Cannabis and Cannabinoid Signaling: Research Gaps and Opportunities.

Cannabis and its products have been used for centuries for both medicinal and recreational purposes. The recent widespread legalization of cannabis has vastly expanded its use in the United States across all demographics except for adolescents. Meanwhile, decades of research have advanced our knowledge of cannabis pharmacology and particularly of the endocannabinoid system with which the components of cannabis interact. This research has revealed multiple targets and approaches for manipulating the system for therapeutic use and to ameliorate cannabis toxicity or cannabis use disorder. Research has also led to new questions that underscore the potential risks of its widespread use, particularly the enduring consequences of exposure during critical windows of brain development or for consumption of large daily doses of cannabis with high content Δ ⁹-tetrahydrocannabinol. This article highlights current neuroscience research on cannabis that has shed light on therapeutic opportunities and potential adverse consequences of misuse and points to gaps in knowledge that can guide future research. SIGNIFICANCE STATEMENT: Cannabis use has escalated with its increased availability. Here, the authors highlight the challenges of cannabis research and the gaps in our knowledge of cannabis pharmacology and of the endocannabinoid system that it targets. Future research that addresses these gaps is needed so that the endocannabinoid system can be leveraged for safe and effective use.