Major Drugs of Abuse: Adulterants, Overdose, Withdrawal, and Treatment
Opioids (Heroin, Fentanyl, Prescription Opioids)
Common Adulterants
Fentanyl and its analogues are the most dangerous adulterants, frequently mixed into heroin, cocaine, and methamphetamine without users' knowledge, dramatically increasing overdose risk. 1 Counterfeit prescription opioid tablets (oxycodone, hydrocodone) also contain illicit fentanyl. 1
Overdose Symptoms
- Respiratory depression (the primary cause of death) 2
- Central nervous system depression with decreased level of consciousness 2
- Miosis (pinpoint pupils) 2
- Bradycardia and hypotension 2
- Coma 1
Overdose Treatment
- Naloxone is highly effective for reversing acute opioid overdose and should be administered immediately 2
- Begin with 0.04-0.4 mg, escalating to 2 mg if inadequate response 2
- Higher doses may be required for fentanyl or massive overdoses 2
- Assisted ventilation with bag-mask before naloxone administration 2
- Critical pitfall: Naloxone duration (45-70 minutes) is shorter than long-acting opioids like methadone, requiring repeat dosing and extended observation 2
Withdrawal Symptoms
- Sweating, piloerection, mydriasis (dilated pupils) 2
- Lacrimation, rhinorrhea, yawning 2
- Vomiting, diarrhea, abdominal cramping 2
- Tachycardia, hypertension, fever, tachypnea 2
- Restlessness, irritability, myalgias, increased pain sensitivity, anxiety 2
- Onset within 12 hours of discontinuation 2
Withdrawal Treatment
Medication-assisted therapy with methadone, buprenorphine, or extended-release naltrexone is the evidence-based standard and should be initiated promptly. 2 Buprenorphine/naloxone (target dose 16 mg daily) combined with counseling significantly reduces relapse, prevents overdoses, and prevents HIV transmission. 3 These medications should not be withheld for patients receiving antiretroviral therapy or hepatitis C treatment due to minimal drug-drug interactions. 2
CNS Stimulants (Cocaine, Methamphetamine, Amphetamines)
Common Adulterants
Fentanyl is increasingly found in cocaine and methamphetamine, creating unexpected opioid overdose risk in stimulant users. 1
Overdose Symptoms
- Tachycardia and hypertension 2
- Hyperthermia 2
- Seizures 2
- Agitation, psychosis, hallucinations 4
- Cardiac arrhythmias 2
- Myocardial infarction and stroke 2
Overdose Treatment
- Benzodiazepines for agitation and seizures 4
- Antipsychotics (haloperidol, quetiapine, or ziprasidone) for severe psychosis 4
- Cooling measures for hyperthermia 2
- Cardiac monitoring and treatment of arrhythmias 2
- No specific antidote exists 2
Withdrawal Symptoms
- Increased appetite and hyperphagia 5
- Psychomotor agitation or retardation 5
- Depression (with suicide risk) 6
- Fatigue and hypersomnia 5
- Anxiety 5
Withdrawal Treatment
Gradual tapering by approximately 25% every 1-2 weeks is recommended over abrupt discontinuation. 5 Provide symptomatic medications for agitation and sleep disturbance. 5 Monitor closely for depression or psychosis requiring immediate specialist consultation. 5 Conduct withdrawal in a supportive environment with regular monitoring. 5 Dexamphetamine is explicitly contraindicated for stimulant withdrawal. 5 Contingency management (behavioral incentivized treatment) is the most efficacious intervention for stimulant use disorders. 2
CNS Depressants (Benzodiazepines, Barbiturates, Alcohol)
Benzodiazepines
Overdose Symptoms
- Sedation and respiratory depression 6
- Confusion and ataxia 6
- Severe respiratory depression when combined with opioids or alcohol 7
Overdose Treatment
- Supportive care with airway management 2
- Flumazenil is NOT recommended in chronic benzodiazepine users due to seizure risk 2
- Benzodiazepines should be tapered, not reversed, in dependent patients 7
Withdrawal Symptoms
- Anxiety, agitation, tremors 2
- Headaches, sweating, insomnia 2
- Nausea, vomiting, myoclonus, muscle cramps 2
- Hyperactive delirium 2
- Seizures (potentially life-threatening) 2
Withdrawal Treatment
Gradual taper is essential; abrupt discontinuation can cause life-threatening seizures. 2 Long-acting benzodiazepines (diazepam, chlordiazepoxide) are preferred for tapering. 8 In patients on concurrent opioid therapy, benzodiazepine cessation is preferred, but gradual tapering to the lowest effective dose may be appropriate when cessation is not feasible. 7
Alcohol
Overdose Symptoms
- Central nervous system depression 2
- Respiratory depression 2
- Hypotension 2
- Hypothermia 2
- Metabolic acidosis 2
Overdose Treatment
- Supportive care with airway protection 2
- Intravenous fluids and glucose 2
- Thiamine administration to prevent Wernicke encephalopathy 2
Withdrawal Symptoms
Delirium tremens (DTs) typically begins 48-72 hours after the last drink, with peak severity at 3-5 days. 8 Initial symptoms (6-24 hours) include tachycardia, hypertension, tremors, hyperreflexia, irritability, anxiety, headache, nausea, and vomiting. 8 DTs manifest as severe confusion, hallucinations, autonomic instability, and seizures. 8
Withdrawal Treatment
Benzodiazepines should be initiated early (within 6-24 hours) to prevent progression to DTs, not just to treat established DTs. 8 Long-acting benzodiazepines (diazepam, chlordiazepoxide) provide superior protection against seizures and delirium compared to shorter-acting agents. 8 Naltrexone and acamprosate are FDA-approved for alcohol use disorder maintenance treatment. 2 Critical pitfall: The highest DTs risk is days 2-5, not the first day; prophylactic treatment during early withdrawal is essential. 8
Synthetic Cannabinoids ("Spice," "K2")
Overdose Symptoms
- Agitation and psychosis 4, 9
- Tachycardia and hypertension 4
- Seizures 4
- Acute kidney injury 4
- Nausea and vomiting 4
Overdose Treatment
Withdrawal
Withdrawal symptoms are less well-defined than traditional cannabis but may include irritability, anxiety, and sleep disturbances. 4
Synthetic Cathinones ("Bath Salts")
Overdose Symptoms
- Severe agitation and violent behavior 9
- Hyperthermia 9
- Tachycardia and hypertension 9
- Psychosis and hallucinations 9
- Seizures 9
- Rhabdomyolysis 9
Overdose Treatment
- Benzodiazepines for agitation and seizures 4
- Cooling measures for hyperthermia 4
- Antipsychotics (haloperidol, quetiapine, ziprasidone) for psychosis 4
- Supportive care with intravenous fluids 4
Dissociative Agents (Ketamine, PCP, Novel Analogues)
Overdose Symptoms
- Dissociation and altered perception 9
- Hypertension and tachycardia 9
- Respiratory depression (especially ketamine) 6
- Agitation and psychosis 9
- Nystagmus 9
Overdose Treatment
- Benzodiazepines for agitation 4
- Supportive care with airway management 4
- Quiet environment to reduce stimulation 4
Emerging Opioids (Desomorphine/"Krokodil," Kratom/Mitragynine)
Desomorphine
Overdose Symptoms
Similar to other opioids: respiratory depression, CNS depression, miosis. 4
Overdose Treatment
Naloxone is effective as an antidote. 4
Unique Complications
Severe tissue necrosis at injection sites due to toxic adulterants in street preparation. 4
Kratom (Mitragynine)
Overdose Symptoms
Opioid-like effects with respiratory depression at high doses. 9
Overdose Treatment
Supportive care; naloxone may have partial efficacy. 9
Animal Tranquilizers (Xylazine)
Xylazine is an emerging adulterant in the illicit opioid supply, particularly with fentanyl. 2 It causes severe sedation, respiratory depression, and bradycardia. 2 Xylazine is not reversed by naloxone, requiring prolonged supportive care. 2 Chronic use causes severe skin ulcerations and necrosis. 2
General Harm Reduction Strategies
All patients who inject drugs should be offered:
- Naloxone dispensation and training 2
- Referral to syringe service programs 2, 10
- Fentanyl and xylazine test strips 2
- Safe injection site information where available 2
- HIV and hepatitis C screening 10
- Integrated substance use disorder treatment with pharmacotherapy 2
Critical principle: Harm reduction services should be offered to all who report drug use, regardless of readiness for abstinence-based treatment. 2