Substance Use Disorders
Substance misuse is usually taught drug by drug, which produces a long list that is easy to confuse under examination pressure.
Two questions reduce it to a pattern.
What does intoxication look like, and what does withdrawal look like? For almost every drug, withdrawal is the mirror image of intoxication. Opioids constrict pupils and cause constipation, so withdrawal dilates pupils and causes diarrhoea. Alcohol sedates, so withdrawal produces tremor, agitation and seizures. Once you know the acute effect, you can derive the withdrawal syndrome instead of memorising it.
Which withdrawals are dangerous? This is the asymmetry that decides management, and it is counterintuitive.
Alcohol and benzodiazepine withdrawal can be fatal. Opioid withdrawal is intensely unpleasant but is not usually life-threatening, despite being the withdrawal that patients and families fear most.
A third idea underpins treatment. Dependence is a chronic relapsing condition, not a moral failure or a single event, so relapse is a feature of the illness to be planned for rather than evidence that treatment has failed.
1. Defining the Terms
Tolerance is a reduced effect from the same dose, or the need for a higher dose for the same effect.
Withdrawal is a characteristic syndrome on stopping or reducing use.
Dependence combines these with impaired control, craving, salience of use over other activities, and continued use despite harm.
Harmful use is a pattern causing damage to physical or mental health without meeting criteria for dependence.
The distinction that matters clinically is between physical dependence and addiction. A patient on long-term opioids for cancer pain may be physically dependent without being addicted, since addiction requires compulsive use and loss of control rather than simply a withdrawal syndrome on stopping.
2. Alcohol
Alcohol accounts for more medical morbidity than all other drugs of misuse combined, and the questions cluster around withdrawal and around thiamine.
Withdrawal by timeline
| Time after last drink | Feature |
|---|---|
| 6 to 12 hours | Tremor, sweating, anxiety, nausea |
| 12 to 24 hours | Alcoholic hallucinosis, typically visual, with clear consciousness |
| 24 to 48 hours | Withdrawal seizures, generalised tonic-clonic |
| 48 to 72 hours and beyond | Delirium tremens |
Alcoholic hallucinosis occurs in clear consciousness, which distinguishes it from delirium tremens, where consciousness is clouded and orientation is lost.
Delirium tremens carries significant mortality even with treatment, and considerably more without. It presents with clouded consciousness, disorientation, marked autonomic overactivity, severe tremor and vivid hallucinations, characteristically visual and often of small animals.
Treatment is with benzodiazepines in adequate doses, guided by symptom severity rather than by fixed schedules, alongside fluids, electrolytes and thiamine.
Wernicke and Korsakoff
Wernicke encephalopathy is the acute, reversible thiamine deficiency syndrome, with the classic triad of confusion, ataxia and ophthalmoplegia.
The triad is present in a minority of cases, which is the point most often missed. Waiting for all three before treating is the reason the condition progresses.
Korsakoff syndrome is the chronic, largely irreversible consequence, with anterograde amnesia, confabulation and relatively preserved other cognitive functions.
Two prescribing rules follow, and both are examined.
Give thiamine before glucose. Administering glucose to a thiamine-deficient patient consumes the remaining thiamine in glycolysis and can precipitate Wernicke encephalopathy.
Treat on suspicion, parenterally. Oral thiamine is poorly absorbed in alcohol dependence, and the cost of treating unnecessarily is negligible against the cost of missing it.
Long-term management
Disulfiram works by aversion, inhibiting aldehyde dehydrogenase so that alcohol produces acetaldehyde accumulation with flushing, vomiting and headache. It requires motivation and supervision.
Acamprosate reduces craving by modulating glutamatergic transmission. Naltrexone, an opioid antagonist, reduces the rewarding effect of drinking and is useful for reducing heavy drinking.
3. Opioids
Intoxication produces pinpoint pupils, respiratory depression and reduced consciousness, and the triad is what identifies overdose.
Naloxone reverses it, and the practical caution is that its half-life is shorter than that of most opioids, so a patient who responds may deteriorate again as it wears off and requires observation or repeated dosing.
Withdrawal is the mirror image: dilated pupils, lacrimation, rhinorrhoea, yawning, piloerection, abdominal cramps, diarrhoea, muscle aches and intense craving.
It is not usually life-threatening, which matters because fear of withdrawal drives continued use and because withdrawal alone is a poor treatment target.
Why detoxification alone fails
Detoxification without maintenance treatment has high relapse rates and increases overdose risk, because tolerance falls during abstinence while the habitual dose does not change in the person's memory.
Opioid substitution therapy with methadone or buprenorphine is the evidence-based treatment, reducing illicit use, criminal activity, transmission of blood-borne viruses and, critically, mortality.
Buprenorphine is a partial agonist with a ceiling effect on respiratory depression, which makes it safer in overdose, but it can precipitate withdrawal if given while a full agonist is still occupying receptors.
4. Other Substances
| Substance | Intoxication | Withdrawal |
|---|---|---|
| Cannabis | Conjunctival injection, tachycardia, increased appetite, altered time sense | Irritability, insomnia, appetite loss, craving |
| Stimulants | Dilated pupils, tachycardia, hypertension, hyperthermia, psychosis | Hypersomnia, hyperphagia, dysphoria, "crash" |
| Benzodiazepines | Sedation, ataxia, slurred speech, anterograde amnesia | Anxiety, insomnia, tremor, seizures |
| Inhalants | Euphoria, disinhibition, then depression; perioral dermatitis | Mild, largely psychological |
| Nicotine | Alertness | Irritability, poor concentration, appetite increase, craving |
Stimulant intoxication is the one that mimics psychiatric illness most closely, producing paranoid psychosis with tactile hallucinations that can be indistinguishable from schizophrenia except by history, urine testing and the time course of resolution.
Cannabis is examined for its association with psychosis, which is dose-related, stronger with early adolescent use and with high-potency preparations, and stronger in those with genetic vulnerability.
Inhalant misuse is a particular problem among street children in Indian cities, using correction fluid, adhesives and petrol, and it causes cardiac arrhythmia, renal tubular acidosis and irreversible neurological damage.
Benzodiazepine dependence
This deserves separating because it is usually iatrogenic and because the withdrawal is dangerous.
Dependence develops within weeks of regular use, and tolerance to the anxiolytic effect appears well before tolerance to the sedative effect, so patients escalate the dose to regain an effect that will not return.
Withdrawal mirrors alcohol withdrawal because the mechanism is the same, with anxiety, insomnia, tremor, perceptual disturbance, and seizures at the severe end. Long-acting agents produce a later and more prolonged syndrome than short-acting ones.
Withdrawal is managed by conversion to a long-acting agent such as diazepam and a slow taper, often over months rather than weeks, and abrupt cessation is unsafe.
The most useful preventive point is that the risk is created at the moment of prescribing, so short courses with a stated end date, and an explicit conversation about what the drug is and is not for, prevent the problem more effectively than any withdrawal protocol.
5. The Medical Consequences That Present Elsewhere
Substance-related disease reaches other specialties long before it reaches a psychiatrist, and recognising the pattern is what allows earlier intervention.
Alcohol
Hepatic disease progresses from steatosis, which is reversible, through alcoholic hepatitis to cirrhosis. A ratio of aspartate to alanine aminotransferase above two is characteristic, which is the reverse of most other liver disease.
Pancreatitis, both acute and chronic, is a leading alcohol-related surgical presentation in India, and chronic disease brings exocrine insufficiency and diabetes.
Cardiomyopathy, hypertension and atrial fibrillation are cardiac consequences, with "holiday heart" describing arrhythmia after a binge.
Peripheral neuropathy, cerebellar degeneration and central pontine myelinolysis complete the neurological list, the last being a consequence of correcting hyponatraemia too rapidly rather than of alcohol itself.
Fetal alcohol spectrum disorder produces growth restriction, characteristic facies with a smooth philtrum and thin upper lip, and neurodevelopmental impairment. No safe threshold in pregnancy has been established.
Injecting drug use
Blood-borne virus transmission of HIV, hepatitis B and hepatitis C is the dominant risk, alongside infective endocarditis characteristically affecting the tricuspid valve, deep vein thrombosis, abscess and cellulitis at injecting sites.
This is the biological argument for needle and syringe programmes, which reduce transmission without increasing injecting, and it is why harm reduction is a public health intervention rather than a concession.
Tobacco
Tobacco causes more deaths in India than any other substance, and smokeless forms dominate, driving the country's exceptionally high burden of oral cavity cancer alongside oral submucous fibrosis from areca nut.
Nicotine replacement, bupropion and varenicline all increase cessation rates, and brief advice from any clinician has a small but genuine effect that scales across a population.
The Indian picture
The National Survey on Extent and Pattern of Substance Use in India established the scale, and the ordering is worth carrying.
Alcohol is the most used psychoactive substance after tobacco, with a substantial proportion of users meeting criteria for harmful or dependent use. Cannabis follows, and opioid use in India is proportionally higher than global averages, with pharmaceutical opioids and heroin both contributing.
Two structural problems dominate service delivery. The treatment gap is very large, with only a small minority of people with dependence receiving any treatment, and it is widest for alcohol despite alcohol causing the greatest burden.
Stigma keeps families from seeking help early, and the same stigma leads to treatment being sought in crisis rather than in the long maintenance phase where it works best.
Opioid substitution therapy is delivered through government programmes alongside the National Drug Dependence Treatment Centre network, and expansion of these services rather than the invention of new treatments is the principal lever available.
6. Assessment and Treatment Principles
Screening
CAGE asks about attempts to Cut down, Annoyance at criticism, Guilt about drinking and the need for an Eye-opener. AUDIT is more sensitive and detects hazardous drinking rather than only dependence.
Screening should be routine rather than triggered by suspicion, because the patients who look least likely are often those in whom detection changes most.
The stages of change
Precontemplation, contemplation, preparation, action, maintenance and relapse.
The value of the model is that it matches the intervention to the stage. Giving advice about stopping to a patient in precontemplation produces resistance, whereas exploring ambivalence moves them forward. Motivational interviewing works by resolving ambivalence rather than by supplying information the patient already has.
Relapse is included in the model deliberately, because it is the expected course of a chronic relapsing condition and not a failure of the patient or the treatment.
Harm reduction
Needle and syringe programmes, opioid substitution therapy, supervised consumption and naloxone distribution reduce mortality and blood-borne virus transmission.
The underlying principle is that reducing harm in someone still using is a legitimate goal, and that insisting on abstinence as a precondition for care excludes the people at highest risk.
India's National Mental Health Programme and the National Drug Dependence Treatment Centre framework support these approaches, and opioid substitution therapy is delivered through government programmes.
7. Worked Examples
Example 1. A man admitted after a fall becomes tremulous and anxious 10 hours later, then has a generalised seizure at 30 hours and by day three is disoriented, sweating profusely and seeing insects on the walls. Explain the sequence.
This is the standard timeline of alcohol withdrawal, and each stage is predictable from the last drink.
Tremor, sweating and anxiety at 6 to 12 hours reflect the loss of alcohol's positive modulation at GABA-A receptors, leaving an unopposed excitatory state. Withdrawal seizures characteristically occur at 24 to 48 hours. Delirium tremens follows at 48 to 72 hours or later, with clouded consciousness, disorientation, marked autonomic overactivity and vivid visual hallucinations, classically of small animals.
The distinction from alcoholic hallucinosis matters: that occurs earlier, at 12 to 24 hours, and crucially in clear consciousness with preserved orientation.
Management is benzodiazepines titrated to symptom severity, fluids and electrolytes, and parenteral thiamine. Delirium tremens carries significant mortality even with treatment, so this is an admission requiring close monitoring rather than a ward problem.
Example 2. A malnourished man with alcohol dependence is brought unconscious. The intern sets up an intravenous dextrose infusion. Comment.
Thiamine should be given before glucose.
Thiamine is a cofactor for pyruvate dehydrogenase and transketolase, both central to glucose metabolism. Administering a glucose load to a thiamine-depleted patient consumes the small remaining thiamine reserve in glycolysis, and this can precipitate or worsen Wernicke encephalopathy.
Wernicke encephalopathy classically presents with confusion, ataxia and ophthalmoplegia, but the complete triad is present in only a minority of cases, so waiting for it before treating is the commonest reason the condition is missed and allowed to progress to the largely irreversible Korsakoff syndrome.
Thiamine is given parenterally because oral absorption is unreliable in alcohol dependence, and it is given on suspicion rather than on confirmation, since the risk of treatment is negligible against the cost of missing it.
Example 3. A patient dependent on heroin completes a 10-day inpatient detoxification and is discharged abstinent. Two weeks later he dies of an overdose after using his usual amount. Explain.
Loss of tolerance is what killed him.
Chronic opioid use produces marked tolerance to respiratory depression, so a habitual user can survive doses that would be fatal to a naive person. Abstinence reverses that tolerance within days to weeks, but it does not change the dose the person remembers as normal. On relapse, the familiar amount is now an overdose.
This is why the period immediately after detoxification, after prison release and after hospital discharge carries the highest overdose mortality in this population, and why detoxification alone is not merely ineffective but actively raises risk.
The evidence-based alternative is opioid substitution therapy with methadone or buprenorphine, which reduces illicit use, blood-borne virus transmission and, most importantly, mortality. Take-home naloxone with training for the patient and family is a further specific intervention.
Example 4. A 24-year-old is brought agitated and paranoid, convinced insects are crawling under his skin. Pupils are dilated, he is tachycardic, hypertensive and febrile. How do you approach this?
This picture suggests stimulant intoxication, with amphetamine or cocaine the likely agents.
Several features separate it from a primary psychotic illness. The sympathomimetic signs of mydriasis, tachycardia, hypertension and hyperthermia are not features of schizophrenia. Tactile hallucinations, particularly formication, are characteristic of stimulant use. And the onset is acute rather than developing over weeks.
Assessment includes urine toxicology, temperature and cardiovascular monitoring, creatine kinase for rhabdomyolysis, and an electrocardiogram, while considering hyponatraemia and intracranial haemorrhage.
Management is supportive with benzodiazepines as first-line for agitation, active cooling for hyperthermia and fluids. Antipsychotics are used cautiously since they lower the seizure threshold and impair thermoregulation. The confirming feature is resolution over hours to days, which distinguishes it from a primary psychosis.
Example 5. A patient with alcohol dependence says he knows he drinks too much but has no intention of stopping. The doctor gives him a leaflet about liver damage and advises him to stop. Comment.
The intervention is mismatched to the stage.
He is in contemplation, aware of the problem but ambivalent about change, and information about harm is unlikely to add anything he does not already know. Direct advice to stop typically produces the patient defending his drinking, which strengthens rather than weakens his commitment to it.
Motivational interviewing works differently. It explores ambivalence rather than resolving it for the patient, elicits from him the reasons for change rather than supplying them, avoids argument, and lets him articulate the discrepancy between his drinking and his own goals.
The stages of change model matters because it matches intervention to readiness. It also normalises relapse as part of a chronic relapsing condition rather than as evidence of failure, which affects both how the patient is treated and whether he returns.
Summary
Withdrawal is usually the mirror image of intoxication.
Alcohol and benzodiazepine withdrawal can be fatal; opioid withdrawal usually is not.
Dependence is a chronic relapsing condition, so relapse is planned for rather than treated as failure.
Physical dependence is not the same as addiction.
Alcohol withdrawal: tremor at 6 to 12 hours, hallucinosis at 12 to 24, seizures at 24 to 48, delirium tremens after 48.
Alcoholic hallucinosis occurs in clear consciousness; delirium tremens does not.
Delirium tremens carries significant mortality even when treated.
Wernicke encephalopathy is confusion, ataxia and ophthalmoplegia, but the full triad is uncommon.
Give thiamine before glucose, parenterally, and on suspicion.
Korsakoff syndrome is anterograde amnesia with confabulation and is largely irreversible.
Disulfiram works by aversion; acamprosate and naltrexone reduce craving and reward.
Opioid overdose is pinpoint pupils, respiratory depression and reduced consciousness.
Naloxone has a shorter half-life than most opioids, so the patient must be observed.
Opioid withdrawal dilates pupils and causes diarrhoea, lacrimation and piloerection.
Detoxification alone raises overdose risk by reducing tolerance without changing the remembered dose.
Opioid substitution therapy reduces illicit use, viral transmission and mortality.
Buprenorphine has a ceiling on respiratory depression but can precipitate withdrawal.
Stimulant intoxication mimics psychosis but adds sympathomimetic signs and tactile hallucinations.
Inhalant misuse among street children causes arrhythmia, renal tubular acidosis and neurological damage.
Match the intervention to the stage of change, and treat harm reduction as a legitimate goal.
