Middle East: prohibited by Islamic law, severe penalties

India: Not illegal, but violates social norms

US: socal attitudes and legal structue encourage and punishes use

Race and use of illicit drugs

(metropolitan areas)

White: 12%

Black: 11.2%

Hispanic:10.1%

Asian: 5.1%

Possession of cannabis in Indiana

Penalties

30 grams:1 year/$5,000

>30 grams: 3 years/$10,000

(30 g= 1oz)

Sale or cultivation of cannabis in Indiana

Penalties

30 grams: 1 year/$5,000

30 grams to 10 lbs: 3 years/$10,000

>10 lbs: 8 years/10,000

*One or more during a year leading to significant impairment or distress

1. Failure to fulfill important obligations at work, home, or school as a result of substance abuse

2. Repeated use of substance in psychically hazardous situations

3. Continued use of substance despite repeated social or legal problenms as a result of use

4. Continued use of substance despite problems

*Maladaptive pattern of substance use, leading to 3 or more of the following:

1. Tolerance(the need for increased amounts of substance to acheice intoxication, diminished effect with continued use of same amount)

2. Withdrawal(the characteristic withdrawal syndrome; same substance taken to releive or aviod withdrawal symptoms

3. Substance often taken in larger amounts or over a longer period than intended

4. No desire or unsuccessful attempts to control use

5. Consumes a lot of time

6. Failure to meet demands of daily living

7. Use continued despite appreciation of problem

act on the Ventral Tegmental Area and Nucleus Accumbens-components of the reward circuit

-interconnected with prefrontal cortex, septum, amygdala, nucleus accumbens

-Drugs of abuse act on receptors within the reward circuit

-Ecstasy-> Serotonin

-Cocaine-> Dopamine

-Heroin-> Enkephalins

-Barbituates-> GABA

Alcohol:50%

Cigarettes: 30%

Marijuana: 6%

Sadatives/Opiates: 3%

Cocaine: 1%

Hallucinogens: .4%

Inhalents: .2%

Depressants

Increase GABAergic transmission

-Benzodiazepines and Barbituates

-Opiates

-Inhalents

-Alcohol

-Usually GABA agonists:primary inhibitor neurotransmitter in the cortex

-low doses:relaxation, feeling of well-being

-high doses: alcohol like- loss of coordination, problems concentrting/working, redued inhibition, poor judgement

Valium, Xanax, Halcion, Librium, Klopin

-anti-anxiety, anti-seizure meds

(Quaaludes)

-Initially prescribed as sleeping aid, highly addictive

-Overdose: diaphragm relaxes, causing death suffocation

Morphine-(pain releiver in 17th century)

Heroin

Codeine

Hydrocone (Vicodin)

Oxycodone (Oxycontin)

Methadone

Opiods criminalized in US in 1917

Concentrated in the thalamus-involved in pain, the cerebral cortex, the visual cortex, and the basal ganglia-coordinates movement and emotion

-Number of receptors varies among individuals

-Higher numbers of Mu receptors associated with decreased pain sensitivity

-rush

-depressed respiration

clouded mental functioning

-nausea and vomiting

-suppression of pain

-spontaneous aborition

-Addiction

-Infectious diseases (HIV/AIDS, Hep)

-Collapsed Veins

-Bacterial infections

-Absecces

-Infection of heart lining and valves

-Arthritis and other rheumatologic problems

Two pathways to addiction: medical or after prior drug use

-After physiological dependence develops, injections needed every 4 to 6 hours

-long term course (30 yr follow up):

*17% users

*7% methadone maintenance

*22% abstinent

*11% incarcerated

-Caffeine

-Nicotine

-Amphetamines

-Cocaine

-most heavily used stimulant drug

-75% of caffeine is ingested through coffee

-Avg american drinks 2 cups/day

-stimulates the CNS increasing levels of dopamine, norepinephrine, and serotonin, and blocking the adenosine receptor (adenosine induces sleepiness)

-Causes adrenal glands to produce more adrenalin-increases arousal and activity

Symptoms of Caffeine

Nicotine

-Agonist for nicotinic cholinergic system, monoamine, and opioid systems involved in alertness and reward

-increases arousal, alertness, sympathetic activation

-Prevalance: 30% of population

*men smoke most in Russia, Indonesia, Ukraine, Kenya

Health consequences of smoking

-coronary heart disease

-stroke

-respiratory infections

-emphysema

-lung cancer

-reduced blood flow to skin: with age, gum disease and skin wrinkling

-pipes and cigars: lip, tongue, mouth, esophagus

-a score of 5 or more indicates significant dependence

-a score of 4 or less shows a low to moderate dependence

-Nicotine exposure causes prolonged increase in glutamatergic activity, which stimulates dopamine release in nucleus accumbens

-Nicotine has a transient excitatory effect (2 min) and then inhibits GABAergic inhibition of glutamatergic and dopaminergic neurons

-over 70% of users wish they could quit

-After quitting, most relapse after a few days

-Only 7% are still abstinent after 1 year

-Dexedrine, Benzedrine, Methamphetamine

-Cause release and block reuptake of dopamine and norepinephrine

-Intoxication effects: Increased attention, decreased fatigue, decreased need for sleep, euphoria, self-confidence, alertness, agitation, paranoia, cardiovascular and cerebrovascular stress

-Rapid tolerance

-Lifetime prevalance: ~4% of population has tried amphetamines

-Dopaminergic downregulation probably persists months/years after discontinuation

Stimulant

-man made

-smoking produces a long lasting high

-50% of the drug is removed from the body after 12 hours

-increases dopamine release and blocks dopamine reuptake

-limited medical use

Stimulant and local anesthetic

-plant-derived

-smoking produces a breif high

-50% of the drug is removed from the body in 1 hr

-blocks dopamine reuptake

-limited use as local anesthetic in some surgical procedures

-blocks DA and NE, increasing the effects of these NTs(reward, increased arousal)

-Symptoms-Behavioral changes, irritability, restlessness, anxiety, paranoia, rapid heartbeat, dilation of pupils, change in bp, nausea/vomiting, muscular weakness, slowed breathing, chest pain, confusion, seizures, cardiac arrest, coma

binging can result in paranoid psychosis

-prolonged use terminates in severe withdrawal associated with physical and emotional depression

Hallucinogens and PCP

Intoxication symptoms

Hallucinogens and PCP

Withdrawal symptoms

MDMA (ecstacy)

effects

-Cause the release of serotonin

-block the reuptake of serotonin by the synaptic terminal that releases it

-deplete the amount of serotonin in the brain

-binds to dopamine and NE transporters, potentiating both neurotransmitters

-produces widespread dose dependent depletion of 5HT transporter(SERT) at concentrations similar to humen use on autoradiogram assays.

-Acts w/in 1 hr

-Increased alertness and energy

-Emotional warmth, empathy

-sense of well being and elaxation

-Decrease social anxiety

-Enhanced sensory perception

-Possible hyperthermia

-Midweek blues-depressed mood which persists several days after intoxication

-increased aggression and anger-peaks about 4 days after episode

-In rats, a dose dependent increase in anxiety like behaviors for up to several months after administration

MDMA can cause increase in body temperature which can cause breakdown of skeletal muscles and kidney failure.

-Drinking of very large amounts of water to counteract hyperthermia can cause water intoxication, in which sodium levels in blood are disturbed by dilution(hyponatremia)

-Short term working memory and learning deficits

-long term effects on cognitive function not well documented, but memory may be affected-effects may be potentiated ir caused by other types of drug

-Genetics play a substantial role in at least some forms of addiction

-genetics influence personality characteristics associated with risk for substance abuse-impulsivity, lack of concern for long term consequences, sensation seeking, aggression

-Genetics may also act through comorbid disorders such as MDD, bipolar disorder, schizophrenia, and antisocial personality disorder

-Reward circuit activated when behavior enhances individual survival, social status, and reproduction

-drugs can hijack reward system

Biological mechanisms

Nucleus accumbens and reward

1. Frontal, subcortical nucleus with high density of dopaminergic and opioid neurotransmitter systems

2. In animals, both naturally occuring rewards and rewarding drugs increase activity of accumbens

3. Electrical brain stimulation of accumbens often appears reinforcing

4. In humans, brain imaging suggests that accumbens is activated by rewarding experiences and drigs, most ultimately thoguh dopamine projections

shell-receives dopaminergic projections from VTA and excitatory projections from amygdala, hippocampus, medial prefrontal cortex. Integral to reinforcement experience and learning

-Core-triggers motor response to cues that a reinforcer will be available in environment

-Release of NTs such as DA and cause reduction in # of receptos or damage to neurons

-Reduction in receptors or NT production may cause craving and withdrawal symptoms

-With addiction, craving or seeking behavior is maintained by glutamatergic modulation by orbitofrontal and cingulate cortex

-animals and humans form classical conditioned links between environment and stimuli and effects of intoxication

-merely seeing a picture of a cue (syringe), can elicit intense craving and physiological activation associated with substance use

-Stress increases use of substances and likelihood of relapse

-stress causes corticotrophin-releeasing hormone which initiates hormonal and physiological stress response.

-Children learn substance related behaviors from modeling of parents and important others

-substance use is a way of coping with stress

-substance use can substitute for failure to attain natural goals.

Sociocultural approaches

-Chronic stress combined w/ a substance supported invironment increases the risk of abuse

-substance use is more acceptable for men than women in many societies

-women's patterns of substance use and reasons differ from men's

Detoxification: controlled withdrawal from substance

Antidepressants and Sedatives: may ease withdrawal from some substances

(unclear if effective in reducing relapse)

-Antagonist meds block effects of drugs

-Naltrexone, nalaxone- opioid antagonists (used to reduce alcohol effects)

-Disulfiram (antabuse): induces nausea when alcohol is consumed: compliance poor

Methadone: synthetic, oral opioid which is used to replace heroin

-blocks receptors for heroin

-no high, but methadone also addictive

-methadone users show relatively good outcome, less likely to relapse or engange in criminal activity

-Aversive classical conditioning

-covert sensitixation therapy (imagine bad consequences)

-Cue exposure and responses prevention (expose to cues for drug or alcohol use, but prevent use. Should lead to extinction)

-Cognitive and social therapy

-prevention

1/3 of Americans live w/ extreme stress

-psychological symptoms: anger, irritability, nervousness, lack of energy, fearfullness

-physical symptoms: fatigue, headache, upset stomach, muscle tension

-lie awake at night, overeating, unhealthy eating, skipping a meal, drinkers drank or smoke

Physical threat- bear attack

Exposure to severe cold

Sleep deprivation

Early research on ovarian extract on rats

-inject daily-> ulcers, enlarged adrenal glands, shrunken immune tissues

-Other subjected to cold, heat, forced exercise, surgical procedures had same effects

-General rather than specific responses

1. Alarm Stage (emergency reaction, fight or flight)

2. Resistance stage (coping and fighting)

3. Exhaustion stage (onset of stress pathology)

-Initial response (sympathetic nervous system fast, hormonal responses minutes to hours)

-Mobilize energy from storage, inhibit further storage

-increast HR, BP, breathing

-Analgesia

-Increase alertness, inhibit sleep

-automatic response, but can be modified by learning

-wide range of hormonal adjustments

Stressor->brain->anterior pituitary->adrenal cortex->glucocorticoids

or

Stressor->brain->sympathetic nervous system->adrenal medulla->NE and E

-Controlled by bunches of nerves called ganglions

-branches from the spine throughout the body

-during the stress response, functions to divert energy away from processes such as digestion, immune function

-fight/flight, increase carb/fat availability

-reinforces the sympathetic nervous system

-Mobilize energy stores

-Enhance metabolism

Growth hormone

-breif response

-increases mobilization of stored energy

-can be used for growth or for exercising muscle

-therefore, increased energy and growth of muscles

Resistance or Adaptation stage

-Resistance, or adaptation if stressor continues

-Fat: decrease glucose uptake, increase lipid mobilization

-Skeletal muscle:Decrease protein synthesis, increase degradation, decrease glucose uptake

-increased cortisol

-increased appetite

-increase vulnerability to anxiety and depression

-immunosuppression: decrease antibody production, decrease circulating lymphocytes

-resources depleted

-never store extra energy, fatigue rapidly, increase chance of diabetes

-increased BP, heart diseases, stroke

-Reproductive disorders

-hippocampus neurons destroyed

-immune suppression

exacerbating factors common in underclass:

-lack of control over stressors

-Inability to predict stressors

-Lack of outlets for frustration

-Interpretation of stressors as worsening

-Lack of social support

-for men, keeping quiet during a fight had no measureable effect on health

-for women, four times as likely to die during the 10 yr study compared to women who told husbands their feelings

children- 8%

sex- 8%

money- 7%

leisure- 7%

alcohol- 6%

housework- 6%

during 6 of the 7 german soccer games, there was an increase in the number of cardiovascular events , even more so during a dramatic match where the winning goal was scored in the alst minute

-more than doubles risk

- mild and transient stress may enhance learning

-prolonged stress has severe consequences primarily due to cortisol effects on neurons and secondary glutamatergic excitotoxicity

-Glucocorticoids damage hippocampal neurons

-dendrite and axon retraction

-inhibition of hippocampal neurogenesis

-long term depression( opposite of long term potentiation, which is basis for memory formation)

-Hippocampus size reduced in elderly with higher levels of cortisol

-stress can cause amygdala hypertrophy

-probably associated with negative affect, anxiety, aggression

-confined, stressed rates increases fighting behavior

Effects of sleep deprivation to 4 hrs/night:

-increased BP

-decreased parasympathetic tone

-increased evening cortisol & insulin levels

-Increased appetite & weight gain

-Increased ghrelin(appetite increasing hormone)

-Decreased leptin levels

-Degreased neurogenesis in hippocampus

-amygdala hyperactivated in response to bad things in sleep deprived

-connectivity analysis: amygdala appears to inhibit frontal cortex activity, while activating locus coeruleus(NE)

*More reactive to negative inputs when stressed

-reduction in vigilance

-impaired fear conditioning

-spatial memory

-sleep deprived medical residents make 36% more serious errors than residents with sleep

-sleep deprivation results in similar or greater cognitive impairment than a BAC of .05

-Immunosuppression

-Increases fighting behavior in rats

-negative impact on mood

-distractability

Coping strategies for stress

-Be sociable

-have a happy family

-grooming/touching/massage

-exercise

-gain control in life

-keep positive outlook

-Have a nurturing mother

Animal exposed to a larger, more aggressive animal and is defeated in a single encounter

-avoid defeat & humiliation

Severe, often very persistent disorder subsequent to traumatic event(s) such as combat, natural disaster, rape, assault

-associated with reexperience of traumatic event, enhanced arousal and avoidance of trauma related stimuli

A) exposure to traumatic event in which

*person experienced actual or threatened death or serious injury, or threat to others

*Person responded with intense fear, helplessness, or horror

B) Traumatic event reexperienced:

*Recurrent, intrusive memories

*recurrent nightmares

*acting or feeling as if event is recurring

*intense distress to cues that resemble event

*phsyiological reactivity to cues that resemble event

C) Avoidance of stimuli associated with trauma and numbing of responsiveness

*avoidance of evocative thoughts/situations

*inability to recall aspects of trauma

*diminished interest in activity

*social detatchment

*restricted range of affect

*sense of foreshortened future

-Duration more than 1 month

-causes psychosocial or occupational distress/impairment

-Called shell shock in WW I

-Combat fatigue in WW II

-occurs in 40% of rape victims

-20% of vietnam veterans

-Also common in first responders to disasters -firemen, police, rescue workers

10% lifetime prevalence in women

5% lifetime prevalence in men

Trauma exposure reported by over half of sample

Higher rates in developing countries

50 years after experiment, 32% of the soldiers had current PTSD

factors that increased likelihood:

-being ordered to participate

-not having protective training

-seeing others in distress

-hispanic ethnicity

-more exposures

-physical symptoms during test

Childhood sexual abuse associated with risk for:

Major depression

Suicide attempt

Conduct disorder

Alcohol dependence

Nocotine dependence

Social anxiety

Rape after age 17

Divorce

-Alcohol and other substance disorders

-Partner aggression

-Divorce

-Depression

-Occupational instability

-Legal problems

-Physical health problems

-severity of trauma

-small genetic factor

-female

-physiological hyperactivity

-history of adversity and trauma

-small effect of prior psychopathology

-lack of social support after trauma

-Associated with reduced cortisol levels; indicative of hypersensitivity of HPA axis

-may be secondary to trauma stress response, but could precede illness

-affected individuals have reduced hippocampal gray matter on MRI scans

-may be secondary to trauma stress response, but could precede illness

-exposure therapies(real or imaginary)

*extinction of response

*reduce avoidance, increase mastery

-Anxiety management

*relaxation training

*breathing therapy

*self-dialouge & cognitive restructuring

*education

-avoiding self-blame

Antidepressants (SSRIs) have modest effects

Atypical antipsychotic meds also appear promising, especially for psychotic symptoms (hallucinations), paranoia, dissociation, intense anger