Behavioral pattern of compulsive drug use, characterized by an owerwhelming involvement with the use of a drug, the securing of its supply and a high tendency to relapse after withdrwal.

This should imply:

Extreme compulsive use

Psychological dependence

Addiction should not be used intercahngeable with physiological dependence

AKA chemical dependence

• Altered physiological state as a result of chronic drug use
• The degree of physiological dependence can only be determined by the severity of the withdrawal 

• Rebound hyperexcitability; withdrawal symptoms typically are opposite of drug effects
• Withdrawal intensity is related to the degree of altered function (physical dependence)
• High Doses
• Frequent administration
• Long Period of use
• Rate at which the drug is removed  

• More drug is needed to elicit the same response or a reduced response is elicited by the same dose.  Required more or less continuous exposure.
• Drug dispositional, metabolic pharmacokinetic tolerance: Less drug gets to the site of action because more of the drug is metabolized. 
•  Pharmacodynamic cellular or functional tolerance: Same amount of drug gets to the site of action but the resonse is reduced.  Down regualtion of receptors on the surface of the cell.
• Acute Tolerance: A rapidly developing pharmacodynamic tolerance
• Reverse tolerance or sensitization: Intermittent exposure causes a progressive increase in the sensitivity to drugs

• Individual feels that the effects of a drug or the conditions associated with its uses are necessary to maintain an optimal state of well being.
• Positive Reinforcement: Drug induces euphoria or other pleasurable effects
• Negative Reinforcement: Drug terminates pain, anxiety, or withdrawal distress 
• Conditioning or secondary reinforcers
• Induced by sight of the drug or the environment in which the drug was taken
• The conditioned abstinence and severe craving that can occur when the individual returns to the old environment.  This can be an important factor in:
• Relapse of the drug
• Development of compulsive drug use

• Attempt to measure the reinforcing properties of drugs and predict their potential for compulsive use
• Cross-dependence to drugs that are abused
• Discrimination or substitution paradigms: animals are trained to differentiate a drug from a placebo
• Self-administration: determine if the animal will take the drug and the pattern of administration

• Cocaine is extracted fro mthe leaves of Erthroxylon Coca
• Central effects are the same as amphetamine, except the duration of action is shorter for cocaine  
• Cocaine HCL:Salt form is water soluble and is readily absorbed across mucous membranes
• Freebase or Crack: The nonsalt form is not water soluble but is readily volatized by smoking.  The drug is rapidly absorbed by the lungs and wuickly enter the brain because of the high lipid solubility of the base form.
• Cocaine is rapidly metabolized by plasma esterase.
• t1/2 = 30 min
• In the presence of ethanol, liver esterases metabolize cocaine to cocaethylene.  Cocathylene has all the activity of cocaine.
• With low doses : garrulousness, increased motor activity, euphoria
• With high doses: paranoid psychoses, hallucinations, seizures, coma
• Cocaine produces Reverse Tolerance: sensitization with chronic use.  After long period of chronic use the paranois and convulstions occur at low blood levels.
• Limited Physical Dependence: similar to amphetamine except that the drug seeking behavior is more obvious
• Sever Psychological Dependence due to the following:
• Strong reinforcing properties
• Short duration of action
• High Doses (especially with crack)
• Rapid routes of administration
• Mechanism of Action of cocaine
• Block reuptake of biogenic amines, inculding dopamine. The psychic effects are probably due to an action on the mesolimbic dopamine system
• Arrhythmias associated with cardiac toxicity of cocaine probably are due to inhibition of NE reuptake
• Local anesthetic probably not related to CNS effects

• Behavioral Effects:
• Increases wakefulness, alertness, vigilance, initiative and self-confidence
• Decreases the sense of fatigue
• Improved simple mental tasks
• Enhanced motor activity
• Produces euphoria which is positive reinforcement that will elicit self-administration
•  Analeptic- Stimulates respiration by a central mechanism. Not usually recommended for respiratory depression
• Anorectic- Inhibits appetite by acting on the hypothalamic feeding center
• Pharmcodynamic/functional tolerance
• Cross tolerance to other amphetamines, methylphenidate, and cocaine, NOT caffeine
• Limited physical dependence-not life threatening
• Strong psychological dependence
• Mechanism of Action
• Acts to inhibt the uptake and cause the release of biogenic amines, including dopamine. The rewarding properities and other psychic effects are due to amphetamine action on the mesolimbic dopamine system.
• CNS toxicity
• Dizziness, agitation, confusion, insomnia
• Grinding of teeth, picking of the face
• Hallucinations
• Toxic psychoses: Paranoid schizophrenia. Patients tend to be aggressive, irritable and hallucinating.  No tolerance develops to amphetamine psychoses
• Seizures, coma
• Cardiovascular toxicity: May be seen as a hypertensive crises, tachycardia, or arrhythmias. Because of tolerance these symptoms may not appear in chronic abusers
• Uses of amphetamine
• ADD
• Obesity
• Narcolepsy

• Pharmacology essentially the same as amphetamine
• Drug of choice for ADD

• General properities include CNS stimulation, diuresis, tachycardia, bronchodilation, dilation of peripheral blood vessels, and constriction of cerebral blood vessels.
•  CNS effects (1-3 cups of coffee)
• Decreased drowsiness and fatigue
• Enhanced intellectual effort and a decreased reaction time.
• Increased gross motor activity that may be associated with increased muscular strength
• Stimulation of Medullary Respiratory Centers
• Mechanism of Action
• Translocation of intracellular calcium
• Inhibition of phosphodiesterase
• Adenosine receptor antagonist.
• Uses:
• Migraine in combination with ergotamine to induce vasoconstriction of the cerebral casulature
• Recurrent apnea in preterm infants
• Maintain wakefulness
• Bronchial asthma-theophylline

• Mediates the addictive properties of tobacco
•  Pharmacology: Psychic effects- arousal and euphoria. Also enhances attention, learning, reaction time, problem solving.  Decreasing irritability. Acts as an agonist at central nicotinic receptors and may activate mesolimbic dopaminergic neurons
• Peripheral Effects:
• Low doses activate nicotinic receptors in autonomic ganglia. Increase blood pressure, increases heart rate and induces peripheral vasoconstriction
• High doses antagonize nicotinic receptors in ganglia
• High doses stimulate CTZ to induce nausea and vomiting
• Psychological dependence can be severe-induces euphoria and is self-administered and is discriminated as a psychostimulant
• Limited physical dependence
• Limted tolerance

• Cause Hallucination and delusions
•  Can be caused by posions-cause organic brain syndromes. The mechanism of action is a generalized metabolic disruption of neural and non-neural tissue more than a discete neuropharmacological action
• Types of compounds involved:
• Therapeutic Drugs: sulfanomides, penicillin, prednisolone, thyroxin, cardiac glycosides and ethanol
• Industrial Chemicals: carbon disulfide, carbon tetrachloride, and heavy metals
• Aromatics: solvents used in glue, or the propellants used in spray cans.  Benzene, toluene, eylene, chloroform, trichloroethane, naphtha, and isopropyl alcholo.
• All cause damage to major organs: Acute toxicity can result in cardiac arrhythmias and hypoxia
• CNS effects:
• exhilaration, lightheadedness
• Impaired judgement and preception
• Hallucinations
• Loss of consciousness or coma

• Deleriants produce delusions associated with hallucinations without metabolic disturbances
•  Anticholinergics: High doses can cause confuction, drowsiness, dysphoria, agitation, and unpleasant delusions (hallucinations) that the patient is amnestic of. Can be produced by atropine, scopolamine, benztropine, and trihexiphenidyl

• This group is represented by phencyclidine (PCP) and Ketamine (Ketalar). Only Ketamine is used clinically in humans and veterinary medicine.
• CNS effects of PCP
• Produces a dose-related continuum of behavioral states. Each of these states is associated with various degrees of delusions, hallucinations, and analgesia
• Does related states of PCP
• Stimulated, activated state
• Bizarre and agressive behavioe
• Unresponsive and catatonic
• Seizures and coma
• Mechanism of action of PCP
• Noncompetitive antagonsit of NMDA receptor
• Some activity at opiate (not really opiate) sigma receptor

• Hallucinogenic but without the general metabolic disturbance and with a reduced delirious state
•  General Effects of Hallucinogens:
• Physiological: Sympathomimetic
• Sensory: Perceptual distortions ranging from simple to complex hallucinations in more than one modality
• Psychic: Produces psychotic episodes that look like a schizophrenic state and respond to phenothiazines, antipsychotics or major tranquilizers

• Potent: 1/2 ug/kg will produce effects for 8-12 hours
• Tolerance develops very rapidly
• No physical dependence and therefore no abstinence or withdrawal syndrome
• Psychological dependence occurs very rarely 
• Cross tolerant to psilocin and mescaline but is not cross tolerant to the hallucinogenic effects of scopolamine, marijuana, PCP, or ketamine
• Mechanism of action: 5-HT receptors
• Sympathomimetic effects: increased blood pressure, tachycardia
• CNS actions:memory, thinking impairment, mood changes, distortion of sensory perception
• Adverse reactions: panic, dysphoria (anxiety, paranoia, confusion)

• Effects similar to LSD, produces vivid colorful hallucinations with fewer psychotic reactiosn than LSD
• Less Potent
•  Cross Tolerance to LSD, psilocybin

• Found in the mushrooms stropharia and psilcoybe
• Effects similar to LSD
• Cross tolerance among LSD like drugs 

MDMA (Ecstasy)

• Psychotomimetic effects
• CNS stimulant properties
•  Works on serotonin system (destorys serotonin neurons)
• A derivative of amphetamine
• Short Term effects: Changes brain chemistry and behavior
• Long Term effects: Changes brain structure and behavior

• Plant source: Cannabis Sativa (hemp)
• Active component: THC
• Pharmacokinetics: absorption is rapid via inhalation
• THC and metabolites are highly lipid soluble
•  CNS effects:
• Euphoria, relaxation
• Impairment of short term memory, time perception, and motor coordination
• Acute toxic psychosis
• Acute panic reactions
• Cardiovascular effects: tachycardia, vasodilation
• Mechanism of action: cannabinoid receptors
• Tolerance
• Adverse reactions:
• Bronchitis
• Amotivational syndrome
• Potential therapeutic uses of THC
• Glaucoma
• Prevent emetic effect of chemotherapy
• Analgesic effect (Multiple sclerosis)

• Experimentation
• Social Use
• Situational Use
• Compulsive Use 

• The individual
• Societies, groups
• Behavioral modification
• Medical management-alteration of drug effect to prevent further comulsive use 

• Reduce Risk Factors
• Ineffective parenting
• Chaotic home environment
• Lack of mutual attachments/nurturing
• Inappropriate behavior in the classroom
• Failure in school performance
• Poor social coping skills
• Affilations with deviant peers
• Perceptions of approval of drug-using behaviors in the school, peer, and commiunity environments
•  Enhance Protective Factors
• Strong family bonds
• Parental monitoring
• Parental involvement
• Success in school performance
• Prosocial institutions
• Conventional norms about drug use

• Detoxification safely manages the physical symptoms of withdrawal
• Only first stage of addiction treatment
• Alone does little to change long term drug use 

• Methadone  -used for opioid dependence (mu agonist)
• LAAM-used for opioid dependence (mu agonist)
• Nicotine Replacement
• Patches
• Gun
• Buproprion
• Drug effect is blocked
• Naltrexone (ReVia): opiate antagonist that is long lasting and orally effective with few side effects
• Buprenorphine (Buprenex): as a partial agonist of the mu receptor acts to reduce the craving associated with opioid abstinence
• Drug become a punishment
• Disulfiram (antabuse)-inhibts aldehyde dehydrogenase which results in nausea and vomiting when ethanol is ingested