Cocaine & Amphetamines 6.1

Psychostimulant Drugs

Cocaine & amphetamines are part of a larger class of drugs known as stimulants, psychomotor stimulants, psychostimulants, or “uppers”

Major behavioral properties:

Stimulate alertness & arousal (“psycho-”) and Stimulate motor activity (“-motor”)

Stimulants include:

Cocaine, Amphetamines, Nicotine, Caffeine

Cocaine

Psychoactive alkaloid found in coca leaves (natural)

Cocaine is a weak base

1800s & early 1900s: widely used; doctors & scientists lauded (praised) its properties

Forms of Cocaine: Raw Leaves

Route of Administration: Raw coca leaves are chewed w/ lime powder or ash to increase saliva pH which enhances absorption by decreasing ionization of cocaine (weak base). Absorption in mouth

Cocaine Concentration: <2% cocaine

Forms of Cocaine: Coca Paste

Coca paste is a crude extraction from leaves by mixing w/ sulfuric acid

Cocaine Concentration: ~80% cocaine sulfate

Route of Administration: Can only be smoked (often w/ tobacco or marijuana)—too caustic for other routes

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

Forms of Cocaine: Cocaine HCl

Cocaine HCl (hydrochloride) is a crystalline powder extracted & purified from coca paste

Cocaine concentration: Very high, usually cut with other powders

Route of Administration: Water soluble & can be taken orally (e.g. Coca-Cola), intranasally, or injected IV. Cannot be smoked vaporization temperature is close to burn temperature

Forms of Cocaine: Cocaine Free Base

Cocaine free base made from cocaine HCL + water + base → extraction with ether (flammable solvent)

Route of Administration: can be vaporized or smoked (“freebasing"). Residual ether can be dangerous & explode with flame

Forms of Cocaine: Crack Cocaine

“Crack” or “rock” cocaine is a cruder preparation of free base, made from cocaine HCL. Safer to make because baking soda is used instead of solvent

Cocaine Concentration: 75-90%

Route of Administration: Smoked

Led to new epidemic of cocaine use in 1980s-90s

History of Cocaine Use: Cocaine products

Coca/cocaine was widely used in many products by late 1800s

Until 1903, Coca-Cola had ~60mg per 8oz serving

Current Medical Use for Cocaine

Has local anesthetic effects (DEA Schedule II)

Primary Mechanism of Cocaine: blocks monoamine transporters (like DAT)

High Doses: inhibits voltage-gated Na⁺ channels (involved in action potentials)

Cocaine Absorption & Distribution

Extremely rapid absorption of cocaine with smoking or IV

Peak Subjective Effect: “when people feel the high”

• PSE for cocaine is ~1-2 mins, over within 5-15 minutes

Cocaine Metabolism & Elimination

Half-life of cocaine is 0.5-1.5 hrs (very short)

Inactive major metabolite benzoylecgonine is detectable in urine for several days

Active metabolite cocaethylene is formed when cocaine & ethanol are ingested simultaneously

• longer half-life than cocaine

Amphetamines & Related Compounds

Chemical family of synthetic & natural psychostimulants

• act as sympathomimetic amines (mimic catecholamines like DA)

Forms of Amphetamines (natural): Ephedrine

Comes from Ephedra or “Mormon tea” (natural)

Active components are ephedrine & pseudoephedrine

• Decongestants: pseudoephedrine is major cold treatment, 2006 → moved behind the counter

  • Pseudoephedrine is easily reduced into methamphetamine or oxidized into methcathinone (bath salts)

Forms of Amphetamine (natural): Cathinone

Comes from “khat” or “qat” shrub leaves (natural)

Commonly chewed in East Africa and Yemen

Increases HR, excitement, euphoria, more talkative ; oral route → slow onset, relatively mild

Forms of Amphetamines (synthetic): Bath Salts

Methcathinone (“cat”) and Mephedrone (“meow meow”) are synthetic variants of cathinone

Designer drugs disguised as household products (bath salts). Placed on DEA Schedule I

Forms of Amphetamines (synthetic): Amphetamine & Methamphetamine

Amphetamine synthesized 1887

Methamphetamine synthesized ~1919

History of Use:

• 1920-30s: Medical use developed

  • Denzedrine inhaler (for congestion) - 1932

  • First use for narcolepsy - 1935

• 1940s: Widespread adoption during WWII

• Early 1970s: Peak use of “speed”

Forms of Amphetamines (synthetic): Amphetamine

• D-Amphetamine

• L-amphetamine (less potent)

• Amphetamine (Adderall)

Route of Administration: taken orally or by injection (IV, SC)

Forms of Amphetamines (synthetic): Methamphetamine

Meth, crystal, crank, speed, ice, glass

Most potent of amphetamines

Route of Administration: oral, snorted, injected IV, or smoked

Amphetamine-related Synthetics

“Amphetamine-like” stimulants differ in chemical structure (used medically):

Methylphenidate: attention deficit disorder

Modafinil: narcolepsy, sleep apnea

History of Amphetamine Use: Congestion

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

History of Amphetamine Use: Mood & Weight Control

Amphetamines used for narcolepsy due to wake-promoting effects

Could elevate mood & suppress appetite, was also used for mild depression and as a diet pill (NOT a current medical use though)

History of Amphetamine Use: Military

Amphetamines used widely by military during WWII and subsequent conflicts

Used to increase attention and reduce fatigue (increase wakefulness)

Standard in Air Force

History of Amphetamine Use: General use for Fatigue

1970: >10% of population were regular users (truckers, housewives)

1971: control began

Current Methamphetamine Use: Meth Epidemic

As crack wave diminished in mid-late 90s, meth use increased

High purity, can be smoked

Easily prepared from common household ingredients

Current Medical Uses for Amphetamines

DEA, Schedule II

• Narcolepsy

• Attention Deficit Disorder (ADD, ADHD)

Amphetamines Metabolism & Excretion

Amphetamines have a slower metabolism & elimination as compared to cocaine

Half-life is 7-30 hrs

Can be detected in urine test

Stimulants: Major Effects

Mild-to-moderate effects:

mood amplification, sleep disturbance, talkativeness, anger, anorexia, inflated self-esteem

Severe effects:

irritability, total insomnia, rambling, possible extreme violence, total anorexia, delusions of grandiosity

Autonomic effects also: increase BP, hyperthermia (increased body temp), bronchodilation

Cocaine vs Amphetamines

Cocaine:

Shorter duration of action (0.5-1.5 hrs)

Worse cardiovascular effects, possibly lethal (due to actions of sodium channels)

Higher convulsive/seizure properties of cocaine (sensitize w/ repeated use)

Stimulants: Major effects on animals

Animals: hyperlocomotion

Locomotor activity can appear to go down w/ high AMPH dose because rats perform stereotypy behavior instead

Reinforcing/rewarding effects: self-administration, CPP

Stereotypy

Performing of the same movement over and over again for long periods of time

Effects of repeated stimulant use: Withdrawal

Chronic, high-dose users of stimulants (cocaine/amphetamines), withdrawal symptoms are mostly psychological (as opposed to physical) and not fatal

• anxiety, drug craving, fatigue, increased appetite, lack of motivation, depressed mood

Can last for 3-4 weeks

• drug craving lasts even longer

Effects of repeated stimulant use: Tolerance & sensitization

Tolerance to some effects of psychostimulants:

• autonomic effects

• anorexic effects (have to increase dose constantly)

Sensitization to other effects of psychostimulants:

• rewarding effects

• psychotomimetic effects (psychosis)

• locomotor stimulant effects

Negative Effects of Chronic Amphetamine Use

Psychosis: such as delusional parasitosis (crawling sensation on skin causes hallucination of bugs, crank drugs, meth mites)

Anorexia: decreased eating, weight loss

Physical damage: “faces of meth”

• Meth mouth: tooth decay due to neglected oral hygiene & reduced saliva

• Skin sores: due to skin dehydration, delusional parasitosis, & obsessive picking/punding (repetitive purposeless movement (often skin associated)) (speed bumps, meth sores)

MDMA & Related Drugs

MDMA: methylenedioxymethamphetamine

• ecstasy, E, X, XTC, adam (pills)

• M, molly (pure powder/crystal form)

MDA: methylenedioxyamphetamine

• pre-dates more widely used MDMA

MDE or MDEA: methylenedioxy-N-ethylamphetamine

• eve

• milder, shorter acting

History of MDMA

First synthesized - early 1900s

Patented as cough syrup & anorectic, never used clinically

Currently used by some psychotherapists: recent evidence that MDMA can enhance communication & openness (similar to psychedelics)

FDA rejected MDMA for PTSD therapy

MDMA Use

First became popular as a club drug during 1980s-90s at raves

Schedule I classification in 1985

Mostly taken orally; long half-life (8hrs)

MDMA: Major Effects

MDMA Effects at Low Doses:

Behavioral: increased energy & sociability/empathy; mild euphoria

Autonomic: increased HR & temperature; decreased appetite; jaw clenching

MDMA Effects at High Doses:

Behavioral: mild hallucinogenic effects, more amphetamine-like effects, “hangover”

Autonomic: hyperthermia & dehydration; increased HR & BP → stroke