Chapter 6: Cocaine, Amphetamines, and Related Stimulants
The Coca Leaf
erythroxylon coca, the coca bush
history of use of coca
incas in bolivia, ecuador, and peru
spanish conquistadores
european naturalists studied coca
cocaine is extracted from coca leaves
Early Use of Cocaine
1800s: praised by physicians
used for many conditions, including morphine addiction
reports of addiction diminished its popularity
cocaine was controlled under the Harrison Narcotics Act of 1914
cocaine use declined
but, new stimulants entered
Rise of Amphetamines
synthetic compounds
amphetamine: Adderall, Benzadrine
dextroamphetamine: Dexedrine, Biphetamine
Methamphetamine: Desoxyn
uses
treats cold and sinus symptoms
assist weight loss efforts
counter narcolepsy
treat ADD/ADHD
stimulate wakefulness and alertness
abuse
increased after methamphetamine was prescribed to treat heroin addiction
injection → flash or rush
stimulant psychosis
The Return of Cocaine
1970s: movie stars and pro athletes glamorized cocaine
1980s: “smokeable”, less expensive forms became widely available
freebase cocaine
crack
all forms of cocaine can be lethal
Return of Methamphetamine
in 1980s & 90s, methamphetamine returned to popularity under new names
meth epidemiology
spread across US
club drug
involved in many treatment admissions
smokeable meth → intense rush
making meth involves explosive chemicals
effects of meth use
high-dose users: risk seizures, convulsions, and cardiovascular collapse
stimulant psychosis associated with violent behavior
depression is common feature of withdrawal syndrome
“meth mouth”
Bath Salts
rarely seen in US prior to 2009
marketed legally over the internet as bath salts or plant food
synthetic methcathinone is often sold as bath salts or plant food
three main synthetic cathinones
mephadrone
methylone
MDPV
administration
can be taken orally
more commonly consumed nasally or intravenously
effects
high-doses → acute psychotic effects and paranoia
regulation
three main synthetic cathinones: schedule 1 status
two of these drugs banned by the Prevention of Synthetic Drugs Act of 2012
mephadrone
MDPV
declined in popularity in US since 2012
Stimulant Pharmacokinetics
routes of administration
oral: 10-15 minutes
intranasal: 10-15 minutes
intravenous: 30 seconds
inhalation: even faster
duration of action
cocaine → metabolized rapidly
amphetamines → longer lasting
cocaine, amphetamine, and metabolites detectable in urine for 2-3 days
mechanisms of action
affect monoamine neurotransmitters
cocaine and amphetamines block reuptake
amphetamine and methylphenidate increase dopamine release
Mechanisms of Action
limbic system: reward system/circuit
dopamine released to dopamine receptors → proteins carry signal to rest of cell & leftover dopamine reenters presynaptic cell
when cocaine is in one’s system, it goes to brain and blocks the reuptake of dopamine, creating an influx of dopamine
Mechanisms of Action: Long Term
cocaine blues
features of cocaine-mood connection
depressed mood occurs: after single session, over long-term use
chronic users: depression of mood is greater and lasts longer
some alterations may be long-term or even permanent
Acute Effects: Low & Moderate Doses
physiological effects
similar for amphetamines, cocaine, and methylphenidate but duration differs
stimulants mimic sympathetic nervous system activity
anorectic effects
behavioral effects
increased elation & mood
more talkativeness and sociability
higher alertness and arousal
insomnia
enhanced physical endurance and strength
Stimulants & ADHD
most widely prescribed?
methylphenidate (ritalin, concerta)
amphetamines
adderall
stimulants do improve performance in kids with ADHD
ADHD: lower levels of dopamine and norepinephrine in PFC → trouble focusing, staying organized, & controlling impulses
stimulant medications increase dopamine and norepinephrine → help normalize brain activity
increase focus and sustained attention
decreased impulsivity and hyperactivity
increased ability to start and complete tasks
important note: stimulants don’t make people "smarter” but allow them to function more effectively in school, work, and daily life
not all behaviors can increase simultaneously
one type of activity may interfere with another
hyperactivity decrease because on-task activity increase
side effects?
are they overprescribed?
if you prescribe earlier on in life when they are children, children tend to have some of those symptoms naturally
Stimulant Effects in ADHD vs. Non-ADHD
in people with ADHD
boost dopamine & norepinephrine in underactive brain areas
improve focus, attention, and task completion
reduce impulsivity and hyperactivity
help normalize daily functioning (school, work, relationships)
in people without ADHD
may increase alertness or wakefulness (similar to caffeine)
mixed effects on memory and learning - no consistent academic benefit
no improvement in higher-level reasoning or problem-solving
risks: anxiety, insomnia, dependency, heart issues
Acute Effects: Stimulants as Study Aids
state-dependent learning
stimulants may impair performance in complex tasks and complex reasoning
Acute Effects: High Doses
stimulant psychosis
paranoid delusions
hallucinations
sometimes formication: feeling of things crawling on your skin
overdose death
heart attack, stroke, respiratory collapse from seizures
Effects of Chronic Use
tolerance
cocaine
acute tolerance to cocaine develops
protracted tolerance may occur
methamphetamine
tolerance develops to the positive subjective effects
reverse tolerance sometimes occurs
dependence
long abstinence syndrome
“crash”: several days of intense craving and exhaustion
withdrawal: several weeks of intense craving, depression, and inability to feel normal pleasure
extinction: months or years of cued craving
Effects of Chronic Use
exposure in utero
infants born to cocaine-using mothers have lower birth weights and higher mortality
they perform poorly on intellectual tasks, but no worse than other babies from similar backgrounds of maternal neglect and impoverished environments