Elevated striatal glutamate glutamine in recreational cannabis users during abstinence.
Cannabis withdrawal symptoms contribute to relapse, but the underlying mechanism remains unclear. We hypothesize that cannabis withdrawal may be associated with a reset of regional γ-amino butyric acid (GABA) and glutamate concentrations secondary to changes in the endocannabinoid system during abstinence and conducted a study on this issue. We used magnetic resonance spectroscopy (MRS) to detect the associated changes of these neurochemicals in twenty-six frequent, recreational cannabis users and eleven age-matched non-using controls. Twenty users (8F12M) and ten control (5F5M) participants completed a verified 21-day abstinence period. Striatal GABA and glutamine concentrations were measured at baseline and on abstinence days 7 and 21 in conjunction with measures of cannabis withdrawal symptoms and mood state. Cannabis users reported increased self-reported ratings of cannabis-withdrawal-symptoms on abstinence day 7 relative to controls. Striatal glutamate glutamine (Glx) group concentrations were elevated in cannabis users at baseline and abstinence days 7 and 21 (F 7.16, p 0.012), and changes in GABA concentration and withdrawal symptoms between baseline and abstinence day 7 were positively correlated (r 0.550, p 0.010). In addition, baseline striatal GABA concentrations were negatively correlated with withdrawal symptoms on abstinence day 7 (r -0.680, p 0.003). Our data demonstrate that striatal Glx was elevated in cannabis users and baseline striatal GABA correlated with withdrawal during the abstinence. In addition, striatal GABA may temporally correlate with self-reported withdrawal symptoms during the initial days of abrupt cannabis abstinence. These findings provide preliminary evidence that striatal GABA and Glx are associated with the severity of cannabis withdrawal.