In this cross-sectional study of ZaUMS students, perceived stress was positively and independently associated with addiction readiness. Students reporting higher stress also reported a stronger vulnerability profile, as captured by IAPS-based addiction readiness scores, and this association persisted after adjustment for demographics, field of study, and self-reported substance use.
These findings align with conceptual models proposing that stress contributes to substance-related vulnerability through psychological and neurobehavioral pathways. Stress may undermine self-regulation, increase negative affect, and promote maladaptive coping strategies; substances may be perceived as short-term emotion-regulation tools, consistent with the self-medication framework (
4). At the neurobehavioral level, stress is linked to dysregulation of reward and stress systems that can increase craving, impair inhibitory control, and facilitate habit learning and relapse (
5-
7). Importantly, the outcome in this study was not substance use itself but addiction readiness, an IAPS-based vulnerability construct that may precede overt behaviors.
Because of the cross-sectional design, these findings should be interpreted as associations rather than causal effects. The present data cannot determine whether perceived stress preceded addiction readiness, whether students with higher addiction readiness experienced greater stress, or whether both were influenced by unmeasured psychosocial factors. Therefore, the results should not be interpreted as evidence that stress directly causes addiction readiness or that screening and stress management would necessarily reduce addiction vulnerability without further longitudinal or interventional evaluation.
Sex-stratified analyses suggested a stronger stress-addiction readiness relationship in females than in males, despite higher mean addiction readiness among males. This difference was supported by Fisher r-to-z testing of sex-specific correlations (P = 0.00002) and by a significant perceived stress × sex interaction in sensitivity analysis (b = -2.32; 95% CI, -3.14 to -1.51; P < 0.001). Several explanations are plausible. Stress may co-occur more strongly with internalizing symptoms and ruminative coping in women, potentially amplifying vulnerability signatures captured by addiction readiness measures. Alternatively, social desirability and stigma may differentially influence the reporting of addiction-related attitudes in cultural contexts, thereby affecting correlations. This interpretation is consistent with recent evidence among Iranian medical interns showing poorer mental health among female students and supporting the need for sex-sensitive student mental health services (
19). These hypotheses warrant longitudinal and mixed-methods research.
Field-of-study differences in addiction readiness, but not in perceived stress, suggest that vulnerability patterns may reflect contextual factors beyond stress exposure alone. Peer norms, shift patterns, workload, and clinical environment characteristics may shape attitudes and perceived access to substances. Recent Iranian evidence also suggests that structured psychological interventions, such as acceptance and commitment therapy, can reduce perceived stress in student populations, whereas workplace-based research indicates that stress and anxiety may become severe under context-specific organizational pressures (
20,
21). Tailored prevention strategies that account for educational, clinical-training, and organizational contexts may therefore be more effective than uniform approaches.
The findings should also be interpreted within Iran's broader evidence base. National and student-focused studies indicate that substance-use risk is shaped by multiple determinants, including the peer environment, attitudes, and family influences (
8-
12). Recent studies in student populations have also emphasized the relevance of psychological distress, loneliness, interpersonal problems, and stress symptoms in addiction-related outcomes and student mental health (
15-
17). Within this context, the stress-vulnerability association observed in Zahedan supports the need for future evaluation of integrated mental health and stress-management services in student health systems, especially for medical sciences students who encounter additional stressors during clinical training. This interpretation is also supported by qualitative evidence from Zahedan University of Medical Sciences indicating that clinical-training environments, particularly operating-room settings, may be experienced by students as stressful and challenging educational contexts (
22).
5.1. Implications
The results suggest that stress and addiction readiness may be useful targets for further prevention-oriented research in university settings. Routine screening for high perceived stress and elevated IAPS-based vulnerability may help identify students who could benefit from psychological support; however, the effectiveness of such screening should be evaluated prospectively. Future interventions may examine whether evidence-informed stress reduction and coping-skills training, such as problem-solving, sleep hygiene, time management, and mindfulness-based approaches, can improve student mental health and reduce addiction-related vulnerability indicators.
5.2. Limitations
The cross-sectional design precludes causal inference. Sampling within strata was convenience-based, and 95 of 707 questionnaires (13.4%) were excluded because of substantial missingness, which may introduce selection bias and limit generalizability. Because excluded questionnaires were not retained in the final analyzable dataset, detailed demographic comparisons between included and excluded questionnaires were not possible. Self-report measures are subject to recall and social desirability bias, particularly for substance use. In addition, substance use was measured using a single item without details on substance type, timing, frequency, duration, or amount, which limits interpretation and precludes dose-response analyses. The setting-based recruitment strategy likely improved coverage; however, selection bias remains possible if students who were absent from data collection sites differed systematically. Residual confounding is also likely because factors such as socioeconomic status, mental health symptoms, trauma exposure, sleep quality, and academic performance were not measured.
5.3. Strengths
The study included a relatively large sample and recruited students from academic, residential, and clinical training settings. The use of commonly applied instruments for perceived stress and addiction readiness, together with the persistence of associations in multivariable models, supports the robustness of the main finding.
5.4. Conclusions
Among ZaUMS students in 2023 - 2024, higher perceived stress was significantly associated with greater addiction readiness. Because this was a cross-sectional study, the findings should be interpreted as evidence of association rather than causation. Universities, particularly medical sciences institutions, should consider evaluating integrated prevention strategies that combine stress screening, targeted psychological support, and coping-based interventions in longitudinal and interventional research designs.