The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18–46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects

Determining the subjective and physiological effects of BZP combined with TFMPP in human males

Abstract Background &quot;Party pills&quot; containing benzylpiperazine (BZP) used to be widely and legally available as recreational drugs in New Zealand. There are only two published trials on human subjects (1973), which suggested that 100 mg of BZP produced subjective and physiological effects similar to 10 mg of dexamphetamine. The purpose of this study is to further investigate the subjective and physiological responses to BZP in females. Methods/study design In a randomised, double blind, placebo-controlled study, the subjective and physiological effects of BZP were investigated in 27 healthy, right-handed non-smoking females (mean age 22±3 years). Two groups were tested before and approximately 120 minutes after administration of a single oral dose of either 200 mg BZP (n=14) or placebo (n=13). Participants were required to comment on the subjective effects of BZP using three rating scales-the Addiction Centre for Research Inventory, the Profile of Mood States and the Visual Analogue Scale. Participants&apos; blood pressure, heart rate and temperature were also measured. Results/findings Statistical analysis using a split-plot analysis of variance and t tests revealed that BZP significantly increases blood pressure and heart rate (p&lt;0.05) Likewise, the subjective reports revealed that BZP has significant stimulant effects, increases euphoria and dysphoria and increases sociability and drug liking (p&lt;0.05). Discussion/interpretation Physiological and subjective data reflected a clear similarity between the effects of BZP and those of other commonly known stimulants such as amphetamine and 3,4-methylenedioxymethamphetamine

Changes in resting EEG following methadone treatment in opiate addicts

Objective: This study investigated the electrophysiological activity associated with methadone maintenance treatment (MMT). Methods: The resting EEG spectrum of beta (14.5-30. Hz), alpha (8-13. Hz), theta (4-7.5. Hz) and delta (1.5-3.5. Hz) rhythm were measured in 32 patients undertaking chronic MMT, 17 opiate users and 25 healthy volunteers. Differences in the EEG components of each group were evaluated using a repeated measures Analyses of Variance (ANOVA). Post-hoc comparisons were Bonferroni corrected. Results: Our results show that either patients undertaking MMT or active opiate users exhibited a significant increase in the power of beta and theta bands relative to healthy control subjects. However, the spectral power of patients undertaking MMT fell between that of current opiate users and healthy control subjects on many regional EEG measures. There was an inverse correlation between the power of beta or theta bands and cognitive performance. Conclusion: The abnormal neural electrical activity present in those still using illicit opiates might be reduced following MMT. Significance: The present findings provide further support for MMT of opiate dependence and demonstrates potentially positive effects of substitution treatment on brain function

Neuropsychological performance of methadone-maintained opiate users

Methadone maintenance treatment (MMT) has been used to treat opiate dependence since the mid-1960s. Previous studies have investigated the effects of methadone on cognitive function however the findings have been inconsistent. Some report a complete absence of deficits while others report different types of cognitive impairment. Our research aimed to investigate the effects of MMT on cognitive function by comparing the performance of patients currently enrolled in MMT (n=32) with opiate-dependent subjects (n=17) and healthy control subjects (n=25) on a computerised neuropsychological test battery. Both the patients undertaking MMT and the opiate users showed less efficient interaction between visual searching and manually connecting digits and letters during the Switching of Attention Task than the healthy control subjects (F(2,64)=3.25, p=0.05), which indicates deficits in information processing. Nevertheless, the performance of the MMT group was similar to that of healthy control subjects in all other tasks, in contrast to the group of opiate users who performed poorly when compared to healthy control subjects during tests of attention (mean difference (MD)=2.8, 95% confidence interval (CI) (0.9-4.7), p=0.001) and executive function (MD=5.9, 95% CI (1.3-10.5), p=0.007). These findings suggest that cognitive function in patients undertaking MMT is improved compared to those dependent on illicit opiates

Investigation of the effects of ‘piperazine-containing party pills’ and dexamphetamine on interhemispheric communication using electroencephalography

Background: ‘Piperazine-containing party pills’ were marketed and sold as legal alternatives to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. The major constituents of these ‘pills’ were benzylphenylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP). Despite their popularity, there is a paucity of knowledge about their central effects in humans. This study investigated their effects on human neural processing using electroencephalographic techniques. Methods: A randomised, double-blind, placebo-controlled study investigated the effects of an acute dose of these compounds on the interhemispheric transfer of information (IHTT) using the Poffenberger task. Reaction time data were also collected. Healthy, right-handed males were given an oral dose of either BZP (n = 13) (200 mg), TFMPP (n = 15) (60 mg), a combination of BZP + TFMPP (n = 15) (100 mg/30 mg), dexamphetamine (n = 16) (20 mg), or placebo (n = 23) and tested both before and 120 min after drug administration. Results: A mixed factorial repeated measures analysis of variance of absolute N160 latency and contrast analysis revealed that only TFMPP (F(1,77) = 17.30, p ≤ 0.001) significantly reduced the absolute N160 latency. Analysis of the IHTT revealed that only TFMPP (F(1,77) = 5.266, p ≤ 0.02) significantly reduced the IHTT, while BZP, BZP + TFMPP and dexamphetamine had no effect. Contrast analysis revealed that both TFMPP (F(1,77) = 17.30, p ≤ 0.001) and placebo (F(1,77) = 15.08, p ≤ 0.001) preserved the laterality of information transfer from one hemisphere to the other. Reaction time (p > 0.05) was not significantly affected by any of the drug treatments. Conclusions: The usual directional asymmetry (i.e. faster R-to-L transfer relative to L-to-R) observed in healthy control group was absent following the administration of either BZP, BZP + TFMPP or dexamphetamine. Surprisingly, lateralised hemispheric function was not affected by TFMPP. Our findings highlight how the administration of BZP, TFMPP and BZP + TFMPP leads to changes in the pattern of information transfer

Determining the subjective and physiological effects of BZP combined with TFMPP in human males

Abstract Rationale &apos;Party Pills&apos; containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been used in a recreational context since the 1990s and, prior to April 2008, were legally available in New Zealand. Taken together, they have been reported to produce a &apos;high&apos; similar to that produced by 3,4-methylenedioxymethamphetamine (MDMA). Objectives There has been little research on the subjective effects of piperazines in humans. The purpose of this study is to further investigate the subjective and physiological responses following an oral dose of BZP combined with TFMPP in males. Methods In a randomised, double-blind, placebo-controlled study the subjective and physiological effects of BZP/ TFMPP were investigated in 36 healthy, non-smoking males (mean age 22±4 years). Participants were tested before and approximately 120 min after administration of a single dose of placebo (n=16) or 100/30 mg BZP/TFMPP (n=20). Participants were required to comment on the subjective effects using three rating scales-the Addiction Research Centre Inventory (ARCI), the Visual Analogue Scale (VAS) and the Profile of Mood States (POMS). Participants&apos; blood pressure, heart rate and body temperature were also measured. Results Statistical analysis using repeated-measures analysis of variance (ANOVA) and planned comparisons revealed that BZP/TFMPP significantly increases blood pressure and heart rate (p&lt;0.05). Likewise, the subjective rating scales revealed that BZP/TFMPP has significant dexamphetamine-like effects, increases dysphoria and feelings of self-confidence (p&lt;0.05). Conclusion These physiological and subjective data reflect clear similarities between the effects of BZP/TFMPP and commonly known stimulants such as dexamphetamine and MDMA

Acute effects of BZP, TFMPP and the combination of BZP and TFMPP in comparison to dexamphetamine on an auditory oddball task using electroencephalography: a single-dose study

Rationale: Piperazine-based designer drugs such as benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been marketed and sold as legal alternatives to dexamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. When administered in combination, BZP + TFMPP have been reported to produce drug-drug synergism in rodents by stimulating the release of dopamine and serotonin. Objectives: This study was to evaluate the acute event-related potential effects of BZP, TFMPP or the combination of BZP + TFMPP compared with dexamphetamine in young healthy male adults. Methods: A double-blind, randomised, placebo-controlled study investigated the effects of BZP, TFMPP, the combination of BZP + TFMPP, and dexamphetamine on the event-related potentials during an auditory oddball task. Healthy, right-handed males were given a single oral dose of either BZP (200 mg), TFMPP (60 mg), a combination of BZP + TFMPP (100/30 mg), dexamphetamine (20 mg) or placebo (lactose) and tested both before and 120 min after drug administration. Results: A single dose of either TMFPP (t = -2.29, p = 0.03) or dexamphetamine (t = -2.33, p = 0.02) significantly reduced the P300 amplitude. A similar trend was also found in BZP. In contrast, BZP and TFMPP in combination has no effect. Neither P300 latency nor the mean reaction time was affected by any of the drug treatments. In addition, neither the P100 nor the P200 component was significantly affected following any of the drug treatments. Conclusions: A single oral dose of BZP or TFMPP, but not the combination of BZP/TFMPP, affected auditory sensory-evoked P300 potential in a manner similar to dexamphetamine