• high potential for abuse
• no currently accepted medical use in treatment in the US
• examples
  • LSD
  • heroin
  • marijuana

• high potential abuse
• abuse may lead to severe psychological or physical dependence
• accepted medical uses in US
• examples
  • morphine
  • amphetamine
  • cocaine
  • barbituates

• potential for abuse less than on I, II
• abuse may lead to moderate or low physical dependence OR high psychological dependence
• examples
  • codeine with acetomenaphin
  • steroids

• low potential for abuse relative to the drugs in III
• abuse may lead to limited physical or psychological dependence
• examples- benzodiazepines

• low potential for abuse relative to drugs in schedule V
• examples- OTC cough medicine with codeine

• all psychoactive drugs are rewarding by stimulating the brain reward
• stimulation via mesocorticolimbic system
• experimental proof
  • place preference showed animals given a drug in one environment and a vehicle in another
    • if they perceive drug as rewarding they will choose drug associated with environment
  • self administration of drug is hallmark of abuse liability
  • drug discrimination studeis showed animals learn to discriminate between a test drug and vehicle, or another drug they have previously learned to choose

• cellular tolerance (adaptation of response)
  • can be changes in receptors, cell signaling, or other mechanisms
  • vastly different time rates for different mechanisms (seconds to days)
• metabolic tolerance (enhanced elimination rate of drug)
  • less common, although does occur with alcohol

• coupling to intracellular effectors can be inhibited
  • ex: beta arrestin binds to phosphorylated receptor, inhibited coupling to G protein
• receptor can be removed from cell surface (internalization/down regulation)
  • can be temporary (sequestration) or can lead to breakdown of receptor
• synthesis of new receptors can be inhibited
• expression of related signaling proteins can be altered

• definition- appearance of withdrawal symptoms (abstinence syndrome) when drug is stopped
  • percipitated withdrawal when occurs in administration with antagonist (faster and more severe symptoms)
• it occurs with:
  • repeated chronic use
  • clinical use
  • many drugs (even those that are not abused)

So the presence of physical dependence is not a sign of abuse, even though it is a common occurance with a drug of abuse

• a behavioral syndrome (compulsive drug seeking behavior)
• primary, chronic, relapsing disease with genetic, psychosocial and enviornmental factors influencing development and manifestation

• major portion of individuals life is devoted to drug seeking behavior and drug use
• individual cannot stop use without experiencing significant physical discomfort and/or psychological disruption
• drug use dominates the individuals existence, often interfering with normal functioning
• drug use continues despites presence of significant medial, social, and legal consequences

• methylxanthines (caffeine, theobromine)
• nicotine (stimulant, anxiolytic)
• ephedrine (main ingredient: ma huang)
• pseudoephedrine

• Modafinil, Pemoline- for narcolepsy
• Sibutramine, Diethylpropion, phentermine- appetite suppresant

• Benzphetamine
• phendimetrazine

for appetite suppression

• methylphenidate- ADHD
• amphetamine, dextroamphetamine- narcolepsy, ADHD, chronic fatigue syndrome, nausea
• methamphetamine (crystal meth)
• cocaine (limited use as anethesthetic)

• cathinone (active ingredient in khat)

• enhance synaptic release of DA and NE
• also weak effect blocking MAO and as direct receptor agonist

• block reuptake of DA (less so of NE, serotonin)

• when given via the same route of administration, response of body is very similar
  • studies show subjects unable to distinguish subjective effects of amphetamine and cocaine (except nasal numbing of cocaine)
  • similar CV response

• meth has slightly more CNS effects and less peripheral effects

• arousal, alertness, insomnia, relief from fatigue
• euphoria, increased confidence, flow of ideas, talkativeness
• increase in temperature, respiration, sex drive
• decrease in appetite and thirst

• sympathomimetic- increase HR, bp
• adrenergic effects
  • sweating
  • nausea
  • cramps
  • headache
• muscle twitching
• teeth grinding

• lethargy
• hunger
• depression

Increased energy is borrowed

• cardiac arrhythmias
• MI
• cerebral vasoconstriction, possible stroke
  • w/cocaine, potential seizure (due to local anesthetic activity in CNS)

• continued wakefulness
• profound anorexia
• hyperactivity
• hyperirritability
• labile mood
• violent behavior
• compulsive behavior
• confusion, anxiety, hallucination = psychosis

• can develop rapid tolerance to euphoric effects
• sensitization to other effects
  • sensitization to cardiac or cerebral vascular effects can be fatal
• physical dependence occurs, but less prominant than with other drugs like alcohol or opioids
  • withdrawal cause depression
• psychological dependence
  • can be profound
  • liability related to route of administration (highest IV, smoke crack)
  • very difficult to treat stimulant addicts

• cocaine is active ingredient in coca leaf
• extract is in form of hydrochloride salt, which is readily soluble, so it can be snorted or injected
• if you remove the hydrochloride, you get a free base form that is not soluble and forms chuncks and rocks, so you have to smoke it via vaporization = crack
  • gets into the brain very rapidly by smoking it, increasiing its abuse liability compared to other routes

• smoking cessation
• neurolgic diseases
  • Parkinsons
  • Alzheimers
  • Tourette's

• calming
  • reduce anxiety
  • relaxation
• stimulant effcts
  • arousal
  • increased concentration
  • loss of appetite