Effects of adolescent psychoactive substance exposure: Developmental vulnerability and long-term pathophysiology outcomes

Background: Adolescence is a critical neurodevelopmental period characterized by heightened vulnerability to psychoactive substance exposure. The increasing prevalence of cannabis use among young people, together with persistent misconceptions regarding its safety, raises important public health concerns. Objective: This scoping review aims to summarize current evidence on the biological and clinical consequences of psychoactive substance exposure during adolescence, with a focus on developmental vulnerability and long-term pathophysiological effects. Methods: A Narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science databases, focusing on studies published in English from 2000 to 2026. Evidence from experimental, clinical, epidemiological, and review studies was included, prioritizing high-quality research such as longitudinal cohort studies, systematic reviews, meta-analyses, and clinical guidelines. Results: Adolescence is characterized by ongoing maturation of brain structures involved in executive function, impulse control, and emotional regulation, with increased sensitivity of the endocannabinoid system. Exposure to cannabis during this period is associated with alterations in neurotransmission, synaptic plasticity, and neurodevelopmental trajectories, with potential long-term effects on cognition and mental health. Respiratory consequences include airway inflammation, impaired mucociliary function, and increased risk of chronic bronchitic symptoms, while cardiovascular effects involve sympathetic activation, endothelial dysfunction, and potential increased risk of acute ischemic events, although evidence remains partly inconsistent due to confounding factors. Endocrine effects include disruption of hypothalamic–pituitary–gonadal and stress axis function, with possible implications for reproductive health, metabolic regulation, and stress responsivity. Environmental and psychosocial factors, including peer influence, availability, and perceived risk, strongly modulate initiation and persistence of use. Conclusions: Psychoactive substance use during adolescence represents a significant public health challenge due to the interaction between biological vulnerability and environmental exposure. Although some neurobiological changes may be partially reversible, early exposure may result in persistent functional consequences. Pediatricians play a central role in prevention through early education, screening, and brief interventions, supported by multidisciplinary and community-based strategies aimed at reducing adolescent substance use and promoting healthy development.