Key Facts

Cannabis is the most widely used controlled substance globally and in the UK. While often perceived as relatively harmless, increasing evidence demonstrates significant harms, particularly with high-potency products, early-onset use, and heavy/daily use. There is a strong association between cannabis use and psychotic disorders.

Epidemiology

• ~2.6 million adults in England and Wales used cannabis in the past year
• Prevalence highest: 16-24 age group (~18% past-year use)
• Dependence: ~9% of ever-users; ~17% of adolescent-onset users; ~25-50% of daily users
• Cannabis-related hospital admissions are increasing
• Treatment presentations: cannabis is the most common primary drug for under-18s entering treatment services

Aetiology

• Pharmacology: THC acts on CB1 cannabinoid receptors (primarily in brain — hippocampus, prefrontal cortex, basal ganglia, cerebellum) and CB2 receptors (periphery/immune)
• Endocannabinoid system: THC mimics endogenous cannabinoids (anandamide, 2-AG); modulates dopamine, GABA, and glutamate transmission
• Risk factors for dependence: early onset of use (<16 years), high-potency products, daily use, family history of addiction, co-morbid mental illness, social adversity
• CBD (cannabidiol): non-intoxicating cannabinoid; may have anxiolytic and antipsychotic properties; attenuates some effects of THC

Pathophysiology

• Acute THC effects: stimulates mesolimbic dopamine release → euphoria and reinforcement
• Chronic use: CB1 receptor downregulation and desensitisation → tolerance
• Adolescent vulnerability: endocannabinoid system is critical for neurodevelopment; exogenous THC disrupts normal pruning and myelination of prefrontal cortex
• Cannabis and psychosis: THC increases dopamine in mesolimbic pathway; gene-environment interaction (COMT Val158Met polymorphism moderates risk)

Acute Cannabis Intoxication

• Euphoria and relaxation: sense of wellbeing
• Altered perception: time distortion, enhanced sensory experience
• Impaired short-term memory and concentration
• Increased appetite ("munchies")
• Conjunctival injection (red eyes), dry mouth
• Tachycardia: dose-related increase in heart rate
• Anxiety or paranoia: particularly with high-THC products or in inexperienced users
• Psychomotor impairment: slowed reaction time, impaired coordination

Cannabis Use Disorder

• Impaired control over use
• Continued use despite social, occupational, or health consequences
• Tolerance and withdrawal
• Neglect of other activities

Cannabis Withdrawal Syndrome

• Onset 24-72 hours after cessation; peak 3-4 days; duration 1-2 weeks
• Irritability, anger, aggression
• Anxiety, nervousness
• Insomnia, disturbed sleep, vivid dreams
• Decreased appetite, weight loss
• Restlessness, depressed mood
• Physical: headache, sweating, abdominal pain, tremor (less common)

Red Flags

• First-episode psychosis: auditory hallucinations, paranoid delusions, thought disorder — urgent psychiatric assessment
• Cannabinoid hyperemesis syndrome: cyclical vomiting, compulsive hot bathing, abdominal pain — may mimic surgical abdomen
• Severe anxiety/panic attacks: can be distressing; usually self-limiting
• Adolescent use: disruption of brain development, educational failure, increased psychosis risk
• Driving under the influence: impaired psychomotor function; UK law: 2 μg/L blood THC legal limit

Bedside

• Urine drug screen: THC metabolites detectable for 3-4 days (occasional use) to >30 days (chronic heavy use)
• Mental state examination: assess for psychotic symptoms, mood disorder, anxiety
• Screening tools: CUDIT-R (Cannabis Use Disorder Identification Test — Revised), SDS (Severity of Dependence Scale)
• Risk assessment: suicide risk, safeguarding (particularly in young people)

Bloods

• Routine bloods: generally unremarkable in isolated cannabis use
• LFTs: if co-existing alcohol or other substance use
• Blood-borne virus screen: if concurrent injecting drug use
• Inflammatory markers: if cannabinoid hyperemesis (to exclude other causes of vomiting)

Imaging

• Not routinely indicated for cannabis use disorder
• MRI brain: if first-episode psychosis (exclude organic cause)
• CT abdomen: if cannabinoid hyperemesis mimics acute surgical abdomen

Special Tests

• Neuropsychological testing: if persistent cognitive concerns; may show deficits in memory, attention, processing speed
• Blood THC levels: not routinely measured clinically; used in medicolegal settings (driving offences)

Non-pharmacological

• Brief intervention: structured advice on risks of cannabis use; particularly effective for young people
• Motivational enhancement therapy (MET): 2-4 sessions; enhances motivation to change
• Cognitive behavioural therapy (CBT): address maladaptive thoughts and behaviours around cannabis use; NICE CG51 recommended
• Contingency management: incentive-based approach; NICE TA114 supports use in drug misuse
• Family therapy: particularly for adolescents — multidimensional family therapy (MDFT)
• Education and harm reduction: information about potency, legal consequences, mental health risks

Pharmacological

• No licensed pharmacotherapy for cannabis use disorder
• Symptomatic treatment during withdrawal:
  • Insomnia: short-term use of non-benzodiazepine hypnotics (e.g. zopiclone 3.75-7.5 mg, maximum 2 weeks); sleep hygiene
  • Anxiety: SSRIs if persistent anxiety disorder identified
  • Irritability/agitation: reassurance; in severe cases, short course of diazepam
• N-acetylcysteine (NAC): some evidence for reducing cannabis use in adolescents (Gray et al., 2012); not yet licensed for this indication
• Treatment of co-morbid psychosis: antipsychotics as per standard guidelines; cannabis cessation essential for recovery

Surgical

• Not applicable

Referral Criteria

• Community drug services: if dependence established, failed self-help, associated harms
• CAMHS/young people's substance misuse service: adolescents with cannabis use disorder
• Early Intervention in Psychosis (EIP): if first-episode psychosis associated with cannabis use
• Psychiatry: co-morbid severe mental illness, suicidality
• Gastroenterology: cannabinoid hyperemesis with severe vomiting, dehydration, electrolyte disturbance

Outcomes

• Spontaneous remission: many cannabis users reduce or cease use in their late 20s/30s
• Treatment outcomes: CBT + MET → abstinence rates of 20-30% at 12 months; significant reduction in use in further 30%
• Psychosis: cannabis-associated psychosis may remit with cessation; ~50% progress to chronic psychotic disorder (schizophrenia)
• Cognitive recovery: most deficits improve after 4 weeks of abstinence; adolescent-onset heavy use may have more persistent effects

Complications

• Psychotic disorders: strong dose-response relationship; ~33% of psychosis cases in London attributable to high-potency cannabis (Di Forti et al.)
• Amotivational syndrome: apathy, reduced goal-directed behaviour in chronic heavy users
• Respiratory effects: chronic bronchitis symptoms; smoking cannabis with tobacco increases lung cancer risk
• Cardiovascular: acute tachycardia; rare reports of acute coronary syndrome and stroke
• Cannabinoid hyperemesis syndrome: cyclical vomiting; resolves only with permanent cessation
• Impaired driving: increased accident risk; second most common intoxicant after alcohol in road traffic collisions
• Educational and occupational impairment: particularly with adolescent-onset use

Cannabis Potency and Risk

Key Studies in Cannabis and Psychosis

Legal Classification (UK)