Dopamine function during early withdrawal predicts recovery in methamphetamine users

Objectives Studies in methamphetamine abusers (METH) showed decreases in dopamine (DA) brain function might recover with protracted abstinence (PA). The extent to which DA function in METH during early withdrawal (EW) can predict recovery has not been evaluated.

Methods Fifteen METH (39.2±4.9 yr) were evaluated with PET and [¹¹C]raclopride. Changes in extracellular DA in the striatum were evaluated after placebo and after oral methylphenidate (MP, 60 mg) during EW (< 6 months since last use) and after 9 months of abstinence. In parallel, 15 controls (NC) were tested and 10 NC were retested at 9 months. D2R availability (Bmax/Kd) was analyzed with ROI method.

Results METH had lower D2R in caudate (CA) during EW (2.5±0.2) than NC (2.8±0.3, p < 0.03). Both METH during EW and NC at initial decreased D2R after MP (-4±7.3%, p < 0.04; -8.7±8.5%, p < 0.001). Decrement in left putamen (PU) in METH was less than NC (p < 0.05). D2R changes after MP in 9 METH during EW showed decrement (-7.5±8%, p < 0.01) that was similar to during PA (-5.1±8.8%, p < 0.01). NC did not differ in D2R changes after MP between initial and retest in CA and PU but decreased in ventral striatum (p < 0.02). Post hoc analysis EW of 6 METH who relapsed revealed no D2R changes after MP (-0.5±10%) during EW.

Conclusions The results replicated our prior studies of DA dysfunction in METH. METH with better DA function during EW predicted recovery in PA. Poor DA response after MP during EW in the METH who later relapsed suggests a more severe addictive state. Early detection of the extent of DA dysfunction will be helpful in predicting the outcome of the rehabilitation.

Research Support NIDA/NIAAA/GCRC/DOE