Overall, we found that factors associated with benzodiazepines use and opioid medications use were female sex, older age, positive ADHD screening, psychiatric/psychologic follow-up and associated substance use. These factors were even more strongly associated with concomitant use of benzodiazepines and opioids. Furthermore, concomitant use was associated with having repeated at least 2 years of school.

Our results showed that most benzodiazepines and opioid medication users were older than nonusers. In line with our results, an American literature review performed in 2020 found that age was positively associated with an increase in the prevalence of prescription drug misuse, rising from adolescence and peaking in early adulthood³¹. This reinforces the importance of intervening as early as possible to avoid a slide toward chronic use and drug dependence. The association between female sex and the use of benzodiazepines and opioid medication was also reported in previous studies: women have been shown to have higher levels of consumption of both drugs separately and concomitantly^3,8,32. It remains unclear whether this difference between sexes is due to the reason for consumption, which varies across genders. In the general population, Maust et al. found that women consumed more benzodiazepines than men but were less prone to misuse²⁴. Also, Schepis et al. found that men aged between 18 and 49 had lower rates of benzodiazepines misuse than women³³. However, there was no significant association between gender and benzodiazepine misuse in the youngest age group, between the ages of 12 and 17³³. Weyandt et al. reported that opioid misuse was more likely to be recreational among male students, while young women were more likely to self-medicate²³. With regard to illicit substances, a cross-sectional study carried out on a sample of Italian high school students between 2014 and 2016 found a predominance of lifetime use among male individuals, as well as more poly-drug use³⁴. The COSYs study also described a predominance of illicit substance use among male students compared to females⁸. In the same study, prescribed substances were more prevalent among young women, particularly during exam periods⁸. The association between type of substance and reason for use according to gender may merit further investigation in the future. Our results showed an association between being in a couple and the concomitant use of benzodiazepines and opioid drugs. This raises the question of whether the fact of having a partner who is a substance user, and the greater availability of the substance through this partner, may be at the root of this association. In 2010, a study showed that among women in a relationship, the fact that the partner had prescribed drugs encouraged misuse, not because the partner was a user, but because of easier access to the drug³⁵. Among men, neither partner use nor relationship factors were associated with nonmedical use of prescription drugs after considering the impact of individual-level risk factors³⁵. To our knowledge, the question of marital status and drug misuse in the specific population of adolescents and young adults is still poorly documented in the literature and could be further explored.

In our sample, we found that around 10% of non-user students showed positive symptomatology for the ADHD screening tests, which is higher than the known prevalence of ADHD in general population. This prevalence was higher among students using benzodiazepines and opioid drugs and tripled in the case of combined use. In addition, there was an association between repetition and the use of opioid drugs, and the combined use of opioid drugs and benzodiazepines. This is in line with the findings of the literature. In 2009, DuPaul et al. found a prevalence of 2% to 8% of students reporting clinically significant levels of ADHD symptomatology³⁶. Furthermore, at least a quarter of students experiencing difficulties in their studies were diagnosed with ADHD³⁶. In this study, the diagnosis of ADHD was generally ascertained using individual and parent clinical interviews, and multimethod assessment of ADHD with scales such as the WURS, the College ADHD Response evaluation System, and the internal restlessness scale³⁶. In 2018, Romo et al. found that the prevalence of ADHD in a sample of French students was 5.6% using ASRS-6 and WURS-25 scales²². Furthermore, 42.2% of students with ADHD had already repeated a year in their studies, compared with a quarter of students in the general population²². An American study published in 2018 found a lifetime diagnostic prevalence of ADHD (self-reported) in the student population of 11.3%²¹. 40% of ADHD participants in this study reported using psychotropic medication²¹. In this vein, Di Nicola et al. showed, using a self-report survey, that addictive behavior was more prevalent among young people with difficulties at school³⁴.The fact that positive screenings for ASRS and WURS, and grade repetition were associated with benzodiazepines and opioid drugs use raises the question of the impact of these substances on psychocomportemental symptoms, leading to academic difficulties. Conversely, we may hypothesize that schooling difficulties due to ADHD could be at the root of benzodiazepine and opioid drug use. Indeed, it is known that the use of psychoactive substances, including benzodiazepines and opioid medications, can lead to attentional difficulties, which may have a positive influence on scores on the ASRS, thus supporting the first hypothesis. However, we also found that benzodiazepine and/or opioid medication use were associated with childhood ADHD symptoms, thus supporting the second hypothesis. As the WURS and ASRS are only screening scales and cannot be used to diagnose ADHD, those results underline the need to screen at-risk populations and then to perform further clinical evaluation.

In our results, a high proportion of drug users had psychiatric follow-up, which seems to highlight a significant level of distress in the student population. It remains unclear whether the combination of precarious mental health and difficulties at school can constitute a breeding ground for substance abuse. A longitudinal study in the USA found an independent association between mental health difficulties and academic performance in adolescents; hyperactivity disorders at this age were also described as predisposing to poorer academic performance³⁷. Likewise, Weyandt et al. showed in 2016 that students with ADHD performed less well on executive functions than their peers, and all the more so if there was an associated psychiatric comorbidity³⁸. Interestingly, benzodiazepine use was inversely associated with addiction follow-up, suggesting that users of these substances may be less inclined to start addiction treatment, perhaps due to a lack of psychoeducation on the effects of dependence.

We also found an association between paid student internships and the use of benzodiazepines alone or in combination with opioids. For these students, it was their only source of income, raising the question of financial stress. In 2019 in the UK, a literature review explored the issue of financial stress among students and the link with their mental health³⁹. Financial difficulties were shown to be cross-sectionally associated with mental health disorders in general among students, however, the results remained mixed and the evidence limited on larger samples and in longitudinal studies³⁹. It would be interesting in the future to explore this question in relation to substance use among students.

Our results concerning the use of associated substances are worrying in terms of the number of young people who have already experimented with poly-drug use since the start of their studies. In the literature, Weyandt et al. reported that the students most at risk of opioid misuse were those with concomitant use of alcohol and illicit substances²³. Similarly, Maust et al. found that in almost all cases, past-year use of tobacco, alcohol, cannabis, heroin, opioid drugs or prescription stimulants was associated with benzodiazepine use²⁴. Regular consumption of tobacco, alcohol or cannabis could be targeted as markers for identifying young people most at risk of prescription drug misuse in prevention programs.

The question of the combined use of benzodiazepines and opioid medications is important because in our results, combining users seem to be more concerned by psychiatric follow-up, ADHD symptomatology and grade repetition. Whereas previous data evaluated the combined use of benzodiazepines and opioid medication, only a few studies have specifically explored the subject in the student population. The risk factors associated with the use of benzodiazepines and opioid drugs identified in our study could enable us to develop appropriate prevention programs. First of all, it seems important to provide healthcare professionals with the best possible training in the early identification of young people at risk of addiction, in the screening and diagnosis of ADHD, and in weighing up the benefit-risk balance when prescribing drugs at risk of addiction. Secondly, the psychoeducation of young people and their supervisors, through targeted addictology prevention programs, seems highly relevant. Several mental health prevention programs for young people have proved their worth^6,40–42.

We should acknowledge certain limitations of this study: (i) the monocentric design, (ii) the response rate that may have induced self-selection bias, and (iii) the self-reported questionnaires, which may be the source of recall or prevarication bias. The results may also have been influenced by the global SARS-CoV-2 pandemic, as the study was conducted at the time of the third lockdown in France. It will be interesting to see how consumption evolves outside the pandemic context.

In all, our results underline the need for better-targeted prevention programs in high schools and university campuses concerning medication misuse and ADHD screening in at-risk populations.