DB Exam 2

cocaine history

• derived from coca leaves in high-altitude rainforests

• originally was chewed (still is in some cultures)

• first isolated in 1859 by German chemist Albert Niemann

  • mixed into beverages and topical creams (prescribed for toothaches and given to children)

Vin Mariani

• 1883- mix of cocaine and wine said to restore energy and health

  • has a half-life 5x longer than cocaine alone

  • endorsed by “celebrities” (i.e. The Pope)

coca-cola

• originally created in 1885- like vin mariani but without the wine/alcohol

  • by 1903, cocaine was removed

stimulant

• drug that increases physiological and mental functioning by speeding up messages traveling between brain and body

coca leaves

• type of cocaine

• administration: oral (chewed)

cocaine hydrochloride

• type of cocaine

• administration: inhalation (snorted), IV injection

free base

• type of cocaine

  • subunit of cocaine hydrochloride

• administration: inhalation(smoked)

crack

• type of cocaine

  • subunit of cocaine hydrochloride

• administration: inhalation(smoked)

cocaine immediate effects

• burst of energy (rush/high), improved sense of self, sexual arousal, increased sympathetic nervous system activity (high HR, BP, respiration, etc.) and inhibited parasympathetic NS activity

• Followed by a crash, feelings of depression, and cravings

cocaine long-term effects

• irritation, depression, paranoia, hallucinations

• “cocaine bugs” under skin

  • scratched or even cut out

• cocaine psychosis

cocaine psychosis

• chronic cocaine use disorder characterized by hallucinations, anxiety, and paranoia

dopamine agonist

• Cocaine is an example

  • blocks reuptake of dopamine, more available dopamine in synapse

  • nucleus accumbens

incentive sensitization theory

• the more a person uses cocaine, the less it becomes about liking the drug and the more it becomes about wanting the drug

  • less enjoyment and more craving

kindling effect

• over time, users develop a tolerance to the euphoria, but become sensitized to motor activation and brain excitation

  • can lead to seizures

reinforcer

a stimulus that increases the likelihood of a behavior occurring again in the future

reinforcement potential

• can be measured by answering:

  • how often will a subject use the reinforcer with unrestricted access to it?

  • what are they willing to give up in order to receive the reinforcement (e.g. time, money, effort)

pickens and thompson

• set of experiments conducted to examine the reinforcement potential of cocaine on different reinforcement schedules

  • methods: cocaine admin. dependent on lever press

• results:

  • free access: consistent, high response levels

  • faster response rate for lower doses

  • response rates increased as number of lever presses required increased

• tells us that cocaine has a high addiction potential because it is extremely reinforcing

cocaine treatment approaches

• first phase- detox and abstinence

  • first 24-48 hours: depression, headaches, agitation, irritability, insomnia

  • inpatient detox

• support groups: cocaine anonymous

• CBT

• Contingency management programs

• No FDA approved drugs yet

cocaine medical uses

• mostly a recreational drug

• topical treatment that blocks nerve impulses

  • nasal and throat surgeries

  • nosebleeds

amphetamine history

• ephedrine isolated in 1887 by german chemists

  • by 1932, synthetic form of ephedrine is marketed as a CNS stimulant, appetite suppressant, and bronchial dilator

• WW2- given to German and US troops to keep them awake and alert (Kamikaze pilots and Nazi Germany)

• After war, drugs kept people awake (college students, truck drivers)

• Abuse peaked in 1967, declined over 70s as cocaine use rose

• By 1970, 10% of the US population had used meth

• 90’s- meth labs spread across rural areas

ephedrine

• active ingredient in the Ma Huang plant; stimulates the nervous system

speedball

• a stimulant mixed with a depressant

  • Hitler did this

comprehensive methamphetamine control act

• 1996

• increased legal penalties for manufacturing and trafficking meth

combat methamphetamine control act

• 2005

• established restrictions and penalties for the sale of meth’s precursor chemicals

  • ex: HCl, ephedrine, red phosphorus, liquid ammonia

• looked like it was working, however meth trafficking switched from domestic labs to being smuggled in from Mexico

recreational amphetamines

• methamphetamine crystal meth, bath salts

instrumental amphetamines

• adderall, ritalin

amphetamine acute effects

• increased sympathetic nervous system activity, euphoria, and invincibility, decreased appetite, boost in energy and alertness

• acts similarly to cocaine, but lasts longer

amphetamine chronic effects

• hallucinations, delusions of parasites in skin, obsession compulsions, paranoia, violent tendencies, mood swings

  • amphetamine psychosis

• acts similarly to cocaine, but lasts longer

amphetamine psychosis

• chronic amphetamine use disorder characterized by paranoia, hallucinations, and disordered thinking

amphetamine on the brain

• dopamine and norepinephrine agonist

• nucleus accumbens and frontal lobe

amphetmaine treatment approaches

• total abstinence first

• then support groups or CBT

• abusers are less likely to receive treatment because they believe they are in control of their use

  • denial and invincibility

  • high relapse rates

amphetamine medical use

• prescribed for ADHD (ritalin, adderall, vyvanse)

  • medication more effective than behavioral treatment

• prescribed for narcolepsy (Modafinil) and nasal decongestants

stimulant decreasing hyperactivity

• amplifies the effects of important environmental stimulation and decreases noise from unimportant stimuli

• increases motivation

tobacco history

• 1492- Christopher Columbus arrives in San Salvador and receives a welcome gift of tobacco leaves

  • Crew member tried to share the hobby back home and was imprisoned for witchcraft

• 1559- Official introduction to Europe

• 1604- King James 1 of England condemns use

• 1700s- snuff and chewing tobacco

• 1800’s- civil war

• 1900’s cigarette use rapidly increased in first half

• 1971- TV advertising banned

• 1993- research cam out that secondhand smoke inhaled by nonsmokers also caused lung cancer

  • public places started becoming smoke-free

snuff

• finely shredded tobacco placed or sniffed into the nose

  • dominant form of tobacco in Europe

• 1700’s tobacco use

chewing tobacco

• shredded tobacco leaves placed between gum and cheek (absorbed through membrane)

  • dominant form of tobacco in America

  • Cheap, but health hazard with spitting

• 1700’s tobacco use

civil war

• tobacco use during 1800’s

  • cigars and cigarettes became dominant tobacco forms

  • cigars seen as “manly,” cigarettes seen as “sissy” or “dainty”

1900 tobacco use

• rapidly increased in the first half of the century

  • cheapest form of tobacco

  • easiest for soliders to carry

  • women challenged the idea that only men could smoke tobacco

1964

• year that the First US Surgeon General report on smoking and health

  • causally linked smoking to lung cancer, throat cancer, bronchitis, heart disease, and birth defects

• 25% drop in cigarette consumption in the next month

  • bounced back shortly after due to relapse

1993

year that research came out that secondhand smoke inhaled by nonsmokers also caused lung cancer

• public places started becoming smoke-free

Tobacco Settlement of 1998

• settlement where the tobacco industry agreed to pay the states compensation for the costs of treating people with smoking-related illnesses

  • paid states ~ 246 billion over a 24 year period

  • refrained from marketing tobacco products to people under 18 year old

  • donated 24 million annually for 10 years to foundations researching how to reduce smoking habits in youth

  • most states used their settlement money to pay off state debt

  • less than 3% of funds actually went to prevention programs

  • cigarette prices increased so tobacco companies could finance the settlement (kind of worked)

tobacco control act of 2009

• gave the FDA full authority of regulating tobacco products sold in the US; led to creation of new FDA center for Tobacco Products

  • oversaw science-based tobacco regulation, full disclosure of ingredients in tobacco products, mandated warning labels highlighting health risks, banned candy-flavored cigarettes, etc.

impact of surgeon general report

• smoking prevalence decreased from 42%-14%

• ~ 8 million premature deaths from tobacco use were avoided

• tobacco control contributed extra 2.3 years to male life expectancy and 1.6 years to female life expectancy

tobacco use today

• regular smokers (all ages):

  • 1940: over 50%

  • 1960: ~40%

  • 2020: ~15%

• regular smokers (college students)

  • 1999: ~30%

  • 2007: ~20%

  • 2020: ~4%

tobacco components

1. gas phase

2. particulate phase

gas phase

• gas compounds within tobacco smoke

  • carbon monoxide, carbon dioxide, ammonia, acetone, etc.

particulate phase

• small particles suspended in tobacco smoke

  • tar, nicotine, and water droplets

dangerous compounds in tobacco

• carbon monoxide- cardiovascular risk

• tar- lung cancer risk

• nicotine- dependence/addiction

carbon monoxide

• odorless, colorless, tasteless gas that prevents blood cells from carrying oxygen throughout the body

  • primary factor elevating the risk of cardiovascular disease in smokers

tar

• sticky material filled with pollutants and carcinogens

  • primary factor that elevates the risk of lung disease (cancer, COPD, emphysema)

nicotine

• primary psychoactive ingredient in tobacco that acts as a stimulant and is responsible for the addictive properties of tobacco

  • ~60mg of pure nicotine is lethal for an adult

  • around 2-8mg of nicotine is ingested by someone who smokes one pack per day

goldberg’s nicotine study

• 1981

• Training

  • Monkeys press lever for nicotine admin

  • administration paired with light

• testing conditions

  • free response

  • nicotine swapped with saline

  • light stimulus removed

• results

  • free response- pretty high and consistent rates

  • saline swap- response rates dropped significantly

    • response was due to nicotine, not just random responding or conditioning to light

  • light removed- response rate decreased

    • drug paired cues contributed significantly to drug-seeking behavior

• conclusion

1. nicotine is an effective reinforcer

2. drug related cues significantly affect drug craving

• implications for treatment approaches (identifying cues)

  • treatment should focus on biological and environmental components

nicotine on the brain

• cholinergic agonist

  • receptors: nicotinic acetylcholine receptors (nAChRs)

  • Increases acetylcholine, dopamine, norepinephrine

  • fast acting: inhalation, lipid soluble

physical effects of nicotine

• nausea, dizziness (usually only for new users)

• increased HR, BP, adrenaline

• promotes concentration

  • feels “relaxing”

nicotine tolerance

• mixed effects

• tolerance to nausea/dizziness, not as much to sympathetic effects (HR, BP, adrenaline)

withdrawal from nicotine

• symptoms start ~6 hours after last administration

• decreased HR and BP, headaches, lack of concentration irritability, drowsiness

• strong cravings (dopamine deficits)

tobacco adverse heath effects

1. cardiovascular disease

   1. coronary heart disease (CHD), arteriosclerorsis, atherosclerosis

2. respiratory disease

   1. COPD, asthma, stroke

   2. 80-90% of COPD cases result from smoking

3. cancer

   1. responsible for 80% of lung cancer deaths and 30% of all cancer deaths in the US

• tobacco use in the leading cause of preventable death in the US

• smokers live around 10 years less than nonsmokers

• life expectancy shortened by ~14 minutes every cigarette

secondhand smoke

• presents a major health risk to nonsmokers and is known to cause cancer in humans and animals

• causes the premature death of 41,000 adults and more than 400 infants each year

• 67.2% of youth who live with a smoker have been exposure to this

secondhand aerosol

• from e-cigarettes is a known source of secondhand exposure to nicotine and can also contain aldehydes and heavy metals, which are also found in cigarette smoke

• in 2019, less than half of working adults reported that their employer had a formal policy addressing vaping in the workplace

tobacco regulation

1. taxation of tobacco products

   1. cigarette smuggling

2. restricting access of young people

   1. federal minimum age moved from 18-21

3. education approaches

   1. graphic, dramatic displays

   2. warnings on cigarette packs

vape

• device that heats up a liquid mixture of nicotine and other liquid chemicals for the user to inhale

  • In 2020, 25% of high school seniors and 19% of college students did this regularly

vape health risks

• nicotine is responsible for dependence

• vapors inhaled contain chemical carcinogen

• accidental poisoning associated with refillable cartridges

• development of e-cigarette or vaping product use associated lung injury (EVALI)

• increased risk of diseases associated with lung function

vaping regulations

• restricting locations where vaping is allowed

• restricted age requirements for retail sales access

• first FDS approved e-cigarette

  • potential benefit of smokers fully switching to vaping outweighed potential risk to youth

nicotine recovery timeline

• 8 hours; carbon monoxide levels drop to normal

• 24 hours; heart attack risk decreases

• 2wks-3months- lung function increases up to 30%

• 1 year: excess risk of heart disease cut in half

• 5-10 years- stroke risk back to nonsmoker level

• 10 years- excess risk of death from lung cancer cut in half

• 15 years: heart disease risk back to nonsmoker level

nicotine quitting

• high relapse risk

  • 1/3 of all smokers in the US try to quit each year

    • <1/10 successfully quit

  • on average, it takes a person 8 attempts to quit nicotine

  • longer you use, harder it is to quit

    • majority of adult smokers started as teenagers

• nicotine replacement therapies: nicotine gum (nicorette), nicotine pathces, nasal spray or inhaler (Nicortol)

  • other approach: hypnosis, acupuncture, craving reduction prescription drugs, medical education (smokers told their “lung age” are twice as likely to quit)

xanthines

• compounds that act as CNS stimulants

• include:

  • caffeine

  • theobromine

  • theophylline

caffeine

• fastest acting xanthine, but shortest lasting

• first isolated from the coffee bean in 1819

theobromine

• xanthine that is found in chocolate; only 1/10th as strong of a stimulant as caffeine

  • slowest acting, longest lasting

theophylline

• xanthine that is found in tea; used in prescriptions as a bronchodilator

  • in between caffeine and theobromine

coffee arabica

• type of coffee bean

• first type of harvested coffee bean; native to the Middle East, now primarily grown in South America

coffee robusta

• type of coffee bean originally grown on the Indonesian island of Java, now grown mainly in Indonesia, Brazil, and Africa

coffee houses

• started popping up in England in mid 1600’s

• places where intellectuals could meet and argue

• America followed suit in the 1700s

coffee

• after the revolutionary war, this was considered America’s national drink

  • by 1860, Americans were consuming ¾ of the worlds production

• xanthines: caffeine only

  • average: 100mg in 5oz cup (ranges form 57-145)

tea

• world’s oldest caffeine containing beverage

• brought from Asia to Western Europe in the early 1600’s

• Mixed reviews

• Ultimately led to the Opium War

• 1773- British gov. allowed British agents to sell tea directly into the American colonies, bypassing American tea merchants → Boston tea party

• Xanthines: caffeines and theophylline

  • average: 60g in 5oz cup (based on type)

  • in America, most of this is consumed iced

chocolate

• comes from cocoa bean on cacao trees native to Mexico and Central America

• Brought from the Aztecs to Spain in 1528

  • added sugar to the recipe, typically consumed as a drink until the invention of the chocolate bar in 1847

  • 1700’s- chocolate houses were operating similarly to coffee houses

• Xanthines: caffeine and theobromine

  • Average: 10mg in 1oz

caffeine administration

• levels peak in bloodstream around 1hr after administration

  • average half life: 5-6 hours

  • highly variable (liver functioning, age, medications, smoking, etc.)

caffeine physical effects

• a “buzz” or energy boost, increased HR, BP, body temperature, adrenaline

• trouble falling asleep or staying asleep

• increased feelings of anxiety, tingling sensations, or shakiness

• lots feel the effects of the drug immediately

caffeine on the brain

• “Double-negative” effect

  • inhibits an inhibitory neurotransmitter (adenosine)

• blocks adenosine so users experience the opposite effects of adenosine

adenosine

• inhibitory neurotransmitter that binds to receptors to produce feelings of sleepiness, blood vessel dilation, and constriction of bronchial pathways

  • caffeine blocks, so induces opposite effect

caffeine not working

• the more you believe caffeine works, the more it will

• caffeine works better when you’re already tired or bored

• genetics

• tolerance

• interactions with other drugs

• psychiatric conditions (ADHD)

• age

• biological sex

• time of day

caffeine health benefits

• could lower the risk of developing Parkinson’s for men

  • reproduced in handful of studies

• correlational evidence shows that people who drink coffee live longer

• could act similarly to Ritalin or amphetamine and reduce hyperactivity (not confirmed)

caffeine health risks

• cardiovascular effects

  • mostly seen in people who drink 5-6 cups per day, have preexisting heart conditions, or who smoke

• effects on bones

  • elderly people who drink more than 3.5 cups per day had ~80% greater risk of developing osteoporosis

• pregnancy risks

  • high consumption early in pregnancy increases the risk of low birth weight, extremely high consumption could increase miscarriage risk

• panic attacks

  • sometimes seen with high consumption (4-5 cups), more likely in individuals with panic disorder

caffeinism

• condition that occurs when ~1000mg of caffeine is consumed over a short period of time (~10 cups of coffee)

  • results in extreme agitation and anxiety, muscle hyperactivity and twitching, insomnia, heart palpitations, and nausea

• lethal dose of caffeine: ~5,000-10,000mg

caffeine dependence

• > 85% of adults in the US consume caffeine every day

• Average daily intake = ~280 mg (around 3 cups of coffee

caffeine tolerance

• strongest for cardiovascular effects

  • unless large amount of caffeine is consumed, you probably wont feel heart racing

caffeine withdrawal symptoms

• headaches, impaired concentration, drowsiness, irritability, muscle aches, other flu-like symptoms

caffeine craving

• physical dependence is obvious based on withdrawal symptoms, psychological dependence is less clear

opioid

drug with analgesic (pain-reducing) properties that act like opium in the brain

• schedule II (except heroin-1)

opium

analgesic and euphoriant drug acquired from the dried juice of the opium poppy

• pipes from Bronze Age

• Ancietn egyptian writings

opium extracts

1. morphine

2. codeine

3. thebaine

types of opioids

1. opium extracts

2. morphine derivatives

3. codeine/thebaine derivatives

4. synthetic opioids

morphine derivatives

• heroin, hydromorphone, oxymorphone

codeine/thebaine derviatives

oxycodone (percocet, oxycontin), hydrocodone (vicodin, hycodan), buprenorphine (suboxone)

synthetic opioids

• methadone, tramadol (ultram/ultracet), propoxyphene (darvon/darvocet)

  • fentanyl and fenanyl-analog compounds (carfentanil)

opium history

• 1500-1800’s Laudanum was prescribed for everything

• late 1800’s- was cheaper than beer or gin in the US

  • Principal recreational drug along with alcohol and tobacco

  • given to babies

• 1773- First Opium War

laudanum

drink from opium dissolved in alcohol

first opium war

• how did it start?

  • Chinese government confiscated and destroyed an opium delivery from British traders

• what was the result?

  • Britain got control of Hong Kong, trading rights in Chinese harbors, and $300 million

second opium war

• how did it start?

  • Chinese government seized a British ship and imprisoned its crew

• what was the result?

  • opium was legalized in China

morphine and heroin history

• 1803- morphine is isolated from raw opium by a German drug clerk

  • derived from Morpheus, the Greek god of dreams

• 1856- Hypodermic syringe is invented (faster absorption than drinking)

• 1860’s- Civil War

  • “Soldier’s Disease” —morphine dependence

• 1898- The Bayer company introduced heroin to the market (prescribed as a cough suppressant and chest pain reliever)

  • abuse potential not realized (3x > morphine)

• 1980’s- price of heroin increased due to shortage, crime rates increased; drug taking was “cool”

  • 20% of soldiers in Vietnam were doing it

  • black tar heroin + fentanyl became available

• 1990’s- shift away from injected heroin and toward cocaine and inhaled heroin

• 2000’s- rise in synthetic opioids (fentanyl and fentanyl analogs accounted for 82% of opioid overdose deaths)

Harrison act

• 1914

• required anyone importing, manufacturing, selling , or dispensing opium-related drugs or cocaine to register with the treasury department, pay a special tax, and keep records of all transactions

  • by early 1920’s, it was illegal to prescribe opioids for nonmedical use