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Substance-related and addictive disorders

Last updated: October 1, 2021

Summarytoggle arrow icon

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.

Overview of 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., 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, neglect 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

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

Definitions of 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)

Substance intoxication and withdrawal [4]

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
  • Respiratory arrest

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][10]
  • Clinical features of 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 [11]
    • Withdrawal: psychosocial support and interventions [12]
  • Complications [13]
    • 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 [14]
      • 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) [15]
      • 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:
        • Clinical features of cannabis withdrawal (see above)
        • Substance use to alleviate or avoid withdrawal symptoms
    • 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 [4]

Phenethylamine derivatives

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


See benzodiazepine intoxication, benzodiazepine withdrawal, and barbiturate intoxication in the article on sedative-hypnotic drugs.

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 [38]
  • Epidemiology [39]
    • 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 [38][40]
    • 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 [38][40]

  • Definition: : a disorder in which the affected individual feels the compulsion to gamble despite negative consequences and/or multiple attempts to stop [1]
  • Epidemiology [1][41]
    • Sex: >
    • No specific age group
  • Etiology: combination of factors (genetic, environmental, neurochemical abnormalities) [1][41]
  • Diagnosis: ≥ 4 of the following in a 12 month period [1]
    • Using increasing amounts of money to gamble
    • Relying on others for financial support to maintain habit
    • Restlessness or irritability 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
    • Gambling when feeling helpless, guilty, anxious or depressed
  • Treatment [41][42]
  • Complications [1][41]

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)

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM–5). undefined. 2013 . doi: 10.1176/appi.books.9780890425596 . | Open in Read by QxMD
  2. Heard K, Hoppe J. Phencyclidine (PCP) intoxication in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: April 9, 2018. Accessed: March 20, 2019.
  3. Walls R, Hockberger R, Gausche-Hill M. Rosen's Emergency Medicine. Elsevier Health Sciences ; 2018
  4. Dominici P, Kopec K, Manur R, Khalid A, Damiron K, Rowden A. Phencyclidine Intoxication Case Series Study. Journal of Medical Toxicology. 2014; 11 (3): p.321-325. doi: 10.1007/s13181-014-0453-9 . | Open in Read by QxMD
  5. Lande RG. Nicotine Addiction. In: Xiong GL, Nicotine Addiction. New York, NY: WebMD. Updated: August 10, 2017. Accessed: December 9, 2017.
  6. Current Cigarette Smoking Among Adults in the United States. Updated: November 18, 2019. Accessed: February 28, 2020.
  7. Rigotti N. Overview of smoking cessation management in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: August 9, 2018. Accessed: March 20, 2019.
  8. Overview of the Drug Overdose Epidemic: Behind the Numbers. Updated: December 19, 2018. Accessed: March 19, 2019.
  9. National practice guideline for the use of medications in the treatment of addiction involving opioid use. Updated: June 1, 2015. Accessed: December 4, 2017.
  10. Monte AA, Shelton SK, Mills E, et al. Acute Illness Associated With Cannabis Use, by Route of Exposure. Ann Intern Med. 2019; 170 (8): p.531. doi: 10.7326/m18-2809 . | Open in Read by QxMD
  11. Turner AR, Spurling BC, Agrawal S. Marijuana Toxicity. StatPearls. 2020 .
  12. Walther L, Gantner A, Heinz A, Majiić T. Evidence-based Treatment Options in Cannabis Dependency. Deutsches Aerzteblatt Online. 2016 . doi: 10.3238/arztebl.2016.0653 . | Open in Read by QxMD
  13. Gorelick DA. Cannabis Use and Disorder: Epidemiology, Comorbidity, Health Consequences, and Medico-Legal Status. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: October 28, 2016. Accessed: December 5, 2017.
  14. A. Galli J, Andari Sawaya R, K. Friedenberg F. Cannabinoid Hyperemesis Syndrome. Curr Drug Abuse Rev. 2011; 4 (4): p.241-249. doi: 10.2174/1874473711104040241 . | Open in Read by QxMD
  15. Patterson DA, Smith E, Monahan M, et al. Cannabinoid Hyperemesis and Compulsive Bathing: A Case Series and Paradoxical Pathophysiological Explanation. The Journal of the American Board of Family Medicine. 2010; 23 (6): p.790-793. doi: 10.3122/jabfm.2010.06.100117 . | Open in Read by QxMD
  16. Gorelick DA. Cocaine Use Disorder in Adults: Epidemiology, Pharmacology, Clinical Manifestations, Medical Consequences, and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: August 1, 2017. Accessed: December 5, 2017.
  17. Nelson L, Odujebe O. Cocaine: Acute Intoxication. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: June 21, 2017. Accessed: December 5, 2017.
  18. Richards JR, Garber D, Laurin EG, et al. Treatment of cocaine cardiovascular toxicity: a systematic review. Clin Toxicol. 2016; 54 (5): p.345-364. doi: 10.3109/15563650.2016.1142090 . | Open in Read by QxMD
  19. Morgan JP. Clinical Manifestations, Diagnosis, and Management of the Cardiovascular Complications of Cocaine Abuse. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: October 25, 2017. Accessed: December 5, 2017.
  20. Goldman L, Schafer AI. Goldman-Cecil Medicine, 25th Edition. Elsevier ; 2016
  21. Boyer EW, Seifert SA, Hernon C. Methamphetamine: Acute Intoxication. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: April 6, 2017. Accessed: December 5, 2017.
  22. Paulus M. Methamphetamine Use Disorder: Epidemiology, Clinical Manifestations, Course, Assessment, and Diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: June 15, 2017. Accessed: December 5, 2017.
  23. Campbell GA, Rosner MH. The Agony of Ecstasy: MDMA (3,4-Methylenedioxymethamphetamine) and the Kidney. Clin J Am Soc Nephrol. 2008; 3 (6): p.1852-1860. doi: 10.2215/cjn.02080508 . | Open in Read by QxMD
  24. Orsolini L, Papanti GD, De Berardis D, Guirguis A, Corkery JM, Schifano F. The “Endless Trip” among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review. Frontiers in Psychiatry. 2017; 8 . doi: 10.3389/fpsyt.2017.00240 . | Open in Read by QxMD
  25. Devlin RJ, Henry JA. Clinical review: Major consequences of illicit drug consumption. Critical Care. 2008; 12 (1): p.202. doi: 10.1186/cc6166 . | Open in Read by QxMD
  26. Barile FA. Barile's Clinical Toxicology. CRC Press ; 2019
  27. Teter CJ, Guthrie SK. A Comprehensive Review of MDMA and GHB: Two Common Club Drugs. Pharmacotherapy. 2001; 21 (12): p.1486-1513. doi: 10.1592/phco.21.20.1486.34472 . | Open in Read by QxMD
  28. Fallon JK, Shah D, Kicman AT, et al. Action of MDMA (Ecstasy) and Its Metabolites on Arginine Vasopressin Release. Ann N Y Acad Sci. 2006; 965 (1): p.399-409. doi: 10.1111/j.1749-6632.2002.tb04181.x . | Open in Read by QxMD
  29. Liechti ME. Effects of MDMA on body temperature in humans. Temperature. 2014; 1 (3): p.192-200. doi: 10.4161/23328940.2014.955433 . | Open in Read by QxMD
  30. PubChem - 3,4-Methylenedioxymethamphetamine (Compound). . Accessed: August 10, 2020.
  31. Dugosh KL, Cacciola JS. Clinical Assessment of Substance Use Disorders. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: April 18, 2017. Accessed: December 4, 2017.
  32. Krause RS. Alcohol and Substance Abuse Evaluation. In: Brenner BE, Alcohol and Substance Abuse Evaluation. New York, NY: WebMD. Updated: February 12, 2016. Accessed: December 4, 2017.
  33. Jones AW, Holmgren A, Kugelberg FC. Driving under the influence of gamma-hydroxybutyrate (GHB). Forensic Science, Medicine, and Pathology. 2008; 4 (4): p.205-211. doi: 10.1007/s12024-008-9040-1 . | Open in Read by QxMD
  34. Zvosec DL, Smith SW. Gamma Hydroxybutyrate (GHB) Intoxication. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: March 8, 2017. Accessed: September 14, 2017.
  35. Zvosec DL, Smith SW. Gamma Hydroxybutyrate (GHB) Dependence and Withdrawal. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: August 7, 2012. Accessed: September 14, 2017.
  36. Perry H. Inhalant Abuse in Children and Adolescents. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: October 27, 2017. Accessed: December 9, 2017.
  37. Domino FJ. Overview of Gambling Disorder. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: July 14, 2017. Accessed: December 9, 2017.
  38. Slutske WS. Natural recovery and treatment-seeking in pathological gambling: Results of two U.S. national surveys. Am J Psychiatry. 2006; 163 (2): p.297-302. doi: 10.1176/appi.ajp.163.2.297 . | Open in Read by QxMD
  39. Karila et al. Synthetic cathinones: a new public health problem.. Current neuropharmacology. 2015; 13 (1): p.12-20. doi: 10.2174/1570159X13666141210224137 . | Open in Read by QxMD
  40. Weinstein et al.. Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health. Frontiers in Psychiatry. 2017; 8 . doi: 10.3389/fpsyt.2017.00156 . | Open in Read by QxMD
  41. Murray A, Traylor J. Caffeine Toxicity. StatPearls. 2020 .
  42. Willson C. The clinical toxicology of caffeine: A review and case study. Toxicology Reports. 2018; 5 : p.1140-1152. doi: 10.1016/j.toxrep.2018.11.002 . | Open in Read by QxMD
  43. Bordeaux B, Lieberman HR. Benefits and Risks of Caffeine and Caffeinated Beverages. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. updated: October 11, 2017. Accessed: December 9, 2017.
  44. Yew D. Caffeine Toxicity. In: Miller MA, Caffeine Toxicity. New York, NY: WebMD. Updated: June 6, 2017. Accessed: December 9, 2017.
  45. Gershman and Fass. Synthetic cathinones ('bath salts'): legal and health care challenges.. P & T : a peer-reviewed journal for formulary management. 2012; 37 (10): p.571-95.
  46. Opioids portal. Updated: September 6, 2019. Accessed: October 28, 2019.