Stability of cognitive functioning in sample I
The pattern of means in Table identifies change over time in cognitive performance in each group. There were statistically significant overall group differences in all attention and memory measures. As apparent from the Table , the methadone-treated patient group constantly lagged behind the healthy control group in the TAP reaction time tests measuring alertness and selective attention. Planned contrasts confirmed that the healthy controls outperformed the methadone group in these measures (p = 0.002 for the TAP tonic alertness/simple reaction time; p = 0.002 for the TAP phasic alertness/reaction time with-auditory-warning-signal; and p = 0.001 for the TAP Go/NoGo reaction time/selective attention). There were neither significant time nor group by time interaction effects in these measures. Errors in the Go/NoGo task were rare in all groups, and no significant between groups differences were observed. In both working memory measures there was an overall group effect. In the PASAT the planned contrast revealed that both patient groups performed overall worse than the healthy controls at the level of p = 0.001. In the Letter-Number Sequencing the values were p = 0.016, for healthy controls vs. buprenorphine patients and p = 0.008 for healthy controls vs. methadone patients. However, because there was also time effect (the PASAT), or a group by time interaction effect (the Letter-Number Sequencing) in these measures, further analyses are needed before the final interpretation. In the PASAT the improvement in overall performance between T1 and T2 turned out to be non-significant, but the overall improvement between T2 and T3 was significant, p = 0.01. As apparent from Figure , the source of group by time interaction in the Letter-Number Sequencing was due to differences between the groups between T2 and T3. This was confirmed by a planned contrast which showed improved performance in the buprenorphine patients between T2 and T3 relative to healthy control group, p = 0.017. Effect size of the T2 - T3 improvement in the buprenorphine group, as measured by Cohen's d, was 0.77. In verbal memory, there was a significant overall group effect both in immediate and delayed condition of the Logical Memory. Both patient groups performed worse than the healthy controls in the immediate Logical Memory, p = 0.029 for the buprenorphine group; and p = 0.007 for the methadone group. In the delayed Logical Memory the values were p = 0.005, and p = 0.028, respectively.
Group comparisons of cognitive performances using repeated measures ANOVA in sample I
Group performances in the Letter-Number Sequencing Task during the study period in sample I.
Cognitive functioning in sample II
The cognitive group comparisons in the part II (T2 - T3) sample brought results that were in line with the part I sample analyses. Buprenorphine patients outperformed methadone patients in the combined attention performance (p = 0.004), and no significant time or group by time effect were seen. In working memory as measured by the Letter-Number Sequencing there was a main effect of time (p = 0.01) and a significant group by time interaction, (p = 0.04) indicating again that improvement in this measure was due to enhanced performance in the buprenorphine patients between T2 and T3. In the combined verbal memory measure there were no significant differences between groups, time effect, or group by time interaction.
Correlations between medication variables and non-cognitive variables in sample II
At T2, buprenorphine dose correlated substantially with BZD dose (.62, p = 0.006) and moderately with the number of psychoactive drugs (.40, ns). In the methadone group, respective values were (.47, ns; and .58, p = 0.013). At T3, buprenorphine dose correlated at moderate level with BZD dose (.33, ns) and at very low level with the number of psychoactive drugs (.10, ns). In the methadone group respective values were mild (.25, ns; and .20, ns). In general, buprenorphine or methadone doses did not show significant correlations with substance abuse or demographic variables. As an exception buprenorphine dose correlated negatively with years of alcohol abuse, at T2 the value was -.56 (p = 0.016) and at T3 -.64 (p = 0.004). In the methadone group, no significant correlations emerged. Other significant correlations between medication variables and other non-cognitive variables of interest are presented in Table . It can be noted that high BZD dose was associated with high frequency of substance abuse in the past month and younger age at both time points.
Significant correlations between medication variables and other non-cognitive variables in sample II
Correlates of cognitive performances in sample II
As shown in Table , the only significant correlate for attention performance at both test points was the opioid substitution drug group. High frequency of substance abuse correlated negatively with the Letter-Number Sequencing performance at both time points. Figures and depict this association. It can be noted from these Figures that the association between working memory performance and frequency of substance abuse in the past month is similar in both groups. The T2 negative correlation remained significant after controlling for two next highest correlates. The T3 correlation dropped to non-significant level after controlling for two next highest correlates (-.18). At T3, high benzodiazepine dose correlated negatively with the Letter-Number Sequencing performance. After controlling for the two other highest correlates, this association was no longer significant (-.22). In further analysis no evidence in support of high association between BZD dose and the Letter-Number Sequencing performance was seen, because T2 correlation between these variables was at zero level (.02). Belonging to the buprenorphine group was the only variable that correlated significantly (.34) with change of the Letter-Number Sequencing performance. After controlling for two other highest correlates, this association was no longer significant.
Highest correlations between cognitive and non-cognitive variables in sample II
Correlation between the frequency of the past month substance abuse and the performance in the Letter-Number Sequencing at T2 in sample II.
Correlation between the frequency of the past month substance abuse and the performance in the Letter-Number Sequencing at T3 in sample II.
The number of psychoactive drugs correlated positively with verbal memory performances at both testing points. At T3, the positive association with the number of psychoactive drugs reached significant level after two other correlates were taken into account. At T2, there was a negative association with the highly frequent past month substance abuse and verbal memory performance. After controlling for two other highest this correlation dropped to non-significant level (.28). Furthermore, at T3 the correlation between highly frequent substance abuse in the past month and verbal memory was very low and to the opposite direction (-.08).
Correlations between opioid substitution drug dose and cognitive performances opioid drug doses could be examined only group-wise (n = 18 in both groups). None of the correlations reached statistical significance. Because there was a significant group by time interaction in the Letter-Number Sequencing indicating specific improvement in this task in the buprenorphine group, correlates for the improvement in the buprenorphine group were examined. No significant correlates for the change score emerged.