Professional Documents
Culture Documents
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INTRODUCTION
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Form of communication with sun god = cocaine not only used but its effects
unique and powerful = suggest an association with gods (only priestly class
used cocaine)
New testament = Do not get drunk on wine Ephesians 5:18
Poppy flower seed = milk = latex = opium = morphine
Use of drugs = persisting and continuing (long-standing use) = humans are
somehow vulnerable to using drugs (we are ready to take them even if in a
destructive pattern)
Brain is set up to like drugs = brain is co-conspirator in drug use and abuse =
abuse and addiction = brain disorder
Darwin = monkeys also go through same experiences = hint to
vulnerability = appealing to our biological nature
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1) ALCOHOL
2) TOBACCO (contain nicotine)
3) CAFFEINE (most widely used psychoactive substance in the world)
4) MARIJUANA (THC, tetrahydrocannabinol = active ingredient)
5) INHALANTS (solvents found in glue or gasoline) = major health problem in
3rd world + children
6) OPIOIDS (importance in medicine pain killers)
7) ANTI-ANXIETY AND SEDATIVE DRUGS (medicine)
8) PSYCHOSTIMULANT (e.g., cocaine, amphetamine, methamphetamine)
9) HALLUCINOGENS (PCP = angel dust, LSD = acid)
10) other
Different molecules but all can be abused/addictive
Side effects = loss of control and increased adverse events = toxic side
effects
Increased toxicity w/ repeated use
Toxic side effects (alcohol = liver disease, marijuana = decrease mental and
physical performance)
BEHAVIORAL ADDICTIONS
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acetylaldehyde
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Post-synaptic thickening
NTs = potent, active substances, set off signals in the brain, controlled by
evolutionary forces
o Synthesized when needed (e.g., when levels go down)
o Depolarization = released from terminals
o Released into specific space where there are receptors
Uptake (e.g., dopamine) = increase efficiency of neurotransmission = the
neurotransmitter is re-released + also restricts spread of neurotransmitter
Neurotransmission = very rapid (fractions of s)
Disruption in overall process = dysfunction/disease
Drugs work by altering neurotransmission
Receptor = molecular sites where neurotransmitters bind == signal
NT receptors: G protein coupled receptors, ion channels (changes in charge
distribution)
acetylcholinesterase
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substances)
Neurotransmitter can have multiple receptors
o E.g., acetylcholine = ion channel and GPCRs
o Dopamine = 5 subtype GPCRs
Multiple receptors = multiple locations
Cocaine = alert, stronger, energetic, powerful, euphoric (stimulant effects)
Sigmund Freud = third scourge of mankind after alcohol and opium ==
cocaine
binds to
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2 different sites
(receptors)
Fit into more than one molecular site = multiple effects = different places =
multi-functionally
Cocaine can reduce bleeding, produce euphoria, cause addiction,
and act as a local anesthetic
Drug receptors widely distributed = different receptors
Drug dynamics = absorption, metabolized, excreted
Urine screens = antibody detections = drug/drug class presence tests (GC
& MS)
NTs tightly controlled + packaged
ALCOHOL
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can occur
Effects of ethanol:
Dependency chart:
Synergistic + sedative
effects
NICOTINE
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dopamine levels
increase in nucleus accumbens and prefrontal cortex
Alpha4-beta2 subtype may be responsible for this effect
Affects other neurotransmitters = serotonin, glutamate, opioid
peptides
Dopamine have pre-synaptic = nicotine taken =
MARIJUANA
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Plants = cannabis
compounds =
cannabinoids
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Cannabionoids = get user high, relaxed, more social, calm, mildly euphoric
PSYCHOSTIMULANTS
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= reduce size
of BV and raise BP
cocaine from plant = Erythroxylum coca and Erythroxylum novogranatense
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HALLUCINOGENS
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Dissociative anesthetics
catatonia
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o
o
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PCP
glutamate neurotransmitter at NMDA type glutamate receptor
LSD = acid = visual hallucinations (sometimes lead to suicide) =
persisting perceptual experience even when drugs are not
present
o Binds to serotonin receptors, stimulates 5HT-2A receptors
MDMA, Ecstasy = both simulant + hallucination
Neurotoxicity of MDMA == degeneration of nerve terminals of
neurons containing NT serotonin = neuronally destructive
Hallucinogens (2 types) = PCP type and others (e.g., LSD)
OPIATE DRUGS
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constrict pupils,
- OPIATE OVERDOSE
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Addicts take drugs = satisfy craving or avoid withdrawal feel euphoric, deal
with physical or psychiatric conditions
Treatment medications = methadone (opiate itself but reduce drug
Sedative (calming agent), hypnotic (agent that facilitates sleep; often higher
dose than sedative), antianxiety (anxiolytic)(similar to sedative; reduces
anxiety)
Drug types:
o Benzodiazepines (BZs) Xanax and Valium (very high doses
alone do not automatically cause death by overdose = thus, relatively
safe = most used medication in this class, but when taken with other
depressants = increase lethality of those substances; e.g., with
alcohol)
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o NonBz zolpidem
o Carbamates meprobamate (not really used anymore)
o Barbiturates secobarbital (not really used anymore)
o NonBzs buspirone (little or no abuse or addiction)
o Alcohol or marijuana
Valium (diazepam), Xanax (alprazolam), Ativan (lorazepam), Klonopin
(clonazepam), Halcion
Effects of BZs = sedation (up to intoxication), decreased anxiety, muscle
relaxation, sleep, amnesia, anticonvulsant activity, and addiction
Acts on GABA-A receptor (increase the action of GABA) = make inhibitory
effect of GABA greater
Gamma aminobutyric acid = major inhibitory NT in brain = both ion channel
receptors and GPCRs
Ion channel receptors (GABA-A) mediate flow of Cl- ions
GABA-A receptors = have multiple subunits + grouped as pentamers (5
proteins bundled together)
o NT modulators
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INHALANTS
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Damage to bone, heart, kidneys, lungs, increase risk for other diseases
Often abused by children and adolescents
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brain
No proven medications thus, treat symptoms
Inhalants = easily obtained, used but addicting and very toxic
Inhalants are unique group of abused substances because they are classified
according to their route of administration instead of their pharmacologic
profile or mechanism
Common = INHIBITION OF NMDA AND ENHANCMENT OF GABA-A RECEPTORS
CAFFEINE
- Mild stimulant
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Anabolic steroids
bath salts
(mephedrone found)
ANIMAL MODELS
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Before study:
o experimental plan must be described in detail and approved by
committee
o Required to be beneficial and nontrivial; discomfort must be
minimized
o Experimental plan must include vet care at every stage
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preference
Passive drug administration
(injected)
Drug self-administration (animal chooses to take drug via lever)
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Training phase
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Single drug with many effects = same drug receptor exists in many different
functional circuits/regions that promote different physiological action
o Drug interact w/ many different kinds of receptors for diff. NTs (also in
diff. fnal areas of brain/body)
E.g., NT acetylcholine, nicotine = psychic stimulant, BP elevator, gut muscle
contractor
o Nicotine/acetylcholine receptors found in all of these areas
Drug can interact w/ diff. receptors = involved w/ diff. NTs
o E.g., ethanol = interacts = GABA or glutamate receptors
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Dopamine is important modulator of reward, but not the only factor = there
are many diff. NTs and other reward systems
Dopamine is involved in attracting various stimuli
Post-mortem autopsy
PET = positron emission tomography = measure metabolism in various brain
regions, levels of diff. proteins, receptors
MRI = magnetic resonance imaging = measure structure, volume and
structure of brain
FMR = functional magnetic resonance = measure relative activity of various
brain regions
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- Annihilation
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o
o
o
o
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caudate, nucleus
accumbens
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putamen
(involved in learning
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GTP alpha activate enzyme (kinase = which adds phosphate groups), beta
gamma portions affects other enzymes
Subunits finish activations, then GTP converted to GDP, configuration returns
to how it started = complex ready to go again
Many diff. G-proteins + processes = Richness in variety of G-protein
signalling
TF regulators of gene expression
Activation of GPCR via NT or drugs
TF = protein (e.g., jun, fos, CREB) = required to bind to regulatory region
of DNA; helps translate genetic message in DNA to RNA or proteins
Activate TF via phosphorylation
TF bind to regulatory region so DNA = increase RNA and protein
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VULNERABILITY
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RISK FACTORS
- Cross adoption studies
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Adolescent rats seek more reward than adult rates (intake of sweetened
condensed milk = greater desirability in puberty than adulthood)
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Vulnerability factors
Personality traits = habitual patterns of behavior, thought, emotion
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PROTECTIVE FACTORS/PREVENTION
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TREATMENT
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Treatment can reduce drug abuse by half, criminality up to 80%, arrests 64%,
costs of drug-related crime
Treatment = set of activity (e.g., med or changing behaviors) with goal of
reducing or eliminating drugs
Stigma = attitude of disgust associated with being an addict
o Cruel problem, due to lack of info and rationality
o Prevents treatment (we want to avoid problem and topic)
o Prevents addict from coming forward to get treatment (in denial)
Cardiovascular, asthma, diabetes
Atherosclerosis and addicts
o Serious health problems
o Biologic/genetic vulnerability
o Slowly progressing and chronic
o Prone to relapse
o Require change in lifestyle
Addiction is brain disorder like many other diseases found in other organs
o Compares in many ways to atherosclerosis and other chronic relapsing
diseases
o No reason for stigma; must be overcome
Individual therapies evolve and vary
Treatment principles:
o Remain in treatment for duration (3 months = to get control of drug
taking and get the most out) = repetition
o Counseling
o Medications
o Comorbid conditions
Withdrawal = detoxification (good start in treatment)
Brain chain for long time and healing process slow
Avoid relapse = must undergo long-term treatment
Voluntary or mandated treatment (need to want) = urban myth? Does not
need to be voluntary
Monitoring (only way to concretely and objectively assess the progress)
Judicial mandate, 12-step programs
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Medications:
o Opioids = methadone, buprenorphine, naltrexone medications
o Tobacco = nicotine patch, spray, gum, lozenges, bupropion and
varenicline
o Alcohol = naltrexone, acamprosate and disulfiram
Vaccines against drugs
o Injection to produce antibodies = long lasting effects (months) vs. med
dose lasts several hours
o Antibodies do not need to get into brain, enter blood, thus do not have
side effects
o Vaccine stimulates immune system to create antibodies (antibodies
bind drugs in blood and prevent them from getting into brain)
Treatment yields for every dollar $4-7 = saves and reduces overall costs
General policies
o Drug abuse = public health issue; not criminal or morality issue
o Reduce demand through education, prevention and treatment
o Reduce and eradicate drug-related illness
o Enact laws supporting drug use reduction = no smoking in public
places
o Avoid harsh laws for possession of small amounts of drugs for personal
use
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