Vulnerability in the womb: Charting the effects of prenatal cannabinoid exposure to mitigate developmental actions on dopamine metabolic capacities and circuits.

Brandalise F.; Lorenzi E.; Melis M. · International review of neurobiology · 2026

**Background & Methods** This is a narrative review article synthesizing current evidence on prenatal cannabis exposure (PCE) and its developmental neurotoxicological effects. The authors examine mechanistic pathways through which cannabinoid exposure during pregnancy alters fetal and postnatal brain development, with emphasis on dopaminergic circuit maturation and mitochondrial function rather than discrete synaptic changes. **Key Findings** • Prenatal cannabinoid exposure induces long-lasting developmental reprogramming affecting neural circuits, metabolic capacity, and endocrine regulation, rather than causing only acute synaptic disturbances. The effects involve altered mesolimbic dopamine circuit maturation through disrupted neuronal excitability, impaired mitochondrial bioenergetics, and dysregulated stress-related hormonal signaling. • Mitochondrial cannabinoid receptors (mtCB1) localized on dopaminergic neurons may play a critical role in shaping long-term neuronal function and metabolic capacity, suggesting that PCE-induced mitochondrial dysfunction is a central mechanism of developmental harm rather than a secondary effect. • PCE generates latent neurobiological vulnerabilities that may remain clinically silent until adolescence or later life, when environmental or physiological stressors unmask deficits. These latent vulnerabilities may include increased susceptibility to age-related neurodegenerative diseases such as Alzheimer's disease. • Glial cells (astrocytes and microglia) and neuroimmune signaling processes play essential roles in determining individual vulnerability or resilience trajectories following PCE, suggesting that immune-metabolic coupling influences long-term developmental outcomes. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported in detail. The review discusses PCE as causing developmental reprogramming with latent vulnerabilities that may manifest as neurological dysfunction in adolescence and adulthood, but specific adverse effects are not enumerated. **Evidence Quality** This is a narrative review synthesizing existing literature rather than original research. It lacks the methodological rigor of systematic reviews or meta-analyses and does not provide quantitative risk assessment. The authors propose a novel conceptual framework reinterpreting PCE as a "disorder of developmental coordination" involving mitochondrial-circuit coupling. While this integrative perspective is innovative, the evidence quality is limited by reliance on synthesized data from heterogeneous studies. The proposed mechanisms regarding mtCB1 and latent vulnerabilities require empirical validation. The review's strength lies in identifying novel research directions and highlighting understudied mechanisms, but conclusions regarding specific developmental outcomes remain partially speculative pending primary research confirmation.

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