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What is a psychoactive drug?

- Chemical or group of chemicals
- Excludes common chemicals used to sustain health
Sugars, amino acids, salts
Vitamins
- Alters biological function
Psychoactive drugs
- have behavioral, emotional or cognitive effects
- impact biological processes in the brain
Can heighten perception
Can dull perception (pain)
Can distort
- act in the synapse

Why Study Psychoactive Drugs?

- They influence psychological processes.
- Used for many reasons, have many possible consequences
- Powerful psychological tools something that can be used to modify your
psychological abilities in a manner that is useful to you.
- Have a pervasive influence in our society
Commodities - Political and economic impacts
Social harms
Personal harms substance abuse (relationships, physiology,
academics)

Poison or Panacea?
- The dual nature of drugs
- Pharmacology is derived from the Greek words with dual meanings
Pharmakon - meaning medicine or poison
Pharmakeuin - the practice of medicine or witchcraft
- The Greeks recognized the dual nature of drug effects, they can have
both:
Therapeutic effects
Adverse effects
The effects always interact with individuals genetic makeup. So
something can be adverse or therapeutic depending on the person
Problems in the Drug Store
- Quick fixes magic bullet (comes to us courtesy of pencillin. Drugs as a
fixall)
- SOMA (the name of the drug in brave new world)
- Iatrogenic Abuse prescription based abuse.
- Many psychoactive drugs have positive effects
- All drugs have negative consequences
- Be wary of confirmation bias
Users then to embrace benefits and minimize harms
Those who regulate ten to ignore benefits and maximize harms
- The practice of prescribing opiates correlates with deaths (iatrogenic
effects)

Biopsychosocial Approach takes into account all influences with drug use
and how they interact with each other:
- Biological
- Psychological
- Social

Biological Factors
- Pharmacology Absorption, Elimination, Distrbitution
- Neuroscience Site of drug action in NT systems
- Genetic Individual differences

Psychological Processes Human Psychopharmacology

- Two Important Aspects
Drugs affect how the individual thinks, feels, and acts
Psychological processes influence drug effects
- Some Examples
Alcohol memory loss

Caffeine arousal

Social & Cultural Influences

- Society regulates drug use
 Social norms
Social influence
Availability
Laws

Drugs in Perspective: Historical and contemporary use and misuse

- Drugs must be understood from their past roles and uses
- Current patterns of use and abuse change, but are predictable (how is the
drug marketed to the audience?)

Psychotherapeutic Drugs
- Lorazepam/Diazepam (benzos)
- escitalopram
- antipsychotics
- atypical antipsychotics

Too much caffeine can cause memory loss.

All drugs have potential adverse effects
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Sources of Alcohol
- Fermentation
- Distilling
- Brewing

Sources of nicotine
- Nicotiana rustica
- Nicotiana tabacum

Methylxanthine
- Coffee Beans caffeine
- Tea Leaves Theophylline/Caffiene
Green tea not oxidized. Otherwise the same as black.
Black tea is oxidized (d/t passage of time)
- Cacao caffeine & theobromine
- New plant sources
Guarana 2-6% caffeine (highest natural concentration)

Cannabis Sativa
- Genetic variation in form
- Male/Female plants
Dried leaves Bhang/Ganga
Distilled - Hashish/Hash oil
Medical Forms THC/nabilone

Sources of Psychomotor Stimulants

- Natural Sources
Coca: cocaine
Ma Huang: Ephedra Amphetamine
Khat: Cathionine
- Derived Sources
Amphetamine: D/L isomers. Methamphetamine
Synthetics: Methylphenidate. Pipradol

Poppy Plant Opium sap exudes from incisions of the poppy pod. Oral &
smoking.
Types of Opiates
- Naturally Occuring morphine, codeine
- Semisynthetics heroin
- Synthetics meperidine, methadone, propoxyphene
- Antagonists naloxone, naltrexone

Peyote
- most widespread hallucinogenic drugs in the New World
- In Canada, Native Americans can legally take peyote (Mescaline is a
schedule II drug under the CDSA, but peyote is exempt)

Other Hallucinogens
- Salvia sage plant
- Betel Arecoline (actual compound in it), alkaloid from Areca nut
- Absynthe thujone (actual compound in it) from wormwood

Classical Poison Hemlock (kills you)

Origin of Drug (natural/unnatural) does not correlate with:

- poisons
- contaminants
- overdose
Natural drug does not mean safe or healthy.

Naming drugs
- Experimental Name RO23
- Generic name (nonproprietary name)
- Brand name (proprietary)
- Street name

MATCHING QUESTION DRUG CLASSIFICATION

Morphine and Codiene are chemicals found in the opium poppy

Anticholinergics atropine, belladonna

Depressants: Disinhibition Intoxication Sedation Sleep Coma

Death
FILL IN THE BLANKS Q

Defining Drug Use & Abuse

- Medical
Drug use and addiction are illnesses
Various forms of treatment
- Moral
Drug use is bad
Prohibition and enforcement
- Behavioral
Drug use is a learned habit that can cause harm
Regulation, prevention, treatment, and harm reduction

DSM formal criteria for mental health disorders

Modern Medical View Substance abuse disorder

Previous DSM included a substance-related disorders section

This category differentiates between substance dependence and
substance abuse

Current DSM
Doesnt differentiate between dependence and abuse
 11 criteria for current substance abuse disorder
o 1-9 focus on addiction
Overwhelming involvement
Psychological Involvement avoiding withdrawal,
craving (+) effects.
o 10-11 focus on tolerance/withdrawal

How Dangerous is Drug Use

- Dependence liability how likely is a drug to produce dependence
- Inherent Harmfulness how likely is the drug to cause harm
- Social Context Factors
o Social Sanction
Social and cultural influences
Legal treatment of the drug
o Availability how easy can you obtain the drug
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Abuse Potential: How dangerous is drug use

- Drug and method of use dependent
Dependence liability - how likely is a drug to produce dependence
Inherent harmfulness - How likely is the drug to cause harm
- Social context factors an unavailable drug isnt very dangerous
Social sanctions - social and cultural influences, and legal
treatment.
- Availability
how easy can you obtain the drug
- Part of abuse potential is drug dependent
- Some drugs are more likely to produce dependence and cause harm
- The risk of dependence and harm is also determined by the method of
administration.
Injection by the user is inherently harmful and more likely to
produce dependence
Injecting cocaine is more dangerous than chewing it
Drinking distilled spirits produces more rapid dependence than
beer.
- Dependence & Harm are positively correlated

Abuse Potential: Social context factors

- Social sanctions, prohibitions, cultural acceptance
Alcohol is less of a problem in Muslim cultures
North American and European youth live in an intoxication culture
- Availability
Khat is not a problem in North America
Tobacco has become a problem in China (because of less smoking
in NA)
Expansion of alcohol outlets increases drinking problems (more
shops = more alcohol problems)

Legal & Social Harms

- The consequences of drug use go beyond physical harms
Arguably more harm is caused by strict enforcement of cannabis
prohibition than by the drug
 - These observations suggest balancing social sanctions and regulations
against the inherent harmfulness of the drug
Cannabis versus Fentanyl

What does history tell us about drugs?

- Drugs have had a pervasive influence in our society
- Drugs as powerful tools (change our mood, how we think, etc)
- Drugs as commodities
- History should help us to prevent the mistakes of the past

Ancient Use
- Close to source of the drug
- Medicinal use (ETOH)
- Spiritual and recreational use (Peyote)

Middle ages 19th century

- Spread of drugs around the world
- Commerce in drugs
- Patent medicines

Modern world 19th to present

- Chemistry changes the potency and specificity of drugs
- Pharmaceutical industry

Earliest Use ETOH as medicine

Scythians oldest direct us of cannabis (intoxication, funerals)
Chinese Emperor Shen Nung Cannabis for menstrual cramps, rheumatism,
gout, malaria and evenhilariouslyabsentmindedness

Early History of Opium

Summerian "joy plant"
The ancient Egyptians discovered medical uses for opiates 3500 years ago.
Therapeutic Papyrus of Thebes
The ancient Egyptian, Greek, and Roman civilizations used opium for a
variety of medical purposes.
Early recreational use accompanied medical use
Effective poison
Chinese invented opium smoking to replace tobacco

Opium in Ancient Greece

Odyssey describes use For sleep and pain Morpheus: God of sleep

Coca Leaves in Incan Peru camels could work harder on it. It increased
alertness and oxygen intake.

Earliest Use of Cocaine

ancient use in Peru shown by burial graves dated to 2500 B.C.
Incas made sacred and carved idols with coca cheeks dating to 500 B.C.
Ma Huang use recorded for medicinal purposes over 5000 years ago
Khat (Bath Salts) use dates to antiquity - Alexander the Great sent it to
one of his generals to cure melancholia

Pre-Pharmaceutical Industry
- Commerce worldwide shipping of drugs.
- Technology
Chemistry
Hypodermics
- Patent Medicines compounds sold as cure-all
- Politics of use
war on drugs
opium wars - british and chinese fought over the importation of
opium. Britain was trying to stop it due to the problems with
addiction

History of Tobacco Used

- In the late 15th century, Columbus and other explorers found First Nations
in the New World smoking dried tobacco leaves.
- The pleasant effects of nicotine caught on like fire, and smoking quickly
became popular among the Europeans.
- At first, same price as silver (restricted to the wealthy)
- By the Early 17th century, tobacco use was widespread
Tobacco as Panacea - Once discovered by Columbus, tobacco was accepted
as having medical therapeutic value.

Cocaine Panacea
- Performance enhancing effects
- Curing depression (melancholia)
- Treating asthma
- General herbal remedy
- Patent medicine uses
- Treating opiate addiction (Freud used it for this)
- Tooth drops (anesthetic and reduce swelling of mucosal membranes)
- Coca wine Angelo Mariani
- Pembertons French Wine Coca
Prohibition eliminated alcohol
Then cocaine became prohibited and high caffeine content as
subbed in
Eventually reduced caffeine to current levels

Apothecaries & Patent Medicines

- Budweiser in 1904 as an alternative to patent medicines
- Coffee
imported from the colonies to America
Coffee houses banned in England
- Chocolate banned in Mexico by the catholic church because they thought it
was an aphrodisiac

Addiction was a significant problem in the 19th century thats why stuff was
being banned.

The Rise of Modern Pharmaceuticals

- New medical treatments
- Promise to relieve human suffering e.g. deinstitutionalization

But remember:
Poison or panacea social and individual side effects
Now huge lobby for profit
Amphetamine
- Medical use
Cold remedy
Diet pill
ADHD
- Soldier use
keep them awake during all-night bombings
Japanese kamikaze pilots
German blitzkrieg pilots
But highly addictive

Trends in Drug Development

- Specificity (SSRIs)
- Reduced side effects
- Time limited (shorter duration)

In search of the perfect drug!

- Heroin as a cough syrup;
- Rapid acting benzodiazepines (cause more addictive behaviors)
- Addiction!

Rate of cirrhosis indicates the rate of consumption

Does Prohibition Work

- Death penalty in China
- Communism and opium in China
- Arab world today
- 20th century US alcohol, cocaine, marijuana
- Chocolate/Coffee?

Permissiveness Lessons Learned - Should society regulate drug use?

- Overdose death (regulation may help)
- 19th century alcohol and opiate use (legal alcohol is better than illegal
alcohol)
- Absinthe
- Designer drugs: ecstasy
- Fentanyl

Regulation Vs Prohibition
- Regulation is the general term for legislated controls over the distribution
and use of drugs
- Prohibition is an extreme form of regulation
- Other forms include:
Taxation
Control of sales
Age restrictions
Location restriction
Activity restrictions
Advertising policies
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Structure & Function Key Points

- The brain includes regions and systems that have specific psychological
and behavioral functions
- Brain systems interact through networks and the activities of these
networks
- The neuron is the cell that communicates information in the brain
- Communication in the brain systems occurs at synapses
- Synapses are the connections that govern the patterns of brain activities

Key Points: Synapses and Neurotransmission

- Synapses are connections between neurons
- Synapses use chemicals called neurotransmitters to
provide information to other neurons
- Neurotransmitters define systems that serve specific functions (sometime
multiple functions)

Key Points: Drugs & Brian Function

- Psychoactive drugs work by changing brain functions
- Drugs work by modifying neurotransmitters and neural communication

How Drugs Work

- At the system level
- Interact with chemical processes of neurotransmission
Increase
decrease
distort natural communication processes (amplification, dampening,
and distortion)
- Homeostasis, setting, learning, and residual effects

Hippocampus learning, memory, spatial stuff.

The Neuron Functions

- Neurons process information
Collect info
Process/integrate info
 Output information
- Neurons have 3 basic parts
Dendrites collect info
Soma (cell body) produces the nutrients that the cell needs.
Axon integrate and output info

Neurons Speak Two languages

- NTs
- Action potentials

Neural Communication
1. Dendrites receive neurotransmitter (NT) signal
2. If excitation > threshold, action potential fired
3. Action potential spreads through neuron, causing NT release at all its
synapses
4. This transmitter affects partner dendrites:
Excite makes an action potential more likely
Inhibit makes an action potential less likely
Modulate alters the neurons in a more lasting way
5. After each action potential:
Released transmitter is cleared/inactivated
A very brief refractory period during which that neuron cant fire
another action potential

Synapse specialized for chemical communication between axon and

dendrite, where the two cells draw very close but dont quite touch (20-nm
synaptic cleft).
Presynaptic side: the axon has vesicles loaded with neurotransmitters.
Postsynaptic side: the dendrite is studded with receptors to detect the
transmitter.

Understanding Drug Effects on Neurotransmission

- Drugs work by modifying neurotransmitter systems
- Two basic functions of these systems
Specific information carried in the pattern of neuronal firing
 Tonal information general signal effecting the level of activity or
sensitivity of other systems or sometimes regions
- Three types of effects
Amplification of the signal
Dampening of the signal
Distortion of the signal

EXAM QUESTION ALERT

Cholinergic Function in the Brain

- Extensive connections throughout
subcortical regions and the cortex
- Major role in attention
- Selective and tonal function that affects many neurons

Major NT Systems
- Monoamines EXAM QUESTION
Norepinephrine
Dopamine
Serotonin

Catecholamines epi, noepi, DA

W 5HT

Indolamines 5HT
- PFC and cerebellum

Endorphins NTs in the brain that are mimicked by opiate drugs

GABA
- gamma-aminobutyric acid
- most abundant inhibitory NT in the brain
- projections in the visual cortex, motor areas, limbic system, and
cerebellum

Glutamine excitatory

Endocannabinoids - Lipid neurotransmitters mimicked by THC

#5*

Pharmacology of Neurotransmission
- Each NT has distinct receptors and enzyme systems attached to them
- Similar classes of NTs may share some biological processes
- Drugs often exert their effects by interacting with these chemical
processes

Drug effects on synaptic transmission

- Drugs interact with specific NT systems
- Drugs may effect each step in the process in qualitative and quantitatively
different ways
- Drugs that enhance or mimic NT activity are called agonists
- Drugs that interfere with or block NT activity are called antagonists
WHY DO WE CALL IT A NEUROTRANSMITTER
 9/12/2017 5:06:00 PM

missed initial 20 mins

Neuropharmacology: Alcohol Effects in the Brain

Not specific to a particular transmitter or receptor site (does
dependent)
Increases Dopamine concentration
Decreases Serotonin neurotransmission Stimulates Opiate
Release
Potentiates GABA receptor function
Impairs glutamate function

ALCOHOL

Dopamine, Serotonin, and Endogenous Opiates (>.01-.05 BAC)

- alcohol increases dopamine concentrations in nucleus acumbens and other
reward centers
- alcohol decreases serotonin activity leading to increased impulsivity and
aggressiveness
- Endorphins and Enkephalins are released by the brain when exposed to
alcohol

Affect on GABA function (~>.06 BAC)

- Alcohol Potentiates GABA receptor function
- GABA is major inhibitory neurotransmitter
- GABA receptor is site of action of
sedative/anesthetic barbiturate, pentobarbitol
sedative/anxiolytic benzodiazipines
- Major Site of Affects include:
medial septal nucleus -- controls arousal state
Purkinje neurons in cerebellar cortex -- controls sensory and motor
activity

Affect on Glutamate Function (~>.2 BAC) BLACKOUT

- Alcohol inhibits glutamate NMDA receptor function
Glutamate is the major neuroexcitatory neurotransmitter in the
brain, accounting for 40% of all synapses.
- Impaired Glutamate Receptor Function Causes:
increased dopamine activation
cognitive impairment and amnesia
inability to learn new information
- Alcohol parallels action of PCP or angel dust

ETOH

- DA release in nucleus accumbens

- inhibits glutamate

- opioid peptides

- GABA

Nicotine and the Brain

To understand the action of nicotine, it is essential to understand the
neurotransmitter acetylcholine (ACH)
- nicotine doesnt enhance attention and learning in non-smokers
- Nicotine works at both central and peripheral acetylcholine receptors
- Specific to nicotinic receptors

ACh
- Dose Dependent Effects
Low dose stimulation
High dose blocking
- Effects in the brain
Cortex attention and learning
Limbic system
o Reward
o Stress hormone release

ACh activates nicotinic and muscarinic receptors depending on which side

of ACh binds.

Neurophysiology of Methylxanthines
 - Main effect is to block inhibitory effects of adenosine a widespread
inhibitory NT
- High doses also block benzodiazepine receptor in GABA complex - anxiety
induction (caffienism)

Neuropharmacology of Cannabinoids
Wide variety of effects
- Most NT systems affected
- Feedback system
Evidence for a specific receptor
- Specificity and low dose effects
- Two receptors now isolated
- Endocannabinoid (EC) found called Anandamide (several others have now
been found)
- CB1 primarily impacted by THC
- CB2 impacted by cannabinolmostly in the peripheral organs, esp
immune system

Endocannabinoid regulations of synapses

- Activation of post synaptic neuron causes synthesis and release of
endogenous cannabinoids (ECs)
- ECs activate receptors on presynaptic neurons inducing chemical changes
that reduce the release of NTs

Hallucinogen subgroups***
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***Bioavailability question on exam

***Inhalation is faster administration than IV

To pharmacologists, the drug experience involves two branches:

pharmacokinetics and pharmacodynamics.
Pharmacokinetics: the branch of pharmacology that concerns the
absorption, distribution, biotransformation, and excretion of drugs
Pharmacodynamics: the branch of pharmacology that concerns the
biochemical and physiological effects of drugs and their
mechanisms of action

Key Terms
Pharmacokinetics
Drug concentration curve
Absorption
Elimination
Site of action
pH
pKa
Lipid solubility
Passive filtration
Pharmacodynamics Dose response curve Tolerance
Sensitization
Compensatory response

Pharmacokinetics
Main Idea is that drugs take time to get into the system and time to
leave with different concentrations at different times.
Kinetics helps to answer questions such why does drinking on an
empty stomach make the effects of alcohol strongerabsorbed
more quickly, dont get as drunk as fast.
Why do people smoke as opposed to eating tobacco?the tobacco
in smokes and chew are different.
Why females are more affected by a drink of alcohol?slower
metabolism
Main Idea
It takes time for drugs to get in and out of the body
The properties of the body interact with a drugs chemical properties
Drug effects are influenced by both the drug and psychological factors

Drug Dose
Drug dose is computed according to the recipients body weight.
Standard way of expressing dose: in milligrams of drug per kilogram of
body weight (mg/kg).

Routes od Admin
Route of administration: site where drug is taken, or how it is taken
Route of administration: chosen according to the drug taken and the goals
and circumstances of administration
What are some of the ways drugs are administered?

By oral ingestion (per oral, PO)

By injection SC/IM/IV/Intraperitoneal
By inhalation
Through the skin or membranes of the oral cavity:
Intranasal
Sublingual
Transdermal

Intravenous drug injection is

Associated with rapid drug effects, making it the preferred route of
some drug abusers.
Considered dangerous because large quantities can reach the
site(s) of action so quickly.
Drug concentration curve is a combo of a absorption curve and an
elimination curve.

Drug concentration curves - Concentration of drug in a solution over time

Deriving drug concentration curves
combining absorption and elimination
rate of onset: how fast does the drug achieve its peak concentration
half-life: the amount of time to eliminate half of the drug
Would be ideal to measure drug concentrations at the site of action

Drug kinetics are important because they tell us how fast drugs get in the
body, where they go, and how long they are in the system
Drug absorption, distribution, and elimination are affected by different
biochemical factors
These factors accentuate the complexity of each individual drug experience
Features that effect absorption: Properties of various routes of
administration
Lungs - inhalation
Skin - topical
Body tissue - s.c.; i.m., i.p.
Ornasal cavities - sniffing, snorting, puffing
Digestive system - p.o., suppositories

Physiology of drug distribution

Body fluids: Circulatory systems and separation
blood
lymph
Cerebral spinal fluid (CSF) separate from other fluids.
interstitial fluid
vascularization of tissue
circulatory flow

Membrane properties and diffusion

lipid bilayer nonpolar drugs pass through
passive diffusion
lipid solubility
active transport

Placental Barrier drugs pass the placenta

Drug Elimination
Drug elimination: occurs through direct excretion of the drug from the
body, or through metabolism of the drug and excretion of its by-products
Drug half-life: commonly used term. Refers to the time that must pass for
the amount of drug in the body to be cut by half. Its a constantso high
concentration means more drugs is getting eliminated
Passive elimination - lungs, skin, digestive system
Enzymatic deactivation - liver function
Kidney reabsorption ETOH is reabsorbed because it passes through
membranes so fast. Kidneys only eliminate ETOH once the liver has
deactivated it.
 Bowman's capsule
proximal and distal tubules
acidification

Features that effect absorption: Chemical properties of drugs

Size matters: some drug molecules are so big that they will not
pass through capillaries and have great difficult passing through
membranes unless actively transported
pH: body fluids differ greatly in their pH
o pH interacts with the drugs properties to determine how well
the drug is absorbed in various tissues
The pH of the drug, and the pH of the fluid determine the absorption
properties of most drugs
Drugs are either weak acids or weak bases
This feature determines the effect of pH on the ionization of the
drug in the fluid (ETOH and cannabis are lipid soluble)
Weak acids are more ionized as pH increases
Weak bases are more ionized as pH decreases
Ionized drugs do not cross lipid membranes
pKa: is the pH of a solution at which 50% of a drug is ionized.
pKa is important because it determines how well a drug is absorbed
across cell membranes in different body cavities

Impact of pKa on Drugs Absorption

The mouth, the digestive system and kidney filtration are not pH
neutral: They are acidic.
o So you wont get ionized weak bases being aborbed
o You might get strongly acidic drugs neutrally charged crossing
cell membranes
Blood and plasma are more pH neutral = 7.4

Weak Bases
Weak bases are drugs that become more soluble as pH increases
The percent ionization decreases as the pH increases
Less ionized drugs more readily cross cell membranes and are
absorbed more quickly
 Caffeine is absorbed and reabsorbed more readily than either heroin or
morphine because it has such a low pKa
Heroin crosses the blood-brain barrier much faster than morphine

They start ionized, then as pH increases they become less ionized.

As the pH lowers, they gain a proton and become positive

***EXAM QANSWER C

Weak Acids
Weak acids are drugs that become more soluble as pH decreases
The percent ionization increase as the pH increases
 Less ionized drugs more readily cross cell membranes and are
absorbed more

Weak acids become more ionized with higher pHs
As the pH increases they lose a proton and become ionized

The Dose-Effect CurveResponse or effect as a function of dose

Prototype dose-effect curve: has an S shape
Effective Dose
Effective dose ED50
Toxic dose TD50
Lethal dose LD50