• Clinical science

Substance-related and addictive disorders


Substance-related disorders are a class of psychiatric disorders characterized by a craving for, the development of a tolerance to, and difficulties in controlling the use of a particular substance or a set of substances, as well as withdrawal syndromes upon abrupt cessation of substance use. While these substances may have different mechanisms of action, their addictive potential typically lies in the way they act on the brain's reward system and affect emotion, mood, and perception – producing what is colloquially referred to as a “high.” Individuals with a substance use disorder will frequently harm themselves and/or others as a result of substance use. Patients with substance use disorders often present with other psychiatric conditions that also require treatment, such as bipolar disorder, major depressive disorder, or anxiety disorder. Generally, treatment for substance use disorders includes long-term psychotherapy or group therapy in addition to medical supervision of withdrawal symptoms.

In gambling disorder, individuals feel a compulsion to gamble despite negative consequences and/or multiple attempts to stop. Gambling disorder is thought to involve many of the same neurobiological mechanisms as substance-related addictions and shares some of the same psychosocial risk factors.


Substance use disorder

  • Definition: pathologic collection of cognitive, behavioral, and physiological symptoms related to the use of a substance
  • Epidemiology
    • Sex: >
    • Alcohol and nicotine use is most common
  • Criteria
    1. Impaired control
      • Using substance inlarger amounts and/or for a longer time than originally intended
      • Repeated failed attempts to cut down on use
      • Spending a great deal of time on substance-related activities (e.g., buying, using, recovering from use, etc.)
      • Intense desire to obtain and use substance (craving)
    2. Social impairment
      • Problems fulfilling work, school, family, or social obligations (e.g., not attending work or school, neglecting children or partner, etc.)
      • Problems with interpersonal relationships directly related to substance use
      • Reduced social and recreational activities (e.g., less time socializing with friends, spending less time with family)
    3. Risky use
      • Use in physically hazardous situations (e.g., operating heavy machinery, driving a car)
      • Use despite awareness of physical problems (e.g., continued alcohol use despite having cirrhosis)
    4. Pharmacologic indicators
      • Drug tolerance
        • Definition: the need for individuals to continuously increase the dose of a substance to achieve the same desired effect
        • Corollary: individuals experience less of an effect despite taking the same amount of a substance
        • The degree of tolerance can vary greatly depending on factors such as route of administration, duration of use, and genetic factors!
      • Drug withdrawal

Withdrawal from some substances such as alcohol, benzodiazepines, and barbiturates can be fatal!


  • DSM-5 defines substance-related and addictive disorders in a distinct class of disorders. The substances included are:
    • Alcohol (ICD-10, F10)
    • Caffeine (ICD-10, F15)
    • Cannabis (ICD-10, F12)
    • Hallucinogens (ICD-10, F16)
    • Inhalants (ICD-10, F18)
    • Opioids (ICD-10, F11)
    • Sedatives, hypnotics, and anxiolytics (ICD-10, F13)
    • Stimulants
    • Tobacco (ICD-10, F17)
    • Other (or unknown) substance (ICD-10, F19)
  • In addition, DSM-5 classifies gambling disorder (ICD-10, F63.0) as a non-substance-related addictive disorder, unlike ICD-10, which classifies it as an impulse disorder.
  • For most substances, DSM-5 distinguishes five distinct subdisorders:
    • Use disorder
      • Specify current severity:
        • Mild
        • Moderate
        • Severe
    • Intoxication
      • With use disorder, mild
      • With use disorder, moderate or severe
      • Without use disorder
      • Without perceptual disturbances
      • With perceptual disturbances
    • Substance withdrawal
      • Without perceptual disturbances
      • With perceptual disturbances
    • Other substance-related disorder
    • Unspecified substance-related disorder
  • Note that substance-induced or medication-induced disorders are classified as separate diagnoses under the respective disorder induced by the use of a certain substance (e.g., amphetamine-induced sleep disorder is a parasomnia classified under sleep-wake disorders rather than a stimulant-related disorder).

Differential diagnosis

Differential diagnosis of drug intoxication
Pupils Blood pressure Pulse Other symptoms
Opioids Miosis Hypotension Bradycardia
  • Respiratory depression
  • Absent proprioceptive reflexes
Cannabinoids Mydriasis Hypertension/hypotension Tachycardia
Cocaine Mydriasis Hypertension Tachycardia
Amphetamines Mydriasis Hypertension Tachycardia
Hallucinogens Mydriasis Hypertension Tachycardia
Gamma-hydroxybutyric acid

Variable pupillary reaction (miotic or mydriatic)

Hypotension Bradycardia
  • Loss of consciousness
  • Amnesia
  • Myoclonic twitches
  • Nystagmus


Alcohol use disorder

See alcohol use disorder.

Opioid use disorder

Overdose with opioid analgesics is the most common cause of death among adults < 50 years.


Cannabis use disorder

  • Substance: cannabis
  • Action: : The main active component is tetrahydrocannabinol (THC); , which influences the cannabinoid receptors CB1 and CB2; inhibition of adenylate cyclase
  • Forms of preparation
  • Street names: weed, grass, pot
  • Clinical features
    • Intoxication
      • Joviality or dysphoria; , anxiety, or panic
      • Conjunctival injection (red eyes), mydriasis
      • Increased appetite (“munchies”)
      • Dry mouth
      • Mild tachycardia; and increased blood pressure
      • Impaired reaction time, concentration, and coordination → ↑ risk of motor vehicle accidents
      • May induce psychosis; with paranoia; , delusional thoughts; , and/or hallucinations
    • Withdrawal: unstable mood; with depression, irritability; , aggression, headaches, insomnia, sweating
  • Treatment: Psychosocial support and interventions
  • Complications

The benefits of medical marijuana include increasing appetite and treating nausea/vomiting in terminally ill patients, acting as an analgesic in cancer patients, and reducing intraocular pressure in patients with glaucoma!


Sedatives and hypnotics use disorder

See section on “benzodiazepine dependence ” in benzodiazepines.

Cocaine use disorder

β-blockers are contraindicated because they can cause unopposed α-agonism, which worsens vasospasm!

Suspect cocaine use in individuals presenting with weight loss, behavioral changes, and erythema of the turbinates and nasal septum!


Amphetamine use disorder


Phencyclidine use disorder

  • Substance: phencyclidine (PCP); liquid form is often sprayed on tobacco or cannabis and smoked.
  • Action: activates dopaminergic neurons and antagonizes NMDA receptors → stimulant or depressive neurological effects (depends on dose)
  • Street names: angel dust, peace pill, elephant tranquilizer
  • Clinical features
    • Intoxication
      • Decreased sensation to pinprick (pain tolerance)
      • Violent, and/or abnormal behavior; , confusion; , amnesia, disorientation, psychosis (e.g., hallucinations), miosis; , seizures, synesthesia; (one sensory stimulation → another sensory perception), ataxia; , dysarthria
      • Hypertension, tachycardia, dysrhythmias
      • Hyperthermia, muscle rigidity
      • Overdose: vertical nystagmus (most common symptom in overdose), delirium, seizures
    • Withdrawal:
      • There are rarely acute symptoms of withdrawal or dependence.
      • Flashbacks may occur.
  • Treatment
    • Reduce environmental stimuli
    • Sedation with benzodiazepines (for severe agitation) or haloperidol (in the presence of psychotic symptoms)


Hallucinogen use disorder


Inhalant use disorder

  • Substances: glue, paint thinners, fuel, nitrous oxide, alkyl nitrites
  • Action: : Varies by specific inhalant, but generally work by depressing the CNS
  • Street names: poppers, whippits
  • Epidemiology: most prevalent in high-school aged individuals
  • Clinical features
    • Intoxication
      • Dizziness, confusion, lethargy within ∼ 30 minutes of use
      • Nystagmus; , muscle weakness, tremor, hyporeflexia, ataxia
      • Lingering odor of inhaled substance
      • Overdose: coma and death (due to respiratory depression)
    • Withdrawal: usually no withdrawal symptoms, but regular users may develop symptoms of CNS excitation (e.g. tachycardia, irritability, or hallucinations)
  • Treatment
    • Symptomatic; treatment (reassurance, intubation may be necessary)
    • Psychotherapy
  • Complications


Gamma-hydroxybutyric acid use disorder

  • Substance: gamma-hydroxybutyric acid (GHB)
  • Action: Direct agonist of GABA receptors (similar to benzodiazepines)
  • Street names: liquid ecstasy (unrelated to MDMA)
  • Clinical features: intoxication
    • In high doses
      • Lightheadedness and loss of consciousness; ; may induce amnesia for the time of intoxication.
      • Vegetative symptoms: perspiration, agitation, nausea
    • In low doses: intensification of experience, well-being, increased desire to make contact
  • Withdrawal
  • Diagnosis
    • Detection is complicated by the fact that GHB is a substance that is normally present in the CNS of mammals. Screening cannot, therefore, provide conclusive evidence of intake.
    • Short half-life (20–45 minutes): Normal GHB-levels are reached after a few hours, making it impossible to establish the consumption of GHB.
  • Treatment: Supportive

Gamma-hydroxybutyric acid is sometimes used as a “date rape” drug because of its quick onset, amnestic effects, and complicated detection!


Bodypacker syndrome

Definition: toxicity and potential overdose from large amounts of substance entering the bloodstream after swallowed/inserted drug packets accidentally open inside the body (depends on the specific substance)

Gambling disorder

  • Definition: : addictive disorder in which individuals feel a compulsion to gamble despite negative consequences and/or multiple attempts to stop.
  • Epidemiology
    • Sex: >
    • No specific age group
  • Etiology: combination of factors (genetic, environmental, neurochemical abnormalities)
  • Diagnosis: ≥ 4 of the following in a 12 month period
    • Relying on others for financial support to support habit
    • Restlessness when attempting to stop gambling
    • Constant preoccupation with gambling
    • Continuous gambling in an attempt to undo losses (“chasing one's losses”)
    • Jeopardizing relationships or careers as a result of gambling
    • Numerous failed attempts to quit gambling
    • Lying to others to conceal the extent of gambling
    • Belief that gambling helps relieve dysphoria
  • Treatment
  • Complications
    • Often occurs in conjunction with other psychiatric disorders (especially anxiety and substance use)
    • Associated with poor general health, including tachycardia and angina


Nicotine use disorder


Caffeine use disorder

  • Substance: caffeine (usually ingested with coffee or tea)
  • Action: adenosine antagonist → increased cAMPneurological excitation
  • Epidemiology: most prevalent psychoactive substance in the US
    • Overdose
      • 2 cups of coffee (∼ 250 mg): anxiety; , restlessness; , twitching; , flushed face, diuresis; , excitement, tachycardia
      • 8 cups of coffee (∼ 1 g): severe restlessness, light flashes, cardiac arrhythmias; , tinnitus
      • Above 10 gseizures or respiratory failure → death
    • Withdrawal: headache, irritability, drowsiness, muscle pain, depression
  • Treatment
    • Overdose: supportive
    • Withdrawal: resolves spontaneously within ∼ 10 days


Synthetic cathinones