cocaine & amphetamines

cocaine and amphetamines are part of which class of drug?

• stimulants

• psychomotor stimulants

• psychostimulants

• “uppers”

what are the major behavioral properties of psychomotor stimulants:

• stimulate alertness and arousal (“psycho-”

• stimulate motor activity (“-motor”)

what does stimulants include?

• cocaine 

• amphetamines 

• nicotine 

• caffeine 

cocaine is a psychoactive alkaloid found in? 

coca leaves 

is cocaine natural or synthetic?

natural

cocaine is what kind of base?

a weak base

in what era was cocaine widely used; doctors and scientists lauded its properties 

• 1800s 

• early 1900s 

what is the route of administration of raw coca leaves?

• raw coca leaves are chewed with lime power or ask to increase saliva pH, which enhances absorption by decreasing the ionization of cocaine (weak base) 

• absorption in mouth 

what is cocaine concentration of raw coca leaves?

• < 2% cocaine

coca paste is a … from leaves

crude extraction

what is the cocaine concentration of coca paste

~ 80% cocaine sulfate

what is the route of administration of coca paste?

can ONLY be smoked

what is coca paste also known as? 

• paco 

• basuco 

what is cocaine hydrochloride, and what is it extracted from?

• a crystalline power 

• extracted and purified from coca paste 

what is the cocaine concentration of cocaine hydrochloride?

very high

what are the routes of administration of cocaine HCl (hydrochloride) and how can it not be taken

• water soluble and can be taken orally, intranasally, or injected IV 

• cannot be smoked 

  • b/c vaporization temperature is close to burn temperature 

cocaine free base made from cocaine HCl + water + base →

extraction with ether (flammable solvent)

what is the route of administration of free base cocaine

• can be vaporized 

• can be smoked 

• residual ether can be dangerous and explode with flame 

what is a cruder preparation of free base cocaine?

“crack” or “rock”

what is made from cocaine HCl, and is safer to make b/c baking soda used instead of solvent 

crack 

what is the cocaine concentration in crack cocaine?

75 - 90%

what is the route of administration for crack cocaine

smoked

crack led to …

a new epidemic of cocaine use in the 1980s-1990s

cocaine was widely used in many products by late 1800s, including?

• coca-cola

• toothache drops

• dandruff “cure”

• “cocarettes”

• wine tonic

due to its use in local anesthetics, what schedule is cociane?

schedule 2

what is the primary mechanism of cocaine?

blocks monoamine transporters (like DAT)

what do high doses of cocaine do?

inhibits voltgae-gates Na+ channels (involved in action potentials)

when is the peak subjective effect for crack cocaine?

• ~1-2 min

• over within 5-15 min 

with smoking or IV, is absorption for cocaine slow or rapid?

extremely rapid

what is the half-life of cocaine

.5 - 1.5 hrs

inactive major metabolite benzolecgonine is detectable in urine for …

several days

active metabolite cocaethylene is formed when cocaine …

and ethanol are ingested simultaneously; longer half-life than cocaine

amphetamines are a chemical family of … psychostimulants

synthetic and natural

ephedrine is a synthetic or natural form of cocaine 

natural 

what are the active components in ephedrine

ephedrine and pseudoephedrine

medically, ephedrine is used as

a decongestant

what does cathinone come from?

“khat” or “qat” shrub leaves (natural)

cathinone is commonly …

chewed

methcathinone (“cat) and mephedrone “meow meow” are synthetic or natural variants of cathinone?

synthetic

methcathinone (“cat) and mephedrone “meow meow” are what kind of drug

designer drugs

an example of methcathinone (“cat) and mephedrone “meow meow” is…

bath salts

methcathinone (“cat) and mephedrone “meow meow” are on schedule …

one

amphetamines where synthesized in

1887

methamphetamines where synthesized in

1919 

a medical use for methamphetamines and amphetamines was developed in? and what is that use? 

• 1920-30s 

  • benzedrine inhaler (for congestion) 

  • narcolepsy 

there was widespread adoption of amphetamines and methamphetamines during which war in the 1940s 

world war 2 

peak use of “speed” occurred when?

early 1970s

what are the different forms of amphetamines

• d-amphetamine 

• l-amphetamine 

• amphetamine 

medically, what is amphetamine used for?

adderall

what is the route of administration for amphetamines

• taken orally 

• taken by injection (IV, SC) 

what is the most potent amphetamine?

methamphetamine

what is the route of administration for methamphetamine

• oral 

• snorted 

• injected (IV) 

• smoked 

what are the “amphetamine-like” stimulants differ in chemical structure? and what are they used for?

• methylphenidate 

  • ritalin, concerta 

  • attention deficit disorder 

• modafinil 

  • narcolepsy; sleep apnea 

ampehtamines used for … due to wake-promoting effects

narcolepsy

because amphetamines could elevate mood and suppress appetite it was also used for… 

mild depression and as a diet pill (NOT a current use though) 

amphetamines where widely used by … during WW2 and subsequent conflicts

military 

in 1970 how much of the population were regular users of amphetamines

>10%

meth can be…

smoked

meth has a faster or slow route of administration

faster, whihc man leave to more abuse potential

meth is easily prepared from

common household ingredients

what are the CURRENT medical uses for amphetamines (DEA schedule 2) 

• narcolepsy

• attention deficit disorder (ADD, ADHD)

amphetamines have a slower or faster metabolism and elimination as compared to cocaine? 

• slower 

• half life is 7-30 hrs 

what are the autonomic effects of stimulants?

• increased blood pressure

• hyperthermia 

• bronchodilation 

what are the behavioral and subjective effects of cocaine and amphetamines in humans 

mild to moderate 

• mood amplification; both euphoria and dysphoria 

• heightened energy 

• sleep disturbance, insomnia 

• motor excitement, restlessness 

• talkativeness, pressure of speech 

• hyperactive ideation 

• increased sexual interest 

• anger, verbal aggression 

• mild to moderate anorexia 

• inflated self-esteem 

severe effects 

• irritability, hostility, anxiety, fear, withdrawal 

• extreme energy or exhaustion 

• total insomnia 

• compulsive motor stereotypies 

• disjointed flight of ideas 

• decreased sexual interest 

• possible extreme violence 

• total anorexia 

• delusions of grandiosity 

the effects of cocaine are (as compared to amphetamines)…

• shorter duration of action ‘

• worse cardiovascular effects (can be lethal)

• higher convulsive/seizure properties of cocaine

what is hyperlocomotion in animals? 

locomotor activity can appear to go down with high AMPH doses because rate perform stereotypy behavior instead 

what are the reinforcing/rewarding effects of hyperlocomotion

• self-administration 

• conditioned place preference 

in chronic, high dose users of stimulants withdrawl symptoms are mostly …

psychological (as opposed to physical) and not fatal

tolerance to some effects of psychostimulants:

• autonomic effects 

• anorexic effects 

sensitization to other effects of psychostimulants:

• rewarding effects

• psychotomimetic effects (psychosis)

• locomotor stimulant effects 

what are the negative side effects of chronic amphetamine use

• psychosis 

• anorexis 

• physical damage (meth mouth, skin sores) 

what are mdma and the related drugs

• MDMA

  • ecstacy, E, X, XTC, adam (pills)

  • m, molly (pure powder/crystal form) 

• MDA 

  • pre-dates more widely use MDMA 

• MDE or MDEA 

  • eve 

  • milder, shorter acting 

MDMA was patented as cough syrup and anorectic, but it was never…

used clinically

recent evidence that MDMA can enhance…

communication and openness (similar to psychedelics)

MDMA first became popular as a …

club drug during 1980s-90s

what schedule is MDMA

schedule 1

how is MDMA most often taken and how long is its half life?

• orally

• long half life, 8 hrs 

what are the MDMA effects at low doses

• behavioral: increased energy and sociability/empathy; mild euphoria 

• autonomic: increased heart rate and temperature 

what are the MDMA effects at high doses

• behavioral: mild hallucinogenic 

• autonomic: hyperthermia & dehydration; increased H.R. and B.P. → stroke 

cocaine blocks…

reuptake of monoamines (DA, NE, and 5-HT) 

two actions of amphetamines lead to very high DA in synaptic cleft 

• drug enter monoamine terminals and cause vesicles to release transmitter 

• drug cause monoamines to be transported out of neuron via reversal of transporter 

Monoamine taxonomy

… is an amino acid and the precursor for catecholamines

tyrosine

the enzyme … is the rate limiting step in catecholamine synthesis

tyrosine hydroxylase (TH)

all monoamines are …

classical neurotransmitters (anterograde signaling)

catecholamines are inactivated by:

reuptake via transporters and/or enzymatic degradation

… into the axon termins is the primary mechaniism for inactivation and is much faster than metabolism

catecholamine reuptake

all monoamines are packaged into vesicles by the same … which is… 

• vesicular transporter 

• vesicular monoamine transporter VMAT2

each monoamine has its own synaptic (plasma membrane) transporters

• DAT = dopamine transporter 

• NET = norepinephrine transporter 

• SERT = serotonin transporter 

each monoamine also has its own …

receptors

two types of enzymes are involved in catecholamine metabolism:

• MAO (monoamine oxidases)

• COMT (catechol-o-methyltransferase) 

what are the five dopamine receptors (all GPCRs):

• d1

• d2

• d3

• d4

• d5 

d1 like receptors (d1, d5) are coupled to?

g_s

d2 like receptors (d2, d3, d4) are coupled to?

g_i

presynaptic autoreceptors are mostly …

d2

dopamine receptors are concentrated in the…

prefrontal cortex areas

the few thousand neurons in the brainstem send broad diffuse projections to large …

areas of the forebrain

the majority of dopamine neurons (cell bodies) can be found in the midbrain, in 

• substantia nigra 

• ventral tegmental area (VTA) 

in the nigrostriatal pathway, da neurons in the … target the …

• substrantia nigra 

• dorsal striatum 

in the mesolimbic pathway, da neurons in the … target the …

• ventral tegmantal area (VTA)

• ventral striatum (nucleus accumbens)

• and the amygdala