to the general population in
Europe (and beyond): Vin Mariani.
Products containing cocaine were widely used
throughout western civilizations because it clearly
“freed the body from fatigue, lifted the spirits, and
caused a sense of well-being”.
The Pope even gave Mariani a medal for his
contributions to society and the use of cocaine was
endorsed by many physicians and national leaders
before the turn of the century (Czar/Czarina of Russia,
Prince of Wales, Kings of Norway, Sweden, and even
President McKinley of the USA).
With the passage of the Harrison Act in 1914, the free
use of cocaine-containing products disappeared because
cocaine was mistakenly classified as a narcotic.
Recognition of the addicting and psychotic properties of
cocaine by medical personnel in the late 1880’s led to
diminished use in medicine.
Effects of cocaine are dependent on dose and route of
administration:
The medical use of cocaine was originally as a treatment
for morphine addiction and as a local anesthetic.
The need for increasing doses with continuing use to
prevent symptoms of narcotic withdrawal led to the
production of paranoid psychosis in patients. With high
enough doses, everyone will experience paranoid
psychotic (& violent) episodes.
Cocaine also is a good local anesthetic providing local
numbness as well as local vasoconstriction – ideal for
oral surgery. The development of derivatives which have
the same anesthetic effects of cocaine without the CNS
stimulation (such as Novocaine in 1906) replaced the
medical use of cocaine.
Oral
usually chewing leaves (or as part of
the many patent medicines and
potions) resulting in a dose of
approximately 20 to 400 mg
slow onset of action
mild & sustained CNS stimulation
least likely to cause addiction
Inhaling
Snorting powder into the nose resulting in an
approximate 100 mg dose into blood
Substantial CNS stimulation within minutes
& lasts 30 – 40 minutes
A rebound depression/dysphoria results within
minutes of the end of the “high”
Low likelihood of causing addiction
Intravenous Administration
Large (hundreds of mg) amounts of cocaine can
be injected
Intense CNS stimulation within seconds and
lasts 10 to 20 minutes
Intense depression and dysphoria; often reinject immediately – paranoia/psychosis
likely at high doses
Highly addicting
Smoking
Most often through use of a water pipe
Cocaine must first be “freebased” - dissolve the
cocaine in a base and then extract cocaine
with a (highly flammable) solvent and
smoke the resulting pure cocaine
More intense CNS stimulation than IV route
More intense depression/dysphoria than IV
route – paranoia/psychosis likely
Highly addicting (even more than IV use)
Crack
Available since 1985/1986; cheaper than cocaine
and can be smoked without use of solvents.
Made by mixing cocaine with baking soda,
removing both impurities and the HCl
Dried paste is ~90% pure cocaine and is smoked
Often considered a better “high” than smoking
freebased cocaine or IV administered cocaine
Most intense depression/dysphoria – paranoia/psychosis
likely
Highly addicting
(MOST?)
Cocaine Use By
High School Seniors
12
10
8
Total Cocaine
6
4
2
Crack
0
1975
1980
1985
1990
1995
2000
Cocaine abuse statistics are somewhat different than
for other drugs of abuse:
Of approximately 3 – 4 million (USA – 1998) regular
users about 650,000 are heavy abusers, about a 20%
incidence (2x the “normal” incidence of compulsive
abuse with most other drugs). Of these abusers, the
majority smoke the drug and usually progressed from
snorting – to IV – to smoking.
By looking at how the drug affects CNS activity one
may determine why the abuse potential of cocaine is so
high.
Cocaine Blocks Dopamine Re-Uptake
Amygdala
Frontal Cortex
Piriform Cortex
Striatum
Nucleus
Accumbens
Septum
High levels of dopamine in the
limbic system are associated
with feelings of intense pleasure
– especially the nucleus
accumbens; the site associated
with reward and locomotor
stimulation
Cocaine Blocks Serotonin Re-Uptake
Hypothalmus
High serotonin levels
enhance the reward
activity of elevated
dopamine in Nucleus
Accumbens
Corpus
Striatum
Substantia
Nigra
Amygdala
Serotonin receptors
are hypersensitive
during cocaine
withdrawal –
especially in amygdala
Cerebellum
Cerebrum
Withdrawal from cocaine leads to a substantial
reduction in serotonin release.
Decreased serotonin is associated with depression,
panic disorder, insomnia, impulsiveness and a hyperaggression behavior disorder.
Cocaine Blocks Norepinephrine Re-Uptake
Hypothalmus
Hippocampus
Amygdala
High levels of NE are
associated with the
feelings of arousal and
with high doses may
be responsible for the
“Rush”. Increased NE
enhances the
dopamine effects on
locomotor stimulation
Cerebral
Cortex
Cerebellum
Cocaine and Ethanol – A Real Problem
Alcohol potentiates the cocaine-induced euphoria and
diminishes the undesirable effects of cocaine
withdrawal. Most cocaine addicts also abuse ethanol
with as much as 77 percent using ethanol and cocaine
simultaneously and thirty percent reporting using
ethanol and cocaine together every time.
Cocaine is normally metabolized to benzoylecgonine
by a liver (lung & heart) carboxylesterase
In the presence of ethanol, however, it is made into
cocaethylene.
Cocaethylene:
~ 25x death incidence vs. cocaine alone
Hypertension due to increased vascular
resistance
Decreased myocardial function ( SV)
Decreased myocardial conduction &
Arrhythmogenic – blocks Na+ channels
much more effectively than cocaine.
Cocaine - Crack – Crime
(from: Goldstein, Inciardi/Pottieger, Fagan, Chin)
Systemic Crime - Resulting from the system of
drug distribution, “economic regulation and
control”: majority of drug-related homocides
Psychopharmacologically Driven Crime – Resulting
from drug use: 5% or less
Economically Compulsive Crime – financially
driven to crime by financial realities of the
drug use; ~ 98% of crimes comprise drug
sales to support habit, ~ half users commit one
property crime/week (shoplifting), prostitution