Substance use disorders involve a pathologic pattern of behaviors in which patients continue to use a substance despite experiencing significant problems related to its use. Diagnosis of a substance use disorder is based on diagnostic criteria for the pattern of behaviors. Treating substance use disorders is challenging and varies depending on the substance and circumstances, but often involves both psychotherapy and pharmacotherapy.
The term "substance use disorder" is more accurate, clearly defined, and has fewer negative connotations than "addiction," "abuse," or "dependence." The substances associated with substance use disorders are included in the Ten Drug Classes Commonly Associated With Substance-Related Disorders.
Use of illicit drugs is not always indicative of a substance use disorder. Conversely, legal substances, such as alcohol and prescription medications (and cannabis in some states or countries), may be involved in a substance use disorder (1).
Recreational drug use, although often not sanctioned by society, is not a new phenomenon, and has existed in some form or another for centuries. People have used drugs for a variety of reasons (2), including the following:
To alter or enhance mood
As part of religious ceremonies
To obtain spiritual enlightenment
To enhance performance
Some users tend to use drugs episodically in relatively small doses without clinical toxicity or development of tolerance and physical dependence. Many recreational drugs (eg, crude opium, alcohol, marijuana, caffeine, hallucinogenic mushrooms, coca leaf) are “natural” (ie, close to plant origin); historically, they contained a mixture of relatively low concentrations of psychoactive compounds and were not isolated psychoactive compounds. However, some substances considered to be "natural" and low-dose substances are consumed in higher doses and carry more risk of harm than in the past. Marijuana, for example, has become more potent over time (both in plant form and in synthetic forms), with more potential for harm (Some users tend to use drugs episodically in relatively small doses without clinical toxicity or development of tolerance and physical dependence. Many recreational drugs (eg, crude opium, alcohol, marijuana, caffeine, hallucinogenic mushrooms, coca leaf) are “natural” (ie, close to plant origin); historically, they contained a mixture of relatively low concentrations of psychoactive compounds and were not isolated psychoactive compounds. However, some substances considered to be "natural" and low-dose substances are consumed in higher doses and carry more risk of harm than in the past. Marijuana, for example, has become more potent over time (both in plant form and in synthetic forms), with more potential for harm (3, 4). Similarly, caffeine is available in high doses in energy drinks marketed towards adolescents (). Similarly, caffeine is available in high doses in energy drinks marketed towards adolescents (5, 6).
Physiologic Effects of Substance Use
These substances all directly activate the brain's reward system and produce feelings of pleasure. The activation may be so intense that patients intensely crave the substance and neglect normal activities to obtain and use it. These substances also have direct physiologic effects (7), including the following:
Intoxication
Withdrawal
Substance-induced psychiatric disorders
The specific biology, manifestations, and treatment of intoxication and withdrawal vary by substance or substance class.
Intoxication
Intoxication refers to development of a reversible substance-specific syndrome of mental and behavioral changes that may involve altered perception, euphoria, cognitive impairment, impaired judgment, impaired physical and social functioning, mood lability, belligerence, or a combination. Taken to the extreme, intoxication can lead to overdose, significant morbidity, and risk of death.
Withdrawal
Withdrawal refers to substance-specific physiologic effects, symptoms, and behavioral changes that are caused by stopping or reducing the intake of a substance. To be classified as a substance-withdrawal disorder, the withdrawal syndrome must cause the patient significant distress and/or impair functioning (eg, social, occupational) (8). Most patients with withdrawal recognize that readministering the substance will reduce their symptoms.
Although some patients with a withdrawal syndrome have a substance use disorder, some drugs, particularly opioids, sedative/hypnotics, and stimulants, can result in withdrawal symptoms even when taken as prescribed for legitimate medical reasons and for relatively brief periods (< 1 week for opioids). Withdrawal symptoms that develop following appropriate medical use are not considered criteria for diagnosis of a substance use disorder (8).
References
1. Wu LT, McNeely J, Subramaniam GA, et al. DSM-5 substance use disorders among adult primary care patients: Results from a multisite study. Drug Alcohol Depend. 2017;179:42-46. doi:10.1016/j.drugalcdep.2017.05.048
2. Lojszczyk A, Wilson R, Wood J, Hutton A. Motivational characteristics of recreational drug use among emerging adults in social settings: an integrative literature review. Front Public Health. 2023;11:1235387. Published 2023 Oct 31. doi:10.3389/fpubh.2023.1235387
3. Chandra S, Radwan MM, Majumdar CG, Church JC, Freeman TP, ElSohly MA. New trends in cannabis potency in USA and Europe during the last decade (2008-2017) [published correction appears in Eur Arch Psychiatry Clin Neurosci. 2019 Dec;269(8):997. doi: 10.1007/s00406-019-01020-1.]. Eur Arch Psychiatry Clin Neurosci. 2019;269(1):5-15. doi:10.1007/s00406-019-00983-5
4. Testai FD, Gorelick PB, Aparicio HJ, et al. Use of Marijuana: Effect on Brain Health: A Scientific Statement From the American Heart Association. Stroke. 2022;53(4):e176-e187. doi:10.1161/STR.0000000000000396
5. Soós R, Gyebrovszki Á, Tóth Á, Jeges S, Wilhelm M. Effects of Caffeine and Caffeinated Beverages in Children, Adolescents and Young Adults: Short Review. . Effects of Caffeine and Caffeinated Beverages in Children, Adolescents and Young Adults: Short Review.Int J Environ Res Public Health. 2021;18(23):12389. Published 2021 Nov 25. doi:10.3390/ijerph182312389
6. van Dam RM, Hu FB, Willett WC. Coffee, Caffeine, and Health. . Coffee, Caffeine, and Health.N Engl J Med. 2020;383(4):369-378. doi:10.1056/NEJMra1816604
7. Testa A, Giannuzzi R, Sollazzo F, Petrongolo L, Bernardini L, Dain S. Psychiatric emergencies (part II): psychiatric disorders coexisting with organic diseases. Eur Rev Med Pharmacol Sci. 2013;17 Suppl 1:65-85.
8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. American Psychiatric Association Publishing; 2022:543-553.
Etiology of Substance Use Disorders
People with a substance use disorder usually progress from experimentation to occasional use and then to heavy use prior to developing a substance use disorder (1). This progression is complex and only partially understood. The process depends on interaction between the drug, user, and setting.
Drug
Drugs in the 10 classes vary in how likely they are to be misused or lead to a substance use disorder. This potential for misuse depends upon a combination of factors, including the following:
Route of administration
Rate at which the drug crosses the blood-brain barrier and stimulates the reward pathway
Time to onset of effect
Ability to induce tolerance and/or withdrawal symptoms
In addition, substances that are legally and/or readily available (eg, alcohol, tobacco) are easier to access and thus the risk of progression to misuse is increased. Further, as perception of the risk in using a particular substance diminishes, there may be subsequent experimentation with and/or recreational use of the drug, increasing exposures to substances that can lead to a use disorder. Fluctuations in perception of risk are influenced by multiple factors, including findings regarding general medical and psychiatric sequelae of use and social outcomes (2).
During treatment of medical illness or following surgical or dental procedures, patients may be prescribed opioids. A substantial portion of these medications go unused but may remain in the home, representing a significant source for children, adolescents, and adults who take them accidentally or wish to use them for nonmedical purposes (3). In response, there has been increased emphasis on the need to do the following:
Advise use of or prescribe nonaddictive analgesics (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) when appropriateAdvise use of or prescribe nonaddictive analgesics (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) when appropriate
Prescribe the number of opioid doses based on evidence-based guidelines (4)
Promote safe storage and disposal of addictive or potentially toxic medications
Expand prescription take-back programs
User
Predisposing factors in users include the following:
Psychological characteristics
Circumstances and disorders
Psychological characteristics of an individual have generally not been proven to be risk factors for a substance use disorder, and the concept of the addictive personality that has variously been described has few data to support it. However, people with low levels of self-control (impulsivity) or high levels of risk-taking and novelty-seeking may have an increased risk of developing a substance use disorder (5).
A number of circumstances and coexisting disorders appear to increase risk. For example, people who are sad, emotionally distressed, or socially alienated may find these feelings are temporarily relieved by a drug; this can lead to increased use and sometimes a substance use disorder. Insecure attachment (referring to a way of relating to others that involves fear, mistrust, or difficulty feeling safe in close relationships, often due to early life experiences), particularly when established in childhood or adolescence, is prospectively associated with increased risk of developing substance use disorders (6). Both anxious and avoidant attachment styles are implicated, with emotion dysregulation frequently mediating this relationship.
Patients with other psychiatric disorders are at increased risk of developing a substance use disorder (7), particularly mood disorders, anxiety disorders, attention deficit disorder, personality disorders, and schizophrenia (8, 9).
Patients with chronic pain often take opioids for relief; many subsequently develop a substance use disorder (10). However, in many of these patients, nonopioid medications and other treatments can adequately relieve pain and suffering.
All substance use disorders are likely polygenic in nature (11). There are a number of genetic and epigenetic factors, which vary by specific substance, that impact the likelihood of developing a substance use disorder and its progression.
Pearls & Pitfalls
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Setting
Cultural and social factors are very important in initiating and maintaining (or relapsing to) substance use. Observing family members (eg, parents, older siblings) and peers misusing substances increases risk that people will begin to misuse substances. Peers are a particularly powerful influence among adolescents (see Drug and Substance Use in Adolescents). People who are trying to stop using a substance find it much more difficult if they are around others who also use that substance (12).
Physicians may inadvertently contribute to harmful use of psychoactive medications by overzealously prescribing them to relieve pain or stress (13). Many social factors, including social media, contribute to patients' expectation that medications and recreational drugs should be used to relieve all distress.
Etiology references
1. Strickland JC, Acuff SF. Role of social context in addiction etiology and recovery. Pharmacol Biochem Behav. 2023;229:173603. doi:10.1016/j.pbb.2023.173603
2. Clay JM, Parker MO. The role of stress-reactivity, stress-recovery and risky decision-making in psychosocial stress-induced alcohol consumption in social drinkers. Psychopharmacology (Berl). 2018;235(11):3243-3257. doi:10.1007/s00213-018-5027-0
3. Stone AL, Qu'd D, Luckett T, et al. Leftover Opioid Analgesics and Disposal Following Ambulatory Pediatric Surgeries in the Context of a Restrictive Opioid-Prescribing Policy. Anesth Analg. 2022;134(1):133-140. doi:10.1213/ANE.0000000000005503
4. Zhang DDQ, Dossa F, Arora A, et al. Recommendations for the Prescription of Opioids at Discharge After Abdominopelvic Surgery: A Systematic Review. JAMA Surg. 2020;155(5):420-429. doi:10.1001/jamasurg.2019.5875
5. Arenas MC, Aguilar MA, Montagud-Romero S, et al. Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models. Curr Neuropharmacol. 2016;14(1):87-100. doi:10.2174/1570159x13666150921112841
6. Schindler A. Attachment and Substance Use Disorders-Theoretical Models, Empirical Evidence, and Implications for Treatment. Front Psychiatry. 2019;10:727. Published 2019 Oct 15. doi:10.3389/fpsyt.2019.00727
7. Groenman AP, Janssen TWP, Oosterlaan J. Childhood Psychiatric Disorders as Risk Factor for Subsequent Substance Abuse: A Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2017;56(7):556-569. doi:10.1016/j.jaac.2017.05.004
8. Volkow ND, Blanco C. Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention. World Psychiatry. 2023;22(2):203-229. doi:10.1002/wps.21073
9. Grant BF, Saha TD, Ruan WJ, et al. Epidemiology of DSM-5 Drug Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III. JAMA Psychiatry. 2016;73(1):39-47. doi:10.1001/jamapsychiatry.2015.2132
10. Stalter N, Ma S, Simon G, Pruinelli L. Psychosocial problems and high amount of opioid administration are associated with opioid dependence and abuse after first exposure for chronic pain patients. Addict Behav. 2023;141:107657. doi:10.1016/j.addbeh.2023.107657
11. Miller AP, Bogdan R, Agrawal A, Hatoum AS. Generalized genetic liability to substance use disorders. J Clin Invest. 2024;134(11):e172881. Published 2024 Jun 3. doi:10.1172/JCI172881
12. Webster LR. Risk Factors for Opioid-Use Disorder and Overdose. Anesth Analg. 2017;125(5):1741-1748. doi:10.1213/ANE.0000000000002496
13. Barnett ML, Olenski AR, Jena AB. Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use. N Engl J Med. 2017;376(7):663-673. doi:10.1056/NEJMsa1610524
Diagnosis of Substance Use Disorders
Medical history and/or psychiatric assessment
Sometimes urine or serum drug screening tests
Laboratory testing, electrocardiography, or imaging studies to evaluate for toxicity
The clinical presentation of a substance use disorder varies widely. Many people with a substance use disorder have no or minimal functional impairment, or the impairment is known only to their closest family or friends. However, some patients present for emergency care due to an overdose or severe toxicity caused by a drug. Patients may seek medical care or concern may be raised by clinicians, family or friends, coworkers, law enforcement personnel, or as a result of drug screening tests required in some workplaces and other settings. Focus on accurate identification of patients with substance use disorders and referral for specialty treatment will help greatly in reducing individual consequences as well as societal impact.
Upon presentation, the patient is evaluated and an initial level of care is determined. (See also Toxicity of Illicit Substances.)
For each class of drugs associated with substance-related disorders (see Ten Drug Classes Commonly Associated With Substance-Related Disorders), the Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR) (1) defines a use disorder, and, where appropriate, intoxication and withdrawal syndromes as well as criteria for unspecified disorders related to that substance or drug class.
Specific substance use disorders
Diagnosis of substance use disorder is based on identifying a pathologic pattern of behaviors in which patients continue to use a substance despite experiencing significant functional impairment related to its use. The DSM-5-TR classification is organized into 4 categories that include a total of 11 criteria. Individuals meeting 2 or more of these criteria within a 12-month period are considered to have a substance use disorder.
Impaired control over use
The person takes the substance in larger amounts or for a longer time than originally planned
The person desires to stop or cut down on use of the substance
The person spends substantial time obtaining, using, or recovering from the effects of the substance
The person has an intense desire (craving) to use the substance
Social impairment
The person fails to fulfill major role obligations at work, school, or home
The person continues to use the substance even though it causes (or worsens) social or interpersonal problems
The person gives up or reduces important social, occupational, or recreational activity because of substance use
Risky use
The person uses the substance in physically hazardous situations (eg, when driving or in dangerous social circumstances)
The person continues to use the substance despite knowing it is worsening a medical or psychological problem
Pharmacologic symptoms
Tolerance: The person needs to progressively increase the drug dose to produce intoxication or the desired effect, or the effect of a given dose decreases over time
Withdrawal: Untoward physical effects occur when the drug is stopped or when it is counteracted by a specific antagonist
The severity of the substance use disorder is determined by the number of symptoms:
Mild: 2 to 3 criteria
Moderate: 4 to 5 criteria
Severe: ≥ 6 criteria
For each severity level, there is also a specifier for early or sustained remission.
Specific substance intoxication syndromes
Diagnosis of an intoxication syndrome generally requires recent use of a substance, clinically significant behavioral or psychological changes, signs or symptoms specific to that substance, and that the signs or symptoms not be attributed to another condition (1).
Intoxication syndromes are defined for all classes of substances except tobacco.
Specific substance withdrawal syndromes
Diagnosis of a withdrawal syndrome generally requires prolonged use of the substance with recent cessation, and signs or symptoms specific to that substance withdrawal syndrome that cause clinically significant functional impairment and are not better attributed to another condition (1).
Note that some drugs, particularly opioids, sedative/hypnotics, and stimulants, can result in tolerance and/or withdrawal symptoms even when taken as prescribed for legitimate medical reasons and for relatively brief periods (< 1 week for opioids). Withdrawal symptoms that develop following such appropriate medical use are not considered criteria for diagnosis of a substance use disorder.
Withdrawal syndromes are defined for all classes of substances except inhalants and hallucinogens.
Diagnosis reference
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, Text Revision. American Psychiatric Association Publishing; 2022:543-553.
Treatment of Substance Use Disorders
Varies depending on substance and circumstances
Treating a substance use disorder is challenging and includes 1 or more of the following:
Acute detoxification
Prevention and management of withdrawal
Cessation (or rarely, reduction) of use
Maintenance of abstinence
With increasing scientific understanding of the biologic processes underlying compulsive drug-taking, substance use disorders are considered medical illnesses. These illnesses are amenable to various forms of treatment. Treatment phases may be managed with counseling and support, pharmacotherapy, and supportive treatment of general medical complications. Treatment is provided in many different clinical settings, including outpatient or inpatient general medical care settings (primary care, mental health care, emergency departments), inpatient or outpatient substance use rehabilitation programs, community or online support groups, or in prisons.
Assessment and management of overdose, toxicity, and withdrawal are discussed for specific substances separately. (See also Toxicity of Illicit Substances.)
Counseling and support may be provided in various forms and many patients are treated with more than 1 form concurrently or serially. These include psychotherapy (eg, motivational enhancement therapy, relapse prevention, cognitive and dialectical behavioral therapy) and support groups (eg, Alcoholics Anonymous, Narcotics Anonymous, and other Twelve Step programs).
Pharmacologic therapy includes agonist therapy (eg, nicotine-replacement therapy for tobacco use disorder, methadone or naltrexone for opioid use disorder), mixed agonist-antagonist therapy (buprenorphine for opioid use disorder), medications that alter or restore neurotransmitter balance to reduce cravings (acamprosate in alcohol use disorder), medications that alter neurotransmitter release to reduce pleasurable effects (topiramate for alcohol use disorder), and medications that cause noxious symptoms during a relapse (disulfiram for alcohol use disorder) (Pharmacologic therapy includes agonist therapy (eg, nicotine-replacement therapy for tobacco use disorder, methadone or naltrexone for opioid use disorder), mixed agonist-antagonist therapy (buprenorphine for opioid use disorder), medications that alter or restore neurotransmitter balance to reduce cravings (acamprosate in alcohol use disorder), medications that alter neurotransmitter release to reduce pleasurable effects (topiramate for alcohol use disorder), and medications that cause noxious symptoms during a relapse (disulfiram for alcohol use disorder) (1, 2).
Treatment references
1. Ray LA, Meredith LR, Kiluk BD, Walthers J, Carroll KM, Magill M. Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e208279. Published 2020 Jun 1. doi:10.1001/jamanetworkopen.2020.8279
2. Perry C, Liberto J, Milliken C, et al. The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Ann Intern Med. 2022;175(5):720-731. doi:10.7326/M21-4011
Screening
Routine screening for substance use disorders is an essential component of primary care, as early identification and intervention can significantly improve health outcomes. Screening should be conducted in a nonjudgmental, confidential manner and can be integrated into regular health maintenance visits.
Conducting universal screening—rather than relying on clinical suspicion—is recommended due to the often-hidden nature of substance use and its associated stigma. Effective screening involves asking about use of common substance categories, including alcohol, tobacco/nicotine, cannabis, prescription medications (eg, opioids, benzodiazepines, stimulants), and illicit drugs. Validated tools such as the AUDIT-C (Alcohol Use Disorders Identification Test - Consumption) (Conducting universal screening—rather than relying on clinical suspicion—is recommended due to the often-hidden nature of substance use and its associated stigma. Effective screening involves asking about use of common substance categories, including alcohol, tobacco/nicotine, cannabis, prescription medications (eg, opioids, benzodiazepines, stimulants), and illicit drugs. Validated tools such as the AUDIT-C (Alcohol Use Disorders Identification Test - Consumption) (1), DAST-10 (Drug Abuse Screening Test) (2), and single-question screens (eg, “How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?”) offer quick, evidence-based approaches.
Screening is most effective when followed by brief assessment to determine risk level and need for further evaluation or treatment. If a patient screens positive, the clinician should assess for severity, functional impact, and comorbid mental health conditions, and consider a referral for specialized care when appropriate. Incorporating motivational interviewing techniques can enhance patient engagement and readiness for change.
Screening references
1. Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998;158(16):1789-1795. doi:10.1001/archinte.158.16.1789
2. Tiet QQ, Leyva YE, Moos RH, Frayne SM, Osterberg L, Smith B. Screen of Drug Use: Diagnostic Accuracy of a New Brief Tool for Primary Care. JAMA Intern Med. 2015;175(8):1371-1377. doi:10.1001/jamainternmed.2015.2438
Prevention
Prevention of substance use disorders encompasses targeted and universal strategies aimed at mitigating risk factors and bolstering protective factors across developmental stages. In clinical practice, prevention efforts should begin early, particularly during adolescence, when initiation of substance use is most likely and neurobiological vulnerability to addiction is heightened. Providers should assess for known risk factors—including family history of substance use disorders, trauma exposure, co-occurring psychiatric disorders, and early behavioral problems—and consider preventive interventions such as psychoeducation, cognitive and behavioral skill development, and family-based support.
At the population level, prevention includes regulatory and environmental strategies such as taxation, age restrictions, and controlled medication-prescribing practices. Within clinical settings, health care providers play a key role by offering anticipatory guidance, counseling patients on substance-related risks, and screening for early signs of misuse. Routine review of prescription monitoring data, cautious opioid prescribing, and patient education about medication safety are essential components of prevention.
Overdose prevention is a critical element of efforts to prevent substance use disorders, particularly in the context of rising opioid-related mortality. Clinicians should educate patients and families about the risks of overdose, especially when opioids are prescribed, and co-prescribe or dispense naloxone (eg, intranasal naloxone/Narcan) to individuals at elevated risk. Equipping patients and communities with naloxone, along with instructions on its use, is an evidence-based harm-reduction strategy that saves lives and facilitates linkage to care.Overdose prevention is a critical element of efforts to prevent substance use disorders, particularly in the context of rising opioid-related mortality. Clinicians should educate patients and families about the risks of overdose, especially when opioids are prescribed, and co-prescribe or dispense naloxone (eg, intranasal naloxone/Narcan) to individuals at elevated risk. Equipping patients and communities with naloxone, along with instructions on its use, is an evidence-based harm-reduction strategy that saves lives and facilitates linkage to care.
Key Points
Substance use disorder involves a pathologic pattern of behaviors in which patients continue to use a substance despite experiencing significant problems related to its use.
Manifestations are categorized into impaired control over use, social impairment, risky use, and pharmacologic symptoms.
The terms "addiction," "abuse," and "dependence" are vague and value-laden; it is preferable to speak of "substance use disorders" and focus on the specific manifestations and their severity.
The consequences and treatment of substance use disorder vary greatly depending on the substance.
