Introduction

The diagnosis of attention-deficit/hyperactivity disorder (ADHD) and stimulant therapy for ADHD have increased substantially over the past 2 decades. Although prescription stimulants are effective when used correctly, controversies perplex the clinical and public health fields as prescription stimulants have emerged as a leading controlled medication class misused among US adolescents and young adults. Along with the increase in prescription stimulant therapy, there has been a 10-fold increase in overall stimulant-related overdose deaths, calling into question the role of prescription stimulants in the initiation of illicit stimulant use.

Despite high exposure to prescription stimulants during adolescence via stimulant therapy for ADHD and prescription stimulant misuse (PSM), longitudinal transitions from prescription stimulants to illicit stimulants remain relatively unknown in population-based studies. Addressing this gap is particularly important during the developmental period from adolescence to adulthood when individuals become more responsible for their medication management and illicit substance use escalates. Most individuals who engage in PSM or illicit stimulant use also engage in polysubstance use. To address the knowledge gaps, the main objective of this study is to examine adolescents who are prescribed stimulant therapy for ADHD and those with PSM and their longitudinal transitions to later illicit stimulant use (ie, cocaine or methamphetamine) during young adulthood compared with adolescents who were not prescribed stimulant therapy for ADHD.

Methods

The Monitoring the Future (MTF) panel study is a multicohort US national longitudinal study of adolescents followed up into adulthood. Procedures and measures are consistent across time; details about methods and procedures are available elsewhere. For the present study, 5034 12th graders (baseline cohort years 2005-2017 [between March and June]) were assessed at baseline and followed up across 3 subsequent survey waves over 6 years to 23 and 24 years of age (follow-up years 2011-2021 [between April and October]; weighted retention rate, 55.3%) (Figure). These respondents were randomized to 1 of 6 survey forms that included questions about stimulant therapy for ADHD, PSM, cocaine, and methamphetamine. The institutional review board of the University of Michigan deemed this study exempt from approval and the need for informed consent due to the use of deidentified data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for a cohort study.

Measures

Stimulant therapy for ADHD was measured at baseline by asking respondents if they had ever taken a prescription stimulant medication for ADHD under a physician’s supervision, such as methylphenidate hydrochloride (Ritalin), combined dextroamphetamine and amphetamine (Adderall), extended-release methylphenidate (Concerta), dextroamphetamine sulfate (Dexedrine), and/or other trade and generic stimulant medications. Respondents were instructed that these medications do not include nonstimulants such as atomoxetine hydrochloride (Strattera), guanfacine hydrochloride (Intuniv), and bupropion hydrochloride (Wellbutrin). The 3 possible response options included no; yes, in the past; and yes, current use.

Prescription stimulant misuse was assessed at baseline and each follow-up survey year by asking respondents on how many occasions (if any) they used prescription stimulants without a physician’s orders in a specific period (lifetime, past year, and past month). Respondents were provided a list of commonly misused prescription stimulants and informed that these are often prescribed for ADHD. The response options for each period ranged from no occasions (option 1) to 40 or more occasions (option 7). Cocaine or methamphetamine use was assessed at baseline and each follow-up survey wave by asking respondents on how many occasions (if any) they used cocaine or methamphetamine (asked separately) in a specific period (lifetime, past year, or past month), using the same response scale as for PSM. Covariates at baseline included self-reported sex, race and ethnicity, grade point average in high school, parental educational level, geographical region, population density, cohort year, binge drinking, cigarette use, marijuana use, prescription opioid misuse, cocaine use, use of nonstimulant therapy for ADHD, and discontinued use of stimulant therapy for ADHD (refers to individuals who reported past but not current use of stimulant therapy for ADHD).

Statistical Analysis

Unadjusted odds ratios (ORs) and adjusted ORs (AORs) were generated in Stata, version 17.0 (StataCorp LLC) to examine the associations between the use of stimulant therapy for ADHD and initiation of PSM at 18 years or older and the use of cocaine or methamphetamine at 19 to 24 years of age. Logistic regression models were fitted using the generalized estimating equations methods with an exchangeable correlation structure to assess the association between history of stimulant therapy for ADHD and PSM at baseline (time invariant) and cocaine or methamphetamine initiation or use (time-varying outcomes) at 19 to 24 years of age. Models assessed both the prevalence (using the full panel sample) and incidence (these models excluded respondents with any history of cocaine or methamphetamine use at baseline) of past-year cocaine and methamphetamine use. Both unadjusted and adjusted models were assessed; AORs and 95% CIs were reported in the generalized estimating equations models. All binary logistic regression models were weighted to adjust for differential attrition at follow-ups; item missingness was handled using listwise deletion. The analysis only considers results at 2-sided α ≤ .001 as statistically significant.

Results

Among 5034 participants at baseline (2589 [52.0% (95% CI, 50.5%-53.3%)] female and 2394 [48.0% (95% CI, 46.6%-49.4%)] male [sex was missing for 51 participants]), an estimated 10.2% (95% CI, 9.4%-11.2%) of adolescents reported lifetime use of stimulant therapy for ADHD (including 294 [6.4% (95% CI, 5.7%-7.1%)] with no PSM history and 176 [3.8% (95% CI, 3.3%-4.4%)] with a PSM history), 671 (14.6% [95% CI, 13.5%-15.6%]) reported PSM only, and 3459 (75.2% [95% CI, 73.9%-76.4%]) did not report stimulant therapy use or PSM and served as population controls. In terms of race and ethnicity, 721 participants (14.3% [95% CI, 13.3%-15.3%]) were Hispanic, 49 (1.0% [95% CI, 0.7%-1.3%]) were non-Hispanic American Indian or Alaska Native, 177 (3.5% [95% CI, 3.0%-4.1%]) were non-Hispanic Asian, 548 (10.9% [95% CI, 10.1%-11.8%]) were non-Hispanic Black, 2747 (54.6% [95% CI, 53.1%-55.9%]) were non-Hispanic White, and 792 (15.7% [95% CI, 14.7%-16.8%]) were other race or ethnicity. Table 1 includes baseline sample demographic, health, and education characteristics.

As shown in Table 2, there were no statistically significant differences (in unadjusted and adjusted models) between adolescents who reported use of stimulant therapy for ADHD and adolescents who never used stimulant therapy in the odds of cocaine or methamphetamine use in the prevalence or incidence at 19 to 24 years of age. eTable 1 in Supplement 1 includes the full set of results for each of the covariates that were included in the models. While there were no associations between the baseline sociodemographic characteristics and the outcomes, there were a number of associations between baseline substance-related covariates (eg, marijuana use) and later cocaine and methamphetamine use during young adulthood.

As shown in Table 3, adolescents with PSM had the highest unadjusted and adjusted odds of later cocaine and methamphetamine use at 19 to 24 years of age in terms of prevalence and incidence vs population controls. Adolescents who reported PSM with no history of stimulant therapy for ADHD at baseline had more than 2.5 times greater adjusted odds than population controls of cocaine or methamphetamine initiation (AOR, 2.64 [95% CI, 1.54-4.55]) at 19 to 24 years of age. eTable 2 in Supplement 1 provides the full set of results for each of the covariates that were included in the models. Although there were no associations between the baseline sociodemographic characteristics and the outcomes, there were a number of baseline substance-related covariates (eg, marijuana use) that were associated with later cocaine and methamphetamine use during young adulthood.

Sensitivity analyses were performed and showed that current use of stimulant therapy for ADHD was not associated with later methamphetamine or cocaine use or initiation in any model compared with population controls who never used or misused prescription stimulants (eTable 3 in Supplement 1). Sensitivity analyses were conducted to examine whether baseline PSM frequency was associated with later incidence or prevalence of cocaine or methamphetamine use at 19 to 24 years of age. For example, among respondents who engaged in baseline PSM with no lifetime history of medical stimulant use, cocaine or methamphetamine use was more prevalent as a function of lifetime PSM frequency ranging from 17.7% (95% CI, 11.1%-26.8%) among those who reported PSM 1 or 2 times, 28.4% (95% CI, 19.2%-39.9%) for PSM 3 to 9 times, and 34.1% (95% CI, 24.7%-44.8%) for PSM 10 or more times. In controlled sensitivity analyses, adolescents who reported past-year PSM 10 or more times with no history of stimulant therapy use for ADHD at baseline had more than 4 times greater adjusted odds of indicating cocaine or methamphetamine use compared with population controls (AOR, 4.27 [95% CI, 1.78-10.25]) at 19 to 24 years of age. Adolescents who reported past-year PSM 1 or 2 times with no history of stimulant therapy for ADHD at baseline had more than 2.5 times greater adjusted odds of indicating cocaine or methamphetamine use when compared with population controls (AOR, 2.60 [95% CI, 1.27-5.32]) at 19 to 24 years of age. We found similar results for incidence of cocaine or methamphetamine use. In controlled analyses, adolescents who reported past-year PSM 1 or 2 times with no history of stimulant therapy for ADHD at baseline had 3 times greater adjusted odds of indicating incident cocaine or methamphetamine use when compared with population controls (AOR, 3.00 [95% CI, 1.26-7.71]) at 19 to 24 years of age.

Discussion

Based on the increases in prescription stimulant therapy for ADHD and psychostimulant-involved overdoses, there is a growing need for public health practitioners and researchers to understand whether exposure to stimulant therapy for ADHD is associated with later illicit stimulant use. This study found that adolescents’ stimulant therapy for ADHD was not associated with cocaine or methamphetamine use during young adulthood. While ADHD is a risk factor for illicit stimulant use and substance use disorders, the present study offers promising results for adolescents who benefit from stimulant therapy for ADHD. The present cohort study found that adolescents’ stimulant therapy for ADHD was associated with prevalence and incidence of illicit stimulant use that was similar to their peers who never used stimulant therapy for ADHD.

Prescription stimulant misuse during adolescence in those not treated with stimulants for ADHD was associated with more than 2 times greater odds of incident cocaine and methamphetamine use during young adulthood (eg, 20% incident cocaine use). Given the high prevalence of PSM in adolescence (>18%), this information supplements the current black box labeling on prescription stimulants regarding addiction liability and warrants additional attention regarding risk reduction strategies. The present study found that cocaine or methamphetamine use was reported by about 1 in 3 (34.1%) individuals during young adulthood (19-24 years of age) among those adolescents who reported PSM 10 or more times. These findings support monitoring adolescents for PSM and inclusion of PSM in brief screening instruments (eg, SBIRT [Screening, Brief Intervention, and Referral to Treatment] or the TAPS [Tobacco, Alcohol, Prescription Medication, and Other Substance Use] Tool) to determine whether education, brief intervention, or more comprehensive assessment and intensive management is required following screening, despite the US Preventive Services Task Force not currently recommending screening for unhealthy drug use during adolescence. The inclusion of PSM in screening instruments seems especially relevant during the transition from adolescence into young adulthood, considering the present study found in controlled analyses that adolescents who reported infrequent past-year PSM with no history of stimulant therapy for ADHD at baseline had 3 times greater adjusted odds of indicating incident cocaine or methamphetamine use when compared with population controls at 19 to 24 years of age. The present study also found associations between baseline marijuana use and later cocaine and methamphetamine use that deserve more attention in monitoring and screening efforts.

Strengths and Limitations

The main strength of the present study is the nationally representative sample of 12th grade students attending US public and private schools with large enough samples to examine exposure to stimulant therapy for ADHD and PSM over time. Limitations of the MTF study include school-based samples that exclude youths who drop out of school or are home-schooled, potential attrition bias, self-report medication therapy, potential unassessed confounders, and treatment differences. Although self-report data in the MTF study generally have been found to be reliable and valid, studies suggest that misclassification and underreporting of substance use do occur. The MTF study attempted to minimize such bias by using conditions that past research has been shown to improve the validity and reliability of substance use data collected via self-report surveys, such as explaining the relevance of the study and informing potential respondents about voluntary participation and anonymity. In the MTF study, no adjustments are made to correct for any underreporting; thus, results from the present study may be conservative and underreport the actual prevalence of sensitive behaviors. The MTF study does not assess some factors that could be associated with stimulant misuse (eg, ADHD severity, medication dose and adherence, nonpharmacological therapy, deviant peers with access to drugs). The MTF study also did not separate amphetamine from methylphenidate treatments, which is important given potentially different misuse liabilities.

Conclusions

In this multicohort study of adolescents exposed to prescription stimulants, adolescents who used stimulant therapy for ADHD did not differ from population controls in initiation of illicit stimulant (cocaine or methamphetamine) use, which suggested a potential protective effect, given evidence of elevated illicit stimulant use among those with ADHD. In contrast, monitoring adolescents for PSM is warranted because this behavior offered a strong signal for transitioning to later cocaine or methamphetamine initiation and use during young adulthood.

Summary

A longitudinal study using data from the Monitoring the Future (MTF) panel study examined the association between adolescent exposure to prescription stimulants (through ADHD treatment or misuse) and subsequent illicit stimulant use in young adulthood. The study employed a large, nationally representative sample of 12th graders followed over six years. Statistical analyses, including logistic regression with generalized estimating equations, assessed the relationship between stimulant exposure and the initiation or prevalence of cocaine or methamphetamine use.

Methods

The study utilized data from the MTF panel study, a nationally representative longitudinal study of adolescents. A sample of 5034 12th graders was followed across three subsequent survey waves. Stimulant therapy for ADHD was assessed via self-report, distinguishing between past and current use. Prescription stimulant misuse (PSM) was measured by the frequency of stimulant use without a prescription. Illicit stimulant use (cocaine or methamphetamine) was also assessed through self-report at each survey wave. Covariates included demographic, academic, and substance use information. Statistical analysis involved generating unadjusted and adjusted odds ratios using logistic regression models. The significance level was set at α ≤ .001.

Results

The study found no significant association between stimulant therapy for ADHD and subsequent illicit stimulant use. However, a strong association emerged between PSM and illicit stimulant use. Adolescents with a history of PSM, especially those with frequent misuse, exhibited significantly higher odds of subsequent cocaine or methamphetamine use compared to controls. Sensitivity analyses confirmed these findings, demonstrating a dose-response relationship between PSM frequency and illicit stimulant use. Other baseline substance use (e.g., marijuana) was also associated with later illicit stimulant use.

Discussion

The findings suggest that stimulant therapy for ADHD does not increase the risk of later illicit stimulant use. Conversely, PSM represents a significant risk factor for the transition to illicit stimulant use in young adulthood. These results highlight the importance of monitoring adolescents for PSM and incorporating it into substance use screening tools. The study’s limitations include the reliance on self-reported data and the potential for underreporting of sensitive behaviors.

Strengths and Limitations

A major strength is the use of a large, nationally representative sample. However, limitations include potential attrition bias, reliance on self-report data (with inherent limitations on accuracy), potential unmeasured confounding variables, and lack of information on specific aspects of stimulant treatment (e.g., dosage, adherence).

Conclusions

This study demonstrates that while stimulant therapy for ADHD does not appear to be associated with increased illicit stimulant use, PSM constitutes a substantial risk factor. These findings underscore the need for focused interventions targeting PSM to mitigate the risk of transition to illicit stimulant use during young adulthood.

Summary

This study investigated the longitudinal relationship between adolescent exposure to prescription stimulants (for ADHD treatment and misuse) and subsequent illicit stimulant use in young adulthood. Utilizing data from the Monitoring the Future (MTF) study, researchers analyzed a nationally representative sample of adolescents. The findings suggest that stimulant therapy for ADHD, in itself, was not associated with increased illicit stimulant use. However, prescription stimulant misuse (PSM) without a prescription was strongly associated with increased odds of later cocaine or methamphetamine use.

Methods

The study employed data from the MTF panel study, following a cohort of 12th graders over six years. Measures included self-reported stimulant therapy for ADHD, PSM frequency, and cocaine/methamphetamine use at multiple time points. Statistical analyses involved logistic regression models with generalized estimating equations to account for repeated measures and potential confounding variables. The study used a weighted sample to account for attrition and listwise deletion to handle missing data. Statistical significance was set at α ≤ .001.

Results

Among the participants, approximately 10% reported lifetime stimulant therapy for ADHD. No significant association was found between stimulant therapy for ADHD and later illicit stimulant use. Conversely, adolescents with a history of PSM showed significantly increased odds of subsequent cocaine or methamphetamine use. This association was particularly strong for those reporting frequent PSM. Sensitivity analyses further confirmed these findings, highlighting the independent risk associated with PSM regardless of stimulant therapy for ADHD.

Discussion

The study's findings suggest that stimulant therapy for ADHD does not appear to increase the risk of later illicit stimulant use. However, PSM represents a substantial risk factor for transitioning to illicit stimulant use in young adulthood. These results highlight the importance of monitoring adolescents for PSM and incorporating it into brief screening tools for substance use. The need for targeted interventions to address PSM and mitigate the risk of transition to illicit drug use is emphasized.

Strengths and Limitations

The study’s strength lies in its large, nationally representative sample, allowing for robust longitudinal analysis. However, limitations include the reliance on self-reported data, potential for underreporting, and the exclusion of individuals who dropped out of school or were homeschooled. The study also did not assess factors like ADHD severity or treatment specifics, which may influence misuse risk. Despite these limitations, the findings provide valuable insights into the relationship between prescription stimulant exposure and subsequent illicit stimulant use.

Conclusions

This study demonstrates that adolescent stimulant therapy for ADHD is not associated with increased illicit stimulant use in young adulthood. Conversely, prescription stimulant misuse presents a significant risk factor for the initiation and continued use of illicit stimulants during this period. These findings underscore the importance of targeted interventions to address prescription stimulant misuse and prevent transition to illicit stimulant use.

Summary

Studies show a significant rise in ADHD diagnoses and stimulant medication use over the past two decades. This increase coincides with a tenfold rise in stimulant-related overdose deaths, raising concerns about the link between prescription stimulants and illicit drug use. A key question remains: Does using prescription stimulants for ADHD increase the likelihood of later illicit stimulant use? This study investigates this question using data from a large, long-term national survey of adolescents.

Methods

Researchers used data from the Monitoring the Future (MTF) study, a national longitudinal survey following adolescents into young adulthood. The study included over 5,000 twelfth graders, followed for six years. Participants answered questions about their use of prescription stimulants for ADHD, misuse of prescription stimulants (PSM), and use of cocaine or methamphetamine. The study used statistical methods to analyze the relationships between these factors.

Measures

The study measured stimulant use for ADHD by asking if participants had ever taken prescription stimulants for ADHD under a doctor's care. PSM was assessed by asking about stimulant use without a prescription. Cocaine and methamphetamine use were also tracked. Baseline information included demographics, grades, parental education, and substance use.

Results

The study found no significant link between using prescription stimulants for ADHD and later cocaine or methamphetamine use. However, adolescents who misused prescription stimulants (PSM) showed a significantly higher likelihood of using cocaine or methamphetamine later in young adulthood, regardless of whether they had been prescribed stimulants for ADHD. The risk increased with the frequency of PSM.

Discussion

The results suggest that while prescription stimulant use for ADHD doesn't appear to increase illicit stimulant use, PSM is a major risk factor. The study highlights the importance of monitoring adolescents for PSM and incorporating it into screening tools to identify those needing intervention. The findings also emphasize the need for continued research into the complexities of ADHD, stimulant medication, and substance use.

Strengths and Limitations

This study's strength lies in its large, nationally representative sample. However, limitations include the use of self-reported data (which may be inaccurate), the exclusion of students who dropped out of school or were homeschooled, and the lack of information on factors such as ADHD severity and medication dosage.

Conclusions

This study indicates that prescription stimulant use for ADHD itself does not predict illicit stimulant use. However, the misuse of prescription stimulants is a strong predictor of later illicit drug use. Therefore, focusing on preventing and addressing PSM is crucial for reducing the risk of illicit stimulant use among adolescents.

Summary

This study looked at whether kids who take medicine for ADHD are more likely to use illegal drugs like cocaine or meth later on. Researchers followed a big group of teens for several years.

Methods

They used information from a long-term study that followed a lot of 12th graders. The study asked teens about their medicine use for ADHD, if they misused prescription drugs, and if they used cocaine or meth.

Measures

Teens were asked if they ever took ADHD medicine. They were also asked how often they used prescription drugs without a doctor's permission. Finally, they were asked how often they used cocaine or meth. Other things like grades, family background, and other drug use were also noted.

Results

Kids who took ADHD medicine weren't more likely to use cocaine or meth later. However, teens who misused prescription drugs were much more likely to use cocaine or meth later. The more often they misused the drugs, the higher the chance they'd use cocaine or meth.

Discussion

This study shows that taking ADHD medicine doesn't seem to make teens more likely to use illegal drugs. But misusing prescription drugs is a big warning sign. It's important to keep an eye on teens who misuse prescription drugs.

Strengths and Limitations

The study used a large group of kids from across the country, which is good. But it only included teens in school, and it relied on teens telling the truth about their drug use, which could be inaccurate. The study also didn't look at things like how severe someone's ADHD was or exactly what type of ADHD medication they took.

Conclusions

Taking ADHD medicine didn't increase the risk of using cocaine or meth. But misusing prescription drugs is a serious problem and needs more attention.