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1

History of Cocaine

- Incas in Peru, chew on coca plant for strength/energy
- Cocaine = active drug in coca, extracted by lime
- Inca religious ceremonies, settler currency
- European interest in last half of 1800s
- 3 individuals
- Mariani - coca wine, other coca products
- Halsted - local anesthesia
- Freud - psychiatric uses, withdrawal
- 1887-1914: 46 states had cocaine regulation laws, bc associated with undesirables "cocaine fiend"
- 1960s concern bc amphetamines harder to obtain, so use grew
- seemed to have few side effects--bulk amounts expensive--restricted access masked negative consequences
- associated with elite until 1985, wealth and fame (60-85)
- mid/late 80s dealers started selling crack--$5-10
- Len Bias 1986, thought died of crack, fr used powder
- Don Rogers
- Oct 1986: Reagan's Crack Cocaine Awareness Month
- Congress passed Anti-Drug Abuse Act of 1986: 100:1 ratio
- 2010: Obama --> 18:1

2

Cocaine Forms

- Coca leaves mixed with organic solvent, such as kerosine or gasoline —> soaked and filtered to form coca paste
- absorbed slowly through mucous membranes, slow onset of effects, lower blood levels
- In SA, paste mixed with tobacco and smoked
- Paste can be made into cocaine hydrochloride, a salt that mixes easily in water and is stable enough that heating can't produce vapors for inhalation
- Either snort or shoot up
- Snorting = most common route
- cocaine hydrochloride powder up nose to nasal mucosa; absorbed rapidly and reaches brain quickly
- Freebase: smokable cocaine/heroin
- Done by extracting it into volatile organic solvent, like ether
- Dangerous: combination of fire + fumes = explosive
- freebase declined in 80s, when crack discovered by mixing with household chems like baking soda+H2O
- Cocaine can be taken by mouth, insufflation (blow/snort), injection, or inhalation
- intravenous > inhalation > oral > intranasal

3

Adulterated

- make something poorer in quality by adding another substance
- bc crack cocaine is very adulterated, actually more expensive than powder

4

Anti-Drug Abuse Act

1986
Reagan
100:1 ratio
add details

2010: Obama 18:1

5

US Sentencing Commission Study

(1) Penalties most impacted blacks (85% of convicted)
(2) Exaggerated relative harmfulness of crack
(3) Penalties sweep too broadly and most often applied to low-level offenders
(4) Quantity-based penalties overstated seriousness of crack offenses and failed to provide proportionality

6

Cocaine Chemical Structure

- Blocks the reuptake of DA, NE, and Serotonin...causing prolonged effect of these neurotransmitters in synapse
- Focus used to be on DA (blockage/destruction of DA neurons lessened animal self-admin rates of cocaine)

7

Cocaine Metabolism

- Metabolized by enzymes in the blood and liver
- Rapidly removed, with half-life of one hour
- Major metabolites: 8 hrs
- 3 days for complete elimination

8

Cocaine Beneficial Uses

Local anesthesia
- Still used in nasal, laryngeal, and esophageal surgeries bc absorbed so well into mucous membranes

Other claims
- overcome fatigue (celebs, athletes)

9

Cocaine Causes for Concern

1. Acute toxicity
- Acute cocaine poisoning leads to profound CNS stimulation, progressing into convulsions, which can lead to respiratory and cardiac arrest
- Toxicity dependent on dosage size, adulteration
- Cocaethylene: (c+alc) more toxic than cocaine in mice, less potent in humans

2. Chronic toxicity
- In a binge (taken repeatedly and at increasingly high dosages) produces irritability, restlessness, paranoia
- Extreme cases: paranoid psychosis—lose touch with reality, auditory hallucinations
- Most recover after drug leaves system

3. Dependence Potential
- Majority do not become addicted
- Powerfully reinforcing drug (lab and animals will perform tasks to receive, big % of drug rehab causes)
- Withdrawal: anxiety, depression, craving, etc.

4. Reproductive Effects
- Increased risk of miscarriage and torn placenta

10

Chronic v. Acute Toxicity

- Acute: effects of single exposure or few in short period of time (24 hrs)
- Chronic: effects of repeated, long-term exposure

11

Supplies of Cocaine

- Price and purity by DEA indicators of supply
- Columbia, Bolivia, Peru

12

Cocaine Trends

1880s: first appeared, positive, benign substance
1890s: more use-->dangers became well known
1990s: society against it, laws to control it

13

Cocaine - Amphetamines

As cocaine use declines, amphetamine use increases

14

History of Amphetamines

- Chinese medicinal tea from herbs
- Active ingredient: ephedrine, used to dilate bronchial passages in asthma patients
- does so by stimulating sympathetic branch of autonomic nervous system
- also raises blood pressure
- in 1920s synthesized similar chemical: amphetamine, patented in 1932

- First use: ASTHMA replacement for ephedrine (potent dilator for nasal and bronchial passages, efficiently delivered through inhalation)

- Stay awake and study longer: students and truck drivers; Adderall

- Narcolepsy

- Appetite suppression

- Hyperactivity in children

Wartime: WWII used to improve soldier efficiency (Germans first)

Misuse in 60s: became widespread after WWII, legally manufactured oral preparation, realized that you could get similar cocaine effect if injected heroin + amph "speed"; widely available and cheap to use with heroin or alone. Not hard to get prescription

Most desired: methamphetamine (liquid or ampules for injection; used to be used to stimulate breathing in sleeping pill OD patients, sometimes injected to treat obesity

Use grew in 60s, by 70s restrictions were in place, associated with drug-abusing hippies

REACTIONS
1. Rise in cocaine use
2. Rise in illicit meth labs (meth called "cranks")
- relative ease, synthesis difficult, so crank often very impure, many chemicals more toxic

1990s "smoking" crystal meth
- meth in more rural areas -- Honolulu, midwest
- cocaine in cities

15

Adderall

mixture of amphetamine salts used to treat ADHD

16

Amphetamines Chemical Structure

- similar structure to catecholamine neurotransmitters, produces its effects bc recognized as catecholamine in CNS and PNS
- the methyl group allows to BBB more readily, increasing CNS potency

- increase activity of monoamine neurotransmitters by stimulating release
- DOPAMINE, norepinephrine, serotonin
- more potent releaser of norepinephrine (NE most likely causes euphoria)

17

Amphetamines Forms

intravenous, smoked, intranasal, oral

intravenous and smoked: 5-10 mins
intranasal: 5-20 mins
oral: 1.5 hrs

18

Amphetamines Metabolism

Half life: 5-12 hrs
Complete elimination: 2-3 days

19

Effect of high amphetamine dosage

Tachyphylaxis
- (rapid tolerance)
- produce effects by displacing/releasing neurotransmitters from their storage sites, monoamines may be depleted with large doses, resulting in reduced effect

20

Amphetamine Beneficial Uses

1. Depression
- in 1950s were TOC for depression and fatigue; stigmatized in 60s, use decreased
- used for depression only in adjunctive therapy (used to assist primary treatment)
- ADV: antidepressant effects within 1-2 days
- potential for abuse, although little evidence in controlled trials

2. Weight Control
- 60s most common use was weight control
- reduce appetite and food intake (few weeks, short term)

3. Narcolepsy

4. ADHD (Ritalin --> increases catecholamine activity in response to deficit)
- suppresses height and weight gain

5. Reduces shift-related disruptions
- reduce performance effects
- fatigue and sleep deprivation

21

Adjunctive Therapy

- Treatment used to assist primary treatment
- Amphetamines

22

Amphetamine Addiction

- Was not thought to produce "withdrawal" therefore soft
- Oral by prescription << intravenous to get high

- Addiction depends on dose, route, and reason for use

23

Table 6.1

- Federal cocaine offenders

- powder:
- crack:

while % were roughly comparable in powder situations (usually mostly hispanic) there was HUGEly disproportionately high for black crack situations (always 80s/90s)

24

Cocaine Individuals

- Mariani - coca wine, other coca products
- Halsted - local anesthesia
- Freud - psychiatric uses, withdrawal

25

ADHD

- inattention, hyperactivity, impulsivity

Treatments:
amphets: Ridalin increases catecholamine activity in response to deficit
Adderal: keep awake

- due to catecholamine deficits

26

General Behavioral Effects of Depressants

- decreased CNS activity
- induce sleep

- relaxation, exhilaration, inebriation, drowsiness, stuporous/uncoordinated

- entered market to keep people calm and relaxed

27

Types of Depressants

Sedatives (anxiety reduction, low-dose prescription)
Hypnotics (sleeping pills)

28

Sedatives

Low doses of prescription depressants used to reduce anxiety

- Xanax, Ativan (both benzodiazapenes)

29

Hypontics

Depressants used as sleeping pills

30

Inhalants

Ex: glue, paint, solvents

Effects can also be similar to depressant drugs