Investigating the effects of an acute dose of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) alone and in combination on the human brain using functional Magnetic Resonance Imaging (fMRI)

Abstract

Party pills containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been widely used for recreational purposes in the past decade, despite a paucity of knowledge about their effects on the human brain. This thesis investigated the effects of an acute dose of BZP (200 mg), TFMPP (60 mg) and the combination of BZP+TFMPP (100 mg + 30 mg) on the neural activity involved in reward and executive function using functional Magnetic Resonance Imaging (fMRI). A validation task was also used to evaluate the direct effect of each drug on the vasculature of the brain. A randomised double blind cross-over study recruited 13 participants. Ninety minutes after an acute dose of BZP, TFMPP, BZP+TFMPP, dexamphetamine (DEX; 20 mg) or placebo, participants performed gambling (guessing), Stroop and validation tasks while undergoing fMRI. To compare these effects, imaging data was pre-processed and analysed then regional activation was identified using SPM8. Behavioural responses were analysed with SPSS. During anticipation, BZP reduced the neural responses in areas associated with uncertainty and inhibition, and increased activation in regions associated with monetary losses during outcome, possibly by dopaminergic modulation. When BZP was compared to DEX, BZP reduced activation in regions associated with uncertainty and risk, whereas DEX did not, and in the outcome stage of reward BZP induced a greater response to loss. TFMPP increased activation in regions associated with emotional processing during anticipation and modulated activation during outcome reflecting serotonergic effects on aversion. BZP+TFMPP reduced activation during anticipation, but caused a wider network of activation during reward outcome, possibly due to opposing drug effects on dopaminergic transmission. During the Stroop task, BZP and TFMPP affected inhibitory control and/or selective attention, resulting in the compensatory recruitment of additional regions. A direct comparison of BZP with DEX revealed distinct differences, BZP increased activation in regions associated with inhibition whereas DEX had the opposite effect. The combination of BZP+TFMPP induced activation which reflected the direct and indirect effects of TFMPP. A validation task demonstrated that drug-induced regional activations in the tasks were not due to the direct effects of each drug on cerebral vasculature. These results indicate that BZP, TFMPP and BZP+TFMPP have differential effects on reward and executive function which might lead to sub-optimal decisions being made whilst under their influence. In addition, although similar drug-induced effects on mood have been reported, this work demonstrates distinct differences between the underlying pharmacological effects of BZP and DEX on the brain.