Substance Use Disorder
Using large 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
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
Which substances have no withdrawal even after repeated use?
PCP, inhalants, hallucinogens
Severity of disorder
Depends on # of symptom criteria endorsed
Mild: 2-3 symptoms
Moderate: 4-5 symptoms
Severe: 6 or more symptoms
Specifiers of substance use disorder?
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 (e.g. jail)
Intoxication
REVERSIBLE substance-specific syndrome due to recent ingestion
Behavioral/psychological changes due to effects on CNS after ingestion (e.g. 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
Withdrawal
Substance-specific syndrome 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
Substance-Induced Mental Disorder
Can be due to any of the 10 classes of substances
During or within 1 month of use
Not an independent mental disorder (can’t have preceded onset of use or persist for substantial time after use)
10 classes of substances?
Alcohol Caffeine Cannabis Hallucinogens (e.g. PCP) Inhalants Opioids Sedatives, hypnotics, anxiolytics Stimulants Tobacco Other (gambling??)
Neuroadaptation
Underlying CNS changes that occurs after repeated use such that person develops tolerance and/or withdrawal
Pharmacokinetic neuroadaptation
Adaptation of metabolizing system
Pharmacodynamic neuroadaptation
Ability of CNS to function despite high blood levels
Tolerance
Need to use an increased amount of substance in order to achieve desired effect
OR
Markedly diminished effect with continued use of same amount of substance
Rates of substance abuse by age
1% of 12 y/o
25 % of 21 y/o
1% of 65 y/o
Does starting substance use at earlier age matter?
Starting at earlier age (<15 y/o), more likely to become addicted
e.g. alcohol addiction is 18% if started use before 15 y/o vs. 4% if started at 18 y/o or older
Demographics associated with substance abuse?
Men American Indians and whites Unemployed Large metro areas Parolees
Alcohol epidemiology
$300 billion/year spent on alcohol
13 million require tx for alcohol
(vs. 5.5 million require tx for drug use)
What percent of population reported using Rx meds non-medically within past month?
2.5%
What percent of hospital admissions have alcohol or drugs associated?
40%
What percent of hospital deaths have alcohol or drugs associated?
25% = 100,000 deaths per year
Intoxication is associated with what % of MVAs, DV cases, murders?
50% of all MVAs
50% of all DV cases
50% of all murders
ER visits due to substances?
1.2 million = non-medical use of pharmaceuticals!! 660 K = alcohol 425 K = cocaine 380 K = marijuana 210 K = heroin 93 K = stimulants
Is substance abuse a “brain disease”?
Changes in structure and neurochemistry transform voluntary drug-using to compulsive using
Changes are not necessary/sufficient (drug-dependent person changes behavior in response to positive reinforcers)
Psychodynamic etiology?
Disturbed ego function (inability to deal with reality)
Self-medication etiology?
Alcohol - panic
Opioids - anger
Amphetamines - depression
Genetic etiology?
Well-established with alcohol
Conditioning etiology?
Behavior is maintained by its consequences:
- Terminate aversive state (pain, anxiety, withdrawal)
- Special status
- Euphoria
- Secondary reinforcers (e.g. paraphernalia)
What happens to cellular receptors with substance abuse?
Too little endogenous opioid activity (i.e. low endorphins) OR too much endogenous opioid antagonist activity = increased risk of dependence
It’s a normal endogenous receptor BUT long-term use modulates it = need exogenous substance to maintain homeostasis
Learning and physiological basis for dependence?
Using drugs or stopping use leads to depleted state resulting in dysphoria and/or cravings, reinforcing the use of more drug
Brain cells respond by downregulating receptors and/or decreasing production of neurotransmitters that are in excess of normal levels
Comorbidity of substance use disorders with other psych disorders?
Up to 50% of addicts have comorbid psychiatric disorder (antisocial PD, depression, suicide)
What percent of patients are eventually able to abstain or decrease use to not meet criteria after treatment?
70%
When to treat in hospital?
Drug OD, risk of severe withdrawal, medical comorbidities, requires restricted access to drugs, psychiatric illness with SI
When to treat in residential treatment unit?
No intensive medical/psychiatric monitoring needs
Require restricted environment
Partial hospitalization
When to treat in outpatient program?
No risk of med/psych morbidity
Highly motivated patient
Behavioral interventions
Must target internal and external reinforcers
Motivation to change (MI), group therapy, individual therapy, contingency management, self-help recovery groups (AA), therapeutic communities, aversion therapy, family involvement/therapy, twelve-step facilitation, relapse prevention
Alcohol intoxication
Blood alcohol level 0.08 g/dL
Progresses from mood lability, impaired judgment, and poor coordination to increased level of neurologic impairment (severe dysarthria, amnesia, ataxia, obtundation)
How can alcohol intoxication be fatal?
Loss of airway protective reflexes
Pulmonary aspiration
Profound CNS depression
Symptoms of early alcohol withdrawal?
Anxiety, irritability, tremor
Headache, insomnia, nausea
Tachycardia, HTN, hyperthermia
Hyperactive reflexes
Symptoms of late alcohol withdrawal?
Seizures (24-48 hours), usually grand mal Delirium tremens (48-72 hours) with altered mental status, hallucinations, marked autonomic instability, LIFE THREATENING
What is CIWA?
Clinical Institute Withdrawal Assessment for Alcohol
- Score orientation, n/v, tremor, sweating, anxiety, agitation, tactile/auditory/visual disturbances, headache
- Total score >10 indicates severe withdrawal
Inpatient treatment for alcohol withdrawal?
- Benzodiazepines - cross-tolerant with alcohol, reduce risk of seizures, provide comfort/sedation
- Anticonvulsants (carbamazepine, valproate) - reduce risk of seizures and maybe kindling, good for protracted withdrawal
- Thiamine supplementation - risk of thiamine deficiency (Wernicke/Korsakoff)
Medications used for alcohol use disorder
Disulfiram, Naltrexone, Acamprosate
Disulfiram (Antabuse)
250-500 mg PO daily
Inhibits aldehyde dehydrogenase and dopamine beta hydroxylase
Aversive reaction when alcohol ingested (vasodilatation, flushing, n/v, hypotension/HTN, coma/death)
Watch out for disguised forms of alcohol (cologne, sauces, mouth wash, OTC cough meds)
Disulfiram side effects?
- Hepatotoxicity - check LFTs and h/o hep C
- Neurologic - polyneuropathy/paresthesias that increase over time, increased risk with higher doses
- Psychiatric - psychosis, depression, confusion, anxiety
- Dermatologic - rashes, itching
Naltrexone
50 mg PO daily Opioid antagonist (blocks mu receptors?) Reduces intoxication euphoria and cravings Hepatotoxicity at high doses - check LFTs
Acamprosate (Campral)
666 mg PO TID
Unknown MOA
Stabilizes neuron excitation and inhibition?
Interacts with GABA and glutamate receptor?
Cleared renally - check kidney fx
Benzodiazepine/barbiturate intoxication?
Similar to alcohol but less cognitive/motor impairment
Variable rate of absorption (lipophilic), onset of action, and duration in CNS
* More lipophilic and shorter duration of action = more “addicting”
Benzodiazepine withdrawal symptoms?
Similar to alcohol but time frame depends on half-life
Anxiety, irritability, tremor, sweating, insomnia, fatigue, headache, poor concentration
Benzodiazepine withdrawal treatment?
Convert short half-life BZD to long half-life BZD, then slowly taper (common mistake is tapering too fast, symptoms worse at end of taper)
Outpatient taper: decrease dose every 1-2 weeks and not more than 5 mg diazepam dose equivalent
Consider carbamazepine or valproate if doing rapid taper
5 mg diazepam is equal to what?
0.5 mg alprazolam = 25 mg chlordiazepoxide = 0.25 mg clonazepam = 1 mg lorazepam
Which BZDs are not affected by age or hepatic insufficiency?
Oxazepam, temazepam, lorazepam
Metabolized through only glucuronidation in liver
Which BZD is least lipophilic?
Chlordiazepoxide
Half-life 30-100 hrs
Which BZD is most lipophilic (more addicting)?
Diazepam
Half-life 30-100 hrs
Opioid MOA
Bind mu receptors in CNS to modulate pain
Opioid intoxication
Pinpoint pupils, sedation, constipation, hypotension, bradycardia, decreased RR
Opioid withdrawal
Not life threatening unless severe medical illness
Extremely uncomfortable
Dilated pupils, lacrimation, goosebumps, n/v, diarrhea, myalgias, arthralgias, dysphoria or agitation
Opioid withdrawal treatment
Symptomatically
Antiemetic, antacid, antidiarrheal
Muscle relaxant (methocarbamol)
NSAIDs, clonidine, maybe BZD
Opioid neuroadaptation
Increased dopamine
Decreased NE
Medications used for opiate use disorder
Methadone, Naltrexone, Buprenorphine
Naltrexone
Opioid blocker, mu antagonist
50 mg PO daily
Methadone
Mu agonist
Start at 20-40 mg, titrate up to 80-100 mg daily
Needs to be enrolled in a certified opiate substitution program
Buprenorphine
Partial mu agonist with ceiling effect
Any physician can Rx after taking certified ASAM course
Helpful for highly motivated people who do not need high doses
Acute stimulant intoxication
Psychological: euphoria, enhanced vigor, gregariousness, hyperactivity, restlessness, interpersonal sensitivity, anxiety, tension, anger, impaired judgment, paranoia
Physical: tachycardia, papillary dilation, HTN, n/v, diaphoresis, chills, weight loss, chest pain, cardiac arrhythmias, confusion, seizures, coma
Chronic stimulant intoxication
Affective blunting, fatigue, sadness, social withdrawal, hypotension, bradycardia, muscle weakness
Stimulant withdrawal
Not severe but have exhaustion with sleep (crash)
Treat with rest and support
Cocaine use?
Nasal, IV, smoked
Vasoconstrictive effects (may outlast use), increased risk for CVA and MI - get EKG
Rhabdomyolysis with compartment syndrome from hypermetabolic state
Psychosis associated with intoxication (resolves)
No medications FDA-approved for tx of use disorder
Cocaine neuroadaptation
Prevents reuptake of dopamine
Amphetamine use?
Oral, IV, nasal, smoked
Similar intoxication syndrome to cocaine but usually longer
No vasoconstrictive effects
Chronic use = neurotoxicity from glutamate and axonal degeneration?
Permanent amphetamine psychosis with continued use
No medication treatment (atypical antipsychotics?)
Amphetamine neuroadaptation
Inhibits reuptake of DA, NE, 5HT - greatest effect on DA
Most important preventable cause of death/disease in the U.S.?
Tobacco
How many current tobacco smokers? Ex-smokers?
25% current smokers, 25% ex-smokers
Percent of all U.S. deaths attributed to tobacco?
20%
How many smokers die of tobacco-induced disorder?
45%
What percent of schizophrenic patients smoke tobacco?
75-90%
Drug interactions with tobacco?
Induces CYP1A2 - watch for interactions with olanzapine
Tobacco intoxication, tolerance, withdrawal?
No intoxication diagnosis! (dizziness, headache, nausea)
Rapid tolerance
Withdrawal: dysphoria, irritability, anxiety, decreased concentration, insomnia, increased appetite
Tobacco neuroadaptation?
Nicotine ACh receptors on dopamine neurons in ventral tegmental area release dopamine in nucleus accumbens
Tobacco use disorder treatment?
CBT
Agonist substitution therapy (nicotine gum or lozenge, transdermal patch, nasal spray)
Meds: bupropion 150 mg PO BID, varenicline 1 mg PO BID
Hallucinogens
Naturally occurring mescaline, magic mushroom
Synthetic - LSD, DMT, STP, MDMA
MDMA (ecstacy) effects
Enhanced empathy, personal insight, euphoria, increased energy
3-6 hour duration
MDMA intoxication
Illusions, hyperacusis, sensitivity of touch/taste/smell, “oneness with the world”, tearfulness, euphoria, panic, paranoia, impaired judgment
MDMA tolerance/dependence?
Tolerance develops quickly
Unpleasant side effects (teeth grinding) = dependence less likely
MDMA neuroadaptation
Affects 5HT, dopamine, NE but predominantly 5HT2 receptor agonist
MDMA psychosis
Hallucinations generally mild
Paranoid psychosis with chronic use
Serotonin neural injury associated with panic, anxiety, depression, flashback, psychosis, cognitive changes
MDMA withdrawal
Unclear syndrome
Maybe similar to mild stimulants - sleepiness and depression due to 5HT depletion
What is the most commonly used illicit drug in the U.S.?
Cannabis
Cannabis blood levels?
THC levels peak in 10-30 min
Lipid soluble = long-half life of 50 hours
Cannabis intoxication
Appetite and thirst, colors/sounds/tastes are clearer, increased confidence and euphoria, relaxation, increased libido, transient depression/anxiety/paranoia
Tachycardia, dry mouth, conjunctival injection
Slow reaction time/motor speed
Impaired cognition, psychosis
Cannabis neuroadaptation
CB1, CB2 cannabinoid receptors in brain/body are coupled with G proteins and adenylate cyclase to Ca2+ channels, inhibiting Ca2+ influx
Neuromodulator effect = decreased uptake of GABA and DA
Cannabis withdrawal
Insomnia, irritability, anxiety, poor appetite, depression, physical discomfort
No pharmacological treatment
PCP (“Angel Dust”) MOA
Anesthetic
Similar to ketamine - NMDA antagonist
PCP intoxication
Severe dissociative reactions (paranoid delusions, hallucinations, agitation/violence with decreased awareness of pain)
Cerebellar symptoms - ataxia, dysarthria, nystagmus (vertical and horizontal)
Severe PCP overdose?
Mute, catatonic, muscle rigidity, HTN, hyperthermia, rhabdomyolysis, seizures, coma, death
PCP treatment?
Antipsychotic drugs or BZD if needed
Low stimulation environment
Acidify urine if severe toxicity/coma
PCP neuroadaptation
Opiate receptor effects
Allosteric modulator of glutamate NMDA receptor
PCP tolerance/withdrawal?
NO tolerance or withdrawal!