Major Drugs of Abuse and Their Management

Learning objectives

• Classify major psychoactive substances by their predominant CNS and physiological effects.
• Recognise typical intoxication, overdose, toxidromes, and withdrawal syndromes.
• Prioritise emergency assessment logically from point of contact: triage, primary survey (ABCDE), secondary survey, targeted diagnostics, and disposition.
• Outline evidence-based acute care, withdrawal care (including clinical scoring tools like CIWA-Ar and COWS), relapse-prevention treatment and harm reduction.
• Identify and manage emerging or less common substances of abuse including GHB, MDMA, synthetic cathinones, and anticholinergics.
• Understand the modalities, goals, and phases of formal addiction rehabilitation.
• Give a respectful, non-stigmatising clinical explanation of substance use disorders.

1. The clinical map: depressants, stimulants, and perceptual drugs

A psychoactive substance changes mental processes such as consciousness, perception, mood or cognition. It may be legal, prescribed, traditional, commercially sold or illicit. Legal status does not tell us whether a substance is safe, whether it is causing harm, or whether a patient deserves care.

2. First priorities: A logical flow from point of contact

The name of the substance matters, but physiology comes first. A patient with reduced consciousness can deteriorate while staff are still trying to identify what was taken. Approach the patient systematically.

Phase 2: Secondary Survey and Targeted History

Once stable, gather the AMPLE history (Allergies, Medications, Past medical history, Last meal/use, Events leading up):

• What was used, by which route (oral, smoked, insufflated/snorted, injected IV/IM/SC), how much, when, and with whom?
• Was it prescribed? Was there an intention to self-harm, or was the use accidental/recreational? Did bystanders give any home remedies or antidotes before arrival?
• What else was taken: alcohol, sedatives, opioids, stimulants, over-the-counter medicines (like paracetamol/acetaminophen), herbal remedies?
• Usual pattern of use, time of last use, past withdrawal seizures or delirium tremens, previous overdoses and treatment.
• Comorbid illness: epilepsy, liver disease, cardiac disease, pregnancy, HIV/hepatitis/TB risk, underlying psychiatric illness (schizophrenia, bipolar) and medication interactions.

Phase 3: Targeted Investigations

Do not delay resuscitation for lab results. Use clinical findings to guide tests:

• Universal: Capillary glucose, 12-lead ECG (look for QRS widening, QTc prolongation, ischaemia), paracetamol (acetaminophen) and salicylate levels in all intentional self-harm cases.
• Targeted: Pregnancy testing for all women of childbearing age; renal/liver function tests, electrolytes, and creatine kinase (CK) in severe illness, prolonged immobilisation, or hyperthermia (rhabdomyolysis risk).
• Toxicology screens: Use only when the result will change care. A negative urine screen does not exclude exposure (many synthetics don’t show up), and a positive result does not prove current impairment (cannabis can stay positive for weeks).

3. Alcohol (Ethanol)

Alcohol is a CNS depressant that enhances inhibitory GABA signalling and disrupts excitatory glutamate (NMDA), dopamine, and other systems. Acute effects range from disinhibition to coma. Repeated heavy use leads to neuroadaptation, tolerance, dependence, and multi-system organ damage.

Managing alcohol intoxication

• Supportive care: Airway protection (lateral position), close observation, glucose assessment/correction, antiemetics for vomiting, and a safe, supervised environment.
• Differential Diagnosis is crucial: Do not dismiss altered consciousness as “just drunk.” Consider subdural haematoma, sepsis, hypoglycaemia, post-ictal state, stroke, co-ingestion (especially opioids), and methanol/ethylene glycol poisoning.
• Agitation: Requires verbal de-escalation, quiet surroundings, and ruling out hypoxia, hypoglycaemia, head injury or full bladder before chemical sedation is considered.
• Disposition: Assess suicide risk, safeguarding risk, sexual assault risk, and capacity before discharge. Do not allow an impaired patient to drive.

Managing alcohol withdrawal

Withdrawal is a predictable, potentially lethal medical syndrome; it is not a lack of willpower. Assess severity using a validated tool like the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised). People at risk of severe withdrawal, those with serious medical comorbidity, or those without support need monitored/inpatient care.

• Benzodiazepines: The gold standard. They act on GABA receptors to reduce withdrawal distress, prevent seizures, and halt progression to delirium.
  • Long-acting (Diazepam, Chlordiazepoxide): Preferred for smooth tapering, but avoid in severe liver failure or the elderly due to active metabolites.
  • Short-acting (Lorazepam, Oxazepam): Preferred in severe hepatic impairment, advanced age, or respiratory compromise.
• Nutritional Support: Give IV/IM thiamine (Vitamin B1) BEFORE or alongside any IV glucose. Giving glucose without thiamine can precipitate Wernicke encephalopathy (classic triad: confusion, ataxia, ophthalmoplegia/nystagmus). Follow up with folate and multivitamins.
• Electrolytes: Monitor fluid balance and electrolytes. Hypokalaemia and hypomagnesaemia are very common and lower the seizure threshold; correct them aggressively.
• Avoid antipsychotics as monotherapy: Agents like haloperidol lower the seizure threshold and do not address the underlying GABA/Glutamate imbalance. Use them only as adjuncts for severe agitation/hallucinations after adequate benzodiazepine loading.

Pharmacotherapy for relapse prevention

Withdrawal treatment is only detoxification, not definitive treatment. Pharmacotherapy options (prescribed by trained clinicians alongside psychosocial support) include:

• Acamprosate: Modulates NMDA glutamate receptors to reduce craving. Safe in liver disease; requires dose adjustment in renal impairment.
• Naltrexone: Opioid receptor antagonist that reduces the euphoric reward of drinking. Contraindicated in patients needing opioid analgesia or in acute liver failure.
• Disulfiram (Antabuse): Irreversibly inhibits aldehyde dehydrogenase. Drinking alcohol causes a severe, aversive physical reaction (flushing, nausea, hypotension). Requires highly motivated patients.

4. Opioids

Opioids include prescription analgesics (morphine, codeine, tramadol, methadone, fentanyl, buprenorphine) and illicit drugs (heroin). Their overdose danger arises from activation of µ-opioid receptors in the brainstem respiratory centres.

Opioid overdose: immediate management

1. Call for emergency help and assess ABCDEs.
2. Ventilate: Support ventilation with a bag-valve-mask (BVM) attached to high-flow oxygen. This is the most crucial, immediate lifesaving step and prevents hypoxic brain injury while preparing antidotes.
3. Naloxone: Administer naloxone (IV, IM, IN, or SC) according to local protocol. The goal is to restore adequate spontaneous breathing (respiratory rate > 10-12/min), not to suddenly wake the patient up fully, which can trigger severe withdrawal, agitation, and vomiting (aspiration risk).
4. Observe: Naloxone’s half-life (30-90 minutes) is much shorter than most opioids (e.g., methadone lasts >24 hours). The patient must be observed for recurrent respiratory depression (renarcotization) and may require a continuous naloxone infusion.
5. Assess for complications: Check for aspiration pneumonitis, non-cardiogenic pulmonary oedema, compartment syndrome/rhabdomyolysis from lying unconscious, and paracetamol co-ingestion in prescription opioid overdoses.

Opioid withdrawal

Assess severity using the COWS (Clinical Opiate Withdrawal Scale). While extremely distressing, opioid withdrawal is rarely fatal in healthy adults. Treat symptomatically (antiemetics, antispasmodics, clonidine for autonomic hyperactivity, NSAIDs for bone pain).

• Early signs: Yawning, lacrimation, rhinorrhoea, sweating, piloerection (goosebumps – origin of the phrase “cold turkey”).
• Late signs: Dilated pupils, abdominal cramps, severe diarrhoea, bone/muscle aches, anxiety, and insomnia.
• High-risk populations: Danger rises significantly with severe dehydration, pregnancy (risk of foetal distress/loss), serious comorbidity, or concurrent sedative withdrawal.

Long-term management of opioid use disorder

Evidence-based care relies on Opioid Agonist Therapy (OAT), which dramatically reduces mortality, HIV/HCV transmission, and illicit drug use.

• Methadone: Full µ-opioid agonist. Given as a daily supervised liquid dose. High risk of overdose if taken excessively; requires QTc monitoring.
• Buprenorphine: Partial µ-opioid agonist with high receptor affinity. Milder withdrawal profile and ceiling effect on respiratory depression (safer than methadone). Caution: It must only be started when the patient is already in mild-to-moderate withdrawal, otherwise it causes precipitated withdrawal.
• Naltrexone: Long-acting antagonist (oral or monthly injection). The patient must be completely detoxified from opioids for 7-10 days before starting.

Do not abruptly stop established opioid agonist treatment without a robust plan; relapse risk is extremely high, and due to loss of tolerance, a return to previous doses is often fatal.

5. Sedative-hypnotics: Benzodiazepines, Barbiturates, Z-Drugs, and GHB

These drugs generally act by enhancing GABAergic inhibition in the CNS.

Intoxication features

• General Presentation: Drowsiness, slurred speech, ataxia, nystagmus, and reduced consciousness resembling alcohol intoxication.
• Benzodiazepines / Z-Drugs (Zolpidem, Zopiclone): Rarely cause fatal respiratory depression when taken alone orally. However, when mixed with alcohol or opioids, they are highly lethal.
• Barbiturates (Phenobarbital): Have a narrow therapeutic index. They can independently open chloride channels at high doses, leading to profound coma, loss of brainstem reflexes, shock, and profound respiratory depression. Alkalinization of urine can enhance elimination.

GHB and GBL (Gamma-hydroxybutyrate / Gamma-butyrolactone)

• Often known as “liquid ecstasy.” GHB causes profound, sudden-onset coma (often within 15-30 minutes of ingestion).
• The coma is sometimes punctuated by abrupt awakening, severe agitation, or myoclonus.
• Bradycardia, hypothermia, and respiratory depression are common.
• Management: Strict airway control, often requiring intubation for a few hours until the rapidly metabolised drug wears off.

Why routine flumazenil is unsafe

Flumazenil is a competitive benzodiazepine antagonist. While it reverses sedation, it can precipitate intractable seizures or dangerous withdrawal in people with long-term benzodiazepine dependence, underlying epilepsy, or mixed overdoses (especially with tricyclic antidepressants or other pro-convulsants). It is never a routine antidote for an unknown unconscious patient.

Sedative Withdrawal

Anxiety, insomnia, severe tremors, sweating, perceptual disturbance, psychosis, and seizures occur after abrupt cessation.

• Warning: Benzodiazepine, barbiturate, and GHB withdrawal can be rapidly life-threatening.
• Action: Never advise a dependent patient to stop abruptly. Arrange medically supervised, gradual tapering (often switching to a long-acting agent like diazepam first) using a strict local protocol.

6. Stimulants: Cocaine, Amphetamines, Methamphetamine, and Khat

Stimulants increase monoamine activity (dopamine, norepinephrine, serotonin), producing alertness, intense euphoria, reduced appetite, insomnia, and massive sympathetic overactivity.

Management of stimulant intoxication

• De-escalation: Start with a quiet, low-stimulation environment, verbal de-escalation, and close monitoring.
• Sedation: Benzodiazepines are the cornerstone of medical therapy. They calm the patient, reduce heart rate and blood pressure, halt seizures, and decrease heat generation from muscle hyperactivity.
• Temperature Control: Hyperthermia is an absolute emergency. Temperature > 40°C requires rapid, active cooling (ice baths, evaporative cooling) and aggressive IV fluid resuscitation to prevent rhabdomyolysis and multi-organ failure.
• Cardiovascular Care: For cocaine-induced chest pain, use benzodiazepines, oxygen, and nitrates (nitroglycerin). Caution: Pure beta-blockers (like propranolol) have traditionally been avoided in acute cocaine toxicity due to the theoretical risk of “unopposed alpha-adrenergic stimulation” worsening coronary vasospasm and hypertension.
• Restraints: Avoid physical restraint when possible; struggling against restraints causes fatal isometric muscle contractions, worsening hyperthermia and severe lactic acidosis.

Synthetic Cathinones (“Bath Salts”)

These are synthetic derivatives of the stimulant found in khat. They cause extreme sympathetic activation, profound paranoia, “superhuman” strength, and excited delirium syndrome that can last for days, often requiring massive doses of sedatives and ICU admission.

7. Entactogens (MDMA / Ecstasy)

MDMA has both stimulant and hallucinogenic properties, heavily releasing serotonin along with dopamine and norepinephrine. It produces euphoria, emotional openness, and energy.

Specific Risks and Management

• Hyperthermia: Worsened by dancing in hot, crowded clubs. Muscle breakdown (rhabdomyolysis) and renal failure can follow. Treat with aggressive cooling.
• Exercise-Induced Hyponatraemia: MDMA causes inappropriate ADH secretion. Users sweat profusely, feel thirsty, and drink massive amounts of free water, diluting their sodium. This leads to cerebral oedema, seizures, coma, and death. Management: Fluid restriction or hypertonic saline if seizures occur—do NOT give standard hypotonic IV fluids.
• Serotonin Syndrome: Hyperthermia, autonomic instability, altered mental status, and neuromuscular hyperactivity (clonus, hyperreflexia). Treat with supportive care, benzodiazepines, and occasionally serotonin antagonists (cyproheptadine).
• Jaw Clenching (Bruxism): Often seen clinically; users may chew pacifiers or gum to prevent dental damage.

8. Cannabinoids and Synthetic Cannabinoids

Cannabis acts mainly through CB1 and CB2 receptors.

Acute Effects and Complications

• Common effects: Relaxation, altered time perception, impaired memory/coordination, conjunctival injection (red eyes), dry mouth, tachycardia, and increased appetite.
• Psychiatric risk: High-potency products can precipitate severe anxiety, panic attacks, paranoia, or acute psychosis, especially in those with underlying psychiatric vulnerability (e.g., schizophrenia).

Cannabinoid Hyperemesis Syndrome (CHS)

Chronic, daily cannabis users can paradoxically develop CHS: intractable cyclical nausea, vomiting, and abdominal pain.

• Diagnostic clue: The patient reports that symptoms are only relieved by taking compulsively hot showers or baths.
• Management: Standard antiemetics often fail. Treatment includes stopping cannabis, IV hydration, topical capsaicin cream applied to the abdomen, and sometimes haloperidol or droperidol.

9. Hallucinogens, Dissociatives, and Anticholinergics

Classic Hallucinogens (LSD, Psilocybin, Ayahuasca/DMT, Mescaline)

• Act primarily via serotonin 5-HT2A receptors. They massively distort perception, causing visual illusions, synaesthesia (seeing sounds, hearing colours), and profound emotional shifts.
• Management: Most uncomplicated “bad trips” improve with calm reassurance, a safe low-stimulation room, a supportive “sitter” or staff member, and time. If severe agitation occurs, benzodiazepines are the treatment of choice.
• Note: Ayahuasca contains an MAOI; combining it with SSRIs can cause fatal Serotonin Syndrome.

Dissociatives (Ketamine, PCP – Phencyclidine)

• Act via NMDA receptor antagonism. They produce profound detachment from self and environment, intense analgesia, and sometimes severe behavioural disturbance.
• PCP: Classic presentation includes extreme agitation, lack of pain sensation, violent behaviour, and distinct rotary nystagmus.
• Ketamine: Causes a deep dissociative state (“K-hole”). Chronic abuse destroys the bladder lining, causing ketamine-induced ulcerative cystitis (severe pelvic pain, haematuria, contracted bladder).

Anticholinergics (Datura/Jimsonweed, Diphenhydramine abuse)

Block muscarinic acetylcholine receptors. Tox-screen negative delirium is often anticholinergic.

• Toxidrome mnemonic: “Hot as a hare (hyperthermia), blind as a bat (dilated pupils, loss of accommodation), dry as a bone (no sweating, dry mouth), red as a beet (flushed skin), mad as a hatter (delirium/hallucinations), and full as a flask (urinary retention).”
• Management: Treat with cooling, benzodiazepines, and in severe cases (refractory delirium/arrhythmias), physostigmine under careful ECG monitoring.

10. Inhalants

Inhalants include volatile solvents (petrol, glue, paint thinner), aerosols, and gases. They are cheap, highly accessible to children/adolescents, and cause intoxication within minutes by rapidly crossing the blood-brain barrier.

Specific Inhalant Risks:

• Nitrous Oxide (Laughing Gas / Whippets): Causes euphoria and dissociation. Chronic abuse irreversibly inactivates Vitamin B12, leading to severe megaloblastic anaemia and subacute combined degeneration of the spinal cord (profound peripheral neuropathy, loss of proprioception/vibration sense, irreversible paralysis).
• Amyl Nitrite (“Poppers”): Used to enhance sexual pleasure. Relaxes smooth muscle, causing profound hypotension and syncope. Can induce methaemoglobinaemia (cyanosis unresponsive to oxygen; blood appears chocolate brown; treat with methylene blue).
• Aspiration Risk: Do not induce vomiting due to high risk of chemical pneumonitis.

11. Anabolic-Androgenic Steroids

Often abused by athletes and bodybuilders to increase muscle mass.

Effects and Complications

• Physical effects: Severe acne, striae, and premature balding. In men: testicular atrophy, gynecomastia (due to conversion of excess testosterone to oestrogen), and profound hypogonadism upon cessation. In women: virilization (deepened voice, hirsutism, clitoromegaly).
• Systemic risks: Severe dyslipidaemia (low HDL, high LDL), left ventricular hypertrophy, increased risk of myocardial infarction, stroke, deep vein thrombosis, and liver toxicity (peliosis hepatis, hepatic adenomas).
• Psychiatric effects: Mania, irritability, extreme aggression (“roid rage”), and severe depression/suicidality during the withdrawal (crash) phase.

Management requires gentle tapering, psychiatric support, and endocrine monitoring to help the hypothalamic-pituitary-gonadal axis recover.

12. Nicotine and tobacco

Nicotine is highly dependence-producing, binding to nicotinic acetylcholine receptors. Tobacco causes a major, preventable cardiovascular, respiratory, and cancer burden. Shisha is not a harmless alternative, and vaping products can deliver substantial, rapidly absorbed nicotine.

Withdrawal produces intense irritability, low mood, poor concentration, increased appetite, restlessness, and craving that peaks within 2-3 days but can last for weeks.

Smoking/tobacco cessation: practical approach

1. Ask about all tobacco/nicotine products at every relevant contact.
2. Advise clearly, personally, and respectfully that stopping is one of the most powerful health interventions they can make.
3. Assess readiness to quit and level of dependence; set a specific quit date if they are ready.
4. Assist with behavioural support, trigger planning, and pharmacotherapy where available (e.g., Nicotine Replacement Therapy [patches/gum], varenicline, or bupropion).
5. Arrange follow-up: relapse is common and should trigger re-engagement and protocol adjustment, not blame.

13. Harm reduction is clinical prevention

Harm reduction means practical, evidence-based actions that reduce death, infection, injury, and social harm even when a person is not ready or able to stop using immediately. It is not approval of unsafe use; it is the same clinical logic as giving a motorcycle rider a helmet or a diabetic a clean syringe.

14. Rehabilitation and Long-Term Recovery

Medical detoxification treats the physiological crisis of withdrawal, but it is not a cure for addiction. Substance use disorders involve profound changes in brain circuitry, coping mechanisms, and social environments. Long-term rehabilitation addresses the bio-psycho-social roots of the disorder.

Types of Rehabilitation Programs

• Inpatient / Residential Rehab: Patients live at a facility (usually for 30, 60, or 90 days). Best for patients with severe dependence, polysubstance abuse, high risk of withdrawal complications, or those lacking a safe home environment.
• Intensive Outpatient Programs (IOP): Patients attend structured therapy sessions for several hours a day, multiple days a week, but sleep at home. Good for step-down care or those with strong family support.
• Sober Living Homes (Halfway Houses): Transitional, substance-free living environments that bridge the gap between intensive rehab and independent living.

Core Components of Rehabilitation

• Individual Therapy: Cognitive Behavioural Therapy (CBT) helps identify triggers and change maladaptive thought patterns. Dialectical Behaviour Therapy (DBT) is excellent for emotional regulation and distress tolerance.
• Group Therapy and Peer Support: Reduces isolation and builds accountability. Includes 12-Step programs (Alcoholics Anonymous / Narcotics Anonymous) which focus on surrender and spiritual growth, or SMART Recovery, which focuses on self-empowerment and CBT principles.
• Dual Diagnosis Treatment: Over 50% of people with severe substance use disorders have a co-occurring mental illness (depression, PTSD, bipolar disorder). Both must be treated simultaneously; treating one and ignoring the other guarantees relapse.
• Contingency Management: Provides tangible rewards (vouchers, privileges) for positive behaviours (e.g., negative drug screens). Highly effective, especially for stimulant use disorders where medications are lacking.

Aftercare and Relapse Prevention

• Developing a Relapse Prevention Plan: Identifying high-risk situations (people, places, things), recognizing early warning signs of emotional relapse (stress, isolation), and establishing emergency coping strategies.
• Family Therapy: Addiction is a family disease. Healing involves educating the family, setting healthy boundaries, and addressing codependency or enabling behaviours.
• Ongoing Pharmacotherapy: Maintaining MAT (Medication-Assisted Treatment) such as buprenorphine, methadone, naltrexone, or acamprosate as prescribed.

15. A respectful management plan for any substance use disorder

16. High-yield exam and OSCE points

• Opioid overdose: Depressed consciousness + slow breathing + pinpoint pupils (miosis). Priority is ventilation with a BVM, then naloxone titrating to a respiratory rate >12, not full wakefulness.
• Alcohol withdrawal (CIWA-Ar): Tremor, autonomic overactivity, seizures, DTs. Benzodiazepines are first-line. Administer IV thiamine BEFORE glucose to prevent Wernicke encephalopathy.
• Benzodiazepine withdrawal: Potentially fatal (seizures). Do not stop abruptly in a dependent patient; taper gradually. Flumazenil is generally contraindicated in chronic users.
• Stimulant toxicity: Agitation + severe hypertension + mydriasis + dangerous hyperthermia. Cool rapidly, monitor ECG, use benzodiazepines to calm and lower BP. Avoid physical restraints.
• Cannabinoid Hyperemesis Syndrome: Intractable vomiting in chronic users, uniquely relieved by compulsive hot showering.
• MDMA (Ecstasy): Think hyperthermia, severe hyponatraemia from free-water intake, and serotonin syndrome.
• Inhalant use: Think ventricular arrhythmias (sudden sniffing death) and hypoxia. Nitrous oxide causes irreversible B12 deficiency (neuropathy).
• Every patient: Always check a capillary blood glucose, perform an ECG for abnormal vitals, and ask about mixed use, trauma, suicidality, and safeguarding.

Knowledge check

Further study and clinical references

• Supplied class resource: Drug abuse
• WHO: Drugs (psychoactive)
• WHO mhGAP: Management of alcohol withdrawal
• WHO: Community management of opioid overdose
• UNODC/WHO: International standards for treatment of drug use disorders