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

Cannabis use is increasing across a broad range of ages as legal access and social acceptance continue to expand. Its neurobiological effects, however, are unlikely to be uniform across the lifespan. Adolescent cannabis use is associated with later psychiatric and neurocognitive outcomes, whereas responses in older adults appear more variable and may include both adverse and potentially beneficial effects. Increasing evidence indicates that microglia and astrocytes contribute to cannabinoid effects on brain function. Importantly, the functional states of these glial cells change substantially with age. During development, microglia and astrocytes participate in circuit maturation and neural homeostasis, whereas aging is accompanied by marked changes in their homeostatic, inflammatory, and metabolic functions. Preclinical studies increasingly implicate glial mechanisms in the effects of adolescent cannabinoid exposure, while emerging evidence suggests that age-related glial changes may also influence cannabinoid responses in the aging brain. In this review, we discuss how age-related changes in microglial and astrocytic function may shape brain responses to cannabis in adolescence and aging.