Stimulant Drugs (Cocaine and Amphetamine)

what are the routes of administration for cocaine and amphetamine?

ingested, injected, snorted, smoked, topically (cocaine)

what neurotransmitters are directly affected by cocaine & amp?

dopamine, norepinephrine, serotonin

why do usually take cocaine?

rush and euphoria

• greater self-confidence

• super social, more flirtatious

what is the most common route of administration for cocaine?

inhalation

what culture has a big history of cocaine?

Inca culture in south America

what are the three places are the most common for cocaine cultivation?

• Columbia

• Peru

• Bolivia

which psychologists was a big advocator for cocaine use?

Freud

Is cocaine in the top 5 most used drugs in Canada?

yes, it is the 3rd highest drug

what age group is reported to use cocaine the most (based on 2018 report)?

young adults from the age of 20-24

Internationally, which countries have the most use of cocaine?

• USA

• England and Wales

• Australia

What are the two methods in which cocaine HCL can be smoked?

• freebasing

• crack

what is the fastest route of administration for cocaine?

IV

what is the slowest route of administration for cocaine?

oral

What is the half life for cocaine?

0.5 - 1.5hours

Which dopamine system plays the biggest role in cocaine mechanism of action?

mesolimbic DA system

What voltage fate does cocaine have an effect on for higher concentrations?

inhibits voltage-gated Na+ channels in axons, blocking nerve conduction

sympathomimetic drugs

produces symptoms of sympathetic nervous system activation

formication

delusion that insects are crawling in and under one’s skin

why is methamphetamine more likely to cross the BBB?

the added methyl component

which molecular form of amphetamine is most typically used recreationally?

d-amphetamine

modern day use: amphetamines are used to treat what type of disorder/illness?

narcolepsy

“go pills” or “pep pills”

soldiers in WWII used amphetamines to fight fatigue

psychomotor stimulants

class of drugs that produce strong sensorimotor activation characterized by increased alertness, heightened arousal, and behavioral excitation

amphetamine

increases neurotransmitter release from catecholaminergic neurons

methylphenidate

synthetic psychostimulant that blocks catecholamine and serotonin reuptake and is used to treat ADHD

characteristics stimulants

• ability to increase alertness

• heighten arousal

• cause behavioral excitement

Differences in mechanism of action in amphetamine compared to cocaine

• they go into the neuron

• stimulate dopamine release from vesicles

• move through transporter outside of the cell

• end up with dopamine depletion

what is the “crash” stage during an amphetamine binge?

you fall below baseline/normal state, you become extra tired or depressed

Why do they add mineral lime or ash to make the pH of the saliva more alkaline when chewing coca?

it decreases ionization of the cocaine and promotes absorption across the mucous membranes of the oral cavity

cocaine use disorder

DSM-5 diagnostic category referring to maladaptive use of cocaine

what is the chemical structure of alkaloidal cocaine

contains two rings:

• six-carbon phenyl ring

• unusual nitrogen (N) containing ring

how can cocaine HCL (hydrochloride salt) be consumed?

water soluble

• orally

• intranasally

• IV injection

freebasing

smoking the form of cocaine obtained by dissolving cocaine HCL in water, adding an alkaline solution, and then extracting with an organic solvent

crack

form of cocaine made by adding baking soda to a solution of cocaine HCL, heating the mixture, and drying the solid

which form of consumption produces chemical products that can be detected in urine and used by forensic chemists to verify crack use?

heat involved in smoking crack

which forms of consumption occur extremely rapidly?

IV injection and smoking

benzoylecgonine

major metabolite of cocaine

cocaethylene

metabolite formed from the interaction of cocaine and alcohol. it produces biological effects similar to those of cocaine

what three monoamine neurotransmitters does cocaine block the reuptake for?

• norepinephrine

• dopamine

• serotonin

how are the affects of cocaine binding to transporters?

• inhibits their function

• increased neurotransmitter levels in the synaptic cleft

• increase in transmission at the affected synapses

the blockade of the reuptake of which neurotransmitter is considered to be most important for cocaine’s stimulating, reinforcing and addictive properties?

dopamine

what is the most important mechanism occurring when cocaine causes an increase in extracellular DA levels

inhibition of DA reuptake following cocaine binding to DAT

what is the second mechanism involving DA?

increase firing of ventral tegmental area dopaminergic cells and the frequency of transient DA release events

why can cocaine be used as a local anesthetic?

high concentrations cause inhibition of voltage-gated sodium channels which are necessary to generate action potentials, blockage of nerve conduction

what two widely used anesthetics were developed from the structure of cocaine?

Novocain and lidocaine

what are the typical aspects/characteristics of cocaine?

• feelings of exhilaration and euphoria

• sense of well-being

• enhanced alertness

• heightened energy

• diminished fatigue

• great self-confidence

• sociability and talkativeness

focused stereotypes

behaviors produced by high doses of psychostimulants and characterized by repetitive and aimless movement

sympathomimetic

substance that produces symptoms of sympathetic nervous system activation

ex:

• increased heart rate

• narrowing of blood vessels

• increased blood pressure

• elevated body temperature

drug-seeking behavior

performance of an operant response such as a lever-press or a nose-poke with the expectation of receiving delivery of a drug dose

which D receptor leads to knockout mice not self-administering cocaine and what does that suggest?

D1, suggests a critical role for this receptor subtype in the drug’s reinforcing effects

• plays a central role in the behavioral effects of cocaine in rodent models

cocaine binges

periods of cocaine use lasting hours or days with little or no sleep

what are the three phases of abstinence syndrome?

• crash

• withdrawal

• extinction

crash phase

feelings of exhaustion, experiences intense dysphoria, anhedonia, insomnia, and other psychological symptoms

withdrawal phase

anhedonia continues and is accompanied by anergia, disinterest in the environment, growing craving for cocaine

extinction phase

• occasional episodes of craving

• spontaneous or cue induced, may trigger relapse

cocaine priming

exposure to small amount of the drug that elicits craving for more

time-dependent

increase in drug craving and drug seeking behavior during abstinence

how long does it take for sensitization to kick in for cocaine usage?

just a few exposures

what are the effects of high-dose cocaine use?

panic attacks or the development of a temporary paranoid psychosis with delusions and hallucinations

what are the two naturally occurring plant compounds that have similar structures to those of amphetamine and methamphetamine?

• cathinone

• ephedrine

cathinone

psychostimulant that is the primary active ingredient in khat

what was amphetamine first marketed for?

treatment for narcolepsy, depression, and a form of Parkinsonism

how is amphetamine typically taken?

orally or by IV or subcutaneous injection

how can methamphetamine be consumed?

orally, snorted, injected, intravenously, or smoked

what is a “run”

drug is typically injected approximately every 2 hours for as long as 3 to 6 days or more

how does amphetamine differ from cocaine mechanisms

amphetamine and methamphetamine release catecholamines from nerve terminals

what are the drug related actions for amphetamine?

• DA molecules released from inside the vesicles into the cytoplasm of the nerve terminal (causes massive increase in synaptic DA concentrations)

principal symptoms of methamphetamine withdrawal

• depressed mood, increased anxiety, sleep disturbances, cognitive deficits and craving for the drug

methylphenidate

synthetic psychostimulant that blocks catecholamine and serotnin reuptake and is used to treat adhd