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the federal drug policy under which the manufacture, importation, possession, use and distribution of certain substances is regulated
Categorized certain drugs into 5 classes
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high addictive potential – not considered of medicinal value
There is a lack of accepted safety for use of the drug or other substance under medical supervision
No prescriptions may be written for Schedule I substances, and such substances are subject to production quotas by the DEA.◦ mescaline, lysergic acid diethylamide, heroin,
and marijuana, gamma hydroxy butyrate (GHB), ibogaine
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Drugs with a high abuse risk, but also have safe and accepted medicinal uses
Abuse of the drug or other substances may lead to severe psychological or physical dependence stimulants, opiates, methadone, codeine,
methylphenidate (Ritalin), mixed salt amphetamine (Adderall),
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less abuse potential than Schedule I or II
has a currently accepted medical use in treatment in the United States.
abuse of the drug may lead to moderate or low physical dependence or high psychological dependence.“ ◦ – includes barbiturates, anabolic steroids,
ketamine (?), buprenorphine, marinol (synthetic THC)
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medical use, less abuse liablity, less risk of physical dependence◦ benzodiazepenes (?) – although n of prescriptions
is controlled◦ some barbiturates
Schedule V◦ cough suppressants with small amounts of
codeine
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History◦ Cocaine◦ Source: leaves of E. coca (indigenous to western
South America◦ word spread through explorers, naturalists,
botanists
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History◦ Cocaine◦ Source: leaves of E. coca (indigenous to western
South America◦ word spread through explorers, naturalists,
botanists 1860’s – a variety of medicinal uses
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History◦ Cocaine◦ Source: leaves of E. coca (indigenous to western
South America◦ word spread through explorers, naturalists,
botanists 1860’s – wine tonics
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Launched in 1863- Europeansuccess; the world's most popular prescription
Some of its advocates; Henrik Ibsen, Jules Verne, Alexander Dumas, Robert Louis Stephenson, Sir Arthur Conan Doyle, Queen Victoria; King George 1 of Greece; King Alphonse XIII of Spain; the Shah of Persia; William McKinley, President of the United States.
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double the amount of work could be undergone when Peruvian Wine of Coca was used, and positively no fatigue experienced....."
Sears and Roebuck, 1900
"...sustains and refreshes both the body and brain....It may be taken at any time with perfect safety...
it has been effectually proven that in the same space of time more than
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History◦ Cocaine◦ Source: leaves of E. coca (indigenous to western
South America◦ word spread through explorers, naturalists,
botanists 1860’s – wine tonics 1884 - Freud
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as a mental stimulant as a possible treatment for digestive
disorders as an appetite stimulant in case of
wasting diseases as a treatment for morphine and
alcohol addiction as a treatment for asthma as an aphrodisiac as a local anaesthetic
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mid 1880’s –◦ Atlanta druggist John
Pemberton – devised a patent medicine that contained two naturally occurring stimulants; cocaine and caffeine Coca-cola – advertised as an
intellectual beverage a temperance drink; a brain tonic
Pemberton sold 2/3 of his interest in 1887 for $283.29
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late 1800’s until 1903◦ Coca Cola had ~ 60 mg/ 8 ounces◦ 1903 Coca Cola stopped having cocaine
1914 – Harrison Narcotic Act –◦ listed cocaine as a narcotic
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synthesized in the lab (in early 1900’s) first marketed in 1927 drug has been abused since its
introduction benzedrine inhalers used by a wide
segment of population during 1930’s amphetamines and war amphetamines and weight reduction
◦ 1967 – estimates of 23,000,000 prescriptions in US for weight reduction
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Cocaine use still rose during the 1920’s but then decreased in 1930’s because amphetamines became available (and at the time cost less, were more easily available AND the euphoria lasted longer)
Amphetamine took over in popularity during the 1940’s – 1960’s. In 1970’s restrictions on amphetamine tightened ◦ made amphetamine a schedule II drug so….
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some estimate 1.8 million Americans users of cocaine in 1998; majority between 18 and 34◦ males more likely than females◦ males more likely to use higher amount◦ males more likely to use for longer duration◦ significant proportion met criteria for ADHD
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coca leaves◦ leaves can be soaked and mashed to form coca
paste oral – 70 – 80% broken down by liver
biotransformation
cocaine hydrochloridecoca paste treated to form saltwater soluble and can be taken intranasally or injected
IV
snorting – not very efficient because cocaine hydrochloride is ionized; also cocaine has vasoconstrictive properties (so it limits its own passage into blood vessels)
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IV – onset is rush ~ 30 – 45 secs◦ duration lasts 10 – 20 min; ◦ 100% reaches circulatory system
freebase- extracted from crystalline from with either ether or sodium hydroxide◦ vaporized at lower temps than cocaine hydrochloride
and so can be inhaled
crack – freebase but extracted with alkaline water and premade (or prepackaged)
smoking not really efficient for delivering cocaine to body because significant portion is lost to pyrolysis – but remaining dose produces intense effect
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originally regional specificity
spreading across nation (ease of production although dangerous- explosions, toxic substances, etc)
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illicit amphetamine production estimated to be in the billions/year
methamphetamine◦ made in growing numbers of clandestine labs◦ produces greater cortical stimulation than
some other amphetamines◦ huge profit margin
ice – free base form of amphetamine
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Estimated that for each pound of methamphetamine produced, between five and six pounds of highly toxic waste is generated.
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amphetamine◦ causes release of newly synthesized monoamines◦ also blocks reuptake of monoamines
cocaine◦ blocks reuptake of monoamines
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stereotypic behavior◦ high doses result in stereotyped behaviors
representative for respective species in rat, can be sniffing, licking, biting or gnawing
Appetite suppression◦ weight loss
Aggression◦ several descriptions of murder and other
violent offenses attributed to amphetamine intoxication
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cardiovascular◦ heart disease increased risk for CVA◦ cardiac arrhythmia◦ increased blood pressure
respiratory◦ chest pain respiratory complications◦ difficulty breathing
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neurotoxic◦ seizures intracranial hemorrhages◦ cocaine or amphetamine induced psychosis◦ formication
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methylphenidate (Ritalin)◦ causes release of newly synthesized DA◦ also blocks reuptake of DA
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“Adderall”
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Strattera –atomexetine HCl◦ first non stimulant pharmacotherapy for ADHD◦ blocks reuptake of NE instead of DA
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methylated amphetamine – text covers this in chapter with
hallucinogens (affects 5HT as well)
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UNTIL RECENTLY - sold in health food stores and on internet
Now – no longer on US market!
◦ ephedra – also known as ma huang; herb ◦ FDA received many reports from doctors, government
health authorities and others about adverse-based ephedrine based products
Currently – OTC subject to FDA regulations HOWEVER herbal supplements currently are
essentially unregulated – may soon change!
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◦ either decreased effectiveness or potency of a drug
How does tolerance occur?
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Data is mixed
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acute tolerance
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acute tolerance
animal models – ◦ sensitization
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Psychological dependence – very strong!
Physical dependence – WD? ◦ Cocaine crash
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operant performance
animals will self administer in absence of tolerance, physical dependence, withdrawal or prior drug taking history
two bar test
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variation in extent and rate of self administration depends on drug being administered
ex. opiates – uniform and constant administration (moderate and measured with voluntary abstinence)
cocaine – frenzied intake followed by abstinence
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enhances basal neuronal firing or basal NT release in “reward circuit”
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1. dose-response rates at fixed ratios
2. progressive ratio schedule
◦ how hard is the animal willing to work for drug
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drug discrimination –
◦ 2 bar discrimination
◦ what does this tell us?
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initially trained to self administer drugs
followed by extinction
priming or nondrug stimuli
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good predictive validity - reinstate heroin and cocaine seeking in laboratory animals including as drug reexposure, drug cues, and stress (Self and Nestler, 1998; Shaham et al., 2000a; Stewart, 2000)
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1. non specific drug effects
2. only test the rewarding component of drug during “intoxicated” state
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rewarding stimulus is repeatedly paired with neutral environmental stimulus
food, water, brain stimulation, sexual partner
drugs
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1. can study reinforcing effects of a drug in drug free state
2. can sometimes see CPP in one trial(IV particularly)
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Animals find amphetamine and cocaine highly rewarding