Opioids

Opioids are a class of drugs that bind to opioid receptors in the central nervous system. They include both prescription medications (oxycodone, hydrocodone, morphine) and illicit drugs (heroin). Opioids produce analgesia, euphoria, and respiratory depression. Street supplies are increasingly contaminated with fentanyl, a synthetic opioid 50-100 times more potent than morphine. The opioid crisis is the leading cause of overdose death in North America.

How It Works

Opioids bind to mu, delta, and kappa opioid receptors throughout the nervous system and gastrointestinal tract. Mu receptor activation produces analgesia, euphoria, and respiratory depression. Activation of receptors in the brainstem depresses respiration by reducing sensitivity to carbon dioxide. This respiratory depression is dose-dependent and the primary cause of fatal overdose. Tolerance develops to euphoric and analgesic effects but NOT to respiratory depression, making overdose risk persistent even in regular users.

Legal Status

Heroin is Schedule I (US) / Class A (UK) — illegal everywhere with no medical use. Prescription opioids (oxycodone, hydrocodone, morphine) are Schedule II-III controlled substances available by prescription only. Fentanyl is Schedule II in pharmaceutical form but illicit fentanyl is criminalized. Possession of any non-prescribed opioid is a criminal offense in most jurisdictions.

Dosage Guide (Variable — varies dramatically by substance, purity, tolerance, and route)

Note: CRITICAL: Fentanyl doses are measured in MICROGRAMS not milligrams — 1 mg fentanyl = 1000 mcg. Street fentanyl concentration is EXTREMELY inconsistent and uncontrolled, ranging from undetectable amounts to lethal doses in a single tablet or dose. A lethal fentanyl dose is estimated at 2 mg for naive users. Tolerance prevents constant dosing — regular users require much higher doses and have different thresholds than first-time users. Prescription oxycodone dosing is 5-30 mg every 4-6 hours depending on tolerance and indication. Heroin purity on street is typically 5-15%, but fentanyl content is unknown. ALWAYS use fentanyl test strips before consuming any powder or pill. Switching between substances or routes dramatically increases overdose risk.

Organ System Impacts

cardiovascular — High

Opioids cause peripheral vasodilation, hypotension, and bradycardia. Overdose causes circulatory collapse. Chronic use associated with endocarditis (especially IV use), arrhythmias, and cardiomyopathy. Fentanyl causes more pronounced bradycardia than heroin.

neurological — High

Central nervous system depression, cognitive impairment, tolerance, psychological dependence, withdrawal symptoms (hyperalgesia, anxiety, insomnia). Chronic use causes changes in pain processing and reward circuits. Seizure risk increased, particularly with some opioids (tramadol). Tolerance develops to euphoria and analgesia but NOT respiratory depression.

ocular — Low

Pupil constriction (miosis), especially during active effects. Pinpoint pupils are a classic overdose sign. Nystagmus may occur with very high doses. Generally reversible.

dermatological — Moderate

IV use causes track marks, abscesses, cellulitis, collapsed veins, skin infections. Chronic scratching from itching causes lesions and infections. Histamine release can cause flushing and itching. Subcutaneous injection (skin popping) causes abscesses and necrosis.

respiratory — Dangerous

CRITICAL: Respiratory depression is the primary cause of opioid overdose death. Opioids reduce respiratory drive by decreasing CNS sensitivity to CO2. Effects are dose-dependent and synergistic with other depressants. Overdose produces Cheyne-Stokes respiration, then complete respiratory arrest. Pulmonary edema (fluid in lungs) is common in fatal overdoses. Chronic smoking of opioids causes airway irritation and increased infection risk. LETHAL RISK: Tolerance develops to euphoria and analgesia but NOT to respiratory depression, making overdose risk persistent in regular users.

hepatic — Moderate

IV opioid use increases Hepatitis C risk dramatically. Heroin itself causes minimal direct liver damage, but contaminated supplies and needle sharing spread viral hepatitis. Oxycodone and morphine undergo hepatic metabolism; liver disease increases overdose risk.

hematological — High

IV injection dramatically increases bloodborne infection risk (HIV, Hepatitis B/C, bacterial infections). Infected injection drug users have 77 times higher risk of endocarditis. Needle sharing is primary transmission route for viral hepatitis among PWID (people who inject drugs).

renal — Low

Rhabdomyolysis from overdose and immobility can cause acute kidney injury. Chronic IV use increases infection-related renal damage. Opioids have minimal direct nephrotoxicity but metabolites require renal clearance. Dehydration common during use increases renal strain.

gastrointestinal — Moderate

Severe constipation (mu receptors in GI tract), nausea, vomiting (especially initial use, stimulation of chemoreceptor trigger zone). Reduced GI motility can cause fecal impaction. Opioid-induced bowel dysfunction is persistent and requires proactive management.

musculoskeletal — Low

Rhabdomyolysis during severe overdose causes muscle breakdown. Chronic immobility from sedation increases bone loss (osteoporosis), muscle atrophy. IV use sites experience muscle and tendon damage. Withdrawal causes severe muscle and joint aches.

Effects

Desired Effects

• Euphoria (intense pleasure rush, especially IV)
• Pain relief (analgesia)
• Relaxation and anxiolysis
• Sedation and mental clouding
• Sense of warmth and comfort
• Cough suppression

Negative Effects

• Respiratory depression (dose-dependent, potentially fatal)
• Nausea and vomiting (especially initial use)
• Constipation (very common, persistent)
• Pupil constriction (pinpoint pupils)
• Hypotension (dangerous drop in blood pressure)
• Bradycardia (dangerously slow heart rate)
• Miosis (constricted pupils)
• Urinary retention

Rare but Serious

• Severe respiratory depression (death)
• Pulmonary edema (fluid in lungs, often fatal)
• Circulatory collapse
• Anaphylaxis (rare, but can occur)
• Seizures (particularly with tramadol; buprenorphine can lower seizure threshold)
• Rhabdomyolysis (muscle breakdown from immobility/overdose)

Drug Interactions

Detection Times

Opioids are included in standard drug panels. Synthetic opioids may require specific testing.

Urine

Standard immunoassay for opiates. Synthetics (fentanyl) need specific tests. Detection window: up to 4 days.

Blood

Short blood detection window for most opioids. Detection window: up to 2 days.

Hair

Hair follicle testing detects opioid use over months. Detection window: up to 90 days.

Saliva

Oral fluid testing for recent use. Detection window: up to 3 days.

Harm Reduction Tips

• NEVER use alone. Always use with someone present who is trained in overdose recognition and naloxone administration. Overdose deaths frequently occur alone without witness to call for help.

• Carry naloxone (Narcan) at all times and teach others to use it. Naloxone is freely available at most pharmacies, health departments, and harm reduction programs without prescription in most US states. Know how to administer it — both intranasal (easiest) and IM (if available). Naloxone reverses overdose but only works for 30-90 minutes; call 911 after administration.

• Use fentanyl test strips on ALL supplies before consuming. Fentanyl is now present in heroin, cocaine, counterfeit pills, and other drugs. Test strips can detect fentanyl, but do not detect all fentanyl analogs (xylazine, carfentanil). Even negative tests are not 100% safe — always assume drugs are contaminated.

• Start LOW and go SLOW, especially after periods of non-use. Tolerance drops rapidly (within days); users who resume at previous doses often fatally overdose. Reduce expected dose by 50% after any break (week, jail, treatment, hospitalization). Wait 15 minutes between doses.

• NEVER mix with depressants — absolutely no alcohol, benzodiazepines, barbiturates, or other CNS depressants. This is the most common cause of overdose death. If using multiple substances, delay dosing between them.

• Use the lowest effective dose. Seek medication-assisted treatment (MAT) with buprenorphine or methadone. These medications satisfy cravings, prevent withdrawal, and can reduce overdose risk by 50%.

• Avoid injection when possible; insufflation and oral use have lower overdose risk. If injecting: use sterile equipment (never share needles/cookers/filters/water), rotate injection sites, use proper injection technique. Access syringe service programs for sterile equipment.

• Consider transition to buprenorphine or methadone. These are long-acting synthetic opioids that prevent withdrawal, reduce cravings, and have much lower overdose risk than heroin/illicit fentanyl. Suboxone (buprenorphine + naloxone) can be prescribed in office-based practice.

• Recognize overdose signs immediately: pinpoint pupils, blue/gray lips and fingertips, unconsciousness, gurgling/snoring breathing (pulmonary edema), slow/stopped breathing, unresponsiveness. Do NOT wait — call 911 immediately. Overdose can progress rapidly.

• Know your local naloxone/Narcan distribution — most areas have free or low-cost programs. Download the Naloxone Finder app or contact your local health department. Train family and friends on administration.

• Avoid taking opioids with benzodiazepines unless medically supervised. If both are prescribed, ensure prescriber awareness and discuss overdose risk. Alcohol + opioids is the second-deadliest combination after opioids + benzodiazepines.

• Be aware of xylazine contamination ('Tranq Dope'). Xylazine causes severe sedation and is not reversed by naloxone alone. May require medical treatment. Signs: extreme sedation, necrotic wounds, withdrawal symptoms.

• Have a overdose action plan: post naloxone instructions, teach friends to recognize overdose, agree on who to call, know legal protections (Good Samaritan laws protect callers in 36+ US states from prosecution).

• Access mental health and addiction services. Opioid use disorder is a treatable medical condition. MAT combined with counseling has the highest success rates for sustained recovery.

• Seek regular health monitoring: hepatitis C/B and HIV testing (especially if injecting), TB screening, STI testing, dental care, vaccination (Hep B, flu, COVID). Establish healthcare relationships to discuss harm reduction.

Withdrawal Symptoms

Severity: Dangerous

Short-acting (heroin, oxycodone): onset 8-24 hours, peak 36-72 hours, acute phase 5-7 days. Long-acting (methadone): onset 36-72 hours, peak 4-6 days, acute phase 14-21 days. Protracted withdrawal (cravings, mood, sleep): months to over a year.

Physical

• Muscle aches and bone pain
• Diarrhea and abdominal cramps
• Nausea and vomiting
• Goosebumps and chills ('cold turkey')
• Runny nose and tearing eyes
• Yawning
• Dilated pupils
• Restless legs
• Insomnia

Psychological

• Intense cravings
• Severe anxiety and dysphoria
• Agitation and irritability
• Depression
• Inability to feel pleasure (anhedonia)

Emergency Information

Call 911 If:

• ANY suspected overdose — do not hesitate or wait. Even if unsure, call. Paramedics are trained for this.
• Breathing is slow (fewer than 8 breaths per minute), shallow, or completely stopped
• Person is unresponsive to loud noises or physical touch
• Lips, fingertips, or face turns blue or gray (cyanosis)
• Skin is cold, clammy, or pale
• Pupils are pinpoint-sized
• Person is making gurgling or snoring sounds (suggests fluid in lungs)
• Person is choking, foaming at mouth, or has vomited
• Person is seizing
• Pulse is very slow, irregular, or absent
• Person used fentanyl or counterfeit pills (extremely high overdose risk)
• Person mixed opioids with alcohol, benzodiazepines, or other depressants
• This is the person's first time using or they used after a break (tolerance reset)

Warning Signs

• Pinpoint pupils (constricted to pinhead size)
• Blue or gray lips, fingertips, or skin (cyanosis)
• Slow, shallow, or completely stopped breathing
• Gurgling or snoring sounds (suggests pulmonary edema/fluid in lungs)
• Unresponsiveness to sound or touch
• Loss of consciousness
• Limp body
• Severe bradycardia (slow pulse) or absent pulse
• Pale or clammy skin
• Seizure activity
• Choking or vomiting while unconscious

What To Do

1. CALL 911 IMMEDIATELY — do not delay. Most overdose deaths occur when no one calls emergency services.
2. Administer naloxone (Narcan) immediately if available — intranasal or IM. Use every 2-3 minutes if no response after first dose. Have multiple doses available as redosing may be necessary.
3. Place person in recovery position (on their side) if unconscious and breathing — prevents aspiration if vomiting occurs.
4. Start rescue breathing if trained and person is not breathing: pinch nose, give 2 rescue breaths every 5 seconds. Continue until emergency services arrive or person revives.
5. Do NOT leave the person alone — stay until emergency services arrive.
6. Perform rescue breathing or CPR if trained — chest compressions can help distribute naloxone and maintain circulation.
7. Stay calm and provide clear location information to 911 dispatcher.
8. If naloxone reverses overdose, person may become aggressive due to sudden withdrawal symptoms — remain calm and safe.
9. Tell paramedics what substance was used (if known), when, how much, and route. Full honesty helps treatment.
10. Ensure person is transported to hospital even if they initially revive with naloxone — overdose symptoms can return when naloxone wears off (30-90 minutes).