Purpose of the TIP

Major U.S. institutions responded slowly to the dangers of stimulants throughout the 1970s and 1980s, partly because researchers and clinicians had only a partial picture of the basic biologic and psychological effects of these powerful psychostimulants. Knowledge gained over the past four decades about the properties of these substances can help clinicians understand, prevent, and treat the problems created by the use of cocaine and methamphetamine (MA) and the misuse of prescription stimulant medications (e.g., methylphenidate). This TIP summarizes the latest research as well as firsthand clinical experience of substance use disorder (SUD) treatment professionals.

Since the mid-1980s, there has been an explosion of knowledge about the effects of stimulants. Because these psychostimulants alter the functioning of the body and the brain, physicians and physician assistants, nurses and nurse practitioners, psychologists, social workers, licensed professional counselors, marriage and family counselors, SUD counselors, other behavioral health service providers, and peer recovery support specialists must understand the biologic aspects of stimulant use disorders. New areas of expertise include pharmacology, genomics, neurobiology, psychiatric and psychological manifestations, and treatment approaches for stimulant use disorders.

Stimulant use disorders do more than harm the people who have them. They can also negatively affect the lives of these individuals' family members, friends, neighbors, and coworkers. This wider effect makes it all the more important to help individuals with stimulant use disorders engage in SUD treatments and services.

This TIP presents current knowledge about the nature and treatment of stimulant use disorders. Because the Food and Drug Administration (FDA) has to date not approved any medications for stimulant use disorders, this TIP does not discuss pharmacology as a treatment strategy. The TIP is designed to provide scientifically established information about the effects of stimulants in a manner that makes it available and relevant for frontline treatment providers. In addition, the document reviews what is known about treating the medical, psychiatric, and SUD problems associated with the use of cocaine and MA and misuse of prescription stimulants. The treatment section emphasizes those approaches that have empirical support.

Organization of the TIP

This TIP opens with a broad overview of the current state of stimulant use disorders in the United States (Chapter 1) and then moves into the neurobiologic aspects (Chapter 2), assessment and diagnosis (Chapter 2), and medical management (Chapter 3) of stimulant use disorders. Chapter 4 introduces readers to empirically supported nonpharmacologic treatments for stimulant use disorders, and Chapter 5 takes an indepth look at important clinical factors affecting the full continuum of care, including treatment initiation and abstinence maintenance. Chapter 6 discusses stimulant use among a range of special populations and specific considerations to improve engagement and treatment for the described populations. Finally, Chapter 7 provides a compendium of resources, including links to online information and tools.

Exhibit 1.1 defines important terms used in this publication. Also, note that the term “clinician” covers all healthcare providers and behavioral health service providers who work with people with stimulant use disorders and other SUDs. This could include psychologists, psychiatrists, national certified addiction counselors, licensed alcohol and drug counselors, marriage and family therapists, social workers, licensed professional counselors, physicians, nurses, and advanced practice healthcare providers (e.g., nurse practitioners, physician assistants). However, this term does not refer to peer recovery support specialists. Also, the TIP uses the term “patients” rather than “clients” or “consumers” to refer to people who are receiving any preventive services or care for stimulant use disorders or related conditions.

Box

EXHIBIT 1.1. Key Terms.

Scope of the TIP

This TIP looks at stimulants derived from the coca plant (cocaine hydrochloride and its derivatives) and the synthetically produced amphetamines. Regarding amphetamines, the TIP focuses on MA—the major illicitly produced and misused drug in this group—in its various forms. Certainly, there are other stimulants that are more widely used (e.g., caffeine) or that produce major health and social problems (e.g., nicotine); however, discussion of these substances is beyond the scope of this document.

Although considered drugs of misuse, MA analogs are not included in this document. These analogs are compounds with MA-like molecular structures but not necessarily effects similar to MA. Sometimes called designer drugs, they include MDA (3,4-methylenedioxy-amphetamine) and MDMA (3,4-methylene-dioxymethamphetamine).

Current Stimulant Use in the United States

Stimulant epidemics of the 1980s and 1990s had a devastating impact on American society. The impact of illicit stimulant use affected international politics, the U.S. legal system, and the U.S. healthcare system.

As the end of the 20th century neared, the powerful psychostimulants cocaine and MA and their derivatives joined opioids and alcohol as primary targets in the efforts to combat SUDs and misuse of prescription stimulants. The pressing need to effectively address the stimulant epidemic and treat people with stimulant use disorders produced a tremendous amount of scientific and clinical research. The results of this research broadened our knowledge of the human brain and expanded our understanding of SUDs.

Recent statistics demonstrate the scope of stimulant use in the United States. For instance (Center for Behavioral Health Statistics and Quality [CBHSQ], 2020a):

•

Past-month cocaine use by people in the United States ages 18 to 25 increased from approximately 552,000 in 2016 to 665,000 in 2017, which then decreased to 524,000 in 2018, and increased slightly to 540,000 in 2019.

•

Among people age 26 and older, past-month cocaine use increased slightly from 1.3 million in 2016 to 1.5 million in 2017, and essentially remained level for the next 2 years.

•

Past-year MA use among people ages 18 to 25 increased moderately from 2016 to 2017 (approximately 256,000 to 375,000), but then leveled out around 275,000 in 2018 and 2019.

•

Past-year MA use among people age 26 and older increased each year, from 1.1 million in 2016 to 1.7 million in 2019.

•

Past-year prescription stimulant misuse was steady among people age 26 and older from 2016 to 2019. However, among people ages 18 to 25, misuse has decreased, from about 2.5 million in 2016 and 2017 to 2 million in 2019.

Stimulant-involved overdose deaths in the United States have skyrocketed over the past 20 years. From 1999 to 2019, overdose fatalities from psychostimulants with misuse potential other than cocaine (e.g., MA) grew more than 29-fold, from 547 deaths in 1999 to 16,167 in 2019 (National Center for Health Statistics [NCHS], 2020; National Institute on Drug Abuse [NIDA], 2021a). In that same time, overdose deaths due to cocaine increased from 3,822 in 1999 to 15,883 in 2019 (NCHS, 2020; NIDA, 2021a).

More recently, overdose deaths involving cocaine increased by 26.5 percent from the 12 months ending in June 2019 to the 12 months ending in May 2020. Overdose deaths involving other psychostimulants (e.g., methamphetamine, prescription stimulants, amphetamines) are provisionally calculated to have increased by 34.8 percent across the same comparison periods (Centers for Disease Control and Prevention [CDC], 2020c).

Figure

These patterns appear to be strongly driven by the increasingly popular trend of combining cocaine or MA with synthetic opioids (e.g., fentanyl) or nonsynthetic opioids (e.g., heroin). Most MA in the United States is cultivated and produced in Mexico, whereas Colombia is the United States' main supplier of cocaine (although the Mexico-Southwest border is the primary port of entry into the United States; Drug Enforcement Administration [DEA], 2019, 2021). Increasing amounts of the MA produced by Mexican cartels and transported into the United States now contain fentanyl in varying amounts. Much of the stimulant product sold on the street currently includes fentanyl.

Like MA, cocaine is increasingly being combined with fentanyl (or with both heroin and fentanyl, in what is known as a super speedball) to help offset the steep decline individuals experience when a cocaine “high” subsides (DEA, 2019, 2021). Most cocaine is adulterated with fentanyl at the “retail” level and not the “wholesale” level—that is, after it enters the United States (DEA, 2019, 2021).

The connection of stimulant use to the opioid epidemic is very real and very dangerous:

•

The State Unintentional Drug Overdose Reporting System found that, from January to June 2019, the most common stimulant in stimulant–opioid combinations leading to overdose death was cocaine (68.5% of cases), followed by MA (33.3%; O'Donnell et al., 2020).

•

For both cocaine and MA, the number of overdose deaths also involving opioids has increased steadily since 2014. For cocaine, overdose deaths are primarily due to combinations with fentanyl or fentanyl analogs specifically (NIDA, 2021a).

•

Data from the National Vital Statistics System found the percentage of cocaine-related overdose deaths also involving any opioid increased from almost 30 percent in 2000 to 63 percent in 2015 (McCall Jones et al., 2017).

Price and purity have likely played a role in the changing statistics on U.S. stimulant use, overdose, and fatalities. In 2018, the average purity of wholesale cocaine bricks analyzed by DEA's Cocaine Signature Program was 85 percent (DEA, 2019). In the first half of 2019, the average purity of MA was over 97 percent (DEA, 2021). From 2013 to 2017, the price of MA purchased in the United States decreased by more than 17 percent, from $68 to $56 per pure gram (DEA, 2019). Like MA, domestic purchases of cocaine also became less expensive from 2013 to 2017, falling from $213 to $153 per pure gram (DEA, 2019).

Also contributing to the increased lethality of MA is the shift toward production using phenyl-2-propanone as the chemical precursor to synthesis rather than ephedrine or pseudoephedrine. Using pseudoephedrine has been hindered somewhat by reduced access to sales of the over-the-counter product as a result of the Combat Methamphetamine Act of 2005 (see the text box “Legislative and Regulatory Milestones Since 2000”). The phenyl-2-propanone method bypasses the use of strictly controlled chemicals (i.e., ephedrine, pseudoephedrine) and yields a highly potent form of MA. More than 99 percent of MA samples analyzed in the first half of 2019 by the DEA Methamphetamine Profiling Program were manufactured using the phenyl-2-propanone method (DEA, 2021).

The breakdown of stimulant overdose patterns by race/ethnicity underscores differential effects among people of color. In 2019, the highest total number of psychostimulant-related deaths by race occurred among Whites (13,987), but the highest crude death rate by race was among American Indian/Alaska Native populations, at 8.1 deaths per 100,000 people (NCHS, 2020). (Crude death rates are a measure of the number of deaths within a given population during a specified period.) For cocaine, the highest crude death rate by race was among Blacks/African Americans, at 10.9 deaths per 100,000 people—more than twice that of the next-highest crude death rate (4.3 deaths per 100,000 Whites) and more than 4 times that of American Indian/Alaska Native populations (2.5 deaths per 100,000; NCHS, 2020).

Figure

Treatment for stimulant use disorders has been increasing recently. From 2015 to 2017, treatment admissions (i.e., the formal acceptance of a client into SUD treatment) for crack cocaine increased by 11 percent, for nonsmoked cocaine by 37 percent, for amphetamines by 41 percent, and for other stimulants by 62 percent (CBHSQ, 2020b).

But unmet treatment need is pervasive across SUDs broadly, with data from the Substance Abuse and Mental Health Services Administration's (SAMHSA) 2019 National Survey on Drug Use and Health indicating that only 10 percent of people age 12 and older who had a past-year SUD received any SUD treatment, and only 1 percent received treatment at an SUD specialty facility (CBHSQ, 2020a).

Treatment dropout is also a problem. A meta-analysis of 151 studies looking at SUD treatment rates (Lappan et al., 2020) found that the overall treatment dropout rate across all SUDs is 30.4 percent. By comparison, the treatment dropout rate is 53.5 percent for MA and 48.7 percent for cocaine (Lappan et al., 2020).

Prescription Stimulant Misuse

Stimulant medication is FDA approved for treating attention deficit hyperactivity disorder (ADHD) and narcolepsy (a disorder of extreme sleepiness). Commonly prescribed stimulants include dextroamphetamine, dextroamphetamine/amphetamine combination product, and methylphenidate.

The prescribing of these medications has been increasing. National prescription stimulant dispensing rates grew significantly from 2014 to 2019, from 5.6 prescriptions per 100 persons to 6.1 per 100 persons, with the growth attributable in large part to increases among women and adults age 20 and older (Board et al., 2020). Total usage of prescription amphetamine, methylphenidate, lisdexamfetamine, and prescription MA, including extended-release formulations, doubled from 2006 to 2016 (Piper et al., 2018; Sembower et al., 2013). Further, from 2007 to 2011, the prevalence of children taking medication for ADHD increased by 28 percent, from 4.8 to 6.1 percent (Visser et al., 2014). Between 2013 and 2015, CDC reported a 344-percent increase in ADHD prescription medication claims by privately insured women ages 15 to 44 (K. N. Anderson et al., 2018).

Rates of nonmedical prescription stimulant use also are concerning. In 2019, almost 4.5 million adults in the United States reported past-year misuse, 1.4 million reported past-month misuse, and 492,000 met criteria for a stimulant use disorder involving prescription stimulant misuse (CBHSQ, 2020a).

Data suggest diversion of stimulant medication is increasing among U.S. adolescents and may occur out of a desire to enhance academic performance (Colaneri et al., 2017). Additionally, among young adults, anywhere from 5 to 35 percent of college students reportedly misuse prescription stimulants not just for enhanced neurocognitive performance but for euphoric effects or weight control as well (Benson et al., 2015; Kilwein et al., 2016; Weyandt et al., 2013, 2016; Wilens et al., 2016).

Prescribers can help limit diversion of stimulants by adhering to DSM-5 criteria when diagnosing ADHD so that the medication is appropriately prescribed. When a prescription is written, the prescriber should cross-reference the prescription information with data available in state-run prescription drug monitoring programs. Prescribers can also help prevent stimulant medication misuse through numerous strategies, including (Colaneri et al., 2017):

•

Using medication contracts.

•

Educating patients, especially high school and college students who are diagnosed with ADHD, about the danger of sharing their medication with friends and the legal implications of this.

•

Limiting prescriptions to a smaller number of pills.

•

Implementing pill counts.

•

Prescribing long-acting instead of immediate-release formulations.

Additionally, because overdiagnosis and incorrect diagnosis can lead to inappropriate prescribing, primary care providers should not diagnose ADHD themselves. Rather, they should refer patients to an appropriate mental health service professional (such as a psychiatrist or psychologist) for evaluation.

Prescribing nonstimulant medications for ADHD is another option that is particularly relevant for patients with a stimulant use disorder and co-occurring ADHD who want to pursue abstinence. Atomoxetine is a norepinephrine reuptake inhibitor that is not a DEA-controlled substance because it has very low misuse/stimulant use disorder potential (Clemow & Walker, 2014). Guanfacine and clonidine are alpha2-adrenergic receptor agonists that also have demonstrated good efficacy in reducing ADHD symptoms but have low misuse potential (Clemow & Walker, 2014). To learn more about managing ADHD in people with co-occurring stimulant use disorder, see Chapter 6.

Box

LEGISLATIVE AND REGULATORY MILESTONES SINCE 2000.

Importance of Science in Building Future Treatments

The original TIP's consensus panel believed that scientifically derived knowledge should serve as the foundation of treatment for stimulant use disorders. Findings from basic and clinical research efforts funded by NIDA, as well as other government and private institutions, have given treatment providers a set of strategies and tools to assist people with stimulant use disorders.

At this time, the approaches with the greatest empirical support combine psychosocial and behavioral strategies delivered in outpatient settings (e.g., contingency management, cognitive–behavioral therapy/relapse prevention). Emerging treatment techniques include exercise and mindfulness meditation. As knowledge of stimulants and brain functioning rapidly increases, thanks to active research funded by federal agencies and private foundations, other new approaches should soon be forthcoming. The development of pharmacotherapies for the treatment of stimulant use disorders remains a major priority of research efforts, and these efforts will likely provide some important new options in the near future.

Summary

Stimulant use and related deaths in the United States are growing problems that are intertwined with the current opioid epidemic. Stimulant use disorders have direct effects on the health and functioning of people with these disorders as well as secondary effects on others around them. This is partly what makes treatment so critical. SUD treatments and services not only help individuals with stimulant use disorders, but also benefit their entire support system and surrounding environment (e.g., family, friends, workplace, neighborhood). Treatment rates are lower than needed to keep pace with the number of individuals using stimulants and developing stimulant use disorders each year. New knowledge about how these substances influence the basic electrical and chemical activity of the human brain has allowed a better understanding of how and why stimulants affect human behavior, and this knowledge has rapidly influenced the development of new treatment efforts. This TIP provides an overview of:

1.

The new knowledge about stimulants.

2.

The treatment efforts to address stimulant use disorders.

3.

Other clinical, medical, and social interventions developed in response to these disorders.