Substance Related Disorders

Substance Use Disorder

The term "addiction" is omitted from the official DSM-5 substance use disorder diagnostic terminology

  • Continued use of substance despite associated problems (except caffeine)

  • Substance use disorders ➔ underlying change in brain circuits that may persist beyond detoxification

  • Brain changes ➔ behavioral effects like relapses and intense craving (especially when exposed to drug related stimuli)

DX of Substance Use Disorder

2 of following within 12mo period:

Impaired control over substance

  1. Larger quantity of substance/duration of use than intended

  2. Persistent desire to cut down or regulate use (reports multiple unsuccessful attempts)

  3. Significant time obtaining/using/recovering from use

  4. Craving: intense desire or urge (could not think of anything else)

Social impairment

  1. Use affects major role obligations (work/school)

  2. Use causes recurrent social/interpersonal problems

  3. Use ➔ given up or ↓eased activities

Risky use

  1. Recurrent use in physically hazardous situations

  2. Continued use despite known physical or psychological problems from use

Pharmacological criteria

  1. Tolerance

    • ↑ dose required to achieve desired effect

    • OR ↓ effect with usual dose

  2. Withdrawal

    • MC in etOH, opioids, sedatives/hypnotics/anxiolytics

    • ↓ SSX with stimulants, tobacco, cannabis

    • Generally not present in phencyclidine/hallucinogen/inhalant use disorder

Neither tolerance nor withdrawal is required for dx of substance use disorder

  • Pharmacological tolerance and withdrawal during medical tx IS NOT "addiction"

  • Medications taken as prescribed can ➔ physical dependence (dependence ≠ addiction)

  • Prescription medications used inappropriately ➔ compulsive, drug-seeking behavior ➔ substance use disorder

TX for SUD is always psychosocial (CBT, 12-step groups) ± meds

  • Insufficient evidence to establish diagnostic criteria and course descriptions needed to identify repetitive behaviors/excessive behavioral patterns as mental disorders

    • "sex addiction," "exercise addiction," "shopping addiction," "internet gaming addiction"

Alcohol (etOH)

Alcohol Intoxication

  • MOA: GABA agonist (main MOA)

  • Initially ➔ talkativeness, sense of well-being; BAC ↓ ➔ depressed/withdrawn ↓ cognition


    • Recent drinking ➔ problematic behavioral

    • One or more:

      • Slurred speech, incoordination, unsteady gait, nystagmus, ↓ attention/memory, stupor/coma

    • Not from something else:

      • Always get glucose level

        • Electrolytes, consider co-ingestion, r/o hypoxia and trauma

          • (etOH and head trauma needs c-spine precaution)


    • Comatose/severe intox ➔ thiamine and dextrose (prevent Wernicke's encephalopathy)

      • Protect airway

        • EtOH absorbed fast so activated charcoal/lavage usually not helpful

    • Agitation ➔ benzos/haldol but ↑ risk of respiratory depression

Blood Alcohol Concentration (BAC)

Ingesting 10g etOH ➔ BAC 20mg/dL = 0.02%

  • Legal driving: 0.08% = (80mg/dL)

  • Standard drink (14g etOH):

    • 100lbs ➔ BAC ~ 0.05%

      • 2 drinks in 1 hour ➔ ~0.08%

    • 200lbs ➔ BAC ~ 0.02%

      • 3-4 drinks in 1 hour ➔ ~0.08%

  • Body metabolizes ~ 1 drink/hour (~ 0.015mg/dL)

    • Time since stopping X 0.015 = current BAC

Alcohol Use Disorder


  • At least 2 within 12 month period (3 sx = Mild; >6 sx = Severe)

    • Drink more than intended

    • Difficulty cutting back

    • Spend a lot of time spent obtaining, using, or recovering from

    • Craving

    • Fail to fulfill major role obligations (work/school)

    • Continued drinking despite recurrent problems

    • Responsibilities/activities given up or ↓

    • Continued drinking despite physically hazardous situations

    • Drinking despite awareness it is causing problem

    • Tolerance

    • Withdrawal or using benzos to keep from withdrawal


  • ↑ GGT (most sensitive for abuse)

  • ↑ AST, ↑ ALT (AST > ALT in etOHism)

  • Megaloblastic anemia (↓ folic acid, ↓ B12)


  • Psychosocial (12 step group)

  • Naltrexone reduces cravings

  • Disulfiram (antabuse): drinking ➔ ↑ acetaldehyde

    • N/V and hypotension

    • Must be 48hrs from last drink before starting

    • CI in CAD, psychosis hx

EtOH Withdrawal

  • Chronic etOH use:

    • GABA receptor desensitization (↓ inhibition)

    • NMDA receptor hypersensitization (↑ excitability)

  • Hours-days after stopping or decreasing heavy etOH use ➔ at least two:

    • Autonomic hyperactivity (diaphoresis, tachy)

    • Hand tremor

    • Insomnia

    • N/V

    • Transient a/v/tactile hallucinations

    • Psychomotor agitation

    • Anxiety

    • Tonic-clonic seizures

EtOH Withdrawal SSX timing:

  • SX generally start within 6-24hrs after stopping

    • Early/mild ➔ anxiety, insomnia, tremor, diaphoresis, HTN, hyperreflexia (last ~1-2days)

  • Hallucinations begin 12-24hrs after stopping

  • Seizures from 6-48hrs after stopping (peak at 24hrs)

    • Usually multiple seizures

  • Withdrawal delirium (delirium tremens) begins 72-96hrs after stopping

    • Rapid onset of ↓ attention/cognition, ± hallucinations

    • Extreme DTs ➔ autonomic hyperactivity (HTN, fever, severe tachy and diaphoresis)

    • CIWA >15, benzo use ➔ ↑ risk of DTs

EtOH w/d TX:

  • Abstinent for 5d (and CIWA <10) ➔ management not needed

  • Diazepam OR lorazepam OR chlordiazepoxide (librium)

    • psychomotor agitation and prevent progression to severe withdrawal

  • Thiamine, folate, and dextrose

Points 0-7 each:

  • N/V

  • Tremor

  • Paroxysmal sweats

  • Anxiety

  • Agitation

  • Tactile sx

  • Auditory sx

  • Visual sx

  • Headache

  • Orientation (max 4 points)

Total: 0- 67 points

  • CIWA 8-10 ➔ Benzos or librium

  • CIWA 10-20 Standing/PRN benzos

  • Consider ICU if CIWA >20

  • Diazepam, clonazepam, and midazolam have active metabolites and may have prolonged duration in pts with liver impairment

  • Lorazepam, oxazepam, temazepam (LOT) are less dependent on liver function and have more predictable kinetics in pts with cirrhosis



  • Main MOA: GABA agonist ➔ ↑ frequency of Cl channel opening ➔ ↑ intracellular Cl ➔ hyper-polarization ➔ ↓ neuronal excitability

  • CNS depression muscle relaxant, anti-epileptic, drowsy, clumsy, anterograde amnesia (brown/blackouts)

  • Addictive, causes tolerance and withdrawal

  • Contraindicated in: hx of SUD, pregnancy (except for 2nd line in eclampsia), narrow angle glaucoma, myasthenia gravis

Short acting (sleep onset insomnia, sedation/induction)

  • Midazolam (versed), alprazolam (xanax)

Intermediate acting (sleep onset/maintenance insomnia, status epilepticus, etOH w/d)

  • Lorazepam (ativan)

Long acting (status epilepticus, etOH w/d)

  • Diazepam (valium), clonazepam (klonopin), chlordiazepoxide (librium)

Diazepam, midazolam s have ↑ lipophilicity ➔ faster onset

Benzodiazepine overdose

  • Lethargy/somnolence, ↓ respirations, hypotension, hyporeflexia

  • Usually benzo OD is not life-threatening BUT risk of dying from OD ↑ with other substances (opioids, etOH)

  • TX is generally supportive (airway protection)

    • Flumazenil is antidote to benzo OD but ➔ seizures in benzo dependent pts

      • Only use if pt is KNOW BENZO NAIVE

      • Shorter acting than benzos (so don't discharge)

Benzodiazepine withdrawal

  • Sympathetic nervous system on blast ➔ anxiety, insomnia, sweating, HTN, tremors, psychosis (a/v hallucinations)

  • TX is to taper dose (usually with long acting diazepam) and BOLO for seizures


  • Main MOA: GABA agonist ➔ ↑duration of Cl channel opening ➔ ↑ intracellular Cl ➔ hyper-polarization ➔ ↓ neuronal excitability

    • ↓ glutamate (excitatory NT)

    • Highly lipophilic ➔ rapid onset and prolonged duration of action

  • CNS depression sedation, anti-epileptic, ↓ ICP

  • Intra-arterial injection (accidental) ➔ vessel injury/spasm ➔ necrosis/gangrene (TX with dilution and intra-arterial lidocaine)

Rapid acting (anesthesia, ↓ICP)

  • Thiopental

Short/intermediate acting (sedation)

  • Pentobarbital

Long acting (Go to anti-convulsant when benzos don't work)

  • Phenobarbitol

Barbiturate overdose

  • Hypotension, respiratory depression/arrest, laryngo/bronchospasm

  • TX is generally supportive (airway protection)

Barbiturate withdrawal

  • Sympathetic nervous system on super blast ➔ delirium, HYPOtension

Melatonin receptor agonists

  • Ramelteon (rozerem) binds MT1 and MT2 receptors ➔ sleepiness

  • For sleep onset insomnia

Orexin receptor antagonist

  • Suvorexant (belsorma) bind and ⊣ orexin receptors ➔ sleepiness

  • For sleep onset/maintenance insomnia


  • MOA: Inhibition of presynaptic Ca channels ➔ ↓ Ach, NE, 5HT, glutamate and inhibition of postsynaptic K channels

  • Full agonists:

    • Codeine

    • Morphine

    • Hydrocodone (vicodin)

    • Oxycodone (percocet)

    • Hydromorphone (dilaudid)

    • Methadone

    • Fentanyl

  • Partial agonist

    • Buprenorphine

  • Full antagonists

    • Naloxone

    • Naltrexone

Opioid SSX

  • CNS depression, euphoria, analgesia

  • Constipation, ↓ respiration, miosis, bradycardia

  • Urinary retention, hyperprolactinemia

TX opioid use disorder

Medication assisted treatment (MAT)

    • Methadone (TX chronic long-term use by replacing problematic opioid with "less euphoric and longer acting" opioid)

      • Moderate euphoria (full agonist)

      • Does not precipitate withdrawal (can use other opioids on top)

      • Typically involves visiting a clinic for daily dosing

      • Cheap

      • Can TX pts with chronic pain

    • Buprenorphine

      • Mild euphoria (partial agonist)

      • Can precipitate withdrawal (using opioids on top ➔ withdrawal sx)

        • High affinity for receptor knocks of other opiates but partial agonist doesn't give same effect ➔ w/d ssx

      • More expensive and less accessible than methadone

    • Naltrexone (vivitrol IM)

      • No euphoria (antagonist) BUT ↓ craving for opioids and etOH

      • Antagonist with long half-life and duration of action

      • Can precipitate withdrawal (using opioids on top ➔ withdrawal sx)

      • More expensive and less accessible than methadone

    • Buprenorphine/naloxone (suboxen - SL)

      • Mild euphoria

      • Partial agonist ➔ ↓ craving/antagonist ⊣ using opioids on top

      • More expensive and less accessible than methadone

Opioid overdose

  • Miosis "pinpoint pupils" (<2mm), ↓ RR, ↓ HR


    • Then administer naloxone (narcan) slowly (pushed too fast ➔ aggression and vomiting)

      • Naloxone duration of action is shorter than most opioids (don't discharge the pt)

Opioid withdrawal

  • Anxiety, irritability, and flu like sx (myalgia, chills ➔ piloerection, rhinorrhea, yawning, diarrhea, mydriasis)

    • Withdrawal is not life-threatening but super uncomfortable

  • TX is supportive


PCP (phencyclidine)

  • Liquid sprayed on tobacco or cigarette dipped in (smells like magic markers)

  • MOA: ⊣ 5HT, DA, NE reuptake and NMDA antagonist

PCP intoxication

  • Behavior ∆ : stupor, impulsive, violent

  • For some reason they get naked...

  • Tachy, HTN, nystagmus

  • ± miosis (most other hallucinogens cause mydriasis)

  • BOLO seizures, rhabdo, and agitation/psychosis


  • Benzos or haldol for agitation


  • Amphetamine, meth-amphetamine, MDMA, mescaline

  • MOA: Depending on functional groups added to amphetamine: 5HT/D2 agonists, DART antagonist

  • MDMA ➔ ↑ ADH secretion

    • Excess water intake ➔ hypoNa (have to drink gatorade when taking molly)


  • Euphoria, agitation, insomnia, diaphoresis

  • Tachy, HTN, bruxism (teeth grinding)

  • Hyperthermia

  • MDMA can ➔ serotonin syndrome

  • Methamphetamine can ➔ delusional parasitosis (bug infestation)


  • Benzos or haldol for agitation

  • Control hyperthermia (>41.1)

    • Control excessive muscle activity (usually controlled with sedation) and aggressive cooling

    • Severely intoxicated may require paralytics and airway control: use nondepolarizing agents (rocuronium)

      • Succinylcholine is relatively contraindicated (↑ risk of rhabdo)

    • ANTIPYRETICS (Tylenol) does NOT help hyperthermia from amphetamine intox

  • Control tachy, HTN and BOLO arrhythmias

    • Sedation generally controls tachy and HTN but

      • If HR >180: diltiazem

      • If severely hypertensive: use nitroprusside or NTG

      • Avoid β-blockers


  • Cocaine can be heated with NaHCO3 (baking soda) to form the free-base of cocaine (crack)

    • Cocaine powder is snorted and crack-cocaine is smoked

  • MOA: ⊣ 5HT, DA, NE reuptake

    • ⍺1 activation ➔ vasoconstriction of cardiac vasculature and peripheral vasculature

      • Dose-dependent coronary vasoconstriction and ↑ risk of cardiac issues (dysrhythmias, MI, cardiomyopathy)

      • Perforated ulcers, ischemic bowel, PE

    • Na channel blockade ➔ ↓ Na permeability ➔ ↓ excitability of membrane ➔ anesthetic

    • ↑ concentration of glutamate and aspartate (excitatory neurotransmitters)

Cocaine intoxication

  • Euphoria, hyperarousal, paranoia

  • Tachy, HTN

  • Mydriasis

  • ± hyperthermia


  • Benzos

  • Control tachy, HTN and BOLO arrhythmias

    • Sedation generally controls tachy and HTN but

      • If severely hypertensive: use nitroprusside or NTG; CAN use phentolamine

    • Avoid β-blockers (↑ vasospasm)

Cocaine/stimulant withdrawal

SSX: "Crashing"

  • Fatigue

  • Insomnia/hypersomnia/unpleasant dreams

  • Increased appetite

  • Psychomotor retardation/agitation

  • Pts stopping etOH or benzos CAN DIE FROM WITHDRAWAL and need to be watched for seizures

  • Opioid and stimulant withdrawal doesn't kill people (generally)

  • TX for SUD is always psychosocial (CBT, 12-step groups) ± meds

  • Methadone is easiest way to get someone to ↓ "problematic use". Pt's dose is typically ↑ until the pt starts giving clean urines...

  • Pts with more resources can access MAT options other than methadone (suboxone, naltrexone) but the lack of full agonist ➔ ↑ craving

  • Pts can try to overcome buprenorphine and naltrexone by taking large doses (first they get sick from withdrawal then they knock out respiratory drive)

  • Overdose with possible benzos or opiates ➔ respiratory compromise: give naloxone (won't cause seizure) NOT flumazenil (may cause seizure)

  • Activated charcoal usually more harm than good (↑ risk of aspiration)

    • Only use if airway is protected (maintained by pt or tubed), co-ingestion with other toxin, and ingestion was 30-60mins ago


  • Over 100 cannabinoids (bind cannabinoid receptors) present in marijuana

    • ∆ 9-TetraHydroCannabinol (THC) is most psychoactive active

    • Binds cannabinoid receptors CB1 and CB2 ➔ adenylate cyclase inhibition

  • Medical marijuana - dronabinol

Marijuana intoxication

  • Euphoria, distorted sense of time, joviality (laughing)

  • Can cause anxiety/paranoia

  • ↑ appetite (munchies) junk food junky - potato chips and lunch meat, up in the front seat

  • Dry mouth, conjunctival injection (red eyes), ± mydriasis

  • Associated with psychosis and development of schizophrenia - pot ➔ schizophrenia OR schizophrenia ➔ self-medication (chicken or egg)

  • Long-term use can ➔ cannabinoid hyperemesis syndrome

    • ABD pain, N/V ± relieved with hot water exposure (shower/bath)

    • TX is cessation


  • Tobacco use is bad...

  • Smoking if a RF for most things

  • Smoking is protective for UC

  • TX: Bupropion (Wellbutrin), nicotine replacement (patch, gum, lozenges)

Gambling disorder

  • Persistent and recurrent problematic gamblingimpairment or distress

  • Gambling problem is NOT from/during manic episode

  • At least 4 in 1 year:

    • Needs to ↑ amount gambled for effect

    • Restless or irritable when attempting to cut down/stop

    • Unsuccessful efforts cut down/stop

    • Preoccupied with gambling

    • Gambles when feeling distressed

    • Returns after losing money to "get even"

    • Conceals extent of gambling (lies about how much)

    • Jeopardizes/lost significant other/job/opportunity

    • Relies on others to relieve desperate financial situation


    • 12-step program, CBT