Substance-related and addictive disorders

Last updated: September 5, 2022

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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 symptoms 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.

Classification [1]

Substance use disorder [1][2][3]

  • Description: a chronic condition in which an uncontrolled pattern of substance use leads to significant physical, psychological, and social impairment or distress, with continued use despite substance-related problems.
  • Epidemiology
  • Characteristics: features that are typical for all substance use disorders (≥ 2 features must occur within 1 year to fulfill the DSM-V criteria)
    • Impaired control
      • Using a substance in larger amounts and/or for a longer time than originally intended
      • Repeated failed attempts to cut down on use
      • A great deal of time spent on substance-related activities (e.g., seeking out, buying, using, recovering from use)
      • Intense desire to obtain and use substance (craving)
    • Social impairment
      • Problems fulfilling work, school, family, or social obligations (e.g., not attending work or school, neglecting children or partner)
      • Problems with interpersonal relationships directly related to substance use (withdrawal from relationships, marital issues)
      • Reduced social, occupational, and recreational activities (e.g., less time socializing with friends, neglecting hobbies)
    • Risky use
      • Use in physically hazardous situations; (e.g., driving a car under the influence, unprotected sex, operating heavy machinery)
      • Continued use despite awareness of problems related to or exacerbated by substance use (e.g., continued alcohol use despite having cirrhosis)
    • Pharmacologic indicators
      • Drug tolerance: the need to continuously increase the dose of a substance to achieve the same desired effect
      • Drug withdrawal: a substance-dependent collection of symptoms that appear after cessation of prolonged heavy drug use accompanied by a strong urge to readminister the substance
  • Exception: patients undergoing supervised treatment with certain psychoactive substances (e.g., stimulants, cocaine, opioids, nitrous oxide, sedative-hypnotic drugs, anxiolytic drugs, cannabis) [4]
    • Tolerance and withdrawal can be normal physiological adaptations.
    • In the absence of other DSM-V criteria, tolerance and withdrawal do not necessarily indicate substance use disorder.

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

Substance-induced disorders

  • Intoxication: a temporary condition caused by recent ingestion of a substance that alters a person's consciousness, cognition, perception, judgment, affect, and/or behavior; commonly occurs in substance use disorders but also in one-off use
  • Withdrawal: a condition characterized by behavioral, physiological, and cognitive changes caused by a sudden reduction or cessation of substance intake after a prolonged period of heavy intake; usually occurs in association with substance use disorders
  • Substance/medication-induced mental disorders: a psychiatric disorder that develops within 1 month of intoxication or withdrawal of a substance and is not attributable to an independent mental disorder (e.g., substance/medication-induced anxiety disorder)

Related definitions

  • Abuse
    • In the context of substance use, the term “abuse” should generally be avoided due to its impreciseness and the historical burden of stigma.
    • “Substance use” is generally the preferred term in this context, with “substance misuse” being appropriate in the context of prescription drugs.
  • Drug-seeking behavior
    • A maladaptive behavioral response to substance addiction that involves manipulative and/or demanding behaviors to obtain the desired substance
    • Often indicative of an underlying substance use disorder
    • Examples of drug-seeking behavior
      • Faking/aggravating symptoms
      • Bribes, threats, theft (e.g., prescription pads)
      • Forging prescriptions or using those of others (e.g., under the names of family members)
      • Pretending to lose prescriptions and asking for new ones
      • Insisting that a treatment that does not involve one or more certain (addictive) drugs is ineffective or not tolerated (e.g., due to an alleged allergy)
      • Demanding a stronger medication or higher dose due to an allegedly high drug tolerance
      • Claiming that another, an ostensibly more experienced or more caring, physician would prescribe the desired drug or threatening to see another physician if the desired drug is not prescribed.
  • Medication-assisted treatment (MAT): treatment for substance use disorder that combines counseling with pharmacological and behavioral therapy, tailored to each patient's needs. [5]

Overview of distinguishing features of substance intoxication and withdrawal [6]

Overview of substance intoxication and withdrawal
Intoxication Withdrawal
Substance Pupils Cardiovascular system Concomitant symptoms


  • Normal (mild intoxication)
  • Mydriasis (severe intoxication)
  • Autonomic symptoms (e.g., sweating, hypertension)
  • Gastrointestinal symptoms (e.g., nausea, vomiting)
  • Neurological symptoms (e.g., seizures, tremors)
  • Psychiatric symptoms (e.g., depressive moods, insomnia)
  • ↓ Appetite, weight loss
  • ↑ Libido

Synthetic cathinones

  • Aggression, confusion
  • Muscle spasms
  • Euphoria
  • Restlessness, anxiety, insomnia
  • ↑ Gastrointestinal motility, weight loss
  • Conjunctival injection (red eyes)
  • ↑ Appetite, dry mouth
  • Impaired reaction time, concentration, and motor coordination
  • Social detachment
  • Irritability, anxiety, depression
  • ↓ Appetite, anorexia
  • Restlessness, sleep disturbances

Lysergic acid diethylamide (LSD)

  • None
  • Changes in sleep and appetite
  • Difficulty concentrating
  • Fatigue, depression, anxiety
Phencyclidine (PCP)
Gamma-hydroxybutyric acid (GHB) Low dose
  • Intensification of sensory experience
  • Enhanced empathy and libido
  • Disinhibition
High dose

See the article on alcohol-related disorders.

  • Substance: cannabis
  • Street names: weed, grass, pot, ganja, skunk, spliff
  • Forms of preparation (most commonly smoked; vaporized; ingested orally via pill, capsules, oil, food)
  • Mechanism of action: tetrahydrocannabinol (THC; main active component) interacts with cannabinoid receptors CB1 and CB2 inhibition of adenylate cyclase
  • Clinical features of intoxication:
    • DSM-V requires the following features to be present: [1]
      • Any of the following behavioral/mental disturbances must occur during or shortly after cannabis consumption
        • Euphoria
        • Perceptual disturbances (e.g., distorted sense of time)
        • Impaired reaction time, concentration, and motor coordination
        • Social detachment
        • Impaired judgment
        • Joviality, anxiety, panic
      • At least two of the following symptoms must be present within two hours after cannabis consumption:
    • Additionally, the following features may be present [1][12]
  • Clinical features of cannabis withdrawal: DSM-V requires ≥ 3 of the following features to occur within one week following cessation of prolonged cannabis use [1]
    • Irritability, aggression
    • Anxiety
    • Depression
    • ↓ Appetite and/or weight loss
    • Restlessness
    • Sleep disturbances
    • Anorexia
    • At least one of the following physical symptoms must also be present: headaches, tremors, abdominal pain, fever, chills, sweating.
  • Treatment:
    • Intoxication: symptomatic treatment [13]
    • Withdrawal: psychosocial support and interventions [14]
  • Complications [15]
    • Cannabis; -induced psychosis with paranoia, delusional thoughts, and/or hallucinations
    • Cannabis-induced anxiety disorder
    • Cannabis-induced sleep disorder
    • Higher lifetime probability of other substance use disorders
    • Cannabinoid hyperemesis syndrome [16]
      • Side effect of long-term cannabis use
      • Pathophysiology: remains incompletely understood
      • Clinical features
        • Episodic abdominal pain, nausea, and vomiting.
        • Relief with exposure to hot water (e.g., a bath) [17]
      • Treatment: complete cessation of cannabis use
    • Cannabis use disorder: DSM-V requires ≥ 2 of the following features to occur within a 1-year period of cannabis use, accompanied by agitation and severe impairment of functioning
      • Using cannabis in larger amounts or over a longer period than intended
      • Persistent desire to cut down the amount of cannabis used or repeated unsuccessful efforts to stop using it
      • A large amount of time is spent using cannabis, trying to acquire it, or recovering from its effects
      • Strong craving to consume cannabis
      • Cannabis use has a negative impact on social and professional function (e.g., at work, school, or home)
      • Continued cannabis use despite social or interpersonal problems that are directly caused or exacerbated by its use
      • Loss of interest in activities that were important to user prior to regular cannabis use
      • Recurrent use of cannabis in situations in which its use is associated with the risk of physical harm (e.g., driving a car)
      • Continued cannabis use despite persistent or recurrent psychological or physical problems that can most likely be attributed directly to the use of cannabis
      • Tolerance, which can manifest as:
        • The need to markedly increase the amount of cannabis to achieve the desired effect/intoxication
        • A reduced effect over time when the same amount of cannabis is used
      • Withdrawal, which can manifest in the form of:
    • Long-term effects include pulmonary problems (e.g., wheezing, shortness of breath), immunosuppression, and sex hormone imbalance.

DroNABINOl is an example of medical canNABINOids.

  • Because hallucinogens are not typically associated with symptoms of withdrawal, the information about the clinical features provided below pertains specifically to the issues associated with intoxication with the corresponding substances.

General considerations

Tryptamine derivatives [6]

Phenethylamine derivatives

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


β-blockers can cause unopposed α-agonism, which worsens vasospasm!

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



  • Substance: nicotine from the tobacco plant (consumed in cigarettes, cigars, pipes, e-cigarettes)
  • Mechanism of action: stimulates nicotinic receptors in autonomic gangliasympathetic and parasympathetic stimulation [40]
  • Epidemiology [41]
    • Approx. 13% of adults in the US smoke cigarettes
    • Most prevalent cause of preventable morbidity and mortality in the US
  • Clinical features
  • Assessment: Smoking history is measured in pack years, which is used to quantify a person's lifetime exposure to tobacco.
    • The number of cigarette packs (20 cigarettes) that a person smokes per day multiplied by the number of years of cigarette consumption, e.g., (1 pack/day) x (10 years smoking history) = 10 pack years.
  • Treatment [40][42]
    • Counseling and support
    • Varenicline (alpha-4-beta-2 nACHR partial agonist): reduces positive symptoms and prevents withdrawal
    • Bupropion: reduces craving and withdrawal symptoms
    • Nicotine replacement therapy; (inhaler, lozenges; , transdermal patch; , nasal spray, gum)
  • Complications [40][42]

GHB is sometimes used as an acquaintance rape drug because it is hard to detect and has amnestic effects and a rapid onset of action.

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

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