The METH abusers differed from the controls in that they had lesser years of education (12.7±1.6 vs. 14.3±8.1 years, p < 0.001) and there was a greater proportion of cigarette smokers (16 METH abusers vs. 4 controls, p < 0.001) and heavier cigarette smoking. Four METH abusers had moderate alcohol use and none of the controls use alcohol more than once per week. The METH abusers had a history of 13.1±7.2 years METH use and 1.2±1.0 grams per day.
After placebo administration, the 16 METH abusers had lower D2R availability in caudate (2.5±0.2) than controls (2.8±0.3, p < 0.04), . Both METH abusers and controls reported greater ratings of drug effect (+1.5±1.7, p < 0.003; +2.3±2.8, p < 0.007) and alertness (+2.0±2.0, p < 0.001; +1.2±1.7, p < 0.02) after MPH than after placebo administration but the magnitude of these effects did not differ between groups. The controls but not the METH abusers reported greater ratings of “high” (+1.6±2.5, p < 0.03) after MPH. Neither group reported increased anxiety or restlessness after MPH. MPH administration increased pulse rate (METH abusers: +28.5±28.1%, p < 0.001; control: 19.8±16.8%, p < 0.0004) and diastolic pressure (METH abusers: +6.3±10.7%, p < 0.03; subjects: +7.8±12.1%, p < 0.03) in both groups and increased systolic pressure in the METH abusers (+8.5±6.5%, p < 0.0001) but not in the controls (+3.8±9.2%, NS). However, the self-report ratings and cardiovascular changes after MPH were not significantly different between the groups. The plasma MPH concentrations at 30 and at 60 minutes were similar for the METH abusers (5.9±6.1, 19.1±6.2 ng/ml) and the controls (8±11.5, 21.8±8.9 ng/ml).
Comparison of DA D2 receptor availability of METH subjects during early withdrawal and control subjects during their first visit after oral placebo and after oral methylphenidate (60 mg) administration.
After MPH administration, both METH abusers (caudate: −4±7.3%, p < 0.04; putamen: −5.5±8.3%, p < 0.01; ventral striatum: −4.1±14%, p < 0.06) and controls had decreased D2R availability (caudate: −6.4±9.2%, p < 0.002; putamen: −10.5±10%, p < 0.001; ventral striatum: −9.5±13.5%, p < 0.007; ) presumably reflecting DA increases. Comparison for groups’ interaction effects was only significant for MPH-induced DA in left putamen (p < 0.05). The MP-induced decreases in left putamen in METH abusers were significantly smaller than in controls. There was no association between placebo or MPH-induced DA release with clinical variables as cigarette smoking, years of METH use, amount of METH use and days of last METH use in the METH abusers. The plasma MPH levels were not associated with MPH-induced DA increases neither in METH abusers nor controls.
SPM analysis, using a correction for small volume and multiple comparisons (p < 0.005), showed significantly decreased D2R availability in striatum after MPH in both controls and METH abusers. The METH abusers had less decrement in putamen than controls [Coordinates in the MNI frame of reference: x = 38, y = −12, z = 6 mm; cluster volume = 482 voxels (2-mm isotropic); statistical significance: Z-score = 2.5; p < 0.036, FDR-corrected for multiple comparisons using a small volume correction (10-mm spherical volume), ]. There were no significant correlations between MPH-induced changes in BPND and the behavioral effects of MPH.
Figure 1 A) Averaged DA D2 receptor availability (D2R) images with oral methylphenidate (MPH 60 mg) and placebo between MPH and placebo (PL) of 16 METH abusers and 15 control subjects. The D2R images are scaled with respect to the maximum Vd ratio value of the (more ...)
Six METH abusers (2 female and 4 male) relapsed after the PET scan visit. Four of these subjects had positive drug screens during the course of the study and two of the subjects were lost to follow up but the center was given informal feedback that the subjects had relapsed. There were no demographic (age, education) or clinical differences (years of METH, alcohol, tobacco use, amount of METH, alcohol, tobacco use and days of last METH use) between the six METH abusers who relapsed and those who did not. There were also no differences in self-report ratings and cardiovascular response to MPH administration between those who relapsed and those who did not.
The six METH abusers who relapsed showed no D2R availability changes after MPH (caudate: −0.7±11%, NS; putamen: −0.5±10%, NS) whereas in 10 METH abusers who did not relapse MPH induced significant reduction in D2R availability (caudate: −6.6±5%, p < 0.002; putamen: −8.5±5.6%, p < 0.001, ). Post hoc analysis showed that METH abusers who relapsed had significant lower D2R availability in caudate (p < 0.014) and putamen (p < 0.015) at baseline and less DA release after MPH in putamen (treatment × diagnosis, p < 0.037). The amount of METH used by the 6 relapsed subjects did not correlate with baseline D2R availability and not with MPH-induced DA changes. The 10 METH abusers who remained abstinent showed a trend for lower baseline D2R availability (p < 0.07) and less MPH-induced DA release (treatment × diagnosis, p < 0.07) in caudate than the controls.
Comparison of DA D2 receptor availability of METH subjects (n = 10) with protracted abstinence and METH users (n = 6) relapsed after scan visit after oral placebo and after oral methylphenidate (60 mg).