What Is Epidemiology?
The field of epidemiology involves investigation of the distribution and determinants of health conditions in populations or population subgroups. Epidemiological investigations fall under two common domains: descriptive and analytic. Descriptive epidemiological studies provide estimates of the incidence and prevalence of illnesses or health behaviors. Incidence refers to the proportion of new cases of a particular health outcome during a specific period of time in a specific at-risk population (i.e., among individuals free of the outcome at the beginning of the time period). Prevalence refers to the proportion of a group or population affected with a health condition at a particular point in time. This includes new cases as well as chronic cases that began earlier and continued into the period of observation. Analytic epidemiological studies focus on identifying causes/risk factors (e.g., genetic variants, contextual circumstances) of illness, often through retrospective comparison of cases with noncases or prospective study of disease development among individuals exposed versus unexposed to a particular hypothesized causal factor.
This chapter covers the epidemiology of alcohol and drug abuse and dependence (referred to together as “substance use disorders” [SUDs]). From an epidemiological standpoint, SUDs have common as well as unique characteristics. This chapter identifies common characteristics of the epidemiology of alcohol and drug use disorders and highlights some important characteristics unique to specific substances.
Substance Use in the United States: Historical Overview and Recent Prevalence Trends
Alcohol Consumption
The use of substances to alter mood states has been a part of civilization from prehistoric through modern time periods. Archeological records document the conversion of sugar into fermented beverages for recreational use, as part of religious ceremonies, and as an analgesic or disinfectant as early at 10,000 BCE. Alcohol remains incorporated in the fabric of many cultures for a variety of uses, including social and recreational use, as a part of religious ceremonies and secular festivities, and as a normative aspect of daily life. Furthermore, moderate consumption is associated with health and longevity, and is considered to be protective against several adverse health outcomes including cardiovascular disease.
Long-term historical information on US alcohol consumption is available through per-capita alcohol consumption statistics derived from sales records. These records show that drinking levels in the United States varied greatly over time from the early days of the United States to the 21st century. Per-capita consumption ranged from extraordinarily high levels during the US colonial period (from an estimated 5.8 gallons per year per capita in 1790 to 7.1 gallons in 1830) to very low levels before and during Prohibition (from an estimated 1.96 gallons in 1916 to 0.97 gallons in 1934). Prohibition refers to the period during which the United States prohibited the manufacture, sale, and transportation of alcoholic beverages by the 18th Amendment to the US Constitution. This period began in 1920 and ended in 1933 with the repeal of the 18th Amendment by the 21st Amendment.
From 1935 until 1982, shown in Fig. 2.1 , per-capita alcohol consumption increased steadily to a peak of nearly 2.8 gallons of ethanol per year in 1982. After that, consumption declined until the late 1990s, and then began to increase again.
These data are generally consistent with US general population survey data from 2001–2002 to 2012–2013, showing an increase in the prevalence of drinking, as well as volume and frequency of drinking and prevalence of at least monthly heavy episodic drinking among drinkers. Liver cirrhosis mortality statistics show similar variations over time, including an uptick in alcohol-related liver cirrhosis mortality since 2009, especially notable in young adults 25–34 years of age.
Worldwide, alcohol consumption patterns vary considerably. Consumption is lowest in predominantly Muslim countries (e.g., individuals in Afghanistan and Pakistan consume 0.03 and 0.31 pure alcohol per capita, respectively) and eastern Mediterranean countries, and highest in eastern European countries (e.g., individual in Ukraine and the Russian Federation consume 15.58 and 15.23 L pure alcohol per capita, respectively) and western European countries such as France, Germany, and the United Kingdom.
Alcohol consumption is also heterogeneous within countries. For example, about one-third of US adults do not drink, although US per-capita consumption is 2.32 gallons per year. Abstainers are rare in Eastern Europe (including Russia and Ukraine), where per-capita consumption is the highest in the world. After immigration, immigrants tend to retain the drinking levels of their country of origin rather than hanging onto the patterns of their new country, for example, Mexican immigrants in the United States and Russian immigrants in Israel.
Drug Use
Drugs such as cannabis, opium, and cocaine have been cultivated and used medicinally as well as recreationally for centuries. Opium poppies are believed to have been first grown in the region near modern-day Iraq as early as 3400 BCE. Opium was used primarily as an analgesic and anesthetic, but medical use did not become widespread until the development of the hypodermic needle in the early 1800s. Historical analysis also indicates that marijuana was smoked recreationally and medically in ancient China as early as 2737 BCE. In South America, societies have grown and consumed coca, the plant grown to create cocaine, for centuries. The most common mode of administration is to chew the leaves of the coca plant, or to mix the leaves into a tea. In the 20th century, innovations in pharmacological knowledge led to the development of synthetic drugs such as lysergic acid diethylamide, categorized as a hallucinogen, and methylenedioxymethamphetamine (or “ecstasy”), categorized as an amphetamine.
In Western countries prior to the 1960s, drug use was rare and the few studies that addressed prevalence focused on heroin, with widely varying results. Morphine is believed to have been prescribed often in the 19th and early 20th centuries mainly as a cough suppressant to ease the suffering of individuals with tuberculosis, although no data are available to empirically estimate incidence and prevalence. During the Civil War, it is believed that more than 400,000 soldiers became dependent on morphine, as it was liberally prescribed for pain associated with battle wounds.
Systematic surveys of US drug use began in the 1960s with a series of national household surveys on drug use conducted by the National Institute on Drug Abuse (NIDA) and later by the Substance Abuse and Mental Health Services Administration (SAMHSA). These were originally known as the Household Surveys on Drug Use, and are now known as the National Survey on Drug Use and Health (NSDUH ). A series of three national surveys conducted by the National Institute on Alcohol Abuse and Alcoholism have also provided important information on US adult alcohol and drug use in the years 1991–1992, 2001–2002, and 2012–2013. The survey conducted in 1991–1992 is known as the National Longitudinal Alcohol Epidemiologic Survey (NLAES ). The survey conducted in 2001–2002 is known as the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC ). The third survey, conducted in 2012–2013, is known as the National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III).
Earlier, Household Surveys on Drug Use surveys showed that illicit drug use, especially marijuana, increased greatly after the late 1960s. Heroin use also increased in the late 1960s, when the profile of users changed from “bohemians” to inner-city, unemployed males.
More recent NSDUH data on adults provides time trend information from 2002 to 2013 ( Fig. 2.2 ). This shows that since about 2007, drug use has increased in the US general population, largely driven by increases in the use of marijuana. More detailed examination of NSDUH marijuana data shows increases in adults age 18 or older since 2007 in use, daily/near-daily use, and other cannabis indicators, with increases particularly concentrated within male users from lower income families The increases in marijuana use since the early 2000s are consistent with findings from the NESARC (2001–2002) and NESARC-III (2012–2013 , ), which also show marked increases in marijuana use among adults, including men, younger individuals, and those from lower-income households.
An area of illicit drug use that has become a source of much concern over the last 10 years is prescription opioids, largely fueled by an epidemic of unintentional fatal opioid overdoses, which became a leading cause of injury death and hospital admissions. NSDUH data show increases in nonmedical use of prescription opioids up to about 2006, and a steadying in these rates among adults aged 26 or older, and some decline in the 12–17 and 18–25 age groups. NESARC data show that between 2001–2002 and 2012–2013, nonmedical opioid use increased among adults, as did heroin. NSDUH data do not show overall increases in cannabis use in adolescents 12–17 years of age since 2002.
Another source of information on drug use among adolescents is the Monitoring the Future (MTF) series of annual national surveys of 8th, 10th, and 12th grade students. MTF data since 1991 show that in 1991, 44.1% of 12th graders had ever used an illicit drug, increasing to 54.3% in 1997, and decreasing to 48.9% in 2015. In 1991, 18.7% of 8th graders, 30.6% of 10th graders, and 44.1% of 12th graders had ever used an illicit drug. By 1997, these had increased to 29.4%, 47.3%, and 54.3%, respectively. In 2015, the prevalences were 20.5%, 34.7%, and 48.9%, respectively. By far the most commonly used drug was marijuana (15.5%, 31.4%, and 44.7% among 8th, 10th, and 12th graders in 2015).
Substance Use in the United States: A Public Health Problem
Although alcohol and drug use is common both in the United States and in many countries worldwide, excess alcohol consumption is estimated to be the third largest cause of US preventable mortality and the fifth largest cause of preventable disability worldwide. Excess substance use and SUDs are associated with a broad range of adverse outcomes including but not limited to crashes and traffic fatalities, domestic violence, fetal alcohol syndrome and other prenatal and perinatal insults, neuropsychological impairment, poor medication adherence (e.g., HIV), economic costs, lost productivity, psychiatric comorbidity, and functional disability. Thus, prevention and intervention of excess substance use is an important public health priority.
When Does Use Become Pathological? Substance Abuse and Dependence
The Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association defines psychiatric disorders, including substance use disorders (or SUDs) within a common framework for individuals and groups with different training, experience, and interests. Users include medically and behaviorally trained clinicians, neuroscientists, geneticists, investigators conducting clinical trials, epidemiologists, policymakers, insurance companies, and others. The Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition (DSM-IV ) was published in 1994, and was in use until the publication of Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-5 ). Thus, although DSM-5 is more recent, the DSM-IV definitions of SUD were the basis of a very large body of research, including many of the references cited in this chapter.
Substance Disorders in the Diagnostic and Statistical Manual of Mental Disorders
For SUDs, DSM-IV provided diagnostic criteria for two disorders, dependence and abuse ( Table 2.1 ), as well as symptoms for diagnosing substance-specific intoxication and withdrawal syndromes, and methods for diagnosing substance-induced psychiatric disorders. Note that DSM-IV-TR, published in 2000, provided updated text but did not change the diagnostic criteria. The DSM-IV substance dependence criteria, shown in Table 2.1 , are based on the alcohol dependence syndrome, which was generalized to drugs in 1981. Dependence was considered a combination of physiological and psychological processes leading to increasingly impaired control over substance use in the face of negative consequences. Dependence was considered one “axis” of substance problems, and the consequences of heavy use (social, legal, medical problems, hazardous use) considered a different axis of substance problems. This biaxial concept led to the distinction between abuse criteria (social, role, legal problems, or hazardous use, most commonly driving while intoxicated) and dependence (tolerance, withdrawal, numerous indicators of impaired control over use).
| DSM-IV Abuse(≥1 criterion a ) | DSM-IV Dependence(≥3 criteria b ) | DSM-5 SUD(≥2 criteria c ) | |
|---|---|---|---|
| Hazardous use | X | — | X |
| Social/interpersonal problems related to use | X | — | X |
| Neglected major roles to use | X | — | X |
| Legal problems | X | — | — |
| Withdrawal d | — | X | X |
| Tolerance | — | X | X |
| Used larger amounts/longer | — | X | X |
| Repeated attempts to quit/control use | — | X | X |
| Much time spent using | — | X | X |
| Physical/psychological problems related to use | — | X | X |
| Activities given up to use | — | X | X |
| Craving | — | — | X |
a One or more abuse criteria within a 12-month period AND no dependence diagnosis; applicable to all substances except nicotine for which DSM-IV abuse criteria were not given.
b Three or more dependence criteria within a 12-month period.
c Two or more SUD criteria within a 12-month period.
d Withdrawal not included for cannabis, inhalant, and hallucinogen disorders in DSM-IV; cannabis withdrawal added in DSM-5.
The focus on dependence is based on its centrality in research and on its psychometric properties. DSM-IV defined dependence similarly to the definition found in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). These definitions had good to excellent reliability across samples and instruments, a
a References 25, 27, 95, 122, 123, 125, 300.
with few exceptions (rare substances; hallucinogens). Dependence validity has also been shown to be good via several study designs. These include multimethod comparisons bb References 46, 91, 125, 132, 246, 259, 270.
; longitudinal studies cc References 93, 121, 122, 127, 267, 269.
; latent variable analysis ; and construct validation. Animal models of a syndrome of cocaine dependence symptoms (as distinct from use patterns) lend credence to the dependence syndrome not only as a cross-cultural phenomenon, as suggested by a World Health Organization (WHO) study but as a cross-species phenomenon as well.Substance abuse was a different case. Contrary to clinical assumptions, abuse did not necessarily lead to dependence. d
d References 93, 121, 127, 133, 267, 269.
Furthermore, not all cases of alcohol or drug dependence manifested abuse symptoms. Dependence is more familial than abuse is. DSM-IV–defined alcohol abuse was most often diagnosed in the general population based on one symptom, driving while intoxicated ; preliminary analyses of national data show this was also the case for drug abuse. The DSM-IV definition of abuse was problematic in that it depended on the availability of a car, while dependence was a heritable, complex condition.Various psychometric analyses were conducted to examine the validity of the Edwards and Gross taxonomy of two distinct, correlated factors for substance abuse and dependence criteria prior to the start of the DSM-5 Substance-Related Disorders Workgroup (of whom one of the authors, DH, was a member). Confirmatory factor analysis on the alcohol abuse and dependence items provided mixed evidence; several studies show that a two-factor model best described abuse and dependence items but with very high correlations between the factors, whereas several other studies found evidence of similar model fit for one- and two-factor models and selected the one-factor model on the basis of parsimony and high factor correlations. Factor analyses of cannabis abuse and dependence items have generally found support for a one-factor model or similar fit of one- and two-factor models, although results from a general population survey support a two-factor model. Taken together, these studies showed some support for combining abuse and dependence, albeit with some evidence to the contrary. Differences across studies may also have occurred due to characteristics of the populations studied (e.g., general population versus community sample, adults versus adolescents).
One of the main issues for the DSM-5 Substance-Related Disorders Workgroup was how to address the distinction between abuse and dependence. Workgroup members and other investigators conducted many studies of the dependence and abuse criteria in different adolescent and adult samples and populations. These studies were based on Item Response Theory (IRT) analyses, which provide more nuanced information on the relationship of abuse to dependence symptoms than the factors analyses that had been done before. By the time DSM-5 criteria were finalized, studies on this issue had included more than 200,000 participants. Results were very consistent: abuse and dependence formed a single, unidimensional construct, leading the DSM-5 Substance-Related Disorders Workgroup to eliminate the distinction between abuse and dependence, and combine most of the criteria into a single disorder (see Table 2.1 ). Additional changes of note in DSM-5 were the addition of a craving criterion, removal of the DSM-IV legal problems criterion, and addition of a withdrawal criterion for cannabis, since considerable evidence had accumulated since DSM-IV that a cannabis withdrawal syndrome existed.
Substance Disorders: A Categorical or Dimensional Trait?
Recent psychometric analyses of the substance abuse and dependence criteria have suggested that these disorders are not categorical entities; instead, evidence supports an underlying continuum of alcohol severity across a variety of samples and populations. e
e References 136, 169, 197, 217, 245, 261.
Such information may be critical when statistical power is limited, as it often is in studies of gene-gene or gene-environment interaction. The DSM-5 addressed this issue by providing definitions of mild, moderate, and severe SUD: 2–3 criteria for mild, 4-5 criteria for moderate, and 6 or more criteria for severe.Descriptive Epidemiology: The Incidence and Prevalence of Substance Disorders
Prevalence and Incidence of Substance Disorders
The most comprehensive epidemiologic US information on the incidence, prevalence, and psychiatric comorbidity of alcohol and drug disorders comes from the two NESARC surveys. The NESARC was a longitudinal survey of 43,093 respondents 18 years or older conducted in 2001–2002 with a 3-year follow-up of 34,653 respondents. The NESARC-III was a survey of a fresh sample of 36,309 participants conducted in 2012–2013. The diagnostic interview for both surveys was the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS), a structured interview for nonclinicians with high reliability and validity for SUDs. f
f References 27, 95, 105, 125, 141, 142, 260, 300.
The AUDADIS-IV was used to assess DSM-IV criteria for SUD and other disorders in the NESARC, and the AUDADIS-5 was used to assess DSM-IV and DSM-5 criteria for SUD in the NESARC-III, and DSM-5 criteria for other disorders.In the NESARC, the prevalence of current (past 12 month) DSM-IV alcohol use disorder (abuse or dependence) was 8.5%, whereas the prevalence of lifetime DSM-IV alcohol use disorder was 30.3%. In the NESARC-III, the prevalence of current (past 12 months) DSM-5 alcohol use disorder was 13.3%, whereas the prevalence of lifetime alcohol use disorder was 20.1%. Corresponding DSM-IV rates of current and lifetime alcohol use disorder (12.7% and 43.6% in NESARC-III) showed that substantial increases had occurred in the prevalence of alcohol use disorders in the more recent NESARC-III. Current and lifetime alcohol disorders were more prevalent in men than women in both surveys, and compared with individuals of white race/ethnicity, blacks, Hispanics, and Asians had a lower prevalence of current and lifetime alcohol disorders in both surveys. In both surveys, alcohol disorder prevalence is inversely related to age; persons in younger age groups are most likely to have an alcohol disorder. As shown in the Wave 2 follow-up interview for the NESARC, the incidence of alcohol dependence was 1.66 per 100 person-years, meaning 1.66 cases per year of alcohol dependence for every 100 individuals without alcohol dependence at the beginning of that year. The incidence of alcohol abuse was slightly lower at 1.03 per 100 person-years. In general, predictors of incidence were similar to predictors of prevalence.
Drug disorders were substantially less common than alcohol disorders. In the NESARC, the prevalence of current (past 12 months) DSM-IV drug use disorder (abuse and dependence) was 2% for any current drug use disorder, whereas the lifetime prevalence was 10.3%. In the NESARC-III, the prevalence of current (past 12 months) DSM-IV drug use disorder (abuse and dependence) was 3.9% for any current drug use disorder, whereas the lifetime prevalence was 9.9%. Using DSM-IV criteria in the NESARC-III survey, current and lifetime prevalence of DSM-IV drug use disorder were 4.1% and 15.6%, respectively, indicating substantial national increases in the prevalence of drug use disorders in the United States between the two surveys. Of the substances, cannabis use disorders were the most common in both surveys. The past-year prevalence of DSM-IV marijuana use disorder was 1.5% in the 2001–2002 NESARC and 2.8% in the 2012–2013 NESARC-III, a substantial and significant increase ( P < .05) in prevalence.
Current and lifetime drug disorders are more prevalent in men than in women in both surveys. Drug disorder prevalence is inversely related to age; persons in younger age groups are most likely to have a drug disorder. There was no consistent trend by race for drug disorders. In the NESARC, incidence of drug dependence was estimated at 0.32 per 100 person-years of observation ; incidence of drug abuse was slightly lower at 0.28 per 100 person-years. In general, predictors of incidence were similar to predictors of prevalence.
The Course of Substance Disorders
Initiation of alcohol consumption and drug use often occurs during adolescence. Onset of alcohol abuse and dependence is most likely among individuals 18–29 years of age, although 15% of alcohol dependence cases begin before age 18. Often, substance disorders are not lifelong conditions. Indeed, a high rate of recovery has been documented in general population samples, even among individuals who have never sought treatment. Studies of alcohol disorders in the general population also show that a high proportion of recovered individuals return to moderate drinking as opposed to abstinence. Data from the NESARC has indicated that approximately 75% of individuals diagnosed with alcohol dependence at some point in the past did not have a current (i.e., past year) diagnosis, but that only about 20% of these individuals were abstinent from alcohol. Follow-up of this sample indicates that low-risk drinking represents a risk factor for relapse to an alcohol disorder compared with abstinence. However, using WHO indicators of very high risk, high risk, moderate risk, and low risk drinking, any shifts downward in WHO risk drinking levels from very high risk or high risk at baseline (2001–2002) to a lower level at the 3-year follow-up (2004–2005) was associated with a significant decrease in the likelihood of current alcohol dependence at follow-up.
The transition to adulthood represents a key developmental phase in which alcohol disorders often remit, in a process termed “maturing out.” Major predictors of recovery include key lifestyle components, such as employment, marriage, and childbirth. Whether or not these factors have a causal influence on recovery or reflect common factors underlying the positive lifestyle components and the recovery remains unknown.
Despite substantial progress in the development of treatments for alcohol and drug disorders, only about one-fifth of those individuals with an alcohol disorder and one-sixth of individuals with a drug disorder seek treatment for the condition during their lifetime. Furthermore, the delay from onset of disorder to treatment is typically 8–10 years. Finally, in contrast to sharp increases in treatment utilization for disorders such as depression between 1990 and 2003, a corresponding increase in the proportion of individuals seeking treatment for alcohol and drug disorders did not occur during this period. Data from NESARC-III continue to show poor rates of treatment for those with alcohol and drug use disorders.
The path from first use to dependence to treatment also differs by gender. Women who use alcohol and drugs often start using later than men, have a faster progression from first use to dependence, and enter treatment sooner than men given equal ages of dependence onset, although no such differences have been observed for crack-cocaine users. This phenomenon has been termed “telescoping.”
Evidence is accumulating that these well-documented gender differences in the course of alcohol disorders are converging. Studies of adolescent alcohol use have consistently shown a convergence in rates of alcohol and drug use initiation in younger birth cohorts, especially those born after World War II. Furthermore, several genetically informative samples have researched gender differences in DSM-IV–defined alcohol and drug disorders over time, also finding support for such a convergence. Similarly, large, representative cross-sectional studies in the United States support gender convergence in rates of DSM-IV–defined alcohol abuse and dependence. Finally, evidence indicates that the traditional “telescoping” phenomenon whereby women exhibit later onset of use and disorder but earlier treatment and shorter course may be diminishing, as women are more closely approximating men in both onset and course of disorder. Searches into the causes of these shifts are ongoing, but this evidence indicates increased social acceptability of alcohol use by women in younger generations.
Analytic Epidemiology: The Etiology of Substance Disorders
SUDs have a complex etiology involving genetic and environmental factors. These occur along a continuum, ranging from the macro level consisting of broad social influences, to the micro level, consisting of molecular-level influences. These can be thought of as external to internal levels ( Fig. 2.3 ). In the remainder of this chapter, we address these levels in turn. We begin with macro/external factors, including societal availability and desirability of the substances, geographic and temporal differences, pricing, laws, and advertising. We next consider externally imposed stress. Intermediate-level factors include religiosity and parental and peer social influences. Moving increasingly toward the micro and internal levels, we consider cognitive and personality variables, subjective responses to substances, and specific genetic risk variants.
Availability—Temporal and Geographical
Political Events
Political events, both local and global, influence the availability of substances and thus the risk of substance use and dependence. In 2004, for example, religiously motivated attacks on alcohol retailers in Iraq reduced the availability of alcohol locally for that region. After the Taliban government fell in Afghanistan in 2001, heroin production in Afghanistan increased greatly, coinciding with increased heroin use among American teenagers. Political instability in South American countries such as Bolivia and Colombia, especially in the 1970s, influenced the production of cocaine and increased the availability of cocaine in the United States. Thus, political events at a great geographic distance may influence local substance use availability and patterns of use.
Outlet Density
Counties, cities or states with a higher density of alcohol outlets (places were alcohol is sold) have higher alcohol consumption and higher rates of alcohol-related problems, including hospital admissions, pedestrian injury collisions, and crashes and crash fatalities. Ecologic and multilevel analysis controlling for individual level factors indicates that outlet density is related to higher mean group rates of consumption and drinking norms scores and to driving after drinking. Community-based interventions to limit access to alcohol by reducing the density of outlets have been shown to reduce alcohol-related traffic injury and self-reported consumption. Although information regarding outlet (“dealer”) density is unavailable for drugs, the vigorous efforts of parents, schools, and law enforcement agencies to keep drug dealers away from schools are consistent with the same idea.
Pricing, Laws, and Advertising
Pricing
Alcohol taxation is the major determinant of state variation in the price of alcohol and is thus a government intervention. An inverse relationship exists between state-level price of alcohol and per-capita consumption or adverse consequences of drinking. Furthermore, higher state-level beer tax is associated with lower prevalence of DSM-IV–defined alcohol dependence. Outside the United States, cutting the tax on spirits has been followed by increased per-capita alcohol consumption.
Laws and Law Enforcement: Alcohol
Laws and their enforcement also affect consumption patterns. In the United States, the 18th Amendment to the Constitution outlawed the manufacture, transport, and sale of alcohol from 1920 to 1933. Fig. 2.1 shows that in 1935, per-capita ethanol consumption was very low, but increased steadily afterwards, consistent with cirrhosis mortality rates from the same period. Thus, the 18th Amendment achieved its purpose, but was repealed because it was unacceptable to the public. Similar events occurred in the former Soviet Union, an area of very high per-capita alcohol consumption. In the mid-1980s, the government attempted to restrict consumption. The policies were successful in reducing consumption, but so unpopular that they contributed to the downfall of the government and were eventually reversed.
More recently in the United States, enforcement of laws related to drinking and driving has been shown to be an important deterrent to alcohol-related crashes and fatalities. These include driver’s license suspensions and lowering the maximum legal blood alcohol concentration among drivers. In addition, stricter driving-under-the-influence laws and their enforcement are consistently related to decreased hazardous use and alcohol-related traffic fatalities.
Minimum-age drinking laws influence the availability and acceptability of consumption among young people. Laws vary considerably by country both in scope and in minimum age. For example, the minimum consumption age in the United States is 21, while in Cyprus it is 12. Israel did not have a minimum legal drinking age until 2004, but public concern about increased risky drinking among young adults led to the establishment of a national minimum drinking age (18 years) at that time. Some countries have separate age restrictions for consumption and purchase. For example, in Greece, the minimum consumption age is 14, whereas the minimum purchase age is 17. In Italy, there is no age restriction on consumption in private but a minimum age requirement of 16 to drink in public.
Minimum drinking age laws have a positive effect on community health as well as the health and safety of adolescents. Research in the United States and other developed countries has indicated that minimum drinking age laws reduce traffic crash and fatality rates ; positive effects among adolescents include reducing alcohol consumption and high risk drinking. In addition, several studies have documented an association between minimum drinking age laws and a reduction in youth suicide.
State Distribution Policies
In the United States, states differ in the ways they control the availability of alcohol. Some states exert more control through the operation of state alcoholic beverage sales, whereas others exert less control through the licensing of alcohol outlets. This difference affects sales and consumption patterns. Compared with “wet” counties, “dry” counties, where alcohol is not sold, have lower rates of alcohol-related accidents, driving-under-the-influence arrests, and cirrhosis mortality. International studies corroborate these findings; in Norway, stringent alcohol regulations, such as mandatory closing on Saturdays, led to lower detoxification admissions.
Grass-Roots Efforts
Mothers Against Drunk Driving (MADD) was started in 1980 by a group of women after a teenage girl was killed by a repeat-offense drunk driver. MADD, a very active organization, national since the early 1980s, has been highly effective in influencing state legislation pertaining to intoxicated driving, such as increasing the minimum drinking age from 18 to 21, and the enforcement of maximum-blood-alcohol-level laws among drivers. In particular, a highly publicized media campaign called “Rate the State” in which states were graded A through D on driving-under-the-influence countermeasures, put pressure on legislators to increase the stringency of these laws, shown as an effective strategy in reducing alcohol-impaired driving.
Alcohol Marketing and Advertising
Product development and marketing aim to increase sales and consumption. Alcohol companies allocate substantial resources to researching consumer preferences, developing new products and promoting them. For example, the alcohol beverage industry spent 696 million dollars on magazine advertising alone between 1997 and 2001, largely targeted to adolescents. The alcohol industry does not publish the results of its marketing research, and resources necessary for definitive public health studies of advertising and other marketing effects are limited by comparison.
Public health concerns often focus on marketing that targets adolescents. Existing data from longitudinal studies show associations between late childhood-early adolescent exposure to advertising and subsequent drinking initiation and frequency.
Cross-sectional studies also show associations of various marketing and advertising strategies with positive attitudes about drinking and drinking frequency. Furthermore, an imaging study of adolescent response to alcohol advertising indicated greater brain activation in areas linked to reward and desire among adolescents with alcohol use disorders than infrequent drinkers, suggesting that advertisements are especially salient to vulnerable adolescents.
Laws and Law Enforcement: Drugs
The literature on government efforts to reduce illicit drug use overall by reducing availability is inconsistent. Some studies suggest that the strategies are ineffective, while others find supply reductions efficacious. Reducing the supply of specific illicit drugs can have unintended consequences, including increased use of other substances. Data from US college studies, however, indicate that increased restrictions on alcohol use does not increase marijuana use, as has been hypothesized, but instead serves to decrease both alcohol and marijuana use. Thus, the evidence is inconsistent on the efficacy of government attempts to limit illicit drug use through supply reduction via law enforcement.
The legal status of marijuana has undergone large-scale changes in the United States over the last two decades. Throughout this time, marijuana has been illegal at the federal level, where it is considered a Schedule I substance (high addiction potential, no evidence of medical efficacy or safety). However, 33 states and the District of Columbia have now passed laws legalizing the use of marijuana for medical purposes, beginning with California in 1996 ( Table 2.2 ). Further, among the states that have passed medical marijuana laws (MMLs), 10 (see Table 2.2 ) have now passed laws legalizing use for recreational purposes (recreational marijuana laws [RMLs]).
| State | Year Passed Medical Law | Year Passed Recreational Law |
|---|---|---|
| California | 1996 | 2016 |
| Alaska | 1998 | 2014 |
| Oregon | 1998 | 2014 |
| Washington | 1998 | 2012 |
| Maine | 1999 | 2016 |
| Colorado | 2000 | 2012 |
| Hawaii | 2000 | — |
| Nevada | 2000 | 2016 |
| Maryland | 2003 | — |
| Montana | 2004 | — |
| Vermont | 2004 | 2018 |
| Rhode | 2006 | — |
| New Mexico | 2007 | — |
| Michigan | 2008 | 2018 |
| Arizona | 2010 | — |
| New Jersey | 2010 | — |
| Delaware | 2011 | — |
| Connecticut | 2012 | — |
| Massachusetts | 2012 | 2016 |
| Illinois | 2013 | — |
| New Hampshire | 2013 | — |
| Minnesota | 2014 | — |
| New York | 2014 | — |
| North Dakota | 2016 | — |
| Arkansas | 2016 | — |
| Louisiana | 2016 | — |
| Florida | 2016 | — |
| Ohio | 2016 | — |
| Pennsylvania | 2016 | — |
| West Virginia | 2017 | — |
| Missouri | — | 2018 |
| Oklahoma | 2018 | — |
| Utah | 2018 | — |
Considerable attention has been paid to the potential for MMLs to increase marijuana use and have other unintended adverse consequences in the states in which MMLs were passed. With the use of cross-sectional designs, illicit marijuana use in adolescents and adults was shown to be higher in states with MMLs than in other states. However, using more informative pre-post designs that appropriately controlled for contemporaneous trends in non-MML states, studies of ours and many others have shown that within the states that passed these laws, post-MML increases in adolescent marijuana use did not occur. Only two studies have been done so far to address the effects of MMLs on adult illicit marijuana use using pre-post designs, one using NSDUH data from 2004 to 2013, and a study of ours using NESARC survey data extending from 1991–1992 to 2012–2013. Both of these studies showed post-MML increases in the adult prevalence of illicit cannabis use and DSM-IV cannabis use disorders, suggesting that MMLs were having an influence on rates of adult illicit marijuana use. Many questions remain to be answered about the effects of MMLs on other substances and on other potentially related outcomes.
Because RMLs have been passed so recently, little is known about their impact on adolescent and adult marijuana use and related consequences. One study addressing this among adolescents in the states of Colorado and Washington found post-RML increases in Washington but not Colorado. Because recreational marijuana laws eliminate the need for medical personnel to authorize access to marijuana, such laws may have broader impacts on the use of marijuana and other substances than MMLs. Research on the effects of these laws will be needed as data accumulate after the laws have been passed.
Parental and Peer Influences
Parental Modeling of Substance Use
Twin studies indicate that up to half the liability to alcohol dependence is environmental, and parental modeling has been proposed as one such environmental factor affecting subsequent substance use in their children. Adoption studies do not support this, however, since rates of alcoholism in adopted children of alcoholics are not elevated. One etiologic model with empirical support from twin studies posits that influential factors for substance use and the progression to dependence change over time; environmental and social factors mediate the initiation and use of substances in childhood and adolescence, whereas genetic factors become more influential in the adult substance use and dependence.
Parenting Practices
Poor parental monitoring increases the association with substance-abusing peers, a risk factor for alcohol misuse. Harsh, inconsistent parenting predicts earlier initiation of alcohol use, conduct problems, and poor regulatory competencies. On the other hand, warm yet authoritative parenting styles protect adolescents from alcohol problems.
Peers
Peer influence is a strong predictor of adolescent drug and alcohol use and problems. Twin studies show that shared environmental influences such as peers have a significant effect on initiation of alcohol and any drug use. Two models have been proposed to explain peer influence on adolescent substance use, social selection, and socialization. The social selection theory proposes that young adolescents selectively “mate” with friends; those children who display deviant behavior as children will be prone to choose deviant friendships in adolescence. This can lead to the initiation of drug use (especially marijuana use) and may be a factor in the transition to “heavier” drugs. It has been further proposed that an underlying trait such as sensation seeking (see later) influences both the selection of peers and substance use. In contrast, the socialization theory proposes that adolescents can be influenced to use substances by peers in their environment via modeling, offers, development of expectancies, and social norms. Substance use by older siblings is also associated with individual substance use. Studies that could examine these various environmental effects while controlling for genetic and other biological influences are needed to resolve the social selection/causation debate.
Peers may also be protective. Some US ethnic/immigrant groups use substances less than the norm. Adolescents from these groups with ethnically homogeneous peers encounter less pressure to use substances.
Stress
Drug disorders are often preceded and accompanied by disruptive behavior and conduct problems that have a shared genetic vulnerability with drug disorders. These behaviors evoke negative reactions from the environment, resulting in stressful life events that are not always independent of the individuals, making a causal direction between stress and disease onset difficult to discern. In animal studies where stress can be experimentally applied, cause and effect are clearer, as is also the case in studies of early stressful experiences in humans that antedate the onset of SUDs.
Animal Models
In animal studies, the timing of stress relative to normal development can be experimentally manipulated. In adult animals, substance use increases after exposure to physical stressors and social stressors.
Early life stressors also contribute to drug-using behaviors in animals. Neonatally isolated rats are more likely than handled rats to acquire stimulant self-administration behaviors and show higher dopamine levels in response to cocaine, suggesting that early stress leads to greater cocaine reward. Early life rearing stressors predict ethanol seeking in primates. Isolated rearing led to increased drinking of morphine solution under various conditions. Animal models of Δ9-tetrahydrocannabinol self-administration may allow similar studies for cannabis.
Early Stressors and Drug Use in Humans
Childhood stressors, including parental separation, neglect, and abuse (physical and sexual) are associated with later substance use, problems, and dependence. However, up to about 10 years ago, most studies had failed to control for parental history of substance abuse, a potential confounder given that substance abuse is associated with poor parenting. Since then, many studies with appropriate controls for parental history of substance abuse have shown a relationship between childhood maltreatment and adult substance abuse problems, g
g References 29, 70, 71, 77, 184, 186–190, 223, 233
and a recently published 30-year prospective study showed transmission of child abuse from one generation to the next. One informative study showed that among adolescents with a substance-abusing parent, strong family cohesion (the opposite of neglect) protected against drug problems. Twin studies allow the study of environmental stressors while controlling for genetic influences, and have shown that childhood sexual abuse is an environmental risk factor for SUDs.Religiosity
Religiosity has been called “one of the more important environmental factors that affect the risk for substance use and dependence.” An inverse relationship between religiosity and drinking is cross-cultural. Longitudinal studies of adolescents and college and professional students show that religiosity protects against later heavy drinking. Religiosity is strongly correlated within twin pairs due to shared environmental effects. Heritability of drinking differs between religious and nonreligious twins, an example of gene-environment interaction. In twins studied longitudinally, religiosity predicted later drinking more than drinking predicted later religiosity, suggesting that religiosity is more likely to influence drinking than the reverse . These studies indicate that religiosity is largely environmental and protects against alcohol use disorders. Religiosity also protects against drug disorders, although this literature is less extensive.
Cognition, Personality
Substance Expectancies and Motivations
Positive substance expectancies constitute an important risk factor for the development of alcohol dependence. For example, alcohol expectancies are considered the beliefs that drinking alcohol will result in decreased negative emotions or enhanced positive emotions. These expectancies can be derived from parents and peers, and are believed to be environmentally influenced rather than genetically influenced. Motivations for drinking often fall under four main domains: (1) drinking to obtain social rewards or enhance social interactions; (2) drinking to enhance positive mood; (3) drinking to reduce negative mood; and (4) drinking to avoid social rejection and conform to social norms. Although individuals with alcohol disorders often rate all motivations highly, reduction of negative affect and enhancement of positive affect have been prospectively associated with heavy use and alcohol and drug disorders.
Personality Traits
No single personality trait predicts alcoholism, but traits associated with the development of alcohol use disorders include novelty seeking and sensation seeking, , traits that are often associated. The heritability of sensation seeking is unclear, with some twin studies suggesting that approximately half of the variance can be attributed to genetic factors, and another suggesting a much weaker influence of genetic factors. Additional personality traits related to alcohol use disorders, albeit less consistently, are neuroticism/negative emotionality, impulsivity/disinhibition, and extraversion/sociability. Similar traits have been examined in relation to drug use disorders. For example, research has shown that impulsivity/inhibition is reliably lower among individuals with drug abuse/dependence, whereas negative emotionality tends to be higher.
Subjective Reactions
The level of response to alcohol indicates the quantity needed to obtain an effect. Individuals with a low level of response need to drink more to obtain an effect. This is a genetically influenced characteristic associated with enhanced risk for alcohol use disorders. Level of response varies by ethnicity. Several groups at high risk for alcohol use disorders show low response, including children of alcoholics, Native Americans, and Koreans, while high response is found among Jews, a group with relatively low levels of alcohol disorders. A low level of response predicts later onset of alcohol dependence in young adult males, and may contribute to transition from lighter to heavier drinking in individuals in a heavy-drinking environment. Several chromosomal regions have shown suggestive linkage results to level of response, and an association with variations in the ADH1B gene (one of the genes that influences metabolism of alcohol in the liver) has been documented, but replication is needed.
Subjective reactions can also be characterized by whether they are positive or negative. A stimulating (reinforcing), rather than sedating, effect of alcohol has been identified in moderate/heavy drinkers, as well as untreated alcoholics. In contrast, a flushing reaction to alcohol, found among Asians, includes unpleasant physical sensations. A strong flushing reaction precludes drinking, while moderate flushing protects against alcohol dependence. Individuals also vary in their subjective responses to marijuana, and positive and/or negative responses are moderately heritable.
Psychiatric Comorbidity
Individuals with SUDs exhibit higher rates of mood, anxiety, and personality disorders than the general population. For example, national surveys indicate that individuals with an alcohol disorder are approximately 3.0 times more likely to be diagnosed with major depression; the association between drug disorders and major depression is even stronger, with odds ratios around 7.0. A strong association has also been documented between substance disorders and personality disorders. For example, the NESARC data estimates that 39.3% and 72.4% of individuals with antisocial personality disorder meet criteria for lifetime drug disorders and alcohol disorders, respectively. Borderline personality disorder was also strongly associated with alcohol and drug disorders in the NESARC, and antisocial, borderline, and schizotypal personality disorder were associated with persistent course of alcohol and drug use disorders at the 3-year follow-up interview of the NESARC. New findings from the 2012–2013 NESARC-III replicate the strong relationships between SUDs and psychiatric comormidity.
The strong and consistent relationships between SUDs and other psychiatric disorders have prompted etiologic researchers to evaluate evidence for an underlying vulnerability to psychiatric disorders in general. Adult twin studies indicate at least moderate genetic heritability across disorders, and some genetic studies have indicated specific genetic variants associated with the transmission of several psychiatric disorders in general, rather than particular disorders. “Internalizing” and “externalizing” domains have been proposed as a means of organizing individual disorders into larger, more meaningful groups. Internalizing disorders are often characterized by the anxiety and depression domains, whereas externalizing disorders are often characterized by alcohol, drug, and antisocial personality disorders. Research into the validity and utility of broad versus narrow categorizations of disorders has been a major area of psychiatric research for decades, and is ongoing.
Genetics
Family and Twin Studies of Alcohol and Drug Dependence
Alcoholism and drug disorders are familial. Genetic epidemiology studies of heritability use twin samples to compare concordance for a disorder between monozygotic (identical) and dizygotic (nonidentical) twins. In these studies, significantly higher concordance in identical twins, who share 100% of their genes, compared with nonidentical twins, who share only an average of 50% of their genes, indicates genetic heritability for a disorder. Twin studies of alcohol dependence show substantial heritabilities (50%–60%). Heritability estimates from studies of illicit drugs are more variable, perhaps due to more varied phenotypes (use, heavy use, abuse, and dependence); for drug dependence, heritability estimates are similar to those for alcohol dependence. For all substances, environmental factors appear to influence initiation and continuation of use, whereas genetic factors move individuals from use to dependence. In addition, as noted previously, environmental and social factors mediate the initiation and use of substances in childhood and adolescence, whereas genetic factors become more influential in adult substance use and dependence. Some twin studies investigating shared heritability of dependence on different substances showed high shared genetic variance between substances, whereas other studies suggest that dependence on different classes of drugs is not genetically interchangeable. Molecular genetics studies may be able to clarify these issues.
Genetics in Epidemiology Studies
Some genetic variants that affect the process of alcohol metabolism in the liver such as alcohol dehydrogenase 4 ( ADH4 ) are related to both alcohol and drug dependence. Alcohol dehydrogenase 2 ( ADH2 or ADH1B ) and aldehyde dehydrogenase ( ALDH2 ) have also shown well-replicated relationships to alcohol phenotypes. However, genetic linkage and candidate gene association studies, used for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to SUDs, have been only moderately successful in identifying relevant genetic variants. Recently, genome-wide association (GWAS) studies have become a major tool for identifying genetic variants related to alcohol and drug use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status or related underlying endophenotypes. GWAS studies are just beginning to uncover novel biology. However, although the functional significance of results remains a matter of extensive debate and uncertainty, genetics remains an important field of study in the etiology of SUDs. The availability of a panel of genetic variants from over 20,000 participants in the NESARC-III may offer new information from a large sample that has been well characterized in terms of phenotypes and other characteristics.
Although twin studies show that genetic and environmental factors are both important, relatively few studies have addressed whether the relationship of specific genetic variants to alcohol and drug dependence is modified by environmental circumstances. Examples of this approach involving candidate genes are studies showing that exposure to childhood maltreatment interacts with a gene influencing stress reactions to predict early onset of drinking among adolescents, and interacts with ADH1B on risk for alcohol phenotypes in Jewish Israeli drinkers. GWAS studies remain to be conducted.
Studying the interaction between certain genes and specific environmental factors has important implications for the prevention and treatment of alcohol and drug use disorders. First, better knowledge in this area may help early identification of individuals who are unlikely to be able to use drugs or alcohol in moderation for early education, additional support, or supervision. Second, the knowledge may help identify individuals exposed to particular stressors who would particularly benefit from intervention. Finally, clearer knowledge of the interaction of environmental with genetic effects may suggest new lines of investigation to determine the biological mechanisms of protective or risk-enhancing environmental events or conditions, which may eventually aid in developing better treatments.
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