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Lecture 7

PSYT 301 Lecture Notes - Lecture 7: Cocaine Dependence, Stimulant, Vin Mariani


Department
Psychiatry
Course Code
PSYT 301
Professor
Kathryn Gill
Lecture
7

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Chapter 7: Cocaine, the Amphetamines, and Other Psychostimulants
- the psychostimulants are drugs that exert their behavioural effects by augmenting the
action of the monoamine (biogenic amine) neurotransmitters, the most important of
which is dopamine
- sometimes these drugs are referring to as sympathomimetics because they activate
the neurotransmitters that stimulate the SNS and mimic sympathetic arousal
Cocaine:
History:
- cocaine is derived from the leaves of the erythroxylon coca plant, grown in the Andes
region of South America
- the plants ability to reduce fatigue, thirst and hunger was appreciated by the
aboriginal populations of the region, especially due to the effects of altitude sickness,
the original use included chewing or brewing a tea from the leaves
- in 1857 after Spanish settlers conquered the region, the compound was isolated and
named cocaine by the chemist Albert Niemann
- cocaine became a very popular additive to drinks and elixirs, most famously to Vin
Mariani, a mix of wine and cocaine
- John Pemberton created a similar product, but removed the alcohol when the city of
Atlanta banned alcohol, added soda water and kola nut syrup (containing caffeine),
this was the beginning of Coca-Cola
- at around the same time, with the invention of the syringe and needle, cocaine was
used as a local anaesthetic until procaine was developing in 1918, which was devoid
of the psychological and dependence-producing effects
- Sigmund Freud was an advocate of cocaine, to treat depression and alleviate chronic
fatigue, after he began to perceive its side effects (tolerance, dependence,
psychosis, withdrawal depression) he called it the “third scourge” of humanity, after
heroin and alcohol
- only in the late 1800s did the toxic effects of cocaine begin to worry policymakers, in
1914 the Harrison Narcotic Act banned the incorporation of cocaine in patent
medicines and beverages and cocaine use decreased in the 30s, and was replaced
by the use of amphetamines instead
- cocaine use remained very low until the 60s when federal restrictions on
amphetamine distribution raised costs, making cocaine more attractive
- in the 1980s the new epidemic of cocaine use began with the widespread availability
of crack cocaine which could be smoked (freebased)
Forms of cocaine:
- the E.coca leaf contains around 1% cocaine
- the leaves are soaked and mashed and cocaine is extracted in the form of
coca paste (60-80% cocaine)
- the paste is then treated with HCl to form the less potent, water-soluble salt
cocaine hydrochloride before it is exported, this form can be snorted or
injected
- cocaine base (crack cocaine) is insoluble in water but is soluble in alcohol,
acetone, or ether and is therefore smoked

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- very potent and addictive, as 60-90% of the cocaine reaches the brain
in about 10 seconds
- formed by mixing cocaine hydrochloride with baking soda and water
and heated until the cocaine crystals precipitate
- when sniffed, cocaine users might sniff around 50mg to 100mg of cocaine at
a time, whereas smoking crack yields average doses in the range of 250mg
to 1g
Pharmacokinetics:
- cocaine is absorbed from all sites of application, including the mucous membranes,
the stomach and the lungs
- Cocaine HCl crosses the mucosal membranes poorly because it is a potent
vasoconstrictor, therefore limiting its own absorption, and up to ~80% of the drug
may be biotransformed by the liver before it reaches the brain, so only ~20% of the
drug actually enters the blood
- when crack cocaine is smoked, absorption is rapid and complete, effects begin within
seconds and peak at 5 minutes
- IV cocaine HCl bypasses all barriers to absorption and places the total dose of drug
immediately into the bloodstream, takes 30-60s to circulate around the body and
reach the brain
- cocaine penetrates the brain rapidly, and brain concentrations far exceed the
concentrations in plasma
- after it penetrates the brain, it is rapidly redistributed to other tissues, and cocaine
freely crosses the placental barrier achieving equal levels in the fetus
- cocaine has a half-life of only about 50 minutes, as enzymes in plasma and the liver
metabolize it rapidly and almost completely
- butyrylcholinesterase is the major enzyme for metabolizing cocaine in humans
- cocaine is removed from the plasma rapidly, but it is more slowly removed from the
brain in which it can be detected for 8 or more hours after initial use
- urine can test positive for cocaine up to ~12 hours after use
- the major metabolite of cocaine is the inactive compound benzoylecgonine (BE),
which can be detected in the urine for between 48 hours and up to 2 weeks for
chronic users
- the persistence of BE in urine implies that high-dose, long-term users might
accumulate the drug in their body tissues
- cocaine and BE can also be detected in hair for several months, hair closest
to the scalp tested positive up to 4 months after use
- when alcohol and cocaine and injested together, the liver enzymes that metabolize
the two drugs produce a unique ethyl ester of benzoylecgonine called cocaethylene
which is pharmacologically as active as cocaine in blocking the PS dopamine
reuptake transporter, which increases the effect of cocaine
- this increases the risk of dual dependency, and the severity of withdrawal with
chronic use
- cocaethylene is more toxic than cocaine and is a potent calcium channel
blocker in the heart, this exacerbates cocaine’s toxicity, its half-life is also 3
times that of cocaine's, therefore outlasting it in the body
Mechanism of Action:

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- cocaine is the only drug that contains the 3 following pharmacological effects: it is a
potent local anesthetic, it is a vasoconstrictor and a powerful psychostimulant
- the vasoconstrictive and cardiac depressant actions contribute to severe
cardiovascular and cerebrovascular toxicities, while the stimulant properties are
responsible for the addictive potency
- cocaine blocks the reuptake of all monoamine neurotransmitters, most of its effects
are due to the blockade of dopamine reuptake
- raises the levels of dopamine in the synaptic cleft, increased DA levels in the
NAc and other components of the dopaminergic reward system are
responsible for the euphoric effects of the drug)
Pharmacological Effects in Humans:
- increased heart rate, blood pressure, vasodilation and bronchodilation
- body temp rises, pupils dilate, BG levels increase, blood flow to the muscles
increases
- subjective effects (low doses): increased energy and alertness, decrease in fatigue,
increased libido, euphoria, elevation of mood, reduced appetite, increased activity,
- typical duration is 10-20 minutes, followed by a mild depression
- tolerance develops quickly, can result in continuous cycles of cocaine use (“coke
runs”)
- may cause some users to switch from intranasal administration to injection or
freebasing
- as the dose or duration of use increases, the effects are intensified
- subjective effects at high doses: agitation, impulsiveness, anxiety, paranoia, paranoid
psychosis, unique symptom of cocaine-related psychosis is the feeling of bugs
crawling under your skin (formication), a compulsive, repetitive pattern of behaviour
may occur
- associated physiological toxicity may result in arrhythmias, convulsions,
stroke or fatal cardiorespiratory arrest
- even with no symptoms, heart imaging showed structural damage, fibrosis
and edema in cocaine users, 2 days after last dose
- complications associated with the cardiac effects can occur after a single
dose or repeated doses, and is the single largest cause of death associated
with cocaine, chronic cocaine users have an increase in aortic stiffening,
higher systolic BP and greater thickness of the left ventricle
- when the acute effects wear off, a user may experience depression, dysphoria,
anxiety, somnolence and drug craving, sexual dysfunction is common in heavy and
chronic users as they lose interest in interpersonal and sexual interactions
- cocaine dependence can cause brain damage, overall loss of grey matter, duration of
cocaine use was related to the amount of brain damage (matter) lost
- cocaine also plays a role in car crashes, as it may cause visual deficits, alterations in
judgment, incoordination and feeling of power
- an acute toxic dose of cocaine is about 2mg per kg of body weight, thus 150mg of
cocaine is a toxic one-time dose for a ~150lb person, serious physiological toxicity
follows higher doses
Comorbidity:
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