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

Abstract

The eects 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 (D 9 -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 ®ndings have concluded that abstinence from smoking results in depressed cerebral metabolism in chronic users, while acute exposure reverses this condition, producing higher cerebral blood¯ow 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.

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study

“…Our fMRI findings of widely increased activation among very recently abstinent cannabis users appear consistent with previous studies that have found increased cerebral blood flow and glucose metabolism in acutely intoxicated or very recently abstinent users (Loeber and Yurgelun-Todd 1999). However, with the exception of the studies of O' Leary et al (2000Leary et al ( , 2002Leary et al ( , 2003, these previous studies are not directly comparable to ours in that they examined subjects at rest, rather than during the performance of a cognitive task.…”

Depressive symptoms in adolescents: associations with white matter volume and marijuana use

“…Still, we believe it is unlikely that marijuana use is directly or solely responsible for the subtle white matter abnormalities associated with depressive symptoms in this sample. A possible alternative is that chronic marijuana use worsens existing depressive symptoms by disrupting the neuronal functioning of the frontal and limbic brain circuits (Loeber & Yurgelun‐Todd, 1999; Lundqvist, Jönsson, & Warkentin, 2001; Martin et al, 2002). Due to compromised neuronal functioning in these areas, adolescent marijuana users may be less able to compensate for additional neuropathological processes associated with depressive symptoms.…”

Altered regional blood volume in chronic cannabis smokers.

“…Earlier animal studies have demonstrated that direct application of delta-9-THC or the endogenous cannabinoid anandamide to rabbit cerebral arterioles induces vasodilation of the vessels (Ellis, Moore, & Willoughby, 1995), thus suggesting a possible direct effect of cannabis on vasculature. However, the interaction between delta-9-THC and CB 1 receptors may induce overall changes in neural activity at the neurotransmitter level (Dewey, 1986; Grotenhermen, 2003; Loeber & Yurgelun-Todd, 1999), and vascular changes may occur as secondary phenomena. Furthermore, the lack of an association between increases in rCBV and measures of cannabis use, such as urinary THC-COOH level or lifetime episodes of smoking, suggests that regional blood volumes during recent abstinence are not associated with total lifetime marijuana use or with the amount of recent marijuana use.…”