Misuse Of Substance

• Worldwide, ~275 million people used drugs at least once in 2020 (UNODC World Drug Report 2023)
• Cannabis is the most widely used drug globally, followed by opioids, amphetamines, and cocaine
• Substance use disorders account for a significant burden of disability-adjusted life years (DALYs), particularly through opioid-related mortality, alcohol-related liver disease, and injection-related infections (HIV, HCV)
• Approximately 10% of people who experiment with drugs will develop dependence ^[2] — this is a critical statistic that underscores the role of individual vulnerability beyond mere exposure

Epidemiology in HK (2017) ^[2]:

• Burden: 6725 in all of HK, with 1535/year being newly reported drug abusers (downgoing trend)
• Demographics: average age of onset 18 years (overall 41 years), M:F ≈ 1:4.4
• Type (descending order): heroin > ice (methamphetamine) > ketamine > hypnotics > cocaine > cannabis

Updated HK trends (Central Registry of Drug Abuse, latest available data ~2023-2024):

• The downward trend in overall reported drug abuse has continued, though methamphetamine (ice) has remained a major concern
• Cannabis has been gaining popularity especially among younger users, reflecting global trends ^[2]
• Ketamine use, once Hong Kong's hallmark party drug, has declined significantly from its peak around 2009-2012
• Cocaine use has remained relatively stable at low levels
• There is an emerging concern about synthetic drugs and non-medical use of prescription drugs (benzodiazepines, opioids)

What substances are involved? ^[1]:

• Alcohol
• Opioids (e.g., heroin, morphine, codeine, methadone)
• Cocaine (e.g., cocaine, crack)
• Amphetamines
• Sedatives, hypnotics, anxiolytics
• Hallucinogens (e.g., LSD, ecstasy)
• Phencyclidine (e.g., PCP, ketamine)
• Inhalants
• Cannabis
• Nicotine
• Caffeine

Key structures ^[1][2]:

• Ventral Tegmental Area (VTA): Contains dopaminergic (DA) cell bodies. This is the "source" of the reward signal. When something pleasurable happens (food, sex, social bonding), VTA neurons fire and release dopamine.
• Nucleus Accumbens (NAc): The "pleasure centre." Receives DA projections from VTA. Activation of the NAc underlies the subjective experience of reward and reinforcement ^[1]. All drugs of abuse, directly or indirectly, increase dopamine availability in the NAc.
• Prefrontal Cortex (PFC) / Orbitofrontal Cortex (OFC): Top-down executive control over impulses, judgment, and decision-making ^[2]. This is the "brake pedal" of the brain. In addiction, PFC function becomes progressively impaired → loss of self-control.
• Amygdala (extended amygdala): Emotional colouring of memory ^[2]. Associates drug-related cues with positive emotional responses (during use) and negative emotional states (during withdrawal). This drives conditioned craving.
• Hippocampus: Contextual information processing ^[2]. Encodes the where/when/who of drug experiences, so that contextual cues (a particular place, person, or even time of day) can trigger craving.
• Anterior Cingulate Cortex (ACC): Involved in craving/preoccupation phase — monitors conflict between desire to use and awareness of harm ^[1].

This is the cornerstone concept. Addiction is not simply "liking drugs" — it is a progressive neuroadaptive process ^[2]:

1. Early use (Impulsive stage): Drug → ↑DA in NAc → positive reinforcement → "I like this"
2. Repeated use: Tolerance develops (need more drug for same effect). Reward system recalibrates — natural rewards (food, social interaction) become less satisfying.
3. Withdrawal/Negative affect stage: When drug wears off, the brain is in a state of dopamine deficit → dysphoria, anxiety, irritability. Negative reinforcement now drives use — "I use to feel normal, not to feel good" ^[2].
4. Craving/Preoccupation stage: Drug use cues are paired with positive emotional response, and abstinence is paired with negative emotional response (classical conditioning involving hippocampus and amygdala) ^[2].
5. Compulsive stage: Diminishing of top-down prefrontal/orbitofrontal control over desire for drug-seeking ^[2]. The PFC — which should be putting the brakes on — is weakened. Simultaneously, there is an increase in striatal activity, indicating a shift from dopamine/reward-based circuitry to a glutamate/habit-based circuitry ^[2]. The behaviour is now automatic, like a deeply ingrained habit, rather than a deliberate choice.

"Cannabis" — from the plant Cannabis sativa. Contains several pharmacologically active substances, the most potent being δ-9-tetrahydrocannabinol (THC) ^[2].

Forms ^[2]:

• Cannabis (weed, marijuana, 大麻, 草) — dried vegetative parts
• Cannabis resin (大麻精) — resin from flowering female plant
• Synthetic cannabinoids (skunk, K2, SPICE) — more potent with ↑↑ THC content

Pharmacology ^[2]:

• Acute: Agonist at cannabinoid receptor CB1 in CNS → ↓ GABA/glutamate, ↑ DA release
• Chronic: Tolerance occurs but withdrawal tends to be mild. Chronic use → downregulation of GABA receptors → ↓ inhibition on DA release → ↑ risk of schizophrenia ^[2]

Medical uses: ↓ chronic pain, ↓ muscle spasms, ↓ N/V in chemotherapy, ↓ anorexia in HIV, ↑ sleep, tics in Tourette syndrome ^[2]

HK context: Uncommon in HK but gaining popularity ^[2], especially among younger demographics reflecting global legalization trends. Cannabis remains illegal in HK.

Physical signs ^[2]:

• Needle tracks, thrombosed veins, wearing long-sleeved shirts in hot weather (to hide injection marks)
• Scars, subcutaneous/deep abscesses
• Hepatitis B/C (from needle sharing)

Behavioural signs ^[2]:

• ↓ self-care, absence from work/occupational decline
• Social isolation
• Minor criminal offences (especially for cash, e.g., theft, prostitution)

Seeking medical attention ^[2]:

• Drug-seeking behaviour (e.g., exaggerating pain for prescriptions)
• Route-related complications (cellulitis, pneumonia, hepatitis)
• Drug-related complications (intoxication, withdrawal)

Establishing time frame: 1st use, daily use, abstinence and relapse ^[2]

Types and quantity of drugs taken according to above time frame ^[2]

Describe a typical drug-using day and the day before consultation ^[2]

S/S of dependence: CANT Control Withdraw ^[2]

Impact: physical, psychological, social ^[2]

(Risky behaviour): dangerous injection (into groin, neck, infected sites), sharing needles ^[2]

Medical impact includes ^[1]:

• Route-related (infections from IV use, nasal septal perforation from snorting, lung damage from smoking)
• Form/substance-related (state of intoxication/withdrawal)
• Chronic use effects
• Self-care deterioration

These are psychiatric syndromes directly caused by the pharmacological effects of the substance. They should resolve with abstinence (though some persist):

Alcohol use can be a cause or effect of other psychiatric disorders ^[2]. Alcohol use can be a maladaptive response to ↓ distress from other psychiatric disorders ^[2]. This "self-medication hypothesis" applies to all substances:

When a patient presents with psychosis in the context of substance use, the differential includes ^[2]:

In real clinical practice — and frequently in exams — patients use multiple substances simultaneously. This creates overlapping toxidromes that are harder to disentangle:

• Alcohol + benzodiazepines: synergistic CNS depression (cross-tolerance exists because both act on GABA-A) — risk of respiratory arrest even at moderate doses of each
• Cocaine + alcohol: produces cocaethylene (a unique metabolite formed only when both are co-ingested), which has its own cardiotoxicity and longer half-life
• Opioids + benzodiazepines: the combination most likely to cause fatal respiratory depression (the epidemic in Western countries)
• Stimulants + depressants ("speedballing" = cocaine + heroin): users try to balance the "up" and "down" — extremely dangerous, unpredictable vital sign fluctuations

• Adolescents: Differentiate substance-induced behavioural change from normal adolescent rebellion, emerging personality disorders (particularly BPD), ADHD, and early psychosis
• Elderly: Differentiate BDZ misuse/dependence from dementia (both cause confusion, memory impairment); differentiate alcohol-related cognitive decline from neurodegenerative dementia; polypharmacy effects

This comes up repeatedly in exams. The key differentiators:

However, the reality is messier: chronic cannabis use can precipitate a primary psychotic disorder (schizophrenia) in genetically vulnerable individuals, meaning the distinction can be impossible to make at first presentation. These patients need follow-up.

Timeline and features (critical for clinical management) ^[2]:

Delirium tremens features ^[2]:

• Delirium: altered, fluctuating consciousness, marked cognitive impairment
• Vivid hallucinations and illusions, e.g., Lilliputian visual hallucinations, formication (tactile hallucination of insects crawling under skin)
• Autonomic hyperactivity: heavy sweating, ↑HR, ↑↑BP, diaphoresis, fever
• Paranoid delusions
• Occurs in 1–4% of hospitalised patients for alcohol withdrawal
• Risk factors: history of DT, chronic alcoholism, concurrent physical illness, withdrawal from CNS depressants, age > 30, prior significant withdrawal symptoms despite ↑BAC ^[2]

Onset depends on half-life: short-acting (heroin) → 6–12h; long-acting (methadone) → 24–36h ^[2]

Features: mydriasis, piloerection, rhinorrhoea, lacrimation, yawning, muscle aches, diarrhoea, nausea, abdominal cramps, intense craving, anxiety, restlessness, insomnia. Peak 36–48h, wanes by 5–7 days. Rarely life-threatening.

Onset: 24–48h (short-acting, e.g., lorazepam) to up to 3 weeks (long-acting, e.g., diazepam) ^[2]

Features: anxiety, irritability, tremor, insomnia, depersonalisation, derealisation, hypersensitivity to stimuli, seizures, delirium. Can be life-threatening (seizures, DTs).

The urine drug screen is the most commonly used and most important investigation ^[2]. It is an immunoassay-based screening test that detects drug metabolites.

Interpretation principles:

• UDS is a screening test — positive results should be confirmed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) for legal or definitive purposes
• False positives occur: e.g., poppy seeds → morphine positive; pseudoephedrine → amphetamine positive; sertraline → BDZ positive
• False negatives occur: drug not in panel, used outside detection window, dilute specimen, synthetic drugs not covered by standard assays
• A positive UDS does not diagnose dependence — it only confirms exposure. Clinical criteria are still needed
• A negative UDS does not rule out substance use — consider timing and detection limits

• Saliva: increasingly used; non-invasive; reflects recent use (hours to 1–2 days)
• Hair: detects use over months (each cm of hair ≈ 1 month of growth); useful for retrospective assessment, forensic/legal cases, or monitoring in treatment programmes
• Sweat patches: worn for days to weeks; integrative measure of use over that period

• Scoring: ≥2 "yes" = positive screen
• ↑ Sensitivity but modest specificity only ^[2] — good for catching cases but has false positives
• Best used as a rapid screening tool, not a diagnostic instrument

• 10-item screening tool by WHO ^[2]
• ↑ Sensitivity + ↑ Specificity, probably most useful ^[2]
• Covers three domains: hazardous alcohol use (questions 1–3), dependence symptoms (questions 4–6), harmful alcohol use (questions 7–10)
• Score 0–40; threshold of ≥8 suggests hazardous or harmful drinking
• Validated across cultures and settings; translated into many languages including Chinese

Aim of treatment: Ideally, complete abstinence with good personal and social adjustment. If this cannot be achieved, then aim for harm reduction. ^[2]

This two-tier approach is pragmatic:

• Complete abstinence is the gold standard for dependent patients — particularly for alcohol, opioids, and benzodiazepines where continued use causes progressive organ damage
• Harm reduction acknowledges reality — some patients are not ready or able to stop completely. Reducing the amount, switching to safer routes (e.g., oral methadone instead of IV heroin), needle exchange programmes, and reducing risky behaviours (sharing needles, driving intoxicated) are all valid intermediate goals

The goal of treatment depends on severity ^[2]:

• Controlled drinking (or controlled use): for those detected early, non-dependent, with minimal health sequelae
• Total abstinence: for those who are dependent, with failed prior attempts at controlled use

Assessment of motivation can be done based on Prochaska and DiClemente's stages of change model ^[2].

Significance: facilitates motivational interviewing to enhance the patient's own motivation ^[2].

This is critical because addiction treatment only works when the patient is internally motivated. Imposing abstinence on a pre-contemplative patient is futile — they'll relapse immediately. Your job is to match the intervention to the stage:

Understanding why people take drugs is important to devise a management plan that can address this reason ^[2]:

• Pleasure-seeking: for the "high and buzz"
• Self-medication: for underlying anxiety/depression, social anxiety, anger, pain, boredom
• Social pressure: peer effect, life events, adversity
• Others: search for meaning or mystical experiences

In practice, flumazenil is used cautiously and infrequently — supportive care with airway management is often preferred over pharmacological reversal in dependent patients.

This is one of the most commonly tested management scenarios. Alcohol withdrawal can kill — it requires structured, protocol-driven management.

Setting — Indications for in-patient detoxification ^[2]:

• Severe dependence (e.g., SADQ > 30)
• History of severe withdrawal symptoms (e.g., seizures, DT)
• Very high alcohol consumption ( > 30 units/day)
• Concomitant BDZ misuse (↑↑ withdrawal severity)
• Significant medical/psychiatric comorbidity

Step-by-step management ^[2]:

BDZ prescribing details ^[2]:

• Indication: symptom-triggered (CIWA-Ar ≥ 8) — this requires intensive monitoring (e.g., Q1h). May be prophylactic if not possible (i.e., fixed-schedule dosing if monitoring resources insufficient) ^[2]
• Choice: prefer long-acting BDZs, e.g., diazepam (Valium), chlordiazepoxide (Librium) ^[2]
  • Why long-acting? They provide a smoother decline in blood levels, reducing breakthrough withdrawal symptoms and the risk of seizures. The drug essentially "auto-tapers" via its long half-life.
  • Oxazepam if severe liver disease present ^[2] — because oxazepam undergoes glucuronidation (Phase II) only, which is preserved even in advanced liver disease, unlike diazepam which requires oxidation (Phase I)

For refractory cases ^[2]:

• Barbiturates or propofol for refractory DT ^[2]
• BDZs, phenobarbital, propofol for status epilepticus ^[2]

Prophylaxis ^[2]:

• Oral chlordiazepoxide; oxazepam if severe liver disease
• Indication: ↑ risk of severe withdrawal (e.g., Hx of seizures/DT) after heavy alcohol consumption, but currently admitted for other reasons with minimal withdrawal symptoms

Opioid withdrawal is rarely life-threatening, but often so distressing that it triggers drug-seeking behaviour ^[2]. Management can be symptomatic or substitution-based:

Symptomatic treatment (for patients NOT going onto maintenance):

Substitution therapy (see Section E below for long-term maintenance):

• Methadone or buprenorphine can be initiated during withdrawal to provide a smooth transition to maintenance treatment
• Buprenorphine must NOT be given until the patient is in moderate withdrawal (typically ≥ 12h after last heroin dose), otherwise it precipitates withdrawal (see below)

Treatment of withdrawal and dependence ^[2]:

• Switch to long-acting BDZ, e.g., diazepam ^[2]
  • Why? Convert all BDZ use to a single long-acting equivalent. Diazepam has a long half-life (~100h including active metabolites) → provides smoother blood levels, easier to taper
• Gradual withdrawal over a period of ≥ 8 weeks, usually lower 1/8 of dose every 2 weeks ^[2]
  • Why so slow? GABA-A receptor recovery takes time. Too-rapid tapering → rebound anxiety, insomnia, seizures
• Withdrawal symptoms are most troublesome when the dose is completely tapered off ^[2] — the final steps are the hardest
• Some patients may continue to experience withdrawal-like symptoms for months to years (prolonged withdrawal) ^[2]

There is no specific pharmacotherapy for stimulant withdrawal — management is primarily supportive ^[2]:

Approach to management of alcohol misuse (NICE 2014) ^[2]:

• For mild dependence: offer a high-intensity psychotherapy
• For moderate/severe dependence: offer acamprosate/PO naltrexone in combination with a high-intensity psychological treatment
• For those with ↑ intake ( > 15 units/day) and/or ≥ 15–30 on SADQ: offer acute treatment vs withdrawal in community or inpatient settings

Understanding the pharmacology of disulfiram from first principles: Normal alcohol metabolism: ethanol → (alcohol dehydrogenase) → acetaldehyde → (aldehyde dehydrogenase / ALDH) → acetate → CO₂ + H₂O. Disulfiram blocks ALDH → acetaldehyde accumulates → toxic reaction. This is essentially the same reaction that occurs naturally in East Asians with the ALDH2 inactivating mutation — the "Asian flush" is a mild form of the disulfiram reaction.

Opioid substitution/maintenance therapy is one of the most evidence-based treatments in addiction medicine:

Treatment of amphetamine dependence can be difficult as the drug effect can be intense ^[2]:

Why is there no good pharmacotherapy for stimulants? Unlike opioids (where you can use a longer-acting opioid as substitution) or alcohol/BDZs (where you can use cross-tolerant GABAergic agents), stimulants act primarily via monoamine release/reuptake blockade. There is no safe "replacement" stimulant that provides a controlled, sustained dopamine effect without the reinforcing rush. Methylphenidate and dexamfetamine have been trialled but results are inconsistent.

• No established pharmacotherapy
• Treatment is entirely psychosocial: CBT, motivational interviewing, contingency management
• Withdrawal is mild and self-limiting; symptomatic treatment (sleep aids, anxiolytics short-term) if needed

• Switch to long-acting BDZ (diazepam), then gradual withdrawal over ≥ 8 weeks (1/8 dose Q2w) ^[2]
• Adjunct CBT for insomnia and anxiety during taper
• After attaining abstinence, 73% and 59% maintain abstinence at 3 and 10 years respectively ^[2]

• Basis: transtheoretical model of behaviour change asserts that there are different levels of readiness to change among individuals ^[2]
• MI assesses readiness for change followed by attempts to build internal motivation to change based on patient's stage ^[2]
• Principles: express empathy, develop discrepancy, roll with resistance, support self-efficacy ^[2]
• Techniques ^[2]:
  • Engage patient thoughtfully by reflective listening
  • Focus on a specific issue to be changed
  • Evoke the patient's own thoughts that motivate them towards change
  • Planning, at least in the conceptual aspect, for changes
• Efficacy: effective at short- and long-term across all substances ^[2]
• Utility: allows patient to generate own arguments and motivation for change; facilitates change especially when patient is ambivalent ^[2]

• Involves ^[2]:
  • Psychoeducation to let patients understand how their thought processes contribute to their behaviour
  • Behavioural treatment to help patients develop new and adaptive ways of behaving and alter their social environment → in turn leads to change in thoughts and emotions
• Efficacy: modest positive effects on substance use ^[2]
• Particularly useful for identifying triggers, developing coping strategies, managing cravings, and addressing comorbid anxiety/depression

• Efficacious for non-dependent, at-risk alcohol use ^[2]
• Involves: simple education and advice about safe levels of alcohol consumption ^[2]
• Efficacy: usually modest reduction in alcohol consumption over next few years ^[2]
• Utility: best for those with at-risk drinking (alcohol use above limit but non-dependent) ^[2]

• E.g., Alcoholics Anonymous (AA) ^[2], Narcotics Anonymous (NA)
• 12-step programme model: peer support, sponsorship, shared experience
• Free, widely available, ongoing (lifetime)
• Evidence base: moderate-quality evidence of benefit, particularly when combined with professional treatment

• Cue exposure therapy: to ↓ effect of drinking cues and to prevent relapse ^[2] — systematic desensitisation to environmental triggers
• Contingency management: offer incentives to encourage abstinence or discourage substance use ^[2] — particularly effective for stimulants and cannabis
• Family therapy: address family dynamics, improve communication, reduce enabling behaviour

The route of administration determines which organ systems are damaged mechanically and which infectious risks the patient faces.

Alcohol comorbid psychiatric disorders ^[3]:

• Schizophrenia: 30% of patients with schizophrenia have comorbid alcohol problems ^[3]

  • Alcohol decreases feelings of isolation
  • Temporarily reduces symptoms of anxiety/depression/insomnia
  • But increases psychotic symptoms and mood swings
  • Leads to disruptive behaviour, suicide, treatment non-compliance, drug abuse, poor clinical outcome
  • Drug accumulation due to hepatic damage ^[3] — liver impairment → ↓ metabolism of antipsychotics → toxicity

• 20% of drug abusers are alcoholic; alcoholics are 6 times more prone to become drug abusers ^[3] — polysubstance use is the rule, not the exception

This is critically important:

7% of alcohol abusers die of suicide ^[3]

Alcoholism is a factor in 30% of all completed suicides ^[3]

50% of suicide attempts have consumed alcohol at the time of the attempt ^[3]

96% of alcoholics who die by suicide continue alcohol use up to the end of their lives ^[3]

Why is the link so strong? Multiple mechanisms converge:

• Alcohol causes and exacerbates depression (direct neurotoxic effect on serotonergic pathways)
• Alcohol causes disinhibition → lowers the threshold for acting on suicidal thoughts
• Chronic alcoholism leads to social losses (relationships, employment, housing) → hopelessness
• Withdrawal states include severe anxiety and agitation → impulsive self-harm
• Comorbid psychiatric disorders (depression, personality disorders) are both risk factors for alcoholism and suicide

Medical comorbidity in bipolar disorder — risk factors include ^[4]:

• Alcohol and substance use
• Unhealthy diet, physical inactivity
• Social isolation, unemployment
• Side effects of pharmacotherapy (e.g., sodium valproate, atypical antipsychotics)

These factors collectively explain the significantly ↑ mortality and ↓ life expectancy by ~13 years (M) and 9 years (F) in bipolar disorder ^[2], with suicide (1/3 of mortality): ~8% (M) and 5% (F) hospitalised patients die by suicide over 40 years ^[2].