The central effects of BZP and TFMPP in humans: An investigation using electroencephalography

Abstract

‘Party Pills’ containing 1-benzylpiperazine (BZP) and 1-(3- trifluoromethylphenyl)piperazine (TFMPP) were legally available in New Zealand and marketed as safe alternatives to 3,4-methylenedioxymethamphetamine (MDMA) until they were banned in 2008; however, they continue to be available in some parts of the world. BZP and TFMPP are known to stimulate the release and inhibit the reuptake of dopamine, serotonin and noradrenaline in rodents. Studies in humans report that these compounds produce changes in blood pressure, heart rate and subjective feelings comparable to amphetamine and MDMA (also known as ‘Ecstasy’). However, there is currently no information available about the acute effects of these drugs on central processing in humans and the extent to which their effects are similar or different to those of better characterised stimulant drugs, such as dexamphetamine. The aim of the work reported in this thesis was to investigate the effects of BZP, TFMPP and the combination of BZP+TFMPP on human neural processing using electroencephalographic techniques and to compare their effects to dexamphetamine (a positive control) and placebo. Randomised, double blind, placebo-controlled studies using electroencephalography investigated the effects of these compounds on the interhemispheric transfer of information using the Poffenberger task, and efficiency of attention allocation using an auditory oddball task. In addition, reaction time data were collected. Healthy, right-handed males were given an 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 minutes after drug administration. We measured three variables using the Poffenberger task; absolute N160 latency, interhemispheric transfer time and the mean reaction time pre- and post-drug administration. 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 interhemispheric transfer time revealed that only TFMPP (F(1,77)=5.266, p≤0.02) significantly reduced the interhemispheric transfer time, 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 (i.e. faster Right-to-Left transfer compared to Left-to-Right transfer), whereas this asymmetry was not present in the BZP, BZP+TFMPP and dexamphetamine groups. The reaction time (F(4,91)=0.373, p>0.05) was not significantly affected by any of the drug treatments. Using the auditory oddball paradigm, we collected the P100, P200 and P300 amplitude, latency and mean reaction time data to determine drug effects. A mixed factorial repeated measures analysis of variance of the P300 amplitude revealed a significant Time×Drug effect (F(4,82)=2.379, p≤0.05). Contrast analysis revealed that BZP, TFMPP and dexamphetamine significantly reduced the P300 amplitude (F(1,82)=9.09, p≤0.004), whereas BZP+TFMPP and placebo had no effect. Neither P300 latency (F(4,82)=0.339, p=0.093) nor the mean reaction time (F(4,82)=1.274, p=0.960) was affected by any of the drug treatments. In addition, none of P100 amplitude (F(4,82)=0.680, p=0.608), P100 latency (F(4,82)=0.919, p=0.458) , P200 amplitude (F(4,82)=1.430, p=0.234), nor P200 latency (F(4,82)=0.460, p=0.765) components were affected following any of the drug treatments. To conclude, the work described in this thesis has demonstrated that BZP, TFMPP and BZP+TFMPP act centrally to alter neural processing in humans.