Cocaine & Amphetamines

1. What are the forms of cocaine?

1. Raw leaves

2. Coca paste

3. Cocaine HCl (powder)

4. Cocaine free base or crack cocaine

1. What are the forms of Amphetamine?

1. Naturally occurring amphetamines

2. Bath salts

3. Amphetamine

4. Methamphetamine

5. Amphetamine related synthetic

1. What are the effects of repeated use of stimulants?

1. Withdrawal, tolerance, sensitization

1. What are the forms of MDMA and related drugs?

1. MDMA 

2. MDA

3. MDE

1. What is the name of the larger class of drugs like cocaine and amphetamines?

1. Stimulants

2. Psychomotor stimulants 

3. Psychostimulants

4. “Uppers”

1. What are the major behavioral properties of psychomotor stimulants?

1. Stimulate alertness and arousal (“psycho-”)

2. Stimulate motor activity (“-motor”)

1. What are some stimulates?

1. Cocaine

2. Amphetamines

3. Nicotine

4. Caffeine

1. Cocaine is a psychoactive alkaloid found in coca leaves (Erythoxylon coca) in _____________ (natural).

1. South America

1. Cocaine is weak ___.

1. Base 

1. When were the earliest reports of coca use?

1. ~8000 years

1. When was the first reported use by europeans

1. 1499

When was the active agent of cocaine isolated by German chemists?

1. 1859

1. What did Freud first say about cocaine?

1. “ … exhilaration and lasting euphoria, which in no way differs from the normal euphoria of the healthy person… you perceive an increase of self-control and possess more vitality and capacity for work… In other words, you are simply normal, and it is soon hard to believe you are under the influence of any drug … long intensive physical work is performed without any fatigue… This result is enjoyed without any of the unpleasant after effects that follow exhilaration brought about by alcohol…Absolutely no craving for the further use of cocaine appears after the first or even after repeated taking of the drug…”

2. Freud later changed his mind

1. Describe the route of administration used for raw cocaine leaves?

1. Raw coca leaves are chewed with lime powder or ash to increase saliva pH, which enhances absorption by decreasing the ionization of cocaine (weak base)

2. Absorption by mouth

1. What is the cocaine concentration in the raw leaves?

<2%

_________ is a crude extraction from leaves by mixing with sulfuric acid.

1. Coca paste

1. What is the cocaine concentration in coca paste?

1. ~80% cocaine sulfate

1. What is the route of administration for coca paste?

1. Can only be smoked (often with tobacco or marijuana)

2. Too caustic for other routes

____ or “basuco” is very cheap, low-grade cocaine, abused in low income areas of South America

1. “Paco”

_______________ is the crystalline powder extracted and purified from coca paste.

1. Cocaine HCl (hydrochloride)

1. Describe the cocaine concentration in cocaine HCl

1. Very high, but usually cut with other powders

1. What is the route of administration for cocaine HCl?

1. Water soluble and can be taken orally (coca-cola), intranasally (20-30% enters the bloodstream), or injected IV. 

2. Cannot be smoked because vaporization temperature is close to burn temperature

1. How is cocaine free base made?

1. From cocaine HCl + water + base (ammonia) 

2. Extraction with ether (flammable solvent)

1. What is the route of administration for cocaine free base?

1. Lower melting point, so can be vaporized and smoked (“freebasing”)

2. But, residual ether can be dangerous and explode with flame

1. _______ or “rock” cocaine is a cruder preparation of free base, made from cocaine HCl. Safer to make because baking soda use instead of solvent.

1. “Crack”

1. What is the concentration of cocaine in crack cocaine?

1. 75-90%

1. What is the route of administration for crack cocaine?

1. Smoked

_______ led to a new epidemic of cocaine use in the 1980s-90s, particularly in poor US neighborhoods; stiff criminal sentences.

1. Crack

1. The ____________, passed in 1986, imposed mandatory minimum sentences that were far harsher on users of crack cocaine than on those found with the drug in powdered form.

Federal anti-drug abuse act

The _____________ reduced that disparity in sentencing from 100:1 to 18:1.

1. Fair Sentencing Act

Coca/Cocaine was widely used in many products by late ______

1. 1800s

1. Until _____, Coca-Cola has ~60mg per 8 oz serving.

1. 1903

1. What schedule is cocaine and why?

1. Local anesthetic effects thus schedule III

1. What is the primary mechanism of cocaine?

1. Blocks monoamine transporters (like DAT)

What does high doses of cocaine cause?

1. Inhibits voltage gated Na+ channels 

   1. Involved in action potential

1. What are the topical/local anesthetics developed from cocaine?

1. Procaine (Novocain)

2. Lidocaine (Xylocaine)

3. Benzocaine

4. Tetracaine

1. Extremely rapid absorption of cocaine with ___________.

1. Smoking or IV

   1. Lipophilic enough to easily pass cross BBB within seconds

1. How long is the peak subjective effect for crack cocaine?

1. 1-2 minutes over 5 -15 minutes

Since cocaine undergoes rapid metabolism (via enzymes in blood and liver) and elimination, what is the half-life of cocaine?

1. 0.5 - 1.5 hours

1. ________ major metabolite benzolecgonine is detectable in urine for several days (weeks in heavy users).

1. Inactive

1. _________ metabolite cocaethylene is formed when cocaine and ethanol are ingested simultaneously; longer half-life than cocaine.

1. Active

1. What are amphetamines?

1. Chemical family of synthetic and natural psychostimulants that act a sympathomimetic amines (mimic catecholamines like DA)

1. What are the natural forms of amphetamines?

1. Ephedrine

2. Cathinone

1. Where does ephedrine come from?

1. Ephedra or “Mormon tea” plant (natural)

2. Traditional Chinese medicine for asthma, cold

1. What are the active components of ephedrine?

1. Ephedrine

2. Pseudoephedrine

1. What is the active component of decongestants?

1. Pseudoephedrine has long been a major cold treatment, but since 2006, purchases are more restricted (behind the counter)

What can the active component pseudoephedrine in ephedrine be reduced to?

1. Methamphetamine or oxidized into methcathinone (bath salts)

1. What is the substitute in OTC forms (over the counter) of ephedrine?

1. Phenylephrine

1. Where does Cathinone come from?

1. Khat or qat shrub leaves (natural)

1. Where is Cathinone common chewed in?

1. East Africa and Yemen 

2. ~80% of men in Yemen use khat 

3. Spend about 17% of income

1. What are they effects of Cathinone?

1. Increases heart rate

2. Excitement

3. Euphoria

4. More talkative

5. Oral route produces slow onset

6. Relatively mild effects

1. What are the synthetic forms of amphetamines?

1. Bath salts 

2. Amphetamines

3. Methamphetamine

1. What is methacathinone and mephedrone?

1. Synthetic variants of cathinone

2. These designer drugs are disguised as household products, such as bath salts.

What DEA schedule are bath salts (methacathinone and mephedrone)?

1. I

1. When was amphetamine synthesized?

1. 1887

1. When was methamphetamine synthesized?

1. 1919

1. When were synthetic amphetamines used medically and for what?

1. 1920-30s

   1. 1932

      1. Benzedrine inhaler (for congestion)

   2. 1935

      1. First use for narcolepsy

When was the widespread adoption of amphetamines?

1. During WWII in the 1940s

When was the peak use of “speed,” 10 billion tablets sold?

1. 1970s

1. What are the different forms of amphetamines?

1. D-Amphetamine (dexotroamphetamine)

   1. Vyanse (prodrug)

   2. Dexedrine, dexies

2. L-amphetamine (levoamphetamine)

   1. Less potent

3. Amphetamine (racemic) - mixture of enantiomers (D&L)

   1. Adderall 

      1. 25% lev0, 75% dextro

   2. Benzedrine (50/50), bennies, speed

1. What is the route of administration for amphetamine?

1. Taken orally or by injection (IV, SC)

1. Which is the most potent of amphetamines?

1. Methamphetamine (dl-methylamphetamine)

   1. Methadrine

   2. Meth, crystal, crank, speed, ice, glass

1. What is the route of administration for methamphetamine?

1. Oral, snort, injected IV, or smoked

1. What are some amphetamine related structures?

1. Methylphenidate

   1. Ritalin, concerta

   2. Attention deficit disorder

2. Modafinil

   1. Narcolepsy

   2. Sleep apnea

1. What is the history of amphetamine use for congestion?

1. Wide acceptance of amphetamines (Benzedrine inhaler for congestion) in medical community when initially introduced in 1932, but stimulant and mood effects were noticed

Why were amphetamines used for narcolepsy and when?

1. Starting in 1935 due to wake-promoting effects

2. It could elevate mood and suppress appetite, also was used for mild depression and as a diet pill (NOT a current medical use though)

1. What is the history of amphetamine and military use?

1. Amphetamines used widely by military during WWII and subsequent conflicts

2. Used to increase attention and reduce fatigue (increase wakefulness)

3. Still standard in US Air Force

What is the history of amphetamines and fatigue?

1. 1970

   1. More than 10% of the population were regular users (truckers, housewives)

      1. 10 billion tablets legally made in US

2. 1971

   1. Control began

1. When crack wave was diminished in mid-late 90s, _____ increased?

1. Meth use

1. What is the route of administration of crack?

1. High purity can be smoked

2. Faster route of administration = more abuse potential

3. Easily prepared from common household ingredients

1. What is the current medical uses for amphetamines?

1. Narcolepsy

2. Attention deficit disorder (ADD, ADHD)

1. What DEA schedule are amphetamines?

1. II

T/F: Almost all ADHD medications are stimulants.

1. True

   1. Adderall (amphetamine)

   2. Desoxyn (methamphetamine)

   3. Ritalin (methylphenidate)

   4. Exception: Strattera (atomoxetine), but often less effective

1. What percent of the US population is diagnosed with ADHD?

9%

1. T/F: ⅔ of ADHD children receive pharmacological treatment.

1. True 

1. What do recent medical use formulations of amphetamines aim to do?

1. For slow release 

   1. Little or no high

1. Compare amphetamines to cocaine.

1. Amphetamines

   1. Slower metabolism and elimination

   2. Halflife is 7-30 hours

2. Cocaine

   1. Shorter duration of action

      1. 0.5 - 1.5 hours

   2. Worse cardiovascular effects (can be lethal)

      1. Higher danger of cerebrovascular accident (stroke hemorrhage) or cardiac problems (heart failure) with cocaine, due to actions on sodium channels

   3. Higher convulsive.seizure properties of cocaine

      1. Sensitize with repeated use

1. Do amphetamines make inactive or active products?

1. Both 

2. 30-40% is excreted unchanged (can be detected in urine test)

1. What are the mild effects of cocaine and amphetamines?

1. Mood amplification; both euphoria and dysphoria

2. Heightened energy

3. Sleep disturbance, insomnia

4. Motor excitement, restlessness

5. Talkativeness, pressure of speech

6. Hyperactive ideation

7. Increases sexual interest

8. Anger, verbal aggression

9. Mild to moderate anorexia

10. Inflated self-esteem

1. What are the severe effects of cocaine and amphetamines?

1. Irritability, hostility, anxiety, fear, withdrawal

2. Extreme energy or exhaustion

3. Compulsive motor stereotypes

4. Rambling, incoherent speech

5. Decreased sexual interest

6. Possible extreme violence

7. Total anorexia

8. Delusions of grandiosity 

1. Explain the drug discrimination between amphetamines and cocaine in humans and rats.

1. Human users and lab animals cannot discriminate between IV cocaine and amphetamines

1. What are the autonomic effects of cocaine and amphetamines?

1. Increased blood pressure, hyperthermia, bronchodilation

1. What are the major effects in animals using stimulants?

1. Hyperlocation

   1. Locomotor activity can appear to go down with high AMPH doses because rats perform stereotypy behavior instead

      1. Persistent, repetitive behaviors with no purpose

2. reinforcing/rewarding effect

   1. Self administration

   2. Conditioned place preference

1. In chronic, high-dose users of stimulants (cocaine or amphetamines), what are the withdrawal symptoms (mostly psychological and not fatal)?

1. Anxiety

2. Drug craving

3. Depressed mood

4. Fatigue

5. Increased appetite

6. Lack of motivation

1. How long can the withdrawal of amphetamines last?

1. 3-4 weeks

1. What are the effects of repeated stimulant use?

1. Tolerance 

   1. Autonomic effects

   2. Anorexic effects

2. Sensitization 

   1. Rewarding effects

   2. Psychotomimetic effects (psychosis)

   3. Locomotor stimulant effects

1. What are the negative effects of chronic amphetamine use?

1. Psychosis

2. Anorexia

3. Physical damage

1. Describe psychosis as a negative effect of chronic amphetamine use?

1. Delusional parasitosis

   1. Crawling sensation on skin causes hallucination of bugs, crank bugs, meth mites

1. Describe physical damage as a negative effect of chronic amphetamine use?

1. Meth mouth

   1. Tooth decay due to neglected oral hygiene and reduced saliva

2. Skin sores

   1. Due to skin dehydration, delusional parasitosis, and obsessive picking/punding (speed bumps, meth sores)

1. What is MDMA?

1. Methylenedioxymethamphetamine

2. Ecstacy, E, X, XTC, adam (pills)

3. M, molly (pure powder/crystal form)

1. What are MDMA related drugs?

1. MDA

2. MDE or MDEA

1. What is MDA?

1. Methylenedioxyamphetamine

2. Pre-dates more widely used MDMA

1. What is MDE or MDEA?

1. methylenedioxy-N-ethylamphetamine?

2. Eve

3. Milder, shorter acting

1. When was MDMA first synthesized?

1. Early 1900s

1. What is the history of MDMA?

1. Patented as cough syrup and anorectic, but never used clinically

2. Largely forgotten until 1970s when Alexander Shulgin resynthesized and tried out

3. Currently used by some psychotherapists

   1. Recent evidence that MDMA can enhance communication and openness (similar to psychedelics)

4. August 2024

   1. FD rejected MDMA for PTSD Therapy

When did MDMA first become popular?

As a club drug during 1980s-90s at raves with electronic dance music

1. What schedule was MDMA in 1985?

I

1. What is the route of administration for MDMA?

1. Orally

   1. Long half-life 8 hours

1. What are the MDMA effects at low doses?

1. Behavioral

   1. Increased energy and sociability/empathy; mild euphoria

2. Autonomic

   1. Increased heart rate and temperature; decreased appetite; jaw clenching