Stimulant use disorder

Background

• A substance use disorder that includes cocaine (freebase, crack, rock), methamphetamine (crystal meth, meth, crystal, jib, speed, ice, tina, side), and other amphetamine-like substances (including prescription stimulants)

Stimulant	Mechanism	Half-life	Routes of administration
Cocaine
Powder cocaine	dopamine reuptake inhibitor	30 to 120 minutes	snorted, but can be mixed with water and injected
Crack cocaine			smoked, but can be mixed with an acid and injected
Freebase			similar to crack, but may explode when smoked
Methamphetamine
Powder	dopamine reuptake inhibitor, also increases dopamine release	wide variability, about 10 to 30 hours	snorted or pressed into a pill and taken orally
Base			swallowed or injected
Crystal			smoked, dissolved and injected, or snorted

Epidemiology

• Stimulants are the second-most commonly used illicit substances after marijuana

Pathophysiology

• All stimulants act mainly on the dopamine system

Clinical Manifestations

Acute intoxication

• Common symptoms include tachycardia or bradycardia, pupillary dilatation, high or low blood pressure, sweating, chills, nausea or vomiting, weight loss, psychomotor agitation or retardation, muscular weakness, respiratory depression, chest pain, arrhythmias, confusion, seizures, dyskinesia, dystonia, and coma
• Severe intoxication may cause mania, paranoia, severe delirium, hypertension, agitation, sweating, formication and skin picking, choreoathetosis, and ataxia

Stimulant-induced psychosis

• Schizophrenia complicates about 15 to 25% of chronic stimulant use within 2 to 5 years
• Unclear what the causal relationship is between stimulants and schizophrenia

Other sequelae

• Cardiovascular or cerebrovascular disease, including myocardial infarction, stroke, and acute kidney injury
• Psychiatric diseases including psychosis, depression, and suicidal ideation
• Increased risk of HIV and hepatitis C
• Death

Withdrawal

• Symptoms include depressed mood, vivid dreams, fatigue, insomnia, hypersomnia, cravings, psychomotor agitation or impairment, increased appetite, agitation, irritability, and cognitive impairment

Investigations

Urine drug screen

• Cocaine metabolites are detectable for about 3 to 5 days
  • False positives: none
• Methamphetamines may be detectable for 3 to 5 days, with some variability
  • False positives: nasal inhalers, ADHD medications, bupropion, trazodone, chlorpromazine, promethazine, ranitidine

Management

Intoxication

• Generally focussed on supportive care

Withdrawal

• Generally focussed on supportive care, including good nutrition
• Cognitive behavioural therapy and sleep hygiene may be helpful

Chronic treatment

• There is no good evidence in favour of any pharmacologic treatment, and medication-based treatment is generally not recommended1
  • Stimulants may be helpful21, including dexamphetamine and methylphenidate
    • Lisdexamfetamine (Vyvanse) is currently under investigation at doses of 150 mg to 250 mg daily3 (compared to a usual maximum of 70 mg)
  • Other promising medications include naltrexone and topiramate
  • Other medications that may eventually prove useful include:
    • Buproprion
    • Riluzole
    • Mirtazapine
    • N-acetylcysteine: unclear if it reduces cravings4
    • Disulfiram: may treat cocaine use disorders5
  • Others that have been studied include: anticonvulsants67 including topiramate8, many stimulants91011 including modafinil, dopamine agonists12, antidepressants1314, and antipsychotics15
• The main focus is on psychosocial treatments, including contingency management, cognitive behavioural therapy, motivational interviewing, relapse prevention, and psychodynamic therapy
  • Long-term abstinence is around 30 to 50% for people in treatment, with 40-50% dropout rate
  • Contingency planning with or without cognitive behavioural therapy seems to be the most promising