Considerations for Determining Whether Drug Addiction Is a Disability
Joseph A. Hirsch
Search for other papers by Joseph A. Hirsch in
Current site
Google Scholar
PubMed
Close
,
Steven Mandel
Search for other papers by Steven Mandel in
Current site
Google Scholar
PubMed
Close
,
Kurt T. Hegmann
Search for other papers by Kurt T. Hegmann in
Current site
Google Scholar
PubMed
Close
,
Alexandra G. Stratyner
Search for other papers by Alexandra G. Stratyner in
Current site
Google Scholar
PubMed
Close
,
Stuart Gitlow
Search for other papers by Stuart Gitlow in
Current site
Google Scholar
PubMed
Close
,
James B. Talmage
Search for other papers by James B. Talmage in
Current site
Google Scholar
PubMed
Close
, and
Christopher R. Brigham
Search for other papers by Christopher R. Brigham in
Current site
Google Scholar
PubMed
Close
Free access

Abstract

There is an epidemic of drug overdose–related fatalities. Recent data indicate that the age-adjusted death rate from overdoses nearly quintupled over a 20-year period (2001-2021) to 32.4 per 100,000. More than 70% of these fatalities were caused by opioid overdose, especially the synthetic drug, fentanyl. Despite an increase in substance abuse and dependency treatment, mortality and morbidity associated with opioid, cocaine, psychostimulant, benzodiazepine, alcohol, and tobacco use disorders continue to rise. To better understand the factors contributing to this crisis, the multifaceted phenomenon of drug addiction is explored. The controversial chronic, relapsing “disease of the brain” model, which emphasizes the role of the neurotransmitter dopamine, the ventral tegmental area, and the nucleus accumbens, is critically considered. In addition, more expansive neurobiological models that include a host of other neurotransmitters, brain regions, and cognitive processes, as well as classical and operant conditioning and social learning theory to help better understand compulsive drug taking, tolerance, risk-taking, and relapse, were examined. For this, the roles of genetics and epigenetics vs individual agency in drug addiction were considered. The economic and occupational consequences borne both individually and societally are enormous. Ultimately, whether the presence of drug addiction satisfies the criteria for a disability remains a conundrum, especially from the perspectives of financial support (eg, Social Security, private insurance companies) vs regulation (eg, licensing agencies).

Introduction

Beginning in early 2020, two large, overlapping epidemics affected the United States (US). The coronavirus disease 2019 (COVID-19) pandemic quickly became the third leading cause of death, contributing to the deaths of more than 350,000 people by the end of 2020.1 Predating and then overlapping with COVID-19 was an epidemic of deaths from drug overdose in the US. Between 2001 and 2021, the age-adjusted death rate from overdoses nearly quintupled, to 32.4 per 100,000.2 In 2021, this accounted for more than 106,000 deaths, with a 14% increase from 2020. More than 70% of these fatalities were caused by opioid overdose, most involving synthetic opioids other than methadone. Cocaine and psychostimulants also contributed to increasing drug overdose deaths (approximately 17% of the total in 2021). For the first half of 2020, there were almost 3,000 fatal overdoses owing to benzodiazepines, with 92.7% also involving opioids.3

The enormous surge in morbidity and mortality associated with drug use and addiction piqued our curiosity. The characterization of drug addiction as a chronic, relapsing disease of the brain is controversial, with some arguing in favor of that position, while others argue that this model is incomplete or oversimplified, especially regarding the neurotransmitter dopamine (DA) hypothesis.4-8 This distinction may be important in determining whether drug addiction is a disability in a selected subpopulation of abusers. Are users able to adjust their behavior and discontinue abusing substances? Or is their substance abuse determined by genetic factors? Or are both factors at play?9

With this in mind, a multidisciplinary task force of clinicians and researchers with expertise in addiction, psychopharmacology, mental illness, disability, and medicine were assembled. The goal was to investigate drug addiction and determine if the assignment of disability is appropriate. Insights into the multifaceted disease of substance use disorder (SUD) with brief discussions of the epidemiology, neurobiology, psychology, medical and social roots, and consequences of addiction are offered.

Epidemiology of SUD

A minority of individuals who use illicit substances go on to meet the diagnostic criteria for an SUD, but it is helpful to put the numbers in context. The total number of users of an illicit substance(s) among those 12 years or older in the US in 2020 was estimated to be 59.3 million, with marijuana the most commonly used illicit substance, followed by stimulants, opioids, and hallucinogens.10 However, substance use is not limited to illicit substances, as alcohol use continues to dwarf the use of opioids. More than 2.3 billion people (43% of the world's population) drink alcohol, with a 12% per-capita increase from 2000 to 2016.11

More relevant for this review is the specifically targeted population of those diagnosed as having SUD. Note that the data and estimates discussed herein are likely considerably underestimated owing to soaring rates of substance use and abuse and changing social policies (eg, legalization of marijuana). Thus, the date of data collection in this body of research is important. Overall, the 12-month and lifetime prevalence rates of DSM-5 drug use disorder (DUD) in the US in 2012-2013 were 3.9% and 9.9%, respectively.12 In the US, the lifetime prevalence rate of alcohol use disorder was 30.3%, higher than (unspecified) drug use disorder (10.3%), major depressive disorder (13.2%), dysthymia (3.2%), bipolar I disorder (3.3%), and bipolar II disorder (1.1%).13 These comparisons are noteworthy because mental illness is a criterion for disability benefits under Social Security guidelines, whereas drug addiction is not.14

Nevertheless, the global addiction-treatment market for substances other than tobacco (for which the market has been present for decades) has only surged relatively recently and is predicted to continue trending upward sharply.15 Roughly $7 billion is projected to be spent for addiction treatment in the US by 2026. However, this will predominantly go toward the treatment of tobacco-smoking addiction. Premature mortality affects up to half of tobacco users, and tobacco-related fatalities worldwide are now 8 million per year.16 Only 4% of users who attempt to quit tobacco on their own will succeed, but professional support and proven cessation medications can more than double a tobacco user's chance of successfully quitting.16

Polysubstance use is common, and many individuals develop multiple comorbid SUDs.17 For example, among those with heroin use disorder, 66% also have nicotine use disorder, 25% also have alcohol use disorder, and more than 20% also have cocaine use disorder. Among those with cocaine use disorder, almost 60% also have alcohol use disorder, 48% also have nicotine use disorder, and more than 21% also have marijuana use disorder. Such comorbidity complicates treatment.17

Historical Perspective of Substance Use and Abuse

Psychoactive drugs have been used worldwide since the dawn of humankind for medical and religious or other ritualistic purposes.18,19 Use and abuse of chemical substances have been described and sometimes extolled in literature, from ancient texts to classical writing, to memoirs of the 19th and 20th centuries, to the Beat Generation,20-25 and to the popular music of 20th-century America and England.26-30

While billions of individuals have used and abused alcohol and other chemical substances, they were not necessarily permanently impaired—at least occupationally, much less permanently disabled.

Although the public is fascinated with celebrities, especially in the performing arts, who have been implicated in illicit drug use or abuse, they make up only a small minority of individuals with addictive disease.31 In fact, the prevalence of SUDs and substance abuse among individuals employed in the arts, entertainment, and recreation was almost 25% less than those employed in hospitality and food service and 10% less than those employed in construction.31 Nevertheless, the influence of celebrities' views, attitudes, and behaviors has enormously impacted drug use, especially among younger individuals.32

Substance Use vs Addiction: General Considerations

Many individuals try psychoactive drugs for various reasons—curiosity, societal glamorization, imitation of celebrities, social pressure, rebelliousness, escapism, medical or psychiatric need, or religious custom. Susceptible populations (eg, youth) may first become disposed to trying licit or illicit psychoactive substances through depictions in film, music, and literature.32 Advertising, a form of social (vicarious) learning, has also targeted the young and specific ethnic groups to drink alcohol or smoke cigarettes.32,33

Most recreational users of chemical substances do not become addicted.34 However, a minority of individuals with a propensity for risk taking, despite known inherent consequences, develop an addiction to psychoactive substances that is characterized by compulsive, poorly controlled self-administration.34 (The profile for iatrogenic addicts may be different, which is discussed below.)

Important Distinctions Between Substance Use and SUD

Substance use is defined as a behavioral or lifestyle decision made by individuals who do not have the more debilitating addiction (addictive disease).35 Sometimes, such individuals who do not have addictive disease may nevertheless take substances in excess; however, they do not have the morbidity or mortality associated with an addictive disease. For example, an 18-year-old whose first experience with alcohol results in loss of consciousness and sudden death does not die of an addictive disease, nor does a previously drug naïve 26-year-old who experiences respiratory arrest after accidentally overdoses on fentanyl.36 On the other hand, the death of a 45-year-old who is 6 months' sober after previously abusing alcohol because of hepatic failure would be considered a drug addiction–fatality, as would the death of a 30-year-old who had three previous arrests for driving under the influence and who fatally crashes a car while inebriated.

Neurobiology of Tolerance and Dependence

Physical tolerance may occur with many potentially addictive drugs upon repeated administration. Repeated (chronic) administration of drugs causes molecular changes to occur within organisms (either pharmacodynamically [eg, receptor density changes] or pharmacokinetically [ie, metabolic]) that dampen the drugs' pharmacological effects and require that higher dosages be administered to achieve the same effects.37 (Tolerance can sometimes occur rapidly, even after acute administration, and is known as tachyphylaxis.38) Importantly, tolerance does not always develop to the same degree or at the same rate for all the pharmacological effects of a particular drug. For example, tolerance to the euphoric effects of opioids occurs quickly, while tolerance to the respiratory depressant effect of opioids is incomplete, rendering addicts at risk for respiratory arrest as ever higher dosages are required to achieve the same degree of euphoria.39,40

Due to the adaptational changes that occur with chronic drug administration, physical dependence manifests after acute withdrawal of some substances.41,42 However, abstinence syndrome (withdrawal symptoms following drug abstinence as a result of physical dependence on a drug) is not unique to drugs of abuse. For example, antidepressants and beta-blocker drugs used for cardiovascular conditions may cause physical dependence, but these drugs are not abused.41 Thus, unlike substances of abuse, individuals who are prescribed beta-blockers and antidepressants will not resort to behaviors that risk their employment, relationships, or work functioning or engage in illegal activity to acquire their medications. Therefore, a more apt term than abstinence syndrome may be discontinuation syndrome.38

Behavioral conditioning to environmental or other cues (stimuli) associated with the drug may also result in drug tolerance, especially with abused substances.41 This includes the premises where the drugs are self-administered or associated with paraphernalia. This phenomenon, which is an extension of the experimentally derived conditioned-place preference (CPP), has been demonstrated in animals and humans and can elicit craving and/or relapse in the abstinent addict.43 Another problem with CPP is the risk of unexpected respiratory arrest. For example, previously nonlethal doses of heroin in rats or humans may become lethal if the drug is administered in physical circumstances atypical to where heroin is typically taken (eg, in a different cage for rodents or different room for humans).44

Neurobiology of Drug Addiction

Neurobiology utilizes complicated body processes controlled by the nervous system (eg, sensory perception, associative and nonassociative learning, emotions, decision-making) to shape an organism's response to environmental stimuli and enhance its ability to exploit their predictable features and adapt to unpredictable ones.45 The application of neuroscientific technologies in humans and laboratory animals has led to remarkable advances in the understanding of the neurobiological underpinnings of drug reinforcement and addiction.

Reward

The first preclinical research on drug addiction focused on the phenomenon of reward. Reward is a behavioral and neurobiological phenomenon well known to experimental psychologists and neuroscientists, beginning with Olds and Milner's46 seminal research in which rats were trained to electrically self-stimulate critical areas of the brain (intracranial self-stimulation [ICS]). The experimental paradigm used was based on Skinner's47 research on operant conditioning and reinforcement, whereby the consequences of a behavior increase the probability that the behavior will be repeated. Subsequent research demonstrated that the administration of psychoactive drugs has similar effects; thus, these substances may be abused in susceptible animals and humans because of the direct pharmacological effects on the same areas of the brain.48 These studies conclusively show the relationship between the abuse potential of a drug and its ability to lower this threshold for rewarding ICS, including differentiating between acute and chronic self-administration in animals and humans.48,49 The latter parameter is significant because it reflects the behavior maintenance of the disorder, a reflection of compulsive drug abuse. This paradigm explains not only opioid abuse maintenance but also that of psychostimulants (some of which are used in the treatment of attention-deficit/hyperactivity disorder [ADHD]), alcohol, nicotine, and the anesthetic hallucinogens ketamine and phencyclidine.

From a neurochemical perspective, DA was the first neurotransmitter to be identified as common to all drugs of abuse.45 DA release from one region of the brain (ventral tegmental area) stimulates another region (nucleus accumbens), which is key to the initial reward mechanism. Although naturally occurring primary reinforcers such as food and sex stimulate this pathway, the effect is far more pronounced with abused drugs. The preoccupation with drug(s) to the detriment of other primary reinforcers or areas of importance (eg, health) is a result of the now-greater salience of the addictive drug(s)'s effects over other life functions.34

More Brain Circuits and Neurotransmitters Are Involved

A plethora of brain pathways may contribute to addictive behaviors that affect the mesocorticolimbic pathways, including reward circuitry, prefrontal executive pathways, and the limbic system.50-52 This may explain why SUD may be affected by or, in turn, may affect impulse control, judgment, planning, attention, working memory, and mood. Besides DA, other neurotransmitters and neuromodulators that have been identified include endogenous opioids, anandamide, corticotropin-releasing hormone, and glutamate.50-52

The Psychology of Drug Addiction

Drug addiction is now envisioned as being far more complicated than the hedonic effect first envisioned by Kornetsky et al.48 According to Koob and Volkow,53 drug addiction is a “chronically relapsing disorder, characterized by a compulsion to seek and take the drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented.”

This has been simplified to a three-stage addiction cycle54:

  1. Binge/intoxication

  2. Withdrawal/negative affect

  3. Preoccupation/anticipation

The DSM-5-TR also considers craving; poor impulse control or other difficulties with executive function; and the emotional states of dysphoria, anxiety, and irritability as characteristics of SUD or a consequence of drug withdrawal.55

From a psychological perspective, instrumental and classical conditioning and social learning influence drug-seeking behavior and incorporate reward, drug salience, pronounced associations to environmental cues, and neuroplastic changes.34,561-58

Importance of Genetics

Genetics or epigenetics may contribute to all phases of the addiction cycle, including initial vulnerability to risk factors, maintenance, and relapse, by affecting brain architecture.53,59,60 Preclinical (ie, animal) studies show that early life events may contribute to this vulnerability on a genetic level.61,62 Other research shows that genetic polymorphism on one or more DA receptors may make mice more vulnerable to abusing substances like ethanol (alcohol), cocaine, and methamphetamine.8,63,64 Many of these changes are due to transcriptional or translational changes in the genome.60

Reconceptualized Biopsychosocial Model of Drug Addiction

In its current view, drug addiction encompasses an individual's internal and external dimensions that mutually influence one another. Although most individuals who use chemical substances do not succumb to addiction, those who do may be more vulnerable owing to genetics, development, or exposure to adverse social conditions.57 Drug addicts' reward circuits are less able to respond to normal stimuli, but their stress sensitivity may become amplified.41 Thus, their ability to self-regulate is attenuated. In time, owing to tolerance, substance abusers do not experience the same intensity of drug-induced euphoria that they did initially. Alternatively, it has been suggested that a reward deficiency syndrome, either secondary to DA 2(D2) receptor mutation or from insufficient DA stimulation, results in decreased reward.8,65 The motivation for addicts may subsequently shift to taking more drugs to ward off the heightened stress, dysphoria, and other symptoms, which are experienced secondary to withdrawal.41

Other Contributing Factors of SUD

Other contributing factors of SUD include comorbid psychiatric disorders, stress, increased opioid-prescribing practices, pharmaceutical marketing, and co-prescriptions of nonopioid drugs used to treat epilepsy and pain disorders. These contributing factors, among others, are discussed below.

Psychiatric Comorbidity

Patients with comorbid psychiatric disorders demonstrate poorer treatment adherence and higher rates of treatment dropout than those without mental illness, which negatively affects outcomes.66 There is a reciprocal relationship between SUD and comorbid psychiatric disorders, especially for major depressive disorders (eg, generalized anxiety disorder; bipolar I disorder; dysthymia; posttraumatic stress disorder; and borderline and schizotypal personality disorder [except mild]) and panic disorder, social phobia, and antisocial personality disorder, across severity levels.67,68 Each disorder contributes to the worsening of the other. From clinical and social perspectives, patients with SUD and psychiatric comorbidity represent a substantial proportion of people in treatment and often present with greater severity of disorder than those diagnosed with only one type of disorder.69,70 However, there is significant undertreatment in this cohort of comorbidities.70 Unless both disorders are successfully treated, relapse of both is likely. This calls for an integrated approach to intervention that identifies and evaluates each disorder concurrently and provides treatment as appropriate for each patient's particular constellation of disorders.66

Stress

A major relapse contributor is the presence of stressful life events, including recent deaths or illnesses among friends and family, unemployment, interpersonal problems, divorce, financial crises, and crime (being a victim or being arrested).71,72 DA pathways have been implicated in how stress can increase vulnerability to SUDs.72 Both the hypothalamic-pituitary-adrenal axis and brain stress system mediated by corticotropin-releasing hormone are dysregulated by the chronic administration of all major drugs with dependence or abuse potential, which leads to dysphoria and the aforementioned risk of relapse after drug abstinence.53

Iatrogenesis, Marketing, Regulatory, and Legal Factors

The initiating causes of the opioid epidemic in the US are considered to have been a combination of pharmaceutical marketing, court actions, health care provider licensing requirements, and iatrogenesis.73 Pharmaceutical marketing of opioids for chronic pain treatment started in the 1990s after several small case series74-76 were first reported in 1986. Disciplinary action against health care providers for not prescribing enough pain medications began in the late 1990s.77 In 2000, the Department of Veterans Affairs launched pain as the fifth vital sign, and the Joint Commission incorporated a right of patients to pain management.78-80 In a 2001 California civil lawsuit, the jury found a physician liable for elder abuse for providing insufficient pain medication to patient(s).81 These actions had enormous effects and influence on the rates of opioids prescribing in the US, which soared in the 2000s.

Extensive research from the Centers for Disease Control and Prevention and the Substance Abuse and Mental Health Services Administration showed that in the past 17 years, prescription opioid-related overdose deaths have increased dramatically in parallel with increased opioid-prescribing practices.82 Subsequently, public attention to these problems, guidelines, opioids prescribing–training requirements, and other actions have been associated with sharp declines in opioids prescriptions. However, there is now a stark decoupling of the falling rates of opioid prescription–related fatalities from the soaring rates of opioids-related fatalities, which is largely driven by illicit fentanyl.

Co-prescriptions

Nonopioid gabapentinoids, which include pregabalin and gabapentin, are drugs used to treat epilepsy and pain disorders; generalized anxiety disorder; diabetic peripheral neuropathy; postherpetic neuralgia; and fibromyalgia.83 They have euphoriant properties, especially in higher doses, and they have abuse potential. Health care providers also frequently prescribed nonopioid gabapentinoids with opioids. The synergistic consequences of co-administration of these drugs may result in enhanced euphoria, exaggerated abuse potential, and greater risk of toxicity, including fatality.83,84 Gabapentinoids are also available for street purchase as drugs of abuse.

Abuse of benzodiazepines was initially thought to be low but is now considered neither rare nor benign.85 In fact, benzodiazepines are the third most misused illicit or prescriptive substance among adults and adolescents in the US. Fatalities owing to overdose increased by more than 400% from 1996 to 2013, and visits to the emergency room increased by more than 300% from 2004 to 2011. The risk of fatality increases when benzodiazepines are co-administered with other central nervous system depressants.86 The 41% increase in benzodiazepines being co-prescribed with opioids in the years 2002 to 2014 is quite alarming. In addition to overdosage, behaviors leading to increased incidence of diseases such as human immunodeficiency virus (HIV) and hepatitis C virus, poor self-reported quality of life, criminal behavior, and continued substance use during treatment were identified as attendant risk factors. Abuse of other substances, including psychostimulants, must be considered, whether iatrogenic or malingering.87,88

Major Concerns of Drug Addiction

According to Koob and Volkow,53 drug addiction is a “chronically relapsing disorder.” The morbidity and mortality of cigarettes, alcohol, stimulants, opioids, cannabinoids, and other substances are myriad: cancers; liver, renal, and cardiovascular disease; respiratory disease; depression; automobile crashes or other accidents; dementia, stroke, or other neurologic or neurocognitive disorders; teratogenic effects; infectious diseases; malnutrition; and suicidality.34,89

Psychiatric Consequences of Substance Use Disorder

Paranoid psychosis secondary to abuse of stimulants like amphetamines or cocaine is well known.90 Although marijuana is sometimes mischaracterized as benign, it may exacerbate anxiety or agitation or precipitate first psychotic breaks in vulnerable individuals.91 Several studies have linked cannabis consumption in otherwise healthy patients with adverse cardiovascular complications, such as acute coronary syndrome, myocardial infarction, cardiac arrhythmia, and stroke. Chronic use may also lead to hepatotoxicity.92 Marijuana is also a well-known cause of workplace and motor vehicle accidents.

Respiratory Failure

The risks of a drug overdose, especially respiratory failure, are a major concern, particularly for opioids, alcohol, benzodiazepines, and other sedative-hypnotics, when used in combination.85,86 Intentional and/or accidental overdosage in severely depressed individuals has been documented.93 Risk of an intentional or accidental overdose of psychostimulants, including amphetamines and cocaine, is also of concern. Overdosage with these drugs may result in cardiovascular events, respiratory failure, and stroke.94,95

Drug Interactions and Complications

Polysubstance abuse presents a plethora of problems owing to the multiple potential toxic effects of the various substances and requires substantially greater health care intervention.96 Another rarely discussed problem is that abuse of one substance may mitigate the successful treatment of another. For example, psychostimulant abuse reduces abstinence in patients treated for opioid addiction.97

Overt and covert drug interactions increase the risk of toxic effects, including lethality. With opioids, the greatest population-based risk is likely respiratory depression. With the co-administration of other central nervous systems depressants, including benzodiazepines, alcohol, and barbiturates, this risk is potentiated.98 For example, xylazine, the veterinary sedative, analgesic, and muscle relaxant, is toxic at high concentrations.99 More recently, xylazine has been discovered as an adulterant in fentanyl, cocaine, and heroin.100,101 It has intentionally been co-administered for its euphoriant effect.102 Naloxone, the rescue opioid antagonist, is ineffective in reversing respiratory depression secondary to xylazine; however, the administration of naloxone is still recommended because naloxone may address symptoms of respiratory suppression if opioids are present, albeit less effectively.98

Abrupt Withdrawal

The risk of withdrawal symptoms in patients with SUD varies from substance to substance. Most worrisome is acute withdrawal in highly dependent alcohol abusers, especially delirium tremens, which can be life-threatening.34 Although generally less severe, benzodiazepines can produce withdrawal symptoms that include seizures, delirium, and fatality.34 Acute withdrawal from most other substances is generally not fatal but results in symptoms such as nausea, diarrhea, vomiting, shaking and shivering, and insomnia.

Birth Defects

Lastly, one needs to be concerned with possible teratogenicity. This is most severe when alcohol is consumed during pregnancy, especially early in gestation. The well-described fetal alcohol syndrome invariably results in central nervous system dysfunction, including low intelligence and microcephaly, stunted growth, and characteristic facial abnormalities.103,104 The presence of heroin and other opioids during pregnancy causes a five-fold increase in the number of infants born who are opioid dependent.105 Adjusting for covariates, Wouldes and Woodward105 demonstrated that methadone exposure during gestation resulted in infants with significantly worse attention, behavioral regulation, and quality of movement. They were more excitable and easily aroused or showed other symptoms.

Regarding cocaine, a plethora of neurodevelopmental and cognitive deficits have been reported106; however, it is challenging to assign teratogenicity to cocaine because of the mother's possible co-abuse of other substances and the possibility of other maternal and sociodemographic risk factors being contributory.104,106 These confounding risk factors also make the assignment of teratogenicity or low maternal birth weight to methamphetamine and cannabis questionable.101

Tobacco smoking during pregnancy is associated with infertility, intrauterine growth restriction, miscarriage, premature birth, and sudden infant death syndrome.107 Nicotine is readily absorbed in high levels in the fetal brain.107 However, it is not certain if nicotine or contaminants are responsible for the teratogenic effects (eg, oral clefts, limb reduction, gastroschisis, subsequent cognitive and behavioral problems, including ADHD) or preterm birth in humans or animals that inhale the smoke of typical cigarettes and electronic cigarettes (e-cigarettes).107,108

Risks and Economic Consequences of Drug Addiction

The most frequently used addictive substance is nicotine. While overdose to nicotine, in the form of smoking tobacco products, is extremely rare, those products of combustion are highly toxic owing to long-term sequelae. The Surgeon General's Report of 1964 was revolutionary in its attempt to educate and limit the abuse of a legal drug found within tobacco smoke.109 (Previous attempts to limit alcohol abuse in the US led to the 18th amendment to the Constitution in 1919, which was later repealed with the 21st amendment in 1933.110) The Surgeon General's report, alongside subsequent research, showed that chronic exposure to cigarette smoke, even secondhand, may lead to cardiovascular disease, pulmonary disease (including lung cancer), and pregnancy complications.111 The costs of these illnesses are borne by the patient and the entire health care system. This, in turn, potentially affects the economy, writ large and small. The introduction of e-cigarettes to nicotine-naïve adolescents has increased, not decreased, the risk of subsequent cigarette smoking.112 In addition, the electronic delivery system may not be benign, as there are non-nicotine toxic substances in e-cigarettes that may increase the risk of vascular disease and possible cognitive impairment.113,114

Besides xylazine, other adulterants in abused legal (licit) and illicit substances must be considered. As noted above, the Surgeon General's advisory warned of the carcinogenic risks of tobacco, including lung cancer.109 More recently, 72 known carcinogens have been identified in cigarette smoke.115 Although e-cigarettes have lower concentrations of carcinogens, they contain solvents and flavorants that adversely affect the health of the pulmonary, cardiovascular, and immune systems.116 Adulterants and contaminants have been identified in botanical supplements and herbal remedies.117 Thirty-seven states have legalized marijuana for medical use and 21 states for recreational use (medical use remains illegal under federal law). The determination of safety and purity has been left up to each state, with some using state laboratories while others outsource third-party laboratories or do not require monitoring.18,118 Adulterants and contaminants should be considered as potential risks for all psychoactive drugs, especially those not regulated by the Food and Drug Administration. Such risks would be amplified when these drugs are consumed chronically and/or in high concentrations.

Social and Personal Sequelae

Despite good psychotherapeutic and self-help treatment approaches, relapse may contribute to illness and under- or unemployment in susceptible patients. In some individuals, this may be a consequence of being denied licenses to drive, practice medicine or other professions, or attain a security clearance. Other social consequences include motor vehicle crashes, exposure to secondhand smoke, spread of sexually transmitted diseases, violence, homelessness, vagrancy, crime, and family problems.119,120

While the Social Security Administration considers mental illness as a diagnosable disability, it does not recognize drug addiction for the same purposes. However, as noted, comorbidity with drug addiction is frequent. Also, if one is denied a livelihood, which may provide an individual's medical insurance, because of addiction, a spiral of impoverishment, poor health, and relapse may ensue.121

Disability vs Impairment in Addiction

What is the significance of disability vs impairment addiction, and how does one differ from the other? Each needs to be considered separately. Before defining drug addiction as a disability, it is critical to consider the procedure for rating drug addiction using the sixth edition of the AMA Guides to the Evaluation of Permanent Impairment (2008) and the definition of disability, including the necessary considerations.

Definition of Disability: Significance of Long-term Impairment

The legal concept of disability is based, in part, on the medical concept of impairment. While there may be short-term impairments and temporary disabilities, this article only addresses permanent impairments and disabilities. The Americans with Disabilities Act defines a person with a disability as someone who has a physical or mental impairment that substantially limits one or more major life activity(ies). Impairment is a long-term loss of a body part or reduction of body function.122

Impairment can be assessed both ipsatively and normatively. Each needs to be assessed, with a strong preference for objective measures when available. Ipsative assessment specifically compares an individual's current performance with premorbid functioning, while normative assessments are meaningful only when comparing an individual with a “standard” individual, preferably of the same age and profession.

To illustrate this concept, consider a hypothetical 30-year-old male sharpshooter who presents with complaints of blurry vision. He is assessed as having 20/20 distant vision. He would not be considered as partially disabled unless his vision is compared to his premorbid 20/10 distant vision and his current abilities to his premorbid abilities. Thus, to diagnose impairment, much depends on the comparison group the evaluator considers: the patient's own occupation or any substantial gainful activity vs premorbid capabilities.123,124

Diagnosis of Disability in Addiction: Challenges

To determine whether there is a disability, it would be best to determine which variables are relevant, such as impairment at a point in time (eg, currently) or the likelihood of impairment for a given period (eg, next month). There are two major difficulties or challenges:

  1. Rating drug addiction is addressed in Chapter 14 of the AMA Guides, Sixth Edition (2008); however, in Section 14.1c, Diagnostic Criteria (6th ed, 349), a list of disorders that are not ratable in Chapter 14 includes:

    • Substance use disorder. Affective or other mental disorders due to substance abuse are not rated.

  2. On the other hand, Chapter 14 also includes Table 14-6, Factors That May Affect Motivation (6th ed, 353), which includes substance intoxication and abuse as one of these factors, which contradicts the list in Section 14.1c.

Nevertheless, drug addiction is not a ratable impairment, even though it may interfere with activities of daily living (ADLs). (Note: Although it is not a ratable impairment according to the AMA Guides, local jurisdiction that considers drug addiction as a ratable impairment may have statutes or rules that supersede the AMA Guides.)

Assignment of Disability: Possible Considerations

As previously noted, one of the challenges is how to qualify for and quantify disability in addiction. Mental health professionals and addictionologists currently use the 11 criteria from the DSM-5 to diagnose opioid use disorder (OUD) and rate severity of impairment or the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule–5.12,55,125 Are these the most accurate instruments for determining the presence and severity of disability secondary to drug addiction? The evaluator also needs to consider the validity of existing medical and psychological measures, especially when there is an incentive for claimants to exaggerate symptoms to receive the desired outcome of guaranteed financial assistance, which may then further subsidize a habit.

Who Adjudicates

Social Security or disability insurance plans may apply different standards. There may also be state regulations or specific regulatory issues, such as physician licensure or safety–critical work requirements (eg, pilots, overhead crane operators, railroad engineers). In addition, there may be conflicts between what physicians determine as “recovery” vs an authorizing body with stricter standards based on fixed criteria. For example, if a pilot or a physician has had several relapses but is now successfully treated, should that person be denied meaningful work?126

Course and Duration of Disability

Research suggests that after adjusting for sociodemographic and psychiatric covariates, respondents with a 12-month drug use disorder had significantly lower mental health, social functioning, role emotional functioning, and mental component summary scores.12 Disability increases as SUD severity increases.

Determination of permanent disability vs time-limited disability has enormous importance in terms of subsequent decisions regarding financial assistance and support for addiction. Noteworthy in this regard is alcoholism. Sustained sobriety can improve brain structure and function, indicative of damage reversal or compensatory mechanisms that can be identified with formal neuropsychological testing and longitudinal, quantitative, structural, and functional brain imaging.127

Cautionary Considerations Before Determining Drug Addiction as a Disability

There are several considerations before defining drug addiction as a disability:

  1. Disability status is associated with increased mortality and reduced lifespan. Therefore, assigning drug addiction as a disability may have adverse consequences for the individual and society.

  2. Beyond fraud and advocagenic and similar claims, there is no comparable class of disorders in which there must be an active, conscious decision to opt-in and maintain a disabled status. If a determination of disability was made regarding a conscious decision to opt-in, could there then be other classes of disorders to be similarly managed?

  3. There is a risk of reinforcing drug addiction by providing financial assistance for drug dependence disability.

  4. The financial costs to Social Security and private disability systems may likely be unsustainable.

Conclusions

This article takes no position for or against a determination of disability for those with SUD. A consensus on whether drug addiction is a disability, or the advisability of financial support for drug addiction as a disability in the absence of a comorbid disorder could not be reached; however, the overarching goal to raise awareness regarding drug addiction impairment considerations for addictionologists and disability evaluators was achieved. Disability is ultimately a decision of a legal system based on statutes, rules, or contracts.

REFERENCES

  • 1.

    Centers for Disease Control and Prevention, National Center for Health Statistics. 2020 final death statistics: COVID-19 as an underlying cause of death vs. contributing cause. Page last reviewed January 7, 2022. Accessed March 2, 2023. https://www.cdc.gov/nchs/pressroom/podcasts/2022/20220107/20220107.htm.

    • Search Google Scholar
    • Export Citation
  • 2.

    Spencer MR, Miniño AM, Warner M. Drug overdose deaths in the United States, 2001-2021. NCHS data brief. December 2022 (No. 457). National Center for Health Statistics. doi: 10.15620/cdc:122556.

    • Search Google Scholar
    • Export Citation
  • 3.

    Liu S, O'Donnell J, Gladden RM, et al. Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019–2020. MMWR Morbid Mortal Wkly Rep. 2021;70(34):11361141. doi: 10.15585/mmwr.mm7034a2.

    • Search Google Scholar
    • Export Citation
  • 4.

    Leshner AI. Addiction is a brain disease, and it matters. Science. 1997;278(5335):4547. doi: 10.1126/science.278.5335.45.

  • 5.

    Heilig M, MacKillop J, Martinez D, et al. Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology. 2021;46(10):17151723. doi: 10.1038/s41386-020-00950-y.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lie AK, Hansen H, Herzberg D, et al. The harms of constructing addiction as a chronic, relapsing brain disease. Am J Public Health. 2022;112(S2): S104S108. doi: 10.2105/AJPH.2021.306645.

    • Search Google Scholar
    • Export Citation
  • 7.

    Nutt DJ, Lingford-Hughes A, Erritzoe D, Stokes PR. The dopamine theory of addiction: 40 years of highs and lows. Nat Rev Neurosci. 2015;16(5):305312. doi: 10.1038/nrn3939.

    • Search Google Scholar
    • Export Citation
  • 8.

    Blum K, Bowirrat A, Braverman ER, et al. Reward deficiency syndrome (RDS): a cytoarchitectural common neurobiological trait of all addictions. Int J Environ Res Public Health. 2021;18(21):11529. doi: 10.3390/ijerph182111529.

    • Search Google Scholar
    • Export Citation
  • 9.

    Alexander DR. Are We Slaves to Our Genes. Cambridge University Press; 2020. doi: 10.1017/9781108566520.

  • 10.

    Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results From the 2020 National Survey on Drug Use and Health. HHS Publication No. PEP21-07-01-003, NSDUH Series H-56. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, 2021. Retrieved from https://www.samhsa.gov/data/.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ilhan MN, Yapar D. Alcohol consumption and alcohol policy. Turk J Med Sci. 2020;50(5):11971202. doi: 10.3906/sag-2002-237.

  • 12.

    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):3947. doi: 10.1001/jamapsychiatry.2015.2132.

    • Search Google Scholar
    • Export Citation
  • 13.

    Hasin DS, Grant BF. The national epidemiologic survey on alcohol and related conditions (NESARC), waves 1 and 2: review and summary of findings. Soc Psychiatry Psychiatr Epidemiol. 2015;50(11):16091640. doi: 10.1007/s00127-015-1088-0.

    • Search Google Scholar
    • Export Citation
  • 14.

    Social Security Administration. Disability Evaluation Under Social Security, section 12.00: Mental Disorders—Adult. Accessed March 2, 2023. https://www.ssa.gov/disability/professionals/bluebook/12.00-MentalDisorders-Adult.htm.

    • Search Google Scholar
    • Export Citation
  • 15.

    Addiction treatment market to hit US$ 7.0 billion by 2025 - TMR: Addiction treatment market: Tobacco/Nicotine addiction treatment dominates the market followed by opioid addiction treatment. Oct 1, 2019. NASDAQ OMX's News Release Distribution Channel. Retrieved from https://www.proquest.com/wire-feeds/addiction-treatment-market-hit-us-7-0-billion/docview/2299414535/se-2.

    • Search Google Scholar
    • Export Citation
  • 16.

    World Health Organization. Tobacco [fact sheet]. May 24, 2022. Accessed March 4, 2023. https://www.who.int/news-room/fact-sheets/detail/tobacco.

    • Search Google Scholar
    • Export Citation
  • 17.

    National Institute on Drug Abuse. Common comorbidities with substance use disorders research report: introduction. August 3, 2021. Accessed January 21, 2023. https://nida.nih.gov/publications/research-reports/common-comorbidities-substance-use-disorders/introduction.

    • Search Google Scholar
    • Export Citation
  • 18.

    Li L, Duffy BC, Durocher LA, et al. Potency analysis of medical marijuana products from New York State. Cannabis Cannabinoid Res. 2019;4(3):195203. doi: 10.1089/can.2018.0037.

    • Search Google Scholar
    • Export Citation
  • 19.

    Schultes RE. Hallucinogenic Plants. New York City: NY; Western Publishing Company; 1976.

  • 20.

    Lattimore R. The Odyssey of Homer. New York City: NY; Harper and Row; 1968.

  • 21.

    Macbeth Shakespeare W.. In: The Complete Works of William Shakespeare (Original work published 1623). The Hamlyn Publishing Group Limited; 1958:922944.

    • Search Google Scholar
    • Export Citation
  • 22.

    De Quincey T. Confessions of an English Opium-Eater. Taylor & Hessey; 1823.

  • 23.

    Pepper A, Pepper L. Straight Life: The Story of Art Pepper. Shirmer Books; 1979.

  • 24.

    Burroughs W. The Naked Lunch. Grove Press; 1959.

  • 25.

    Kerouac J. On the Road. Viking Press; 1957.

  • 26.

    Dixon W. Spoonful. [Single recorded by Howlin' Wolf]. Chess Records; 1960.

  • 27.

    Slick G. White Rabbit. [Single from Surrealistic Pillow, recorded by Jefferson Airplane]. RCA Victor; 1967.

  • 28.

    Jagger M, Richards K. Mother's Little Helper. [Single from Aftermath, recorded by the Rolling Stones]. RCA; 1965.

  • 29.

    Lennon J, McCartney P. Day Tripper. [Single, recorded by the Beatles]. EMI; 1965.

  • 30.

    Winehouse A. Rehab. [Single from Back to Black, recorded by Amy Winehouse]. Island; 2006.

  • 31.

    Bush DM, Lipari RN. Substance use and substance use disorder by industry. In: The CBHSQ Report. (April 16, 2015.) Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Rockville, MD. Accessed March 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK343537/.

    • Search Google Scholar
    • Export Citation
  • 32.

    Motyka MA, Al-Imam A. Representations of psychoactive drugs' use in mass culture and their impact on audiences. Int J Environ Res Public Health. 2021;18(11):6000. doi: 10.3390/ijerph18116000.

    • Search Google Scholar
    • Export Citation
  • 33.

    Grier SA, Kumanyika S. Targeted marketing and public health. Annu Rev Public Health. 2010;31:349369. doi: 10.1146/annurev.publhealth.012809.103607.

    • Search Google Scholar
    • Export Citation
  • 34.

    O'Brien CP. Chapter 24: Drug addiction. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 12th ed. McGraw Hill; 2011: 649668.

    • Search Google Scholar
    • Export Citation
  • 35.

    American Society of Addiction Medicine. Public Policy Statement: Definition of Addiction. August 15, 2011. Accessed March 2, 2023. https://www.asam.org/docs/default-source/public-policy-statements/1definition_of_addiction_long_4-11.

    • Search Google Scholar
    • Export Citation
  • 36.

    Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, et al. Effectiveness of naltrexone in the prevention of delayed respiratory arrest in opioid-naive methadone-intoxicated patients. Biomed Res Int. 2013;2013:903172. doi: 10.1155/2013/903172.

    • Search Google Scholar
    • Export Citation
  • 37.

    Nies A, Spielberg SP. Chapter 3: Principles of therapeutics. In: Molinoff PB, Ruddon RW, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York City: NY; McGraw-Hill; 1996: 4361.

    • Search Google Scholar
    • Export Citation
  • 38.

    Advokat, CD, Comaty, JE, Julien, RM. Chapter 1: Pharmacokinetics: how the body handles drugs. In: Julien's Primer of Drug Action. 14th ed. UK; Worth Publishers; 2019: 339.

    • Search Google Scholar
    • Export Citation
  • 39.

    Algera MH, Olofsen E, Moss L, et al. Tolerance to opioid-induced respiratory depression in chronic high-dose opioid users: a model-based comparison with opioid-naïve individuals. Clin Pharmacol Ther. 2021;109(3):637645. doi: 10.1002/cpt.2027.

    • Search Google Scholar
    • Export Citation
  • 40.

    White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction. 1999;94(7):961972. https://doi.org/10.1046/j.1360-0443.1999.9479612.x.

    • Search Google Scholar
    • Export Citation
  • 41.

    Advokat CD, Comaty JE, Julien RM. Chapter 4: Epidemiology and neurobiology of addiction. In: Julien's Primer of Drug Action. 14th ed. UK; Worth Publishers; 2019:105-133.

    • Search Google Scholar
    • Export Citation
  • 42.

    Kalant H, Grupp LA. Drug abuse and drug dependence. In: Kalant H, Roschlau WHE, eds. Principles of Medical Pharmacology. 6th ed. Oxford University Press; 1998: 904916.

    • Search Google Scholar
    • Export Citation
  • 43.

    Napier TC, Herrold AA, de Wit H. Using conditioned place preference to identify relapse prevention medications. Neurosci Biobehav Rev. 2013;37(9, pt A):20812086. doi: 10.1016/j.neubiorev.2013.05.002.

    • Search Google Scholar
    • Export Citation
  • 44.

    Siegel S. Drug anticipation and drug addiction: the 1998 H. David Archibald Lecture. Addiction. 1999;94(8):11131124.

  • 45.

    Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev. 2019;99(4):21152140. doi: 10.1152/physrev.00014.2018.

    • Search Google Scholar
    • Export Citation
  • 46.

    Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiologic Psychol. 1954;47(6):419427. doi: 10.1037/h0058775.

    • Search Google Scholar
    • Export Citation
  • 47.

    Skinner BF. The Behavior of Organisms: An Experimental Analysis. Appleton-Century; 1938.

  • 48.

    Kornetsky C, Esposito RU, McLean S, Jacobson JO. Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse. Arch Gen Psychiatry. 1979;36(3):289292. doi: 10.1001/archpsyc.1979.01780030055004.

    • Search Google Scholar
    • Export Citation
  • 49.

    Negus SS, Miller LL. Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev. 2014;66(3):869917. doi: 10.1124/pr.112.007419.

    • Search Google Scholar
    • Export Citation
  • 50.

    Potenza MN. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond B Biol Sci. 2008;363(1507):31813189. doi: 10.1098/rstb.2008.0100.

    • Search Google Scholar
    • Export Citation
  • 51.

    Scherma M, Muntoni AL, Riedel G, et al. Cannabinoids and their therapeutic applications in mental disorders. Dialogues Clin Neurosci. 2020;22(3):271279. doi: 10.31887/DCNS.2020.22.3/pfadda.

    • Search Google Scholar
    • Export Citation
  • 52.

    Yohn SE, Galbraith J, Calipari ES, Conn PJ. Shared behavioral and neurocircuitry disruptions in drug addiction, obesity, and binge eating disorder: focus on group I mGluRs in the mesolimbic dopamine pathway. ACS Chem Neurosci. 2019;10(5):21252143. doi: 10.1021/acschemneuro.8b0060.

    • Search Google Scholar
    • Export Citation
  • 53.

    Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016;3(8):760773. doi: 10.1016/S2215-0366(16)00104-8.

    • Search Google Scholar
    • Export Citation
  • 54.

    Uhl GR, Koob GF, Cable J. The neurobiology of addiction. Ann NY Acad Sci. 2019;1451(1):528. doi: 10.1111/nyas.13989.

  • 55.

    American Psychiatric Association. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR®). Washington: DC; American Psychiatric Publishers, Inc; 2022.

    • Search Google Scholar
    • Export Citation
  • 56.

    Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ. 2001;164(6):817821.

    • Search Google Scholar
    • Export Citation
  • 57.

    Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev. 2019;99(4):21152140. doi: 10.1152/physrev.00014.2018.

    • Search Google Scholar
    • Export Citation
  • 58.

    Smith MA. Social learning and addiction. Behav Brain Res. 2021;398:112954. doi: 10.1016/j.bbr.2020.112954.

  • 59.

    Jones JD, Comer SD. A review of pharmacogenetic studies of substance-related disorders. Drug Alcohol Depend. 2015;152:114. doi: 10.1016/j.drugalcdep.2015.03.003.

    • Search Google Scholar
    • Export Citation
  • 60.

    Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci. 2011;12(11):623637. doi: 10.1038/nrn3111.

    • Search Google Scholar
    • Export Citation
  • 61.

    Bardo MT, Hammerslag LR, Malone SG. Effect of early life social adversity on drug abuse vulnerability: focus on corticotropin-releasing factor and oxytocin. Neuropharmacology. 2021;191:108567. doi: 10.1016/j.neuropharm.2021.108567.

    • Search Google Scholar
    • Export Citation
  • 62.

    Onaivi ES, Ishiguro H, Gong JP, et al. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLOS One. 2008;3(2):e1640. doi: 10.1371/journal.pone.0001640.

    • Search Google Scholar
    • Export Citation
  • 63.

    Botticelli L, Micioni Di Bonaventura E, Del Bello F, et al. Underlying susceptibility to eating disorders and drug abuse: genetic and pharmacological aspects of dopamine D4 receptors. Nutrients. 2020;12(8):2288. doi: 10.3390/nu12082288.

    • Search Google Scholar
    • Export Citation
  • 64.

    Ho MK, Goldman D, Heinz A, et al. Breaking barriers in the genomics and pharmacogenetics of drug addiction. Clin Pharmacol Ther. 2010;88(6):779791. doi: 10.1038/clpt.2010.175.

    • Search Google Scholar
    • Export Citation
  • 65.

    Madigan MA, Gupta A, Bowirrat A, et al. Precision behavioral management (PBM) and cognitive control as a potential therapeutic and prophylactic modality for reward deficiency syndrome (RDS): is there enough evidence. Int J Environ Res Public Health. 2022;19(11):6395. doi: 10.3390/ijerph19116395.

    • Search Google Scholar
    • Export Citation
  • 66.

    National Institute on Drug Abuse. What are the treatments for comorbid substance use disorder and mental health conditions. April 13, 2021. Accessed February 15, 2023. https://nida.nih.gov/publications/research-reports/common-comorbidities-substance-use-disorders/what-are-treatments-comorbid-substance-use-disorder-mental-health-conditions.

    • Search Google Scholar
    • Export Citation
  • 67.

    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):3947. doi: 10.1001/jamapsychiatry.2015.2132.

    • Search Google Scholar
    • Export Citation
  • 68.

    Vekaria V, Bose B, Murphy SM, et al. Association of co-occurring opioid or other substance use disorders with increased healthcare utilization in patients with depression. Transl Psychiatry. 2021;11(1):265. doi: 10.1038/s41398-021-01372-0.

    • Search Google Scholar
    • Export Citation
  • 69.

    Torrens M, Rossi PC, Martinez-Riera R, et al. Psychiatric comorbidity and substance use disorders: treatment in parallel systems or in one integrated system. Subst Use Misuse. 2012;47(8-9):10051014. doi: 10.3109/10826084.2012.663296.

    • Search Google Scholar
    • Export Citation
  • 70.

    Han B, Compton WM, Blanco C, Colpe LJ. Prevalence, treatment, and unmet treatment needs of us adults with mental health and substance use disorders. Health Aff (Millwood). 2017;36(10):17391747. doi: 10.1377/hlthaff.2017.0584.

    • Search Google Scholar
    • Export Citation
  • 71.

    McCabe SE, Cranford JA, Boyd CJ. Stressful events and other predictors of remission from drug dependence in the United States: longitudinal results from a national survey. J Subst Abuse Treat. 2016;71:4147. doi: 10.1016/j.jsat.2016.08.008.

    • Search Google Scholar
    • Export Citation
  • 72.

    Cleck JN, Blendy JA. Making a bad thing worse: adverse effects of stress on drug addiction. J Clin Invest. 2008;118(2):454461.

  • 73.

    World Health Organization. Curbing prescription opioid dependency. Bull World Health Organization. 2017;95(5):318319. doi: 10.2471/BLT.17.020517.

    • Search Google Scholar
    • Export Citation
  • 74.

    Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. 1986;25(2):171186. doi: 10.1016/0304-3959(86)90091-6.

    • Search Google Scholar
    • Export Citation
  • 75.

    Bovill JG. Which potent opioid? important criteria for selection. Drugs. 1987;33(5):520530. doi: 10.2165/00003495-198733050-00006.

  • 76.

    Bannwarth B. Risk-benefit assessment of opioids in chronic noncancer pain. Drug Safety. 1999;21(4):283296. doi: 10.2165/00002018-199921040-00004.

    • Search Google Scholar
    • Export Citation
  • 77.

    Charatan F. Doctor disciplined for “grossly undertreating” pain. BMJ. 1999;319:728. doi: 10.1136/bmj.319.7212.728a.

  • 78.

    Department of Veterans Affairs website. Pain as the 5th vital sign toolkit. October 2000. Accessed March 4, 2023. https://www.va.gov/PAINMANAGEMENT/docs/TOOLKIT.pdf.

    • Search Google Scholar
    • Export Citation
  • 79.

    Merboth MK, Barnason S. Managing pain: the fifth vital sign. Nurs Clin North Am. 2000;35(2):375383.

  • 80.

    Berry PH, Dahl JL. The new JCAHO pain standards: implications for pain management nurses. Pain Manag Nurs. 2000;1(1):312. doi: 10.1053/jpmn.2000.5833.

    • Search Google Scholar
    • Export Citation
  • 81.

    Tucker KL. The debate on elder abuse for undertreated pain. Pain Med. 2004;5(2):214228. doi: 10.1111/j.1526-4637.2004.4029_2.x.

  • 82.

    Gleber R, Vilke GM, Castillo EM, et al. Trends in emergency physician opioid prescribing practices during the United States opioid crisis. Am J Emerg Med. 2020;38(4):735740.

    • Search Google Scholar
    • Export Citation
  • 83.

    Hägg S, Jönsson AK, Ahlner J. Current evidence on abuse and misuse of gabapentinoids. Drug Safety. 2020;43(12):12351254. doi: 10.1007/s40264-020-00985-6.

    • Search Google Scholar
    • Export Citation
  • 84.

    Peckham AM, Evoy KE, Covvey JR, et al. Predictors of gabapentin overuse with or without concomitant opioids in a commercially insured U.S. population. Pharmacotherapy. 2018;38(4):436443. doi: 10.1002/phar.2096.

    • Search Google Scholar
    • Export Citation
  • 85.

    Votaw VR, Geyer R, Rieselbach MM, McHugh RK. The epidemiology of benzodiazepine misuse: a systematic review. Drug Alcohol Depend. 2019;200:95114. doi: 10.1016/j.drugalcdep.2019.02.033.

    • Search Google Scholar
    • Export Citation
  • 86.

    Wilson KC, Saukkonen JJ. Acute respiratory failure from abused substances. J Intensive Care Med. 2004;19(4):183193. doi: 10.1177/0885066604263918.

    • Search Google Scholar
    • Export Citation
  • 87.

    Clemow DB, Walker DJ. The potential for misuse and abuse of medications in ADHD: a review. Postgrad Med. 2014;126(5):6481. doi: 10.3810/pgm.2014.09.2801.

    • Search Google Scholar
    • Export Citation
  • 88.

    Sadek J. Malingering and stimulant medications abuse, misuse and diversion. Brain Sci. 2022;12(8):1004. doi: 10.3390/brainsci12081004.

  • 89.

    French MT, Martin RF. The costs of drug abuse consequences: a summary of research findings. J Subst Abuse Treat. 1996;13(6):453466. doi: 10.1016/s0740-5472(96)00128-6.

    • Search Google Scholar
    • Export Citation
  • 90.

    Alexander PD, Gicas KM, Willi TS, et al. A comparison of psychotic symptoms in subjects with methamphetamine versus cocaine dependence. Psychopharmacology (Berl). 2017;234(9-10):153547. doi: 10.1007/s00213-017-4551-7.

    • Search Google Scholar
    • Export Citation
  • 91.

    Mohamed BA, Potvin S. Cannabis and psychosis: what is the link. J Psychoactive Drugs. 2007;39(2):13142.

  • 92.

    Merve AO, Sobiecka P, Remeškevičius V, et al. Metabolites of cannabis induce cardiac toxicity and morphological alterations in cardiac myocytes. Int J Mol Sci. 2022;23(3):1401. doi: 10.3390/ijms23031401.

    • Search Google Scholar
    • Export Citation
  • 93.

    Eigner G, Henriksen B, Huynh P, et al. Who is overdosing? an updated picture of overdose deaths from 2008 to 2015. Health Serv Res Manag Epidemiol. 2017;4. doi: 10.1177/2333392817727424.

    • Search Google Scholar
    • Export Citation
  • 94.

    Mantinieks D, Schumann J, Drummer OH, et al. Stimulant use in suicides: a systematic review. Forensic Sci Int. 2022;338:111391. doi: 10.1016/j.forsciint.2022.111391.

    • Search Google Scholar
    • Export Citation
  • 95.

    Rita RB, Faria AC, Andreia Machado Brito-da-Costa, et al. Cocaine: an updated overview on chemistry, detection, biokinetics, and pharmacotoxicological aspects including abuse pattern. Toxins. 2022;14(4):278. doi: 10.3390/toxins14040278.

    • Search Google Scholar
    • Export Citation
  • 96.

    Klenk L, von Rütte Christina, Henssler JF, et al. Resource consumption of multi-substance users in the emergency room: a neglected patient group. PLOS One. 2019;14(9). doi: 10.1371/journal.pone.0223118.

    • Search Google Scholar
    • Export Citation
  • 97.

    Frost MC, Lampert H, Tsui JI, et al. The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review. Addict Sci Clin Pract. 2021;16(1):62. doi: 10.1186/s13722-021-00266-2.

    • Search Google Scholar
    • Export Citation
  • 98.

    National Institute on Drug Abuse website. Research topics: Xylanzine. Accessed January 22, 2023. https://nida.nih.gov/research-topics/xylazine.

    • Search Google Scholar
    • Export Citation
  • 99.

    Mittleman RE, Hearn WL, Hime GW. Xylazine toxicity–literature review and report of two cases. J Forensic Sci. 1998;43(2):400402.

  • 100.

    Wong SC, Curtis JA, Wingert WE. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office. J Forensic Sci. 2008;53(2):495498. doi: 10.1111/j.1556-4029.2007.00648.x.

    • Search Google Scholar
    • Export Citation
  • 101.

    Kariisa M, Patel P, Smith H, Bitting J. Notes from the field: xylazine detection and involvement in drug overdose deaths - United States, 2019. MMWR Morb Mortal Wkly Rep. 2021;70(37):13001302. doi: 10.15585/mmwr.mm7037a4.

    • Search Google Scholar
    • Export Citation
  • 102.

    Reyes JC, Negrón JL, Colón HM, et al. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health. 2012;89(3):519526. doi: 10.1007/s11524-011-9662-6.

    • Search Google Scholar
    • Export Citation
  • 103.

    Hobbs W, Rall TW, Verdorn, TA. Chapter 17: Hypnotics and sedatives: ethanol. In: Molinoff PB, Ruddon RW, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. McGraw-Hill; 1996: 361396.

    • Search Google Scholar
    • Export Citation
  • 104.

    Sebastiani G, Borrás-Novell C, Casanova MA, et al. The effects of alcohol and drugs of abuse on maternal nutritional profile during pregnancy. Nutrients. 2018;10(8):1008. doi: 10.3390/nu10081008.

    • Search Google Scholar
    • Export Citation
  • 105.

    Wouldes TA, Woodward LJ. Neurobehavior of newborn infants exposed prenatally to methadone and identification of a neurobehavioral profile linked to poorer neurodevelopmental outcomes at age 24 months. PLOS One. 2020;15(10):e0240905. doi: 10.1371/journal.pone.0240905.

    • Search Google Scholar
    • Export Citation
  • 106.

    Cressman AM, Natekar A, Kim E, et al. Cocaine abuse during pregnancy. J Obstet Gynaecol Can. 2014;36(7):628631. doi: 10.1016/S1701-2163(15)30543-0.

    • Search Google Scholar
    • Export Citation
  • 107.

    Sailer S, Sebastiani G, Andreu-Férnández V, García-Algar O. Impact of nicotine replacement and electronic nicotine delivery systems on fetal brain development. Int J Environ Res Public Health. 2019;16(24):5113. doi: 10.3390/ijerph16245113.

    • Search Google Scholar
    • Export Citation
  • 108.

    McGrath-Morrow SA, Gorzkowski J, Groner JA, et al. The effects of nicotine on development. Pediatrics. 2020;145(3):e20191346. doi: 10.1542/peds.2019-1346.

    • Search Google Scholar
    • Export Citation
  • 109.

    US Department of Health, Education, and Welfare Public Health Service. Smoking and Health. Public Health Service Publication No. 1103, U.S. Government Printing Office; 1964.

    • Search Google Scholar
    • Export Citation
  • 110.

    Jack Miller Center website. The Eighteenth and Twenty-First Amendments: Prohibition in America. Accessed March 4, 2023. https://jackmillercenter.org/eighteenth-twenty-first-amendments.

    • Search Google Scholar
    • Export Citation
  • 111.

    Lightwood J, Glantz SA. Smoking behavior and healthcare expenditure in the United States, 1992-2009: panel data estimates [published correction appears in PLOS Med]. 2016;13(6):e1002070]. PLOS Med. 2016;13(5):e1002020. doi: 10.1371/journal.pmed.1002020.

    • Search Google Scholar
    • Export Citation
  • 112.

    Soneji SS, Sung HY, Primack BA, et al. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLOS One. 2018;13(3):e0193328. doi: 10.1371/journal.pone.0193328.

    • Search Google Scholar
    • Export Citation
  • 113.

    Heldt NA, Reichenbach N, McGary HM, Persidsky Y. Effects of electronic nicotine delivery systems and cigarettes on systemic circulation and blood-brain barrier: implications for cognitive decline. Am J Pathol. 2021;191(2):243255. doi: 10.1016/j.ajpath.2020.11.007.

    • Search Google Scholar
    • Export Citation
  • 114.

    McGrath-Morrow SA, Gorzkowski J, Groner JA, et al. The effects of nicotine on development. Pediatrics. 2020;145(3):e20191346. doi: 10.1542/peds.2019-1346.

    • Search Google Scholar
    • Export Citation
  • 115.

    Hecht SS. More than 500 trillion molecules of strong carcinogens per cigarette: use in product labelling. Tobacco Control. 2011;20(5):387. doi: 10.1136/tc.2011.042853.

    • Search Google Scholar
    • Export Citation
  • 116.

    Eltorai AE, Choi AR, Eltorai AS. Impact of electronic cigarettes on various organ systems. Respir Care. 2019;64(3):328336. doi: 10.4187/respcare.06300.

    • Search Google Scholar
    • Export Citation
  • 117.

    Vaclavik L, Krynitsky AJ, Rader JI. Mass spectrometric analysis of pharmaceutical adulterants in products labeled as botanical dietary supplements or herbal remedies: a review. Anal Bioanal Chem. 2014;406(27):67676790. doi: 10.1007/s00216-014-8159-z.

    • Search Google Scholar
    • Export Citation
  • 118.

    Brody JE. Medical marijuana is not regulated as most medicines are. New York Times. March 8, 2021. Accessed March 4, 2023. https://www.nytimes.com/2021/03/08/well/live/medical-marijuana.html.

    • Search Google Scholar
    • Export Citation
  • 119.

    National Institute on Drug Abuse website. Addiction and health. March 22, 2022. Accessed February 15, 2023. https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/addiction-health.

    • Search Google Scholar
    • Export Citation
  • 120.

    Sartor R. The social impact of drug abuse on community life. Med Law. 1991;10(2):205208.

  • 121.

    Henkel D. Unemployment and substance use: a review of the literature (1990–2010). Curr Drug Abuse Rev. 2011;4(1):427. doi: 10.2174/1874473711104010004.

    • Search Google Scholar
    • Export Citation
  • 122.

    Rondinelli RD, Genovese E, Katz RT, et al. AMA Guides to the Evaluation of Permanent Impairment. 6th ed. Chicago: American Medical Association; 2023. doi: 10.1001/978-1-64016-282-2.

    • Search Google Scholar
    • Export Citation
  • 123.

    Social Security Administration website. Substantial gainful activity. Accessed March 4, 2023. https://www.ssa.gov/oact/cola/sga.html.

  • 124.

    National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Committee on Identifying Disabling Medical Conditions Likely to Improve With Treatment. Selected Health Conditions and Likelihood of Improvement With Treatment. National Academies Press (US); April 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 125.

    Talmage JB. Rating opioid use disorder for permanent impairment. AMA Guides Newsletter. January/February 2020;47:89. doi: 10.3109/10826084.2012.663296.

    • Search Google Scholar
    • Export Citation
  • 126.

    Altman v New York City Health and Hospital Corporation. 1996. Accessed March 4, 2023. https://caselaw.findlaw.com/us-2nd-circuit/1380123.html.

  • 127.

    Sullivan EV. Contributions to understanding the neuropsychology of alcoholism: an INS legacy. J Int Neuropsychol Soc. 2017;23(9-10):84359. doi: 10.1017/S1355617717000674.

    • Search Google Scholar
    • Export Citation

Contributor Notes

EDITORIAL COMMENT

Drug addiction and dependency are critical issues that evaluators must consider carefully, especially when evaluating patients' pain and other somatic complaints. Although substance abuse disorders are not considered a ratable impairment according to the AMA Guides to the Evaluation of Permanent Impairment, addiction can substantially limit one or more major life activities. Drug addiction may be considered a disability under certain circumstances; however, there are many complex issues associated with defining it as a disability. Evaluators need to be aware of the potential implications of drug addiction and take appropriate steps to identify and address them.

The opinions expressed in this article are those of the team of authors. Individual authors may have different perspectives, and in no way are these opinions meant to convey the position of the American Medical Association.

  • 1.

    Centers for Disease Control and Prevention, National Center for Health Statistics. 2020 final death statistics: COVID-19 as an underlying cause of death vs. contributing cause. Page last reviewed January 7, 2022. Accessed March 2, 2023. https://www.cdc.gov/nchs/pressroom/podcasts/2022/20220107/20220107.htm.

    • Search Google Scholar
    • Export Citation
  • 2.

    Spencer MR, Miniño AM, Warner M. Drug overdose deaths in the United States, 2001-2021. NCHS data brief. December 2022 (No. 457). National Center for Health Statistics. doi: 10.15620/cdc:122556.

    • Search Google Scholar
    • Export Citation
  • 3.

    Liu S, O'Donnell J, Gladden RM, et al. Trends in nonfatal and fatal overdoses involving benzodiazepines—38 states and the District of Columbia, 2019–2020. MMWR Morbid Mortal Wkly Rep. 2021;70(34):11361141. doi: 10.15585/mmwr.mm7034a2.

    • Search Google Scholar
    • Export Citation
  • 4.

    Leshner AI. Addiction is a brain disease, and it matters. Science. 1997;278(5335):4547. doi: 10.1126/science.278.5335.45.

  • 5.

    Heilig M, MacKillop J, Martinez D, et al. Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology. 2021;46(10):17151723. doi: 10.1038/s41386-020-00950-y.

    • Search Google Scholar
    • Export Citation
  • 6.

    Lie AK, Hansen H, Herzberg D, et al. The harms of constructing addiction as a chronic, relapsing brain disease. Am J Public Health. 2022;112(S2): S104S108. doi: 10.2105/AJPH.2021.306645.

    • Search Google Scholar
    • Export Citation
  • 7.

    Nutt DJ, Lingford-Hughes A, Erritzoe D, Stokes PR. The dopamine theory of addiction: 40 years of highs and lows. Nat Rev Neurosci. 2015;16(5):305312. doi: 10.1038/nrn3939.

    • Search Google Scholar
    • Export Citation
  • 8.

    Blum K, Bowirrat A, Braverman ER, et al. Reward deficiency syndrome (RDS): a cytoarchitectural common neurobiological trait of all addictions. Int J Environ Res Public Health. 2021;18(21):11529. doi: 10.3390/ijerph182111529.

    • Search Google Scholar
    • Export Citation
  • 9.

    Alexander DR. Are We Slaves to Our Genes. Cambridge University Press; 2020. doi: 10.1017/9781108566520.

  • 10.

    Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental Health Indicators in the United States: Results From the 2020 National Survey on Drug Use and Health. HHS Publication No. PEP21-07-01-003, NSDUH Series H-56. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, 2021. Retrieved from https://www.samhsa.gov/data/.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ilhan MN, Yapar D. Alcohol consumption and alcohol policy. Turk J Med Sci. 2020;50(5):11971202. doi: 10.3906/sag-2002-237.

  • 12.

    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):3947. doi: 10.1001/jamapsychiatry.2015.2132.

    • Search Google Scholar
    • Export Citation
  • 13.

    Hasin DS, Grant BF. The national epidemiologic survey on alcohol and related conditions (NESARC), waves 1 and 2: review and summary of findings. Soc Psychiatry Psychiatr Epidemiol. 2015;50(11):16091640. doi: 10.1007/s00127-015-1088-0.

    • Search Google Scholar
    • Export Citation
  • 14.

    Social Security Administration. Disability Evaluation Under Social Security, section 12.00: Mental Disorders—Adult. Accessed March 2, 2023. https://www.ssa.gov/disability/professionals/bluebook/12.00-MentalDisorders-Adult.htm.

    • Search Google Scholar
    • Export Citation
  • 15.

    Addiction treatment market to hit US$ 7.0 billion by 2025 - TMR: Addiction treatment market: Tobacco/Nicotine addiction treatment dominates the market followed by opioid addiction treatment. Oct 1, 2019. NASDAQ OMX's News Release Distribution Channel. Retrieved from https://www.proquest.com/wire-feeds/addiction-treatment-market-hit-us-7-0-billion/docview/2299414535/se-2.

    • Search Google Scholar
    • Export Citation
  • 16.

    World Health Organization. Tobacco [fact sheet]. May 24, 2022. Accessed March 4, 2023. https://www.who.int/news-room/fact-sheets/detail/tobacco.

    • Search Google Scholar
    • Export Citation
  • 17.

    National Institute on Drug Abuse. Common comorbidities with substance use disorders research report: introduction. August 3, 2021. Accessed January 21, 2023. https://nida.nih.gov/publications/research-reports/common-comorbidities-substance-use-disorders/introduction.

    • Search Google Scholar
    • Export Citation
  • 18.

    Li L, Duffy BC, Durocher LA, et al. Potency analysis of medical marijuana products from New York State. Cannabis Cannabinoid Res. 2019;4(3):195203. doi: 10.1089/can.2018.0037.

    • Search Google Scholar
    • Export Citation
  • 19.

    Schultes RE. Hallucinogenic Plants. New York City: NY; Western Publishing Company; 1976.

  • 20.

    Lattimore R. The Odyssey of Homer. New York City: NY; Harper and Row; 1968.

  • 21.

    Macbeth Shakespeare W.. In: The Complete Works of William Shakespeare (Original work published 1623). The Hamlyn Publishing Group Limited; 1958:922944.

    • Search Google Scholar
    • Export Citation
  • 22.

    De Quincey T. Confessions of an English Opium-Eater. Taylor & Hessey; 1823.

  • 23.

    Pepper A, Pepper L. Straight Life: The Story of Art Pepper. Shirmer Books; 1979.

  • 24.

    Burroughs W. The Naked Lunch. Grove Press; 1959.

  • 25.

    Kerouac J. On the Road. Viking Press; 1957.

  • 26.

    Dixon W. Spoonful. [Single recorded by Howlin' Wolf]. Chess Records; 1960.

  • 27.

    Slick G. White Rabbit. [Single from Surrealistic Pillow, recorded by Jefferson Airplane]. RCA Victor; 1967.

  • 28.

    Jagger M, Richards K. Mother's Little Helper. [Single from Aftermath, recorded by the Rolling Stones]. RCA; 1965.

  • 29.

    Lennon J, McCartney P. Day Tripper. [Single, recorded by the Beatles]. EMI; 1965.

  • 30.

    Winehouse A. Rehab. [Single from Back to Black, recorded by Amy Winehouse]. Island; 2006.

  • 31.

    Bush DM, Lipari RN. Substance use and substance use disorder by industry. In: The CBHSQ Report. (April 16, 2015.) Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Rockville, MD. Accessed March 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK343537/.

    • Search Google Scholar
    • Export Citation
  • 32.

    Motyka MA, Al-Imam A. Representations of psychoactive drugs' use in mass culture and their impact on audiences. Int J Environ Res Public Health. 2021;18(11):6000. doi: 10.3390/ijerph18116000.

    • Search Google Scholar
    • Export Citation
  • 33.

    Grier SA, Kumanyika S. Targeted marketing and public health. Annu Rev Public Health. 2010;31:349369. doi: 10.1146/annurev.publhealth.012809.103607.

    • Search Google Scholar
    • Export Citation
  • 34.

    O'Brien CP. Chapter 24: Drug addiction. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 12th ed. McGraw Hill; 2011: 649668.

    • Search Google Scholar
    • Export Citation
  • 35.

    American Society of Addiction Medicine. Public Policy Statement: Definition of Addiction. August 15, 2011. Accessed March 2, 2023. https://www.asam.org/docs/default-source/public-policy-statements/1definition_of_addiction_long_4-11.

    • Search Google Scholar
    • Export Citation
  • 36.

    Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, et al. Effectiveness of naltrexone in the prevention of delayed respiratory arrest in opioid-naive methadone-intoxicated patients. Biomed Res Int. 2013;2013:903172. doi: 10.1155/2013/903172.

    • Search Google Scholar
    • Export Citation
  • 37.

    Nies A, Spielberg SP. Chapter 3: Principles of therapeutics. In: Molinoff PB, Ruddon RW, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York City: NY; McGraw-Hill; 1996: 4361.

    • Search Google Scholar
    • Export Citation
  • 38.

    Advokat, CD, Comaty, JE, Julien, RM. Chapter 1: Pharmacokinetics: how the body handles drugs. In: Julien's Primer of Drug Action. 14th ed. UK; Worth Publishers; 2019: 339.

    • Search Google Scholar
    • Export Citation
  • 39.

    Algera MH, Olofsen E, Moss L, et al. Tolerance to opioid-induced respiratory depression in chronic high-dose opioid users: a model-based comparison with opioid-naïve individuals. Clin Pharmacol Ther. 2021;109(3):637645. doi: 10.1002/cpt.2027.

    • Search Google Scholar
    • Export Citation
  • 40.

    White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction. 1999;94(7):961972. https://doi.org/10.1046/j.1360-0443.1999.9479612.x.

    • Search Google Scholar
    • Export Citation
  • 41.

    Advokat CD, Comaty JE, Julien RM. Chapter 4: Epidemiology and neurobiology of addiction. In: Julien's Primer of Drug Action. 14th ed. UK; Worth Publishers; 2019:105-133.

    • Search Google Scholar
    • Export Citation
  • 42.

    Kalant H, Grupp LA. Drug abuse and drug dependence. In: Kalant H, Roschlau WHE, eds. Principles of Medical Pharmacology. 6th ed. Oxford University Press; 1998: 904916.

    • Search Google Scholar
    • Export Citation
  • 43.

    Napier TC, Herrold AA, de Wit H. Using conditioned place preference to identify relapse prevention medications. Neurosci Biobehav Rev. 2013;37(9, pt A):20812086. doi: 10.1016/j.neubiorev.2013.05.002.

    • Search Google Scholar
    • Export Citation
  • 44.

    Siegel S. Drug anticipation and drug addiction: the 1998 H. David Archibald Lecture. Addiction. 1999;94(8):11131124.

  • 45.

    Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev. 2019;99(4):21152140. doi: 10.1152/physrev.00014.2018.

    • Search Google Scholar
    • Export Citation
  • 46.

    Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiologic Psychol. 1954;47(6):419427. doi: 10.1037/h0058775.

    • Search Google Scholar
    • Export Citation
  • 47.

    Skinner BF. The Behavior of Organisms: An Experimental Analysis. Appleton-Century; 1938.

  • 48.

    Kornetsky C, Esposito RU, McLean S, Jacobson JO. Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse. Arch Gen Psychiatry. 1979;36(3):289292. doi: 10.1001/archpsyc.1979.01780030055004.

    • Search Google Scholar
    • Export Citation
  • 49.

    Negus SS, Miller LL. Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev. 2014;66(3):869917. doi: 10.1124/pr.112.007419.

    • Search Google Scholar
    • Export Citation
  • 50.

    Potenza MN. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond B Biol Sci. 2008;363(1507):31813189. doi: 10.1098/rstb.2008.0100.

    • Search Google Scholar
    • Export Citation
  • 51.

    Scherma M, Muntoni AL, Riedel G, et al. Cannabinoids and their therapeutic applications in mental disorders. Dialogues Clin Neurosci. 2020;22(3):271279. doi: 10.31887/DCNS.2020.22.3/pfadda.

    • Search Google Scholar
    • Export Citation
  • 52.

    Yohn SE, Galbraith J, Calipari ES, Conn PJ. Shared behavioral and neurocircuitry disruptions in drug addiction, obesity, and binge eating disorder: focus on group I mGluRs in the mesolimbic dopamine pathway. ACS Chem Neurosci. 2019;10(5):21252143. doi: 10.1021/acschemneuro.8b0060.

    • Search Google Scholar
    • Export Citation
  • 53.

    Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016;3(8):760773. doi: 10.1016/S2215-0366(16)00104-8.

    • Search Google Scholar
    • Export Citation
  • 54.

    Uhl GR, Koob GF, Cable J. The neurobiology of addiction. Ann NY Acad Sci. 2019;1451(1):528. doi: 10.1111/nyas.13989.

  • 55.

    American Psychiatric Association. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR®). Washington: DC; American Psychiatric Publishers, Inc; 2022.

    • Search Google Scholar
    • Export Citation
  • 56.

    Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ. 2001;164(6):817821.

    • Search Google Scholar
    • Export Citation
  • 57.

    Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev. 2019;99(4):21152140. doi: 10.1152/physrev.00014.2018.

    • Search Google Scholar
    • Export Citation
  • 58.

    Smith MA. Social learning and addiction. Behav Brain Res. 2021;398:112954. doi: 10.1016/j.bbr.2020.112954.

  • 59.

    Jones JD, Comer SD. A review of pharmacogenetic studies of substance-related disorders. Drug Alcohol Depend. 2015;152:114. doi: 10.1016/j.drugalcdep.2015.03.003.

    • Search Google Scholar
    • Export Citation
  • 60.

    Robison AJ, Nestler EJ. Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci. 2011;12(11):623637. doi: 10.1038/nrn3111.

    • Search Google Scholar
    • Export Citation
  • 61.

    Bardo MT, Hammerslag LR, Malone SG. Effect of early life social adversity on drug abuse vulnerability: focus on corticotropin-releasing factor and oxytocin. Neuropharmacology. 2021;191:108567. doi: 10.1016/j.neuropharm.2021.108567.

    • Search Google Scholar
    • Export Citation
  • 62.

    Onaivi ES, Ishiguro H, Gong JP, et al. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLOS One. 2008;3(2):e1640. doi: 10.1371/journal.pone.0001640.

    • Search Google Scholar
    • Export Citation
  • 63.

    Botticelli L, Micioni Di Bonaventura E, Del Bello F, et al. Underlying susceptibility to eating disorders and drug abuse: genetic and pharmacological aspects of dopamine D4 receptors. Nutrients. 2020;12(8):2288. doi: 10.3390/nu12082288.

    • Search Google Scholar
    • Export Citation
  • 64.

    Ho MK, Goldman D, Heinz A, et al. Breaking barriers in the genomics and pharmacogenetics of drug addiction. Clin Pharmacol Ther. 2010;88(6):779791. doi: 10.1038/clpt.2010.175.

    • Search Google Scholar
    • Export Citation
  • 65.

    Madigan MA, Gupta A, Bowirrat A, et al. Precision behavioral management (PBM) and cognitive control as a potential therapeutic and prophylactic modality for reward deficiency syndrome (RDS): is there enough evidence. Int J Environ Res Public Health. 2022;19(11):6395. doi: 10.3390/ijerph19116395.

    • Search Google Scholar
    • Export Citation
  • 66.

    National Institute on Drug Abuse. What are the treatments for comorbid substance use disorder and mental health conditions. April 13, 2021. Accessed February 15, 2023. https://nida.nih.gov/publications/research-reports/common-comorbidities-substance-use-disorders/what-are-treatments-comorbid-substance-use-disorder-mental-health-conditions.

    • Search Google Scholar
    • Export Citation
  • 67.

    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):3947. doi: 10.1001/jamapsychiatry.2015.2132.

    • Search Google Scholar
    • Export Citation
  • 68.

    Vekaria V, Bose B, Murphy SM, et al. Association of co-occurring opioid or other substance use disorders with increased healthcare utilization in patients with depression. Transl Psychiatry. 2021;11(1):265. doi: 10.1038/s41398-021-01372-0.

    • Search Google Scholar
    • Export Citation
  • 69.

    Torrens M, Rossi PC, Martinez-Riera R, et al. Psychiatric comorbidity and substance use disorders: treatment in parallel systems or in one integrated system. Subst Use Misuse. 2012;47(8-9):10051014. doi: 10.3109/10826084.2012.663296.

    • Search Google Scholar
    • Export Citation
  • 70.

    Han B, Compton WM, Blanco C, Colpe LJ. Prevalence, treatment, and unmet treatment needs of us adults with mental health and substance use disorders. Health Aff (Millwood). 2017;36(10):17391747. doi: 10.1377/hlthaff.2017.0584.

    • Search Google Scholar
    • Export Citation
  • 71.

    McCabe SE, Cranford JA, Boyd CJ. Stressful events and other predictors of remission from drug dependence in the United States: longitudinal results from a national survey. J Subst Abuse Treat. 2016;71:4147. doi: 10.1016/j.jsat.2016.08.008.

    • Search Google Scholar
    • Export Citation
  • 72.

    Cleck JN, Blendy JA. Making a bad thing worse: adverse effects of stress on drug addiction. J Clin Invest. 2008;118(2):454461.

  • 73.

    World Health Organization. Curbing prescription opioid dependency. Bull World Health Organization. 2017;95(5):318319. doi: 10.2471/BLT.17.020517.

    • Search Google Scholar
    • Export Citation
  • 74.

    Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain. 1986;25(2):171186. doi: 10.1016/0304-3959(86)90091-6.

    • Search Google Scholar
    • Export Citation
  • 75.

    Bovill JG. Which potent opioid? important criteria for selection. Drugs. 1987;33(5):520530. doi: 10.2165/00003495-198733050-00006.

  • 76.

    Bannwarth B. Risk-benefit assessment of opioids in chronic noncancer pain. Drug Safety. 1999;21(4):283296. doi: 10.2165/00002018-199921040-00004.

    • Search Google Scholar
    • Export Citation
  • 77.

    Charatan F. Doctor disciplined for “grossly undertreating” pain. BMJ. 1999;319:728. doi: 10.1136/bmj.319.7212.728a.

  • 78.

    Department of Veterans Affairs website. Pain as the 5th vital sign toolkit. October 2000. Accessed March 4, 2023. https://www.va.gov/PAINMANAGEMENT/docs/TOOLKIT.pdf.

    • Search Google Scholar
    • Export Citation
  • 79.

    Merboth MK, Barnason S. Managing pain: the fifth vital sign. Nurs Clin North Am. 2000;35(2):375383.

  • 80.

    Berry PH, Dahl JL. The new JCAHO pain standards: implications for pain management nurses. Pain Manag Nurs. 2000;1(1):312. doi: 10.1053/jpmn.2000.5833.

    • Search Google Scholar
    • Export Citation
  • 81.

    Tucker KL. The debate on elder abuse for undertreated pain. Pain Med. 2004;5(2):214228. doi: 10.1111/j.1526-4637.2004.4029_2.x.

  • 82.

    Gleber R, Vilke GM, Castillo EM, et al. Trends in emergency physician opioid prescribing practices during the United States opioid crisis. Am J Emerg Med. 2020;38(4):735740.

    • Search Google Scholar
    • Export Citation
  • 83.

    Hägg S, Jönsson AK, Ahlner J. Current evidence on abuse and misuse of gabapentinoids. Drug Safety. 2020;43(12):12351254. doi: 10.1007/s40264-020-00985-6.

    • Search Google Scholar
    • Export Citation
  • 84.

    Peckham AM, Evoy KE, Covvey JR, et al. Predictors of gabapentin overuse with or without concomitant opioids in a commercially insured U.S. population. Pharmacotherapy. 2018;38(4):436443. doi: 10.1002/phar.2096.

    • Search Google Scholar
    • Export Citation
  • 85.

    Votaw VR, Geyer R, Rieselbach MM, McHugh RK. The epidemiology of benzodiazepine misuse: a systematic review. Drug Alcohol Depend. 2019;200:95114. doi: 10.1016/j.drugalcdep.2019.02.033.

    • Search Google Scholar
    • Export Citation
  • 86.

    Wilson KC, Saukkonen JJ. Acute respiratory failure from abused substances. J Intensive Care Med. 2004;19(4):183193. doi: 10.1177/0885066604263918.

    • Search Google Scholar
    • Export Citation
  • 87.

    Clemow DB, Walker DJ. The potential for misuse and abuse of medications in ADHD: a review. Postgrad Med. 2014;126(5):6481. doi: 10.3810/pgm.2014.09.2801.

    • Search Google Scholar
    • Export Citation
  • 88.

    Sadek J. Malingering and stimulant medications abuse, misuse and diversion. Brain Sci. 2022;12(8):1004. doi: 10.3390/brainsci12081004.

  • 89.

    French MT, Martin RF. The costs of drug abuse consequences: a summary of research findings. J Subst Abuse Treat. 1996;13(6):453466. doi: 10.1016/s0740-5472(96)00128-6.

    • Search Google Scholar
    • Export Citation
  • 90.

    Alexander PD, Gicas KM, Willi TS, et al. A comparison of psychotic symptoms in subjects with methamphetamine versus cocaine dependence. Psychopharmacology (Berl). 2017;234(9-10):153547. doi: 10.1007/s00213-017-4551-7.

    • Search Google Scholar
    • Export Citation
  • 91.

    Mohamed BA, Potvin S. Cannabis and psychosis: what is the link. J Psychoactive Drugs. 2007;39(2):13142.

  • 92.

    Merve AO, Sobiecka P, Remeškevičius V, et al. Metabolites of cannabis induce cardiac toxicity and morphological alterations in cardiac myocytes. Int J Mol Sci. 2022;23(3):1401. doi: 10.3390/ijms23031401.

    • Search Google Scholar
    • Export Citation
  • 93.

    Eigner G, Henriksen B, Huynh P, et al. Who is overdosing? an updated picture of overdose deaths from 2008 to 2015. Health Serv Res Manag Epidemiol. 2017;4. doi: 10.1177/2333392817727424.

    • Search Google Scholar
    • Export Citation
  • 94.

    Mantinieks D, Schumann J, Drummer OH, et al. Stimulant use in suicides: a systematic review. Forensic Sci Int. 2022;338:111391. doi: 10.1016/j.forsciint.2022.111391.

    • Search Google Scholar
    • Export Citation
  • 95.

    Rita RB, Faria AC, Andreia Machado Brito-da-Costa, et al. Cocaine: an updated overview on chemistry, detection, biokinetics, and pharmacotoxicological aspects including abuse pattern. Toxins. 2022;14(4):278. doi: 10.3390/toxins14040278.

    • Search Google Scholar
    • Export Citation
  • 96.

    Klenk L, von Rütte Christina, Henssler JF, et al. Resource consumption of multi-substance users in the emergency room: a neglected patient group. PLOS One. 2019;14(9). doi: 10.1371/journal.pone.0223118.

    • Search Google Scholar
    • Export Citation
  • 97.

    Frost MC, Lampert H, Tsui JI, et al. The impact of methamphetamine/amphetamine use on receipt and outcomes of medications for opioid use disorder: a systematic review. Addict Sci Clin Pract. 2021;16(1):62. doi: 10.1186/s13722-021-00266-2.

    • Search Google Scholar
    • Export Citation
  • 98.

    National Institute on Drug Abuse website. Research topics: Xylanzine. Accessed January 22, 2023. https://nida.nih.gov/research-topics/xylazine.

    • Search Google Scholar
    • Export Citation
  • 99.

    Mittleman RE, Hearn WL, Hime GW. Xylazine toxicity–literature review and report of two cases. J Forensic Sci. 1998;43(2):400402.

  • 100.

    Wong SC, Curtis JA, Wingert WE. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office. J Forensic Sci. 2008;53(2):495498. doi: 10.1111/j.1556-4029.2007.00648.x.

    • Search Google Scholar
    • Export Citation
  • 101.

    Kariisa M, Patel P, Smith H, Bitting J. Notes from the field: xylazine detection and involvement in drug overdose deaths - United States, 2019. MMWR Morb Mortal Wkly Rep. 2021;70(37):13001302. doi: 10.15585/mmwr.mm7037a4.

    • Search Google Scholar
    • Export Citation
  • 102.

    Reyes JC, Negrón JL, Colón HM, et al. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health. 2012;89(3):519526. doi: 10.1007/s11524-011-9662-6.

    • Search Google Scholar
    • Export Citation
  • 103.

    Hobbs W, Rall TW, Verdorn, TA. Chapter 17: Hypnotics and sedatives: ethanol. In: Molinoff PB, Ruddon RW, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. McGraw-Hill; 1996: 361396.

    • Search Google Scholar
    • Export Citation
  • 104.

    Sebastiani G, Borrás-Novell C, Casanova MA, et al. The effects of alcohol and drugs of abuse on maternal nutritional profile during pregnancy. Nutrients. 2018;10(8):1008. doi: 10.3390/nu10081008.

    • Search Google Scholar
    • Export Citation
  • 105.

    Wouldes TA, Woodward LJ. Neurobehavior of newborn infants exposed prenatally to methadone and identification of a neurobehavioral profile linked to poorer neurodevelopmental outcomes at age 24 months. PLOS One. 2020;15(10):e0240905. doi: 10.1371/journal.pone.0240905.

    • Search Google Scholar
    • Export Citation
  • 106.

    Cressman AM, Natekar A, Kim E, et al. Cocaine abuse during pregnancy. J Obstet Gynaecol Can. 2014;36(7):628631. doi: 10.1016/S1701-2163(15)30543-0.

    • Search Google Scholar
    • Export Citation
  • 107.

    Sailer S, Sebastiani G, Andreu-Férnández V, García-Algar O. Impact of nicotine replacement and electronic nicotine delivery systems on fetal brain development. Int J Environ Res Public Health. 2019;16(24):5113. doi: 10.3390/ijerph16245113.

    • Search Google Scholar
    • Export Citation
  • 108.

    McGrath-Morrow SA, Gorzkowski J, Groner JA, et al. The effects of nicotine on development. Pediatrics. 2020;145(3):e20191346. doi: 10.1542/peds.2019-1346.

    • Search Google Scholar
    • Export Citation
  • 109.

    US Department of Health, Education, and Welfare Public Health Service. Smoking and Health. Public Health Service Publication No. 1103, U.S. Government Printing Office; 1964.

    • Search Google Scholar
    • Export Citation
  • 110.

    Jack Miller Center website. The Eighteenth and Twenty-First Amendments: Prohibition in America. Accessed March 4, 2023. https://jackmillercenter.org/eighteenth-twenty-first-amendments.

    • Search Google Scholar
    • Export Citation
  • 111.

    Lightwood J, Glantz SA. Smoking behavior and healthcare expenditure in the United States, 1992-2009: panel data estimates [published correction appears in PLOS Med]. 2016;13(6):e1002070]. PLOS Med. 2016;13(5):e1002020. doi: 10.1371/journal.pmed.1002020.

    • Search Google Scholar
    • Export Citation
  • 112.

    Soneji SS, Sung HY, Primack BA, et al. Quantifying population-level health benefits and harms of e-cigarette use in the United States. PLOS One. 2018;13(3):e0193328. doi: 10.1371/journal.pone.0193328.

    • Search Google Scholar
    • Export Citation
  • 113.

    Heldt NA, Reichenbach N, McGary HM, Persidsky Y. Effects of electronic nicotine delivery systems and cigarettes on systemic circulation and blood-brain barrier: implications for cognitive decline. Am J Pathol. 2021;191(2):243255. doi: 10.1016/j.ajpath.2020.11.007.

    • Search Google Scholar
    • Export Citation
  • 114.

    McGrath-Morrow SA, Gorzkowski J, Groner JA, et al. The effects of nicotine on development. Pediatrics. 2020;145(3):e20191346. doi: 10.1542/peds.2019-1346.

    • Search Google Scholar
    • Export Citation
  • 115.

    Hecht SS. More than 500 trillion molecules of strong carcinogens per cigarette: use in product labelling. Tobacco Control. 2011;20(5):387. doi: 10.1136/tc.2011.042853.

    • Search Google Scholar
    • Export Citation
  • 116.

    Eltorai AE, Choi AR, Eltorai AS. Impact of electronic cigarettes on various organ systems. Respir Care. 2019;64(3):328336. doi: 10.4187/respcare.06300.

    • Search Google Scholar
    • Export Citation
  • 117.

    Vaclavik L, Krynitsky AJ, Rader JI. Mass spectrometric analysis of pharmaceutical adulterants in products labeled as botanical dietary supplements or herbal remedies: a review. Anal Bioanal Chem. 2014;406(27):67676790. doi: 10.1007/s00216-014-8159-z.

    • Search Google Scholar
    • Export Citation
  • 118.

    Brody JE. Medical marijuana is not regulated as most medicines are. New York Times. March 8, 2021. Accessed March 4, 2023. https://www.nytimes.com/2021/03/08/well/live/medical-marijuana.html.

    • Search Google Scholar
    • Export Citation
  • 119.

    National Institute on Drug Abuse website. Addiction and health. March 22, 2022. Accessed February 15, 2023. https://nida.nih.gov/publications/drugs-brains-behavior-science-addiction/addiction-health.

    • Search Google Scholar
    • Export Citation
  • 120.

    Sartor R. The social impact of drug abuse on community life. Med Law. 1991;10(2):205208.

  • 121.

    Henkel D. Unemployment and substance use: a review of the literature (1990–2010). Curr Drug Abuse Rev. 2011;4(1):427. doi: 10.2174/1874473711104010004.

    • Search Google Scholar
    • Export Citation
  • 122.

    Rondinelli RD, Genovese E, Katz RT, et al. AMA Guides to the Evaluation of Permanent Impairment. 6th ed. Chicago: American Medical Association; 2023. doi: 10.1001/978-1-64016-282-2.

    • Search Google Scholar
    • Export Citation
  • 123.

    Social Security Administration website. Substantial gainful activity. Accessed March 4, 2023. https://www.ssa.gov/oact/cola/sga.html.

  • 124.

    National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Committee on Identifying Disabling Medical Conditions Likely to Improve With Treatment. Selected Health Conditions and Likelihood of Improvement With Treatment. National Academies Press (US); April 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 125.

    Talmage JB. Rating opioid use disorder for permanent impairment. AMA Guides Newsletter. January/February 2020;47:89. doi: 10.3109/10826084.2012.663296.

    • Search Google Scholar
    • Export Citation
  • 126.

    Altman v New York City Health and Hospital Corporation. 1996. Accessed March 4, 2023. https://caselaw.findlaw.com/us-2nd-circuit/1380123.html.

  • 127.

    Sullivan EV. Contributions to understanding the neuropsychology of alcoholism: an INS legacy. J Int Neuropsychol Soc. 2017;23(9-10):84359. doi: 10.1017/S1355617717000674.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 355 355 159
PDF Downloads 0 0 0
Save