 General Issues

 More Specific Drugs and how they work

 Psychopharmacology – study of drugs and
behavior
 Drugs and behavior – PSY 459
 Clinical Psychopharmacology – PSY 565

 Psychoactive drugs – drugs that change the

way you feel

 All these must reach the brain!

1. To feel good
(positive reinforcement – likely cause DA
release!)

 psychological dependence

**greatest amount of psychological

dependence occurs if the rewarding
effects of drugs happen very quickly after
behaviors associated with them.
drug rewards that happen very soon after a
behavior – strong positive reinforcement for
that behavior

ex. prep for heroin injection, crack smoking,

etc.
2. To avoid feeling bad (reduce withdrawal)
(negative reinforcement)

◦ chemical dependence-
 Often a combination of positive and negative
reinforcing effects or transition from positive
to negative……
 pharmacokinetics:
 includes how the drug is taken in (absorption)
 how it gets to the brain (distribution)
 what it does in the brain (nt?;
pharmacodynamics)
 how it is broken down (metabolism)
 how it leaves the body (excretion)
- how a drug is taken into the body……

- for drugs of abuse - the more rapidly the drug

gets to the brain – the greater the abuse liability!
 oral

 injection
◦ subcutaneous
◦ intramuscular
◦ intravenous - reaches brain in ~ 10 secs
 quick response but also most dangerous
 inhalation - reaches brain in ~8 secs

 dermal – absorbed through the skin

 buccal or nasal membranes

1. cocaine – blocks reuptake of monoamine
neurotransmitters (most important DA)

2. nicotine
◦ acts as an agonist at nicotinic cholinergic receptors

3. alcohol
◦ works on virtually every neurotransmitter
4. metabolism (detoxification or breakdown)
• how a drug is broken down or made into inactive
forms
• mostly done by the liver – via enzymes!
5. excretion (elimination)
• how a drug once broken down (or not) is
eliminated from body

• most psychoactive drugs metabolites excreted in

urine
 tolerance – either decreased effectiveness or
potency of a drug
 metabolic tolerance –
◦ enzyme induction-
 enzymes – speed up a chemical reaction

◦ with repeated exposure, enzymes get better at

breaking down drug or liver makes more enzymes
 metabolic tolerance –

◦ enzyme induction- enzymes are either better at

breaking down drug or liver makes more of them

◦ implications?
 metabolic tolerance –
◦ enzyme induction

 cross tolerance – tolerance to one drug

results in tolerance to other drugs (usually
that need similar enzymes for breakdown)
◦ Implications:
 cross tolerance – tolerance to one drug
results in tolerance to other drugs (usually
that need similar enzymes for breakdown)
◦ Implications:

◦ Person shows up unconscious at ER and is an

alcoholic – given a barbiturate for surgery;
 tolerance can still occur when the amount of
drug reaching the brain/body is unchanged

 pharmacodynamic or physiological tolerance

–
 pharmacodynamic or physiological tolerance
–

“for every action, there is an equal and

opposite reaction (in your brain)”
 Use alcohol as an example –

 Acutely – alcohol decreases glutamate activity

and increases GABA activity

 Chronic alcohol -------- brain’s

compensatory response?
 upregulation of GLU receptors –
◦ increase the number or sensitivity of glutamate
receptors to compensate for decreased activity and
try to get activity back to normal levels….

 what happens during alcohol withdrawal?

◦ now have too many (or too sensitive) glutamate
receptors – overexcitation, seizures, etc.
 Use alcohol as an example –

 Acutely – alcohol decreases glutamate activity

and increases GABA activity

 Chronic alcohol -------- brain’s

compensatory response?
 down regulation of GABA receptors –
◦ to compensate for increased activity and try to get
activity back to normal levels…. – reduce n or
sensitivity of GABA receptors

 what happens during alcohol withdrawal?

◦ now have too few (or too insensitive) GABA
receptors – overexcitation, seizures, etc.
 the exposure of compensatory changes in
brain (and body perhaps) likely explain a
number of withdrawal symptoms (that are
often opposite of the effects that the drug
causes)
 chemical see-saw

drug Change from norm

 chemical see-saw

heroin constipation
The brain wants to rebalance the activity
heroin WD
diarrhea
 Drugs taken in the same environment can
also display tolerance associated with the
conditioned cues

 ex. heroin

 explanation – compensatory changes in brain

in EXPECTATION of drug
 most treatments do best with both
pharmacotherapy and behavioral therapy (of
some sort) but the data is still LOUSY!!!
 In terms of health –
 Which drugs have the most significant health
effects (for the largest number of people)?

 KY issues?
 most treatments do best with both
pharmacotherapy and behavioral therapy (of
some sort) but the data is still LOUSY!!!
 Psychostimulants – increase arousal;
sympathetic nervous system
◦ cocaine
◦ amphetamines
 methamphetamine
 drugs used to treat ADD
 Ritalin (methylphenidate)
 Adderall (mixed salts amphetamine)
 naturally derived (often from plants)
◦ cocaine – comes from the coca plant

 synthetically derived (in the lab)

◦ amphetamine – synthesized in laboratories
 Cocaine – block reuptake (DA, NE)
◦ block the transporter

 amphetamines – block reuptake (actually

reverse the transporter) and stimulate
release!
 methylphenidate – blocks reuptake
 stereotypic behavior
◦ repetitive behaviors
 Appetite suppression
◦ weight loss
 Possible aggression
◦ several descriptions of murder and other violent
offenses attributed to amphetamine intoxication
 Psychological dependence –
◦ very strong for drugs that are either smoked, or
injected IV
 Psychological dependence –
◦ very strong for drugs that are either smoked, or
injected IV

 Physical dependence-
◦ do we see a withdrawal syndrome?
◦ “cocaine crash” – cause less certain
 cardiovascular
◦ increased risk for CVA
◦ cardiac arrhythmia
◦ increased blood pressure
 respiratory
◦ chest pain respiratory complications
◦ difficulty breathing
 CNS
CNS
◦ seizures
◦ intracranial hemorrhages (strokes)
◦ cocaine or amphetamine induced psychosis
◦ formication
 produce relaxation, sleep and ultimately (for
some sedative hypnotics), unconsciousness
and death from respiratory depression if dose
is too high
 alcohol, barbiturates, benzodiazepenes
 virtually all sedative hypnotic drugs work on
the GABA receptor to make GABA bind better
to its receptor!
 First written “recipe” for making beer – about
3000 BC (Egyptians)

 fermenting fruit – sugar dissolved in H20 and

exposed to air – microorganisms (yeasts)
LOVE it
 http://videosift.com/video/Drunk-Animals-
of-Africa-the-longer-version
 Biphasic Alcohol Effects Scale

Stimulant scale
Elated Talkative Sedative scale
Energized Up Inactive Sedated
Excited Vigorous Down Slow thoughts
Stimulated Heavy head Sluggish
Difficulty concentrating
 Alcoholism costs the nation $150 Billion /
annum

 many organ systems are affected including

◦ liver- fatty liver and cirrhosis
◦ pancreas - pancreatitis
◦ heart - cardiomyopathy
◦ immune function - compromised
◦ endocrine function - altered
 ethanol affects many NT
 chronic ethanol is not good for CNS
◦ Wernicke’s – thiamine deficiency?
◦ Korsakoff’s – more permanent memory deficits
 affects many neurotransmitter systems

 inhibits glutamate activity

 enhances GABA activity

◦ R0-15-4513
Copyright © Allyn & Bacon 2007
 Psychological – perhaps some but certainly
not as strong as psychostimulants

 Physical dependence – absolutely

◦ alcohol withdrawal – only withdrawal syndrome that
is potentially LETHAL if not done under medical
supervision!!!!
 First need to treat acute withdrawal

 Then follow up with more long-term

strategies
◦ pharmacotherapies
◦ groups like Alcoholics Anonymous
 GABA
◦ a down regulation of GABA receptors

 Glutamate
◦ an upregulation of GLU receptors

 Treat with benzodiazepenes during WD

◦ reduces the risk of seizures
 probably 2nd most commonly used drug in US
 rewarding, pleasurable effects
◦ how?

 paradoxical effects on arousal

◦ biphasic effect with increased attention at lower
doses but decreased anxiety/arousal at higher
doses

 decreased hunger and resulting weight

reduction
◦ nt release and increased metabolism because of
sympathetic NS activation
 nACh receptors – nicotinic subtype of ACh
receptors
 Where are these receptors found?
◦ PNS
 autonomic ns – so can affect heart rate; blood
pressure, etc
 muscles – all postsynaptic receptors on muscles are
nicotinic!
 Where are these receptors found?
◦ PNS
 autonomic ns
 muscles

 biphasic effect
◦ low dose – stimulation; high dose – brief
stimulation followed by blockade of transmission
◦ (WHICH IS WHY NICOTINE IS SUCH A POTENT
POISON)
 OH YES!!!!!
 Psychological Dependence
◦ nicotine produces strong psychological dependence
 Physical Dependence
◦ for regular smokers – nicotine produces strong
physical dependence

◦ TTFC – time to first cigarette –

 sometimes used as an indicator of dependence
 Pharmacotherapy-
◦ substitution therapy – provide nicotine via a safer
(and less rewarding route)
◦ intent is to reduce the positive reinforcing effects
AND provide negative reinforcement (ie reducing
withdrawal symptoms)
 Opioid based drugs
◦ heroin, morphine, oxycodone, methadone, etc
◦ activate endogenous opiate receptors
 treatment often uses substitution therapy
◦ methadone
◦ buprenorphine ( )
 hallucinogens – a mix of types of drugs

 some examples -
◦ LSD like hallucinogens – work on 5HT neurons
◦ Amphetamine like hallucinogens – MDMA (Ecstasy)
– seems to have effects on serotonin (in some cases
it is neurotoxic to 5HT neurons)
◦ psychedelic anesthetics – PCP; ketamine
 work on the glutamate receptor