Substance Related

Disorders
Brian Smart, M.D.
Harborview Medical Center

Objectives. At the end of this

talk you will be able to:

Identify the diagnostic criteria for substance-

related disorders
Describe the epidemiology of substancerelated disorders
Describe treatment options
Discern intoxication/withdrawal of different
substances
Apply the information above to clinical cases

Substance Classes

Alcohol
Caffeine
Cannabis
Hallucinogens

PCP
others

Inhalants

Opioids
Sedatives, hypnotics,
and anxiolytics
Stimulants
Tobacco
Other

Gambling

Substance-Related Disorders
2 Groups:

Substance Use Disorders

Previously split into abuse or dependence
Involves: impaired control, social impairment, risky
use, and pharmacological criteria

Substance-Induced Disorders

Substance Use Disorder

Using larger amounts or for longer time than

intended
Persistent desire or unsuccessful attempts to
cut down or control use
Great deal of time obtaining, using, or
recovering
Craving
Fail to fulfill major roles (work, school, home)
Persistent social or interpersonal problems
caused by substance use

Substance Use Disorder

Important social, occupational,

recreational activities given up or reduced

Use in physically hazardous situations
Use despite physical or psychological
problems caused by use
Tolerance
Withdrawal (not documented after repeated
use of PCP, inhalants, hallucinogens)

Severity
Severity

Depends on # of symptom criteria endorsed

Mild: 2-3 symptoms
Moderate: 4-5 symptoms
Severe: 6 or more symptoms

Specifiers
Specifiers

In early remission: no criteria for > 3 months

but < 12 months (except craving)
In sustained remission: no criteria for > 12
months (except craving)
In a controlled environment: access to
substance restricted (ex. Jail)

Substance-Induced

Intoxication
Withdrawal
Psychotic Disorder
Bipolar Disorder
Depressive Disorder

Anxiety Disorder
Sleep Disorder
Delirium
Neurocognitive
Sexual Dysfunction

Intoxication
Reversible substance-specific syndrome

due to recent ingestion of a substance

Behavioral/psychological changes due to
effects on CNS developing after ingestion:

ex. Disturbances of perception, wakefulness,

attention, thinking, judgement, psychomotor behavior
and interpersonal behavior

Not due to another medical condition or

mental disorder
Does not apply to tobacco

Clinical picture of intoxication

depends on:

Substance
Dose
Route of
Administration
Duration/chronicity
Individual degree of
tolerance

Time since last dose

Persons expectations
of substance effect
Contextual variables

Withdrawal
Substance-specific syndrome problematic

behavioral change due to stopping or

reducing prolonged use
Physiological & cognitive components
Significant distress in social, occupational
or other important areas of functioning
Not due to another medical condition or
mental disorder
No withdrawal: PCP; other hallucinogens;
inhalants

Substance-Induced Mental
Disorder
Potentially severe, usually temporary, but

sometimes persisting CNS syndromes

Context of substances of abuse,
medications, or toxins
Can be any of the 10 classes of
substances

Substance-Induced Mental
Disorder

Clinically significant presentation of a

mental disorder
Evidence (Hx, PE, labs)

During or within 1 month of use

Capable of producing mental disorder seen

Not an independent mental disorder

Preceded onset of use

Persists for substantial time after use (which
would not expect)

Neuroadaptation:
Refers to underlying CNS changes that

occur following repeated use such that

person develops tolerance and/or
withdrawal

Pharmacokinetic adaptation of metabolizing

system
Pharmacodynamic ability of CNS to function
despite high blood levels

Tolerance
Need to use an increased amount of a

substance in order to achieve the desired

effect
OR
Markedly diminished effect with continued
use of the same amount of the substance

Epidemiology: Prevalence

NIDA 04: 22.5M > 12yo substance-related d/o

15M Alcohol Dependence or Abuse
Start at earlier age (<15yo), more likely to
become addicted ex. alcohol: 18% vs. 4% (if
start at 18yo or older)
Rates of abuse vary by age: 1% (12yo) - 25%
(21yo) - 1% (65yo)
Men; American Indian; whites; unemployed;
large metro areas; parolees

Epidemiology (cont.)
ETOH - $300 billion/year
13 million require treatment for alcohol
5.5 million require treatment for drug use
2.5% population reported using Rx meds

nonmedically within past month

Epidemiology (cont.)
40% of hospital admission have alcohol
or drugs associated

25% of all hospital deaths

100,000 deaths/year

Intoxication is associated with 50% of all

MVAs, 50% of all DV cases and 50% of
all murders

ER Visits (NIDA 09)

1.2M: non-medical use of pharmaceuticals
660K: alcohol
425K: cocaine
380K: marijuana
210K: heroin
93K: stimulants

Etiology
Multiple interacting factors influence using

behavior and loss of decisional flexibility

Not all who become dependent experience
it same way or motivated by same factors
Different factors may be more or less
important at different stages (drug
availability, social acceptance, peer
pressure VS personality and biology)

Etiology
Brain Disease changes in structure and

neurochemistry transform voluntary drugusing compulsive

Changes proven but necessary/sufficient?
(drug-dependent person changes behavior
in response to positive reinforcers)
Psychodynamic: disturbed ego function
(inability to deal with reality)

Etiology
Self-medication

EtOH - panic; opioids -anger; amphetamine depression

Genetic (well-established with alcohol)

Conditioning: behavior maintained by its

consequences

Terminate aversive state (pain, anxiety, w/d)

Special status
Euphoria
Secondary reinforcers (ex. Paraphernalia)

Etiology
Receptors

Too little endogenous opioid activity (ie low endorphins) or too much
endogenous opioid antagonist activity = increased risk of
dependence.
Normal endogenous receptor but long-term use modulates, so need
exogenous substance to maintain homeostasis.

Neurotransmitters
o
o
o
o

Opioid
Catecholamines
GABA
Serotonin

Pathways

Learning and Physiological Basis for

Dependence
After using drugs or when stop leads to
a depleted state resulting in dysphoria
and/or cravings to use, reinforcing the
use of more drug.
Response of brain cells is to
downregulate receptors and/or decrease
production of neurotransmitters that are
in excess of normal levels.

Comorbidity
Up to 50% of addicts have comorbid

psychiatric disorder

Antisocial PD
Depression
Suicide

Typical Presentation and Course:

Present in acute intoxication, acute/chronic

withdrawal or substance induced mood, cognitive
disorder or medical complications
Abstinence depends on several factors: social,
environmental, internal factors (presence of other
comorbid psychiatric illnesses)
Remission and relapses are the rule (just like any
other chronic medical illness)
Frequency, intensity and duration of treatment
predicts outcome
70 % eventually able to abstain or decrease use
to not meet criteria

Options for where to treat

Hospitalization-Due to drug OD, risk of severe withdrawal, medical

comorbidities, requires restricted access to drugs,
psychiatric illness with suicidal ideation

Residential treatment unit

-No intensive medical/psychiatric monitoring needs
-Require a restricted environment
-Partial hospitalization

Outpatient Program -No risk of med/psych morbidity and

highly motivated patient

Treatment
Manage Intoxication & Withdrawal

Intoxication
Ranges: euphoria to life-threatening emergency

Detoxification

outpatient: "social detox program

inpatient: close medical care
preparation for ongoing treatment

Treatment

Behavioral Interventions (target internal and external reinforcers)

Motivation to change (MI)
Group Therapy
Individual Therapy
Contingency Management
Self-Help Recovery Groups (AA)
Therapeutic Communities
Aversion Therapies
Family Involvement/Therapy
Twelve-Step Facilitation
Relapse Prevention

(motivational --interviewing)

-EBxplore desire to stop drinking/using vs perceived benefits of ongoing use

-Gentle confrontation with education (risks to health) / therapeutic alliance
-Involve family and friends for support
-Education about substance dependence
and need for rehabilitation plan

Treatment
Pharmacologic Intervention
Treat Co-Occurring Psychiatric Disorders

50% will have another psychiatric disorder

Treat Associated Medical Conditions

cardiovascular, cancer, endocrine, hepatic,

hematologic, infectious, neurologic,
nutritional, GI, pulmonary, renal,
musculoskeletal

Alcohol

ALCOHOL- CNS depressant

Intoxication

Blood Alcohol Level 0.08g/dl

Progress from mood
lability, impaired
judgment, and poor
coordination to
increasing level of
neurologic impairment
(severe dysarthria,
amnesia, ataxia,
obtundation)

Can be fatal (loss of

airway protective
reflexes, pulmonary
aspiration, profound CNS
depression)

Alcohol Withdrawal

Early

Seizures

anxiety, irritability, tremor, HA, insomnia, nausea,

tachycardia, HTN, hyperthermia, hyperactive reflexes
generally seen 24-48 hours
most often Grand mal

Withdrawal Delirium (DTs)

generally between 48-72 hours

altered mental status, hallucinations, marked
autonomic instability
life-threatening

Alcohol Withdrawal (cont.)

CIWA (Clinical Institute Withdrawal Assessment

for Alcohol)
Assigns numerical values to orientation, N/V,
tremor, sweating, anxiety, agitation, tactile/
auditory/ visual disturbances and HA. VS
checked but not recorded. Total score of > 10
indicates more severe withdrawal
Based on severity of withdrawal or history of
previous withdrawal seizures or DTs, med
therapy can be scheduled or symptom-triggered

Alcohol Withdrawal (cont.)

Benzodiazepines

GABA agonist - cross-tolerant with alcohol

reduce risk of SZ; provide comfort/sedation

Anticonvulsants

reduce risk of SZ and may reduce kindling

helpful for protracted withdrawal
Carbamazepine or Valproic acid

Thiamine supplementation

Risk thiamine deficiency (Wernicke/Korsakoff)

Alcohol treatment
Outpatient CD treatment:

support, education, skills training, psychiatric

and psychological treatment, AA

Medications:

Disulfiram
Naltrexone
Acamprosate

Medications - ETOH Use Disorder

Disulfiram (antabuse) 250mg-500mg po daily

Inhibits aldehyde dehydrogenase and dopamine beta hydroxylase

Aversive reaction when alcohol ingested- vasodilatation, flushing,
N/V, hypotenstion/ HTN, coma / death
Hepatotoxicity - check LFT's and h/o hep C
Neurologic with polyneuropathy / paresthesias that slowly
increase over time and increased risk with higher doses
Psychiatric side effects - psychosis, depression, confusion,
anxiety
Dermatologic rashes and itching
Watch out for disguised forms of alcohol - cologne, sauces, mouth
wash, OTC cough meds, alcohol based hand sanitizers, etc

Medications - ETOH Use Disorder

Naltrexone 50mg po daily

Opioid antagonist thought to block mu receptors

reducing intoxication euphoria and cravings
Hepatotoxicity at high doses so check LFT's

Acamprosate(Campral) 666mg po tid

Unknown MOA but thought to stabilize neuron

excitation and inhibition - may interact with GABA and
Glutamate receptor - cleared renally (check kidney
function)

Benzodiazepine( BZD)/
Barbiturates

Benzodiazepine( BZD)/
Barbiturates
Intoxication

similar to alcohol but less cognitive/motor

impairment
variable rate of absorption (lipophilia) and
onset of action and duration in CNS
the more lipophilic and shorter the duration of
action, the more "addicting" they can be
all can by addicting

Benzodiazepine
Withdrawal

Similar to alcohol with anxiety, irritability, insomnia, fatigue, HA,

tremor, sweating, poor concentration - time frame depends on
half life
Common detox mistake is tapering too fast; symptoms worse at
end of taper
Convert short elimination BZD to longer elimination half life drug
and then slowly taper
Outpatient taper- decrease dose every 1-2 weeks and not more
than 5 mg Diazepam dose equivalent
5 diazepam = 0.5 alprazolam = 25 chlordiazepoxide = 0.25 clonazepam = 1
lorazepam

May consider carbamazepine or valproic acid especially if doing

rapid taper

Benzodiazapines

Alprazolam (Xanax) t 1/2 6-20 hrs

*Oxazepam (Serax) t 1/2 8-12 hrs
*Temazepam (Restoril) t 1/2 8-20 hrs
Clonazepam (Klonopin) t 1/2 18-50 hrs
*Lorazepam (Ativan) t1/2 10-20 hrs
Chlordiazepoxide (Librium) t1/2 30-100 hrs (less
lipophilic)
Diazepam (Valium) t 30-100 hrs (more lipophilic)

*Oxazepam, Temazepam & Lorazepam- metabolized

through only glucuronidation in liver and not affected by
age/ hepatic insufficiency.

Opiods

OPIOIDS
Bind to the mu receptors in the CNS to modulate pain

Intoxication- pinpoint pupils, sedation, constipation,

bradycardia, hypotension and decreased respiratory rate

Withdrawal- not life threatening unless severe medical

illness but extremely uncomfortable. s/s dilated pupils
lacrimation, goosebumps, n/v, diarrhea, myalgias,
arthralgias, dysphoria or agitation

Rx- symptomatically with antiemetic, antacid,

antidiarrheal, muscle relaxant (methocarbamol),
NSAIDS, clonidine and maybe BZD

Neuroadaptation: increased DA and decreased NE

Treatment - Opiate Use Disorder

CD treatment

support, education, skills building, psychiatric and psychological

treatment, NA

Medications

Methadone (opioid substitution)

Naltrexone
Buprenorphine (opioid substitution)

Treatment - Opiate Use Disorder

Naltrexone

Methadone

Opioid blocker, mu antagonist

50mg po daily
Mu agonist
Start at 20-40mg and titrate up until not craving or using illicit opioids
Average dose 80-100mg daily
Needs to be enrolled in a certified opiate substitution program

Buprenorphine

Partial mu partial agonist with a ceiling effect

Any physician can Rx after taking certified ASAM course
Helpful for highly motivated people who do not need high doses

Stimulants

STIMULANTS

Intoxication (acute)

psychological and physical signs

euphoria, enhanced vigor, gregariousness,
hyperactivity, restlessness, interpersonal sensitivity,
anxiety, tension, anger, impaired judgment, paranoia
tachycardia, papillary dilation, HTN, N/V, diaphoresis,
chills, weight loss, chest pain, cardiac arrhythmias,
confusion, seizures, coma

STIMULANTS
(cont.)
Chronic intoxication

affective blunting, fatigue, sadness, social

withdrawal, hypotension, bradycardia, muscle
weakness

Withdrawal

not severe but have exhaustion with sleep

(crash)
treat with rest and support

Cocaine

Route: nasal, IV or smoked

Has vasoconstrictive effects that may outlast use
and increase risk for CVA and MI (obtain EKG)
Can get rhabdomyolsis with compartment
syndrome from hypermetabolic state
Can see psychosis associated with intoxication
that resolves
Neuroadaptation: cocaine mainly prevents
reuptake of DA

Treatment - Stimulant Use

Disorder (cocaine)
CD treatment including support,

education, skills, CA
Pharmacotherapy

No medications FDA-approved for treatment

If medication used, also need a psychosocial
treatment component

Amphetamines

Similar intoxication syndrome to cocaine but

usually longer
Route - oral, IV, nasally, smoked
No vasoconstrictive effect
Chronic use results in neurotoxicity possibly
from glutamate and axonal degeneration
Can see permanent amphetamine psychosis
with continued use
Treatment similar as for cocaine but no known
substances to reduce cravings
Neuroadaptation

inhibit reuptake of DA, NE, SE - greatest effect on DA

Treatment Stimulant Use

Disorder (amphetamine)
CD treatment: including support,

education, skills, CA
No specific medications have been found
helpful in treatment although some early
promising research using atypical
antipsychotics (methamphetamine)

Tobacco

Tobacco

Most important preventable cause of death /

disease in USA
25%- current smokers, 25% ex smokers
20% of all US deaths
45% of smokers die of tobacco induced disorder
Second hand smoke causes death / morbidity
Psychiatric pts at risk for Nicotine dependence75%-90 % of Schizophrenia pts smoke

Tobacco (cont.)

Drug Interactions

No intoxication diagnosis

nicotine acetylcholine receptors on DA neurons in

ventral tegmental area release DA in nucleus
accumbens

Tolerance

initial use associated with dizziness, HA, nausea

Neuroadaptation

induces CYP1A2 - watch for interactions when start or

stop (ex. Olanzapine)

rapid

Withdrawal

dysphoria, irritability, anxiety, decreased concentration,

insomnia, increased appetite

Treatment Tobacco Use

Disorder
Cognitive Behavioral Therapy
Agonist substitution therapy

nicotine gum or lozenge, transdermal patch,

nasal spray

Medication

bupropion (Zyban) 150mg po bid,

varenicline (Chantix) 1mg po bid

Hallucinogens

HALLUCINOGENS

Naturally occurring - Peyote cactus (mescaline);

magic mushroom(Psilocybin) - oral
Synthetic agents LSD (lysergic acid
diethyamide) - oral
DMT (dimethyltryptamine) - smoked, snuffed, IV
STP (2,5-dimethoxy-4-methylamphetamine)
oral
MDMA (3,4-methyl-enedioxymethamphetamine)
ecstasy oral

MDMA (XTC or Ecstacy)

Designer club drug

Enhanced empathy, personal insight, euphoria,
increased energy
3-6 hour duration
Intoxication- illusions, hyperacusis, sensitivity
of touch, taste/ smell altered, "oneness with the
world", tearfulness, euphoria, panic, paranoia,
impairment judgment
Tolerance develops quickly and unpleasant side
effects with continued use (teeth grinding) so
dependence less likely

MDMA (XTC or Ecstacy)cont.

Neuroadaptation- affects serotonin (5HT), DA,

NE but predominantly 5HT2 receptor agonists

Psychosis

Hallucinations generally mild

Paranoid psychosis associated with chronic use
Serotonin neural injury associated with panic, anxiety,
depression, flashbacks, psychosis, cognitive changes.

Withdrawal unclear syndrome (maybe similar

to mild stimulants-sleepiness
and depression due to 5HT depletion)

Cannabis

CANNABIS

Most commonly used illicit drug in America

THC levels reach peak 10-30 min, lipid soluble; long half life of 50
hours
IntoxicationAppetite and thirst increase
Colors/ sounds/ tastes are clearer
Increased confidence and euphoria
Relaxation
Increased libido
Transient depression, anxiety, paranoia
Tachycardia, dry mouth, conjunctival injection
Slowed reaction time/ motor speed
Impaired cognition
Psychosis

CANNABIS (cont.)

Neuroadaptation

CB1, CB2 cannabinoid receptors in brain/ body

Coupled with G proteins and adenylate cyclase to CA
channel inhibiting calcium influx
Neuromodulator effect; decrease uptake of GABA and
DA

Withdrawal - insomnia, irritability, anxiety, poor

appetite, depression, physical discomfort

CANNABIS (cont.)
Treatment

-Detox and rehab

-Behavioral model
-No pharmacological treatment but
may
treat other psychiatric symptoms

PCP

PHENACYCLIDINE ( PCP)
"Angel Dust"

Dissociative anesthetic
Similar to Ketamine used in anesthesia
Intoxication: severe dissociative reactions paranoid
delusions, hallucinations, can become very agitated/
violent with decreased awareness of pain.
Cerebellar symptoms - ataxia, dysarthria, nystagmus
(vertical and horizontal)
With severe OD - mute, catatonic, muscle rigidity, HTN,
hyperthermia, rhabdomyolsis, seizures, coma and death

PCP cont.

Treatment

Neuroadaptation

antipsychotic drugs or BZD if required

Low stimulation environment
acidify urine if severe toxicity/coma

opiate receptor effects

allosteric modulator of glutamate NMDA receptor

No tolerance or withdrawal

Websites
SAMHSA www.samhsa.gov

Substance Abuse and Mental Health Services Administration

NIDA

www.drugabuse.gov

National Institute on Drug Abuse

AAAP www.aaap.org

American Academy of Addiction Psychiatry

ASAM

www.asam.org

American Society of Addiction Medicine