A glial perspective on the neuropsychiatric effects of cannabis in adolescence and aging.

Kawai H.; Kamiya A.; Hasegawa Y. · International review of psychiatry (Abingdon, England) · 2026

**Background & Methods** This is a narrative review examining the neurobiological mechanisms underlying cannabis effects across the lifespan, with particular emphasis on glial cell contributions. The authors synthesize preclinical and emerging clinical evidence to explain differential responses to cannabinoids in adolescents versus older adults. **Key Findings** • Cannabis use shows age-dependent neuropsychiatric outcomes: adolescent exposure is associated with adverse psychiatric and neurocognitive sequelae, while responses in older adults are more heterogeneous and may include both detrimental and potentially therapeutic effects. • Microglia and astrocytes—key glial cell populations—undergo substantial functional changes across the lifespan that critically modulate cannabinoid effects on brain function, with developmental stages characterized by roles in circuit maturation and neural homeostasis, while aging involves marked alterations in homeostatic, inflammatory, and metabolic functions. • Preclinical evidence increasingly implicates glial mechanisms in mediating adverse effects of adolescent cannabinoid exposure, and age-related glial remodeling may similarly explain variable cannabinoid responses observed in aging brains. **Dosage & Administration** Not reported. **Safety & Adverse Effects** The review indicates that adolescent cannabis use is associated with later psychiatric and neurocognitive adverse outcomes. Specific adverse effects are not systematically detailed; however, the authors emphasize that glial inflammatory responses during development may contribute to long-term psychiatric consequences. In older adults, effects appear more variable with both adverse and potentially beneficial outcomes possible, though specific adverse effects are not enumerated. **Evidence Quality** This review is limited by its narrative rather than systematic design, lacking formal meta-analysis or structured evidence synthesis protocols. The evidence base is heavily weighted toward preclinical studies, with acknowledged gaps in translational human data linking specific glial mechanisms to clinical outcomes. The 2026 publication date suggests emerging but potentially limited clinical evidence in this mechanistic area. Conclusions regarding causality between glial changes and cannabinoid effects should be considered provisional, as most cited evidence appears mechanistic rather than confirmatory in human populations. The review's strength lies in synthesizing a novel developmental neurobiology framework; however, direct clinical applicability remains limited pending additional human neuroimaging and longitudinal studies.

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