Human neuroimaging of acute and chronic marijuana use: implications for frontocerebellar dysfunction

The effects of cannabis use on the human brain are not well understood. Recently neuroimaging research has begun to address the question of metabolic changes secondary to (1) long‐term chronic cannabis use, and (2) acute intoxication due to cannabis smoke or injection of delta‐9‐tetrahydrocannabinol (Δ9‐THC) solution. A comprehensive review of the neuroimaging literature was performed. To further interpret and understand this research, literature addressing animal receptor and neurochemical models were also surveyed. Neuroimaging findings have concluded that abstinence from smoking results in depressed cerebral metabolism in chronic users, while acute exposure reverses this condition, producing higher cerebral blood flow in chronic users compared to controls. These changes are hypothesized to be associated with alterations of cannabinoid receptors secondary to chronic exposure. Findings from animal models are consistent with the proposition that adaptation to chronic exposure results in adjustment of normal neurotransmitter levels. The frontopontocerebellar network is implicated as a site sensitive to cannabinoid‐induced alterations in the levels of dopaminergic activity derived through the medial forebrain bundle, which projects from the ventral tegmental area. This network is involved in the modulation of a range of human behavior that is clearly altered by use of cannabis. The combined neuroimaging and animal data suggest that metabolism of component regions of the frontopontocerebellar network are altered by acute and chronic exposure to cannabis through modulation of both the cannabinoid and the dopamine system. Copyright © 1999 John Wiley & Sons, Ltd.