Spatial working memory (SWM) is the ability to transiently store and manipulate spatial- and temporal-related information in order to perform many activities of daily life such as finding a key or driving a car. When you are turning a car to the left, for example, spatial information (e.g., “toward left”) and temporal information (e.g., “right now”) are mixed and online-processed within neural circuits or networks of a brain region called the hippocampus. It is well documented that SWM can be impaired in both humans and animals by an acute, heavy consumption of cannabis or marijuana and cannabinoids, the most commonly used illicit drug worldwide. However, how cannabinoids and endocannabinoids impair SWM is not clear. We have been conducting research to reveal the cascade of cannabinoid- and endocannabinoid-induced signaling changes that lead to LTD/LTP induction at hippocampal excitatory CA3-CA1 synapses and subsequent SWM impairment.