Effect of Cannabinoids on Brain Metabolites: A Review of Animal and Human Studies

Cannabis has been widely used medically and recreationally for centuries. With a renewed interest in the therapeutic use of cannabinoids, which are active components of Cannabis sativa, it has become important to understand the cannabinoids' neurobiological mechanisms related to both therapeutic and harmful effects. This review summarizes the effects of two major cannabinoids, delta-9-tetrahydrocannabinol and cannabidiol, on brain metabolites. We focus on human studies applying H-1-magnetic resonance spectroscopy (MRS) and animal studies using more invasive and direct methods to measure brain metabolites associated with glutamatergic neurotransmission or glial and neuronal functions. Although studies are limited in number, current evidence suggests that two major cannabinoids, which are thought to have differential effects on the brain, may alter the brain metabolite levels in distinct ways from each other. Potential limitations of present studies of cannabinoids on brain metabolites and suggestions regarding future studies are also discussed. We believe that issues clarified in this review may contribute to the design of future studies of cannabinoids on brain metabolites. Public Health Significance Understanding how cannabinoids act in the brain is important for the development of cannabis-derived therapies. This review summarizes the studies demonstrating the effects of two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on brain metabolites. Distinct effects of THC and CBD on brain metabolite levels and suggestions for future studies are discussed in this review.