Amidst a growing prevalence of adolescent mental ill-health, there is a pressing need to develop effective therapeutic interventions. Despite promising results from adult trials of psychedelic-assisted therapies (P-AT), translating these interventions to adolescents presents challenges. Therapeutic outcomes in paediatric contexts cannot be inferred from adult studies due to age-dependent somatic and psychological effects. Administering psychedelics during adolescence, a period of significant psychological, social, and biological change, demands careful ethical consideration. Emphasising the pro-plasticity nature of psychedelics, we advocate for a systems-psychological approach to P-AT for adolescent depression. Compared to adults, this population is more dependent on, and less able to modify, the socio-ecological context in which their psychopathology emerges. The reduced autonomy of adolescents, coupled with the pro-plasticity effects of psychedelics, creates a distinctive risk-benefit profile that warrants a systems-psychological treatment approach to mitigate risks and enhance benefits. Expanded screening, psychosocial formulation, psychoeducation for family members, and bespoke integration and post-trial support are introduced as accommodations for P-AT in this population. Our interdisciplinary approach, drawing on bioethical and clinical considerations, foregrounds the matrix within which adolescents exist and their psychopathology develops. We aim to ensure that P-AT for adolescents is safe, effective, and ethically sound, ultimately laying the foundation for developmentally appropriate and contextually sensitive interventions.