What Do Thirty Years of Neuroimaging Research Tell Us About Recreational Cannabis Use and Brain Integrity? A Narrative Review of the Multimodal Neuroimaging Evidence to Date.

Acute intoxication with delta-9-tetrahydrocannabinol (THC) is consistently associated with greater brain activity in fronto-striatal pathways. Regular cannabis users, compared to non-users, show lower hippocampal volume, reduced white matter microstructure in the superior longitudinal fasciculus, and altered fronto-striatal activity and connectivity during cue-reactivity tasks and at rest. Emerging evidence from Positron Emission Tomography studies indicates lower N-acetyl aspartate, reduced glucose metabolism in the frontal cortex, and lower density of cannabinoid receptors in fronto-striatal pathways, which may reverse with abstinence. Longitudinal multimodal neuroimaging studies are needed to determine whether these brain differences precede or follow cannabis use and whether they dissipate with abstinence.

Study at a glance

Abstract

The consumption of cannabinoids is highly prevalent and has been associated with altered structural, functional, and metabolic brain integrity, measured using PET and neuroimaging tools. However, the current neuroimaging evidence has been summarized by distinct modalities that measure different metrics of brain integrity, precluding a comprehensive understanding of the underlying neurobiology. A non-systematic narrative review method was used to summarize the multimodal neuroimaging evidence on brain integrity from experimental studies of cannabinoid intoxication and observational studies in non-intoxicated cannabis users. Consistent evidence showed that acute intoxication with delta-9-tetrahydrocannabinol (THC) was associated with greater brain activity in fronto-striatal pathways. For regular cannabis users compared to controls, there was consistent cross-sectional evidence of lower hippocampal volumetry and white matter microstructure of the superior longitudinal fasciculus, and of different fronto-striatal activity and connectivity during cue-reactivity tasks and resting-state. In cannabis users, there was emerging evidence from Positron Emission Tomography studies of altered neurochemistry in fronto-striatal pathways (eg, lower N-acetyl aspartate); lower glucose metabolism in the frontal cortex; and lower density of cannabinoid receptors, which may reverse with abstinence. Longitudinal multimodal neuroimaging studies are required to confirm if brain differences predate or follow the onset of cannabis use or cannabis use disorder, and whether changes in brain integrity in people who use cannabis dissipate with abstinence.