Nonmedical Use of Controlled Medications by Adolescents and Young Adults: Clinical Report

Adolescents and young adults (AYAs) under the age of 25 are at a higher risk for substance use and addiction compared with older adults.^1,2  AYAs are biologically primed to seek larger and riskier rewards at the expense of safer and less rewarding alternatives because of a developmental imbalance in the prefrontal cortex and subcortical regions involved in hedonic drive.³  As a result, they are at high risk for nonmedical prescription drug use (NMPDU) and its sequelae.^4,5 

Nonmedical prescription drug use is defined as follows: use of a controlled prescription medication that was prescribed for someone else, regardless of intended use; use of one’s own controlled prescription medication in any way that was not as prescribed (eg, differing amount, frequency, or indication); use of one’s own prescription leftovers regardless of indication; and/or any intentional use of such medications for the feeling they caused (eg, intoxication or euphoric effects).

In this clinical report, NMPDU refers primarily to the use of controlled prescription medications, even though several of the concepts and recommendations discussed can also apply to noncontrolled prescription or over-the-counter medications for which nonmedical use has been reported (eg, clonidine, diphenhydramine, pseudoephedrine).^6–8  As such, the scope of this report is centered on controlled medications (with abuse potential) that fall under US Drug Enforcement Agency schedule classifications II through V,⁹  which includes opioids (eg, codeine, morphine, oxycodone, hydrocodone, tramadol, fentanyl, meperidine, and buprenorphine), stimulants (eg, methylphenidate, amphetamine, and dextroamphetamine), sedative-hypnotics (eg, benzodiazepines, barbiturates, and nonbenzodiazepine “Z-drugs,” such as zopiclone and zolpidem), and other medications that are commonly used off-label for pain, irritability, and anxiety, such as pregabalin and gabapentin (which is classified as a controlled substance in some states). “Medical” cannabis, illicit drugs (eg, heroin), alcohol, ketamine, and physical performance-enhancing drugs (ie, anabolic steroids) are not discussed in this report.

Nonmedical use of prescription opioid, stimulant, and sedative-hypnotic medications by AYAs concerns a small yet important proportion of this population.¹⁰  Their use is associated with several short- and long-term harms as well as with other risky behaviors.^11–13  For example, although the attention given to the ongoing opioid crisis has led to increased precautions around this class of medications, and rates of nonmedical use of prescription opioids have been decreasing steadily among AYAs,¹⁰  there were 672 prescription opioid overdose deaths in AYAs ages 15 to 24 years in the United States in 2019.¹⁴ 

Pediatricians are in a key position to prevent and address NMPDU with their patients. However, there is limited guidance available for pediatricians attempting to prevent or reduce NMPDU among AYAs. This clinical report will begin with a discussion of the epidemiology of NMPDU. Then, it will discuss the risk and protective factors as well as medical consequences of NMPDU. Finally, guidance for prevention, early intervention, and treatment of NMPDU by AYAs will be provided.

Whereas rates of lifetime abstinence from all substances among high school seniors have been increasing steadily since 1991,^15,16  trends in rates of NMPDU vary by medication class. Past-year nonmedical use of prescription opioids—hydrocodone, oxycodone, and codeine being the most common—decreased among people 12 through 17 years of age, from 3.9% in 2015 to 2.3% in 2019.¹⁰  This decrease has been taking place in parallel with increasing provider awareness of the addictive potential of opioid medications and small decreases in opioid medication prescriptions among pediatric providers.¹⁷  Nonmedical use of prescription stimulants, including amphetamines and methylphenidate, has been relatively stable between 2015 and 2019, with approximately 2% of adolescents ages 12 through 17 years reporting nonmedical use in the past year.¹⁰  Past-year nonmedical use of sedatives, mainly benzodiazepines such as alprazolam, clonazepam, and lorazepam, has followed a similar trend to stimulants, with stabilization of rates at approximately 2% among adolescents ages 12 through 17 years between 2015 and 2019 but after a notable increase of more than 50% in rates of exposure and benzodiazepine-related overdoses between 2000 and 2015.¹⁸  In parallel with a decline in the use of barbiturates in outpatient clinical practice,¹⁹  rates of nonmedical use for this class of medications have been decreasing steadily among high school seniors since 2005.²⁰  Conversely, nonmedical use of gabapentinoids has drawn increased attention, especially among AYAs with concurrent opioid use disorder.²¹ 

Rates of NMPDU vary among different racial and ethnic groups. For instance, past-year rates of nonmedical opioid use among 12- through 17-year-olds in 2019 was 2.3% overall, 2.6% among Hispanic or Latino adolescents, and 2.2% among non-Hispanic or Latino adolescents, including 2.3% among white adolescents, 0.3% among Asian adolescents, 2.9% among American Indian and Alaska Native adolescents, and 2.5% among Black or African American adolescents.¹⁰  Although all of these rates have decreased since 2016, it is important to understand that racial differences in substance use rates are a reflection of the differential impact of social drivers of health as well as indirect and direct effects of racism and discrimination across historically marginalized racial and ethnic groups.^22,23  There are no known biological characteristics that can be differentiated by the social construct of race for any health condition, including substance use and substance use disorders.²⁴  Survey studies have shown mixed findings with regard to disparities in rates of NMPDU in different racial and ethnic groups, and more research is needed to better elucidate disparities and mechanisms underlying these disparities.²⁵ 

Rates of lifetime NMPDU are also significantly higher among lesbian, gay, bisexual, and questioning students in grades 9 through 12 (26%) compared with adolescents identifying as heterosexual (16%).^26,27  Similarly, in 2019, rates of past-year nonmedical prescription opioid use among lesbian, gay, and bisexual (LGB) young adults ages 18 through 25 years (8.5%) were significantly higher compared with 18- to 25-year-olds overall (5.2%).^10,28  Studies that have explored the increased rates of NMPDU by LGB adolescents have findings that suggest that increased emotional stress and victimization as well as lack of school social support can be factors contributing to increased use in this population.²⁹  It was also found that higher reports of childhood sexual abuse and earlier age of being prescribed a drug among LGB youth could contribute to the increased rates of NMPDU in this population.^30,31 

In 2019, there were 4777 overdose deaths among 15- to 24-year-olds in the United States.¹⁴  Approximately 14% of overdose deaths in this age group involved nonmedical use of prescription opioids, and a similar proportion involved benzodiazepines.¹⁴  Although some of these overdose deaths were intentional and others were not, it is worth noting that opioids are associated with the highest relative risk for poisoning death by suicide (5.2 times higher than all other substances combined including sedatives, stimulants, alcohol, and acetaminophen).³²  Within the AYA population, rates of nonmedical use of opioid, stimulant, and sedative or tranquilizer medications have followed similar trends in younger (ages 12–17) and older (ages 18–25) AYAs. However, in 2019, for all 3 classes of medications, NMPDU rates were 2 to 4 times higher among young adults (ages 18–25) than among adolescents (ages 12–17).¹⁰  What is most concerning is the upward trajectory of this mortality trend since 2015 for synthetic opioids other than methadone, primarily fentanyl (Fig 1). This illicit drug supply is adulterated with fentanyl and novel synthetic opioids.^33,34  Youth may be unknowingly exposed to lethal doses of fentanyl in counterfeit or “pressed” pills that they may perceive to be prescription medications.

Young adults have access to prescription medications through various sources, including their own leftover or ongoing prescriptions and those of family members, friends, and other social sources.³⁵  Many adolescents have unsupervised access to their own controlled prescription medication.³⁶  In and of itself, this may not be problematic, especially as an older adolescent is learning to take more responsibility for their own care. However, many adolescents report accessing their own prescription leftovers for the purpose of nonmedical use.³⁷  Family members or peers with a valid prescription represent the most common initial source, suggesting an important opportunity for physician education at the time of prescribing.³⁷  It is important for pediatric providers to be aware of and keep a high level of concern for drug diversion, which refers to the transfer of a controlled substance from a lawful to an unlawful channel of distribution or use,³⁸  which family members may engage in inadvertently without intending harm. In addition, increased precautions around storage and disposal of prescription medications in the home can significantly decrease risk of NMPDU.³⁹  Unknown drug dealers and the internet tend to be less frequent sources of prescription medications initially, although sedatives have been reported to be readily available online with very few age-verification mechanisms to limit access.^5,40  Sources vary significantly by medication category; although friends are the most common source of stimulant medications, family sources tend to be more common sources for opioids and sedatives.^35,41,42  Notably, AYAs who report nonfamily sources tend to also report higher alcohol and drug use than those who report family sources.⁵ 

Several motives can lead to NMPDU, generally falling under 2 broad categories of “recreational use” and “self-medication.”^43,44  With nonmedical use of prescription opioids, AYAs may be seeking pain relief but may also be trying to “get high,” which has been associated with a greater risk of developing an opioid use disorder.⁴⁵  With nonmedical use of prescription stimulants, AYAs may be seeking self-medication for untreated attention-deficit/hyperactivity disorder (ADHD) symptoms, appetite control/weight loss, or performance enhancement at school.^46,47  With nonmedical use of prescription sedatives, AYAs may seek self-medication for anxiety or insomnia, but use to achieve euphoria is also common.⁴⁸ 

Risk factors that may increase rates of NMPDU often overlap with those seen with other commonly used licit and illicit psychoactive substances, such as alcohol, nicotine, or marijuana. Stigma, discrimination, and adversity facing certain groups, including LGB youths, represent separate risk factors and may also explain higher rates of NMPDU observed in this group.⁴⁹  Trends in which AYAs may be at higher risk can also vary between studies and types of medications.^50,51  In understanding who is at higher risk, other factors, such as exposure to the child welfare system,⁵²  exposure to adverse childhood experiences,⁵³  a tendency toward sensation-seeking,⁵⁴  and personal and family history of substance use and other mental health disorders,⁵⁵  have all been associated with increased risk of initiation of NMPDU.

Risk factors specific to NMPDU can be divided into 3 broad categories: environmental factors, interpersonal (ie, family and peer), and individual risk factors. Access and availability of prescription medications are key environmental factors for nonmedical use of prescription opioids and stimulants among AYAs.⁵⁶  Studies have considered the impact of living in an urban or rural setting on risk of NMPDU; although some studies have found increased risk of NMPDU in rural communities,⁵⁷  geographic locations appears to impact the type of prescription medication nonmedically used more so than overall rates of NMPDU.⁵⁸  Lower school attendance and achievements in high school and college have been significantly associated with NMPDU.^35,59  However, high-performing students and those with fraternity or sorority involvement may also be at risk for NMPDU, specifically nonmedical use of prescription stimulants.⁶⁰ 

Parental monitoring, supervision, and involvement as well as avoidance and disapproval of substances play an important role in shaping AYAs’ perceptions and behaviors around NMPDU.⁵⁶  For instance, adolescents whose parents are perceived as more tolerant toward substance use in general are more likely to report NMPDU.⁶¹  As such, pediatric providers are in a key position to support parents in maintaining open communication about medication and substance use in general and remind them about the harms of drug diversion, including diversion to their AYA. Peer engagement in and beliefs around NMPDU also represent important risk factors.^62–64  Specifically, AYAs who have close friends who engage in NMPDU are more likely to engage in NMPDU on a regular basis.⁶⁵ 

At the individual level, low perceived self-efficacy⁵⁵  as well as positive expectations and low perceived risk related to NMPDU, often influenced by social media exposure and messaging around NMPDU, are 2 important contributors to NMPDU among AYAs.⁴⁸  In addition, AYAs with untreated or poorly controlled medical conditions leading to increased pain, concern, or distress are at higher risk of nonmedical use of prescription opioids through attempts to self-medicate symptoms.²⁵  Similarly, untreated mental health conditions, such as anxiety, depression, and ADHD, are associated with increased NMPDU among AYAs.^46,66 

Although there are many risk factors for NMPDU, several protective and resilience factors can also contribute to decreased risk of NMPDU through adolescence and young adulthood. The presence of a protective family environment with consistent parenting rules and monitoring⁵²  and AYA involvement in fulfilling extracurricular activities can mitigate some of the risk factors identified above, although participation in competitive sports may have mixed effects.⁶⁷  Although there is no known association between competitive sports participation and nonmedical use of prescription opioids,⁶⁸  an increased risk of nonmedical use of prescription stimulants, notably dextroamphetamine, has been identified among boys (but not girls) engaging in certain individual and team sports.⁶⁹  Importantly, the effects of family, school, physician, and system-level education, combined with timely access to medical care and physician awareness of the risk of NMPDU, have high potential to decrease the prevalence of NMPDU on a population level.^70,71 

Brain development during adolescence and young adulthood follows a predictable stepwise trajectory characterized by specific changes in myelination, neuronal mass, functioning of neurons, reorganization of neuronal connections, and relative functioning of different brain regions.⁷²  This process is genetically programmed and is sensitive to environmental influences. For example, healthy brain maturation depends on multimodal input (eg, visual, sensory, learning, pleasurable experiences, nurturing) that produces changes in neuronal functioning that underly synaptic pruning, apoptosis, and reorganization of connections.⁷³  Conversely, toxic exposures, such as trauma, abuse, deprivation, malnutrition, and exogenous biological agents, can distort this process.⁷⁴ 

The majority of AYAs who report NMPDU do not go on to have a persistent pattern of NMPDU.⁷⁵  In a study using data from cross-sectional surveys from 2002 to 2014, nonmedical use of prescription opioids increases dramatically through adolescence, peaks at ages 18 to 21 years, and declines in early and middle adulthood.⁷⁶ 

It is important to consider NMPDU when AYA patients present with sleep difficulties, hyper- or hyposomnia, nutritional issues, aggression, agitation, violence, and other neurologically abnormal behaviors. Although stimulants may decrease the ability to sleep, sedatives and opioids may increase hours of daytime somnolence, tiredness, or fatigue. These sleep disturbances can have a direct impact on educational success, which may bring AYAs or their parents to seek medical attention.^77,78  Some AYAs may present with dietary changes, including weight loss and loss of appetite with regular nonmedical use of prescription stimulants as well as nonmedical use of sedatives and opioids.⁷⁹  In addition, although adolescent data remain limited, a 10-year longitudinal study of Taiwan residents 18 years and older arrested for nonmedical use of amphetamines showed a fivefold increase in the incidence of psychosis.⁸⁰  Overdose, which could lead to death, is also a possibility with nonmedical use of prescription sedative, opioid, and stimulant medications and needs to be ruled out for any emergency department presentation of increased heart rate, respiratory depression, extreme agitation, or suicidality.⁸¹  Withdrawal from benzodiazepines, which can be severe and even lethal in some cases, is important to recognize as well.⁸²  AYAs who use prescription opioids nonmedically may use benzodiazepines nonmedically to manage opioid withdrawal, and as such, benzodiazepines can be part of a polysubstance use cycle.⁸³ 

Similar to the dangers of other substances, like alcohol, nicotine, and marijuana, NMPDU by AYAs is associated with future sequelae, such as addiction, poor educational attainment, and increased health care utilization.^46,84–87  Similarly, individuals who seek substance use treatment services as adults overwhelmingly initiate substance use during adolescence, including nonmedical use of prescription pain relievers.⁸⁸  Improved educational performance has been given as a reason for nonmedical use of stimulants in high school and college students.⁸⁹  Although there is evidence of improvement in academic performance in those with ADHD, there is no evidence that it improves the performance of those without ADHD. In fact, there is some evidence that in addition to sleep disturbances, increased heart rate, and agitation, performance can be compromised with nonmedical use of stimulants in particular.^46,90  Research has also shown that those with nonmedical use of prescription stimulants are more likely to meet criteria for cannabis or alcohol use disorders.^90,91 

Quality of life may be impacted in AYAs who use prescription drugs nonmedically. A study in Sweden found that overall quality of life was significantly impaired in this population and, in particular, among those who used sedatives and analgesics nonmedically.⁹²  Another morbidity of importance is the progression to substance use disorders. Adolescents who use prescription opioids nonmedically have been found to have a higher risk of developing substance use disorders and progressing to intravenous drug use with its related complications (ie, infections).^93,94  Adolescents who use prescription medications nonmedically are also at increased risk for mental health comorbidities, such as behavioral and conduct difficulties.⁹⁵  Of note, existing evidence on the associations between NMPDU and long-term outcomes does not allow determining causal direction; although it is possible that NMPDU could increase risks of adverse outcomes, it is also possible that adverse outcomes increase risks of NMPDU.

Prevention science is based on the premise that identifiable risk and protective factors affect the probability of later problems⁹⁶  and has been applied for primary prevention of adolescent initiation of substance use.⁹⁷  Evidence shows that primary prevention interventions can have a positive impact on the initiation of substance use in adolescents.⁹⁶  Primary prevention interventions are well aligned with pediatric principles promoting healthy child and adolescent development. Universal prevention can be applied through evidence-based parenting interventions. Many studies have shown decreased substance use into adulthood among children of parents who had received targeted parenting interventions.⁹⁸  These interventions have been adapted successfully to primary care settings.^99–101  For example, programs like Guiding Good Choices (formerly known as Preparing for the Drug-Free Years), Triple P Parenting, and Familias Unidas have been used in the clinical setting with positive results.^102–104  A comprehensive list and references for evidence-based parent focused adolescent prevention programs can be found at www.blueprintsprograms.org. Finally, clinicians are well positioned to advocate for increased support of school and community-based programs. This support may improve access to prevention programs for all AYAs and, more specifically, for AYAs with preexisting risk factors for NMPDU who may benefit most from these interventions.

Secondary prevention is also important for identifying and preventing further NMPDU among AYAs who have already initiated substance use. The American Academy of Pediatrics (AAP) has developed a clinical report on how to best integrate substance use screening, brief intervention, and referral to treatment into pediatric practice, including the use of validated screening tools.¹⁰⁵  With limited time and resources, pediatric providers can effectively address NMPDU by using strengths-based motivational-interviewing approaches to encourage the family and AYA to take the first steps in considering behavior change. Even in AYAs who use prescription drugs nonmedically but do not meet criteria for a substance use disorder, there is benefit in prevention and early intervention.

Adjustments in prescribing practices, such as prescribing only the necessary number of pills when prescribing stimulant, opioid, or sedative-hypnotic medications, can reduce the risk of NMPDU.¹⁰⁶  State prescription drug monitoring programs were created to help monitor patients’ controlled substance prescriptions and, if used consistently, can reduce risks of creating reservoirs of unused medication.¹⁰⁷  Safe storage, disposal, and supervision of all prescription and controlled substances in the home by the parent(s) or the patient (eg, if in college) are other important preventive strategies.

When prescribing psychostimulant medications for the treatment of ADHD, extended-release formulations (versus immediate-release formulations) are preferred given their lower potential for nonmedical use, especially in higher-risk groups, such as college students and AYAs with conduct disorders and substance use disorders.¹⁰⁸  Additional discussion on the topic of ADHD and substance use is found in a separate AAP clinical report.¹⁰⁹ 

For AYAs who meet criteria for a substance use disorder, several medical and nonmedical strategies (including behavioral therapies, psychotherapy, and family support) exist.¹¹⁰  Opioid use disorder is one of the few substance use disorders that have specific treatment recommendations, including US Food and Drug Administration-approved medications that have been shown effective to reduce opioid overdose risk in AYAs. The prescription of naloxone, an opioid antagonist, for AYAs who use opioids nonmedically and their family members can also be lifesaving in the context of an overdose.¹¹¹  Sometimes, AYAs may not be aware that the pills they are using nonmedically are opioids. As such, naloxone can also play an important role in overdose death prevention for AYAs who report nonmedical use of other types of controlled medications. More information can be found in the AAP policy statement on medication to treat opioid use disorder.¹¹² 

NMPDU carries several acute and long-term risks and remains common among AYAs in the United States. There are several ways in which pediatricians can contribute to reducing the burden of NMPDU:

1. Because controlled medications can be prescribed by prescribers from a variety of medical and surgical disciplines, pediatricians should ask patients and caregivers about all controlled medication prescriptions, regardless of prescriber source, and provide appropriate education.

2. Pediatricians should be aware of NMPDU and provide universal anticipatory guidance for all families about the threats of NMPDU and how to protect their children, which includes:

   • Securing medications at home.

   • Supervised access and administration of controlled medications.

   • Proper disposal of unused prescription medications.

   • Anticipatory guidance around sharing, trading, or selling medications at home and at school, including college, and about the role of naloxone in opioid overdose death prevention.

3. When prescribing controlled medications for AYAs, clinicians should:

   • Stay up-to-date on practice guidelines for the treatment of conditions such as ADHD, chronic pain, and mental illness for which controlled medications could be indicated to reduce the rates of NMPDU. Controlled medications should be prescribed after consideration of other therapeutic options and with careful weighing of potential risks and benefits. Shorter prescription lengths with more frequent renewals as well as regular follow-up visits can help reduce risk of NMPDU.

   • Screen for substance use.

   • Be familiar with their state’s legal and practice requirements regarding prescription monitoring databases and make appropriate use of such programs. Any unusual prescription pattern (eg, early and/or frequent refills, prescriptions from several different prescribers) should be discussed and addressed with the patient and/or family while respecting confidentiality (when possible).

   • Explain the risks of NMPDU to AYAs and families.

   • Prescribe naloxone for overdose death prevention (applicable to opioids only).

4. When NMPDU has been identified, pediatricians should:

   • Consider using validated tools to screen for and address common mental health comorbidities, such as anxiety and depression as well as other risk factors, such as trauma, uncontrolled pain, insomnia, and untreated ADHD.

   • Prescribe and recommend naloxone for overdose death prevention and teach patients and families how and when to use naloxone, regardless of the type of medication being used nonmedically.

Nicholas Chadi, MD, MPH, FAAP, FRCPC

Leslie Walker-Harding, MD, FAAP

Deepa R. Camenga, MD, MHS, FAAP, Chairperson

Rita Agarwal, MD, FAAP

Shawn Kelly, MD, FAAP

Kimberly Spence, MD, FAAP

Jasmin N. Zavala, MD, MPH, FAAP

Leslie Walker-Harding, MD, FAAP

Jake Lehman, MD – Section on Pediatric Trainees

Rebecca Ba’Gah, MD, FAAP – American Academy of Child and Adolescent Psychiatry

Andrew Terranella, MD, MPH, FAAP – Centers for Disease Control and Prevention

Renee Jarrett, MPH