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Contemporary Human
Behavioral Pharmacology
Rodney D. Clark, Ph.D.
Department of Psychology and
Program in Neuroscience
Allegheny College
[email protected]
814-332-4960
Orientation
• Where did the “problem” with drugs come
from?
• Drugs are used very frequently in
contemporary society.
• Misconceptions perseverate.
• Misinformation is prevalent.
Orientation
•
•
•
•
Social Influences
Discuss legal Issues
Discuss moral Issues
Applied Behavior Analysts encounter clients
with histories of prescribed drug use,
recreational drug use, or both.
Learning Objectives
At the conclusion the workshop participant will be
able to:
• Describe a general historical context.
• Describe the basic actions of the nervous system.
• Describe the fundamental actions of drugs.
• Describe the environmental determinants of drug
action.
• Describe basic stimulus properties of drugs.
• Describe potential drug interactions.
• Describe clinical actions of therapeutic drugs.
Workshop Format
The format of the workshop will be arranged in
the following way:
• The workshop will be divided up into six units.
• Each unit consists of a sequence of one to
three brief lectures with the first six units
followed by a short quiz.
• The seventh and final unit will be followed by
a group discussion and concluding remarks.
We Begin
The first thing I want to say is:
The phrase
“drugs and alcohol.”
…is grammatically incorrect!
the word “drugs” …is a generic or class
noun of which alcohol is a member.
…That is similar to saying “…sports and
baseball.”
• Humans are not the only animal to consume
psychoactive chemicals on a regular basis.
Many other animals do so.
• Animals, including humans have receptors in
the brain and rest of the body that abused
drugs have an affinity for.
• We have an interesting cultural context in
which many people “understand” how drugs
work.
• From Robert Louis Stevenson we have the
handsome young Dr. Jekyll turning into the
hideous Mr. Hyde when he drinks “the
formula.”
• Many people consider “drugs” to do exactly
that! …turn people into monsters!
• Reference the descriptions used by early
journalists when reporting on the effects of
Marijuana.
• “Drugs do not create behavior, they modify
existing behavior.”
1. Historical Antecedents
HISTORY
• From the colonial era to the present drugs have
been a part of the American fabric. We will
take a brief look at what happened.
• There has never been a time when drugs were
not present.
• Drugs have been both praised for their effects
and villainized for the same effects.
HISTORY in the United States
• We only really began to legally regulate drug
use in the final quarter of the 19th century.
• We only began to require disclosure of the
ingredients of “drugs” in the first part of the
20th century.
• We only began to really view drugs as
“problems” during the first part of the 20th
century.
Historical Antecedents
•
•
•
•
•
•
•
•
•
ALCOHOL
MARIJUANA
NARCOTICS (OPIOIDS)
CAFFIENE
PSYCHOMOTOR STIMULANTS
SEDATIVE-HYPNOTICS
INHALEANTS
HALLUCINOGENS
TOBACCO
ALCOHOL
EARLY HISTORY OF DRUG USE
• ALCOHOL:
– Appears to have been used since 6000 BCE.
– Frequently mentioned in the bible and other early
religious text.
– Egyptians revered wine and associated spiritual
qualities to it.
– Ancient Hebrews, Greeks, and Romans used
alcohol.
EARLY HISTORY OF DRUG
USE…
• ALCOHOL:
– The word “alcohol is derived from the Arabic
word “Alkuhl” (the essence).
– Prominent role of alcohol in U.S. history:
•
•
•
•
The slave trade
Survival of pilgrims
Early settlers
Temperance
DEMON RUM
From: PBS “THE AMERICAN
EXPERIENCE”
MARIJUANA
MARIJUANA
– Use dates back to 2700 BCE.
– Banned in China in 500 BCE.
– Used in India for religious purposes.
– Greeks and Romans used it for clothes and for
intoxicating effects (the Oracle at Delphi).
– Used in colonial America for rope.
– Early 1900s used by farmworkers and jazz
musicians.
– Post WWII “Beats” …And the “Hippy” of 1960s
NARCOTICS
(OPIOIDS):
NARCOTICS (OPIOIDS):
• NARCOTICS (OPIOIDS):
– Opium derivatives made from the plant Papaver
somniferum.
– Intoxicating and euphoric properties known since
6000 BCE.
– Frequently mentioned in writings from ancient
Greece and Rome.
– The central factor in the war between Britain and
China.
NARCOTICS (OPIOIDS):
– Morphine was derived from opium in 1806.
– Many Civil war veterans suffered from morphine
addiction (the “Soldier’s Disease”).
– Heroin was developed to combat morphine
addiction as it was thought to be much safer.
MILD
STIMULANTS
CAFFINE
CAFFINE
• CAFFINE:
– Found in a variety of drinks.
– Coffee as an example
– Use dates back to 900 CE.
– The Koran defines coffee as an intoxicant.
– Drinking became very popular in 1600s Europe.
PSYCHOMOTOR STIMULANTS
PSYCHOMOTOR STIMULANTS
• COCAINE:
– It is believed that the practice of chewing coca
leaves dates back to about 3000 BCE.
– First recorded use of coca leaves traced back to
500 CE in present day Peru.
– Extract of coca leaves was used in Europe in Vin
Mariani’s coca wine.
PSYCHOMOTOR STIMULANTS
• COCAINE:
– Sigmund Freud was an early proponent of the
medicinal value of cocaine.
– Cocaine was introduced in the original formula for
Coca-Cola and other soft drinks.
– Tooth drops for teething children.
PSYCHOMOTOR
STIMULANTS
• AMPHETAMINES:
– First synthesized in 1887.
– Used medicinally since the 1920s.
– Became available in the 1930s as an over-thecounter drug.
DETECTIVE
COKE
ENNYDAY
(Starring Douglass Fairbanks)
DETECTIVE
COKE ENNYDAY
(Starring Douglass Fairbanks)
c. 1916
SEDATIVE-HYPNOTICS:
SEDATIVE-HYPNOTICS:
• SEDATIVE-HYPNOTICS:
– Barbiturates were discovered in the 1860s.
– Used to treat anxiety.
– Non barbiturates such as bromide were developed
in the 1860s as a treatment for epileptic
convulsions.
– Minor tranquilizers were introduced in the 1950s
increasingly used to treat anxiety.
SEDATIVE-HYPNOTICS:
• INHALENTS:
– Solvents, glue, Nitrous oxide, aerosols, gasoline,
anesthetics
– Used in increasing frequency since the 1940s
– Primarily used among teens and young adult
populations.
HALLUCINOGENS
HALLUCINOGENS
– Psilocybin use dates back to 2000 BCE.
– d-LSD-25 first synthesized in 1938.
– N,N,DMT (Dimethyltryptamine) called the
“business man’s LSD” because of the short
duration.
– Gen. Wm. Creasy’s concept of “war without
death” suggested spraying the enemy with LSD.
…to test this idea some suggested
spraying it into the subways of NYC.
HALLUCINOGENS
• HALLUCINOGENS:
– Dr. Sidney Gottlieb, Chief of CIA technical
service, was the head of the secret project …MKULTRA.
– Sometimes tested on unwilling subjects.
– Drs. Timothy Leary & Richard Alpert, Harvard
professors experimented with LSD.
Nicotine
Nicotine
As an Example TOBACCO
– Use in America traced back prior to the 1400s.
– Introduced to Europe in the 1490s and used
medicinally.
– In late 1800s and early 1900s chewing was more
popular than smoking.
– Around World War I, smoking became more
popular than chewing.
– Total U.S. sales have been declining since mid1980s.
A FEW THINGS TO THINK
ABOUT
• Are drugs really a problem?
• Is there cultural tolerance toward certain types
of drug use?
• Do drugs cause violence?
• Do drugs cause family problems?
• Do drugs cause problems in the workplace?
• Can we really be drug free?
QUIZ #1
QUIZ #1
Describe some historical antecedents.
1. We have an interesting ____________in which
many people “understand” how drugs work. An
example may be when …the handsome young
Dr. Jekyll turns into the hideous Mr. Hyde when
he drinks “the formula.”
a.
Cultural context
b.
Mind set
c.
World view
d.
Philosophy
QUIZ #1
Describe some historical antecedents.
2.
Of the following which was not among the
social effects of opioids we discussed?
a. Morphine was derived from opium in 1806.
b. Many Civil war veterans suffered from morphine
addiction (the “Soldier’s Disease”).
c. Heroin was developed to combat morphine addiction
as it was thought to be much safer.
d. The disruptive effects of heroin addiction was first
observed during the post-World War II era.
QUIZ #1
Describe some historical antecedents.
3.Psilocybin use dates back to ____________.
a.
b.
c.
d.
2000 BCE
5000 BCE
1,000,000 BCE
200 CE
10 minute break
Basic neuroanatomy
(Brain & Spinal cord).
Basic Principles of Pharmacology
• Basic neuroanatomy (Brain & Spinal cord).
• Neurochemical functioning (Pharmacology).
• Basic methods in pharmacology, Major Body
systems, and factors).
EXAMPLE OF A MEDIAL VIEW OF
THE HUMAN BRAIN.
BRAIN SECTIONS
The brain: major subdivisions
•
•
•
•
•
•
Frontal Lobe: “Planning”
Temporal Lobe: Hearing
Parietal Lobe: Body sensations
Occipital Lobe: Vision
Pre-central Gyrus: Motor control
Central Sulcus: Divides the frontal and
parietal lobes
• Postcentral Gyrus: Stimulation from touch
THE NERVOUS SYSTEM:
• CENTRAL NERVOUS SYSTEM (CNS): composed
of the BRAIN and SPINAL CORD
• PERIPHERAL (PNS): composed of
– AUTONOMIC NERVOUS SYSTEM: Subdivided into the
Sympathetic (Symp.) and Parasympathetic (Psymp.) NS
• Generally these two systems work in opposition to one another
• Drugs that mimic the Symp. Are called Sympathetics
• Drugs that mimic the PSymp. Are called Parasympathetics
– SOMATIC NERVOUS SYSTEM: Nerves that relay
sensory information into the CNS and motor information
back out
Once again, THE BRAIN
BASIC STRUCTURE OF THE
HUMAN BRAIN…BASAL VIEW
BASIC FUNCTIONS OF SELECTED
STRUCTURES OF THE BRAIN
• The brain and spinal cord (The CNS). Are
composed of several major structures some of
which are:
– Reticular Activating System (RAS): affects
sleep, attention, and arousal.
– Hypothalamus: Maintains homeostasis, affects
stress, aggressiveness, heart rate, hunger, thirst,
consciousness, body temp., blood pressure, and
sexual behavior.
BASIC FUNCTIONS OF SELECTED
STRUCTURES OF THE BRAIN
– Limbic System: Plays a key role in memory and
emotion.
– Medial Forebrain Bundle (MFB): Functions as a
communication route between the Limbic system and
the Brain Stem; affects “pleasure and reward
(reinforcement).”
– Basal Ganglia: Affects one’s ability to stand, walk,
run, carry, throw, and lift. May produce muscular
rigidity of facial, arm, and leg muscles.
– Periventricular System: concerned with punishment
and avoidance behavior
BASIC FUNCTIONS OF SELECTED
STRUCTURES OF THE BRAIN
– Brain Stem: Regulates vital functions such as
breathing, heartbeat, pupil dilation, blood pressure, and
the vomiting reflex
– Cerebral Cortex:
• Hypothalamus: Link between the brain and hormonal
output from the pituitary
• Cerebrum (Frontal Lobe): coordinates planning, inhibition
of inappropriate behavior, and visceral sensations
– Cerebellum:
• Nucleus Accumbens: believed to play a role in emotional
behavior and reinforcement (reward)
• Ventral tegmental area: reinforcement (reward)
AT THE CELLULAR LEVEL
• Neurons (Nerve cells)
• Glia (supporting tissue with modulatory
functions)
• Astrocytes (supporting tissue with some
neurotransmitter functions)
• Phageocytes (waste disposal function)
BASIC STRUCTURE OF THE
NEURON (NERVE CELL)
• Dendrites: allows nerve impulses to be sent
toward the cell body
• Axon: allows nerve impulses to be sent away
from the cell body
• Cell Body (Soma): where basic cellular
functions are carried out
• Axon Hillock: junction between the axon and
cell body
• Synapse: the space between an axon and
dendrite (about 50 microns across)
STYLIZED STRUCTURE OF A
GENERIC NEURON
EXAMPLE OF FOUR DIFFERENT
TYPES OF NEARVE CELLS
NEUROTRANSMITTERS
NEUROTRANSMITTERS
NEUROTRANSMITTERS
• NEUROTRANSMITTERS (NT): are
chemical substances manufactured in the
neuron and released into the synapse.
SOME MAJOR
NEUROTRANSMITTERS:
– Acetylcholine (ACH): An excitatory NT in the
skeletal muscles but inhibitory in the heart; affects
memory, and linked to aggression and depression.
– Serotonin (5HT): Inhibitory NT has a role in
regulating sensory perception, eating, pain, sleep,
and body temp.
SOME MAJOR
NEUROTRANSMITTERS:
• Gamma-amino butyric acid (GABA):
Produces relaxation and sleep.
Catacholamines: Affects emotional states;
increases lead to stimulation and decreases
lead to depression; implicated in mood swings
Dopamine (DA)
Epinephrine (E)
Norepinephrine (NE)
SOME MAJOR
NEUROTRANSMITTERS:
– Glutamate: Excitatory NT plays a role in
substance abuse, psychoses, and neurodegenerative
disorders.
– Peptides: Are substances that link amino acids and
include naturally-occurring opioid-like substances
called endorphins.
• Mu agonists (μ):
• Kappa agonists (k):
• Delta agonists (δ):
* (Sigma agonists) (σ):
• *Once thought to be an opioid
SOME NEUROTRANSMITTERS
AND THEIR FUNCTION
NEURAL TRANSMISSION
Neural Transmission
Neural Transmission
A closer look at the electrical signal.
• The signal is known as an action potential.
• There is a difference in the electrical charge
between the intracellular fluid and the
extracellular fluid.
• The inside is slightly negative relative to the
outside.
The action potential
• This difference is referred to as the Resting
potential (averaging about -70mV).
• This potential difference is the outcome of an
uneven distribution of ions between inside and
outside of the cell.
• As sodium levels in the cell change, the
difference in voltage changes.
The action potential
• Ions are particles that posses an electrical
charge.
• The ions responsible for the resting potential
are ionized molecules of:
– Potassium (K+)
– Sodium (Na+)
– Chlorine (Cl-) (as an ion it is referred to as
Chloride)
The action potential
• The membrane potential is relative, meaning
the inside is compared to the outside.
• The outside of the membrane is always at zero.
• The reason that the resting potential exist is
that the difference in the ratio of negative to
positive ions is higher inside the cell.
The action potential
• There are several processes, both passive and
active, that create the uneven distribution of
ions.
• The resting potential of a neuron is a
description of what occurs when there is no
stimulation.
• As the membrane potential becomes less
negative we call it depolarization.
ACTION POTENTIAL
NEURAL TRANSMISSION
EXAMPLE OF NEURAL
TRANSMISSION
EXAMPLE OF NEURAL
TRANSMISSION
EXAMPLE OF GABA NEURAL
TRANSMISSION / RECEPTOR
INTERACTION
QUIZ #2
QUIZ #2
Describe the basic actions of the nervous system.
1.
Depolarization refers to…
a.
b.
c.
d.
e.
An increase in the resting potential.
A decrease in the resting potential.
Spontaneous fluctuations in the resting potential.
Small leaks of neurotransmitters.
Inhibition.
Glutamate…
2.
a.
b.
c.
d.
e.
Is a major excitatory transmitter.
Primarily acts as an inhibitory transmitter.
Potentiates GABA.
Works at the Sigma receptor.
Both “a” and “d.”
QUIZ #2
Describe the basic actions of the nervous system.
3. The system in the brain that mediates both pain
and punishment is…
•
•
•
•
•
The Raphe’ system.
The RAS.
The basal ganglia.
The periaqueductal grey.
The medial forebrain bundle.
10 minute break
Basic Principles of
Pharmacology
WHAT IS PHARMACOLOGY?
– Relationship or interaction between drugs and
living organisms.
– Drugs that produce profound effects and act
quickly are more likely to be abused.
III. IMPORTANT DEFINITIONS
AND CONSIDERATIONS
• DRUG:
– Any substance, natural or synthetic, that alters the
biological functioning of living organisms.
• DRUG USE:
– Consuming drugs for therapy or recreation.
III. IMPORTANT DEFINITIONS
AND CONSIDERATIONS
• DRUG MISUSE:
– The use of a prescribed drug in quantities more than
what is allowed. The use of a drug in greater amounts
than or for purposes other than prescribed.
• DRUG ABUSE:
– Excessive use to the point of disrupting normal
activity.
I. FOUR BASIC PRINCIPLES OF
PSYCHACTIVE DRUGS
1. Drugs, per se, are not good or bad.
2. Every drug has multiple effects.
3. Both the size and the quality of a drug’s effect
depend largely on the amount the individual has
taken.
4. The effect of any psychoactive drug also depends
on the individual’s history.
II. FOUR PHARMACOLOGICAL
REVOLUTIONS
1.
2.
3.
4.
VACCINES:
ANTIBIOTICS:
PSYCHOPHARMACOLOGY &
BEHAVIORAL PHARMACOLOGY:
ORAL CONTRACEPTIVES:
VACCINES
For the first time in history drugs
worked well in controlling …
• Communicable diseases.
• Insect-borne pathogens
• Pathologies related to
microorganisms
ANTIBIOTICS
For the first time in history drugs
were used in the…
• Prevention of infection
• Cure of infection
PSYCHOPHARMACOLOGY and
BEHAVIORAL
PHARMACOLOGY
– The1920s saw the founding of a systematic and
methodical approach to the study of drug effects
on behavior.
– Development of the scientific approach.
ORAL CONTRACEPTIVES
• For the first time in human history drugs have altered
the pattern of sexual behavior and reproduction.
MEASURMENTS
TERMINOLOGY and
CLASSIFICATION
• DRUGS MAY BE CLASSIFIED ON THE
BASIS OF:
– Molecular structure
– Physiological actions
– Behavioral actions
– Therapeutic usage
MEASURMENTS
TERMINOLOGY and
CLASSIFICATION
• Generally use metric system of measurement
• A milligram is a 1/1000 gram.
• A gram is 1/1000 kilogram.
MEASURMENTS,
TERMINOLOGY and
CLASSIFICATION
• DOSAGE:
– Threshold Dose: smallest dose to achieve an effect.
– Effective Dose (ED): dose needed to achieve a
desired effect.
– Lethal Dose (LD): amount needed to achieve a lethal
effect.
– Safety margin: generally the difference between the
effective dose and the lethal dose. The larger the
difference the safer the drug.
MEASURMENTS,
TERMINOLOGY and
CLASSIFICATION
• Effective Dose 50 (ED50): the dose at which
50% of subjects show the desired effect.
• Lethal Dose 50 (LD50): the dose at which
50% of subjects die.
IMPORTANT DEFINITIONS AND
CONSIDERATIONS
• Drugs may be identified by a variety of names.
• CHEMICAL NAME:
– 1(1-Phenylcyclohexyl) Piperedine
• GENERIC NAME:
– Phencyclidine
• TRADE NAME:
– Sernylan
• SLANG NAME:
– Angel Dust
BASIC METHODS:
PHILOSOPHICAL PERSPECTIVES
• BEHAVIORAL PHARMACOLOGY:
–
–
–
–
–
Operant procedures
Respondent procedures
Unconditioned behavior
Locomotor
Selectionistic
• PSYCHOPHARMACOLOGY:
– Cognitive performance
– Locomotor
– Mentalistic
PHARMACOLOGICAL
INTERACTIONS
• Interactions with the brain and the CNS:
• Interactions with neurotransmission.
• Drug actions:
• Agonist:
• Antagonist:
• Interactions with receptors:
ROUTES OF ADMINISTRATION
– Oral (PO):
– Intravenous (IV):
– Intramuscular (IM):
– Subcutaneous (SC or Sub-Q):
– Topical or transdermal (TD):
– Inhalation (IH):
PLOTTED EXAMPLES ROUTES
OF ADMINISTRATION
(from Poling, 1986)
FATE OF A DRUG
(PHARMACOKINETICS)
• ABSORPTION:
– How drugs get into the body.
• DISTRIBUTION:
– How drugs move to the site of action.
• BIOTRANSFORMATION (METABOLISM):
– How drugs are converted into other chemicals.
• EXCRETION:
– How drugs leave the body.
FATE OF A DRUG
(PHARMACOKINETICS)
from NIDA monograph 73, 1986
SOME BASIC CHEMISTRY
• STEREOISOMERS:
– Many molecules appear in two forms that are
mirror images of one another. These are known as
STEREOISOMERS, which interact quite
differently from each other when combining with
receptor sites on the surface of a neuron.
EXAMPLE OF A
STEREOISOMER.
• They can be thought of as “mirror images” of
one another. The structure on the left is
termed: Levo and the structure on the right is
termed: Dextro. The combination is referred
to as the racemic mixture or the Racemate.
STEREOISOMERS
• The different Isomers as well as the racemate
interact differently with the receptor.
• A good analogy is to place your right hand into
the print of your left hand.
DRUGS & MAJOR BODY
SYSTEMS
• Endocrine system:
• Cardiovascular system:
• Respiratory system:
• Gastrointestinal system:
DRUGS & MAJOR BODY
SYSTEMS
• ENDOCRINE SYSTEM:
– Composed of structures that release hormones
directly into the bloodstream.
• CARDIOVASCULAR SYSTEM:
– Transports drugs throughout the body.
DRUGS & MAJOR BODY
SYSTEMS
• RESPIRATORY SYSTEM:
– Important for drug administration and excretion.
• GASTROINTESTINAL SYSTEM:
– Important in oral drug administration and
distribution.
FACTORS AFFECTING DRUG
EFFECTS
•
•
•
•
•
•
•
AGE:
GENDER (BIOLOGICAL SEX):
DOSAGE:
PURITY AND POTENCY:
DRUG INTERACTIONS:
TOLERANCE:
SET AND SETTING:
FACTORS AFFECTING DRUG
EFFECTS
• AGE:
– Infants and the elderly are more sensitive to drugs
mainly because they are less able to metabolize
and excrete drugs.
– A substantial percentage of newborns in America
are exposed to both licit and illicit drugs prior to
birth.
– As one ages the percentage of adipose tissue
increases, when drugs accumulate in body fat
sensitivity to particular drugs also increases.
FACTORS AFFECTING DRUG
EFFECTS
• GENDER (biological sex):
– There are differences in how males and females
respond to drugs.
– Body adipose tissue.
– Water content.
– Hormones.
– Drugs that cause damage to the fetus are called
teratogenic.
FACTORS AFFECTING DRUG
EFFECTS
• DOSAGE:
– Threshold Dose
– Effective Dose (ED)
– Lethal Dose (LD)
– Safety margin
FACTORS AFFECTING DRUG
EFFECTS
• Doses are usually expressed in metric terms.
• Amount of drug per unit of the organism’s
body weight.
• THUS: mg of drug per kg of body weight.
• EXAMPLE 10.0 mg/kg
FACTORS AFFECTING DRUG
EFFECTS
• SET AND SETTING:
– SET: refers to the drug user’s behavioral history
or “mood, expectations, personality, etc.” when
taking the drug.
– SETTING: refers to the social and physical
environment where the drugs are taken.
FACTORS AFFECTING DRUG
EFFECTS
• PURITY AND POTENCY:
– Purity refers to the quality of the drug.
– Potency refers to the drug’s ability to produce an
effect relative to other drugs.
FACTORS AFFECTING DRUG
EFFECTS
• DRUG INTERACTIONS:
– Additive: The cumulative effects of two or more
substances added together.
– Antagonistic: Refers to a drug’s ability to negate
the effects of another drug.
– Synergistic: Refers to the combined effects of
two drugs that are greater than if they were simply
added together.
FACTORS AFFECTING DRUG
EFFECTS
• TOLERANCE:
– Pharmacological / Physiological refers to the body
adjusting to the presence of a particular drug.
– Behavioral refers to the individual’s behavior
adjusting to the presence of a particular drug.
– Cross refers to the tolerance to a particular drug
resulting from tolerance to a chemically similar drug.
– Reverse refers to the drug user experiencing the
desired effects from lesser amounts of the drug.
TOLERANCE
(from Poling 1986)
Quiz #3
Quiz #3
Describe the fundamental actions of drugs.
A milligram is…
1.
a.
b.
c.
d.
e.
1/10 of a gram.
1/100 of a gram.
1/1000 of a gram.
1/10,000 of a gram.
1000 grams.
2. The LD50 / ED50 is the …
a.
b.
c.
d.
e.
Lethal ratio.
Therapeutic ratio
Index of safety
Therapeutic Index
Ratio of Safety
Quiz #3
Describe the fundamental actions of drugs.
3. Of the following, which might alter the affects
of drugs?
a. age
b. gender (biological sex)
c. dosage
d. purity and potency
e. all of the above
10 minute break
Environmental
Determinants of Drug
Action.
Environmental determinants of drug
action.
We can review the basic principles of behavior
and Segway into the stimulus properties of
drugs.
We will use the following definition
• Behavior: Any muscular movement, neural,
or glandular activity.
Basic Principles of Behavior
• Stimuli in the physical environment, including
people, can develop into drug modulating
events.
• This occurs because of “learning.”
• Behavioral change via Classical conditioning
and Operant conditioning.
CLASSICAL CONDITIONING
CLASSICAL CONDITIONING
• All organisms are born with a set of “reflexes,”
but the types of reflexes are particular to the
species.
• These relationships are invariant and are
biologically based.
CONDITIONING
In every day language people may call operant
conditioning:
“VOLUNTARY BEHAVIOR”
In every day language people may call
respondent conditioning:
“INVOLUNTARY BEHAVIOR”
CLASSICAL CONDITIONING
PRIOR TO CONDITIONING
• We refer to the eliciting event as the
unconditioned stimulus (UCS). No prior
conditioning or learning history.
• We refer to the response as the unconditioned
response (UCR). No prior conditioning or
learning history.
CLASSICAL CONDITIONING
AFTER CONDITIONING
• CONDITIONED STIMULUS (CS)  Prior
conditioning history is necessary.
• CONDITIONED RESPONSE (CR)  Prior
conditioning history is necessary.
• NEUTRAL STIMULUS (NS)  Neutral with
respect to the conditioning procedure.
Basic Principles of Behavior
BASIC RESPONDENT RELATION
OPERANT CONDITIONING
B.F. Skinner
THE ROLE OF OPERANT
CONDITIONING
STIMULI
D
S ,
+
S ) Discriminative: Any stimulus in
whose presence reinforcement is presented
during a particular response. (SΔ, S-) Any
stimulus in whose presence reinforcement is
NOT presented (or extinction is occurring)
during a particular response.
THE ROLE OF OPERANT
CONDITIONING
(SR) Reinforcing: A condition, event or
stimulus that increases the future probability of a
behavior (response) it may follow.
(SP) Punishing: A condition, event, or stimulus
that decreases the future probability of a
behavior (response) it may follow.
THE ROLE OF OPERANT
CONDITIONING
• The Operant: Defined by an effect that
maybe specifiable in physical terms and refers
to a class of responses that are all maintained
by the same consequent event.
• Repertoire: The set of skills, what an
organism (human or non-human) can do.
THE ROLE OF OPERANT
CONDITIONING
• THE MOTIVATING OPERATION (MO).
THEY ALTER:
a) The momentary effectiveness of reinforcers or
punishers.
b) The frequency of operant response classes related
to those particular consequences.
(i) reinforcer-establishing / abolishing effect
(ii) punisher-establishing / abolishing effect
THE ROLE OF OPERANT
CONDITIONING
Quiz #4
Quiz #4
In classical conditioning we refer to the eliciting
event as the ______________. No prior
conditioning or learning history is necessary.
a.
b.
c.
d.
Unconditioned stimulus (UCS).
Conditioned stimulus (CS).
Neutral stimulus (NS).
Conditioned response (CR)
Quiz #4
The Operant may be defined by an effect that
maybe specifiable in physical terms and refers to
a ____________ that are all maintained by the
same consequent event.
a.
b.
c.
d.
Class of stimuli
Class of environmental events
Class of responses
None of the above
Stimulus Properties of
Drugs
And
Drug-Behavior
Interactions
Stimulus Properties of Drugs
THE ROLE OF CLASSICAL
CONDITIONING…
• All drugs have unconditioned stimulus (UCS)
properties.
• Classical conditioning can modulate LDs and
EDs.
THE ROLE OF CLASSICAL
CONDITIONING…
Experiments have shown that conditioned
stimuli (CS) can produce drug-like effects. CSs
play an enormous role in…
• Drug abuse: Heroin overdose phenomenon.
• Modulation of Immune Function
THE ROLE OF CLASSICAL
CONDITIONING…
• Drug tolerance may be viewed as a
conditioned response (CR).
• Siegel et al., 1982 suggested deaths resulted
from a failure of tolerance.
• When a drug is administered in the usual
context, the CSs that counteract the drug allow
for a large dose. When the context changes,
the CSs are not present. The drug dose may
then be sufficient to kill user.
THE ROLE OF CLASSICAL
CONDITIONING…
• Immune function can come under the control
of the environment and may be viewed as a
conditioned response (CR).
• Stimuli (CS) correlated with
immunosuppressive drugs may suppress
immune function (CR)
• The accidental discovery of the
immunosuppressive effects of
Cyclophosamide.
THE ROLE OF CLASSICAL
CONDITIONING…
• Sometimes stimuli that have been paired with
drugs produce internal conditioned responses
(CR) that are opposite to the unconditioned
(UCR) effects of the drug.
• EXAMPLE insulin injections
(UCS)produce reduction in blood sugar
insulin-paired stimuli (CS) produce increases
in blood sugar.
THE ROLE OF OPERANT
CONDITIONING
Drugs may function as:
•
•
•
•
Discriminative Stimuli (SD)
Reinforcing Stimuli (SR)
Punishing Stimuli (SP)
Motivating Operations (MO)
THE ROLE OF OPERANT
CONDITIONING
A drug may come to function as a discriminative
stimulus (SD) with an appropriate history of
conditioning.
Consider the following example:
While he is in a bar and is intoxicated (SD) a man
tells jokes (R) and people laugh (SR).
THE ROLE OF OPERANT
CONDITIONING
When he is in the bar again and is not intoxicated
(SΔ) …the man tells the same jokes (R) and no
one laughs (no reinforcement).
If he begins to tell jokes more frequently when
he is intoxicated and not tell jokes when he is
sober, we may say that the Alcohol has come to
function as an SD.
Discriminative Stimuli (SD)
THE ROLE OF OPERANT
CONDITIONING…
• Drugs may come to function as Reinforcing
stimuli (SR).
• Animal models have been employed to study
the reinforcing properties of drugs since the
early 1960s.
• The abuse potential of a drug may be thought
of as its reinforcing liability.
THE ROLE OF OPERANT
CONDITIONING…
(from Seiden & Dykstra 1977)
Drug use is considered to be an operant
response.
THE ROLE OF OPERANT
CONDITIONING…
We measure the “strength” of a drug as a
reinforcer by infering from the rate of
responding. But there are problems with rate as
a dependent variable:
• Some drugs may stimulate responding.
• Some drugs may have effects that interfere
with the organism’s ability to make the
response.
THE ROLE OF OPERANT
CONDITIONING…
• …as a result, many studies will employ
Progressive Ratio (PR) schedules.
• In PR schedules the response requirement
changes after each reinforcer presentation.
• For example The response requirement may
begin with one. Following the first reinforcer
presentation, the requirement changes to two,
and then four, then eight, then 16 and so forth.
THE ROLE OF OPERANT
CONDITIONING…
• So with the PR schedule the particular ratio
where the animal stops is considered the
“break point.”
• Most non humans will self-administer virtually
the same drugs as humans with a couple of
noted exceptions (with considerable
difficulty):
• Marijuana
• LSD
Internal and external environments
Quiz # 5
Quiz # 5
Describe the environmental determinants of drug
action.
1. In operant terms, abuse potential can be thought
of as the ______ of a drug.
a.
b.
c.
d.
e.
Reinforcing liability
Potency
Ability to create emotional dependence
Ability to create tolerance
Habituation
Quiz # 5
2. The rate of self-administration is not a good measure
of the relative reinforcing capacity of different drugs.
This is because of which of the following?
a. Drugs may have effects that can interfere with the
organism’s ability to make the response.
b. Some drugs may have the effect of stimulating the
response.
c. It has been shown that the rate of responding does not
reflect the reinforcing properties of any stimulus.
d. All drugs are so reinforcing that the animal responds at the
maximum rate possible.
e. Both “a” and “b” are correct.
Describe potential drug interactions.
Clinical Considerations
Drug – Behavior Interactions and Clinical
Considerations. In this segment we take a look
at:
• The wide variety of ways in which drugs may
alter behavior.
• Clinically efficacious drugs and just exactly
what they do.
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
Some history
Basic pharmacological effects
Potential hazards
Psychiatric uses
Drug – Behavior Interactions and
Clinical Considerations
The barbiturates have a long history in
psychiatric medicine as sedative agents
• The barbiturates were developed by Beyer labs
in the 1860s
• The barbiturates are synthesized from
chemicals found in urine.
• The first of the barbiturates (Barbital) was
introduced in 1903.
Drug – Behavior Interactions and
Clinical Considerations
• The non-barbiturate chloral hydrate is what
was referred to, in turn of the century jargon,
as the infamous “MICKY FINN” …or “knock
out” drops.
=
=
Drug – Behavior Interactions and
Clinical Considerations
• The barbiturates are classified by their duration
of action.
– Ultrashort
– Short (under 4 hrs.)
– Intermediate (4-6 hrs.)
– Long acting (over 6 hrs.).
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
•
SOME EFFECTS OF BARBITURATES
Reduced attention span
Impaired behavior
Confusion
Poor judgment
Slurred speech and inadequate emotional
control
Drug – Behavior Interactions and
Clinical Considerations
SOME EFFECTS OF BARBITURATES
• Moderate side effects:
– Nausea
– Vertigo
– Vomiting
– Emotional upset
– Diarrhea
Drug – Behavior Interactions and
Clinical Considerations
SOME EFFECTS OF BARBITURATES
Potentially hazardous effects or serious side
effects:
– Shock
– Coma
– Death
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
•
THE BENZODIAZEPINES
Antianxiety drugs.
Controls seizures.
Interferes with rem sleep.
Interferes with sex drive and performance.
May cause birth defects (e.g. cleft palate).
Drug – Behavior Interactions and
Clinical Considerations
Rohypnol (Flunitrazepam)
“ROOFIES”
• The “date-rape” drugs.
• Related to valium.
+
+
=
Drug – Behavior Interactions and
Clinical Considerations
One of the many properties of the
benzodiazepines is disruption of memory.
• A person can recall previously learned
information but recalling new information
(while under the influence) is difficult.
• Several drugs in this class, including
Rohypnol, are used for nefarious purposes.
MEDICATIONS FOR MENTAL
ILLNESSES
•
•
•
•
•
What is mental illness?
Issues defining mental illness.
The medical model.
Mental illness and medicine.
Types of disorders.
Issues in defining mental illness.
– What is acceptable behavior?
– Should a person who exceeds acceptable behavior be
identified as mentally ill or simply different?
– Should social norms dictate appropriate behavior?
– What is normal?
Drug – Behavior Interactions and
Clinical Considerations
• ANTIDEPRESSANTS
– TRICYCLICS
– MAOIs
– SSRIs
• ANTIPSYCHOTICS
– CONVENTIONAL
– ATYPICAL
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
TREATMENT PRIOR TO THE1950s AND
TREATMENT AFTER THE1950s.
Primitive approaches.
Early pharmacotherapy
Psychosurgery.
Electroconvulsive therapy.
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
Major increase in the use of drugs.
In some cases an exclusive reliance on drugs.
There is no real “cure” (eliminated).
People may be “maintained” on drug therapy.
Drug – Behavior Interactions and
Clinical Considerations
PROBLEMS
• In understanding exactly what mental
disorders are.
• Patient compliance with drug treatments.
• social stigma
Prolonged use drugs for the management
of clinical disorders have many side
effects
Drug – Behavior Interactions and
Clinical Considerations
•
•
•
•
•
ANTIPSYCHOTICS
Known as major tranquilizers.
Also known as neuroleptics.
Discovered by accident by French surgeon.
Chlorpromazine introduced in the U.S. in mid1950s
Revolutionized the treatment of mental illness.
Drug – Behavior Interactions and
Clinical Considerations
CONVENTIONAL
• Blocking of the d2 receptor is the primary mechanism of
action.
• These drugs also block other types of receptors as well.
• Very commonly prescribed
• Erratic absorption pattern makes it hard to establish the
effective dose (ED).
• effects may be teratogenic.
Drug – Behavior Interactions and
Clinical Considerations
ANTIDEPRESSANTS
• In excess of 500,000 people are treated for
depression.
• Depression is a primary factor in suicide.
• Treatment is complicated because everyone is
depressed at some point.
TRICYCLICS
• Originally used to treat psychotic patients.
• Useful in the treatment of phobias.
• Can be toxic
Quiz # 6
Quiz # 6
Describe the clinical actions of therapeutic
drugs.
1. After taking antipsychotic drugs for a period of
time, about 30 percent of patients show a
condition called…
a.
b.
c.
d.
e.
Epilepsy.
Tardive dyskinesia
Delirium tremens.
Akathisia.
Physical dependence.
Quiz # 6
Describe the clinical actions of therapeutic drugs.
2. Prozac is which type of antidepressant?
a.
b.
c.
d.
e.
TCA
SSRI
MAOI
First generation antidepressant
None of the above. Prozac is a tranquilizer
FOR GROUP DISCUSSION
Drug Abuse / Misuse and Ethical Issues. In this
segment we discuss:
• Why drugs are self-administered and what
constitutes abuse and misuse.
• What are the major ethical issues involved?
FOR DISCUSSION
• Controversy. …should psychologists be
allowed to prescribe drugs?
• The DSM-5.
• Diagnostic categories.
Ethical/Legal Issues for Discussion
• Behavioral Pharmacology
• Behavioral Toxicology
• Behavioral Teratology
Behavioral Teratology
Exposure to drugs and other toxic
agents in utero may alter behavioral
functioning of the newborn
Review
•
•
•
•
Describe a general historical context.
Describe the basic actions of the nervous system.
Describe the fundamental actions of drugs.
Describe the environmental determinants of drug
action.
• Describe basic stimulus properties of drugs.
• Describe potential drug interactions.
• Describe clinical actions of therapeutic drugs.
Conclusions
• The interactions between drugs and human
behavior is poorly understood by the general
population.
• The behavioral effects of drugs are lawful.
• The behavioral effects of drugs are dependent
upon an array of behavioral and
pharmacological variables.
Thank You!
Rodney D. Clark, Ph.D.
Department of Psychology and Program in
Neuroscience
Allegheny College
[email protected]
814-332-4960