Substance Use Disorders

Substance Use Disorder (SUD) 

• Uncontrolled use of a substance despite harmful consequences

• Person has an intense focus/craving for the substance

• Use becomes so strong that daily functioning becomes impaired

• Substance changes the brain, especially the reward system

  • Makes the brain “want” the substance more and more

• It is a chronic disease

Addiction

• Chronic brain disorder

• Person seeks drugs and uses them despite harm

• Behavior continues even with negative consequences

Pseudo-addiction

• Looks like “drug-seeking”

• BUT caused by uncontrolled or undertreated pain

• Behavior improves once pain is properly treated

Dependence

• Body adapts to the drug

• Stopping the drug suddenly → withdrawal symptoms (physical + psychological)

Tolerance

• Body gets used to the drug

• Need higher doses to get the same effect

ABCDEs of Addiction

• Abstain

  • Cannot consistently stop using the substance

• Behavioral control

  • Uses more or longer than intended

• Craving

  • Strong urge or “hunger” for the drug or rewarding behavior

• Diminished recognition

  • Doesn’t fully recognize harmful consequences

• Emotional response

  • Mood changes, irritability, emotional instability

Types of Substance Use Disorder

• Alcohol

• Opioids

• Marijuana

• Methamphetamine

• Cocaine

• Hallucinogens

• Inhalants

• Caffeine

• Tobacco

Non-pharmacological → Treatment

must always be done with pharmacological

• Peer Support

  • Talking with others who are going through the same thing

  • Can be one-on-one or in group therapy

  • Includes 12-step programs like:

    • AA (Alcoholics Anonymous)

    • NA (Narcotics Anonymous)

• Cognitive Behavioral Therapy (CBT)

• Combination Therapy

  • Using medications + therapy together often works better than using only one method

• Duration

  • There is no fixed time for treatment; it depends on the person

  • Continuing therapy/support helps people stay sober long-term

Alcohol Use Disorder (AUD)

• A medical condition where someone can’t stop or control their drinking
  even though it causes problems in their life (health, school, work, relationships)

Alcohol Use Disorder (AUD) → Risk Factors

• Drinking at an early age

• Genetics

• Family history

• Mental health + trauma

Normal State → Pathophysiology

• GABA

  • Inhibitory neurotransmitter = slows things down

• Glutamate

  • Excitatory neurotransmitter = speeds things up

• In a normal brain, GABA and glutamate are balanced

Alcohol Use Disorder (AUD) Intoxication → Pathophysiology

• Alcohol messes with the balance between inhibitory (GABA) and excitatory (Glutamate) neurotransmitters in the brain

• In a normal brain, GABA and glutamate are balanced

• Alcohol Increases GABA

  • Alcohol binds to GABA receptors

  • This makes GABA work stronger

  • Result:

    • Brain becomes less excitable

    • You feel relaxed, sedated, slower reaction time

    • Impaired judgement & coordination

• Alcohol decreases Glutamate

Chronic Alcohol Use Disorder (AUD) → Pathophysiology

• Alcohol normally increases GABA

• With long-term use, the brain says “too much GABA — let’s reduce it.”

• So GABA receptors down-regulate (become fewer / less sensitive)

• Result: the brain becomes less responsive to calming signals

• Alcohol normally blocks glutamate

• The brain notices glutamate is too low and compensates by up-regulating receptors

• Result: the brain becomes extra sensitive to stimulating signals

Chronic Alcohol Use Disorder (AUD) Withdrawal → Pathophysiology

• There is less GABA activity now because:

  • Alcohol is gone

  • GABA receptors are still reduced

• Result: very little calming inhibition in the brain

• There is extra glutamate activity because:

  • Alcohol is gone

  • Glutamate receptors are still increased

• Result: too much excitation in the brain

• This creates a dangerous imbalance: LOW GABA + HIGH GLUTAMATE

AUD DSM-5 Criteria

The presence of at least 2 of these symptoms indicates AUD

• Mild: 2–3 symptoms

• Moderate: 4–5 symptoms

• Severe: 6 + symptoms

Beer → Standard Drink Size

• 12 ounces

  • 5% alcohol

Malt Liquor → Standard Drink Size

• 8 ounces

  • 7% alcohol

Wine → Standard Drink Size

• 5 ounces

  • 12% alcohol

Distilled Spirits (liquor) → Standard Drink Size

• 1.5 ounces

  • 40% alcohol

Low Risk Drinking (Recommended Limits)

• Men: ≤ 2 drinks per day

• Women: ≤ 1 drink per day

Heavy Drinking

• Men ≥ 5/day or 15/week

• Women ≥ 4/day or 8/week

Binge Drinking

• Men 5 drinks in 2 hrs

• Women 4 drinks in 2 hrs

AUDIT-C

• 3 questions

• Each scored 0–4 points

• Women ≥3 → positive

• Men ≥4 → positive

Alcohol Use Disorder (AUD) → Laboratory Monitoring

• Blood Alcohol Content (BAC) / Ethanol Level

  • BAC measures how much alcohol is in the bloodstream right now

  • 0.08% = legally intoxicated (cannot drive)

• Ethyl Glucuronide (EtG) & Ethyl Sulfate (EtS)

  • They show recent alcohol use, not current intoxication

  • Detect alcohol use from up to 3–4 days ago

  • Urine alcohol itself is only positive for 12–24 hours, so EtG/EtS is more reliable

EtG/EtS Levels → What They Mean

• > 1000 ng/mL

  • Heavy drinking within last 48 hours OR light drinking same day

• 500–1000 ng/mL

  • Heavy drinking within 3 days OR light drinking in past 24 hours OR exposure to alcohol-containing products (hand sanitizer, mouthwash

• > 500 ng/mL

  • Heavy drinking within 3 days OR light drinking within 36 hours OR incidental alcohol exposure

Stage 1 (Mild) → Stages of Alcohol Withdrawal

• Headache

• Anxiety

• Insomnia

• Mild hand tremors

• Stomach upset

• Heart palpitations

Starts: 6–12 hours after last drink

Stage 2 (Moderate) → Stages of Alcohol Withdrawal

• Symptoms include Stage 1 +:

  • High blood pressure

  • High heart rate

  • Fever or mild hyperthermia

  • Confusion

  • Rapid, abnormal breathing

  • Sweating

Starts: 12–48 hours after last drink

Stage 3 (Severe) → Stages of Alcohol Withdrawal

• Symptoms include Stage 2 +:

  • Visual or auditory hallucinations

  • Seizures

  • Severe confusion / disorientation

  • Delirium tremens

    • agitation

    • hallucinations

    • severe autonomic instability (dangerous vital signs)

Starts: 48–72 hours after last drink

Delirium Tremens

• The most severe and life-threatening form of alcohol withdrawal

• Key Feature:

  • Agitation (restless, can’t stay still)

  • Diaphoresis (heavy sweating)

  • Disorientation (confused, doesn’t know where they are)

  • Hallucinations — mostly visual

  • High blood pressure

  • High heart rate (tachycardia)

  • Low-grade fever

  • Rapid breathing (hyperventilation)

  • Low blood sugar (hypoglycemia)

  • Electrolyte imbalance

• Usually 48–72 hours after the last drink

• Mortality rate: 5–15% if untreated (very dangerous)

Delirium Tremens → Treatment 

• Antipsychotics (for severe agitation or hallucinations)

• Anticonvulsants (prevent seizures)

• Antihypertensives (manage high blood pressure)

• Antiarrhythmics (treat heart rhythm problems)

• Pain management

Tools for Assessing Severity of AWS

• CIWA-AR (Clinical Institute Withdrawal Assessment – Alcohol, Revised) Scale

• SAWS (Short Alcohol Withdrawal Scale)

• RASS (Richmond Agitation-Sedation Scale)

CIWA-AR (Clinical Institute Withdrawal Assessment – Alcohol, Revised)

• Most commonly used and most important tool

  • Provider evaluates symptoms + patient answers questions

  • 10-item questionnaire

  • Used to determine benzodiazepine dosing

  • Protocols differ between hospitals

  • Good for patients who are alert and can talk

SAWS (Short Alcohol Withdrawal Scale)

• Patient-completed version

  • 10-item symptom checklist

  • Completed by the patient

  • Helps decide if outpatient detox is safe

  • Can monitor progress over time

RASS (Richmond Agitation-Sedation Scale)

• Used when the patient cannot answer questions

  • Used in patients who are unresponsive, severely agitated, or intubated

  • Scale ranges from:

    • –5 = deeply sedated / unresponsive

    • 0 = calm

    • +4 = combative / very agitated

Alcohol Withdrawal →Labs, Inpatient or Outpatinet?

• Abnormal labs = in patient

CIWA-AR Score < 10

• Outpatient 

  • Treatment: supportive care ± gabapentin or carbamazepine

CIWA-AR Score 10–18

• Inapatient: 

  • Treatment: Inpatient maintenance

CIWA-AR Score > 19

• Inapatient: 

  • Treatment: Inpatient maintenance

Alcohol Withdrawal Syndrome → Drugs Classes

• Benzodiazepines

• Barbiturates

• Antiemetics

• Antacids

• Anticonvulsants

• Vitamins

Benzodiazepines → Drugs 

• Chlordiazepoxide

• Diazepam

• Lorazepam

• Oxazepam

First Line

Alcohol Withdrawal Syndrome → First Line Benzodiazapines

• Chlordiazepoxide

• Diazepam

Alcohol Withdrawal Syndrome → First Line Benzodiazepines if patient: Elderly, Liver Disease

• Lorazepam

• Oxazepam

Why is ‘Banana Bag’ given to Alcohol Withdrawal patients?

• Alcoholics are often deficient in:

  • Thiamine

  • Folic acid

  • Electrolytes 

  • General vitamins

• Without thiamine = brain damage

• Without folate = anemia, fatigue, depression

• Without ‘Banana Bag’ can lead to Wernicke–Korsakoff Syndrome

Banana Bag

• Thiamine 100 mg

• Folic acid 1 mg

• Multivitamin

• Isotonic saline

• +/- Dextrose (5% D5W)

• +/- Magnesium sulfate 2 g

Wernicke–Korsakoff Syndrome

• Neurologic complication due to low thiamine levels 

• Leads to encephalopathy, oculomotor dysfunction (eye movement problems), and gait ataxia (poor balance)

• Can lead to permanent cognitive impairment

• Prevention: thiamine supplementation

Alcohol Use Disorder → Treatment

• Naltrexone (First Line) 

• Acamprosate

• Disulfiram

• Off-label agents: 

  • Topiramate

  • Gabapentin

Naltrexone

• Competitive Mu-opioid Receptor Antagonist

  • Alcohol normally increases mu-opioid → gives “pleasure.”

  • Naltrexone blocks that reward, so drinking feels less good

• Side Effects: 

  • Nausea/vomiting

  • Headache

  • Insomnia

  • Nervousness

Naltrexone → Black Box Warning 

• Hepatocellular Injury

Naltrexone → Contraindication

• Severe hepatic impairment

• Concurrent Opioid use

  • If patient is taking opioids → naltrexone will cause immediate opioid withdrawal

  • Must be opioid-free for:

    • 7 days for short-acting opioids

    • 14 days for methadone or buprenorphine

When to give Acamprosate?

• BEST OPTION for:

  • Patients with hepatic impairment

  • Patients on opioids

• So if the patient cannot take naltrexone → acamprosate is your go-to!!!

Acamprosate

• Modulating NMDA (glutamate) receptors

• Enhancing GABA activity

  • Reduces alcohol cravings

• Warnings: 

  • Suicidal ideation (rare, but must be monitored)

• Side Effects: 

  • Diarrhea

  • GI upset

  • Insomnia

Disulfiram

• Blocks aldehyde dehydrogenase (ALDH) 

  • This causes acetaldehyde to build up if someone drinks alcohol

  • People drink to reach the “Acetate” stage (feel good stage), so by blocking getting there, it causes issues, which will make the person stop drinking so they don’t have to get these symptoms again 

• Side Effects:

  • Hepatotoxicity

  • Peripheral neuropathy

  • Delirium

Does Disulfiram reduce alcohol cravings?

• NOOOOOOOOO

  • The only one that does NOT reduce alcohol cravings

What happens if someone drinks alcohol on disulfiram?

• Symptoms start within 12–24 hrs of drinking:

  • Flushing/warm face

  • Palpitations

  • Increased HR

  • Low BP

  • N/V

  • Sweating

  • Anxiety

  • Headache

  • SOB

  • Dizziness

  • Blurred vision

  • Confusion

The goal is to make drinking so unpleasant that the person avoids alcohol

Cannot Ingest Alcohol for how long when taking Disulfiram?

• Cannot drink alcohol for 14 days after last dose

Disulfiram → Contraindication

• Alcohol containing products

Topiramate

• Sodium channel blocker

  • increases GABA (calming)

  • decreases glutamate (excitatory)

• Side Effects:

  • GI disturbances

  • CNS effects

  • Cognitive dysfunction

When is the best time to give Topiramate to a patient?

• A drinker + 

  • Binge eating

  • Obesity

Gabapentin

• Increases GABA

• Decreases glutamate

• Also helps with alcohol withdrawal

• Side Effects: 

  • CNS depression

When is the best time to give Topiramate to a patient?

• A drinker +

  • Seizures

  • Postherpetic neuralgia

  • Chronic pain 

  • Neuropathy

Pregnancy/breastfeeding → Special Consideration

• Non-pharmacologic therapy recommended given limited data available with current agents

Renal Impairment → Special Consideration

• Caution with acamprosate

• Dose adjustments with topiramate and gabapentin

Hepatic Impairment → Special Consideration

• Avoid naltrexone in acute hepatitis or severe liver disease

Current/recent alcohol consumption → Special Consideration

• Avoid disulfiram

Concomitant opioid use or Upcoming surgery → Special Consideration

• Avoid naltrexone

Opioid Overdose

• Opioids slow down the body → “depressant” effect

• They make the brain forget to breathe

• If taken with other depressants (“downers”) like alcohol, benzos, or sleeping pills, the effect is even stronger

• Too many opioid molecules attach to opioid receptors in the brain

• These receptors control breathing

• When they are overloaded → breathing slows or stops

• This causes low oxygen (O₂) to important organs like:

  • Brain

  • Heart

  • Lungs

• Low O₂ = coma, brain damage, or death

Naloxone

• Pure Opioid Receptor Antagonis

  • Has a stronger pull (higher affinity) for opioid receptors than opioids

• It kicks opioids off the receptors

• This allows:

  • Breathing to restart

  • Person to wake up

• Works only temporarily → opioids may return to receptors once naloxone wears off (not good → must call 911 immediately or person will not be able to breath again) 

• Rapid onset → works in seconds to minutes

• But… short duration → lasts only 30–120 minutes

• Available OTC

Naloxone → Formulations

• Intranasal

  • 4 mg Narcan

  • 8 mg Kloxxado (stronger)

• Intramuscular or Subcutaneous

• IV

Who might benefit from receiving Kloxxado vs Narcan?

• People using high-potency opioids (especially fentanyl) benefit from Kloxxado (8 mg) because fentanyl binds extremely tightly to opioid receptors and often requires higher naloxone doses to reverse

  • Narcan (4 mg) may not be enough → may require multiple sprays

  • Kloxxado (8 mg) = double the strength, helps reverse fentanyl overdose faster with fewer doses

• People using other potent opioids

• People with history of opioid use disorder (OUD)

Naloxone Counseling

• Recognize an opioid overdose

• Try to wake them up

• Use the naloxone

• CALL 911 immediately

• Re-dose if needed

• Place person in recovery position

• Stay with them until EMS arrives

Naloxone has a short half-life (30–90 minutes)

Many opioids (especially fentanyl, methadone, ER formulations) last much longer

When naloxone wears off → the opioids can reattach to receptors → overdose can come back

This is why calling 911 is mandatory, even if the person wakes up

Opioid Intoxication Symptoms

everything slows down 

• Drowsiness / coma

• Slurred speech

• Poor attention / memory

• Bradycardia (slow HR)

• Hypotension (low BP)

• Pinpoint pupils (miosis = tiny pupils)

• Respiratory depression (MOST dangerous → main cause of death)

THIS is exactly when naloxone is given

Opioid Withdrawal Symptoms

everything speeds up (WET)

• N/V/D (nausea, vomiting, diarrhea)

• Myalgias (muscle aches)

• Lacrimation/rhinorrhea (watery eyes, runny nose)

• Dilated pupils (big pupils)

• Sweating

• Fever

• Anxiety / restlessness

Opioid Withdrawal Timeline

• 72 hours:  Physical symptoms peak (horrible flu-like)

• 1 week: Physical symptoms improve

• 2 weeks: Mood symptoms (anxiety, irritability, depression)

• 1 month: Cravings may continue

Assessing Opioid Withdrawal (COWS)

• It’s an 11-item tool clinicians use to measure how bad withdrawal is

• Helps decide:

  • How severe withdrawal is

  • When to start medication

  • Whether symptoms are improving

Opioid Withdrawal → Treatment

• Clonidine

• Lofexidine

• Antiemetics

• Antidiarrheals

• APAP / NSAIDs (Pain Management)

Clonidine (Off-label)

• Alpha-2 agonist

  • ↓ norepinephrine → ↓ withdrawal symptoms

• Also has mild pain-relief effects

• Major issue: Hypotension (low BP)

• Pros:

  • Cheap

  • Works well

  Cons:

  • Can cause significant hypotension

  • Not FDA-approved

Lofexidine (FDA approved) 

• Central alpha-2 agonist (same concept as clonidine)

• More selective → fewer side effects

• Much lower risk of hypotension

• Pros:

  • FDA-approved

  • Less BP lowering (safer)

  • Better tolerated

  Cons:

  • Very expensive

    • Insurance may not cover it

Why Naloxone is NOT used for Opioid Use Disorder

• Because naloxone is only for emergencies — it is NOT a long-term treatment

Opioid Use Disorder → Treatment

• Buprenorphine

• Methadone

• Naltrexone

Buprenorphine

• Partial Mu-opioid Agonist

• Delta & kappa antagonist

  • Limits respiratory depression (safer than heroin, oxycodone, fentanyl)

  • Limits euphoria → people cannot get “as high” → lowers misuse risk

• Prevents cravings

• Prevents withdrawal symptoms

• Stabilizes the brain

• Allows normal functioning

• High binding affinity (Ki = 0.22)

  • Buprenorphine holds onto the receptor very tightly

  • It can push off weaker opioids

  • It blocks other opioids from binding

• Controlled substance

  • Schedule III

Type of opioid but a safer option

Why do we add naloxone to buprenorphine?

• When taken correctly, naloxone is basically inactive

  • Naloxone has <10% absorption sublingually

  • So you do NOT feel naloxone

  • The buprenorphine still works normally
    → controls cravings & withdrawal

• BUT if someone tries to inject/snort buprenorphine to get high → naloxone suddenly becomes active

  • Naloxone is a strong opioid blocker

  • When injected, naloxone works 100%
    → Instant withdrawal
    → Zero euphoria
    → Feels terrible

Buprenorphine Formulations

• Buprenorphine-naloxone

  • Suboxone: sublingual film

  • Zubsolv: sublingual tablet

  • Bunavil: buccal film

• Buprenorphine

  • Subutex: buccal film

  • Probuphine: implant

  • Sublocade: monthly injection

  • Brixadi: weekly and monthly injection

Buprenorphine Prescriber Requirements

• MAT Act 2022

  • Removed X-waiver requirement

  • Any DEA prescriber can treat OUD with buprenorphine

  Must meet ONE of the following:

  1. Training Pathway

     • ≥ 8 hours training on opioid/SUD topics

     • Required for new or renewing DEA registrations (Schedules II–V)

  2. Certification Pathway

     • Board certified in:

       • Addiction Medicine

       • Addiction Psychiatry

       • (ABMS, ABAM, or AOA)

  3. Recent Graduate Pathway

     • Graduated within 5 years

     • From medical, PA, or NP programs

     • Curriculum included ≥ 8 hours SUD training

     • In good standing

Suboxone → Dosing

• Induction Phase

  • Start when patient is in early withdrawal

  • Must be 12–24 hours abstinent from opioids

  • Initiated in clinic/OTP or supervised setting

  • Goal: safely start buprenorphine without precipitated withdrawal

• Stabilization Phase

  • Begins after reducing or stopping full agonist opioids

  • Patient has reduced cravings → adjust dose as needed

  • Typical daily dose range: 4 mg/1 mg → 24 mg/6 mg

  • Usually divided doses

• Maintenance Phase

  • Patient has no cravings and is stable on buprenorphine

  • Usual maintenance dose: 16 mg/4 mg daily

  • Duration: patient-specific, may be long-term or lifelong

Buprenorphine Patient Counseling (Suboxone films or Subutex tablets)

• Place under the tongue → let dissolve for ~15 minutes

• Do NOT eat or drink while dissolving

• When fully dissolved → rinse mouth with water and swallow

• Wait 1 hour before brushing teeth

• Do NOT cut, tear, chew, or swallow whole (black-box warning)

  • Although some prescribers still split films for dosing adjustments

Sublocade

• Monthly injection

• Must be given by healthcare provider

• Inject into abdomen only

• Refrigeration required

• Only 2 dose strengths

• Good for pts with adherence issues

• Must trial oral buprenorphine first

Brixadi

• Weekly or monthly injection

• Must be given by healthcare provider

• Can inject into abdomen, buttocks, thigh, or upper arm

• No refrigeration needed

• More dosing options available

• Must trial oral buprenorphine first

Buprenorphine → Considerations

• Somnolence

• Constipation

• GI upset

• QTc prolongation (important!)

Buprenorphine → Contraindication

• Severe liver disease

Naltrexone for OUD

• Competitive mu-opioid receptor antagonist

• Must be opioid-free for ≥7 days

• Must stop before surgery in case patient needs opioids afterward

  • PO naltrexone: stop 72 hours prior

  • IM: stop 30 days prior

Methadone

• Full mu-opioid agonist

• NE & 5HT reuptake inhibitor

• NMDA antagonist

• Kappa agonist

• Schedule II controlled substance

Methadone → Considerations

• Can be started immediately (no withdrawal wait time)

• Higher risk of opioid-induced respiratory depression

• Causes constipation

• QTc prolongation

• Very long half-life: 8–59 hours

  • Even longer in chronic users (very lipophilic)

Methadone Dosing

• Induction Phase (Weeks 1–2)

  • Start: 10–30 mg/day

  • Goal: Suppress withdrawal symptoms

• Early Stabilization (Weeks 3–4)

  • Once steady state is reached → Titrate by 5–10 mg every 3–5 days

• Late Stabilization (Week 5+)

  • Minimum treatment duration: 12 months

  • Can stay on same individualized dose for years

• Dosing Interval Option

  • Some patients can use Q48–72 hour dosing

Methadone Clinics

• Outpatient clinics that dispense daily methadone doses

  • Limitation: requires daily visits → transportation, scheduling issues

• Must be an approved OTP site + prescriber

• Patients who show adherence + abstinence may earn take-home doses

  • Usually after several months

  • Amount depends on clinic policy + provider judgment

• NOT reported to PDMP/iSTOP

• Public vs Private Methadone Clinics

  • Differences in:

    • Wait times

    • Chance of being on a waitlist

    • Cost