Cocaine, Amphetamine, and Other Stimulants

Question 1

Coca Leaves

Answer 1

Always chewed.
Contain about 0.5-1% cocaine in the form of the HCl salt.
Main use by chewing by Indians of Columbia, Equador, Peru and Bolivia-these countries are the main source of cocaine for the rest of the world.
This preparation produces no high because of the low dose and slow absorption; decreases hunger, increases energy and helps in performing hard work at high altitudes.

Question 2

Coca Paste

Answer 2

First product in the process of preparing pure cocaine.
Harvest leaves are treated with a series of acids, bases and organic solvents; extract the cocaine and converts it to its alkaloidal free base form.
This form contains 60-90% cocain alkaloid and numerous contaminant.
This is not sold in the US and is a big abuse problem in the countries of origin- the coca paste is mixed with tobacco or pot and smoked as a cigarette.

Question 3

Cocaine HCl

Answer 3

Names: coke, snow, blow, toot, nose candy, lady, white.
Coca paste is converted to relatively pure cocaine HCl; this is the form smuggled into the US disguised as cargo on trucks or ships.
Packers (mules) carry cocaine.
Swallow packets, seal in latex and wax or taped to their body-swallowed packets can rupture and produce severe toxic side effects or death.
Once it reaches the US, it can be cut several times before it reaches the end user.
Local anesthetic like procaine or lidocaine is also often added to provide a good “freeze.”
Powdered cocaine is “street coke” and is the most common variety; it cannot be smoked because it decomposes at its temperature of vaporization (200 C), so USUALLY SNORTED OR IV INJECTED.

Question 4

Cocaine alkaloid

Answer 4

Names: free base, base.
Volatizes at about 100 C and therefore CAN be smoked without massive destruction of the drug.
First type of free base cocaine produced in this country was usually prepared by the end user; product was nearly 100% pure alkaloid crystals.
The user dissolved street cocaine in water and then added a strong alkali, which formed the free base that precipitates.
Precipitated alkaloid is further purified by dissolving it in ether, followed by recrystallization by evaporation of the ether.
This involves a risk of fire.
Making this free base form requires skill and is dangerous.

Question 5

NEW Cocaine Alkaloid

Answer 5

Names: crack, rock.
Was discovered that alkaloidal cocaine cold be made simply and safely: dissolve street coke in water, add sodium bicarbonate, and boil to near dryness-this product is NOT as pure as free base.
Cocaine alkaloid precipitates out as a whitish amorphous mass; dried and broken up into small lumps (rocks), which is 60-90% pure cocaine, weighs about 100-200 mg.
These lumps are smoked like free base cocaine.
Price of a typical 100-200 mg rock is relatively low (10-20$ in 2001), but when a person is hooked on crack, the overall cost can be very high.

Question 6

Snorting Cocaine

Answer 6

Most common route of administration!!!!!!!! Snorting cannot produce a rush but it produces a high of moderate intensity.
Preparation: Cocaine HCl is chopped into a fine powder and formed into “lines” about 2-35 mg each, typically 2-5 lines are snorted through a fine straw or rolled up bill (tooter).
Absorption is through the nasal vascular mucosa.
Rate of absorption is self-limiting due to vasoconstriction; ultimate bioavailability is 80%.
Onset of euphoria is 3-5 minutes-the peak effects is at 10-20 minutes, the total duration of the effects is 45-90 minutes.
(IV is the fastest onset; slower onsets tend to have a little longer duration)

Question 7

Smoking Cocaine

Answer 7

Cocaine alkaloid, either free base or crack, is smoked in a special pipe or by mixing with tobacco or pot and smoking as a joint.
Product goes through a screen in the pipe, mixes with liquid coolant to cool the smoke, and then breathed in.
Extremely rapid absorption; produces blood levels similar to those produced by IV injection.
Peak effects occur at 1-4 minutes- the total duration of the effects is 15-30 minutes.
Bioavailability is about 60%.
Smoking cocaine produces a rush followed by a high; the rush (very high concentrations in the body cause the rush) component is extremely short and lasts only a few minutes- it is extremely reinforcing and is the effect that crack smokers value the most.
Smoking crack can rapidly lead to dependence-occurs in weeks to months compared to months-years for snorting.

Question 8

IV use of Cocaine

Answer 8

Cocaine HCl is dissolved in water and injected- crack cocaine can be dissolved in a little vinegar or lemon juice and injected.
Intensity, onset, and duration are similar to smoking; less drug is required because don’t have a lot of metabolism of the drug and first pass effects.
IV use produces both the rush and the high.
Very highly reinforcing and can rapidly lead to dependence.

Question 9

Other Routes of Administration

Answer 9

Cocain HCl can be applied to any mucus membrane; oral (gums), rectal and vaginal application are not uncommon.
Absorption seems to be similar to snorting.

Question 10

Disposition of Cocaine

Answer 10

Short plasma half life of about 60 minutes.
Plasma pseudocholinesterase, liver esterases and spontaneous hydrolysis metabolize cocaine-products are not pharmacologically active but are long lived.

Question 11

Metabolites of Cocaine

Answer 11

Benzoylecgonine
Cocaine itself is benzoylecgonine methyl ester.
Benoylecgonine is the compound usually used for urine detection of cocaine use-it can be detected by typical tests for up to 72 hours after cocaine use.
Deposited permanently in hair; can be detected by hair analysis months after use.
Passive exposure to crack smoke can lead to false positive test in both hair and urine.
Not an active metabolite, but it is an indicator of cocaine use- focused metabolite, don’t have this if you aren’t doing cocaine.
Long half life.

Question 12

Acute Psychotropic Effects

Answer 12

The “flash” or “rush:”
Describe as pre pleasure or ineffable (too great or extreme to describe in words); impossible to describe but is clearly not the same as for heroin or barbiturates.
Lasts for only few minute and then fades into the “high.”
This rush results only from smoke and IV use.
Later uses might not be as good as the first one was.
The “high:”
Feeling of power, greatly increased energy and vitality, crystal-clear thinking, cleverness, self-confidence, no need for sleep.
The feelings are identical to the manic phase of bipolar disorder.
The high lasts much longer than the rush.
The high is experiences by all routes of administration (except with the lead because the concentration of cocaine is so low there is no effect).

Question 13

Cocaine-Mechanism of Action

Answer 13

Blocks the neuronal reuptake of transporters at the terminal: serotonin, NE, DA neurons; increases the transmitter concentration in the synapse to stimulate post synaptic receptors.

Question 14

Reinforcing Effects of Cocaine

Answer 14

Mainly due to blocks of DA reuptake in the nucleus accumbens.
The potential abuse properties of stimulants stem from their ability to enhance DA release in the nucleus accumbens.
Biggest effects on mesolimbic, DA pathway; pleasure pathway.

Question 15

Autonomic Side Effects of Cocaine

Answer 15

Due to blocks of NE reuptake in the periphery; cocaine also acts in the CNS to increase sympathetic outflow.
Powerful sympathomimetic effects.
Also a potent local anesthetic (interference with sodium movement in axons), but this probably has no influence its reinforcing actions or its sympathomimetic effects or the high.

Question 16

Psychological Dependence and Cocaine

Answer 16

In sufficient dosage, cocaine by any route is extremely reinforcing and has a significant risk of producing psychological dependence.
Smoking or IV injection are the “worst” and they can rapidly lead to dependence.
Have to do with enough drug in the system frequently enough.

Question 17

Patterns of Use- Occasional social or recreational use

Answer 17

Many people start out snorting small amounts of cocaine on an occasional basis-80% of these users will not become compulsive users for several reasons.
This is the lowest grade cocaine euphoria, cocaine is expensive and access is limited.

Question 18

Patterns of Use- Accelerated Use

Answer 18

Used more often but still as single or a few doses at a time; possibly on a daily basis.

Question 19

Patterns of Use- Binge Use

Answer 19

User purchases a supply of drug and then proceeds to take one hit after another at short intervals of 2-60 minutes; done until they run out of drug or become incapacitated.
Binge can last for up to several days; during this time there is little or no sleeping or eating; after recovery, many binge users will start another binge.
This loss of control is a sign that severe dependence has developed.
Results of binge use: rapid social, psychological, and physical deterioration.
Some snorters and most who smoke and inject will go on to binge use; this requires access to a sufficient amount of drug.
Causes of binging: relatively short duration of euphoria (especially the rush), development of acute tolerance to the reinforcing effects, so the drug must be used more often; development of dysphoria soon after th reinforcing effects start to dissipate.

Question 20

Tolerance to Cocaine

Answer 20

Tolerance probably develops to both e subjective and CV effects and can be extensive.
Acute tolerance develops within a binge of cocaine use and is significant after the first dose, some of this tolerance disputes after the end of the binge.
Tolerance probably develops across binges or with daily or near daily use.
Mechanism of tolerance is not known; definitely pharmacodynamic rather than pharmacokinetic!!!!

Question 21

Sensitization

Answer 21

Repeated use of cocaine can result in a sensitization to some of the adverse effects.
Doses that did not produce seizures or cocaine physicist or stereotypy (repetition of an act for no obvious purpose) may do so; this sensitization can persist indefinitely even after prolonged abstinence.

Question 22

Physical Dependence and Withdrawal

Answer 22

NO PHYSICAL DEPENDENCE DEVELOPS!!!!!

Abrupt withdrawal of cocaine; even after prolonged heavy use does not result in classical physical withdrawal syndrome.

Question 23

Psychological Withdrawal Effects

Answer 23

In many chronic heavy users…
Discontinuation leads to unpleasant psychological effects which may lead to relapse; but not all such users will experience these symptoms.
Symptoms observed: craving, fatigue, hypersomnolence, dysphoria. depression, anhedonia, anergia.
Sometimes leads to suicide.
Psychological dependent can occur with everything, but it can vary from person to person with cocaine.

Question 24

Adverse Effects Associated with Usual single Doses or Short Binge

Answer 24

1. Sympathomimetic: increased heart rate, increased BP, palpitations, mydriasis, dry mouth, difficult urination, sweating, tremor.

Question 25

Adverse Effects Associated with Usual single Doses or Short Binge

Answer 25

2. Psychiatric/Bheavioral: grandiosity (feeling of superiority), irritability, anxiety, repetitive or perseverative behavior, stereotypy, tics.
   Grandiosity, repetiive or perseverative behaviors and stereotypy may not be perceived as “adverse” by the user and are often described as pleasurable.

Question 26

Adverse Effects Associated with Usual single Doses or Short Binge

Answer 26

3. Headache and chest pain: both are among the more common adverse effects in frequent users.
   Chest pain is one of the most common presenting companies at emergency rooms; it may be due to myocardial infarction but usually is not; actual case is probably myocardial ischemia.

Question 27

Adverse Effects Associated with Usual single Doses or Short Binge

Answer 27

4. Seizures, stroke, myocardial infarction, cardiac arrhythmias, cardiac arrest.
   Rare but serious.
   There are more likely to occur after high doses or during long binges; they can occur at lower doses which previously had no ill effect.
   Seizures are the most common adverse effect in the list; usually there is a single grand mal convulsion, but can proceed to status epileptics.
   The risk of seizures increases with the length of the run and with total overall usage.
   Users will often continue to use after they recover from a seizure.
   Myocardial infarction is the next most common adverse effect in this list; probably due to extreme vasoconstrictiopn of cardiac vessels; it is the leading cause of myocardial infarction in persons under 30 and the first thing emergency room doctors suspect when a young person presents.
   During the first hour after taking cocaine, the risk of myocardial infarction is 24 times that of an on-user of similar age; myocardial infarction may be delayed for several hours after the last use of cocaine.
   Role of cocaine metabolites in myocardial infarction: benzoylecgonin is a metabolite of cocaine when used alone.
   Cocaethylene is a substance formed when cocaine is used in combination with alcohol.
   They have vasoconstrictive activity and persist much longer than cocaine- they may be responsible for delayed myocardial infarction.

Question 28

Adverse Effects Due to Acute Major Overdosages or Cumulative Toxic Overdosages (Binge)

Answer 28

There is an increased likelihood and intensity of al the adverse symptoms above.
2. Cocaine Psychosis: this is a paranoid psychosis mimicking paranoid schizophrenia; auditory, visual, and tactile hallucinations.
This is inevitable if enough cocaine is used.
Rapidly reversible upon discontinuation (5 days maximum).
“Simple” paranoia is extremely common and may not process to psychosis.

Question 29

Adverse Effects Due to Acute Major Overdosages or Cumulative Toxic Overdosages (Binge)

Answer 29

3. Agitated Delirium; this is severe agitation, there is a reduced awareness of the environment, may be marked muscle tension and extreme hyperthermia.
   This is potentially LETHAL.

Question 30

Adverse Effects Due to Acute Major Overdosages or Cumulative Toxic Overdosages (Binge)

Answer 30

4. Respiratory Arrest; this is due to CNS action on respiratory centers- this is mainly seen in major acute overdose; especially seen in “speedball” cases.

Question 31

Adverse Effects Due to Acute Major Overdosages or Cumulative Toxic Overdosages (Binge)

Answer 31

5. Hyperthermia, rhabdomyolysis (damaged skeletal muscle breaks down rapidly), myoglobinuria, renal shutdown.
   Can occur during agitated delirium or otherwise and can be FATAL.

Question 32

Adverse Consequences of Chronic Frequent Use

Answer 32

1. Psychological/behavioral: Psychological dependence, abstinence effects, cocaine psychosis, chronic insomnia, chronic anorexia, sexual dysfunction, social isolation, deterioration; these can occur rapidly altering binging starts.

Question 33

Adverse Consequences of Chronic Frequent Use

Answer 33

2. Previously cited CV effects, accelerated atherosclerosis, silent myocardial injury, myocarditis, cardiac hypertrophy.

Question 34

Adverse Consequences of Chronic Frequent Use

Answer 34

3. Pulmonary effects (any route), pulmonary edema, pulmonary hemorrhage/hemoptysis-coughing up blood, pulmonary interstitial fibrosis.

Question 35

Adverse Consequences of Chronic Frequent Use

Answer 35

4. Persistent hyperprolactinemia causing menstrual dysfunction, galactorrhea, gynecomastia.

Question 36

Chronic Effects Associated Mainly with Smoking Crack or Freebase

Answer 36

Crack lung, barotrauma, chronic bronchitis, excess and darkened sputum, deterioration of lung function.
Tongue, mouth and throat inflammation or ulcers.

Question 37

Chronic Effects Mainly Associated with Snorting Cocaine

Answer 37

Nasal congestion, chronic rhinorrhea, chronic nasal inflammation, nasal ulceration, chronic sinusitis, decreased sense of small, nasal septum necrosis or perforation.

Question 38

Chronic Effects Mainly Associated with IV Injection of Cocaine

Answer 38

1. Skin lesions; can be due to intense vasoconstriction, can also get general sloughing of skin.
2. Vascular lung lesions due to cutting agents; insoluble cuts like talc, starch and microcrystalline cellulose, can produce vascular occlusions or lung granuloma.
3. Systemic infections

Question 39

Effect on Pregnancy Outcome

Answer 39

About 1% of all pregnant women use cocaine; in black mothers, this figure is 5.1%.
The “crack baby” hype of 1980s; most of the problems can be explained by other factors: the concomitant use of other illegal drugs, the use of alcohol and tobacco, generally poor prenatal health care these women receive.
Not necessarily cocaine causing these problems.
See increased miscarriage, abruptio placentae, premature delivery.
Reduced birth weight, congenital malformations, transient CNS irritability; although, malformations are not well supported by the data, irritability is transit over a few days to a week.
Persisting neurological or behavioral effects is controversial.

Question 40

Amphetamine-like Agents

Answer 40

The psychic effects, as well as most of the other effects of amphetamines, are nearly identical to those of cocaine.
The main difference between these drugs is the duration of the high.
Benzedrine, Vicks, and Benzedrex Inhalers.

Question 41

Meth Labs

Answer 41

Methamphetamine seems to be more popular in the rural areas than in the cities.
Violence occurs due to the drug itself, drug deals and thefts as well as a marked lack of responsibility for spouse and children.
Clandestined meth labs-hundreds have been discovered in affected states; most of these are small time operations with relatively low output; most meth come from other sources; large facilities in Cali and smuggled from Mexico.
Meth lab cleanup: presents a huge problem; cleanup process is expensive and dangerous; anhydrous ammonia, sodium metal, red phosphorus, lye, organic solvents.

Question 42

Racemic Amphetamine Sulfate

Answer 42

Benzedrine
Names: bennies, cartwheels, black beauty, speed.
On the street diverted pharmaceutical product AND clandestinely manufactured product.
Usually taken orally, sometimes injected IV.

Question 43

Dextroamphetamine Sulfate

Answer 43

Dexdrine
Street names: dex, dexies, speed, white cross.
On the street diverted pharmaceutical product AND clandestinely manufactured product.
Usually taken orally and sometimes injected IV.
The D isomer is twice as potent in terms of CNS effects as the L-isomer.

Question 44

Dextromethamphetamine HCl

Answer 44

Desoxyn, Methampex
Street names: meth, speed, crank.
Diverted pharmaceutical grade product, not really manufactured in society.
Usually taken orally.

Question 45

Dextromethamphetamine HCl or racemic methamphetamine HCl

Answer 45

Street names: meth, speed, crank, crystal, crystal meth.
NOT a pharmaceutical, typically called meth.
Clandestinely manufactured, by far the most common parodic available on the street.
Currently most is the dextro isomer.
Can be taken orally, snorted, smoked or injected IV.
White to yellowish powder or lumps, fine crystals or as tablets or capsules.
Current samples average about 50% purity.

Question 46

Extremely pure dextromethamphetamine HCl

Answer 46

Street names: ice, glass, crystal, shabu, batu.
Often presents as transparent crystals; ranges in size from table salt to rock salt.
Almost exclusively smoked.
Used mainly in Hawaii and in certain areas of Cali and Washington.

Question 47

Methylphenidate

Answer 47

Ritalin
Street names: R-ball, vitamin R.
Always diverted pharmaceutical product.

Question 48

Methylamphetamine

Answer 48

The major problems these days even though amphetamine has many of the same properties.
People generally like methamphetamine better because it is more lipid soluble and gets across the BBB faster than other forms.
Also, methamphetatmine produces fewer peripheral autonomic nervous system effects than amphetamine.

Question 49

Methylamphetmaine- Oral Route of Administration

Answer 49

This is the route by which many users start.
Enhane mental or physical performance, stay awake for long periods of work or study, lose weight because methamphetamine inhibits appetite, used to stay energized at rave-type parties, some just take it to get “high,” this does NOT provide a rush.
Patterns: use is initially sporadic, may develop into a sustained daily use of 50-250 mg, person may go onto smoking or injecting, which is a very serious situation.
Onset usually 30-60 minutes.
Peak effects usually in 1-3 hours.
The high duration is eerily 4-6 hours and large doses may produce an even longer effect.

Question 50

Snorting Methylamphetamine

Answer 50

Some users start by snorting, some graduate to it after oral use; produces a faster effect and requires less drug.
This DOES NOT provide a “rush.”
Onset is about 3-5 minutes; methamphetamine is irritating to the nose and can produce pain, inflammation and chronic sores; unlike cocaine, it has no LA effect to mask the irritation.

Question 51

Smoking Methamphetamine

Answer 51

Almost any form of methamphetamine can be smoked, but ice is preferred.
Usually smoked in a special pipe; differs from a crack pipe because the methamphetamine melts before it vaporizes, so you can collect and reheat residue in this kind of pipe.
Used mainly by those heavily into the drug- provides the rush as well as the high; onset is less than 1 minute, the rush appears soon thereafter but is brief; the rush is followed by a long high.
Users often use this route in binges; take a hit every 2-4 hours for several days to a week.
Little eating or sleeping occurs during the run, then the crash occurs; often this is followed by another binge.
Smoking associated binges; very likely to produce amphetamine psychosis; strong, paranoid aspects, violence is common; high incidence of visual and auditory hallucinations, violence is common.
Constant picking at imaginary insects crawling beneath the skin (crank bugs); often results in serious skin and subQ tissue damage.
Consequences; can rapidly lead to profound social, psychological and physical deterioration.

Question 52

IV Use of Methylamphetamine

Answer 52

IV use is similar to smoking in most respects, including the violence and high tendency to binge and rapidly deteriorate.
(Dental problems with methyl amphetamine).

Question 53

Disposition of Methylamphetamine

Answer 53

Long plasma half life, typically about 10-12 hours.
Most metabolism occurs in the liver by CYP450 in a couple different routes.
About 35% of the drug is excreted unchanged in the urine; some users may drink their urine to recycle the methamphetamine, routine urine tests can detect amphetamine out to about 96 hours after the last dose in occasional users, longer in heavy, chronic users.
Major effects on urine pH; excretion of unchanged drug is hastened by acidifying the urine-greatly slowed by raising the urine pH-some users ingest bicarbonate to prolong the high.
Acute psychotropic effects: the flash or rush; when smoked or injected, meth produces a typical cocaine-like rush, this effect is apparently short lasting just like with cocaine.
The high; just as with cocaine, the high is much longer lasting than the rush; the methamphetamine high is much longer than the cocaine high; during binges, dosing is less frequent.

Question 54

Mechanism of Action of Methylamphetamine

Answer 54

Amphetamines act primarily by releasing DA and NE from presynaptic stores; smaller effect on serotonin release.
Like cocaine, they increase synaptic concentrations of neurotransmitters.
Dopaminergic transmission in the pleasure pathway, as with cocaine, their euphoric effects are probably due to this; reinforcing effects, DA mesolimbic pathway.
Autonomic effects are similar to cocaine; due mainly to release of NE at peripheral noradrenergic neuroeffector junctions, also due to an action i the CNS which increases sympathetic outflow.
A significant difference between cocaine and amphetamines is that amphetamines have no LA activity.

Question 55

Other Properties of Methylamphetamine

Answer 55

Generally these properties are very similar to cocaine.
1. Physical and psychological acute and chronic toxic effects: essentially the same for these 2 drugs.
Exception: methamphetamine does significant dental damage; methamphetamine smoke is highly acidic and produces dry mouth with facilitates the damage; eats the enamel off your teeth.

Question 56

Other Properties of Methylamphetamine

Answer 56

There are binge cycles similar to cocaine; the interval between sessions is longer with methamphetamine.

Question 57

Other Properties of Methylamphetamine

Answer 57

Like cocaine, there is a lack of physical withdrawal symptoms after sudden discontinuation; psychological symptoms can be problematic; symptoms start after a few hours and last about a week to 10 days.

Question 58

Other Properties of Methylamphetamine

Answer 58

Like cocaine both acute and chronic tolerance to most effects of amphetamine develops; allows smoked or IV single doses of up to a gram and daily doses of 5-15 grams.

Question 59

Neurotoxicity due to chronic high dose use

Answer 59

This type of toxicity appears after high dose chronic methamphetamine use and it NOT associated with cocaine use.
Long lasting dopaminergic system dysfunction, similar to that produce by MDMA in serotongergic systems.
Apparent long lasting disappearance of long axonal projections and their terminals, no destruction of the cell bodies.
Methamphetamine may produce similar but less extensive effects on serotonin and NE terminals.
Cognitive and motor deficits.
Documented in abstinent long term speed freaks: correlated with the decrease in dopaminergic function, correlates with the extent of past methamphetamine use.

Question 60

Methylphenidate Reinforcement

Answer 60

Like methamphetamine but slightly less potent when given IV.
Considerably less potent as a reinforcer when taken orally for reasons which are not clear.
Definitely can produce a high by either route.

Question 61

Methylphenidate Abuse

Answer 61

Many anecdotal reports of widespread abuse, but very few documented reports in spite of its huge use for ADHD.
Clearly methylphenidate abuse is not a major social problem.
Abuse by kids and adults prescribed the drug for ADHD is minimal- they may sell or give away their drug to peers who then abuse it; parents of kids with ADHD may abuse their drug.
Abuse can be oral, by snorting ground up tablets or by IV injection.
Snorting can cause serous nasal damage due to the high acidity of methylphenidate HCl.
IV injection has caused much toxicity; due to tablet binders and bulking agents which are insoluble; can cause embolic obstruction of capillaries in various organs, including the lung, kidney and the brain.