The endocannabinoid system includes two G-Protein-Coupled-Receptors (GPCRs), which are Cannabinoid Receptor 1 (CB1R) & Cannabinoid Receptor 2 (CB2R). Their endogenous lipid ligands (endocannabinoids) and associated enzymes function to regulate both biosynthesis and degradation.

Since the discovery of endocannabinoids (EC) in 1989, subsequent research has rapidly advanced our understanding of the brain’s expansive cannabinoid system. Further, isolation of endogenous ligands of cannabinoid receptors (CB-1 & CB-2) has increased awareness of their function (synthesis, release, metabolism) at the molecular level, further elucidating the role of the EC system in normal brain function. Of particular interest is the affect on hippocampal functioning.

Groundbreaking research on the hippocampus and ECs has enhanced our knowledge of the role of molecular mechanisms necessary to process lipid EC messengers. It has been established that circuitry between the hippocampus and prefrontal cortex is disrupted by the introduction of exogenous cannabinoid and thus is correlated with impairments in behavior (Kucewicz et al., 2011). Cannabinoids may disrupt cortical function by desynchronizing neuronal communication across cortical domains.

Why Does This Matter?

The deleterious effects of cannabinoids on learning and memory in humans are well documented via observational studies and neuropsychological testing of memory and cognitive abilities. The picture is becoming clearer.

Cannabinoid agonists (marijuana and cannabinoid synthetics) impair long-term potentiation in the hippocampus, resulting in cognitive impairments including attention deficits, poor executive functioning, memory impairment and disruption of temporal perception. Our UF students often described their marijuana smoking as causing ADD or learning problems that required morning cigarettes and psychostimulants to reverse. But they regularly failed, and marijuana succeeded in changing their career path and life trajectory from math, science, medicine or engineering to less rigorous and demanding majors and subsequent careers.

The formation and function of hippocampal circuitry in supporting synaptic plasticity has advanced our understanding of how EC and phytocannabinoid contribute to disordered physiological activity within the hippocampus and its communication with other areas of the brain, as well as specific deficits in brain function subsequent to the use of marijuana or synthetic cannabinoid.

The conundrum is FDA approval process versus the ballot box. The latter is not the means by which important health and medical policy are established.