Inhaled Cannabis Effects on the Aging Brain Explored in MRI Study

Published on February 1, 2023

Imagine you’re a detective investigating the effects of inhaled cannabis on the aging brain. You’ve got some elderly mouse cohorts, and you expose them to vaporized cannabis with either high levels of Δ9-THC or CBD, or a placebo. After 28 days, you gather data using fancy imaging techniques like voxel based morphometry and diffusion weighted imaging. What did you find? Chronic Δ9-THC showed analgesic effects without tolerance, but its anxiolytic and cognitive effects waned over time. Interestingly, CBD had no effect on any of the measured behaviors. The imaging data revealed some fascinating insights – chronic Δ9-THC led to a decrease in midbrain dopaminergic volume followed by an increase after a washout period, hinting at some plasticity. On the other hand, chronic CBD increased network strength and efficiency in the brain even after drug cessation. Where does this leave us? Well, it suggests that inhaled cannabis high in Δ9-THC could be used as an effective analgesic for the aging brain, but not for anxiety or cognitive decline. The midbrain system seems sensitive to chronic Δ9-THC, while CBD enhances brain connectivity in a sustained manner. There’s still more to uncover, so grab your detective hat and explore the underlying research!

With the recent legalization of inhaled cannabis for medicinal and recreational use, the elderly represents one of the newest, rapidly growing cohorts of cannabis users. To understand the neurobiological effects of cannabis on the aging brain, 19–20 months old mice were divided into three groups exposed to vaporized cannabis containing ~10% Δ9-THC, ~10% CBD, or placebo for 30 min each day. Voxel based morphometry, diffusion weighted imaging, and resting state functional connectivity data were gathered after 28 days of exposure and following a two-week washout period. Tail-flick, open field, and novel object preference tests were conducted to explore analgesic, anxiolytic, and cognitive effects of cannabis, respectively. Vaporized cannabis high in Δ9-THC and CBD achieved blood levels reported in human users. Mice showed antinociceptive effects to chronic Δ9-THC without tolerance while the anxiolytic and cognitive effects of Δ9-THC waned with treatment. CBD had no effect on any of the behavioral measures. Voxel based morphometry showed a decrease in midbrain dopaminergic volume to chronic Δ9-THC followed but an increase after a two-week washout. Fractional anisotropy values were reduced in the same area by chronic Δ9-THC, suggesting a reduction in gray matter volume. Cannabis high in CBD but not THC increased network strength and efficiency, an effect that persisted after washout. These data would indicate chronic use of inhaled cannabis high in Δ9-THC can be an effective analgesic but not for treatment of anxiety or cognitive decline. The dopaminergic midbrain system was sensitive to chronic Δ9-THC but not CBD showing robust plasticity in volume and water diffusivity prior to and following drug cessation an effect possibly related to the abuse liability of Δ9-THC. Chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation. The behavioral consequences of this sustained change in brain connectivity remain to be determined.

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