Synaptic signatures of perinatal cannabinoids: A systematic review of rodent hippocampal synaptic plasticity, learning, and memory

The expanding legalization of cannabis raises significant public health concerns about its use during pregnancy, particularly due to the limited understanding of its impact on neurodevelopment. Existing research suggests that perinatal cannabis or cannabinoid exposure may impair learning and memory; however, variations in study design hinder the ability to draw generalizable conclusions. Clinical studies are limited in their observational nature and the lack of insight into neural or cellular mechanisms underlying cognitive changes, underscoring the importance of preclinical studies to explore the effects of perinatal cannabinoids in greater detail. The objective of this systematic review is to consolidate findings from existing preclinical research that investigates the effects of perinatal cannabinoid exposure on learning and memory and the putative mechanism of learning and memory, hippocampal synaptic plasticity, in rodents. This review summarizes studies on hippocampal synaptic plasticity (n = 2), spatial/visual memory (n = 13), working memory (n = 6), recognition memory (n = 12), and associative memory (n = 7). Perinatal cannabinoid-induced impairments were reported in the two synaptic plasticity studies, and in 24 out of 30 studies that examined learning and memory, with spatial memory tasks showing the most consistent deficits. While the existing evidence converges on the notion that perinatal cannabinoid exposure negatively impacts hippocampal physiology and associated memory functions, further research is needed to disentangle the influence of various methodological factors, including offspring sex and age, cannabinoid type, time of gestational exposure, and method of administration.