Chronic cannabis use alters dACC-striatal glutamatergic balance

Abstract

Prefrontal and striatal glutamate plays an important role in modulating striatal dopamine levels and an imbalance in regional glutamate has been identified in several psychiatric conditions. We hypothesized that this imbalance also exists in cannabis use disorder (CUD). We recently quantified the difference in glutamate of dorsal anterior cingulate (dACC) and striatum regions in the frontostriatal pathway using proton MRS at baseline and on verified abstinent days 7 and 21 in chronic users of cannabis (n = 20) in comparison with age- and sex- matched non-using controls (n = 10). In addition, the Barratt Impulsiveness Scale-11 (BIS) was collected as a measure of inhibitory impulse control of the participants. We found that the difference in glutamate concentrations between the dACC and striatum (Δ_dACC-strGlu) of the controls was significantly higher than that of cannabis users across the study timeline (F(1,28) = 18.32, p < 0.0005). The group difference was not affected by age, sex, or alcohol/cigarette consumption. On abstinent day 7, Δ_dACC-strGlu was significantly correlated with the corresponding Δ_dACC-strGABA among the users (r = 0.837, p < 0.00001). On day 21, Δ_dACC-strGlu was negatively associated with monthly cannabis use days (Spearman's rho = -0.444, p = 0.05). Self-reported BIS and its subscales were significantly altered among the users compared to the controls across the study timeline (total F(1,28) = 7.0, p = 0.013; non-planning F(1,28) = 16.1, p < 0.0005; motor F(1,28) = 5.9, p = 0.022; cognitive F(1,28) = 6.1, p = 0.019). These data provide preliminary evidence that chronic cannabis use may lead to a dACC-striatal glutamate imbalance in conjunction with poor impulse control.

Keywords: Cannabis; Glutamatergic imbalance; dACC-striatal.

Figure 1a

Illustration of BIS-11 nonplanning (np) subscale, mean ± sem, from baseline to 21 days of abstinence, where MJ = cannabis users and HC = non-using controls. The group difference between the users and the non-using controls was significant in BIS-11 total (F(1,28)=7.0, p=0.013) and subscales of nonplanning (F(1,28)=16.1, p<0.0005), motor (F(1,28)=5.9, p=0.022), and cognitive (F(1,28)=6.1, p=0.019). However, no change in time among participants across the timeline.

Figure 1b

Group averages of Δ_dACC-strGlu and Δ_dACC-strGABA, mean ± sem, at baseline and abstinent days 7 and 21 of the marijuana users (MJ) and non-using controls (HC). The group difference between the users and the non-using controls was significant in Δ_dACC-strGlu (F=18.32, p <0.0005) but not in Δ_dACC-strGABA (F=3.97, p=0.056), which was only significant on Day 7 (p = 0.020) but not at baseline and Day 21.

Figure 2a

Correlation between Δ_dACC-strGlu and Δ_dACC-strGABA in chronic cannabis users (solid circles) and non-using controls (open circles) on day 7 of abstinence.

Figure 2b

Correlation between Δ_dACC-strGlu and Δ_dACC-strGABA in cannabis users at baseline (BL, solid circles) and abstinent day 21 (Day21, open circles).