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 (8F/12M) and ten control (5F/5M) 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.