Prenatal cannabinoid exposure and the developing brain: Evidence of lasting consequences in preclinical rodent models

Cannabis use by people who are pregnant is increasing. Understanding how prenatal cannabinoid exposure (PCE) affects infants and children is of high public health significance. Epidemiological studies have associated PCE with cognitive symptoms, including impaired learning, memory, attention, and executive control, and affective symptoms, including anxiety, emotional dysregulation, and social impairments, in children, adolescents, and young adults. PCE is also associated with neurobiological changes including decreased corticolimbic white matter and functional connectivity; however, the underlying mechanisms for these persisting effects remain unknown. Rodent models are essential for uncovering the effects of PCE on the developing brain. This review summarizes rodent studies focused on the cognitive and affective behavioral and neurobiological outcomes of PCE. Rodent studies have reported cognitive deficits, including impaired learning, memory, attention, and executive control, and affect-related impairments, including anxiety-like behavior, altered stress coping, social impairments, and anhedonia-like behavior, in adolescent and adult offspring. Studies have also demonstrated that PCE affects several underlying neurotransmitter systems, producing dopamine hyperactivity, glutamate and serotonin hypoactivity, and dysregulating GABA and opioid signaling. Evidence further suggests a marked difference in outcomes between males and females, with males being more susceptible to the enduring effects of PCE. However, studies that investigate female-specific outcomes or sex as a biological variable are scarce. Altogether, rodent studies provide corroborating evidence that PCE produces lasting cognitive and affective impairments underpinned by altered neurobiological mechanisms. Research is critically needed to improve our understanding of the risks associated with cannabis use during pregnancy and effects across the lifespan.