Drugs & Behavior Exam 4

Psychotherapeutic Medications

exert a special or unique effect on the mind or mental functioning

antipsychotics, antidepressants, antimanic/mood supressors, anti-anxiety

Old School Mental Illness Treatments

blood letting, hot irons, flogging, revolving chairs, starvation, sneezing powder, isolation, straight jackets, lobotomy

Howard Dully

lobotomy, Dec 15 1950, child schizophrenia, swollen eyes after, “lost something”

Medicine Revolutions

• 19th cent - vaccines, louis pasteur (rabies/vaccine/germ theory)

• WWII - antibiotics, selmon waksman (streptomycin, neomycin)

• 1950 - Emil Kraepelin, Philip Pinel, JE Esquirol 

  • Mental illness classification system, chlorpromazine (Charpentier)

  • Scientific evidence/understanding prereq for treatment

  • Val-de-Grace - military hospital, calming patients

• Post Chlorpromazine - Reserpine (apathy)

  • LSD as model psychosis

  • advanced anti-anxiety, ketamine, adntidepressants (MAOI and SSRIs)

Cannabis Use as Treatment

Moreau - depression and mania, temporary replacing symptoms effects

Mental Illness 1900s Treatments

• Amphetamine - narcolepsy

• CO2 - psychoses and neuroses

• Antihistamines, insulin shock, psychosurgery, electroshock therapy

• Lithium - 40s Cade, approved 70s (toxic), mania, bipolar disorder

2005 National Comorbidity Survey Replication (NCS-R)

1 in 4 adults yearly have mental illnesses of which 1 in 4 had a serious disorder

18% anxiety, 10% mood, 9% impulse, 15% substance. ½ comorbid

Did not include homeless, institutionalized, or prisoners and did not assess autism or schizophrenia

2021 NIMH

rates have not changed, ~50% adolescents are mentally ill

Patterns Of Psychotherapeutic Use

• 2x higher in women than men

• increases with age (moreso with men)

• higher with living alone, higher education, and money

• issues: criminal, medical, misuse, stigma & misinformation

Famous Patients

John Nash, Elyn Saks - schizophrenia

The Rock - major depressive

Mariah Carey, Demi Lovato - bipolar

Antipsychotic Meds

Phenothiazines - neuroleptic (neural depressants) or major tranquilizers

Chlorpromazine - first

Psychosis

loss of contact with reality, disorganized thinking, bizarre behavior

Schizophrenia

thought disorders - language, affect, perception, behavior ~1% of pop higher in men

dopamine hypoth - increases in dopaminergic activity (from amphetamine induced psychosis model)

Schizoaffective Disorder

depressive and manic episodes, affective and psychotic behaviors

Paranoid Schizophrenia

delusions and/or auditory hallucinations

Antipsychotics

block postsynaptic DA receptors (D2)

treat agitation, mania, hallucinations, delusions, anger, accelerated/disorganized thinking processes, schizophrenia, old age psychosis, emotionally unstable personalities

First Gen Antipsychotics

• D2 dopamine antagonists, nigro-striatal pathway - plan and mod mvmt

• effect reticular activating (behav arousal), limbic (emotion), hypothalamus (metabolism, alertness)

• side effects: dyskinesia (move constantly), tardive dyskinesia (~1/3rd), akinesia (slow mvmt)

• block acetylcholine receptors - dry mouth & eyes, constipation, sexual dysfunction

Second Gen Antipsychotics

• symptom relief and reduced side effects, ATYPICAL, down motor effects

• reduce receptor blockage in nigro-striatal

• impact serotonin more than dopamine, clozapine, risperidone, non-phenothiazine

• side effects: weight gain, agranulocytosis (no WBC made in bone marrow), fatal myocarditis (inflame heart lining)

Aripiprazole (Abilify)

stabilizes dopamine, targets DA D2 receptor

antagonist in hyperdopaminergic state, agonist in hypodopaminergic state

Depression

• ~20% of US in lifetime, varied

• Cause - unknown, decreased catecholamines (serotonin especially), endogenous (genetic) and exogenous (envi)

Catecholamine Hypoth

from reserpine effect studies

amygdala and reticular formation with norepinephrine → depression

Serotonin Hypoth

Depression from reduced 5-HT and metabolism enzymes in cerebrospinal fluid and brainstem

AntiDepressants

• MAOI - monoamine oxidase inhibitors, prevent -HT breakdown

• Tricyclics - “il”, block 5-HT and noradrenaline transporters, norepinephrine

• Heterocyclics - SSRIs, more effective, “ine”, prozac, zoloft, selective serotonin reuptake inhibitors

• Atypical agents - effexor, cymbalta, SNRIs, serotonin and norepinephrine or wellbutrin/buproprion = DNRI, dopamine and norepinephrine

• work ~1/3rd of the time

MAOi Side Effects

temp, low BP, impaired sexual performance, dietary restrictions

MAOi break down tyramine → cheeses and chianti

Tricyclic Side Effects

drowsiness, anticholinergic (dry mouth, constipation, can’t pee, blurred vision, dizziness, decreased libido, weight gain, tachycardia), risk of fractures

Antidepressant Paradox

blackbox effect! sometimes just gives people the motivation to off themselves

immediate monoamine increase BUT 2-10 weeks for behavioral effects, increase neurogenesis, neurotrophic factors (BDNF)

Neurotrophic Hypoth

depression - neurogenesis deficit (new neuron formation)

due to neurotrophic (up neuron survival, neurogenesis, and creation of new and stronger connections) factors in antidepressants

Ketamine

depression treatment, excite and inhibit, very expensive infusion, up plasticity, inhibit GABA, binds to NDMA receptors

Manic Depressive Bipolar

• Mania - elevated mood/increased activity

• Includes increased talkativeness, racing thoughts/ideas, grandiosity, decreased sleep, excessive movement 

• Usually appears 20-30s, mood swings 

• Component of bipolar disorder

Mood Stabilizers

Decrease intensity/duration of manic/depressive episodes, or prevent from occuring

antidepressants + Lithium

Ca2+ blockers, cholinergic agents, adrenergic blockers, ECT, phototherapy, psychosurgery

Lithium

• primarily reduces mania, better for bipolar 1, hyperactivity in kids, premenstrual syndrome, mood stabilization

• Cade, prevent reoccurance, negligible effects in baseline individuals

• prophylactic - dec/prevent future episodes

• inhibit NMDA, DA, glutamate, excitory. Promote GABA, neuroprotection

• slow BBB passage, dependent on sodium intake (ionic balance)

Lithium Side Effects

benign (doesn’t kill), diarrhea, vomit, drowsy, confused, muscle weakness, tremor, fluid retention, weight gain, thirst, frequent urination

Small therapeutic window - drowsy, blurred vision, ataxia, confusion, seizures, coma, cardiovascular issues, death, heart/kidney effects

Bipolar Treatments

lithium, benzodiazepines, anti-epileptics/convulsants, anti-depressants, ECT

some evidence for atypical antipsychotics

Hormone

substance released from one type of cell and exerts its influence on another type of cell. Releasable into the blood stream and must travel some distance to the messenger site. Chemical messengers

Sex Hormones

Hypothalamus - gonadotropin-releasing factor (GnRF/GnRH)

Pituitary Gland - follicle stimulating hormone (FSH) and luteinizing hormone (LH)

F - estrogen and progesterone, M - testosterone/steroids

Female HPG Axis

activation of hypothalamus → +GnRH → activate anterior pituitary → +LH + FSH → ovaries → +estrogen +progesterone → ± hypothalamus and anterior pituitary

Menstruation Cycle

• ~28 days, hormone birth control change fluctuations

• follicular - peak estrogen

• ovulation - estrogen decreases

• luteal - progesterone

• period (menstrual) - estrogen and progesterone low

Oral Contraceptives

• 60s - excessive estrogen and progestin (synth progesterone)

• 90s - proper balance (30-35mg)

• combo of estrogen and progesterone to block FSH and LH release → no ovulation

• multiphasic combo - constant estrogen variable progesterone to reduce hormone, block FSH & LH & ovulation

Types of Contraceptives

Intrauterine device (IUD), vaginal ring, patches (Xulane, Ortho Evra), Injections (prodrug, Lunelle, Depo-Provera)

Oral Contraceptive examples

• mini pills - constant progestin, thickens cervix mucus, no implantation

• seasonale - estrogen & progesterone, taken for 3 months

  • Lybrel - estrogen and progester, low dose combo, daily

Contraceptive Side Effects

• Low dose: early preg, nausea, headaches/dizziness, breast discomfort, weight gain, depression, mood issues

• High dose: cardiovascular and cancer risks, diabetes, adverse effects on fetus

Morning After Pills

Plan B - high progestin dose, take ASAP, prevents ovulation, fertilization, or implantation, does not terminate existing preg, harmful to fetus, over the counter

Mifepristone (RU-486) - antagonist of progesterone, induces abortion, detaches trophoblastic tissue up to 49 days after fertilization, norm given with prostaglandin for contractions

Male HPG Axis

hypothalamus → +GnRH → anterior pituitary → + LH + FSH → testes → + testosterone → - hypothalamus and anterior pituitary

Steroid Uses

delayed puberty, burn victims, wasting victims, enhance athletic performance, increase muscle mass

Steroid History

• 60s - regular use in sports

• 70s - 50-90% of football players on

• 80s - olympics tested for

• 90s - anabolic steroid act, schedule III

• 2000s - BALCO, doping scandal, MLB and Lance Armstrong

Steroid Pharmacokinetics

• oral (intestine adsorb) or intramuscular inject, distributed in blood and stored in fat

• metabolized in liver → estrogen and androstenedione (testosterone precursor)

• excreted through kidney, detectable 4-14 days, up to a year

Steroid Side Effects

liver tumors or hepatitis (shared needles), cardiovascular increased LDL → high BP, heart attack, stroke

testicular shrinkage, reduced sperm count, breast growth OR loss of period, breast reduction

Steroid Psychological Effects

• delayed onset of action - days to weeks

• mood changes: euphoria, irritability & aggression, depression

• sleep problems, loss of appetite, reduced sexual desire

• some evidence of tolerance, known withdrawal

Hormone Mechanism of Action

Once in blood passes through cell wall and attaches to steroid receptor inside cells

Cascade to nucleus → genomic actions

Hormone Behavioral Effects

mood- can enhance, too little → depression, too much → anxiety/agitation

cognition - enhance working and spatial memory, impair other forms of learning

Neurohormones/Neurosteroids

modulate/alter function of receptors

PAM (positive allosteric modulators) - GABA, glutamate, acetylcholine, serotonin

Prenatal Drug Exposure

babies can get withdrawal when drug used in last trimester

cocaine, opiates, cannabis, nicotine, psychotherapeutics, anti-depressants, caffeine, benzodiazepines, alcohol

Caffeine and Pregnancy

congenital abnormalities in animals - reproductive failures, premature birth, low birth rate

advised to reduce/restrict use, no clearly outlined human effect

Nicotine and Pregnancy

• 7.2% did in 2016, mostly 20-24 year olds with high school education

• increased risk of stillbirth, low birth weight, premature labor, and miscarriage

• disturbed maternal-infant interaction, conduct disorder, aggression, down IQ, antisocial, ADHD, alcohol use and dependence

• 39x more likely to get a stoke or circulatory disease when combined with birth control

Marijuana and Pregnancy

• premature birth, childhood cancer

• teratogenic effects - reduced fetal growth, smaller head, decreased aorta diameter

• impaired executive function, impulsivity, attention and visual memory issues

• neuroadaptation in amygdala, dose dependent, reduced DA D2 receptor mRNA (moreso in M)

Cocaine and Pregnany

• crack babies / jittery baby syndrome,

• sympathomimetic effects: mother vasoconstriction, less O2 to placenta, detachment of placenta, pre-term labor, fetal death, low birth weight

• neonatal neurological syndrome - abnormal sleep, tremors, poor feeding, seizures

• overstimulated, difficulty with unstructured, ADHD, learning disabilities

• decreased BDNF embryonic, increased in teen (F>M), increased in adult (M)

Opioids and Pregnancy

• NOWS - neonatal opioid withdrawal syndrome, ~7%, increased

• irritability, anxiety, crying, abdominal distress, strabismus (cross-eye)

• delay in cognitive function, anxiety, aggression, disruptive/inattentive behavior, working mem impaired

• methadone - moreso in F, reduced neurogenesis

Patterns of Drinking During Pregnancy

1. drink in first month (unknown pregnancy)

2. drink throughout pregnancy (addiction)

3. only start drinking in third trimester (cumulative stress, doctors)

Fetal Alcohol Syndrome

• more common than ASD, brain damage, learning disorders, 1-7:1000, growth retardation, brain alteration

• Thin upper lip, smooth philtrum (btwn lips and nose)

• Small head, low nasal bridge, short nose, Short overall

• Neural Crest Cells - stem cells, facial, impaired 

• Learning and memory and motor deficits

• ADHD, anxiety, depression, social behavior problems

• Increased risk for drug and alcohol use/abuse

• Brain volume loss - down brain size (head size)

  • Cerebellum (motor, exec function)

  • Larger openings in brain - looks like larger ventricles 

• Impaired long term potentiation (LTP)

  • Synapse strengthening, memory, learning

• Impaired neurogenesis (including stem cells)

• Epigenetic changes - can be passed down between generations, hereditary

• Affected neuronal migration 

  • Disorganized brain architecture 

• White matter deficits (decreased speed of info transfer, less efficient brain)

Milder FAS Versions

Alcohol-related neurodevelopmental disorder - 1-5:100, functional damage

ARBD - alcohol related birth defects

ARND - alcohol related neurodevelopmental defects

ND-PAE - neuro-behavioral disorder associated with prenatal alcohol exposure

FAS Treatment

anxiolytics, antidepressants, stimulants (ADHD) - inc risk of drug use

choline supplementation (acetylcholine precursor, protein rich foods, helps)

behavioral therapy, social skills intervention, cognitive behavioral therapy

Drug Use Treatment

environment, supervision, abstainment, therapy, activity, remedy symptoms, environment, and underlying cause

Most Important Part of Drug Treatment

accepting that there is a problem

often from intervention, doctor, failure to fulfill major obligations

State of Change Model

pre-contemplation (denial, majority, addiction), contemplation (is there a problem/change), preparation (very long, repeated, previous attempts, verge of taking action), action (acting on goals, specific activities), maintenance (continual behavioral changes, consistency, abstinent)

a repeated cycle, relapses

Models of Substance Abuse Disorder

• Moral - individual personally responsible, choices

• American Disease - product of progressive irreversible disease, gradually gets worse

• Biological - genetic of physiological process and predispositions

• Social Learning - result of learning from environment, due to availability and environment

• Sociocultural - subcultures/societies shape use, normalized, affects large groups/society as a whole

• Biopsychosocial - complicated, many factors

Questions for Treatment Evaluation

• Does the treatment work better than no treatment?

• Does the treatment work better than a placebo?

• Does the treatment work better than standard treatments?

• Does the treatment work for the reasons it claims it does?

Behavioral SUD

quit on their own (spontaneous remission, 1st tried, very low success rate)

self help group (1:200 americans participate, led by people without certification)

Professional treatment (1 on 1, assessment, personalized treatment, doesn’t work for everyone)

Project MATCH (matching alcohol treatments to client heterogeneity)

12-step facilitation (self help group) vs. cog-behavioral coping skills vs. motivation and enhancement therapy

comparable outcome for all three treatments

Alcoholics Anonymous

• Dr. Bob and Bill W., 1935, maintain sobriety, american disease model

• 12 step program, religious influence (admit loss of control), group, accountaility

• hard to study - better than nothing, depends on the person

Self Help Group Examples

• Women for Sobriety - AA variant, progressive illness, psych and social concerns of women

• SMART - self management and recovery training, stopping motives, scientifically validated led by professional coordinator

• SOS - secular organizations for sobriety, save our selves, one day at a time, individuals responsible, peer support meetings

Abstinence

• goal of many self help groups, not questions, very very high relapse

• addiction is a disease, dependence, withdrawal, neuroadapt, DAT (dopamine transporter) can recover

• detoxification and controversial pharmacotherapy

Moderation

controversial, many reports of self-change, dependent on individuals beliefs. more likely to be successful than abstinence

Harm Reduction

• does not condone or criticize substance misuse, emphasis on reducing negative consequences

• education, designated driver, clean available needles, narcan

• resistance due to war on drugs

Alcohol Withdrawal

• acute withdrawal - motor abnormality, some mood, CNS and ANS hyperexcitability, 24-72 hrs

  • BZ’s and antiepileptics for seizes/tremors/hyperexcite

• early abstinence - reduced CNS, up anxiety, hyper-react, negative effect, sleep disturbed, 3 weeks-month

  • benzodiazepines for anxiety/irritability

• Protracted abstinence - cravings, anxiety, negative affect, depression, sleep disturbed, >3 months, neurochem changes

  • SSRIs, BZs (sleep), Naltrexone (opioid antag, craving)

Post-Alcohol Detox Treatment

Disulfiram (antabuse) / temposil - blocks aldehyde dehydrogenase, up aldehyde, aversion therapy, flush,r rapid heart rate, respiration, nausea, vomiting headache, worse hangovers

Dual Diagnosis Patients

substance use disorder AND psychiatric disorder, often self medication

Treatment settings

• Hospital - medical and psychological treatment, detox

• Intermediate - half-way houses, focus on counseling, psychotherapy, self-help

• Outpatient - individual (work with professional one on one) 

  • Group - sessions led by professional 

  • Organized around specific themes (preventing relapse)

Primary Prevention

• Avoid substance misuse before it has a chance to occur 

• “Just say no” advertising towards adolescents

Secondary Prevention

• Interventions when signs of substance use problems begin to appear 

• Legal system encourages alcohol education courses after DUI

Tertiary Prevention

Treatment interventions with people already dependent or misusing substances

Sociocultural Model of Prevention

social norms → drug use. Emphasis on culture’s normative structure, need to integrate drug use into socially meaningful activities, focus on providing for gradual socialization of the drug behavior.

moderation is key, advertisements, does not account for: substance caused pleasure, physical problems, change in culture does not always equal a behavioral change

Distribution of Consumption Model of Prevention

• alcohol focused

• Proportion of heavy alcohol users in a given population is positively correlated with the mean level of alcohol consumption in that population

• heavy alcohol consumption → increased probability of negative alcohol related consequences

• up price → down use, restrict availability (like nicotine)

Proscriptive Model of Prevention

no use of substance = no problem, moral sense, prohibition. only works in theory

Caffeine

overuse with college

~92%

alertness, awake, energy

hypertension or anxiety issues

Theobromine

moodswings, side effects

Impatient New Horizons

• determination of need, abuse assessment, referral, impatient if high risk (health complication, OD, death)

• inappropriate scenarios - severe mental illness, uncontrolled medical condition, unacceptable drug use

• 12 step, 14 days (usually). OASAS

Admission INH

assessment - nursing, counselor, medical-medications, labs, ekg

introductions - peer support, discussion

Treatment INH

different living conditions, exercise, no phones, a few electronics allowed, no drugs, counseling and group therapy

Discharge

completion, therapeutic, administrative, AWOL, AMA (against medical advice)

Suboxone

helps with heroin dependence, causes damage if used too early