Transcript Extra slides: substance abuse

Substance-Related Disorders
Brian Ladds, M.D.
Outline
• A neuro-biological perspective
• Definitions
• Specific substances
Substance Abuse
Why do people use psychoactive substances?
Why do they persist?
Pleasure & Reward Circuit
• Stimulation of this pathway leads to
feelings of pleasure
– Dopamine produces these feelings
Meso-Accumbens Pathway
• From mid-brain to limbic system and back:
• Meso-Accumbens pathway
– From the VTA to the Nucleus Accumbens
• From Nucleus Accumbens back to VTA
Inputs to the
Pleasure/Reward Circuit
• Inputs to VTA and/or Nucleus Accumbens:
– from other parts of brain
– using a variety of neurotransmitters
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Glutamate
GABA
Opioid peptide neurotransmitter
Other inputs
Hijacking the
“Pleasure & Reward Circuit”
• This circuit is hijacked by all substances of
abuse
– All are extremely potent at stimulating this
circuit
• Pleasure from ordinary activities come to
have diminished power in this circuit
Actions of Substances of Abuse
• All substances of abuse increase dopamine
effects in this circuit
• They do so by acting at:
– the VTA, and/or:
– the Nucleus Accumbens
• They act to:
– increase dopamine release, and/or
– block re-uptake
Neuro-adaptations
• Upon repeated use, the brain tries to
counter-act the effects of these substances
• Such neuro-adaptations involve changes in
structure and function
Neuro-adaptations
• Neuro-adaptations, esp. in the brain stem,
may lead to:
• Diminished effects of a given substance
(‘tolerance’)
• Effects upon its discontinuation
(‘withdrawal’)
Relapse
• What triggers a return to use a drug after
prolonged abstinence?
Definitions
• Additional definitions and concepts
• DSM-IV classification and criteria
Behaviors
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Tolerance
Withdrawal
Sensitization
Craving
Dependence
Abuse
Tolerance
• Tolerance develops at different rates for
different actions of a drug
– Euphoria caused by cocaine diminishes faster
than its cardiostimulant effects
Withdrawal
• The signs and symptoms that occur when a
drug is stopped or dose lowered
• Both physiological and psychological
processes contribute
Withdrawal
• Can cause secondary problems
– Depression and anxiety from cocaine
– Excito-toxic brain damage from alcohol
Sensitization
• An increase in an effect of a drug upon its
repeated administration
• Tends to be seen with the stimulating
actions of a drug
Sensitization: Examples
• Cocaine use
– Psychotimimetic effects of cocaine
• Alcohol withdrawal
– Excitatory changes in withdrawal
• alcohol withdrawal progressively worsens
DSM-IV Definitions
• Substance-Related Disorders
– Substance Use Disorders
• Substance Dependence
• Substance Abuse
– Substance-Induced Disorders
Substance-Induced Disorders
• Intoxication
• Withdrawal
• Other
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Delirium
Persisting Dementia
Persisting Amnestic Disorder
Psychotic Disorder
Mood Disorder
Anxiety Disorder
Sexual Dysfunction
Sleep Disorder
Criteria for Substance
Dependence
• A maladaptive pattern of substance use,
• leading to clinically significant impairment
or distress,
• as manifested by at least 3 of the following
7 criteria,
• occurring at any time in the same 12-month
period
Criteria for Substance
Dependence
1. Tolerance
2. Withdrawal
3. The substance is often taken in larger
amounts or over longer periods than was
intended
Criteria for Substance
Dependence
4. There is a persistent desire or unsuccessful
efforts to cut down or control substance use
5. A great deal of time is spent in activities
necessary to obtain the substance, use the
substance, or recover from its effects
Criteria for Substance
Dependence
6. Important social, occupational or
recreational activities are given up or
reduced because of substance use
7. The substance use is continued despite
knowledge of having a persistent or
recurrent physical or psychological problem
that is likely to have been caused or
exacerbated by the substance
Dependence: Sub-types
• Specify subtype:
• ‘With physiological dependence’
– Evidence of tolerance or withdrawal
• ‘Without physiological dependence’
– No evidence of tolerance or withdrawal
Criteria for Substance Abuse
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A maladaptive pattern of substance use,
leading to clinically significant
impairment or distress,
as manifested by at least 1 of the
following criteria,
occurring within a 12-month period
Criteria for Substance Abuse
1. Recurrent substance use resulting in failure
to fulfill major role obligations at work,
school, or home
2. Recurrent substance use in situations in
which it is physically hazardous
3. Recurrent substance-related legal problems
Criteria for Substance Abuse
4. Continued substance use despite having
persistent or recurrent social or
interpersonal problems caused or
exacerbated by the effects of the substance
B. The symptoms have never met the criteria
for Substance Dependence for this class of
substance.
Specific Substances
Prevalence
Pharmacokinetic Factors
• Important in determining the misuse
potential of a drug
• Oral vs. nasal vs. smoked vs. IV
– Cocoa leaves vs. powder cocaine vs. lipophilic
free-base cocaine (“crack”)
Alcohol-related disorders
• Alcohol abuse is several times more
common in men
• Significant increased risk for accidents,
suicide, and violence
Prevalence
• Lifetime prevalence of alcohol abuse or
dependence is approximately 8%
Etiology
• Genetics
– 60% monozygotic twins
– 25% of children of alcoholic parent
– risk increases with:
• number of alcoholic relatives,
• severity of their illness, and
• closeness of genetic relationship
Etiology
• Psychological Theories
• Socio-cultural Theories
12 grams Ethyl Alcohol
• 12 oz beer
• 4 oz glass wine
• 1.5 oz liquor (80 proof)
Blood Alcohol Level (BAL)
• 0.08 Legal intoxication
• 0.40 Lethal dose, 50% of population (LD50)
Mechanism of Action of Alcohol
• Alters the fluidity and organization of cell
membranes throughout the brain
– Alters the function of proteins that transverse
cell membranes, such as neurotransmitter
receptors and ion channels
• Binds to GABA-A receptor
• Acts like a glutamate (NMDA) receptor
antagonist
Alcohol effects on the CNS
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Blackout
Peripheral Neuropathy
Cerebellar Degeneration
Sleep impairment
Sexual dysfunction
Mood, Anxiety & Psychotic Disorders
Alcohol effects on the CNS
Wernicke-Korsakoff’s syndrome
• Severe deficiency of thiamine
1. Ataxia
2. Amnesia
3. 6th Nerve palsy (opthalmoplegia)
Alcohol Effects on the Body
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Vitamin malabsorption
Severe inflammation: esophagus & stomach
Pancreatitis
Bone marrow suppression
Cancer: esophagus, stomach, head, neck
Hypertension and alcoholic cardiomyopathy
Fatty liver, alcoholic hepatitis, cirrhosis
Alcohol Intoxication
• Clinically significant maladaptive
behavioral or psychological changes
• One (or more) of the following signs:
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slurred speech
incoordination
unsteady gait
nystagmus
impairment in attention or memory
stupor or coma
Alcohol Withdrawal
• At least 2 of these, within a few days of
cessation of (or reduction in) use:
– Autonomic hyperactivity (Early)
– Hand tremor (Early)
– Insomnia (Early)
– Nausea and vomiting (Early)
– Psychomotor agitation (Early)
• (Early) = within 6-8 hours of last drink
Alcohol Withdrawal, cont.’
– Hallucinations
• transient visual, tactile, or auditory
– Grand Mal Seizures
• (Later) = 24-72 hours
• Delirium Tremens
• Treatment
Opioids
• Opium: juice of opium poppy, Papaver
Somniferum
• Natural (or synthesized from naturally
occurring opiates): morphine, heroin (diacetylmorphine), codeine (3-methoxy-morphine),
hydromorphone (Dilaudid), oxycodone
• Synthetic: meperidine (Demerol), methadone
(Dolophine), pentazocine (Talwin), proproxyphene
(Darvon)
Opioids
• Endogenous opioids:
– enkephalins, endorphins
• Mixed agonist/antagonists:
– buprenorphine (Buprenex)
• Antagonists:
– naloxone (Narcan), naltrexone (ReVia)
Opioids
• Prevalence
– Less than 1% with current dependence or
abuse
Opioids:
Mechanism of Action
• Binding to Mu opioid receptors influences
mood & reinforcing effects
• Stimulate the release of dopamine in the
Nucleus Accumbens
‘Positive’ Effects of Opioids
• Tranquility
• Euphoria
• Decreased apprehension
Opioids:
Some Possible Symptoms
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Apathy and dysphoria
Analgesia
Decrease respiration
Decrease cough reflex
Constipation
Effects of IV opioids
on the body
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Thrombosed veins
Abcesses
Hepatitis
Endocarditis
HIV and AIDS
Opioid Intoxication
• Constriction of pupils (except with anoxia from severe
overdose) and one (or more):
1. Drowsiness or coma
2. Slurred speech
3. Impairment in attention or memory
Clinical Presentation of
Opioid Overdose
• Pinpoint pupils
• Decreased respiration; Pulmonary edema
– Blue lips, pale skin
• Cardiac arrhythmias
• Seizures
Opioid Withdrawal
3 (or more):
1. Dysphoric mood
2. Nausea or vomiting
3. Muscle aches
4. Lacrimation or rhinorrhea
5. Pupillary dilation, piloerection or sweating
6. Diarrhea
7. Yawning
8. Fever
9. Insomnia
Opioids
• Treatment
Cocaine
• Alkaloid of Erythroxylon coca
• One of the most powerful and reinforcing
CNS stimulants
• Tends to be used in heavy binges vs. daily
Cocaine
• Prevalence
– Less than 1% lifetime dependence
– Over a million people in U.S.
Mechanism of Action
Cocaine & Amphetamines
• Cocaine binds to the dopamine transporter
re-uptake protein pump, blocking dopamine
re-uptake
• Amphetamines can also block this
transporter, but they principally stimulate
the release of dopamine
‘Positive’ Effects of Cocaine
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Increased self-confidence
Sense of alertness
Sense of well being
Increased energy
Heightened sense of pleasure
Signs of Cocaine Intoxication
• 2 or more of these:
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Tachycardia or bradycardia
Increased or decreased blood pressure
Pupillary dilation
Perspiration or chills
Nausea or vomiting
Weight loss
Psychomotor agitation or retardation
Muscles weakness, respiratory depression, chest pain, or
arrhythmias
– Confusion, seizures, dyskinesia, dystonia, coma
Cocaine: effects on the CNS
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Headache
Anxiety
Psychosis
Sexual dysfunction
Cocaine: effects on the body
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Rhabdomyolysis
Hyperthermia
Myocardial ischemia
Cerebral hemorrhage
Sudden death
Cocaine Withdrawal
• Dysphoric mood (and 2 or more):
1. Fatigue
2. Vivid, unpleasant dreams
3. Insomnia or hypersomnia
4. Increased appetite
5. Psychomotor agitation or retardation
• Treatment
Other Substances
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Amphetamines
Hallucinogens
PCP
Cannabis
Inhalants
Nicotine
Amphetamines
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Dextroamphetamine (Dexedrine)
Methylphenidate
(Ritalin)
Dextroamphetamine & Amphetamine (Adderall)
Methamphetamine (Desoxyn)
Designer amphetamines
– 3,4 methylene dioxymethamphetamine (“Ecstacy”)
Hallucinogens
• Natural
– psilocybin (‘mushrooms’)
– mescaline (‘peyote’)
• Synthetic
– Lysergic acid diethylamide (LSD)
Hallucinogens
• Psychosis (‘bad trip’)
• Persisting perception disorder (‘flashbacks’)
• Sympathomimetic effects
Phencyclidine
• 1-(1-phenylcyclohexy-1) piperidine (PCP)
• PCP and Ketamine:
– NMDA antagonists
– Dopamine activators
• Intoxication
Cannabis
• Hemp plant Cannabis Sativa
• 9-tetra-hydro-cannabinol (THC)
• Most commonly used illicit substance
Cannabis
• Receptors widely dispersed
• Immediate effects
• Long term effects
Inhalants
• Solvents, glue, adhesives, aerosols, and paint
thinners, fuels
• CNS depressants
• Dementia
– Neurotoxicity
• Medical Effects