Substance Misuse — UKMLA Guide 2026

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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

Key points

Cocaine/stimulants: sympathomimetic toxicity (hypertension, tachycardia, chest pain, psychosis, seizures). No specific antidote — supportive + benzodiazepines
Cannabis: most commonly used illicit drug in the UK. High-potency cannabis associated with psychosis risk, especially in adolescents
NPS ("legal highs"): synthetic cannabinoids (Spice), synthetic cathinones (mephedrone), dissociatives — unpredictable toxicity
No pharmacological treatments for stimulant or cannabis dependence — psychosocial interventions are first-line (CBT, motivational interviewing)
Cocaine + chest pain: do NOT give beta-blockers (risk of unopposed alpha stimulation → coronary vasospasm). Use benzodiazepines + GTN
Cannabis and psychosis: dose-response relationship. High-potency ("skunk") and adolescent use are major risk factors

Overview

Substance misuse encompasses harmful use of and dependence on a wide range of psychoactive substances beyond alcohol and opioids. Stimulants (cocaine, crack cocaine, amphetamines, methamphetamine, MDMA) produce sympathomimetic effects through catecholamine release or reuptake inhibition. Cannabis (THC) acts on cannabinoid receptors, producing relaxation, euphoria, perceptual changes, and appetite stimulation; high-potency cannabis is associated with psychosis risk. Novel psychoactive substances (NPS) include synthetic cannabinoids (Spice/K2), synthetic cathinones (mephedrone), dissociatives (ketamine, nitrous oxide), and others. These substances carry unpredictable risks as composition and potency are variable. The Psychoactive Substances Act 2016 criminalised production and supply of NPS in the UK.

Epidemiology

Cannabis is the most commonly used illicit drug in the UK (~7% of adults in the past year). Cocaine is the second most common (~3%), with UK use among the highest in Europe. MDMA and amphetamine use is concentrated in younger adults. NPS use peaked around 2013–2016, with synthetic cannabinoids (Spice) causing significant harm particularly among homeless populations and prisoners. Risk factors for substance misuse include male sex, younger age, mental health disorders, adverse childhood experiences, peer influence, social deprivation, and availability. Cocaine-related deaths have tripled in the UK over the past decade.

Clinical Features

Symptoms

Cocaine/stimulants: euphoria, increased energy, grandiosity, reduced appetite, insomnia, agitation

Stimulant toxicity: chest pain, palpitations, hypertension, seizures, psychosis, hyperthermia

Cannabis: relaxation, euphoria, altered perception, increased appetite ("munchies"), anxiety, paranoia

Cannabis (chronic/high-potency): amotivational syndrome, cognitive impairment, psychosis, dependence

NPS: variable effects depending on substance — agitation, psychosis, seizures, cardiovascular collapse (synthetic cannabinoids)

MDMA: euphoria, empathy, jaw clenching, bruxism, hyperthermia, hyponatraemia (from water intoxication)

Nitrous oxide: paraesthesiae, peripheral neuropathy (B12 inactivation), ataxia with chronic use

Signs

Cocaine: mydriasis, tachycardia, hypertension, nasal septum perforation (with chronic snorting)

Cannabis: conjunctival injection (red eyes), tachycardia, relaxed demeanour

Stimulant psychosis: paranoid delusions, visual/tactile hallucinations (formication — "cocaine bugs"), agitation

NPS (synthetic cannabinoids): zombie-like state, catatonia, seizures, severe agitation

Investigations

First-line

Urine drug screenStandard immunoassay detects cocaine (benzoylecgonine), amphetamines, cannabis (THC), MDMA, benzodiazepines. NPS often NOT detected on standard screens

ECGEssential if stimulant use — look for ischaemia, arrhythmia, QTc prolongation

BloodsFBC, U&Es, glucose, CK (rhabdomyolysis with stimulants/NPS), troponin (if chest pain), LFTs

Second-line

CT headIf seizures, focal neurology, or persistent altered consciousness — cocaine causes haemorrhagic stroke

SodiumMDMA + excess water intake → hyponatraemia → cerebral oedema. Can be fatal

Specialist

Toxicology laboratory analysisFor NPS identification — standard screens may miss synthetic substances. Discuss with toxicology service

Management

NICE CG51 (Drug misuse: psychosocial interventions), 2007

Acute stimulant toxicity

Supportive: ABCDE approach, cooling if hyperthermic, IV fluids, cardiac monitoring
Benzodiazepines (diazepam/lorazepam) for agitation, hypertension, seizures, and chest pain
Cocaine + chest pain: benzodiazepines + GTN. Do NOT give beta-blockers (risk of unopposed alpha stimulation → worsening hypertension and coronary vasospasm)
If severe hypertension persists: consider IV phentolamine (alpha-blocker)
MDMA + hyponatraemia: fluid restrict, hypertonic saline if severe (<120 mmol/L with symptoms)

Psychosocial interventions (first-line for stimulant/cannabis dependence)

Motivational interviewing: explore ambivalence, build motivation for change
CBT: address maladaptive thought patterns, identify triggers, develop coping strategies
Contingency management: incentive-based programme rewarding drug-free urine samples (NICE recommended for stimulants)
Brief interventions for hazardous cannabis use

No specific pharmacological treatments

No medications are licensed or recommended for cocaine, cannabis, or NPS dependence
Treat comorbid mental illness (depression, anxiety, psychosis) per respective guidelines
Manage cannabis withdrawal symptomatically: sleep hygiene, anxiolytics short-term if severe

Harm reduction

Education about risks: overdose recognition, safer use advice, BBV transmission
Needle exchange for IV stimulant users
Drug checking services where available

Complications

Cocaine: Myocardial infarction, aortic dissection, haemorrhagic stroke, seizures, nasal septum perforation, rhabdomyolysis
Cannabis: Psychosis (especially high-potency, adolescent use), amotivational syndrome, dependence (~10% of users), cognitive impairment, cannabinoid hyperemesis syndrome
MDMA: Hyperthermia, hyponatraemia, serotonin syndrome (especially with SSRIs), rhabdomyolysis, hepatotoxicity
NPS: Unpredictable toxicity — seizures, cardiovascular collapse, psychosis, dependence (synthetic cannabinoids are highly addictive)
Nitrous oxide: Vitamin B12 inactivation → subacute combined degeneration of the spinal cord (peripheral neuropathy, ataxia)

UKMLA Exam Tips

1Cocaine + chest pain: NEVER give beta-blockers. Use benzodiazepines + GTN (prevent unopposed alpha stimulation)
2High-potency cannabis ("skunk") + adolescent use = strongest modifiable risk factors for psychosis
3MDMA + large water intake → hyponatraemia → cerebral oedema → death. Fluid RESTRICT, not fluid load
4Nitrous oxide abuse → B12 inactivation → subacute combined degeneration (posterior + lateral columns)
5Stimulant psychosis: paranoid delusions + formication (tactile hallucination of bugs crawling on skin)
6Contingency management (reward-based) is NICE-recommended specifically for stimulant misuse
7Cannabinoid hyperemesis syndrome: cyclical vomiting + compulsive hot bathing in chronic cannabis users

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